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ES2651349T3 - Composiciones y métodos para la inhibición de la ruta JAK - Google Patents

Composiciones y métodos para la inhibición de la ruta JAK Download PDF

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ES2651349T3
ES2651349T3 ES06784727.7T ES06784727T ES2651349T3 ES 2651349 T3 ES2651349 T3 ES 2651349T3 ES 06784727 T ES06784727 T ES 06784727T ES 2651349 T3 ES2651349 T3 ES 2651349T3
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pyrimidinediamine
fluoro
phenyl
aminosulfonyl
aminosulfonylphenyl
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Hui Li
Sambaiah Thota
David Carroll
Ankush Argade
Kin Tso
Arvinder Sran
Jeffrey Clough
Holger Keim
Somasekhar Bhamidipati
Vanessa Taylor
Robin Cooper
Rajinder Singh
Brian Wong
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Rigel Pharmaceuticals Inc
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Rigel Pharmaceuticals Inc
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Abstract

Un compuesto de la fórmula III:**Fórmula** o una sal farmacéuticamente aceptable del mismo; en la que: X se selecciona entre el grupo que consiste en metilo y flúor; R es hidrógeno; el anillo A es fenilo; p es 0, 1, 2 o 3; cada R2 se selecciona independientemente entre el grupo que consiste en alquilo C1-10, alquilo C1-10 sustituido, alcoxi, alcoxi sustituido y halo; cada uno de Z1, Z2 y Z3 es carbono; q es 0, 1, 2 o 3; cada R3 se selecciona independientemente entre el grupo que consiste en alquilo C1-10, alquilo C1-10 sustituido, alcoxi y alcoxi sustituido; R4 y R5 se seleccionan independientemente entre el grupo que consiste en hidrógeno, alquilo C1-10, alquilo C1-10 sustituido y acilo, o R4 y R5 junto con el átomo de nitrógeno enlazado al mismo, forma un heterociclilo C1-10 incluyendo 1-4 heteroátomos seleccionados entre el grupo que consiste en oxígeno, nitrógeno y azufre o heterociclilo C1-10 sustituido, incluyendo 1-4 heteroátomos seleccionados entre el grupo que consiste en oxígeno, nitrógeno y azufre; y -SO2NR4R5 es meta con respecto al grupo amino en la posición 2 de la pirimidina; en la que: "alquilo sustituido" se refiere a un grupo alquilo que de 1 a 5 hidrógenos reemplazados por sustituyentes seleccionados entre el grupo que consiste en alcoxi, acilo, acilamino, aciloxi, amino, aminocarbonilo, aminocarbonilamino, aminocarboniloxi, aminosulfonilo, aminosulfonilamino, arilo C6, carboxilo, carboxil éster, ciano, alquinilo C2-C6, halo, hidroxi, heteroarilo seleccionado entre piridinilo, pirimidinilo, pirazinilo, piridizinilo, triazina, pirrolilo, indolilo, tiofenilo y furanilo; "alcoxi" se refiere a los grupos -O-alquilo C1-C10 "Alcoxi sustituido" se refiere a los grupos -O-(alquilo C1-C10 sustituido); "acilo" se refiere a los grupos H-C(O)-, alquil C1-C10-C(O)-, alquenil C2-C6-C(O)-; "acilamino" se refiere a los grupos -NR20C(O)alquilo C1-C10, -NR20C(O)-cicloalquilo C3-C10, - NR20C(O)cicloalquenilo C3-C10, - NR20C(O)alquenilo C2-C6; "aciloxi" se refiere a los grupos alquil C1-C10-C(O)O-, alquenil C2-C6-C(O)O-; "amino" se refiere al grupo -NH2 "aminocarbonilo" se refiere al grupo -C(O)-NH2 "aminocarboniloxi" se refiere al grupo -O-C(O)NR21R22 "aminocarbonilamino" se refiere al grupo -NR20C(O)NR21R22 "aminosulfonilo" se refiere al grupo -SO2NR21R22; "aminosulfonilamino" se refiere al grupo -NR20-SO2NR21R22; "carboxil éster" se refiere a los grupos -C(O)O-alquilo C1-C10, R20 es hidrógeno o alquilo C1-C10; R21 y R22 se seleccionan independientemente entre el grupo que consiste en hidrógeno, alquilo C1-C10, alquenilo C2-C6, o R21 y R22 están unidos opcionalmente junto con el nitrógeno enlazado a los mismos para formar un grupo heterocíclico que tiene de 1 a 10 átomos de carbono, 1 átomo de nitrógeno y opcionalmente un heteroátomo adicional seleccionado entre el grupo que consiste en nitrógeno, azufre u oxígeno; y "heterociclilo sustituido" se refiere a un grupo heterociclilo que está sustituido con 1 a 5 sustituyentes alquilo C1-10; con la condición de que: si p >= 2 y cada uno de R2 es metoxi, halo, trihalometilo o trihalometoxi, entonces R4 y R5 no son ni un hidrógeno ni un metilo; y que es un compuesto seleccionado el grupo que consiste en: N2-[3-Aminosulfonil-4-(4-metilpiperazin-1-il)fenil]-5-fluoro-N4-(4-cianometilenooxifenil)-2,4-pirimidindiamina; N2-[3-Aminosulfonil-4-(4-metilpiperazin-1-il)fenil]-5-fluoro-N4-(4-cianometilenooxi-3-fluorofenil)-2,4- pirimidindiamina; N2-(3-Aminosulfonil-4-clorofenil)-N4-(4-cianometoxi)fenil-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-fluoro)fenil-N4-(4-cianometoxi)fenil-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4- fluoro)fenil-N4-(4-cianometoxi-3-metil)fenil-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-fluoro)fenil-N4-(4- cianometoxi-3,5-dimetil)fenil-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-fluoro)fenil-N4-[4-(1-ciano)etoxi]fenil-5-fluoro-2,4-pirimidindiamina racémica; N2-(3-Aminosulfonil-4-fluoro)fenil-N4-[4-(1-ciano)etoxi-3-metil]fenil-5-fluoro-2,4-pirimidindiamina racémica; N2-(3-Aminosulfonil-4-fluoro)fenil-N4-[4-(1-ciano-1-metil)etoxi]fenil-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-N4-[4-(N-cianoacetil)aminofenil]-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-N4-[4-(N-cianoacetil)aminofenil]-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-5-fluoroN4-[3-metil-4-(N-cianoacetil)aminofenil]-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-5-fluoroN4-[3-metil4-(N-cianoacetil)aminofenil]-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-N4-[3-cloro-4-(N-cianoacetil)aminofenil]-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-N4-[3-cloro-4-(N-cianoacetil)aminofenil]-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-5-fluoroN4-[3-metoxi-4-(N-cianoacetil)aminofenil]-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-5-fluoroN4-[3-metoxi-4-(N-cianoacetil)aminofenil]-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-N4-[4-(N-cianoacetil-N-metil)aminofenil]-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-N4-[4-(N-cianoacetil-N-metil)aminofenil]-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-N4-(4-dimetilaminocarbonilmetoxifenil)-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-N4-(4-dimetilaminocarbonilmetoxifenil)-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-N4-(3-cloro-4-dimetilaminocarbonilmetoxifenil)-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-N4-(3-cloro-4-dimetilaminocarbonilmetoxifenil)-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-N4-(3-cloro-4-dimetilaminocarbonilmetoxifenil)-5-metil-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-N4-(3-cloro-4-dimetilaminocarbonilmetoxifenil)-5-metil-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-N4-(4-dimetilaminocarbonilmetoxi-3-fluorofenil)-5-metil-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-N4-(4-dimetilaminocarbonilmetoxi-3-fluorofenil)-5-metil-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-clorofenil)-N4-(3-cloro-4-dimetilaminocarbonilmetoxifenil)-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-clorofenil)-N4-(3-cloro-4-dimetilaminocarbonilmetoxifenil)-5-metil-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-clorofenil)-N4-(4-dimetilaminocarbonilmetoxi-3-fluorofenil)-5-metil-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-5-fluoro-N4-(4-metilaminocarbonilmetoxifenil)-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-(4-metilaminocarbonilmetoxifenil)-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-N4-(3-cloro-4-metilaminocarbonilmetoxifenil)-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-N4-(3-cloro-4-metilaminocarbonilmetoxifenil)-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-N4-(3-cloro-4-metilaminocarbonilmetoxifenil)-5-metil-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-N4-(3-cloro-4-metilaminocarbonilmetoxifenil)-5-metil-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-clorofenil)-N4-(3-cloro-4-metilaminocarbonilmetoxifenil)-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-clorofenil)-N4-(3-cloro-4-metilaminocarbonilmetoxifenil)-5-metil-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-N4-(3-fluoro-4-metilaminocarbonilmetoxifenil)-5-metil-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-N4-(3-fluoro-4-metilaminocarbonilmetoxifenil)-5-metil-2,4-pirimidindiamina; N4-(4-Alilaminocarbonilmetoxifenil)-N2-(3-aminosulfonilfenil)-5-fluoro-2,4-pirimidindiamina; N4-(4-Alilaminocarbonilmetoxifenil)-N2-(3-aminosulfonil-4-metilfenil)-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-(3-metil-(1H)-pirazol-5-il)metilenooxifenil]-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-N4-[4-(1,3-dimetil-(1H)-pirazol-5-il)metilenooxifenil]-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-N4-[4-(1-bencil-3-metil-(1H)-pirazol-5-il)metilenooxifenil]-5-fluoro-2,4- pirimidindiamina; si p >= 1 y R2 es cloro, entonces R4 y R5 no son ni un hidrógeno ni un metilo;

Description

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N4-(4-Acrilamidometilfenil)-N2-(3-aminosulfonil-4-metilfenil)-5-fluoro-2,4-pirimidindiamina;
N2-(3-Aminosulfonilfenil)-5-fluoro-N-4-[4(1-metilpirazolil-3-aminocarbonilmetileno)fenil]-2,4pirimidindiamina; N2-(3-Aminosulfonilfenil)-N4-[(1-etilpirazolil-5-aminocarbonilmetileno)fenil]-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-5-N4-[(1-etilpirazolil-5-aminocarbonilmetileno)fenil]-5-fluoro-2,4
pirimidindiamina; N4-{4-[2-(Aminocarboniloxi)etil]fenil}-N2-(3-aminosulfonil-4-clorofenil)-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-N4-{4-[2-(dimetilaminocarboniloxi)etil]fenil}-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-N4-{4-[2-(dimetilaminocarboniloxi)etil]fenil}-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-clorofenil)-N4-{4-[2-(dimetilaminocarboniloxi)etil]fenil}-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-{4-[2-(metilaminocarboniloxi)etil]fenil}-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-5-fluoro-N4-{4-[2-(metilaminocarboniloxi)etil]fenil}-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-clorofenil)-5-fluoro-N4-{4-[2-(metilaminocarboniloxi)etil]fenil}-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-clorofenil)-N4-(4-bencilfenil)-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[4-(1-oxido-4piridilmetil)fenil]-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-(2-metil-1-imidazolilmetil)fenil]-2,4-pirimidindiamina; 5-Fluoro-N2-[3-(N-metilaminosulfonil)-4-metilfenil]-N4-[4-(2-metil-1-imidazolilmetil)fenil]-2,4
pirimidindiamina; N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[4-(2-metil-1-imidazolilmetil)fenil]-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[4-(3-metil-1,2,4-oxadiazol-5-il)etilenofenil]-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-5-fluoro-N4-(4-tiomorfolinometilenofenil)-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-(4-tiomorfolinometilenofenil)-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metiloxifenil)-5-fluoro-N4-(4-tiomorfolinometilenofenil)-2, 4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-5-fluoro-N4-{4-[(1,1-dioxotiomorfolin-4-il-)metil]fenil}-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-{4-[(1,1-dioxotiomorfolin-4-il-)metil]fenil}-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metiloxifenil)-5-fluoro-N4-{4-[(1,1-dioxotiomorfolin-4-il-)metil]fenil}-2,4
pirimidindiamina; N2-(3-aminosulfonil)fenil-N4-(3-etilaminocarbonilaminometil)fenil-5-fluoro-2,4-pirimidindiamina; N2-(3-aminosulfonil-4-metil)fenil-N4-(3-etilaminocarbonilaminometil)fenil-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil]-N4-(4-etilaminocarbonilaminometilfenil)-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-N4-(4-etilaminocarbonilaminometilfenil)-5-fluoro-2,4-pirimidindiamina; N2-(3-aminosulfonil)fenil-N4-[4-(2-etilaminocarbonilamino)etil]fenil-5-fluoro-2,4-pirimidindiamina; N2-(3-aminosulfonil-4-metil)fenil-N4-[4-(2-etilaminocarbonilamino)etil]fenil-5-fluoro-2,4-pirimidindiamina; N2-(3-aminosulfonil)fenil-N4-[4-(N-carbamoil-N-propil)aminometil]fenil-5-fluoro-2,4-pirimidindiamina; N2-(3-aminosulfonil-4-metil)fenil-N4-[4-(N-carbamoil-N-propil)aminometil]fenil-5-fluoro-2,4
pirimidindiamina;
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N2-(3-Aminosulfonil-4-metilfenil)-N4-(3-cianometil-1-metil-indol-5-il)-5-fluoro-2,4-pirimidindiamina; N4-[4-(1-Acetil-4-piperizinil)carbonilfenil]-N2-(4-aminosulfonilfenil)-5-fluoro-2,4-pirimidindiamina;
5 N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-(1-metanosulfonil-4-piperazinil)carbonilfenil]-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-(4-tiomorfolinil)carbonilfenil]-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-N4-[4-(1,1-dioxo-4-tiomorfolinil)carbonilfenil]-5-fluoro-2,4-pirimidindiamina;
10 N4-(4-Acetiltiometilcarbonilfenil)-N2-(4-aminosulfonilfenil)-5-fluoro-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-N4-[3,5-dimetil-4-(4-metilpiperazin-1-il]fenil)-5-fluoro-2,4-pirimidindiamina;
15 N2-(4-Aminosulfonilfenil)-5-fluoro-N4-(5-metoxicarbonil-tiofeno-2-il)-2,4-pirimidindiamina; 5-Fluoro-N2-[3-N-(metil)aminosulfonil-4-metilfenil]-N4-[4-(2-piridinil)-3-clorometilenooxifenil]-2,4pirimidindiamina;
20 6-carbonilmetoxi-N4-(3,4-diclorofenil)-N2-(3-N,N-dietilaminosulfonil-6-metoxifenil)-2,4-pirimidindiamina; 6-carbonilmetoxi-(3-N,N-dietilaminosulfonil-6-metoxifenil)-N4-[3-oxo-benz[1,4]oxazin-6-il]-2,4pirimidindiamina; y 25 N2-(3-Aminosulfonilfenil)-5-fluoro-N4-(2-metilindol-6-ilmetileno)-2,4-pirimidindiamina. Otra realización de la invención proporciona un compuesto seleccionado entre el grupo que consiste en:
Comp.
nombre
I-1
N2-(4-Aminosulfonilfenil)-N4-(3-cianometoxi-4,5-dimetoxifenil)-5-fluoro-2,4-pirimidindiamina;
I-2
N2-(3-Aminosulfonil-4-metilfenil)-N4-(3-cianometoxi-4,5-dimetoxifenil)-5-fluoro-2,4-pirimidindiamina;
I-3
N2-(4-Aminosulfonil)fenil-N4-(3-cianometoxi)fenil-5-fluoro-2,4-pirimidindiamina;
I-4
N2-(3-Aminosulfonil)fenil-N4-(3-cianometoxi)fenil-5-fluoro-2,4-pirimidindiamina;
I-5
N4-(3-Cianometoxi)fenil-5-fluoro-N2-[3-(4-metilpiperazin-1-il)sulfonil]fenil-2,4-pirimidindiamina;
I-6
N4-(3-Cianometoxi)fenil-5-fluoro-N2-[4-(4-metilpiperazin-1-il)sulfonil]fenil-2,4-pirimidindiamina;
I-7
N2-(4-Aminosulfonil-3-metoxi)fenil-N4-(3-cianometoxi)fenil-5-fluoro-2,4-pirimidindiamina;
I-8
N2-(3-Aminosulfonil-4-iso-propilfenil)-N4-(4-cianometilenooxifenil)-5-fluoro-2,4-pirimidindiamina;
I-9
N2-[3-Aminosulfonil-4-(4-metilpiperazin-1-il)fenil]-5-fluoro-N4-(4-cianometilenooxifenil)-2,4-pirimidindiamina;
I-10
N2-[3-Aminosulfonil-4-(4-metilpiperazin-1-il)fenil]-5-fluoro-N4-(4-cianometilenooxi-3-fluorofenil)-2,4pirimidindiamina;
I-11
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-(4-cianometilenooxi-3-fluorofenil)-2,4-pirimidindiamina;
I-12
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-(4-cianometilenooxi-3-fluorofenil)-2,4-pirimidindiamina;
I-13
N2-(3-Aminosulfonilfenil)-5-bromo-N4-(4-cianometilenooxifenil)-2,4-pirimidindiamina;
I-14
N2-(3-Aminosulfonil-4-metilfenil)-5-bromo-N4-(4-cianometilenooxifenil)-2,4-pirimidindiamina;
I-15
N2-(3-Aminosulfonilfenil)-N4-(4-cianometilenooxifenil)-5-trimetilsililacetileno-2,4-pirimidindiamina;
I-16
N2-(4-Aminosulfonil)fenil-N4-(4-cianometoxi)fenil-5-fluoro-2,4-pirimidindiamina;
I-17
N2-(3-Aminosulfonil)fenil-N4-(4-cianometoxi)fenil-5-fluoro-2,4-pirimidindiamina;
I-18
N4-(4-Cianometoxi)fenil-5-fluoro-N2-[4-(4-metilpiperazin-1-il)sulfonil]fenil-2,4-pirimidindiamina;
I-19
N4-(4-Cianometoxi)fenil-5-fluoro-N2-[3-(4-metilpiperazin-1-il)sulfonil]fenil-2,4-pirimidindiamina;
I-20
N2-(3-Aminosulfonil-4-metil)fenil-N4-(4-cianometoxi)fenil-5-fluoro-2,4-pirimidindiamina;
I-21
N2-(3-Aminosulfonil-4-clorofenil)-N4-(4-cianometoxi)fenil-5-fluoro-2,4-pirimidindiamina;
I-22
N2-(4-Aminosulfonil)fenil-N4-(4-cianometoxi-3-metil)fenil-5-fluoro-2,4-pirimidindiamina;
I-23
N2-(3-Aminosulfonil)fenil-N4-(4-cianometoxi-3-metil)fenil-5-fluoro-2,4-pirimidindiamina;
I-24
N2-(3-Aminosulfonil-4-metil)fenil-N4-(4-cianometoxi-3-metil)fenil-5-fluoro-2,4-pirimidindiamina;
I-25
N2-(4-Aminosulfonil)fenil-N4-(4-cianometoxi-3,5-dimetil)fenil-5-fluoro-2,4-pirimidindiamina;
I-26
N2-(3-Aminosulfonil)fenil-N4-(4-cianometoxi-3,5-dimetil)fenil-5-fluoro-2,4-pirimidindiamina;
I-27
N2-(3-Aminosulfonil-4-metil)fenil-N4-(4-cianometoxi-3,5-dimetil)fenil-5-fluoro-2,4-pirimidindiamina;
I-28
N2-(4-Aminosulfonil-3-metoxifenil)-N4-(4-cianometoxi)fenil-5-fluoro-2,4-pirimidindiamina;
I-29
N2-(4-Aminosulfonil-3-metoxi)fenil-N4-(4-cianometoxi-3-metil)fenil-5-fluoro-2,4-pirimidindiamina;
I-30
N4-(4-Cianometilenooxi)fenil-5-fluoro-N2-(4-metil-3-propionilaminosulfonil)fenil-2,4-pirimidindiamina (68);
I-31
Sal sódica de N4-(4-cianometilenooxi)fenil-5-fluoro-N2-(4-metil-3-propionilaminosulfonil)fenil-2,4pirimidindiamina (69);
I-32
N2-(4-Aminosulfonil-3-metoxi)fenil-N4-(4-cianometoxi-3,5-dimetil)fenil-5-fluoro-2,4-pirimidindiamina;
I-33
N2-(3-Aminosulfonil-4-fluoro)fenil-N4-(4-cianometoxi)fenil-5-fluoro-2,4-pirimidindiamina;
21
Comp.
nombre
I-34
N2-(3-Aminosulfonil-4-fluoro)fenil-N4-(4-cianometoxi-3-metil)fenil-5-fluoro-2,4-pirimidindiamina;
I-35
N2-(3-Aminosulfonil-4-fluoro)fenil-N4-(4-cianometoxi-3,5-dimetil)fenil-5-fluoro-2,4-pirimidindiamina;
I-36
N2-(3-Acetilaminosulfonil-4-metil)fenil-N4-(4-cianometilenooxi)fenil-5-fluoro-2,4-pirimidindiamina;
I-37
N4-(4-Cianometilenooxi)fenil-5-fluoro-N2-(3-isobutirilaminosulfonil-4-metil)fenil-2,4-pirimidindiamina;
I-38
Sal sódica de N2-(3-acetilaminosulfonil-4-metil)fenil-N4-(4-cianometilenooxi)fenil-5-fluoro-2,4pirimidindiamina;
I-39
Sal sódica de N4-(4-cianometilenooxi)fenil-5-fluoro-N2-(3-isobutirilaminosulfonil-4-metil)fenil-2,4pirimidindiamina;
I-40
N4-(4-Cianometoxi-3,5-dimetilfenil)-5-fluoro-N2-[4-(4-metilpiperazin-1-il)sulfonilfenil]-2,4-pirimidindiamina;
I-41
N2-(4-Aminosulfonilfenil)-N4-(3-cloro-4-cianometoxifenil)-5-fluoro-2,4-pirimidindiamina;
I-42
N2-(3-Aminosulfonilfenil)-N4-(3-cloro-4-cianometoxifenil)-5-fluoro-2,4-pirimidindiamina;
I-43
N2-(3-Aminosulfonil-4-metilfenil)-N4-(3-cloro-4-cianometoxifenil)-5-fluoro-2,4-pirimidindiamina;
I-44
N2-(4-Aminosulfonilfenil)-N4-(4-cianometoxi-3-fluorofenil)-5-fluoro-2,4-pirimidindiamina;
I-45
N2-(4-Aminosulfonilfenil)-N4-(4-cianometoxi-3-metoxifenil)-5-fluoro-2,4-pirimidindiamina;
I-46
N2-(3-Aminosulfonilfenil)-N4-(4-cianometoxi-3-metoxifenil)-5-fluoro-2,4-pirimidindiamina;
I-47
N2-(3-Aminosulfonil-4-metilfenil)-N4-(4-cianometoxi-3-metoxifenil)-5-fluoro-2,4-pirimidindiamina;
I-48
N4-(4-Cianometoxi-3-fluorofenil)-5-fluoro-N2-(4-metil-3-propionilaminosulfonilfenil)-2,4-pirimidindiamina;
I-49
Sal sódica de N4-(4-cianometoxi-3-fluorofenil)-5-fluoro-N2-(4-metil-3-propionilaminosulfonilfenil)-2,4pirimidindiamina;
I-50
N2-(3-Aminosulfonilfenil)-N4-(4-cianometoxi-3-hidroximetilfenil)-5-fluoro-2,4-pirimidindiamina;
I-51
N2-(3-Aminosulfonil-4-metilfenil)-N4-(4-cianometoxi-3-hidroximetilfenil)-5-fluoro-2,4-pirimidindiamina;
I-52
N2-(4-Aminosulfonilfenil)-N4-[4-cianometoxi-3-(1-cianometilpirazol-3-il)fenil]-5-fluoro-2,4-pirimidindiamina;
I-53
N2-(3-Aminosulfonilfenil)-N4-[4-cianometoxi-3-(1-cianometilpirazol-3-il)fenil]-5-fluoro-2,4-pirimidindiamina;
I-54
N2-(3-Aminosulfonil-4-metilfenil]-N4-[4-cianometoxi-3-(1-cianometilpirazol-3-il)fenil]-5-fluoro-2,4pirimidindiamina;
I-55
N2-(3-Aminosulfonilpirid-4-il)-N4-(4-cianometoxifenil)-5-fluoro-2,4-pirimidindiamina;
I-56
N2-(3-Aminosulfonil-4-metoxifenil)-N4-(4-cianometoxifenil)-5-fluoro-2,4-pirimidindiamina;
I-57
N2-(4-Aminosulfonilfenil)-N4-(4-cianometoxifenil-5)-metil-2,4-pirimidindiamina;
I-58
N2-(3-Aminosulfonilfenil)-N4-(4-cianometoxifenil)-5-metil-2,4-pirimidindiamina;
I-59
N2-(3-Aminosulfonil-4-metilfenil)-N4-(4-cianometoxifenil)-5-metil-2,4-pirimidindiamina;
I-60
N2-(4-Aminosulfonil)fenil-N4-[4-(1-ciano)etoxi-3-metil]fenil-5-fluoro-2,4-pirimidindiamina racémica;
I-61
N2-(3-Aminosulfonil)fenil-N4-[4-(1-ciano)etoxi-3-metil]fenil-5-fluoro-2,4-pirimidindiamina racémica;
I-62
N2-(3-Aminosulfonil-4-metil)fenil-N4-[4-(1-ciano)etoxi-3-metil]fenil-5-fluoro-2,4-pirimidindiamina racémica;
I-63
N2-(4-Aminosulfonil)fenil-N4-[4-(1-ciano)etoxi-3,5-dimetil]fenil-5-fluoro-2,4-pirimidindiamina racémica;
I-64
N2-(4-Aminosulfonil-3-metoxi)fenil-N4-[4-(1-ciano)etoxi-3-metil]fenil-5-fluoro-2,4-pirimidindiamina racémica;
I-65
N2-(3-Aminosulfonil)fenil-N4-[4-(1-ciano)etoxi]fenil-5-fluoro-2,4-pirimidindiamina racémica;
I-66
N2-(4-Aminosulfonil)fenil-N4-[4-(1-ciano)etoxi]fenil-5-fluoro-2,4-pirimidindiamina racémica;
I-67
N2-(3-Aminosulfonil-4-metil)fenil-N4-[4-(1-ciano)etoxi]fenil-5-fluoro-2,4-pirimidindiamina racémica;
I-68
N2-(3-Aminosulfonil-4-fluoro)fenil-N4-[4-(1-ciano)etoxi]fenil-5-fluoro-2,4-pirimidindiamina racémica;
I-69
N2-(3-Aminosulfonil-4-fluoro)fenil-N4-[4-(1-ciano)etoxi-3-metil]fenil-5-fluoro-2,4-pirimidindiamina racémica;
I-70
N2-(4-Aminosulfonil-3-metoxi)fenil-N4-[4-(1-ciano)etoxi]fenil-5-fluoro-2,4-pirimidindiamina racémica;
I-71
N2-(3-Aminosulfonil)fenil-N4-[4-(1-ciano)etoxi-3,5-dimetil]fenil-5-fluoro-2,4-pirimidindiamina racémica;
I-72
N2-(3-Aminosulfonil-4-metil)fenil-N4-[4-(1-ciano)etoxi-3,5-dimetil]fenil-5-fluoro-2,4-pirimidindiamina racémica;
I-73
N2-(3-Aminosulfonil-4-metil)fenil-N4-[4-(1-ciano-1-metil)etoxi]fenil-5-fluoro-2,4-pirimidindiamina;
I-74
N2-(3-Aminosulfonil-4-fluoro)fenil-N4-[4-(1-ciano-1-metil)etoxi]fenil-5-fluoro-2,4-pirimidindiamina;
I-75
N2-(4-Aminosulfonil)fenil-N4-[4-(1-ciano-1-metil)etoxi]fenil-5-fluoro-2,4-pirimidindiamina;
I-76
N2-(3-Aminosulfonil)fenil-N4-[4-(1-ciano-1-metil)etoxi]fenil-5-fluoro-2,4-pirimidindiamina;
I-77
N2-(4-Aminosulfonil-3-metoxi)fenil-N4-[4-(1-ciano-1-metil)etoxi]fenil-5-fluoro-2,4-pirimidindiamina;
I-78
N2-(3-Aminosulfonilfenil)-N4-[4-(N-cianoacetil)aminofenil]-5-fluoro-2,4-pirimidindiamina.
I-79
N2-(3-Aminosulfonil-4-metilfenil)-N4-[4-(N-cianoacetil)aminofenil]-5-fluoro-2,4-pirimidindiamina;
I-80
N2-(3-Aminosulfonilfenil)-5-fluoroN4-[3-metil-4-(N-cianoacetil)aminofenil]-2,4-pirimidindiamina;
I-81
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoroN4-[3-metil4-(N-cianoacetil)aminofenil]-2,4-pirimidindiamina;
I-82
N2-(3-Aminosulfonilfenil)-N4-[3-cloro-4-(N-cianoacetil)aminofenil]-5-fluoro-2,4-pirimidindiamina;
I-83
N2-(3-Aminosulfonil-4-metilfenil)-N4-[3-cloro-4-(N-cianoacetil)aminofenil]-5-fluoro-2,4-pirimidindiamina;
I-84
N2-(3-Aminosulfonilfenil)-5-fluoroN4-[3-metoxi-4-(N-cianoacetil)aminofenil]-2,4-pirimidindiamina;
I-85
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoroN4-[3-metoxi-4-(N-cianoacetil)aminofenil]-2,4-pirimidindiamina;
I-86
N2-(3-Aminosulfonilfenil)-N4-[4-(N-cianoacetil-N-metil)aminofenil]-5-fluoro-2,4-pirimidindiamina;
I-87
N2-(3-Aminosulfonil-4-metilfenil)-N4-[4-(N-cianoacetil-N-metil)aminofenil]-5-fluoro-2,4-pirimidindiamina;
I-88
N4-(3-Aminocarbonilmetoxi)fenil-N2-(3-aminosulfonil)fenil-5-fluoro-2,4-pirimidindiamina;
I-89
N4-(3-Aminocarbonilmetoxi)fenil-5-fluoro-N2-[3-(4-metilpiperazin-1-il)sulfonil]fenil-2,4-pirimidindiamina;
I-90
N4-(3-Aminocarbonilmetoxi)fenil-N2-(3-aminosulfonil-4-metil)fenil-5-fluoro-2,4-pirimidindiamina;
22
Comp.
nombre
I-91
N4-(3-Aminocarbonilmetoxi)fenil-N2-(4-aminosulfonil)fenil-5-fluoro-2,4-pirimidindiamina;
I-92
N4-(4-Aminocarbonilmetoxi-3-metil)fenil-N2-(3-aminosulfonil)fenil-5-fluoro-2,4-pirimidindiamina;
I-93
N4-(4-Aminocarbonilmetoxi-3,5-dimetil)fenil-N2-(3-aminosulfonil)fenil-5-fluoro-2,4-pirimidindiamina;
I-94
N4-(4-Aminocarbonilmetoxi)fenil-N2-(3-aminosulfonil-4-metil)fenil-5-fluoro-2,4-pirimidindiamina;
I-95
N4-(4-Aminocarbonilmetoxi-3-metil)fenil-N2-(3-aminosulfonil-4-metil)fenil-5-fluoro-2,4-pirimidindiamina;
I-96
N4-(4-Aminocarbonilmetoxi-3,5-dimetil)fenil-N2-(3-aminosulfonil-4-metil)fenil-5-fluoro-2,4-pirimidindiamina;
I-97
N4-(4-Aminocarbonilmetoxi-3-clorofenil)-N2-(4-aminosulfonilfenil)-5-fluoro-2,4-pirimidindiamina;
I-98
N4-(4-Aminocarbonilmetoxi-3-clorofenil)-N2-(3-aminosulfonilfenil)-5-fluoro-2,4-pirimidindiamina;
I-99
N4-(4-Aminocarbonilmetoxi-3-clorofenil)-N2-(3-aminosulfonil-4-metilfenil)-5-fluoro-2,4-pirimidindiamina;
I-100
N4-(4-Aminocarbonilmetoxi-3-fluorofenil)-N2-(4-aminosulfonilfenil)-5-fluoro-2,4-pirimidindiamina;
I-101
N4-(4-Aminocarbonilmetoxi-3-fluorofenil)-N2-(3-aminosulfonilfenil)-5-fluoro-2,4-pirimidindiamina;
I-102
N4-(4-Aminocarbonilmetoxi-3-fluorofenil)-N2-(3-aminosulfonil-4-metilfenil)-5-fluoro-2,4-pirimidindiamina;
I-103
N4-(4-Aminocarbonilmetoxi-3-metoxifenil)-N2-(4-aminosulfonilfenil)-5-fluoro-2,4-pirimidindiamina;
I-104
N4-(4-Aminocarbonilmetoxi-3-metoxifenil)-N2-(3-aminosulfonilfenil)-5-fluoro-2,4-pirimidindiamina;
I-105
N4-(4-Aminocarbonilmetoxi-3-metoxifenil)-N2-(3-aminosulfonil-4-metilfenil)-5-fluoro-2,4-pirimidindiamina;
I-106
N4-(4-Aminocarbonilmetoxi-3-hidroximetilfenil)-N2-(3-aminosulfonil-4-metilfenil)-5-fluoro-2,4pirimidindiamina;
I-107
N4-(4-Aminocarbonilmetoxi-3-hidroximetilfenil]-N2-(3-aminosulfonilfenil)-5-fluoro-2,4-pirimidindiamina;
I-108
N4-(4-Aminocarbonilmetoxifenil)-N2-(4-aminosulfonilfenil)-5-metil-2,4-pirimidindiamina;
I-109
N4-(4-Aminocarbonilmetoxifenil)-N2-(3-aminosulfonilfenil)-5-metil-2,4-pirimidindiamina;
I-110
N4-(4-Aminocarbonilmetoxifenil)-N2-(3-aminosulfonil-4-metilfenil)-5-metil-2,4-pirimidindiamina;
I-111
N4-(4-Aminocarbonilmetoxi)fenil-N2-(3-aminosulfonil)fenil-5-fluoro-2,4-pirimidindiamina;
I-112
N4-(4-Aminocarbonilmetoxi)fenil-5-fluoro-N2-[3-(4-metilpiperazin-1-il)sulfonil]fenil-2,4-pirimidindiamina;
I-113
N4-(4-Aminocarbonilmetoxi-3-metil)fenil-N2-(4-aminosulfonil)fenil-5-fluoro-2,4-pirimidindiamina;
I-114
N4-(4-Aminocarbonilmetoxi-3,5-dimetil)fenil-N2-(4-aminosulfonil)fenil-5-fluoro-2,4-pirimidindiamina;
I-115
N4-(4-Aminocarbonilmetoxi)fenil-N2-(4-aminosulfonil)fenil-5-fluoro-2,4-pirimidindiamina;
I-116
N4-[4-(1-Aminocarbonil)etoxi]fenil-N2-(4-aminosulfonil)fenil-5-fluoro-2,4-pirimidindiamina racémica;
I-117
N4-[4-(1-Aminocarbonil)etoxi]fenil-N2-(3-aminosulfonil)fenil-5-fluoro-2,4-pirimidindiamina racémica;
I-118
N4-[4-(1-Aminocarbonil)etoxi]fenil-N2-(3-aminosulfonil-4-metil)fenil-5-fluoro-2,4-pirimidindiamina;
I-119
N4-[4-(1-Aminocarbonil)etoxi-3-metil]fenil-N2-(4-aminosulfonil)fenil-5-fluoro-2,4-pirimidindiamina racémica;
I-120
N4-[4-(1-Aminocarbonil)etoxi-3-metil]fenil-N2-(3-aminosulfonil)fenil-5-fluoro-2,4-pirimidindiamina racémica;
I-121
N4-[4-(1-Aminocarbonil)etoxi-3-metil]fenil-N2-(3-aminosulfonil-4-metil)fenil-5-fluoro-2,4-pirimidindiamina racémica;
I-122
N4-[4-(1-Aminocarbonil)etoxi-3,5-dimetil]fenil-N2-(4-aminosulfonil)fenil-5-fluoro-2,4-pirimidindiamina racémica;
I-123
N4-[4-(1-Aminocarbonil)etoxi-3,5-dimetil]fenil-N2-(3-aminosulfonil)fenil-5-fluoro-2,4-pirimidindiamina racémica;
I-124
N4-[4-(1-Aminocarbonil)etoxi-3,5-dimetil]fenil-N2-(3-aminosulfonil-4-metil)fenil-5-fluoro-2,4-pirimidindiamina racémica;
I-125
N4-[4-(1-Aminocarbonil-1-metil)etoxi]fenil-N2-(4-aminosulfonil)fenil-5-fluoro-2,4-pirimidindiamina;
I-126
N4-[4-(1-Aminocarbonil-1-metil)etoxi]fenil-N2-(3-aminosulfonil)fenil-5-fluoro-2,4-pirimidindiamina;
I-127
N4-[4-(1-Aminocarbonil-1-metil)etoxi]fenil-N2-(3-aminosulfonil-4-metil)fenil-5-fluoro-2,4-pirimidindiamina;
I-128
N2-(4-Aminosulfonilfenil)-N4-(4-dimetilaminocarbonilmetoxifenil)-5-fluoro-2,4-pirimidindiamina;
I-129
N2-(3-Aminosulfonilfenil)-N4-(4-dimetilaminocarbonilmetoxifenil)-5-fluoro-2,4-pirimidindiamina;
I-130
N2-(3-Aminosulfonil-4-metilfenil)-N4-(4-dimetilaminocarbonilmetoxifenil)-5-fluoro-2,4-pirimidindiamina;
I-131
N2-(4-Aminosulfonilfenil)-N4-(3-cloro-4-dimetilaminocarbonilmetoxifenil)-5-fluoro-2,4-pirimidindiamina;
I-132
N2-(3-Aminosulfonilfenil)-N4-(3-cloro-4-dimetilaminocarbonilmetoxifenil)-5-fluoro-2,4-pirimidindiamina;
I-133
N2-(3-Aminosulfonil-4-metilfenil)-N4-(3-cloro-4-dimetilaminocarbonilmetoxifenil)-5-fluoro-2,4pirimidindiamina;
I-134
N2-(4-Aminosulfonilfenil)-N4-(3-cloro-4-dimetilaminocarbonilmetoxifenil)-5-metil-2,4-pirimidindiamina;
I-135
N2-(3-Aminosulfonilfenil)-N4-(3-cloro-4-dimetilaminocarbonilmetoxifenil)-5-metil-2,4-pirimidindiamina;
I-136
N2-(3-Aminosulfonil-4-metilfenil)-N4-(3-cloro-4-dimetilaminocarbonilmetoxifenil)-5-metil-2,4pirimidindiamina;
I-137
N2-(4-Aminosulfonilfenil)-N4-(4-dimetilaminocarbonilmetoxi-3-fluorofenil)-5-metil-2,4-pirimidindiamina;
I-138
N2-(3-Aminosulfonilfenil)-N4-(4-dimetilaminocarbonilmetoxi-3-fluorofenil)-5-metil-2,4-pirimidindiamina;
I-139
N2-(3-Aminosulfonil-4-metilfenil)-N4-(4-dimetilaminocarbonilmetoxi-3-fluorofenil)-5-metil-2,4pirimidindiamina;
I-140
N2-(3-Aminosulfonil-4-clorofenil)-N4-(3-cloro-4-dimetilaminocarbonilmetoxifenil)-5-fluoro-2,4pirimidindiamina;
I-141
N2-(3-Aminosulfonil-4-clorofenil)-N4-(3-cloro-4-dimetilaminocarbonilmetoxifenil)-5-metil-2,4pirimidindiamina;
23
Comp.
nombre
I-142
N2-(3-Aminosulfonil-4-clorofenil)-N4-(4-dimetilaminocarbonilmetoxi-3-fluorofenil)-5-metil-2,4pirimidindiamina;
I-143
N2-(4-Aminosulfonilfenil)-5-fluoro-N4-(4-metilaminocarbonilmetoxifenil)-2,4-pirimidindiamina;
I-144
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-(4-metilaminocarbonilmetoxifenil)-2,4-pirimidindiamina;
I-145
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-(4-metilaminocarbonilmetoxifenil)-2,4-pirimidindiamina;
I-146
N2-(4-Aminosulfonilfenil)-N4-(3-cloro-4-metilaminocarbonilmetoxifenil)-5-fluoro-2,4-pirimidindiamina;
I-147
N2-(3-Aminosulfonilfenil)-N4-(3-cloro-4-metilaminocarbonilmetoxifenil)-5-fluoro-2,4-pirimidindiamina;
I-148
N2-(3-Aminosulfonil-4-metilfenil)-N4-(3-cloro-4-metilaminocarbonilmetoxifenil)-5-fluoro-2,4-pirimidindiamina;
I-149
N2-(4-Aminosulfonilfenil)-N4-(3-cloro-4-metilaminocarbonilmetoxifenil)-5-metil-2,4-pirimidindiamina;
I-150
N2-(3-Aminosulfonilfenil)-N4-(3-cloro-4-metilaminocarbonilmetoxifenil)-5-metil-2,4-pirimidindiamina;
I-151
N2-(3-Aminosulfonil-4-metilfenil)-N4-(3-cloro-4-metilaminocarbonilmetoxifenil)-5-metil-2,4-pirimidindiamina;
I-152
N2-(3-Aminosulfonil-4-clorofenil)-N4-(3-cloro-4-metilaminocarbonilmetoxifenil)-5-fluoro-2,4-pirimidindiamina;
I-153
N2-(3-Aminosulfonil-4-clorofenil)-N4-(3-cloro-4-metilaminocarbonilmetoxifenil)-5-metil-2,4-pirimidindiamina;
I-154
N2-(4-Aminosulfonilfenil)-N4-(3-fluoro-4-metilaminocarbonilmetoxifenil)-5-metil-2,4-pirimidindiamina;
I-155
N2-(3-Aminosulfonilfenil)-N4-(3-fluoro-4-metilaminocarbonilmetoxifenil)-5-metil-2,4-pirimidindiamina;
I-156
N2-(3-Aminosulfonil-4-metilfenil)-N4-(3-fluoro-4-metilaminocarbonilmetoxifenil)-5-metil-2,4-pirimidindiamina;
I-157
N4-(4-Alilaminocarbonilmetoxifenil)-N2-(4-aminosulfonilfenil)-5-fluoro-2,4-pirimidindiamina;
I-158
N4-(4-Alilaminocarbonilmetoxifenil)-N2-(3-aminosulfonilfenil)-5-fluoro-2,4-pirimidindiamina;
I-159
N4-(4-Alilaminocarbonilmetoxifenil)-N2-(3-aminosulfonil-4-metilfenil)-5-fluoro-2,4-pirimidindiamina;
I-160
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-(2-piridinil)metilenooxifenil]-2,4-pirimidindiamina;
I-161
5-Fluoro-N2-[3-(N-metilaminosulfonil)-4-metilfenil]-5-fluoro-N4-[4-(2-piridinil)metilenooxifenil]-2,4pirimidindiamina;
I-162
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[4-(2-piridinil)metilenooxifenil]-2,4-pirimidindiamina;
I-163
N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-(2-piridinil)metilenooxifenil]-2,4-pirimidindiamina;
I-164
N2-(3-Aminosulfonilpirid-4-il)-5-fluoro-N4-[4-(2-piridinil)metilenooxifenil]-2,4-pirimidindiamina;
I-165
N2-[4-(2-N,N-Dietilaminoetil)aminosulfonilfenil)-5-fluoro-N4-[4-(2-piridinil)metilenooxifenil]-2,4pirimidindiamina;
I-166
N2-[3-(2-N,N-Dietilaminoetil)aminosulfonilfenil)-5-fluoro-N4-[4-(2-piridinil)metilenooxifenil]-2,4pirimidindiamina;
I-167
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[(4-((piridin-2-il)metoxi)-3-metilfenil)]-2,4-pirimidindiamina;
I-168
N2-(3-Amino-4-metilsulfonilfenil)-5-fluoro-N4-[(4-((piridin-2-il)metoxi)-3-metilfenil)]-2,4-pirimidindiamina;
I-169
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[4-(2-piridinil)-3-fluorometilenooxifenil]-2,4-pirimidindiamina;
I-170
5-Fluoro-N2-[3-N-(metil)aminosulfonil-4-metilfenil]-N4-[4-(2-piridinil)-3-metilmetilenooxifenil]-2,4pirimidindiamina;
I-171
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[4-(2-piridinil)-3-clorometilenooxifenil]-2,4-pirimidindiamina;
I-172
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-(2-piridinil)-3-fluorometilenooxifenil]-2,4-pirimidindiamina;
I-173
5-Fluoro-N2-[3-N-(metil)aminosulfonil-4-metilfenil]-N4-[4-(2-piridinil)-3-fluorometilenooxifenil]-2,4pirimidindiamina;
I-174
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-(2-piridinil)-3-clorometilenooxifenil]-2,4-pirimidindiamina;
I-175
N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-(2-piridinil)-3-clorometilenooxifenil]-2,4-pirimidindiamina;
I-176
N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-(2-piridinil)-3-metilmetilenooxifenil]-2,4-pirimidindiamina;
I-177
N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-(2-piridinil)-3-fluorometilenooxifenil]-2,4-pirimidindiamina;
I-178
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-(3-piridilmetoxi)fenil]-2,4-pirimidindiamina;
I-179
N2-(3-Aminosulfonilfenil)-5-metil-N4-[4-(2-piridinil)metilenooxifenil]-2,4-pirimidindiamina;
I-180
5-Metil-N2-[3-(N-metilaminosulfonil)-4-metilfenil]-N4-[4-(2-piridinil)metilenooxifenil]-2,4-pirimidindiamina;
I-181
N2-(4-Aminosulfonilfenil)-5-metil-N4-[4-(2-piridinil)metilenooxifenil]-2,4-pirimidindiamina;
I-182
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[3-(3-piridinil)metilenooxifenil]-2,4-pirimidindiamina;
I-183
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[3-(3-piridinil)metilenooxifenil]-2,4-pirimidindiamina;
I-184
5-Fluoro-N2-[3-(N-metilaminosulfonil)-4-metilfenil]-5-fluoro-N4-[3-(3-piridinil)metilenooxifenil]-2,4pirimidindiamina;
I-185
N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[3-(3-piridinil)metilenooxifenil]-2,4-pirimidindiamina;
I-186
N2-[4-(2-N,N-Dietilaminoetil)aminosulfonilfenil)-5-fluoro-N4-[3-(3-piridinil)metilenooxifenil]-2,4pirimidindiamina;
I-187
N2-[3-(2-N,N-Dietilaminoetil)aminosulfonilfenil)-5-fluoro-N4-[3-(3-piridinil)metilenooxifenil]-2,4pirimidindiamina;
I-188
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[4-(3-piridinil)metilenooxifenil]-2,4-pirimidindiamina;
I-189
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-(3-piridinil)metilenooxifenil]-2,4-pirimidindiamina;
I-190
5-Fluoro-N2-[3-(N-metilaminosulfonil)-4-metilfenil]-5-fluoro-N4-[4-(3-piridinil)metilenooxifenil]-2,4pirimidindiamina;
I-191
N2-[4-(2-N,N-Dietilaminoetil)aminosulfonilfenil)-5-fluoro-N4-[4-(3-piridinil)metilenooxifenil]-2,4pirimidindiamina;
I-192
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[4-(3-piridinil)-metilenotiofenil]-2,4-pirimidindiamina;
24
Comp.
nombre
I-193
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[4-(4-piridinil)metilenooxifenil]-2,4-pirimidindiamina;
I-194
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-(4-piridinil)metilenooxifenil]-2,4-pirimidindiamina;
I-195
5-Fluoro-N2-[3-(N-metilaminosulfonil)-4-metilfenil]-5-fluoro-N4-[4-(4-piridinil)metilenooxifenil]-2,4pirimidindiamina;
I-196
Sal clorhidrato de N2-(3-aminosulfonilfenil)-5-fluoro-N4-4-[(2-piridinil)metilenooxifenil]-2,4-pirimidindiamina;
I-197
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-(3-metil-(1H)-pirazol-5-il)metilenooxifenil]-2,4pirimidindiamina;
I-198
N2-(3-Aminosulfonil-4-metilfenil)-N4-[4-(1,3-dimetil-(1H)-pirazol-5-il)metilenooxifenil]-5-fluoro-2,4pirimidindiamina;
I-199
N2-(3-Aminosulfonil-4-metilfenil)-N4-[4-(1-bencil-3-metil-(1H)-pirazol-5-il)metilenooxifenil]-5-fluoro-2,4pirimidindiamina;
I-200
N2-(3-Aminosulfonil-4-fluorofenil)-5-fluoro-N4-[4-(2,4-dihidro-3-oxo-1,2,4-triazol-5-il)metilenooxifenil]-2,4pirimidindiamina (76);
I-201
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[4-(2,4-dihidro-3-oxo-1,2,4-triazol-5-il)metilenooxifenil]-2,4pirimidindiamina;
I-202
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-(2,4-dihidro-3-oxo-1,2,4-triazol-5-il)metilenooxifenil]-2,4pirimidindiamina;
I-203
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[4-metil-3-(2-morfolinoetiloxi)fenil]-2,4-pirimidindiamina;
I-204
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-metil-3-(2-morfolinoetiloxi)fenil]2,4-pirimidindiamina;
I-205
N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-(2-morfolinoetiloxi)fenil)-2,4-pirimidindiamina;
I-206
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[4-(2-morfolinoetiloxi)fenil-2,4-pirimidindiamina;
I-207
5-Fluoro-N2-(3-morfolinosulfonilfenil)-N4-[4-(2-morfolinoetiloxi)fenil]-2,4-pirimidindiamina;
I-208
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[4-metil-3-(2-morfolinocarbonilmetilenooxi)fenil]-2,4-pirimidindiamina;
I-209
N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-metil-3-(2-morfolinocarbonilmetilenooxi)fenil]-2,4-pirimidindiamina;
I-210
N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-(2-morfolin-4-il-2-oxo-etoxi)fenil]-2,4-pirimidindiamina;
I-211
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[4-(2-morfolin-4-il-2-oxo-etoxi)fenil]-2,4-pirimidindiamina;
I-212
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-(2-morfolin-4-il-2-oxo-etoxi)fenil]-2,4-pirimidindiamina;
I-213
5-Fluoro-N4-(4-metoxicarbonilmetoxifenil)-N2-(4-metil-3-propionilaminosulfonilfenil)-2,4-pirimidindiamina;
I-214
N2-(3-Aminosulfonil-4-metilfenil)-N4-[3-(5-metilisoxazol-3-il)metilenooxifenil]-2,4-pirimidindiamina;
I-215
5-Fluoro-N2-[3-(N-metoxicarbonilmetileno)aminosulfonilfenil]-N4-[4-(5-metilisoxazol-3-il)metilenooxifenil]2,4-pirimidindiamina;
I-216
N2-(3-Aminosulfonil-5-cloro-4-metilfenil)-5-fluoro-N4-[3-metil-4-(5-metilisoxazol-3-il)metilenooxifenil]-2,4pirimidindiamina;
I-217
N2-(3-Aminosulfonil-4-fluoro-5-metilfenil)-5-fluoro-N4-[4-(5-metilisoxazol-3-il)metilenooxifenil]-2,4pirimidindiamina;
I-218
N2-(3-Aminosulfonil-4-cloro-5-metilfenil)-5-fluoro-N4-[4-(5-metilisoxazol-3-il)metilenooxifenil]-2,4pirimidindiamina;
I-219
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-(5-metilisoxazol-3-il)metilenooxifenil]-2,4-pirimidindiamina;
I-220
N2-(3-Aminosulfonil-4-clorofenil)-5-fluoro-N4-[4-(5-metilisoxazol-3-il)metilenooxifenil]-2,4-pirimidindiamina;
I-221
N2-(3-Aminosulfonil-4-metilfenil)-N4-[3-cloro-4-(5-metilisoxazol-3-il)metilenooxifenil]-5-fluoro-2,4pirimidindiamina;
I-222
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[3-fluoro-4-(5-metilisoxazol-3-il)metilenooxifenil]-2,4pirimidindiamina;
I-223
N2-(3-Aminosulfonil-5-cloro-4-metilfenil)-5-fluoro-N4-[3-fluoro-4-(5-metilisoxazol-3-il)metilenooxifenil]-2,4pirimidindiamina;
I-224
N2-(3-Aminosulfonil-4-fluoro-5-metilfenil)-5-fluoro-N4-[3-fluoro-4-(5-metilisoxazol-3-il)metilenooxifenil]-2,4pirimidindiamina;
I-225
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-metil-N4-[4-(5-metilisoxazol-3-il)metilenooxifenil]-2,4pirimidindiamina;
I-226
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[3-fluoro-4-(5-metilisoxazol-3-il)metilenooxifenil]-N4-metil-2,4pirimidindiamina;
I-227
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-metoxicarbonilmetil-N4-[4-(5-metilisoxazol-3il)metilenooxifenil]-2,4-pirimidindiamina;
I-228
5-Fluoro-N4-[4-(5-metilisoxazol-3-il)metilenooxifenil]-N2-(4-metil-3-propionilaminosulfonilfenil)-2,4pirimidindiamina;
I-229
5-Fluoro-N4-[4-(5-metilisoxazol-3-il)metilenooxifenil]-N2-(4-metil-3-(2-metilpropionil)aminosulfonilfenil)-2,4pirimidindiamina;
I-230
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[4-(5-metilisoxazol-3-il)metilenooxifenil]-2,4-pirimidindiamina (59, X= H);
I-231
N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-(3-metil-1,2,4-oxadiazol-5-il)metilenooxifenil]-2,4-pirimidindiamina;
I-232
N2-(3-Acetamidosulfonilfenil)-5-fluoro-N4-[4-(5-metilisoxazol-3-il)metilenooxifenil]-2,4-pirimidindiamina;
I-233
N2-(3-Aminosulfonil-4-fluorofenil)-5-fluoro-N4-[4-(5-metilisoxazol-3-il)metilenooxifenil]-2,4-pirimidindiamina;
25
Comp.
nombre
I-234
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[3-metil-4-(5-metilisoxazol-3-il)metilenooxifenil]-2,4pirimidindiamina;
I-235
5-Fluoro-N2-[3-(N-metil)aminosulfonil-4-metilfenil]-N4-[4-(5-metilisoxazol-3-il)metilenooxifenil]-2,4pirimidindiamina;
I-236
5-Fluoro-N4-[4-(5-metilisoxazol-3-il)metilenooxifenil]-N2-(3-N-propanamido)sulfonilfenil)]-2,4pirimidindiamina;
I-237
N2-(3-Aminosulfonil-4-fluorofenil)-5-fluoro-N4-[3metil-4-(5-metilisoxazol-3-il)metilenooxifenil]-2,4pirimidindiamina;
I-238
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[3-metil-4-(5-metilisoxazol-3-il)metilenooxifenil]-2,4-pirimidindiamina;
I-239
5-Fluoro-N2-[3-N-(metil)aminosulfonil-4-metilfenil]-N4-[3-metil-4-(5-metilisoxazol-3-il)metilenooxifenil]-2,4pirimidindiamina;
I-240
N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[3metil-4-(5-metilisoxazol-3-il)metilenooxifenil]-2,4-pirimidindiamina;
I-241
N2-[3-(2-N,N-Dietilaminoetil)aminosulfonilfenil)-5-fluoro-N4-[4-(5-metilisoxazol-3-il)metilenooxifenil]-2,4pirimidindiamina;
I-242
Sal sódica de 5-fluoro-N4-[4-(5-metilisoxazol-3-il)metilenooxifenil]-N2-(3-N-propanamido)sulfonilfenil)]-2,4pirimidindiamina;
I-243
Sal sódica de N2-(3-acetamidosulfonilfenil)-5-fluoro-N4-[4-(5-metilisoxazol-3-il)metilenooxifenil]-2,4pirimidindiamina;
I-244
N2-[3-(2-N,N-Dietilaminoetil)aminosulfonilfenil)-5-fluoro-N4-[3-metil-4-(5-metilisoxazol-3-il)metilenooxifenil]2,4-pirimidindiamina;
I-245
N2-[4-(2-N,N-Dietilaminoetil)aminosulfonilfenil)-5-fluoro-N4-[3-metil-4-(5-metilisoxazol-3-il)metilenooxifenil]2,4-pirimidindiamina;
I-246
N2-[4-(2-N,N-Dietilaminoetil)aminosulfonilfenil)-5-fluoro-N4-[4-(5-metilisoxazol-3-il)metilenooxifenil]-2,4pirimidindiamina;
I-247
N2-{3-[(N-5-Metil-1,3-dioxoleno-2-ona-4-il)metileno]aminosulfonilfenil}-5-fluoro-N4-[4-(5-metilisoxazol-3il)metilenooxifenil]-2,4-pirimidindiamina;
I-248
N2-{3-[N-N-Di-[(5-Metil-1,3-dioxoleno-2-ona-4-il)metileno]]aminosulfonilfenil}-5-fluoro-N4-[4-(5-metilisoxazol3-il)metilenooxifenil]-2,4-pirimidindiamina;
I-249
N2-{3-[N-N-Di-[(5-t-Butil-1,3-dioxoleno-2-ona-4-il)metileno]]aminosulfonilfenil}-5-fluoro-N4-[4-(5metilisoxazol-3-il)metilenooxifenil]-2,4-pirimidindiamina;
I-250
N2-{3-[(N-5-t-Butil-1,3-dioxoleno-2-ona-4-il)metileno]aminosulfonilfenil}-5-fluoro-N4-[4-(5-metilisoxazol-3il)metilenooxifenil]-2,4-pirimidindiamina;
I-251
N2-[3-Aminosulfonil-4-(4-metilpiperazin-1-il)fenil]-5-fluoro-N4-[2-fluoro-4-(5-metilisoxazol-3il)metilenooxifenil]-2,4-pirimidindiamina;
I-252
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[3-(3-metil-1,2,4-oxadiazol-5-il)metilenooxifenil]-2,4-pirimidindiamina (60);
I-253
N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[3-(3-metil-1,2,4-oxadiazol-5-il)metilenooxifenil]-2,4-pirimidindiamina;
I-254
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[3-(3-metil-1,2,4-oxadiazol-5-il)metilenooxifenil]-2,4pirimidindiamina;
I-255
5-Fluoro-N2-[3-(N-metilaminosulfonil)-4-metilfenil]-N4-[3-(3-metil-1,2,4-oxadiazol-5-il)metilenooxifenil]-2,4pirimidindiamina;
I-256
N2-[4-(2-N,N-Dietilaminoetil)aminosulfonilfenil)-5-fluoro-N4-[3-(3-metil-1,2,4-oxadiazol-5-il)metilenooxifenil]2,4-pirimidindiamina;
I-257
N2-{3-[(N-5-Metil-1,3-dioxoleno-2-ona-4-il)metileno]aminosulfonilfenil}-5-fluoro-N4-[4-(3-metil-1,2,4oxadiazol-5-il)metilenooxifenil]-2,4-pirimidindiamina;
I-258
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[4-(3-metil-1,2,4-oxadiazol-5-il)metilenooxifenil]-2,4-pirimidindiamina;
I-259
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-(3-metil-1,2,4-oxadiazol-5-il)metilenooxifenil]-2,4pirimidindiamina;
I-260
5-Fluoro-N2-[3-N-(metil)aminosulfonil-4-metilfenil)-N4-[4-(3-metil-1,2,4-oxadiazol-5-il)metilenooxifenil]-2,4pirimidindiamina;
I-261
N2-[3-(2-N,N-Dietilaminoetil)aminosulfonilfenil)-5-fluoro-N4-[3-(3-metil-1,2,4-oxadiazol-5-il)metilenooxifenil]2,4-pirimidindiamina;
I-262
5-Fluoro-N4-[4-(3-metil-1,2,4-oxadiazol-3-il)metilenooxifenil]-N2-[(3-N-propanamido)sulfonilfenil)]-2,4pirimidindiamina;
I-263
N2-[4-(2-N,N-Dietilaminoetil)aminosulfonilfenil)-5-fluoro-N4-[4-(3-metil-1,2,4-oxadiazol-5-il)metilenooxifenil]2,4-pirimidindiamina;
I-264
5-Fluoro-N4-[4-(3-metil-1,2,4-oxadiazol-3-il)metilenooxifenil]-N2-[(3-N-propanamido)sulfonilfenil)]-2,4pirimidindiamina;
I-265
N2-(3-Aminosulfonil-4-cloro-5-metilfenil)-5-fluoro-N4-[4-(3-metil-1,2,4-oxadiazol-5-il)metilenooxifenil]-2,4pirimidindiamina;
I-266
N2-(3-Aminosulfonil-4-fluorofenil)-5-fluoro-N4-[4-(3-metil-1,2,4-oxadiazol-5-il)metilenooxifenil]-2,4pirimidindiamina;
26
Comp.
nombre
I-267
N2-(3-Aminosulfonil-4-fluorofenil)-5-fluoro-N4-[4-(3-metil-1,2,4-oxadiazol-5-il)etilenofenil]-2,4pirimidindiamina;
I-268
N2-(4-Aminosulfonilfenil)-5-fluoro-N4-(4-[3-metil-1,2,4-oxadiazol-5-il]metilenooxifenil)-2,4-pirimidindiamina;
I-269
5-fluoro-N2-(4-N-metilaminosulfonil)-3-metoxifenil-N4-(4-trifluorometoxi-3-clorofenil)-2,4-pirimidindiamina;
I-270
5-Fluoro-N4-(3-hidroxifenil)-N2-(4-N-metilaminosulfonil)-3-metoxifenil]-2,4-pirimidindiamina;
I-271
N2-(5-N,N-Dietilaminosulfonil-2-metoxifenil)-5-fluoro-N4-(4-[3-metil-1,2,4-oxadiazol-5-il]metilenooxifenil)-2,4pirimidindiamina;
I-272
5-Fluoro-N4-(4-[3-metil-1,2,4-oxadiazol-5-il]metilenooxifenil)-N2-(5-piperidinsulfonilfenil)-2,4pirimidindiamina;
I-273
Sal sódica de 5-fluoro-N4-[4-(3-metil-1,2,4-oxadiazol-3-il)metilenooxifenil]-N2-[(3-Npropanamido)sulfonilfenil)]-2,4-pirimidindiamina;
I-274
5-Fluoro-N4-[4-(5-metil-1,2,4-oxadiazol-3-il)metoxi]fenil-N2-[3-(4-metilpiperazin-1-il)sulfonil]fenil-2,4pirimidindiamina;
I-275
N2-(4-Aminosulfonil)fenil-5-fluoro-N4-[4-(5-metil-1,2,4-oxadiazol-3-il)metoxi]fenil-2,4-pirimidindiamina;
I-276
N2-(3-Aminosulfonil)fenil-5-fluoro-N4-[4-(5-metil-1,2,4-oxadiazol-3-il)metoxi]fenil-2,4-pirimidindiamina;
I-277
N2-(3-aminosulfonilfenil)-5-fluoro-N4-[4-(5-metil-1,3,4-oxadiazol-2-il)metilenooxifenil]-2,4-pirimidindiamina (71);
I-278
N2-(3-Aminosulfonil-4-fluorofenil)-5-fluoro-N4-[4-(5-metil-1,3,4-oxadiazol-2-il)metilenooxifenil]-2,4pirimidindiamina;
I-279
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-(5-metil-1,3,4-oxadiazol-2-il)metoxifenil]-2,4pirimidindiamina;
I-280
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-(2-metiltiazol-4-il)metilenooxifenil]-2,4-pirimidindiamina;
I-281
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[4-(2-metiltiazol-4-il)metilenooxifenil]-2,4-pirimidindiamina;
I-282
5-Fluoro-N2-[3-(N-metilaminosulfonil)-4-metilfenil]-N4-[4-(2-metiltiazol-4-il)metilenooxifenil]-2,4pirimidindiamina;
I-283
N2-[3-(2-N,N-Dietilaminoetil)aminosulfonilfenil)-5-fluoro-N4-[4-(2-metiltiazol-4-il)metilenooxifenil]-2,4pirimidindiamina;
I-284
N2-[4-(2-N,N-Dietilaminoetil)aminosulfonilfenil)-5-fluoro-N4-[4-(2-metiltiazol-4-il)metilenooxifenil]-2,4pirimidindiamina;
I-285
N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-(2-metiltiazol-4-il)metilenooxifenil]-2,4-pirimidindiamina;
II-1
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-{3-[(1-metilpiperidin-3-il)oxi]fenil}-2,4-pirimidindiamina racémica;
II-2
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-{3-[(1-metilpiperidin-4-il)oxi]fenil}-2,4-pirimidindiamina;
II-3
N2-(3-Aminosulfonil-4-metilfenil)-N4-{3-cloro-4-[(1-metilpiperidin-3-il)oxi]fenil}-5-fluoro-2,4-pirimidindiamina racémica;
II-4
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-{4-[(1-metilpiperidin-3-il)oxi]fenil}-2,4-pirimidindiamina racémica;
II-5
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-{3-metil-4-[(1-metilpiperidin-4-il)oxi]fenil}-2,4-pirimidindiamina;
II-6
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-{4-[(1-metilpiperidin-4-il)oxi]-3-trifluorometilfenilil-2,4pirimidindiamina;
II-7
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-{4-[(1-metilpiperidin-4-il)oxi]fenil}-2,4-pirimidindiamina;
II-8
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-{3-cloro-4-[(1-metilpiperidin-4-il)oxi]fenil}-2,4-pirimidindiamina;
II-9
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-(N-metilpirrolidin-3-iloxifenil)-2,4-pirimidindiamina;
II-10
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-(N-metilpirrolidin-3-iloxifenil)-2,4-pirimidindiamina;
II-11
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[4-(3-piridiloxi)fenil]-2,4-pirimidindiamina;
II-12
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-(3-piridiloxi)fenil]-2,4-pirimidindiamina;
II-13
5-Fluoro-N2-[3-N-(metilaminosulfonil)-4-metilfenil]-N4-[4-(3-piridiloxi)fenil]-2,4-pirimidindiamina;
II-14
N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-(3-piridiloxi)fenil]-2,4-pirimidindiamina;
II-15
N2-[3,5-bis(Aminosulfonil)fenil)-5-fluoro-N4-[4-(3-piridiloxi)fenil]-2,4-pirimidindiamina;
II-16
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-(4-piridiloxi)fenil]-2,4-pirimidindiamina;
II-17
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[4-(4-piridiloxi)fenil]-2,4-pirimidindiamina;
II-18
5-Fluoro-N2-[3-(N-metilaminosulfonil)-4-metilfenil]-5-fluoro-N4-[4-(4-piridiloxi)fenil]-2,4-pirimidindiamina;
II-19
N2-(3-Aminocarbonil-5-metilfenil)-5-fluoro-N2-[4-(1-metilpirazol-3-il)amidofenil)-2,4-pirimidindiamina;
II-20
N2-(3-Aminocarbonil-5-metilfenil)-5-fluoro-N2-[4-(1-etilpirazol-5-il)amidofenil)-2,4-pirimidindiamina;
II-21
N2-(3-Aminocarbonil-5-metilfenil)-5-fluoro-N2-[4-(1-metilpirazol-5-il)amidofenil)-2,4-pirimidindiamina;
II-22
N2-(3-Aminocarbonil-5-metilfenil)-5-fluoro-N2-[4-(1H-pirazol-5-il)amidofenil)-2,4-pirimidindiamina;
III-1
5-Fluoro-N2-[3-(N-metilaminosulfonil)-4-metilfenil]-5-fluoro-N4-(4-cianometilfenil)-2,4-pirimidindiamina;
III-2
N2-[4-(2-N,N-Dietilaminoetil)aminosulfonilfenil)-5-fluoro-N4-(4-cianometilfenil)-2,4-pirimidindiamina;
III-3
N2-(4-Aminosulfonil)fenil-N4-(4-cianometil)fenil-5-fluoro-2,4-pirimidindiamina;
III-4
N2-(3-Aminosulfonil)fenil-N4-(4-cianometil)fenil-5-fluoro-2,4-pirimidindiamina;
III-5
N4-(4-Cianometil)fenil-5-fluoro-N2-[3-(4-metilpiperazin-1-il)sulfonil]fenil-2,4-pirimidindiamina;
III-6
N4-(4-Cianometil)fenil-5-fluoro-N2-[4-(4-metilpiperazin-1-il)sulfonil]fenil-2,4-pirimidindiamina;
27
Comp.
nombre
III-7
N2-(3-Aminosulfonil-4-metil)fenil-N4-(4-cianometil)fenil-5-fluoro-2,4-pirimidindiamina;
III-8
N2-(3-Aminosulfonil-4-cloro)fenil-N4-(4-cianometil)fenil-5-fluoro-2,4-pirimidindiamina;
III-9
N2-(4-Aminosulfonil-3-metoxi)fenil-N4-(4-cianometil)fenil-5-fluoro-2,4-pirimidindiamina;
III
N2-(3-Aminosulfonil-4-fluoro)fenil-N4-(4-cianometil)fenil-5-fluoro-2,4-pirimidindiamina;
III-11
N2-(3-Aminosulfonil-4-metilfenil)-N4-(4-cianoetilenofenil)-5-metil-2,4-pirimidindiamina;
III-12
N2-(3-Aminosulfonil-4-clorofenil)-N4-[4-(2-cianoetil)fenil]-5-metil-2,4-pirimidindiamina;
III-13
N2-(3-Aminosulfonil-4-clorofenil)-N4-[4-(2-cianoetil)fenil]-5-fluoro-2,4-pirimidindiamina;
III-14
N2-(3-aminosulfonilfenil)-N4-[4-(cianoetileno)fenil]-5-fluoro-2,4-pirimidindiamina;
III-15
N2-(3-Aminosulfonil-4-metilfenil)-N4-[4-(cianoetileno)fenil]-5-fluoro-2,4-pirimidindiamina;
III-16
N2-(3-Aminosulfonil-4-fluorofenil)-N4-[4-(cianoetileno)fenil]-5-fluoro-2,4-pirimidindiamina;
III-17
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-(2-cianoetil)-3-fluorofenil]-2,4-pirimidindiamina;
III-18
N2-(3-Aminosulfonilfenil)-N4-[4-(2-cianoetil)-3-fluorofenil]-5-fluoro-2,4-pirimidindiamina;
III-19
N2-(3-Aminosulfonil-4-metilfenil)-N4-[4-(2-cianoetil)-3-metilfenil]-5-fluoro-2,4-pirimidindiamina;
III
N2-(3-Aminosulfonilfenil)-N4-[4-(2-cianoetil)-3-metilfenil]-5-fluoro-2,4-pirimidindiamina;
III-21
N2-(3-Aminosulfonil-4-metilfenil)-N4-[3-cloro-4-(2-cianoetil)fenil]-5-fluoro-2,4-pirimidindiamina;
III-22
N2-(3-Aminosulfonilfenil)-N4-[3-cloro-4-(2-cianoetil)fenil]-5-fluoro-2,4-pirimidindiamina;
III-23
N2-(3-Aminosulfonil-4-metilfenil)-N4-(4-cianoetileno-2-metilfenil)-5-fluoro-2,4-pirimidindiamina
III-24
N2-(3-Aminosulfonilfenil)-N4-(4-cianoetileno-2-metilfenil)-5-fluoro-2,4-pirimidindiamina
III-25
N2-(3-Aminosulfonil-4-metilfenil)-N4-(4-cianoetileno-3-metoxifenil)-5-fluoro-2,4-pirimidindiamina
III-26
N2-(3-Aminosulfonilfenil)-N4-(4-cianoetileno-2-metilfenil)-5-fluoro-2,4-pirimidindiamina
III-27
N2-(4-Aminosulfonilfenil)-N4-(4-cianoetilenofenil)-5-metil-2,4-pirimidindiamina y su profármaco
III-28
N4-(3-Cloro-4-cianoetileno-fenil)-5-fluoro-N2-(4-metil-3-propionilaminosulfonilfenil)-2,4-pirimidindiamina
III-29
Sal sódica de N4-(3-cloro-4-cianoetileno-fenil)-5-fluoro-N2-(4-metil-3-propionilaminosulfonilfenil)-2,4pirimidindiamina
III
N4-(4-Cianoetileno-3-trifluorometilfenil)-5-fluoro-N2-(4-metil-3-aminosulfonilfenil)-2,4-pirimidindiamina
III-31
N4-(4-Cianoetileno-3-trifluorometilfenil)-5-fluoro-N2-(3-aminosulfonilfenil)-2,4-pirimidindiamina
III-32
N4-(4-Aminocarbonilaminometilfenil)-N2-(4-aminosulfonilfenil)-5-fluoro-2,4-pirimidindiamina;
III-33
N4-(4-Aminocarbonilaminometilfenil)-N2-(3-aminosulfonilfenil)-5-fluoro-2,4-pirimidindiamina;
III-34
N4-(4-Aminocarbonilaminometilfenil)-N2-(3-aminosulfonil-4-metilfenil)-5-fluoro-2,4-pirimidindiamina;
III-35
N2-(4-aminosulfonil)fenil-N4-(4-etilcarbonilaminometil)fenil-5-fluoro-2,4-pirimidindiamina;
III-36
N2-(3-aminosulfonil)fenil-N4-(4-etilcarbonilaminometil)fenil-5-fluoro-2,4-pirimidindiamina;
III-37
N2-(3-aminosulfonil-4-metil)fenil-N4-(4-etilcarbonilaminometil)fenil-5-fluoro-2,4-pirimidindiamina;
III-38
N2-(4-aminosulfonil)fenil-N4-(3-ciclopropilcarbonilaminometil)fenil-5-fluoro-2,4-pirimidindiamina;
III-39
N2-(3-aminosulfonil)fenil-N4-(3-ciclopropilcarbonilaminometil)fenil-5-fluoro-2,4-pirimidindiamina;
III
N2-(3-aminosulfonil-4-metil)fenil-N4-(3-ciclopropilcarbonilaminometil)fenil-5-fluoro-2,4-pirimidindiamina;
III-41
N2-(4-aminosulfonil)fenil-N4-(4-ciclopropilcarbonilaminometil)fenil-5-fluoro-2,4-pirimidindiamina;
III-42
N2-(3-aminosulfonil)fenil-N4-(4-ciclopropilcarbonilaminometil)fenil-5-fluoro-2,4-pirimidindiamina;
III-43
N2-(3-aminosulfonil-4-metil)fenil-N4-(4-ciclopropilcarbonilaminometil)fenil-5-fluoro-2,4-pirimidindiamina;
III-44
N4-(4-Acrilamidometilfenil)-N2-(4-aminosulfonilfenil)-5-fluoro-2,4-pirimidindiamina;
III-45
N4-(4-Acrilamidometilfenil)-N2-(3-aminosulfonilfenil)-5-fluoro-2,4-pirimidindiamina;
III-46
N4-(4-Acrilamidometilfenil)-N2-(3-aminosulfonil-4-metilfenil)-5-fluoro-2,4-pirimidindiamina;
III-47
N4-[4-(2-Aminocarboxiletileno)fenil]-5-fluoro-N2-(4-metil-3-aminosulfonilfenil)-2,4-pirimidindiamina;
III-48
N4-[4-(2-Aminocarboxiletileno)fenil]-N2-(3-aminosulfonilfenil)-5-fluoro-2,4-pirimidindiamina
III-49
N4-[4-(2-Aminocarboxiletileno)fenil]-N2-(4-aminosulfonilfenil)-5-fluoro-2,4-pirimidindiamina
III
N2-(3-Aminosulfonilfenil)-5-fluoro-N-4-[4(1-metilpirazolil-3-aminocarbonilmetileno)fenil]-2,4-pirimidindiamina;
III-51
N2-(3-Aminosulfonilfenil)-N4-[(1-etilpirazolil-5-aminocarbonilmetileno)fenil]-5-fluoro-2,4-pirimidindiamina;
III-52
N2-(3-Aminosulfonil-4-metilfenil)-5-N4-[(1-etilpirazolil-5-aminocarbonilmetileno)fenil]-5-fluoro-2,4pirimidindiamina;
III-53
N4-{4-[2-(Aminocarboniloxi)etil]fenil}-N2-(3-aminosulfonil-4-metilfenil)-5-fluoro-2,4-pirimidindiamina;
III-54
N4-{4-[2-(Aminocarboniloxi)etil]fenil}-N2-(3-aminosulfonilfenil)-5-fluoro-2,4-pirimidindiamina;
III-55
N4-{4-[2-(Aminocarboniloxi)etil]fenil}-N2-(3-aminosulfonil-4-clorofenil)-5-fluoro-2,4-pirimidindiamina;
III-56
N2-(3-Aminosulfonil-4-metilfenil)-N4-{4-[2-(dimetilaminocarboniloxi)etil]fenil}-5-fluoro-2,4-pirimidindiamina;
III-57
N2-(3-Aminosulfonilfenil)-N4-{4-[2-(dimetilaminocarboniloxi)etil]fenil}-5-fluoro-2,4-pirimidindiamina;
III-58
N2-(3-Aminosulfonil-4-clorofenil)-N4-{4-[2-(dimetilaminocarboniloxi)etil]fenil}-5-fluoro-2,4-pirimidindiamina;
III-59
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-{4-[2-(metilaminocarboniloxi)etil]fenil}-2,4-pirimidindiamina;
III
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-{4-[2-(metilaminocarboniloxi)etil]fenil}-2,4-pirimidindiamina;
III-61
N2-(3-Aminosulfonil-4-clorofenil)-5-fluoro-N4-{4-[2-(metilaminocarboniloxi)etil]fenil}-2,4-pirimidindiamina;
III-62
N2-(3-Aminosulfonilfenil)-N4-(4-bencilfenil)-5-fluoro-2,4-pirimidindiamina;
III-63
N2-(3-Aminosulfonil-4-metilfenil)-N4-(4-bencilfenil)-5-fluoro-2,4-pirimidindiamina;
III-64
N2-(3-Aminosulfonil-4-clorofenil)-N4-(4-bencilfenil)-5-fluoro-2,4-pirimidindiamina;
III-65
N2-(3-Aminosulfonil-4-metoxi-5-metilfenil)-N4-(4-bencilfenil)-5-fluoro-2,4-pirimidindiamina;
III-66
N2-(3-Aminosulfonil-4-metoxifenil)-5-fluoro-N4-[4-(4-piridinilmetil)fenil]-2,4-pirimidindiamina;
28
Comp.
nombre
III-67
N2-[4-(2-N,N-Dietilaminoetil)aminosulfonilfenil)-5-fluoro-N4-[4-(4-piridinilmetil)fenil]-2,4-pirimidindiamina;
III-68
5-Fluoro-N4-[4-(4-piridinilmetil)fenil]-N2-[(3-N-propanamido)sulfonilfenil)]-2,4-pirimidindiamina;
III-69
Sal sódica de 5-Fluoro-N4-[4-(4-piridinilmetil)fenil]-N2-[(3-N-propanamido)sulfonilfenil)]-2,4-pirimidindiamina;
III-70
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[4-(4-piridinilmetil)fenil]-2,4-pirimidindiamina;
III-71
N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-(4-piridinilmetil)fenil]-2,4-pirimidindiamina;
III-72
N2-[4-(2-N,N-Dietilaminoetil)aminosulfonilfenil)-5-fluoro-N4-[4-(4-piridinilmetil)fenil]-2,4-pirimidindiamina;
III-73
Sal clorhidrato de N2-(3-aminosulfonilfenil)-5-fluoro-N4-[4-(4-piridilmetil)fenil]-2,4-pirimidindiamina;
III-74
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-(4-piridinilmetil)fenil]-2,4-pirimidindiamina;
III-75
5-Fluoro-N2-[3-(N-metilaminosulfonil)-4-metilfenil]-5-fluoro-N4-[4-(4-piridinilmetil)fenil]-2,4-pirimidindiamina;
III-76
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[4-(4-piridinil)fenetil]-2,4-pirimidindiamina;
III-77
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-(4-piridinil)fenetil]-2,4-pirimidindiamina;
III-78
5-Fluoro-N2-[3-N-(metil)aminosulfonil-4-metilfenil]-N4-[4-(4-piridinil)fenetil]-2,4-pirimidindiamina;
III-79
N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-(4-piridinil)fenetil]-2,4-pirimidindiamina;
III-80
Preparación de N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[4-(1-oxido-4-piridilmetil)fenil]-2,4-pirimidindiamina;
III-81
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[4-(1-imidazolilmetil)fenil]-2,4-pirimidindiamina;
III-82
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-(1-imidazolilmetil)fenil]-2,4-pirimidindiamina;
III-83
5-Fluoro-N2-[3-(N-metilaminosulfonil)-4-metilfenil]-5-fluoro-N4-[4-(1-imidazolilmetil)fenil]-2,4pirimidindiamina;
III-84
N2-[4-(2-N,N-Dietilaminoetil)aminosulfonilfenil)-5-fluoro-N4-[4-(1-imidazolilmetil)fenil]-2,4-pirimidindiamina;
III-85
Clorhidrato de 5-fluoro-N2-[3-(N-metilaminosulfonil)-4-metilfenil]-N4-[4-(1-imidazolilmetil)fenil]-2,4pirimidindiamina
III-86
Diclorhidrato de 5-fluoro-N2-[3-(N-metilaminosulfonil)-4-metilfenil]-N4-[4-(1-imidazolilmetil)fenil]-2,4pirimidindiamina
III-87
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[4-(1-imidazolil)fenetil]-2,4-pirimidindiamina;
III-88
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-(1-imidazolil)fenetil]-2,4-pirimidindiamina;
III-89
5-Fluoro-N2-[3-(N-metilaminosulfonil)-4-metilfenil]-N4-[4-(1-imidazolil)fenetil]-2,4-pirimidindiamina;
III-90
N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-(1-imidazolil)fenetil]-2,4-pirimidindiamina;
III-91
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-(2-metil-1-imidazolilmetil)fenil]-2,4-pirimidindiamina;
III-92
N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-(2-metil-1-imidazolilmetil)fenil]-2,4-pirimidindiamina;
III-93
5-Fluoro-N2-[3-(N-metilaminosulfonil)-4-metilfenil]-N4-[4-(2-metil-1-imidazolilmetil)fenil]-2,4pirimidindiamina;
III-94
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[4-(2-metil-1-imidazolilmetil)fenil]-2,4-pirimidindiamina;
III-95
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-{4-[1-(1,2,3-triazolil)metil]fenil}-2,4-pirimidindiamina;
III-96
N2-4-Aminosulfonilfenil)-5-fluoro-N4-{4-[1-(1,2,3-triazolil)metil]fenil}-2,4-pirimidindiamina;
III-97
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-{4-[1-(1,2,3-triazolil)metil]fenil}-2,4-pirimidindiamina;
III-98
5-Fluoro-N2-[3-(N-metilaminosulfonil)-4-metilfenil]-N4-{4-[1-(1,2,3-triazolil)metil]fenil}-2,4-pirimidindiamina;
III-99
N2-(4-Aminosulfonilfenil)-5-fluoro-N4-{4-[1-(1,2,4-triazolil)metil]fenil}-2,4-pirimidindiamina;
III-100
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-{4-[1-(1,2,4-triazolil)metil]fenil}-2,4-pirimidindiamina;
III-101
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-{4-[1-(1,2,4-triazolil)metil]fenil}-2,4-pirimidindiamina;
III-102
5-Fluoro-N2-[3-(N-metilaminosulfonil)-4-metilfenil]-N4-{4-[1-(1,2,4-triazolil)metil]fenil}-2,4-pirimidindiamina;
III-103
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-(4-N-morfolinometilenofenil)-2,4-pirimidindiamina;
III-104
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-(4-N-morfolinometilenofenil)-2,4-pirimidindiamina;
III-105
N2-(3-Aminosulfonil-4-metilenooxifenil)-5-fluoro-N4-(4-N-morfolinometilenofenil)-2,4-pirimidindiamina;
III-106
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[4-(3-metil-1,2,4-oxadiazol-5-il)etilenofenil]-2,4-pirimidindiamina;
III-107
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-(4-tiomorfolinometilenofenil)-2,4-pirimidindiamina;
III-108
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-(4-tiomorfolinometilenofenil)-2,4-pirimidindiamina;
III-109
N2-(3-Aminosulfonil-4-metiloxifenil)-5-fluoro-N4-(4-tiomorfolinometilenofenil)-2,4-pirimidindiamina;
III-110
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-{4-[(1,1-dioxotiomorfolin-4-il-)metil]fenil}-2,4-pirimidindiamina;
III-111
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-{4-[(1,1-dioxotiomorfolin-4-il-)metil]fenil}-2,4-pirimidindiamina;
III-112
N2-(3-Aminosulfonil-4-metiloxifenil)-5-fluoro-N4-{4-[(1,1-dioxotiomorfolin-4-il-)metil]fenil}-2,4pirimidindiamina;
III-113
N4-(3-Aminocarbonilaminometil)fenil-N2-(4-aminosulfonil)fenil-5-fluoro-2,4-pirimidindiamina;
III-114
N4-(3-Aminocarbonilaminometil)fenil-N2-(3-aminosulfonil)fenil-5-fluoro-2,4-pirimidindiamina;
III-115
N4-(3-aminocarbonilaminometil)fenil-N2-(3-aminosulfonil-4-metil)fenil-5-fluoro-2,4-pirimidindiamina;
III-116
N2-(4-Aminosulfonil)fenil-N4-(3-etilaminocarbonilaminometil)fenil-5-fluoro-2,4-pirimidindiamina;
III-117
N2-(3-Aminosulfonil)fenil-N4-(3-etilaminocarbonilaminometil)fenil-5-fluoro-2,4-pirimidindiamina;
III-118
N2-(3-aminosulfonil-4-metil)fenil-N4-(3-etilaminocarbonilaminometil)fenil-5-fluoro-2,4-pirimidindiamina;
III-119
N2-(4-Aminosulfonilfenil)-N4-(4-etilaminocarbonilaminometilfenil]-5-fluoro-2,4-pirimidindiamina;
III-120
N2-(3-Aminosulfonilfenil]-N4-(4-etilaminocarbonilaminometilfenil)-5-fluoro-2,4-pirimidindiamina;
III-121
N2-(3-Aminosulfonil-4-metilfenil)-N4-(4-etilaminocarbonilaminometilfenil)-5-fluoro-2,4-pirimidindiamina;
III-122
N2-(4-aminosulfonil)fenil-N4-[4-(2-etilaminocarbonilamino)etil]fenil-5-fluoro-2,4-pirimidindiamina;
III-123
N2-(3-aminosulfonil)fenil-N4-[4-(2-etilaminocarbonilamino)etil]fenil-5-fluoro-2,4-pirimidindiamina;
29
Comp.
nombre
III-124
N2-(3-aminosulfonil-4-metil)fenil-N4-[4-(2-etilaminocarbonilamino)etil]fenil-5-fluoro-2,4-pirimidindiamina;
III-125
N2-(4-aminosulfonil)fenil-N4-[4-(N-carbamoil-N-propil)aminometil]fenil-5-fluoro-2,4-pirimidindiamina;
III-126
N2-(3-aminosulfonil)fenil-N4-[4-(N-carbamoil-N-propil)aminometil]fenil-5-fluoro-2,4-pirimidindiamina;
III-127
N2-(3-aminosulfonil-4-metil)fenil-N4-[4-(N-carbamoil-N-propil)aminometil]fenil-5-fluoro-2,4-pirimidindiamina;
III-128
Sal del ácido p-toluenosulfónico de N2-(3-aminosulfonilfenil)-5-fluoro-N4-[4-(4-piridilmetil)fenil]-2,4pirimidindiamina;
III-129
Sal del ácido metanosulfónico de N2-(3-aminosulfonilfenil)-5-fluoro-N4-[4-(4-piridilmetil)fenil]-2,4pirimidindiamina;
IV-1
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[3-(1,3-oxazol-5-il)fenil]-2,4-pirimidindiamina;
IV-2
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[3-(1,3-oxazol-5-il)fenil]-2,4-pirimidindiamina;
IV-3
N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[3-(1,3-oxazol-5-il)fenil]-2,4-pirimidindiamina;
IV-4
5-Fluoro-N2-[3-(N-metilaminosulfonil)-4-metilfenil]-N4-[3-(1,3-oxazol-5-il)fenil]-2,4-pirimidindiamina;
IV-5
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[4-(1,3-oxazol-5-il)fenil]-2,4-pirimidindiamina;
IV-6
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-(1,3-oxazol-5-il)fenil]-2,4-pirimidindiamina;
IV-7
5-Fluoro-N2-[3-(N-metilaminosulfonil)-4-metilfenil]-N4-[4-(1,3-oxazol-5-il)fenil]-2,4-pirimidindiamina;
IV-8
N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-(1,3-oxazol-5-il)fenil]-2,4-pirimidindiamina;
IV-9
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[3-(N,N-dimetilaminosulfonil)fenil]-2,4-pirimidindiamina;
IV-10
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[3-(N,N-dimetilaminosulfonil)fenil]-2,4-pirimidindiamina;
IV-11
N2-(3-Aminosulfonilenil)-5-fluoro-N4-[3-(N-metilaminosulfonil)fenil]-2,4-pirimidindiamina;
IV-12
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[3-(N-metilaminosulfonil)fenil]-2,4-pirimidindiamina;
V-1
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[2-(5-metilisoxazol-3-il)metilenooxipiridin-5-il]-2,4pirimidindiamina;
V-2
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[3-oxo-4-(2-piridilmetil)-benz[1,4]oxazin-6-il]-2,4pirimidindiamina;
V-3
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[3-oxo-4-(2-piridilmetil)-benz[1,4]oxazin-6-il]-2,4pirimidindiamina;
V-4
N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[2-metil-3-oxo-4-(4-metoxibencil)-benz[1,4]oxazin-6-il]-2,4pirimidindiamina racémica;
V-5
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[2-metil-3-oxo-4-(4-metoxibencil)-benz[1,4]oxazin-6-il]-2,4pirimidindiamina racémica;
V-6
N2-(4-Aminosulfonilfenil)-5-fluoro-N4-(3-oxo-4-cianometil-benz[1,4]oxazin-6-il]-2,4-pirimidindiamina;
V-7
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-(3-oxo-4-cianometil-benz[1,4]oxazin-6-il]-2,4-pirimidindiamina;
V-8
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[3-oxo-4-cianometil-benz[1,4]oxazin-6-il]-2,4-pirimidindiamina;
V-9
(R/S)-N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[2-metil-3-oxo-4-(4-metoxibencil)-benzo[1,4]tiazin-6-il]2,4-pirimidindiamina;
V-10
(R/S)-N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[2-metil-3-oxo-4-(4-metoxibencil)-benzo[1,4]tiazin-6-il]-2,4pirimidindiamina;
V-11
N2-(4-Aminosulfonilfenil)-5-fluoro-N4-(3-oxo-4-cianometil-benzo[1,4]tiazin-6-il)-2,4-pirimidindiamina;
V-12
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-(3-oxo-4-cianometil-benzo[1,4]tiazin-6-il)-2,4-pirimidindiamina;
V-13
N2-(3-Aminosulfonil4-metilfenil)-5-fluoro-N4-(3-oxo-4-cianometil-benzo[1,4]tiazin-6-il)-2,4-pirimidindiamina;
V-14
N2-(3-Aminosulfonil-4-metilfenil)-N4-[2,2-dimetil-3-oxo-4-cianometil-5-pirid[1,4]oxazin-7-il]-5-fluoro-2,4pirimidindiamina;
V-15
N2-(3-Aminosulfonil-4-clorofenil)-N4-[2,2-dimetil-3-oxo-4-cianometil-5-pirid[1,4]oxazin-7-il]-5-fluoro-2,4pirimidindiamina;
V-16
N2-(3-Aminosulfonil-4-metilfenil)-N4-(2-cianoetileno-benzotiofen-5-il)-5-fluoro-2,4-pirimidindiamina
V-17
N-2-(3-aminosulfonilfenil)-N4-[2,2-dimetil-3-oxo-4H-pirid[1,4]oxazin-7-il]-5-fluoro-2,4-pirimidindiamina;
V-18
N-2-(3-aminosulfonil-4-metilfenil)-N4-[2,2-dimetil-3-oxo-4H-pirid[1,4]oxazin-7-il]-5-fluoro-2,4pirimidindiamina;
V-19
(4R)-N2-(3-aminosulfonil-4-metilfenil)-N4-(1-cianometilenocarbonil-4-metilpiperidin-3-il)-5-fluoro-2,4pirimidindiamina) o (4S)-N2-(3-aminosulfonil-4-metilfenil)-N4-(1-cianometilenocarbonil-4-metilpiperidin-3-il)5-fluoro-2,4-pirimidindiamina)
VIII-1
5-Fluoro-N4-[4-(5-metilisoxazol-3-il)metilenooxifenil]-N2-(sacarin-6-il)-2,4-pirimidindiamina; y
VIII-2
N4-(3-Cloro-4-cianometilenooxifenil)-5-fluoro-N2-(5-metil-2H-1,1-dióxido-1,2,4-benzotiadiazin-7-il)-2,4pirimidindiamina.
Otra realización de la invención proporciona compuestos seleccionados entre el grupo que consiste en:
Comp.
Nombre
VI-1
5-Fluoro-N4-(3-hidroxifenil)-N2-[4-(N-metil)aminosulfonil-3-metoxifenil]-2,4-pirimidindiamina;
VI-2
N2-(3-Aminosulfonil-4-clorofenil)-N4-(3-cloro-4-metoxifenil)-5-fluoro-2,4-pirimidindiamina;
VI-3
N2-(3-Aminosulfonil-4-clorofenil)-N4-(3,4-diclorofenil)-5-fluoro-2,4-pirimidindiamina;
VI-4
N2-(3-Aminosulfonil-4-metilfenil)-N4-(3-cloro-4-metoxifenil)-5-fluoro-2,4-pirimidindiamina;
30
Comp.
Nombre
VI
N2-(3-Aminosulfonil-4-metilfenil)-N4-(4-cloro-3-metoxifenil)-5-fluoro-2,4-pirimidindiamina;
VI-6
N2-(3-Aminosulfonil-4-metilfenil)-N4-(3,4-diclorofenil)-5-fluoro-2,4-pirimidindiamina;
VI-7
N4-(3-Cloro-4-metoxifenil)-5-fluoro-N2-[3-(N-metoxicarbonilmetileno)aminosulfonilfenil]-2,4pirimidindiamina;
VI-8
N4-(3,4-Diclorofenil)-5-fluoro-N2-[3-(N-metoxicarbonilmetileno)aminosulfonilfenil]-2,4-pirimidindiamina;
VI-9
N4-(3-Cloro-4-metoxifenil)-5-fluoro-N2-[3-(4-metilpiperidin-1-il)aminosulfonilfenil]-2,4-pirimidindiamina;
VI
N4-(3,4-Diclorofenil)-5-fluoro-N2-[3-(4-metilpiperidin-1-il)aminosulfonilfenil]-2,4-pirimidindiamina;
VI-11
N2-(3-Aminosulfonil-4-clorofenil)-N4-(4-cloro-3-metoxifenil)-5-fluoro-2,4-pirimidindiamina;
VI-12
N2-[3-(N-Acetil)aminosulfonil-4-clorofenil]-N4-(3-cloro-4-metoxifenil)-5-fluoro-2,4-pirimidindiamina;
VI-13
N2-(3-Aminosulfonil-5-cloro-4-metilfenil)-N4-(3-cloro-4-metoxifenil)-5-fluoro-2,4-pirimidindiamina;
VI-14
N2-(3-Aminosulfonil-5-cloro-4-metilfenil)-N4-(3-cloro-4-trifluorometoxifenil)-5-fluoro-2,4-pirimidindiamina;
VI
N2-(3-Aminosulfonil-4-fluoro-5-metilfenil)-N4-(3-cloro-4-metoxifenil)-5-fluoro-2,4-pirimidindiamina;
VI-16
N2-(3-Aminosulfonil-4-fluoro-5-metilfenil)-N4-(3-cloro-4-trifluorometoxifenil)-5-fluoro-2,4-pirimidindiamina;
VI-17
N2-(3-Aminosulfonil-4-cloro-5-metilfenil)-N4-(3-cloro-4-metoxifenil)-5-fluoro-2,4-pirimidindiamina;
VI-18
N2-(3-Aminosulfonil-4-cloro-5-metilfenil)-N4-(3-cloro-4-trifluorometoxifenil)-5-fluoro-2,4-pirimidindiamina;
VI-19
N2-(3-Aminosulfonil-4-metilfenil)-N4-(3-cloro-4-metoxifenil)-5-fluoro-N4-metil-2,4-pirimidindiamina;
VI
N2-(3-Aminosulfonil-4-fluoro-5-metilfenil)-N4-(3-cloro-4-metoxifenil)-5-fluoro-N4-metil-2,4-pirimidindiamina;
VI-21
N2-(3-Aminosulfonil-4-cloro-5-metilfenil)-N4-(3-cloro-4-metoxifenil)-5-fluoro-N4-metil-2,4-pirimidindiamina;
VI-22
N2-(3-Aminosulfonil-4-metilfenil)-N4-(3-cloro-4-metoxifenil)-5-fluoro-N4-propil-2,4-pirimidindiamina;
VI-23
N2-(3-Aminosulfonil-4-fluoro-5-metilfenil)-N4-(3-cloro-4-metoxifenil)-5-fluoro-N4-propil-2,4-pirimidindiamina;
VI-24
N2-(3-Aminosulfonilfenil)-5-carboetoxi-N4-(N-carboetoximetileno-N-3-cloro-4-metoxifenil)-2,4pirimidindiamina;
VI
N2-(3-Aminosulfonil-4-metilfenil)-5-carboetoxi-N4-(N-carboetoximetileno-N-3-cloro-4-metoxifenil)-2,4pirimidindiamina;
VI-26
N2-(3-aminosulfonilfenil)-5-bromo-N4-(3-cloro-4-metoxifenil)-2,4-pirimidindiamina;
VI-27
2-(3-aminosulfonil-4-metilfenil)-5-bromo-N4-(3-cloro-4-metoxifenil)-2,4-pirimidindiamina;
VI-28
N2-(3-Aminosulfonilfenil)-N4-(3-cloro-4-metoxifenil)-5-trimetilsililacetileno-2,4-pirimidindiamina;
VI-29
N2-(3-Aminosulfonil-4-metoxifenil)-N4-(3-cloro-4-metoxifenil)-5-fluoro-2,4-pirimidindiamina;
VI
N2-(3-Aminosulfonil-4-metoxi-5-metilfenil)-N4-(3-cloro-4-metoxifenil)-5-fluoro-2,4-pirimidindiamina;
VI-31
N2-(3-Aminosulfonilpirid-4-il)-N4-(3-cloro-4-metoxifenil)-5-fluoro-2,4-pirimidindiamina;
VI-32
N2-(3-aminosulfonil-4-metilfenil)-5-fluoro-N4-(4-trofluorometoxifenil)-2,4-pirimidindiamina;
VI-33
N2-(3-aminosulfonilfenil)-5-fluoro-N4-(4-trofluorometoxifenil)-2,4-pirimidindiamina;
VI-34
N2-(3-Aminosulfonil-4-metoxi-5-metilfenil)-5-fluoro-N4-(4-trifluorometilfenil)-2,4-pirimidindiamina;
VI
N2-(3-Aminosulfonilfenil)-N4-(4-terc-butilfenil)-5-fluoro-2,4-pirimidindiamina;
VI-36
N2-(3-Aminosulfonil-4-metilfenil)-N4-(4-terc-butilfenil)-5-fluoro-2,4-pirimidindiamina;
VI-37
N2-(3-Aminosulfonil-4-metoxi-5-metilfenil)-N4-(4-terc-butilfenil)-5-fluoro-2,4-pirimidindiamina;
VI-38
N2-(3-Aminosulfonilfenil)-N4-(4-cloro-3-trifluorometilfenil)-5-fluoro-2,4-pirimidindiamina;
VI-39
N2-(3-Aminosulfonil-4-metil-fenil)-N4-(4-cloro-3-trifluorometilfenil)-5-fluoro-2,4-pirimidindiamina;
VI
N2-(3-Aminosulfonil-4-metoxi-5-metilfenil)-N4-(4-cloro-3-trifluorometil-fenil)-5-fluoro-2,4-pirimidindiamina;
VI-41
N2-(3-Aminosulfonil-4-clorofenil)-5-fluoro-N4-(4-trifluorofenil)-2,4-pirimidindiamina;
VI-42
N2-(3-Aminosulfonil-4-clorofenil)-5-fluoro-N4-(4-trifluorometoxifenil)-2,4-pirimidindiamina;
VI-43
N2-(3-Aminosulfonil-4-clorofenil)-N4-(4-terc-butilfenil)-5-fluoro-2,4-pirimidindiamina;
VI-44
N2-(3-Aminosulfonil-4-clorofenil)-N4-(3-cloro-4-trifluorometil-fenil)-5-fluoro-2,4-pirimidindiamina;
VI
N2-(3-Aminosulfonil-4-iso-propilfenil)-N4-(3-cloro-4-metoxi-fenil)-5-fluoro-2,4-pirimidindiamina;
VI-46
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-(4-trifluorometilmetilenooxifenil)-2,4-pirimidindiamina;
VI-47
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-(4-trifluorometilmetilenooxifenil)-2,4-pirimidindiamina;
VI-48
N2-(3-Aminosulfonil-4-clorofenil)-5-fluoro-N4-(4-trifluorometilmetilenooxifenil)-2,4-pirimidindiamina;
VI-49
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[3-(metilaminocarboniloximetil)fenil]-2,4-pirimidindiamina;
VI
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-(4-trifluorometilfenil)-2,4-pirimidindiamina;
VI-51
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-(4-trifluorometilfenil)-2,4-pirimidindiamina;
VI-52
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-(4-hidroximetilfenil)-2,4-pirimidindiamina;
VI-53
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-(prop-2-iniloxi)fenil]-2,4-pirimidindiamina;
VI-54
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-(4-vinilfenil)-2,4-pirimidindiamina;
VI
N2-(3-Aminosulfonil-4-clorofenil)-5-fluoro-N4-[4-(prop-2-iniloxi)fenil]-2,4-pirimidindiamina;
VI-56
5-Fluoro-N2-(4-metil-3-propionilaminosulfonilfenil)-N4-[4-(prop-2-iniloxi)fenil]-2,4-pirimidindiamina;
VI-57
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[3-(prop-2-iniloxi)fenil]-2,4-pirimidindiamina;
VI-58
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[3-metil-4-(prop-2-iniloxi)fenil]-2,4-pirimidindiamina;
VI-59
N2-(3-Aminosulfonil-4-metilfenil)-N4-[3-cloro-4-(prop-2-iniloxi)fenil]-5-fluoro-2,4-pirimidindiamina;
VI
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[3-fluoro-4-(prop-2-iniloxi)fenil]-2,4-pirimidindiamina;
VI-61
N2-(3-Aminosulfonil-4-metilfenil)-N4-[4-(but-2-iniloxi)fenil]-5-fluoro-2,4-pirimidindiamina;
VI-62
N2-[3-propionilaminosulfonil-4-metilfenil]-5-fluoro-N4-[4-(prop-2-iniloxi)fenil]-2,4-pirimidindiamina;
VI-63
N2-[3-Aminosulfonil-4-(2-propil)fenil]-5-fluoro-N4-[4-(prop-2-iniloxi)fenil]-2,4-pirimidindiamina;
31
Comp.
Nombre
VI-64
N4-{4-[2-(Dimetilaminocarboniloxi)etil]fenil}-5-fluoro-N2-(3-propionilaminosulfonilfenil)-2,4-pirimidindiamina;
VI-65
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-(prop-2-inilamino)fenil]-2,4-pirimidindiamina;
VI-66
Sal sódica de N4-{4-[2-(dimetilaminocarboniloxi)etil]fenil}-5-fluoro-N2-(3-propionilaminosulfonilfenil)-2,4pirimidindiamina
VI-67
N2-(3-Aminosulfonil-4-metilfenil)-N4-{4-[bis(prop-2-inil)amino]fenil}-5-fluoro-2,4-pirimidindiamina;
VI-68
5-Fluoro-N2-(4-metil-3-metilaminosulfonilfenil)-N4-[4-(prop-2-iniloxi)fenil]-2,4-pirimidindiamina;
VI-69
5-Fluoro-N2-{[4-metil-3-((1-metilpiperidin-4-il)aminosulfonil)]fenil}-N4-[4-(prop-2-iniloxi)fenil]-2,4pirimidindiamina;
VI-70
N2-[3-Aminosulfonil-4-(1-metilpiperazin-4-il)fenil]-5-fluoro-N4-[4-(prop-2-iniloxi)fenil]-2,4-pirimidindiamina;
VI-71
N4-{4-[2-(Aminocarbonilamino)etil]fenil}-N2-(3-aminosulfonil-4-metilfenil)-5-fluoro-2,4-pirimidindiamina;
VI-72
N4-{4-[2-(Aminocarbonilamino)etil]fenil}-N2-(3-aminosulfonilfenil)-5-fluoro-2,4-pirimidindiamina;
VI-73
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-{4-[(prop-2-iniloxi)carbonilaminometil]fenil}-2,4pirimidindiamina;
VI-74
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-{4-[(prop-2-iniloxi)carbonilaminometil]fenil}-2,4-pirimidindiamina;
VI-75
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[4-(prop-2-inilaminosulfonil)fenil]-2,4-pirimidindiamina;
VI-76
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-(prop-2-inilaminosulfonil)fenil]-2,4-pirimidindiamina;
VI-77
N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-(prop-2-inilaminosulfonil)fenil]-2,4-pirimidindiamina;
VI-78
5-Fluoro-N2-[3-(prop-2-inilaminosulfonil)fenil]-N4-[4-(prop-2-iniloxi)fenil]-2,4-pirimidindiamina;
VI-79
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[3-(prop-2-inilaminosulfonil)fenil]-2,4-pirimidindiamina;
VI-80
N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[3-(prop-2-inilaminosulfonil)fenil]-2,4-pirimidindiamina;
VI-81
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[3-(prop-2-inilaminosulfonil)fenil]-2,4-pirimidindiamina;
VI-82
N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-(3-fluoropropil)fenil]-2,4-pirimidindiamina;
VI-83
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[4-(3-fluoropropil)fenil]-2,4-pirimidindiamina;
VI-84
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-(3-fluoropropil)fenil]-2,4-pirimidindiamina;
VI-85
N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-(3-hidroxipropil)fenil]-2,4-pirimidindiamina;
VI-86
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[4-(3-hidroxipropil)fenil]-2,4-pirimidindiamina;
VI-87
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-(3-hidroxipropil)fenil]-2,4-pirimidindiamina;
VI-88
N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-(4-hidroxibutil)fenil]-2,4-pirimidindiamina;
VI-89
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[4-(4-hidroxibutil)fenil]-2,4-pirimidindiamina;
VI-90
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-(4-hidroxibutil)fenil]-2,4-pirimidindiamina;
VI-91
N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-(4-fluorobutil)fenil]-2,4-pirimidindiamina;
VI-92
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[4-(4-fluorobutil)fenil]-2,4-pirimidindiamina;
VI-93
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-(4-fluorobutil)fenil]-2,4-pirimidindiamina;
VI-94
N2-(4-aminosulfonil)fenil-5-fluoro-N4-(4-tiometilcarbonil)fenil-2,4-pirimidindiamina;
VI-95
N2-(3-aminosulfonil-4-metil)fenil-5-fluoro-N4-(4-tiometilcarbonil)fenil-2,4-pirimidindiamina;
VI-96
N2-(3-Butilaminosulfonilfenil)-N4-(3-ciano-4-metilfenil)-5-fluoro-2,4-pirimidindiamina;
VI-97
N2-(3-Butilaminosulfonilfenil)-N4-(3-cloro-4-fluorofenil)5-fluoro-2,4-pirimidindiamina;
VI-98
N2-(3-Aminosulfonilfenil)-N4-(3-ciano-4-fluorofenil)-5-fluoro-2,4-pirimidindiamina;
VI-99
N2-(3-Aminosulfonilfenil)-N4-(3-ciano-4-metilfenil)-5-fluoro-2,4-pirimidindiamina;
VI-100
N2-(3-Aminosulfonil-4-fluorofenil)-5-fluoro-N4-(4-hidroxifenil)-2,4-pirimidindiamina;
VI-101
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-(4-hidroxifenil)-2,4-pirimidindiamina;
VI-102
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-hidroxifenil]-2,4-pirimidindiamina;
VI-103
N4-[4(2-Cianoetil)-3-metilfenil]-5-fluoro-N2-(4-metil-3-propionilaminosulfonilfenil)-2,4-pirimidindiamina;
VI-104
Sal sódica de N4-[4-(2-cianoetil)-3-metilfenil]-5-fluoro-N2-(4-metil-3-propionilaminosulfonilfenil)-2,4pirimidindiamina;
VI-105
N4-(3,4-diclorofenil)-N4-metil-5-fluoro-N2-[3-(N,N-dietil)aminosulfonil-4-metoxifenil]-2,4-pirimidindiamina;
VI-106
N2-(4-Aminosulfonilfenil)-5-fluoro-N4-(4-metoxi-3-clorofenil]-2,4-pirimidindiamina;
VI-107
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-(4-metoxi-3-clorofenil]-2,4-pirimidindiamina;
VI-108
N4-(3-cloro-4-metoxifenil)-N2-(3-N,N-dietilaminosulfonil-4-metoxifenil)-5-fluoro-2,4-pirimidindiamina;
VI-109
N2-(4-Aminosulfonilfenil)-N4-(3,4-diclorofenil)-5-fluoro-2,4-pirimidindiamina;
VI-110
N2-(3-Aminosulfonilfenil)-N4-(3,4-diclorofenil)-5-fluoro-2,4-pirimidindiamina;
VI-111
N2-(3-Aminosulfonil-4-clorofenil)-5-fluoro-N4-[4-(2-metoxietilenooxi)fenil]-2,4-pirimidindiamina;
VI-112
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-(2-metoxietilenooxi)fenil]-2,4-pirimidindiamina;
VI-113
N2,N4-Bis-(3-aminosulfonilfenil)-5-fluoro-2,4-pirimidindiamina;
VI-114
N2,N4-Bis-(3-aminosulfonil-4-metilfenil)-5-fluoro-2,4-pirimidindiamina;
VI-115
N2,N4-Bis-(3-aminosulfonil-4-clorofenil)-5-fluoro-2,4-pirimidindiamina;
VI-116
N2-[3-Aminosulfonil-4-(4-metilpiperazin-1-il)fenil]-N4-(3-cloro-4-metoxifenil)-5-fluoro-2,4-pirimidindiamina;
VII-1
N2-(3-Aminosulfonil-4-metilfenil)-N4-[(2S,4R)-1-(2-cianoacetil)-2-metoxicarbonilpirrolidin-4-il)-5-fluoro-2,4pirimidindiamina;
VII-2
N2-(3-Aminosulfonil-4-metilfenil)-N4-[(2S,4S)-1-(2-cianoacetil)-2-metoxicarbonilpirrolidin-4-il]-5-fluoro-2,4pirimidindiamina;
VII-3
N2-(3-Aminosulfonil-4-metilfenil)-N4-(1-bencil-4-metilpiperidin-3-il)-5-fluoro-2,4-pirimidindiamina racémica;
32
Comp.
Nombre
VII-4
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-(4-metilpiperidin-3-il)-2,4-pirimidindiamina racémica;
VII-5
N2-(3-Aminosulfonil-4-metilfenil)-N4-(1-cianometilenocarbonil-4-metilpiperidin-3-il)-5-fluoro-2,4pirimidindiamina racémica;
VII-6
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-(2-metoxipirid-5-il)-2,4-pirimidindiamina;
VII-7
N2-(3-Aminosulfonilfenil)-N4-(2-amino-3-metoxipirid-6-il)-5-fluoro-2,4-pirimidindiamina;
VII-8
N2-(3-Aminosulfonil-4-clorofenil)-N4-(2-amino-3-metoxipirid-6-il)-5-fluoro-2,4-pirimidindiamina;
VII-9
N2-(3-Aminosulfonil-4-metilfenil)-N4-[2-amino-3-metoxipirid-6-il]-5-fluoro-2,4-pirimidindiamina (66);
VII
N4-(2-Amino-3-metoxipirid-6-il)-N2-[3-(etoxicarbonilmetileno)aminosulfonilfenil)-5-fluoro-2,4pirimidindiamina;
VII-11
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-(2,2,4-trimetil-1,1,3-trioxo-benzo[1,4]tiazin-6-il)-2,4-pirimidindiamina;
VII-12
N2-(4-Aminosulfonilfenil)-5-fluoro-N4-(2,2,4-trimetil-1,1,3-trioxo-benzo[1,4]tiazin-6-il)-2,4-pirimidindiamina;
VII-13
N2-(4-aminosulfonil)fenil-N4-[(N-etilsulfonil)-1,2,3,4-tetrahidroisoquinolin-6-il]-5-fluoro-2,4-pirimidindiamina
VII-14
N2-(3-aminosulfonil)fenil-N4-[(N-etilsulfonil)-1,2,3,4-tetrahidroisoquinolin-6-il]-5-fluoro-2,4-pirimidindiamina
VII-15
N2-(3-aminosulfonil-4-metil)fenil-N4-[(N-etilsulfonil)-1,2,3,4-tetrahidroisoquinolin-6-il]-5-fluoro-2,4pirimidindiamina
VII-16
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-(1,2,3,4-tetrahidroisoquin-7-il)-2,4-pirimidindiamina;
VII-17
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[2-(metilaminocarbonil)-1,2,3,4-tetrahidroisoquin-7-il]-2,4pirimidindiamina;
VII-18
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[2-(dimetilaminocarbonil)-1,2,3,4-tetrahidroisoquin-7-il]-2,4pirimidindiamina;
VII-19
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[1-(metilaminocarbonil)-1,2,3,4-tetrahidroquin-6-il]-2,4pirimidindiamina;
VII
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[1-(metilaminocarbonil)-1,2,3,4-tetrahidroquin-6-il]-2,4pirimidindiamina;
VII-21
N2-(3-Aminosulfonil-4-metilfenil)-N4-[3,4-dihidro-(1H)-quinolin-2-ona-6-il]-5-fluoro-2,4-pirimidindiamina
VII-22
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[1-(3-metoxipropil)indazolin-5-il]-2,4-pirimidindiamina;
VII-23
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[1-(2-metoxietil)indazolin-5-il]-2,4-pirimidindiamina;
VII-24
N4-(3,4-Etilendioxifenil)-5-fluoro-N2-[4-(pirrolidin-1-ilsulfonil)fenil]-2,4-pirimidindiamina;
VII-26
N2-(3-Aminosulfonil-4-metilfenil)-N4-[2-(N,N-dimetilaminocarbonil)-2,3-dihidrobenzofuran-5-il]-5-fluoro-2,4pirimidindiamina racémica;
VII-27
N2-(3-Aminosulfonil-4-clorofenil)-N4-[2-(N,N-dimetilaminocarbonil)-2,3-dihidrobenzofuran-5-il]-5-fluoro-2,4pirimidindiamina racémica;
VII-28
N2-(3-Aminosulfonilfenil)-N4-(croman-4-amina-6-il)-5-fluoro-2,4-pirimidindiamina;
VII-29
N2-(4-Aminosulfonilfenil)-N4-(croman-4-amina-6-il)-5-fluoro-2,4-pirimidindiamina;
VII
N2-(3-Aminosulfonil-4-metilfenil)-5-metil-N4-(3-oxo-benz[1,4]oxazin-6-il)-2,4-pirimidindiamina;
VII-31
N2-(4-Aminosulfonilfenil)-5-metil-N4-(3-oxo-benz[1,4]oxazin-6-il)-2,4-pirimidindiamina;
VII-32
N2-(3-Aminosulfonilfenil)-5-metil-N4-(3-oxo-benz[1,4]oxazin-6-il)-2,4-pirimidindiamina;
VII-33
N2-(3-Aminosulfonil-4-metilfenil)-5-metil-N4-(4-metil-3-oxo-benzo[1,4]tiazin-6-il)-2,4-pirimidindiamina;
VII-34
N2-(4-Aminosulfonilfenil)-5-metil-N4-(4-metil-3-oxo-benzo[1,4]tiazin-6-il)-2,4-pirimidindiamina;
VII-35
N2-(3-Aminosulfonilfenil)-5-metil-N4-(4-metil-3-oxo-benzo[1,4]tiazin-6-il)-2,4-pirimidindiamina;
VII-36
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-(3-oxo-4-cianometil-benzo[1,4]tiazin-6-il)-2,4-pirimidindiamina;
VII-38
N2-(3-Aminosulfonil-4-metoxi-5-metilfenil)-N4-(2,2-difluoro-4H-benz[1,4]oxazin-3-on-6-il)-5-fluoro-2,4pirimidindiamina;
VII-39
5-Amino-N2-(3-amionsulfonilfenil)-N4-(2,2-dimetil-3-oxo-4H-benz[1,4]oxazin-6-il)-2,4-pirimidindiamina;
VII
N2-(4-Aminosulfonilfenil)-5-fluoro-N4-(4-metil-3-oxo-benz[1,4]oxazin-6-il)-2,4-pirimidindiamina;
VII-41
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-(4-metil-3-oxo-benz[1,4]oxazin-6-il)-2,4-pirimidindiamina;
VII-42
N2-(3-Aminosulfonilfenil)-N4-[2,2,4-trimetil-3-oxo-5-pirid[1,4]oxazin-7-il]-5-fluoro-2,4-pirimidindiamina;
VII-43
N2-(4-Aminosulfonilfenil)-N4-[2,2,4-trimetil-3-oxo-5-pirid[1,4]oxazin-5-il]-5-fluoro-2,4-pirimidindiamina;
VII-44
N2-(3-Aminosulfonil-4-metil-fenil)-5-fluoro-N4-(3-oxo-4H-benzo[1,4]tiazin-6-il)-2,4-pirimidindiamina;
VII-45
N2-(3-Aminosulfonil-4-metil-fenil)-5-fluoro-N4-(3-oxo-4H-benzo[1,4]tiazin-6-il)-2,4-pirimidindiamina;
VII-46
N2-(4-Aminosulfonilfenil)-5-fluoro-N4-(2,2,4-trimetil-1,1,3-trioxo-benzo[1,4]tiazin-6-il)-2,4-pirimidindiamina;
VII-47
N2-(4-Aminosulfonilfenil)-N4-cianometil-5-fluoro-N4-[3-oxo-4-metil-benzo[1,4]tiazin-6-il]-2,4pirimidindiamina;
VII-48
N2-(4-Aminosulfonilfenil)-5-fluoro-N4-(4-metil-3-oxo-benz[1,4]tiazin-6-il)-2,4-pirimidindiamina;
VII-49
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-(4-metil-3-oxo-benz[1,4]tiazin-6-il)-2,4-pirimidindiamina;
VII
5-Fluoro-N4-(4-metil-3-oxo-benz[1,4]tiazin-6-il)-N2-(3-piperidinosulfonilfenil)-2,4-pirimidindiamina;
VII-51
N2-(3-Aminosulfonilfenil)-N4-[2,2-dimetil-3-oxo-4H-5-pirid[1,4]oxazin-7-il]-5-fluoro-2,4-pirimidindiamina;
VII-52
N2-(4-Aminosulfonilfenil)-N4-[2,2-dimetil-3-oxo-4H-5-pirid[1,4]oxazin-7-il]-5-fluoro-2,4-pirimidindiamina;
VII-53
N2-(3-Aminosulfonil-4-metilfenil)-N4-(2-cianobenzofuran-5-il)-5-fluoro-2,4-pirimidindiamina;
VII-54
N2-(3-Aminosulfonilfenil)-N4-(2-aminocarbonilbenzofurano-5-il)-5-fluoro-2,4-pirimidindiamina;
VII-55
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[4-(3-piridinilmetil)benzo[1,4]oxazin-7-il]-2,4-pirimidindiamina;
VII-56
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[4-(3-piridinilmetil)benzo[1,4]oxazin-7-il]-2,4-pirimidindiamina;
33
Comp.
Nombre
VII-57
N2-(3-Aminosulfonil-4-metilfenil)-N4-(benzotiofen-5-il)-5-fluoro-2,4-pirimidindiamina;
VII-58
N2-(3-Aminosulfonilfenil)-N4-(benzotiofen-5-il)-5-fluoro-2,4-pirimidindiamina;
VII-59
N2-(4-Aminosulfonilfenil)-N4-(4-N-terc-butoxicarbonilamino-3,4-dihidro-2H-1-benzopiran-6-il)-5-fluoro-2,4pirimidindiamina;
VII-60
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[4-(1-metilsulfonil)indolin-5-il]-2,4-pirimidindiamina;
VII-61
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-(1-metilsulfonil)indolin-5-il]-2,4-pirimidindiamina;
VII-62
5-Fluoro-N2-[3-(N-metilaminosulfonil)-4-metilfenil]-N4-[4-(1-metilsulfonil)indolin-5-il]-2,4-pirimidindiamina;
VII-63
N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-(1-metilsulfonil)indolin-5-il]-2,4-pirimidindiamina;
VII-64
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-(quinolin-2-il)-2,4-pirimidindiamina;
VII-65
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-(quinolin-3-il)-2,4-pirimidindiamina;
VII-66
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-(quinolin-3-il)-2,4-pirimidindiamina;
VII-67
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-(quinolin-5-il)-2,4-pirimidindiamina;
VII-68
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-(quinolin-5-il)-2,4-pirimidindiamina;
VII-69
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-(quinolin-6-il)-2,4-pirimidindiamina;
VII-70
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-(quinolin-6-il)-2,4-pirimidindiamina;
VII-71
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-(2-metilquinolin-6-il)-2,4-pirimidindiamina;
VII-72
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-(2-metilquinolin-6-il)-2,4-pirimidindiamina;
VII-73
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-(2-hidroxi-4-metilquinolin-6-il)-2,4-pirimidindiamina
VII-74
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-(2-hidroxi-4-metilquinolin-6-il)-2,4-pirimidindiamina
VII-75
N2-(3-Aminosulfonil-4-metilfenil)-N4-(2-N,N'-dimetilamina-quinolin-6-il)-5-fluoro-2,4-pirimidindiamina
VII-76
N2-(3-Aminosulfonilfenil)-N4-(2-N,N'-dimetilamina-quinolin-6-il)-5-fluoro-2,4-pirimidindiamina
VII-77
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-(quinolin-8-il)-2,4-pirimidindiamina;
VII-78
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-(quinolin-8-il)-2,4-pirimidindiamina;
VII-79
N2-(3-Aminosulfonil-4-fluorofenil)-5-fluoro-N4-(quinolin-8-il)-2,4-pirimidindiamina;
VII-80
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-(2-metilquinolin-8-il)-2,4-pirimidindiamina;
VII-81
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-(2-metilquinolin-8-il)-2,4-pirimidindiamina;
VII-82
(1R,2R,3S,4S) N4-(3-Aminocarbonilbiciclo[2.2.1]hept-5-en-2-il)-N2-(3-aminosulfonil-4-metilfenil)-5-fluoro2,4-pirimidindiamina;
VII-83
(1R,2R,3S,4S) N2-(3-Aminosulfonil-4-metoxi-5-metilfenil)-N4-(3-aminocarbonilbiciclo[2.2.1]hept-5-eno-2-il)5-fluoro-2,4-pirimidindiamina; y
VIII-3
N4-(3-Cloro-4-metoxifenil)-5-fluoro-N2-(5-metil-2H-1,1-dioxo-1,2,4-benzotiadiazin-7-il)-2,4-pirimidindiamina.
Otro aspecto más de la invención proporciona compuestos seleccionados entre el grupo que consiste en:
Comp.
nombre
IX-1
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[1-(propin-3-il)indol-5-il]-2,4-pirimidindiamina;
IX-2
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[1-(propin-3-il)indol-5-il]-2,4-pirimidindiamina;
IX-3
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[1-(propin-3-il)indol-6-il]-2,4-pirimidindiamina;
IX-4
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[1-(propin-3-il)indol-6-il]-2,4-pirimidindiamina;
IX-5
N2-(3-Aminosulfonilfenil)-N4-(1-cianometilenoindol-5-il)-5-fluoro-2,4-pirimidindiamina;
IX-6
N2-(4-Aminosulfonilfenil)-N4-(1-cianometilenoindol-5-il)-5-fluoro-2,4-pirimidindiamina;
IX-7
N2-(3-Aminosulfonil-4-clorofenil)-N4-(1-cianometilenoindol-5-il)-5-fluoro-2,4-pirimidindiamina;
IX-8
N2-(3-Aminosulfonil-4-metilfenil)-N4-(1-cianometilenoindol-5-il)-5-fluoro-2,4-pirimidindiamina;
IX-9
N4-[3-(Aminocarbonil)-1H-indol-6-il]-N2-(3-aminosulfonil-4-metilfenil)-5-fluoro-2,4-pirimidindiamina;
IX-10
N4-[3-(Aminocarbonil)-1H-indol-6-il]-N2-(3-aminosulfonil-4-clorofenil)-5-fluoro-2,4-pirimidindiamina;
IX-11
N2-(3-Aminosulfonil-4-metilfenil)-N4-(3-cianometil-1H-indol-6-il)-5-fluoro-2,4-pirimidindiamina;
IX-12
N2-(3-Aminosulfonilfenil)-N4-(3-cianometil-1H-indol-6-il)-5-fluoro-2,4-pirimidindiamina;
IX-13
N2-(3-Aminosulfonilfenil)-N4-(3-cianometil-1H-indol-5-il)-5-fluoro-2,4-pirimidindiamina;
IX-14
N2-(3-Aminosulfonil-4-metilfenil)-N4-(3-cianometil-1H-indol-5-il)-5-fluoro-2,4-pirimidindiamina;
IX-15
N2-(3-Aminosulfonilfenil)-N4-(3-cianometil-1H-indol-7-il)-5-fluoro-2,4-pirimidindiamina;
IX-16
N2-(3-Aminosulfonil-4-metilfenil)-N4-(3-cianometil-1H-indol-7-il)-5-fluoro-2,4-pirimidindiamina;
IX-17
N2-[3-Aminosulfonil-4-(4-metilpiperazin-1-il)fenil]-N4-(3-cianometileno-1H-indol-6-il)-5-fluoro-2,4pirimidindiamina;
IX-18
N2-[3-Aminosulfonil-4-(4-metilpiperazin-1-il)fenil]-N4-(3-cianometileno-1H-indol-7-il)-5-fluoro-2,4pirimidindiamina;
IX-19
N4-(3-cianometileno-1H-indol-5-il)-5-fluoro-N2-[3-(1-metil-4-aminopiperidina)sulfonil-4-metilfenil]-2,4pirimidindiamina;
IX-20
N2-(3-Aminosulfonil-4-metilfenil)-N4-(3-cianometil-1-metil-indol-5-il)-5-fluoro-2,4-pirimidindiamina;
IX-21
N2-(3-Aminosulfonil-4-clorofenil)-N4-(2-cianobenzofuran-5-il)-5-fluoro-2,4-pirimidindiamina;
IX-22
N2-(3-Aminosulfonil-4-iso-propilfenil)-N4-(2-cianobenzofuran-5-il)-5-fluoro-2,4-pirimidindiamina;
IX-23
N4-[4-(1-Acetil-4-piperizinil)carbonilfenil]-N2-(3-Aminosulfonilfenil)-5-fluoro-2,4-pirimidindiamina;
IX-24
N4-[4-(1-Acetil-4-piperizinil)carbonilfenil]-N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-2,4-pirimidindiamina;
34
Comp.
nombre
IX-25
N4-[4-(1-Acetil-4-piperizinil)carbonilfenil]-5-fluoro-N2-[3-(N-metilaminosulfonil)-4-metilfenil]-2,4pirimidindiamina;
IX-26
N4-[4-(1-Acetil-4-piperizinil)carbonilfenil]-N2-(4-aminosulfonilfenil)-5-fluoro-2,4-pirimidindiamina;
IX-27
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-(4-metilpiperazin-1-ilcarbonil)fenil]-2,4-pirimidindiamina;
IX-28
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[4-(4-metilpiperazin-1-ilcarbonil)fenil]-2,4-pirimidindiamina;
IX-29
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[4-(1-metanosulfonil-4-piperizinil)carbonilfenil]-2,4-pirimidindiamina;
IX-30
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-(1-metanosulfonil-4-piperizinil)carbonilfenil]-2,4pirimidindiamina;
IX-31
5-Fluoro-N2-[3-(N-metilaminosulfonil)-4-metilfenil]-5-fluoro-N4-[4-(1-metanosulfonil-4piperizinil)carbonilfenil]-2,4-pirimidindiamina;
IX-32
N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-(1-metanosulfonil-4-piperazinil)carbonilfenil]-2,4-pirimidindiamina;
IX-33
5-Fluoro-N2-[3-(N-metilaminosulfonil)-4-metilfenil]-5-fluoro-N4-[4-(4-tiomorfolino)carbonilfenil]-2,4pirimidindiamina;
IX-34
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[4-(4-tiomorfolinil)carbonilfenil]-2,4-pirimidindiamina;
IX-35
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-(4-tiomorfolinil)carbonilfenil]-2,4-pirimidindiamina;
IX-36
N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-(4-tiomorfolinil)carbonilfenil]-2,4-pirimidindiamina;
IX-37
N2-(3-Aminosulfonilfenil)-N4-[4-(1,1-dioxo-4-tiomorfolinil)carbonilfenil]-5-fluoro-2,4-pirimidindiamina;
IX-38
N2-(3-Aminosulfonil-4-metilfenil)-N4-[4-(1,1-dioxo-4-tiomorfolinil)carbonilfenil]-5-fluoro-2,4-pirimidindiamina;
IX-39
N4-[4-(1,1-dioxo-4-tiomorfolinil)carbonilfenil]-5-Fluoro-N2-[3-(N-metilaminosulfonil)-4-metilfenil]-2,4pirimidindiamina;
IX-40
N2-(4-Aminosulfonilfenil)-N4-[4-(1,1-dioxo-4-tiomorfolinil)carbonilfenil]-5-fluoro-2,4-pirimidindiamina;
IX-41
N4-(4-Acetiltiometilcarbonilfenil)-N2-(4-aminosulfonilfenil)-5-fluoro-2,4-pirimidindiamina;
IX-42
N4-(4-Acetiltiometilcarbonilfenil)-N2-(3-aminosulfonilfenil)-5-fluoro-2,4-pirimidindiamina;
IX-43
N4-(4-Acetiltiometilcarbonilfenil)-N2-(3-aminosulfonil-4-metilfenil)-5-fluoro-2,4-pirimidindiamina;
IX-44
N2-(4-Aminosulfonilfenil)-N4-[3,5-dimetil-4-(4-metilpiperazin-1-il]fenil)-5-fluoro-2,4-pirimidindiamina;
IX-45
N2-(3-Aminosulfonil-4-metilfenil)-N4-[(4R)-1-(2-cianoacetil)-pirrolidin-4-il)-5-fluoro-2,4-pirimidindiamina
IX-46
N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-(5-metoxicarbonil-tiofeno-2-il)-2,4-pirimidindiamina
IX-47
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-(5-metoxicarbonil-tiofeno-2-il)-2,4-pirimidindiamina
IX-48
N2-(3-Aminosulfonil-4-fluorofenil)-5-fluoro-N4-(5-metoxicarbonil-tiofeno-2-il)-2,4-pirimidindiamina
IX-49
N2-(4-Aminosulfonilfenil)-5-fluoro-N4-(5-metoxicarbonil-tiofeno-2-il)-2,4-pirimidindiamina
IX-54
5-Fluoro-N2-[3-N-(metil)aminosulfonil-4-metilfenil]-N4-[4-(2-piridinil)-3-clorometilenooxifenil]-2,4pirimidindiamina;
X-1
6-carbonilmetoxi-N4-(3,4-diclorofenil)-N2-(3-N,N-dietilaminosulfonil-6-metoxifenil)-2,4-pirimidindiamina;
X-2
6-carbonilmetoxi-(3-N,N-dietilaminosulfonil-6-metoxifenil)-N4-[3-oxo-benz[1,4]oxazin-6-il]-2,4pirimidindiamina; y
X-3
N2-(3-Aminosulfonilfenil)-5-fluoro-N4-(2-metilindol-6-ilmetileno)-2,4-pirimidindiamina.
En otra realización, la presente invención proporciona un método para inhibir una actividad de una quinasa JAK, que comprende poner en contacto in vitro un quinasa JAK3 con una cantidad de un compuesto eficaz para inhibir una actividad de la quinasa JAK en el que el compuesto se selecciona entre los compuestos de la presente invención, tal
5 como se describe en el presente documento.
En otra realización, la presente invención proporciona un compuesto de la invención para su uso en un método de tratar una enfermedad autoinmunitaria mediada por linfocitos T, que comprende administrar a un paciente que padece este tipo de enfermedad autoinmunitaria una cantidad de un compuesto eficaz para tratar la enfermedad
10 autoinmunitaria.
En otra realización adicional más, la presente invención proporciona un compuesto de la invención para su uso en un método de tratar una enfermedad autoinmunitaria mediada por linfocitos T, que comprende administrar a un paciente que padece dicha enfermedad autoinmunitaria una cantidad de un compuesto eficaz para tratar la
15 enfermedad autoinmunitaria en el que el compuesto se administra en combinación, o junto con, un compuesto que inhibe la quinasa Syk con una CI50 en el intervalo de 10 µM o menos.
En otra realización, la presente invención proporciona un compuesto de la invención para su uso en un método para tratar o prevenir el rechazo de un trasplante de aloinjerto en el receptor del trasplante, que comprende administrar al 20 receptor del trasplante una cantidad de un compuesto eficaz para tratar o prevenir el rechazo. El rechazo puede ser rechazo agudo o rechazo crónico. El rechazo también puede estar mediado por HVGR o GVHR. En ciertas realizaciones, el trasplante de aloinjerto se selecciona entre un riñón, un corazón, un hígado y un pulmón. El compuesto, opcionalmente, se puede administrar junto con, o además de, un inmunosupresor. En algunas realizaciones preferidas, el inmunosupresor se selecciona entre ciclosporina, tacrolimus, sirolimus, un inhibidor de
25 IMPDH, micofenolato, micofenolato de mofetilo, un anticuerpo dirigido contra linfocitos T y OKT3.
35
imagen19
imagen20
imagen21
imagen22
imagen23
imagen24
imagen25
imagen26
imagen27
imagen28
imagen29
imagen30
imagen31
imagen32
imagen33
imagen34
imagen35
imagen36
imagen37
imagen38
imagen39
imagen40
imagen41
imagen42
imagen43
imagen44
imagen45
imagen46
imagen47
TABLA IV
N.º
R1- (R2)p R X Z (R3)q SO2NR4R5
IV-1
3-(oxazol-5-il) - H F C - 3-SO2NH2
IV-2
3-(oxazol-5-il) - H F C 4-Me 3-SO2NH2
IV-3
3-(oxazol-5-il) - H F C - 4-SO2NH2
IV-4
3-(oxazol-5-il) - H F C 4-Me 3-SO2NHMe
IV-5
4-(oxazol-5-il) - H F C - 3-SO2NH2
IV-6
4-(oxazol-5-il) - H F C 4-Me 3-SO2NH2
IV-7
4-(oxazol-5-il) - H F C 4-Me 3-SO2NHMe
IV-8
4-(oxazol-5-il) - H F C - 4-SO2NH2
IV-9
4-(N,N-dimetilsulfamoil) - H F C - 3-SO2NH2
IV-10
4-(N,N-dimetilsulfamoil) - H F C 4-Me 3-SO2NH2
IV-11
4-(N-metilsulfamoil) - H F C - 3-SO2NH2
IV-12
4-(N-metilsulfamoil) - H F C 4-Me 3-SO2NH2
65
imagen48
imagen49
imagen50
imagen51
imagen52
imagen53
imagen54
imagen55
imagen56
imagen57
imagen58
TABLA X
N.º
Estructura
X-1
imagen59
X-2
imagen60
X-3
imagen61
TABLA XI
N.º de Reg. CAS
Estructura
845817-97-2
imagen62
841290-42-4
imagen63
841290-41-3
imagen64
77
imagen65
imagen66
imagen67
imagen68
imagen69
imagen70
imagen71
imagen72
imagen73
imagen74
imagen75
imagen76
imagen77
imagen78
imagen79
imagen80
imagen81
imagen82
imagen83
imagen84
imagen85
imagen86
imagen87
imagen88
imagen89
imagen90
imagen91
imagen92
imagen93
imagen94
imagen95
imagen96
imagen97
imagen98
imagen99
imagen100
imagen101
imagen102
imagen103
imagen104
imagen105
imagen106
imagen107
imagen108
imagen109
imagen110
imagen111
imagen112
imagen113
imagen114
imagen115
imagen116
imagen117
imagen118
imagen119
imagen120
imagen121
imagen122
imagen123
imagen124
imagen125
imagen126
imagen127
imagen128
imagen129
imagen130
imagen131
imagen132
imagen133
imagen134
imagen135
imagen136
imagen137
imagen138
imagen139
imagen140
imagen141
imagen142
imagen143
imagen144
imagen145
imagen146
imagen147
imagen148
imagen149
imagen150
imagen151
imagen152
imagen153
imagen154
imagen155
imagen156
imagen157
imagen158
imagen159
imagen160
imagen161
imagen162
imagen163
imagen164
imagen165
imagen166
imagen167
imagen168
imagen169
imagen170
imagen171
imagen172
imagen173
imagen174
imagen175
imagen176
imagen177
imagen178
imagen179
imagen180
imagen181
imagen182
imagen183
imagen184
imagen185
imagen186
imagen187
Compuesto
Ejemplo 41 Ejemplo 42 Ejemplo 43 Ejemplo 44
I-25
0,05582 1,6129 25,3098 8888
I-26
0,03781 0,40073 4,23449 0,42446
I-27
0,06186 0,91443 3,48033 0,53438
I-28
0,06454 0,5598 7777 1,89233
I-29
0,1196 0,50183
I-30
5,43333 3,57085
I-31
4,62505
I-32
0,16136 2,78095 5,49713 1,96749
I-33
0,0965 0,1705 8888 0,89708
I-34
0,06229 0,80566 7777 1,05493
I-35
0,04696 1,1331 8,58425 1,82151
I-36
8,80466 9999
I-37
0,49851 3,68499 5,73717
I-38
6,44228
I-39
0,84081 9,32297
I-40
0,30838 31,0382 3345,23
1-41
0,03738 10,15
I-42
0,02408 8888
I-43
0,01826 0,18317 36,6502 0,77073
I-44
0,05316 0,34166 9999 5,06833
I-45
0,1036 0,83377 17,0422 3,63512
I-46
0,11322 0,40872 9999 0,75129
I-47
0,12011 0,55068 0,75908
I-48
1,40357
I-49
2,31794 5,55983
I-50
0,37337 25,1264
I-51
0,26268 2,11715 32,1941
I-52
0,15228 5,30087 9999 68,6571
I-53
0,23595 12,2055
I-54
0,27682 7,15982
I-55
9999
I-56
0,10355 0,2618 4,97271 0,42424
I-57
0,02161 0,05314 9999 0,13971
I-58
0,00505 0,01925 0,73026 0,06599
I-59
0,00655 0,02487 0,94741 0,05766
I-60
0,10288 2,17439 7,89243 0,84765
I-61
0,04586 0,12299 8888 0,42748
I-62
0,10056 0,37599 3,52859 0,73487
I-63
0,16924 1,31421 34,3138 0,69103
I-64
0,11281 1,87772 5,16607 1,15237
I-65
0,09651 0,04731 8888 0,31629
I-66
0,10306 0,28704 9999 0,68933
I-67
0,03322 0,15663 4,61611 0,23869
I-68
0,18704 0,48243 4,96049 0,91274
I-69
0,11784 1,02837 5,64408 5000,08
I-70
0,06138 0,57305 3,43038 0,384
I-71
0,06178 0,13591 3,26769 0,32803
I-72
0,05239 0,30295 3,30881 0,57377
I-73
0,11976 0,7281 5,55843 1,06264
I-74
0,24475 1,49815 10,7945 1,75731
I-75
0,19865 3,3 7777 3,1
I-76
0,10102 0,19585 5,13601 1,12224
I-77
0,14716 1,61795
I-78
0,6349 1,2051
I-79
0,4606 1,0611
I-80
0,3649 0,4697
I-81
0,3597 0,9566
I-82
0,2439 1,3819
I-83
0,158 1,7561 14,9
I-84
1,4005
I-85
0,7913
I-86
0,9162
201 202 203 204 205 206 207 208 209 210 211
Compuesto
Ejemplo 41 Ejemplo 42 Ejemplo 43 Ejemplo 44
I-87
1,0381
I-88
1,07518
I-89
5,49992 9999
I-90
0,40109 2,19063 6,16341
I-91
2,03142
I-92
0,16624 0,54302 9999 15,59
I-93
0,26489 1,17393 23,774 11,0701
I-94
0,34492 0,56287 5,66845
I-95
0,11825 0,32508 9999 6,3
I-96
0,13177 0,77151 40,8692 3,30063
I-97
0,21244 0,86883 31,0729 27,4081
I-98
0,29451 37,2587 10,9783
I-99
0,06863 0,14752 9999 3,77549
I-100
0,38027 9999 6670,09
I-101
0,32832 51,1576 36,6028
I-102
0,21893 0,21079 43,7663 15,5943
I-103
1,24843 9999
I-104
1,42542 9999
I-105
1,1675 9999
I-106
2,95316
I-107
1,51103
I-108
0,14545 0,14758 9999 3,97385
I-109
0,30527 0,20336 25,9633 9,93933
I-110
0,35788 0,25307 20,584 3,92933
I-111
0,89035 9999
I-112
2,36464 9999
I-113
0,16466 1,6854 9999 13,5121
I-114
0,44754 6,70638 9999 9999
I-115
0,79259 7777
I-116
0,27394 0,97166 9999 4455,33
I-117
0,35266 0,30095 36,4268 14,5685
I-118
0,292 0,55723 2,42563
I-119
0,21095 2,43898 9,67128 11,8985
I-120
0,20071 0,27964 19,9754 4,45634
I-121
0,18382 0,63384 14,5419 2,98512
I-122
0,29151 3,5 9999 15,6681
I-123
0,15927 0,22497 12,8283 2,2221
I-124
0,10241 0,34199 10,373 1,33026
I-125
0,53802
I-126
0,35476 0,60989 7,20132
I-127
0,2333 0,50965 2,5105
I-128
0,87135
I-129
0,61228
I-130
0,60114 1,73251
I-131
0,26226 3,78086 2,99277
I-132
0,35129 0,46431 2,71959
I-133
0,23656 1,34872 9999
I-134
0,17762 0,50998 9999 3,23999
I-135
0,11208 0,10418 3,24251 1,82933
I-136
0,13205 0,19642 8,11382 1,64002
I-137
0,38672 1,09918 9999 29,5795
I-138
0,4607 0,22286 91,4861 9,46799
I-139
0,37466 0,24038 11,5578 3,26019
I-140
0,38751
I-141
0,1625 0,66903 15,6032
I-142
0,15485 0,85438 9999
I-143
1,19256
I-144
1,00541
I-145
0,54156 0,3493
I-146
0,36436 7777 9999
I-147
0,07985 0,17442 7777 9999
I-148
0,06117 0,24003 9999 9999
Compuesto
Ejemplo 41 Ejemplo 42 Ejemplo 43 Ejemplo 44
I-149
0,1613 0,19724 14,7293
I-150
0,06569 0,06806 7777 10,5387
I-151
0,06185 0,07829 9999 8888
I-152
0,30174 1,5412
I-153
0,11405 0,33375 9999
I-154
0,27631 0,9925 9999
I-155
0,11775 0,09932 9999 65,0584
I-156
0,06549 0,14151 9999 2,62254
I-157
0,24574 1,8906 9999
I-158
0,2967 0,44535 1,38012
I-159
0,33805 0,53944 1,63449
I-160
0,13042 0,2484 0,92282
I-161
0,31398 2,41123
I-162
0,05105 0,13566 9999 0,59381
I-163
0,17656 0,4391 1,40511
I-164
9999
I-165
0,24517 0,44644 1,63555
I-166
0,61646
I-167
0,14175 7777
I-168
0,15437 1,17511 9999
I-169
0,0546 0,1373 8888
I-170
0,4507
I-171
0,11717 0,41497
I-172
0,04734 0,2771 38,674 1,09663
I-173
0,11513 0,907 9999 15,5343
I-174
0,11681 1,23383 8888
I-175
0,14696 3,0806 9999
I-176
0,25875 1,69038
I-177
8888 0,5
I-178
0,0235 0,0293 0,11756
I-179
0,02427 0,01178 0,11711
I-180
0,0624 0,02868 0,4558
I-181
0,01301
I-182
0,18961 1,12876 8888
I-183
0,24913 1,83159 2,27747
I-184
0,48571 2,57372 6,62465
I-185
0,29773 9999
I-186
0,18828 1,08437 3,53394
I-187
2,91228
I-188
0,0427 0,0642 15,0825 0,50022
I-189
0,13708 0,14331 6,74171 0,50811
I-190
0,14533 0,24207 9,30992 1,5006
I-191
0,13487 0,29228 0,79644
I-192
0,13748 0,15499 0,97787
I-193
0,03822 0,05562 9999
I-194
0,02858 0,09935 5,02722
I-195
0,08263 0,12705 9999 9999
I-196
0,12446 0,13926 9999 0,75397
I-197
0,13477 0,32885 1,2782
I-198
0,10154 0,46016 9999 0,80536
I-199
0,23967 3,02692 2,68752
I-200
9999
I-201
9999
I-202
3,075
I-203
0,26472 0,68359 5,77164 3,1332
I-204
0,25571 1,6463 3,92821
I-205
0,31543 1,8632 9,4856 3341,09
I-206
0,72572
I-207
8888
I-208
1,39961
I-209
0,58003 4,46766 2,96679 9999
I-210
0,86614
Compuesto
Ejemplo 41 Ejemplo 42 Ejemplo 43 Ejemplo 44
I-211
1,05253
I-212
0,75778
I-213
11,4811
I-214
0,14442 1,32831 1,30455
I-215
0,97626
I-216
0,20482 0,49337 1,56836
I-217
0,02498 0,21692 36,591 0,4785
I-218
0,07262 0,11588 3,26785 0,43399
I-219
0,03162 0,12305 7,16246 0,58776
I-220
0,12138 1,06662 7777 8888
I-221
0,34372 2,68161 4,43571
I-222
0,03308 0,58244 9999 0,84
I-223
0,08803 0,62525 9,08836 1,20989
I-224
0,03615 0,19417 11,324 0,4936
I-225
0,69987
I-226
0,49797
I-227
1,48242
I-228
3,80514
I-229
3,75639
I-230
0,08426 0,06925 10,477 0,46548
I-231
0,09468 0,29003 9999 8,40421
I-232
1,42979
I-233
0,14834 0,37693 9999 1,74874
I-234
0,10247 1,00762 8,15676 2,01923
I-235
0,17818 0,4695 9999 2,55555
I-236
1,98037
I-237
0,14699 2,04005 9999 3,57746
I-238
0,16477 0,45567 9999 1,12717
I-239
0,23965 9999 7,05758
I-240
0,20499 5,25922 8888
I-241
0,26564 0,44243 2,87423
I-242
0,52009
I-243
0,91747
I-244
0,28501 1,40668 14,7078 3,11959
I-245
0,20153 1,74332 16,6871 4,1888
I-246
0,10624 0,18232 8,87569 0,87257
I-247
0,225 0,1187 11,115 1,0767
I-248
0,38838 0,13774 2,65851
I-249
0,51223 11,0003
I-250
0,67255
I-251
0,16719 0,15516 34,8518 1,09204
I-252
0,0906 0,55777 74,2104 2,46619
I-253
0,12662 2,56423
I-254
0,15452 1,91498 8,95614 1,82459
I-255
0,25614 2,86397 39,3342 5,52062
I-256
0,28206 38,2034 9999 15,9307
I-257
0,14527 0,10222 3,07682 0,95888
I-258
0,02798 0,05539 9999 0,3241
I-259
0,02793 0,06575 7,50745 0,3147
I-260
0,09477 0,22271 8,44012 0,98515
I-261
5031,28
I-262
0,07832 0,16396 3,67509 1,04486
I-263
0,12368 0,06443 0,66548
I-264
0,59917 14,9995
I-265
0,04232 0,0397 4,08382 0,41479
I-266
0,08513 0,20071 9999 0,824
I-267
0,32828 2,01965 5,06578
I-268
0,06074 0,13983 5,0785 0,21895
I-269
0,91657
I-270
0,77962
I-271
9999
I-272
0,78775
Compuesto
Ejemplo 41 Ejemplo 42 Ejemplo 43 Ejemplo 44
I-273
0,47773 0,19296 12,8791 5,10428
I-274
1,17189
I-275
0,22313 0,57744 9999 1,9
I-276
0,13508 0,10582 8,0902 0,8217
I-277
0,15065 0,09153 6,91127 1,47355
I-278
0,19343 0,41215 11,0338 2,26901
I-279
0,12274 0,16744 9999 0,9178
I-280
0,14472 0,9783 1,45628
I-281
0,09321 0,09036 9999 0,97459
I-282
0,33926 0,69745 3,10495
I-283
0,51821 0,3617 2,94063
I-284
0,13587 0,42105 1,54787
I-285
0,13257 0,31358 1,485
II-1
0,18176 1,13989 8,32597
II-2
0,24439 1,51926 4,59317
II-3
0,08404 0,91766 11,921 6,50431
II-4
0,31643 2,37109 3,51083
II-5
2,20619
II-6
0,11067 1,2178 6,38785
II-7
0,14372 0,52156 1,62567
II-8
0,03878 0,56414 9999
II-9
0,23159 1,31747 2,7171
II-10
0,36923 0,8756 1,39632
II-11
0,10669 0,19762 0,91162
II-12
0,05626 0,40891 5,52004 1,19102
II-13
0,32334
II-14
0,04685 0,57852
II-15
0,98189 1,10065
II-16
18,3048 3,71528
II-17
21,2024 8,20964
II-18
2,04279 3,30797
II-19
0,39546 8888 9999
II-20
0,42846 0,96892 11,5294
II-21
0,69755 1,76163 41,7481
II-22
0,85847 7,48812
III-1
0,15102 0,54475 1,11685
III-2
0,22374 3,43534 6,71592
III-3
0,53624
III-4
0,01872 0,17102 8,36734 1,71666
III-5
4,9773 9999
III-6
0,78109 30,674
III-7
0,0851 0,19544 12,3228 1,08953
III-8
0,13823 0,92083 14,4636 2,2522
III-9
0,21457 1,80396 23,6063 6,98319
III-10
0,22461 0,92188 9999 3,52348
III-11
0,0642 0,04604 2,24405 0,16825
III-12
0,07001 0,10746 3,51838 0,32092
III-13
0,2953 0,70092
III-14
0,13985 0,05263 3,60147 0,58483
III-15
0,07596 0,10691 4,65521 0,55294
III-16
0,2733 0,34222 7,23576 1,79675
III-17
0,05674 0,1974 0,78205
III-18
0,03659 0,13567 0,54387
III-19
0,07229 0,17392 21,8899 0,05559
III-20
0,04299 0,76298 6,63588 3,33323
III-21
0,0303 0,11378 0,33867
III-22
0,04545 0,07611 8888 0,44428
III-23
0,39727
III-24
0,25751 1,62056
III-25
0,27162 1,25963
III-26
0,16196 0,58276
III-27
0,05834 0,11898 7777 0,25737
Compuesto
Ejemplo 41 Ejemplo 42 Ejemplo 43 Ejemplo 44
III-28
3,74795 17,4221
III-29
3,63333 12,3622 9999
III-30
0,06455 0,31911 9999
III-31
0,09536 0,32762 1,70465
III-32
4,40366 3,31651 9999
III-33
1,68071 0,85213
III-34
0,47276 0,38085
III-35
1,0814
III-36
0,3944 0,3819
III-37
0,2997 0,834
III-38
0,1976 1,127
III-39
0,1171 0,1297 4,15 1,435
III-40
0,1341 0,2286 1,116
III-41
1,0134
III-42
0,2936 0,6406
III-43
0,2705 0,8975
III-44
1,43012
III-45
0,29277 0,38431
III-46
0,21144 1,05234
III-47
0,21084 0,36642 9999
III-48
0,20373 0,21773 9999
III-49
0,17801
III-50
0,30572 1,96867
III-51
1,00749
III-52
0,18299 1,20459
III-53
0,0977 0,28629 1,13155
III-54
0,13522 0,13989 9999 1,59326
III-55
0,14436 0,97312
III-56
0,19581 0,49929
III-57
0,05356 0,16996 55,5368 0,83776
III-58
0,15671 1,25684
III-59
0,14965 0,45792
III-60
0,13462 0,17751 25,5295 1,01469
III-61
0,25873 1,08295
III-62
0,1715 0,699
III-63
0,3153 1,8768
III-64
0,4473 5,9565
III-65
0,209 0,9359
III-66
0,14152 1,15034 0,96668
III-67
0,34745 3,05467
III-68
3,23069
III-69
3,31825
III-70
0,06446 0,16921 9999 1,64984
III-71
0,09785 0,36848 8,25586 1,70255
III-72
1,95167
III-73
0,13087 0,43435
III-74
0,09524 0,17541 9999 0,93514
III-75
0,16969 0,22009 10,0944 1,77125
III-76
0,1042 0,1348 0,447
III-77
0,1774 0,2095 0,681
III-78
0,2754 0,2041 7777 22,9
III-79
0,16853 0,96749
III-80
3,15582 0,84435
III-81
0,18003 0,20392 48,3461 3,42825
III-82
0,12695 0,15998 24,1674 2,27381
III-83
0,09874 0,09622 9999 1,35976
III-84
0,4428 1,8956
III-85
0,07272 0,12242 9999 3,62044
III-86
0,0976 0,09394 9999 6,44528
III-87
0,14099 0,14172 76,2393 2,94666
III-88
0,14065 0,16557 10,6231 2,03999
III-89
0,11498
Compuesto
Ejemplo 41 Ejemplo 42 Ejemplo 43 Ejemplo 44
III-90
0,35751 0,46822 2,6323
III-91
0,14274 0,46742
III-92
0,32272 1,89757
III-93
0,17308 0,81891
III-94
0,16161 0,71606
III-95
0,1494 0,37003 29,7109
III-96
3,32588 2,18995
III-97
0,27887 1,02568
III-98
0,11654 0,45747
III-99
1,03465 2,17142
III-100
0,16233 0,19656 1,9107
III-101
0,2401 0,4464
III-102
0,30171 0,48559
III-103
0,23001 1,05998 2,42638
III-104
0,24173 1,19132 2,1621
III-105
1,27754
III-106
0,04277 0,07508 5,89649 0,49188
III-107
0,21914 0,5404 1,52384
III-108
0,18343 1,21503 1,50897
III-109
0,14312 0,25198 0,53111
III-110
0,24698 0,99788 13,5631
III-111
0,32121 0,92557 5,34359
III-112
2,47605
III-113
1,0305 0,345
III-114
2,6833
III-115
1,6524
III-116
0,19663 3,94714 7777
III-117
0,39696
III-118
0,62434 2,29421
III-119
1,29867
III-120
0,65536 0,5542
III-121
0,57495 1,0202
III-122
0,53873
III-123
0,17252 1,38789
III-124
0,29523
III-125
0,8356
III-126
0,1972 0,4701
III-127
0,1982 0,6123
III-128
0,14513 0,13942 28,0649 1,43941
III-129
0,17355 0,1799 31,2977 1,187
IV-1
0,07356 0,28652 0,27169
IV-2
0,08002 0,36242 0,70488
IV-3
0,09325
IV-4
0,15095 0,3032 2,42396
IV-5
0,09767 0,11589 16,0697 0,50367
IV-6
0,10292 0,13159 0,88048
IV-7
0,11241 0,20304 1,23784
IV-8
0,16592 0,62672
IV-9
0,19023 1
IV-10
0,13472 0,71395
IV-11
0,3672
IV-12
0,25666 1,21823
V-1
2,00456 9,77279 9999
V-2
1,17796
V-3
0,66409 13,7306
V-4
0,10843 1,53933 9,24355
V-5
0,69624
V-6
0,02185 0,07083 7777 0,57206
V-7
0,05877 0,12703 5,00173 0,82053
V-8
0,02908 0,22532 5,20729 0,61971
V-9
1,11064
V-10
0,26102 8,26777 2,69871
Compuesto
Ejemplo 41 Ejemplo 42 Ejemplo 43 Ejemplo 44
V-11
0,0698 0,79519 8888 1,41593
V-12
0,18817 0,95693 54,0071 3,03787
V-13
0,05289 0,46847 6,86738 1,19717
V-14
0,19711 2,59168 6,84803
V-15
0,17289 9,30756 8888
V-16
8,3722
VI-1
0,20474
VI-2
0,08925 3,57169 9999
VI-3
0,20565 8,79279 9999 9999
VI-4
0,02107 0,2312 9999 9999
VI-5
0,04047 0,71837 8888 1,3851
VI-6
0,03747 1,44938 14,9708 7,70441
VI-7
0,76592
VI-8
2,28135
VI-9
0,05327 0,94453 9,95895 14,5216
VI-10
0,22022 2,39519 24,9026 9999
VI-11
0,25923 4,61735 47,0634 7,13718
VI-12
0,14575 1,3099 9999 8888
VI-13
0,09654 1,34867 8,2263 1,3926
VI-14
0,41325 7777 9,26616
VI-15
0,045 0,46887 0,76722
VI-16
0,25935 3,91458 8888
VI-17
0,04344 0,2436 6,42231 0,45391
VI-18
0,25733 4,36513 6,06278
VI-19
1,02551
VI-20
0,72602
VI-21
11,321
VI-22
0,66268
VI-23
0,59672
VI-24
8,61565
VI-25
9,91092
VI-26
0,04444 0,0289 1,70264 0,257
VI-27
0,07613 3,7609 0,5446
VI-28
0,75443
VI-29
0,04982 0,36201 8888
VI-30
0,01324 0,1702 9999
VI-31
18,2541
VI-32
0,33323 1,65819
VI-33
0,27207 0,66049
VI-34
0,1567 0,8386
VI-35
0,1583 1,2589
VI-36
0,3743 4,4975
VI-37
0,0692 1,0785 12,4
VI-38
0,4143 2,0675
VI-39
0,401 3,139
VI-40
0,2883 1,2369
VI-41
0,3425 6,2401
VI-42
0,4515 6,1678
VI-43
0,7393 6,1404
VI-44
0,4293 7,3093
VI-45
0,1081 1,3279 10,53
VI-46
0,1435 1,2558
VI-47
0,0828 0,2589 9999 0,596
VI-48
0,3153 2,2429
VI-49
0,26786 1,26457 2,09896
VI-50
0,21701 0,94365 1,87806
VI-51
0,15225 0,54688 9999 2,13363
VI-52
0,16844 0,16223 5,91841 1,73898
VI-53
0,05631 0,18115 11,3381 0,56491
VI-54
0,14667 0,96651 31,0319 1,61592
VI-55
0,12204 0,62467 1,36955
VI-56
9,6557
Compuesto
Ejemplo 41 Ejemplo 42 Ejemplo 43 Ejemplo 44
VI-57
0,20172 1,18287
VI-58
0,16427 0,72381 9999
VI-59
0,07598 0,33972 4,98157
VI-60
0,08692 0,18673 3,84551 0,40964
VI-61
0,09897 0,18455 3,11335 0,36684
VI-62
3,9717
VI-63
0,15987 0,36325 1,74329
VI-64
5,80304
VI-65
0,09062 0,20944 4,12861 0,9643
VI-66
6,0949
VI-67
0,14725 0,7175
VI-68
0,1016 0,74156 26,8087 1,80963
VI-69
0,19376 1,34478 18,7049
VI-70
0,07056 0,31112 8888 0,65688
VI-71
1,07371
VI-72
0,45477
VI-73
0,25111 2,01413
VI-74
0,09458 0,34829 9999 3,85373
VI-75
0,90444 0,92854
VI-76
0,54911 0,78345
VI-77
9999 43,2745
VI-78
0,16137
VI-79
0,096
VI-80
0,3601
VI-81
3,1748
VI-82
0,21184 1,63499 8888
VI-83
0,11255 0,29326 7,29592 0,53506
VI-84
0,13247 0,51438 4,58337
VI-85
0,12862 0,76235 24,7027
VI-86
0,1531 0,17808 4,43831 0,48745
VI-87
0,5411 1,24269
VI-88
0,21559 1,18558 24,6776
VI-89
0,13188 0,17139 5,75508 2,04395
VI-90
1,075 3,9664
VI-91
0,22118 1,23424 9999
VI-92
0,0835 0,10732 12,9834 1,1583
VI-93
0,10988 0,5602
VI-94
0,9442
VI-95
1,0032
VI-96
0,80335
VI-97
3,00715
VI-98
0,13555 0,9859 9999 9999
VI-99
0,06845 0,6166 9999 9999
VI-100
0,32107 0,07427 9,1817 4,89859
VI-101
0,91914
VI-102
0,18285 0,13496 14,7259 2,7967
VI-103
3,07902
VI-104
1,98452
VI-105
10,2998
VI-106
0,06219 1,19886 9999 9999
VI-107
0,15912 0,07409 8888 0,85644
VI-108
9999
VI-109
0,13553 2,86926 7777 9999
VI-110
0,08364 0,34532 9999 5,46321
VI-111
0,31375 1,09272 3,43245
VI-112
0,15223 0,77009 1,25566
VI-113
0,6995
VI-114
0,2095 2,2419 9999 33,19
VI-115
0,8899
VI-116
0,0311 0,1742 8,101 0,673
VII-1
6,653
VII-2
36,2228
Compuesto
Ejemplo 41 Ejemplo 42 Ejemplo 43 Ejemplo 44
VII-3
14,0844 16,5455
VII-4
2,49292 9999
VII-5
4,12527
VII-6
0,10208 1,99812 23,4363 3,6535
VII-7
0,50186 3,91608 9999
VII-8
0,39911 8,63335 7777 7777
VII-9
0,24627 2,71965 17,0751 5,34695
VII
0,86258
VII-11
0,60232
VII-12
0,60208 6,68655 31,7728
VII-13
0,13967 0,38047 7777 1,28577
VII-14
0,10259 0,17683 9,92695 0,87716
VII-15
0,06662 0,12058 13,1417 0,56816
VII-16
0,27544 1,07422 24,3537
VII-17
0,35301 2,09765 6,96416
VII-18
0,22688 0,83852 1,29055
VII-19
0,08753 0,51424 12,53 1,25627
VII
0,28603 0,69758
VII-21
0,54792
VII-22
0,1114 0,1276 9999 0,84875
VII-23
0,12929 0,16124 61,259 0,59644
VII-24
0,62303
VII-26
0,54544 1,20006 9,26107
VII-27
0,41342 2,05177 6,2489
VII-28
0,0367 0,70906 16,5843 8888
VII-29
0,0476 1,46279 30,5071 38,4779
VII
0,0358 0,02682 8,91572 0,70135
VII-31
0,12467 0,17419 9999 7,27828
VII-32
0,1071 0,0321 8888 2,057
VII-33
0,02891 0,01839
VII-34
0,04504 0,02248
VII-35
0,0448 0,0461 8888 0,245
VII-36
0,02945 0,11909 82,8107 1,08605
VII-38
0,06234 0,41674
VII-39
0,77157 0,91901
VII
0,23602 6,48486 9999
VII-41
0,04694 0,26426 9999 9999
VII-42
0,6688 7,28447 45,547
VII-43
0,60291 9999
VII-44
0,03299 0,54552 9,12322 1,22643
VII-45
0,04385 0,28169 4,03246 0,47741
VII-46
0,96115
VII-47
2,67352
VII-48
0,03083 0,3365 9999 0,66
VII-49
0,03778 0,05493 3,06481 0,57652
VII
0,34963 0,85602 4,41963 5,0643
VII-51
0,54109 1,79232 9999
VII-52
47,0815
VII-53
0,16792 0,48379 5,46124
VII-54
0,29487 0,59608 64,6261
VII-55
0,18411 0,59857 1,66866
VII-56
0,18495 1,28469 1,92946
VII-57
0,10717 0,8182 10,6982 0,73524
VII-58
0,13577 0,26518 1,09844
VII-59
0,83147 2,98692
VII
0,06501 0,15195 2,60397 0,56965
VII-61
3333,23 0,14031 2,69156 0,35591
VII-62
0,10412 0,14422 9999 0,49561
VII-63
0,23311 0,30064 6,02744
VII-64
0,36258 3,8097
VII-65
0,38533 3,05525
VII-66
0,36866 2,87032
Compuesto
Ejemplo 41 Ejemplo 42 Ejemplo 43 Ejemplo 44
VII-67
0,31467 0,76791
VII-68
0,81157 1,30092
VII-69
0,07673 0,69583 7,50321 0,98982
VII-70
0,06542 0,37513 6,47721 2,76015
VII-71
0,14944 0,56875 5,47023
VII-72
0,08484 0,41516 9,93038 1,18433
VII-73
6,08963 4444,5
VII-74
4,56128 8888
VII-75
0,54401
VII-76
0,67316
VII-77
0,12407 1,78366 3,53562
VII-78
0,08583 0,6825 9999 8888
VII-79
0,20627 3,20167 7777
VII-80
2,03294
VII-81
3,07323
VII-82
0,3126 1,07552 8888
VII-83
0,0775 0,93655 9999
VIII-1
1,58839
VIII-2
0,1777 0,40901 8,54969
VIII-3
0,15335 1,84224 10,0847
IX-1
0,08928 0,58079 4,88106 1,13251
IX-2
0,0795 0,28213 8888 1,76728
IX-3
0,11457
IX-4
0,12037
IX-5
0,02962 0,07382 6,09872 1,84617
IX-6
0,08403 0,53531 36,7836 8888
IX-7
0,10867 0,7509 9999 4,73418
IX-8
0,04643 0,12398 5,24218 0,54254
IX-9
8,87638 5016,37
IX-10
6,40728
IX-11
0,1146 0,21538 7777 2,23698
IX-12
0,09731 0,11725 7777 3,47525
IX-13
0,13847 0,43042 30,2755 1,84616
IX-14
0,05744 0,65645 3,37992 1,08814
IX-15
0,21708 0,15678 7777 5,36404
IX-16
0,20966 0,22281 7777 2,50539
IX-17
0,1084 0,8151 21,95 1,98
IX-18
0,1684 2,4 55,18 6,659
IX-19
0,1179 1,5963 3,368
IX-20
0,12232 1,79208 2,89558
IX-21
0,2709 2,7359
IX-22
0,2953 1,59
IX-23
9,57788
IX-24
6,33149 38,3916
IX-25
6,3071
IX-26
9999
IX-27
1,37969 7,62931
IX-28
1,66076 10,0529
IX-29
3,45769
IX-30
1,93529 6,79992
IX-31
1,4025
IX-32
9999 9999
IX-33
0,52102
IX-34
0,58245 0,57557 3,95135
IX-35
0,45471 0,8665 9999 2,09598
IX-36
1,03601 9999
IX-37
3,70466
IX-38
2,31392
IX-39
1,39641
IX-40
9999 9999
IX-41
0,13318 6,25787 9999
IX-42
0,29236 2,17331 9999
imagen188

Claims (4)

  1. imagen1
    imagen2
    imagen3
    imagen4
    imagen5
    N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[3-(metilaminocarboniloximetil)fenil]-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-clorofenil)-5-fluoro-N4-[4-(prop-2-iniloxi)fenil]-2,4-pirimidindiamina; N4-{4-[2-(Dimetilaminocarboniloxi)etil]fenil}-5-fluoro-N2-(3-propionilaminosulfonilfenil)-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-(prop-2-inilamino)fenil]-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-N4-{4-[bis(prop-2-inil)amino]fenil}-5-fluoro-2,4-pirimidindiamina; N2-[3-Aminosulfonil-4-(1-metilpiperazin-4-il)fenil]-5-fluoro-N4-[4-(prop-2-iniloxi)fenil]-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-{4-[(prop-2-iniloxi)carbonilaminometil]fenil}-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-5-fluoro-N4-{4-[(prop-2-iniloxi)carbonilaminometil]fenil}-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[4-(prop-2-inilaminosulfonil)fenil]-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-(prop-2-inilaminosulfonil)fenil]-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[3-(prop-2-inilaminosulfonil)fenil]-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[3-(prop-2-inilaminosulfonil)fenil]-2,4-pirimidindiamina; N2-(3-aminosulfonil-4-metil)fenil-5-fluoro-N4-(4-tiometilcarbonil)fenil-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-N4-(3-ciano-4-fluorofenil)-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-N4-(3-ciano-4-metilfenil)-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-fluorofenil)-5-fluoro-N4-(4-hidroxifenil)-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-5-fluoro-N4-(4-hidroxifenil)-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-hidroxifenil]-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-clorofenil)-5-fluoro-N4-[4-(2-metoxietilenooxi)fenil]-2,4-pirimidindiamina; N2,N4-Bis-(3-aminosulfonilfenil)-5-fluoro-2,4-pirimidindiamina; N2,N4-Bis-(3-aminosulfonil-4-clorofenil)-5-fluoro-2,4-pirimidindiamina; N2-[3-Aminosulfonil-4-(4-metilpiperazin-1-il)fenil]-N4-(3-cloro-4-metoxifenil)-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-N4-[(2S,4R)-1-(2-cianoacetil)-2-metoxicarbonilpirrolidin-4-il)-5-fluoro-2,4pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-N4-[(2S,4S)-1-(2-cianoacetil)-2-metoxicarbonilpirrolidin-4-il]-5-fluoro-2,4pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-N4-(1-bencil-4-metilpiperidin-3-il)-5-fluoro-2,4-pirimidindiamina racémica; N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-(4-metilpiperidin-3-il)-2,4-pirimidindiamina racémica; N2-(3-Aminosulfonil-4-metilfenil)-N4-(1-cianometilenocarbonil-4-metilpiperidin-3-il)-5-fluoro-2,4-pirimidindiamina racémica; N2-(3-Aminosulfonilfenil)-5-fluoro-N4-(2-metoxipirid-5-il)-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-N4-(2-amino-3-metoxipirid-6-il)-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-clorofenil)-N4-(2-amino-3-metoxipirid-6-il)-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-N4-[2-amino-3-metoxipirid-6-il]-5-fluoro-2,4-pirimidindiamina; N4-(2-Amino-3-metoxipirid-6-il)-N2-[3-(etoxicarbonilmetileno)aminosulfonilfenil)-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-5-fluoro-N4-(2,2,4-trimetil-1,1,3-trioxo-benzo[1,4]tiazin-6-il)-2,4-pirimidindiamina; N2-(3-Aminosulfonil)fenil-N4-[(N-etilsulfonil)-1,2,3,4-tetrahidroisoquinolin-6-il]-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metil)fenil-N4-[(N-etilsulfonil)-1,2,3,4-tetrahidroisoquinolin-6-il]-5-fluoro-2,4pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-(1,2,3,4-tetrahidroisoquin-7-il)-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[2-(metilaminocarbonil)-1,2,3,4-tetrahidroisoquin-7-il]-2,4pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[2-(dimetilaminocarbonil)-1,2,3,4-tetrahidroisoquin-7-il]-2,4pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[1-(metilaminocarbonil)-1,2,3,4-tetrahidroquin-6-il]-2,4pirimidindiamina; N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[1-(metilaminocarbonil)-1,2,3,4-tetrahidroquin-6-il]-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-N4-[3,4-dihidro-(1H)-quinolin-2-ona-6-il]-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[1-(3-metoxipropil)indazolin-5-il]-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[1-(2-metoxietil)indazolin-5-il]-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-N4-[2-(N,N-dimetilaminocarbonil)-2,3-dihidrobenzofuran-5-il]-5-fluoro-2,4pirimidindiamina racémica; N2-(3-Aminosulfonil-4-clorofenil)-N4-[2-(N,N-dimetilaminocarbonil)-2,3-dihidrobenzofuran-5-il]-5-fluoro-2,4pirimidindiamina racémica; N2-(3-Aminosulfonilfenil)-N4-(croman-4-amina-6-il)-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-5-metil-N4-(3-oxo-benz[1,4]oxazin-6-il)-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-5-metil-N4-(3-oxo-benz[1,4]oxazin-6-il)-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-5-metil-N4-(4-metil-3-oxo-benzo[1,4]tiazin-6-il)-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-5-metil-N4-(4-metil-3-oxo-benzo[1,4]tiazin-6-il)-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-5-fluoro-N4-(3-oxo-4-cianometil-benzo[1,4]tiazin-6-il)-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metoxi-5-metilfenil)-N4-(2,2-difluoro-4H-benz[1,4]oxazin-3-on-6-il)-5-fluoro-2,4pirimidindiamina; 5-Amino-N2-(3-amionsulfonilfenil)-N4-(2,2-dimetil-3-oxo-4H-benz[1,4]oxazin-6-il)-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-5-fluoro-N4-(4-metil-3-oxo-benz[1,4]oxazin-6-il)-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-N4-[2,2,4-trimetil-3-oxo-5-pirid[1,4]oxazin-7-il]-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metil-fenil)-5-fluoro-N4-(3-oxo-4H-benzo[1,4]tiazin-6-il)-2,4-pirimidindiamina;
    imagen6
    imagen7
    imagen8
    imagen9
    N2-(3-Aminosulfonil-4-metil-fenil)-N4-(4-cloro-3-trifluorometilfenil)-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metoxi-5-metilfenil)-N4-(4-cloro-3-trifluorometil-fenil)-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-iso-propilfenil)-N4-(3-cloro-4-metoxi-fenil)-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-(4-trifluorometilmetilenooxifenil)-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-5-fluoro-N4-(4-trifluorometilmetilenooxifenil)-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-(4-trifluorometilfenil)-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-5-fluoro-N4-(4-trifluorometilfenil)-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-(4-hidroximetilfenil)-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-(4-vinilfenil)-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[3-(prop-2-iniloxi)fenil]-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[3-metil-4-(prop-2-iniloxi)fenil]-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-N4-[3-cloro-4-(prop-2-iniloxi)fenil]-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[3-fluoro-4-(prop-2-iniloxi)fenil]-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-N4-[4-(but-2-iniloxi)fenil]-5-fluoro-2,4-pirimidindiamina; N2-[3-propionilaminosulfonil-4-metilfenil]-5-fluoro-N4-[4-(prop-2-iniloxi)fenil]-2,4-pirimidindiamina; N2-[3-Aminosulfonil-4-(2-propil)fenil]-5-fluoro-N4-[4-(prop-2-iniloxi)fenil]-2,4-pirimidindiamina; Sal sódica de N4-{4-[2-(dimetilaminocarboniloxi)etil]fenil}-5-fluoro-N2-(3-propionilaminosulfonilfenil)-2,4pirimidindiamina; 5-Fluoro-N2-(4-metil-3-metilaminosulfonilfenil)-N4-[4-(prop-2-iniloxi)fenil]-2,4-pirimidindiamina; 5-Fluoro-N2-{[4-metil-3-((1-metilpiperidin-4-il)aminosulfonil)]fenil}-N4-{4-[2-(aminocarbonilamino)etil]fenil}-N2-(3aminosulfonil-4-metilfenil)-5-fluoro-2,4-pirimidindiamina; N4-{4-[2-(Aminocarbonilamino)etil]fenil}-N2-(3-aminosulfonilfenil)-5-fluoro-2,4-pirimidindiamina; 5-Fluoro-N2-[3-(prop-2-inilaminosulfonil)fenil]-N4-[4-(prop-2-iniloxi)fenil]-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[4-(3-fluoropropil)fenil]-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-(3-fluoropropil)fenil]-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[4-(3-hidroxipropil)fenil]-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-(3-hidroxipropil)fenil]-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[4-(4-hidroxibutil)fenil]-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-(4-hidroxibutil)fenil]-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[4-(4-fluorobutil)fenil]-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-(4-fluorobutil)fenil]-2,4-pirimidindiamina; N2-(3-Butilaminosulfonilfenil)-N4-(3-ciano-4-metilfenil)-5-fluoro-2,4-pirimidindiamina; N2-(3-Butilaminosulfonilfenil)-N4-(3-cloro-4-fluorofenil)5-fluoro-2,4-pirimidindiamina; N4-[4(2-Cianoetil)-3-metilfenil]-5-fluoro-N2-(4-metil-3-propionilaminosulfonilfenil)-2,4-pirimidindiamina; Sal sódica de N4-[4-(2-cianoetil)-3-metilfenil]-5-fluoro-N2-(4-metil-3-propionilaminosulfonilfenil)-2,4pirimidindiamina; N4-(3,4-diclorofenil)-N4-metil-5-fluoro-N2-[3-(N,N-dietil)aminosulfonil-4-metoxifenil]-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-5-fluoro-N4-(4-metoxi-3-clorofenil]-2,4-pirimidindiamina; N4-(3-cloro-4-metoxifenil)-N2-(3-N,N-dietilaminosulfonil-4-metoxifenil)-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-N4-(3,4-diclorofenil)-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-(2-metoxietilenooxi)fenil]-2,4-pirimidindiamina; N2,N4-Bis-(3-aminosulfonil-4-metilfenil)-5-fluoro-2,4-pirimidindiamina.
  2. 6. Un compuesto seleccionado del grupo que consiste en:
    N2-(4-Aminosulfonilfenil)-N4-(3-cianometoxi-4,5-dimetoxifenil)-5-fluoro-2,4-pirimidindiamina; N2-(4-Aminosulfonil)fenil-N4-(3-cianometoxi)fenil-5-fluoro-2,4-pirimidindiamina; N4-(3-Cianometoxi)fenil-5-fluoro-N2-[4-(4-metilpiperazin-1-il)sulfonil]fenil-2,4-pirimidindiamina; N2-(4-Aminosulfonil-3-metoxi)fenil-N4-(3-cianometoxi)fenil-5-fluoro-2,4-pirimidindiamina; N2-(4-Aminosulfonil)fenil-N4-(4-cianometoxi)fenil-5-fluoro-2,4-pirimidindiamina; N4-(4-Cianometoxi)fenil-5-fluoro-N2-[4-(4-metilpiperazin-1-il)sulfonil]fenil-2,4-pirimidindiamina; N2-(4-Aminosulfonil)fenil-N4-(4-cianometoxi-3-metil)fenil-5-fluoro-2,4-pirimidindiamina; N2-(4-Aminosulfonil)fenil-N4-(4-cianometoxi-3,5-dimetil)fenil-5-fluoro-2,4-pirimidindiamina; N2-(4-Aminosulfonil-3-metoxifenil)-N4-(4-cianometoxi)fenil-5-fluoro-2,4-pirimidindiamina; N2-(4-Aminosulfonil-3-metoxi)fenil-N4-(4-cianometoxi-3-metil)fenil-5-fluoro-2,4-pirimidindiamina; N2-(4-Aminosulfonil-3-metoxi)fenil-N4-(4-cianometoxi-3,5-dimetil)fenil-5-fluoro-2,4-pirimidindiamina; N4-(4-Cianometoxi-3,5-dimetilfenil)-5-fluoro-N2-[4-(4-metilpiperazin-1-il)sulfonilfenil]-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-N4-(3-cloro-4-cianometoxifenil)-5-fluoro-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-N4-(4-cianometoxi-3-fluorofenil)-5-fluoro-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-N4-(4-cianometoxi-3-metoxifenil)-5-fluoro-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-N4-[4-cianometoxi-3-(1-cianometilpirazol-3-il)fenil]-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonilpirid-4-il)-N4-(4-cianometoxifenil)-5-fluoro-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-N4-(4-cianometoxifenil-5)-metil-2,4-pirimidindiamina; N2-(4-Aminosulfonil)fenil-N4-[4-(1-ciano)etoxi-3-metil]fenil-5-fluoro-2,4-pirimidindiamina racémica; N2-(4-Aminosulfonil)fenil-N4-[4-(1-ciano)etoxi-3,5-dimetil]fenil-5-fluoro-2,4-pirimidindiamina racémica; N2-(4-Aminosulfonil-3-metoxi)fenil-N4-[4-(1-ciano)etoxi-3-metil]fenil-5-fluoro-2,4-pirimidindiamina racémica; N2-(4-Aminosulfonil)fenil-N4-[4-(1-ciano)etoxi]fenil-5-fluoro-2,4-pirimidindiamina racémica; N2-(4-Aminosulfonil-3-metoxi)fenil-N4-[4-(1-ciano)etoxi]fenil-5-fluoro-2,4-pirimidindiamina racémica; N2-(4-Aminosulfonil)fenil-N4-[4-(1-ciano-1-metil)etoxi]fenil-5-fluoro-2,4-pirimidindiamina; N2-(4-Aminosulfonil-3-metoxi)fenil-N4-[4-(1-ciano-1-metil)etoxi]fenil-5-fluoro-2,4-pirimidindiamina; N4-(3-Aminocarbonilmetoxi)fenil-N2-(4-aminosulfonil)fenil-5-fluoro-2,4-pirimidindiamina; N4-(4-Aminocarbonilmetoxi-3-clorofenil)-N2-(4-aminosulfonilfenil)-5-fluoro-2,4-pirimidindiamina; N4-(4-Aminocarbonilmetoxi-3-fluorofenil)-N2-(4-aminosulfonilfenil)-5-fluoro-2,4-pirimidindiamina; N4-(4-Aminocarbonilmetoxi-3-metoxifenil)-N2-(4-aminosulfonilfenil)-5-fluoro-2,4-pirimidindiamina; N4-(4-Aminocarbonilmetoxifenil)-N2-(4-aminosulfonilfenil)-5-metil-2,4-pirimidindiamina; N4-(4-Aminocarbonilmetoxi-3-metil)fenil-N2-(4-aminosulfonil)fenil-5-fluoro-2,4-pirimidindiamina; N4-(4-Aminocarbonilmetoxi-3,5-dimetil)fenil-N2-(4-aminosulfonil)fenil-5-fluoro-2,4-pirimidindiamina; N4-(4-Aminocarbonilmetoxi)fenil-N2-(4-aminosulfonil)fenil-5-fluoro-2,4-pirimidindiamina; N4-[4-(1-Aminocarbonil)etoxi]fenil-N2-(4-aminosulfonil)fenil-5-fluoro-2,4-pirimidindiamina racémica; N4-[4-(1-Aminocarbonil)etoxi-3-metil]fenil-N2-(4-aminosulfonil)fenil-5-fluoro-2,4-pirimidindiamina racémica; N4-[4-(1-Aminocarbonil)etoxi-3,5-dimetil]fenil-N2-(4-aminosulfonil)fenil-5-fluoro-2,4-pirimidindiamina racémica; N4-[4-(1-Aminocarbonil-1-metil)etoxi]fenil-N2-(4-aminosulfonil)fenil-5-fluoro-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-N4-(4-dimetilaminocarbonilmetoxifenil)-5-fluoro-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-N4-(3-cloro-4-dimetilaminocarbonilmetoxifenil)-5-fluoro-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-N4-(3-cloro-4-dimetilaminocarbonilmetoxifenil)-5-metil-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-N4-(4-dimetilaminocarbonilmetoxi-3-fluorofenil)-5-metil-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-5-fluoro-N4-(4-metilaminocarbonilmetoxifenil)-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-N4-(3-cloro-4-metilaminocarbonilmetoxifenil)-5-fluoro-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-N4-(3-cloro-4-metilaminocarbonilmetoxifenil)-5-metil-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-N4-(3-fluoro-4-metilaminocarbonilmetoxifenil)-5-metil-2,4-pirimidindiamina; N4-(4-Alilaminocarbonilmetoxifenil)-N2-(4-aminosulfonilfenil)-5-fluoro-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-(2-piridinil)metilenooxifenil]-2,4-pirimidindiamina; N2-(3-Aminosulfonilpirid-4-il)-5-fluoro-N4-[4-(2-piridinil)metilenooxifenil]-2,4-pirimidindiamina; N2-[4-(2-N,N-Dietilaminoetil)aminosulfonilfenil)-5-fluoro-N4-[4-(2-piridinil)metilenooxifenil]-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-(2-piridinil)-3-clorometilenooxifenil]-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-(2-piridinil)-3-metilmetilenooxifenil]-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-(2-piridinil)-3-fluorometilenooxifenil]-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-5-metil-N4-[4-(2-piridinil)metilenooxifenil]-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[3-(3-piridinil)metilenooxifenil]-2,4-pirimidindiamina; N2-[4-(2-N,N-Dietilaminoetil)aminosulfonilfenil)-5-fluoro-N4-[3-(3-piridinil)metilenooxifenil]-2,4-pirimidindiamina; N2-[4-(2-N,N-Dietilaminoetil)aminosulfonilfenil)-5-fluoro-N4-[4-(3-piridinil)metilenooxifenil]-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-(2-morfolinoetiloxi)fenil)-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-metil-3-(2-morfolinocarbonilmetilenooxi)fenil]-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-(2-morfolin-4-il-2-oxo-etoxi)fenil]-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-(3-metil-1,2,4-oxadiazol-5-il)metilenooxifenil]-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[3metil-4-(5-metilisoxazol-3-il)metilenooxifenil]-2,4-pirimidindiamina; N2-[4-(2-N,N-Dietilaminoetil)aminosulfonilfenil)-5-fluoro-N4-[3-metil-4-(5-metilisoxazol-3-il)metilenooxifenil]-2,4pirimidindiamina; N2-[4-(2-N,N-Dietilaminoetil)aminosulfonilfenil)-5-fluoro-N4-[4-(5-metilisoxazol-3-il)metilenooxifenil]-2,4pirimidindiamina; N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[3-(3-metil-1,2,4-oxadiazol-5-il)metilenooxifenil]-2,4-pirimidindiamina; N2-[4-(2-N,N-Dietilaminoetil)aminosulfonilfenil)-5-fluoro-N4-[3-(3-metil-1,2,4-oxadiazol-5-il)metilenooxifenil]-2,4pirimidindiamina; N2-[4-(2-N,N-Dietilaminoetil)aminosulfonilfenil)-5-fluoro-N4-[4-(3-metil-1,2,4-oxadiazol-5-il)metilenooxifenil]-2,4pirimidindiamina; N2-(4-Aminosulfonilfenil)-5-fluoro-N4-(4-[3-metil-1,2,4-oxadiazol-5-il]metilenooxifenil)-2,4-pirimidindiamina; 5-Fluoro-N2-(4-N-metilaminosulfonil)-3-metoxifenil-N4-(4-trifluorometoxi-3-clorofenil)-2,4-pirimidindiamina; 5-fluoro-N4-(3-hidroxifenil)-N2-(4-N-metilaminosulfonil)-3-metoxifenil]-2,4-pirimidindiamina; 5-Fluoro-N4-(4-[3-metil-1,2,4-oxadiazol-5-il]metilenooxifenil)-N2-(5-piperidinsulfonilfenil)-2,4-pirimidindiamina; N2-(4-Aminosulfonil)fenil-5-fluoro-N4-[4-(5-metil-1,2,4-oxadiazol-3-il)metoxi]fenil-2,4-pirimidindiamina; N2-[4-(2-N,N-Dietilaminoetil)aminosulfonilfenil)-5-fluoro-N4-[4-(2-metiltiazol-4-il)metilenooxifenil]-2,4pirimidindiamina; N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-(2-metiltiazol-4-il)metilenooxifenil]-2,4-pirimidindiamina; N2-[4-(2-N,N-Dietilaminoetil)aminosulfonilfenil)-5-fluoro-N4-(4-cianometilfenil)-2,4-pirimidindiamina; N2-(4-Aminosulfonil)fenil-N4-(4-cianometil)fenil-5-fluoro-2,4-pirimidindiamina; N4-(4-Cianometil)fenil-5-fluoro-N2-[4-(4-metilpiperazin-1-il)sulfonil]fenil-2,4-pirimidindiamina; N2-(4-Aminosulfonil-3-metoxi)fenil-N4-(4-cianometil)fenil-5-fluoro-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-N4-(4-cianoetilenofenil)-5-metil-2,4-pirimidindiamina; N4-(4-Aminocarbonilaminometilfenil)-N2-(4-aminosulfonilfenil)-5-fluoro-2,4-pirimidindiamina; N2-(4-aminosulfonil)fenil-N4-(4-etilcarbonilaminometil)fenil-5-fluoro-2,4-pirimidindiamina; N2-(4-aminosulfonil)fenil-N4-(3-ciclopropilcarbonilaminometil)fenil-5-fluoro-2,4-pirimidindiamina; N2-(4-aminosulfonil)fenil-N4-(4-ciclopropilcarbonilaminometil)fenil-5-fluoro-2,4-pirimidindiamina; N4-(4-Acrilamidometilfenil)-N2-(4-aminosulfonilfenil)-5-fluoro-2,4-pirimidindiamina; N4-[4-(2-Aminocarboxiletileno)fenil]-N2-(4-aminosulfonilfenil)-5-fluoro-2,4-pirimidindiamina; N2-[4-(2-N,N-Dietilaminoetil)aminosulfonilfenil)-5-fluoro-N4-[4-(4-piridinilmetil)fenil]-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-(4-piridinilmetil)fenil]-2,4-pirimidindiamina; N2-[4-(2-N,N-Dietilaminoetil)aminosulfonilfenil)-5-fluoro-N4-[4-(4-piridinilmetil)fenil]-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-(4-piridinil)fenetil]-2,4-pirimidindiamina; N2-[4-(2-N,N-Dietilaminoetil)aminosulfonilfenil)-5-fluoro-N4-[4-(1-imidazolilmetil)fenil]-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-(1-imidazolil)fenetil]-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-(2-metil-1-imidazolilmetil)fenil]-2,4-pirimidindiamina; N2-4-Aminosulfonilfenil)-5-fluoro-N4-{4-[1-(1,2,3-triazolil)metil]fenil}-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-5-fluoro-N4-{4-[1-(1,2,4-triazolil)metil]fenil}-2,4-pirimidindiamina; N4-(3-Aminocarbonilaminometil)fenil-N2-(4-aminosulfonil)fenil-5-fluoro-2,4-pirimidindiamina; N2-(4-Aminosulfonil)fenil-N4-(3-etilaminocarbonilaminometil)fenil-5-fluoro-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-N4-(4-etilaminocarbonilaminometilfenil]-5-fluoro-2,4-pirimidindiamina; N2-(4-aminosulfonil)fenil-N4-[4-(2-etilaminocarbonilamino)etil]fenil-5-fluoro-2,4-pirimidindiamina; N2-(4-aminosulfonil)fenil-N4-[4-(N-carbamoil-N-propil)aminometil]fenil-5-fluoro-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[3-(1,3-oxazol-5-il)fenil]-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-(1,3-oxazol-5-il)fenil]-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[3-oxo-4-(2-piridilmetil)-benz[1,4]oxazin-6-il]-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[2-metil-3-oxo-4-(4-metoxibencil)-benz[1,4]oxazin-6-il]-2,4-pirimidindiamina racémica; N2-(4-Aminosulfonilfenil)-5-fluoro-N4-(3-oxo-4-cianometil-benz[1,4]oxazin-6-il]-2,4-pirimidindiamina; (R/S)-N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[2-metil-3-oxo-4-(4-metoxibencil)-benzo[1,4]tiazin-6-il]-2,4pirimidindiamina; N2-(4-Aminosulfonilfenil)-5-fluoro-N4-(3-oxo-4-cianometil-benzo[1,4]tiazin-6-il)-2,4-pirimidindiamina; 5-Fluoro-N4-(3-hidroxifenil)-N2-[4-(N-metil)aminosulfonil-3-metoxifenil]-2,4-pirimidindiamina; N2-(3-Aminosulfonilpirid-4-il)-N4-(3-cloro-4-metoxifenil)-5-fluoro-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-(prop-2-inilaminosulfonil) fenil]-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[3-(prop-2-inilaminosulfonil)fenil]-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-(3-fluoropropil)fenil]-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-(3-hidroxipropil)fenil]-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-(4-hidroxibutil)fenil]-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-(4-fluorobutil)fenil]-2,4-pirimidindiamina; N2-(4-aminosulfonil)fenil-5-fluoro-N4-(4-tiometilcarbonil)fenil-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-5-fluoro-N4-(4-metoxi-3-clorofenil]-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-N4-(3,4-diclorofenil)-5-fluoro-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-5-fluoro-N4-(2,2,4-trimetil-1,1,3-trioxo-benzo[1,4]tiazin-6-il)-2,4-pirimidindiamina; N2-(4-Aminosulfonil)fenil-N4-[(N-etilsulfonil)-1,2,3,4-tetrahidroisoquinolin-6-il]-5-fluoro-2,4-pirimidindiamina; N4-(3,4-Etilendioxifenil)-5-fluoro-N2-[4-(pirrolidin-1-ilsulfonil)fenil]-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-N4-(croman-4-amina-6-il)-5-fluoro-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-5-metil-N4-(3-oxo-benz[1,4]oxazin-6-il)-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-5-metil-N4-(4-metil-3-oxo-benzo[1,4]tiazin-6-il)-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-5-fluoro-N4-(4-metil-3-oxo-benz[1,4]oxazin-6-il)-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-N4-[2,2,4-trimetil-3-oxo-5-pirid[1,4]oxazin-5-il]-5-fluoro-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-N4-cianometil-5-fluoro-N4-[3-oxo-4-metil-benzo[1,4]tiazin-6-il]-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-5-fluoro-N4-(4-metil-3-oxo-benz[1,4]tiazin-6-il)-2,4-pirimidindiamina; 5-Fluoro-N4-(4-metil-3-oxo-benz[1,4]tiazin-6-il)-N2-(3-piperidinosulfonilfenil)-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-N4-[2,2-dimetil-3-oxo-4H-5-pirid[1,4]oxazin-7-il]-5-fluoro-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-N4-(4-N-terc-butoxicarbonilamino-3,4-dihidro-2H-1-benzopiran-6-il)-5-fluoro-2,4pirimidindiamina; N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[4-(1-metilsulfonil)indolin-5-il]-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[4-(1-metilsulfonil)indolin-5-il]-2,4-pirimidindiamina; 5-Fluoro-N2-[3-(N-metilaminosulfonil)-4-metilfenil]-N4-[4-(1-metilsulfonil)indolin-5-il]-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-5-fluoro-N4-[4-(1-metilsulfonil)indolin-5-il]-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[1-(propin-3-il)indol-5-il]-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[1-(propin-3-il)indol-5-il]-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-5-fluoro-N4-[1-(propin-3-il)indol-6-il]-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-5-fluoro-N4-[1-(propin-3-il)indol-6-il]-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-N4-(1-cianometilenoindol-5-il)-5-fluoro-2,4-pirimidindiamina; N2-(4-Aminosulfonilfenil)-N4-(1-cianometilenoindol-5-il)-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-clorofenil)-N4-(1-cianometilenoindol-5-il)-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-N4-(1-cianometilenoindol-5-il)-5-fluoro-2,4-pirimidindiamina; N4-[3-(Aminocarbonil)-1H-indol-6-il]-N2-(3-aminosulfonil-4-metilfenil)-5-fluoro-2,4-pirimidindiamina; N4-[3-(Aminocarbonil)-1H-indol-6-il]-N2-(3-aminosulfonil-4-clorofenil)-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonil-4-metilfenil)-N4-(3-cianometil-1H-indol-6-il)-5-fluoro-2,4-pirimidindiamina; N2-(3-Aminosulfonilfenil)-N4-(3-cianometil-1H-indol-6-il)-5-fluoro-2,4-pirimidindiamina;
    imagen10
  3. 18.
    El compuesto para su uso de acuerdo con la reivindicación 17, en el que el inmunosupresor se selecciona entre ciclosporina, tacrolimus, sirolimus, un inhibidor de IMPDH, micofenolato, micofenolato de mofetilo, un anticuerpo dirigido contra linfocitos T y OKT3.
  4. 19.
    El compuesto para su uso en un método para tratar o prevenir una reacción de hipersensibilidad de Tipo IV de acuerdo con la reivindicación 12, en el que dicho método se realiza de manera profiláctica.
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Families Citing this family (137)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
TWI329105B (en) * 2002-02-01 2010-08-21 Rigel Pharmaceuticals Inc 2,4-pyrimidinediamine compounds and their uses
DK1534286T3 (da) 2002-07-29 2010-04-26 Rigel Pharmaceuticals Inc Fremgangsmåder til behandling eller forebyggelse af autoimmune sygdomme med 2,4-pyrimidindiamin-forbindelser
RS53109B (en) 2003-07-30 2014-06-30 Rigel Pharmaceuticals Inc. 2,4 PIRIMIDINDIAMINE COMPOUNDS FOR USE IN TREATMENT OR PREVENTION OF AUTOIMMUNE DISEASES
WO2006068770A1 (en) 2004-11-24 2006-06-29 Rigel Pharmaceuticals, Inc. Spiro-2, 4-pyrimidinediamine compounds and their uses
PT1856135E (pt) 2005-01-19 2010-02-26 Rigel Pharmaceuticals Inc Pró-fármacos de compostos 2,4-pirimidinodiamina e suas utilizações
ES2651349T3 (es) 2005-06-08 2018-01-25 Rigel Pharmaceuticals, Inc. Composiciones y métodos para la inhibición de la ruta JAK
US20070203161A1 (en) * 2006-02-24 2007-08-30 Rigel Pharmaceuticals, Inc. Compositions and methods for inhibition of the jak pathway
US7576053B2 (en) 2005-06-13 2009-08-18 Rigel Pharmaceuticals, Inc. Methods and compositions for treating degenerative bone disorders
WO2007053452A1 (en) 2005-11-01 2007-05-10 Targegen, Inc. Bi-aryl meta-pyrimidine inhibitors of kinases
US8133900B2 (en) 2005-11-01 2012-03-13 Targegen, Inc. Use of bi-aryl meta-pyrimidine inhibitors of kinases
US8604042B2 (en) 2005-11-01 2013-12-10 Targegen, Inc. Bi-aryl meta-pyrimidine inhibitors of kinases
US7713987B2 (en) * 2005-12-06 2010-05-11 Rigel Pharmaceuticals, Inc. Pyrimidine-2,4-diamines and their uses
PT2455382T (pt) 2005-12-13 2017-01-31 Incyte Holdings Corp Pirrolo[2,3-b]piridinas e pirrolo[2,3-b]pirimidinas substituídas por heteroarilo como inibidores de janus quinases
US7659280B2 (en) * 2006-02-17 2010-02-09 Rigel Pharmaceuticals, Inc. 2,4-pyrimidinediamine compounds for treating or preventing autoimmune diseases
WO2007098507A2 (en) 2006-02-24 2007-08-30 Rigel Pharmaceuticals, Inc. Compositions and methods for inhibition of the jak pathway
MX2008016004A (es) 2006-06-15 2009-01-16 Boehringer Ingelheim Int 2-anilino-4-(heterociclo)amino-pirimidinas en calidad de inhibidores de la proteina quinasa c-alfa.
ATE497496T1 (de) 2006-10-19 2011-02-15 Rigel Pharmaceuticals Inc 2,4-pyridimediamon-derivate als hemmer von jak- kinasen zur behandlung von autoimmunerkrankungen
WO2008051547A1 (en) 2006-10-23 2008-05-02 Cephalon, Inc. Fused bicyclic derivatives of 2,4-diaminopyrimidine as alk and c-met inhibitors
DK2078026T3 (da) 2006-11-21 2012-04-30 Rigel Pharmaceuticals Inc Prodrug-salte af 2, 4-pyrimidinediamine-forbindelser og anvendelser deraf
RS53588B1 (en) 2006-12-08 2015-02-27 Irm Llc COMPOUNDS AND COMPOSITIONS AS PROTEIN KINASE INHIBITORS
WO2008118822A1 (en) * 2007-03-23 2008-10-02 Rigel Pharmaceuticals, Inc. Compositions and methods for inhibition of the jak pathway
US7834024B2 (en) 2007-03-26 2010-11-16 Rigel Pharmaceuticals, Inc. Compositions and methods for inhibition of the JAK pathway
NZ581397A (en) * 2007-04-27 2012-02-24 Astrazeneca Ab Pyrimidine compounds for the inhibition of Eph receptors and for the treatment of cancer
ES2903444T3 (es) 2007-06-13 2022-04-01 Incyte Holdings Corp Uso de sales del inhibidor de quinasas Janus (R)-3-(4-(7H-pirrolo[2,3-d]pirimidin-4-il)-1H-pirazol-1-il)-3-ciclopentilpropanonitrilo
BRPI0814432A2 (pt) 2007-07-17 2017-05-09 Rigel Pharmaceuticals Inc pirimidinadiaminas substituídas por amina cíclica como inibidores de pkc
FR2919869B1 (fr) * 2007-08-09 2009-09-25 Sanofi Aventis Sa Nouveaux derives de n, n'-2,4-dianilinopyrimidines, leur preparation a titre de medicaments, compositions pharmaceutiques et notamment comme inhibiteurs de ikk
WO2009109991A2 (en) * 2008-01-23 2009-09-11 Sun Pharma Advanced Research Company Ltd., Novel hydrazide containing tyrosine kinase inhibitors
ES2645689T5 (en) 2008-05-21 2025-06-24 Takeda Pharmaceuticals Co Phosphorous derivatives as kinase inhibitors
US9273077B2 (en) 2008-05-21 2016-03-01 Ariad Pharmaceuticals, Inc. Phosphorus derivatives as kinase inhibitors
PE20110063A1 (es) 2008-06-20 2011-02-16 Genentech Inc DERIVADOS DE [1, 2, 4]TRIAZOLO[1, 5-a]PIRIDINA COMO INHIBIDORES DE JAK
SG178812A1 (en) 2008-06-20 2012-03-29 Genentech Inc Triazolopyridine jak inhibitor compounds and methods
US8338439B2 (en) * 2008-06-27 2012-12-25 Celgene Avilomics Research, Inc. 2,4-disubstituted pyrimidines useful as kinase inhibitors
AU2009262068C1 (en) 2008-06-27 2015-07-02 Celgene Car Llc Heteroaryl compounds and uses thereof
US11351168B1 (en) 2008-06-27 2022-06-07 Celgene Car Llc 2,4-disubstituted pyrimidines useful as kinase inhibitors
EP2341052A4 (en) * 2008-09-05 2011-10-12 Shionogi & Co RING-CONDENSED MORPHOLINE DERIVATIVITY WITH PI3K-INHIBITING EFFECT
MX2011002470A (es) * 2008-09-08 2011-04-05 Merck Patent Gmbh Pirimidinas macrociclicas como inhibidores de aurora cinasa.
US8846908B2 (en) * 2008-09-23 2014-09-30 Rigel Pharmaceuticals, Inc. Tricyclic carbamate JAK inhibitors
CL2009001884A1 (es) * 2008-10-02 2010-05-14 Incyte Holdings Corp Uso de 3-ciclopentil-3-[4-(7h-pirrolo[2,3-d]pirimidin-4-il)-1h-pirazol-1-il)propanonitrilo, inhibidor de janus quinasa, y uso de una composición que lo comprende para el tratamiento del ojo seco.
CA2745004C (en) 2008-11-28 2014-07-15 Kowa Company, Ltd. Pyridine-3-carboxyamide derivative
US8809343B2 (en) * 2008-12-26 2014-08-19 Fudan University Pyrimidine derivative, preparation method and use thereof
CA2749195C (en) 2009-01-15 2017-03-07 Rigel Pharmaceuticals, Inc. Protein kinase c inhibitors and uses thereof
HUE026315T2 (en) 2009-01-23 2016-06-28 Rigel Pharmaceuticals Inc Preparations and methods for inhibiting the JAK pathway
CN102482277B (zh) 2009-05-05 2017-09-19 达纳-法伯癌症研究所有限公司 表皮生长因子受体抑制剂及治疗障碍的方法
TW201100429A (en) 2009-05-22 2011-01-01 Incyte Corp N-(hetero)aryl-pyrrolidine derivatives of pyrazol-4-yl-pyrrolo[2,3-d]pyrimidines and pyrrol-3-yl-pyrrolo[2,3-d]pyrimidines as janus kinase inhibitors
WO2010135621A1 (en) 2009-05-22 2010-11-25 Incyte Corporation 3-[4-(7h-pyrrolo[2,3-d]pyrimidin-4-yl)-1h-pyrazol-1-yl]octane- or heptane-nitrile as jak inhibitors
CN102498110A (zh) 2009-06-10 2012-06-13 雅培制药有限公司 作为激酶抑制剂的2-(lh-吡唑-4-基氨基)-嘧啶
CN106420756A (zh) 2009-07-28 2017-02-22 里格尔药品股份有限公司 抑制jak途径的组合物和方法
AR078012A1 (es) 2009-09-01 2011-10-05 Incyte Corp Derivados heterociclicos de las pirazol-4-il- pirrolo (2,3-d) pirimidinas como inhibidores de la quinasa janus
JP5629324B2 (ja) 2009-10-15 2014-11-19 ファイザー・インク ピロロ［２，３−ｄ］ピリミジン化合物
CA2782720A1 (en) 2009-12-18 2011-06-23 Pfizer Inc. Pyrrolo[2,3-d]pyrimidine compounds
WO2011100455A1 (en) 2010-02-12 2011-08-18 The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services Inhibition of antibody responses to foreign proteins
TWI592413B (zh) 2010-03-10 2017-07-21 英塞特公司 作為ｊａｋ１抑制劑之哌啶-４-基三亞甲亞胺衍生物
US8927547B2 (en) 2010-05-21 2015-01-06 Noviga Research Ab Pyrimidine derivatives
UA111588C2 (uk) 2010-05-21 2016-05-25 Інсайт Холдінгс Корпорейшн Композиція інгібітора jak для місцевого застосування
ES2593256T3 (es) 2010-05-21 2016-12-07 Infinity Pharmaceuticals, Inc. Compuestos químicos, composiciones y métodos para las modulaciones de cinasas
EP2395001A1 (en) 2010-05-21 2011-12-14 Chemilia AB Novel pyrimidine derivatives
KR101531448B1 (ko) 2010-06-04 2015-06-24 에프. 호프만-라 로슈 아게 Lrrk2 조절제로서의 아미노피리미딘 유도체
EP2595982B1 (en) * 2010-07-21 2018-06-13 Rigel Pharmaceuticals, Inc. Protein kinase c inhibitors and uses thereof
RU2013109393A (ru) 2010-08-10 2014-09-20 Сэлджин Авиаломикс Ресеарч, Инк. Безилатная соль ингибитора втк
CA2815858C (en) 2010-11-01 2018-10-16 Celgene Avilomics Research, Inc. Heterocyclic compounds and uses thereof
WO2012061303A1 (en) 2010-11-01 2012-05-10 Avila Therapeutics, Inc. Heteroaryl compounds and uses thereof
US9198911B2 (en) 2010-11-02 2015-12-01 The Trustees Of Columbia University In The City Of New York Methods for treating hair loss disorders
WO2012060847A1 (en) 2010-11-07 2012-05-10 Targegen, Inc. Compositions and methods for treating myelofibrosis
HRP20172006T1 (hr) 2010-11-10 2018-02-09 Genentech, Inc. Derivati pirazol-aminopiridina kao lrrk2-modulatori
JP5957003B2 (ja) 2010-11-10 2016-07-27 セルジーン アヴィロミクス リサーチ， インコーポレイテッド 変異体選択的ｅｇｆｒ阻害剤およびその使用
WO2012068450A1 (en) 2010-11-19 2012-05-24 Incyte Corporation Cyclobutyl substituted pyrrolopyridine and pyrrolopyrimidine derivatives as jak inhibitors
EP2640725B1 (en) 2010-11-19 2015-01-07 Incyte Corporation Heterocyclic-substituted pyrrolopyridines and pyrrolopyrimidines as jak inhibitors
HRP20181286T1 (hr) 2011-03-10 2018-10-05 Rigel Pharmaceuticals, Inc. 2,4 supstituirani pirimidindiamini za uporabu kod diskoidnog lupusa
ES2587864T3 (es) 2011-03-24 2016-10-27 Noviga Research Ab Derivados de pirimidina
EP2502924A1 (en) 2011-03-24 2012-09-26 Chemilia AB Novel pyrimidine derivatives
BR112013027734A2 (pt) 2011-05-04 2017-08-08 Ariad Pharma Inc compostos para a inibição de proliferação celular em cânceres impulsionados pelo egfr, método e composição farmacêutica
US9120785B2 (en) 2011-05-10 2015-09-01 Merck Sharp & Dohme Corp. Pyridyl aminopyridines as Syk inhibitors
JP2014513686A (ja) 2011-05-10 2014-06-05 メルク・シャープ・アンド・ドーム・コーポレーション Ｓｙｋ阻害薬としてのアミノピリミジン
WO2012154518A1 (en) 2011-05-10 2012-11-15 Merck Sharp & Dohme Corp. Bipyridylaminopyridines as syk inhibitors
AU2012273164B2 (en) 2011-06-20 2015-05-28 Incyte Holdings Corporation Azetidinyl phenyl, pyridyl or pyrazinyl carboxamide derivatives as JAK inhibitors
TW201313721A (zh) 2011-08-18 2013-04-01 Incyte Corp 作為ｊａｋ抑制劑之環己基氮雜環丁烷衍生物
MX2014002542A (es) 2011-08-29 2014-07-09 Infinity Pharmaceuticals Inc Compuestos heterociclicos y usos de los mismos.
UA111854C2 (uk) 2011-09-07 2016-06-24 Інсайт Холдінгс Корпорейшн Способи і проміжні сполуки для отримання інгібіторів jak
US9006444B2 (en) 2011-10-05 2015-04-14 Merck Sharp & Dohme Corp. Phenyl carboxamide-containing spleen tyrosine kinase (SYK) inhibitors
EP2763976B1 (en) 2011-10-05 2016-05-18 Merck Sharp & Dohme Corp. 2-pyridyl carboxamide-containing spleen tyrosine kinase (syk) inhibitors
US8987456B2 (en) 2011-10-05 2015-03-24 Merck Sharp & Dohme Corp. 3-pyridyl carboxamide-containing spleen tyrosine kinase (SYK) inhibitors
TW201325593A (zh) 2011-10-28 2013-07-01 Celgene Avilomics Res Inc 治療布魯頓（ｂｒｕｔｏｎ’ｓ）酪胺酸激酶疾病或病症之方法
CA2857189A1 (en) * 2011-12-08 2013-06-13 Rigel Pharmaceuticals, Inc. Topical formulation for administering a compound
EP2825042B1 (en) 2012-03-15 2018-08-01 Celgene CAR LLC Salts of an epidermal growth factor receptor kinase inhibitor
KR102081042B1 (ko) 2012-03-15 2020-02-26 셀젠 카르 엘엘씨 상피 성장 인자 수용체 키나제 억제제의 고체 형태
US20150166591A1 (en) 2012-05-05 2015-06-18 Ariad Pharmaceuticals, Inc. Methods and compositions for raf kinase mediated diseases
WO2013173720A1 (en) 2012-05-18 2013-11-21 Incyte Corporation Piperidinylcyclobutyl substituted pyrrolopyridine and pyrrolopyrimidine derivatives as jak inhibitors
WO2013192128A1 (en) 2012-06-20 2013-12-27 Merck Sharp & Dohme Corp. Imidazolyl analogs as syk inhibitors
EP2863914B1 (en) 2012-06-20 2018-10-03 Merck Sharp & Dohme Corp. Pyrazolyl derivatives as syk inhibitors
WO2013192098A1 (en) 2012-06-22 2013-12-27 Merck Sharp & Dohme Corp. SUBSTITUTED PYRIDINE SPLEEN TYROSINE KINASE (Syk) INHIBITORS
WO2013192088A1 (en) 2012-06-22 2013-12-27 Merck Sharp & Dohme Corp. SUBSTITUTED DIAZINE AND TRIAZINE SPLEEN TYROSINE KINASE (Syk) INHIBITORS
EP2884982B1 (en) 2012-08-20 2017-09-20 Merck Sharp & Dohme Corp. SUBSTITUTED PHENYL SPLEEN TYROSINE KINASE (Syk) INHIBITORS
CA2884710A1 (en) 2012-09-12 2014-03-20 Rigel Pharmaceuticals, Inc. Treatment for vitiligo
EP2711364A1 (en) 2012-09-21 2014-03-26 Chemilia AB 4-(Indolyl or benzimidazolyl)amino-2-(2-(indol-3-yl)ethyl)aminopyrimidines useful for the treatment of cancer
EP2711365A1 (en) 2012-09-21 2014-03-26 Chemilia AB 4-Indazolylamino-2-(2-(indol-3-yl)ethyl)aminopyrimidines useful for the treatment of cancer
US9586931B2 (en) 2012-09-28 2017-03-07 Merck Sharp & Dohme Corp. Triazolyl derivatives as Syk inhibitors
ES2880814T3 (es) 2012-11-15 2021-11-25 Incyte Holdings Corp Formas de dosificación de liberación sostenida de ruxolitinib
US9624210B2 (en) 2012-12-12 2017-04-18 Merck Sharp & Dohme Corp. Amino-pyrimidine-containing spleen tyrosine kinase (Syk) inhibitors
WO2014100748A1 (en) 2012-12-21 2014-06-26 Celgene Avilomics Research, Inc. Heteroaryl compounds and uses thereof
WO2014100314A1 (en) 2012-12-21 2014-06-26 Merck Sharp & Dohme Corp. Thiazole-substituted aminopyridines as spleen tyrosine kinase inhibitors
EP2953457B1 (en) 2013-02-08 2020-04-08 Celgene CAR LLC Erk inhibitors and uses thereof
CR20190518A (es) 2013-03-06 2020-01-10 Incyte Corp PROCESOS E INTERMEDIOS PARA HACER UN INHIBIDOR DE JAK (Divisional 2015-0471)
US9481667B2 (en) 2013-03-15 2016-11-01 Infinity Pharmaceuticals, Inc. Salts and solid forms of isoquinolinones and composition comprising and methods of using the same
US9611283B1 (en) 2013-04-10 2017-04-04 Ariad Pharmaceuticals, Inc. Methods for inhibiting cell proliferation in ALK-driven cancers
EP2988749B1 (en) 2013-04-26 2019-08-14 Merck Sharp & Dohme Corp. Thiazole-substituted aminopyrimidines as spleen tyrosine kinase inhibitors
US9745295B2 (en) 2013-04-26 2017-08-29 Merck Sharp & Dohme Corp. Thiazole-substituted aminoheteroaryls as spleen tyrosine kinase inhibitors
KR20160045081A (ko) 2013-08-07 2016-04-26 인사이트 코포레이션 Jak1 억제제용 지속 방출 복용 형태
US9492471B2 (en) 2013-08-27 2016-11-15 Celgene Avilomics Research, Inc. Methods of treating a disease or disorder associated with Bruton'S Tyrosine Kinase
BR112016008080B1 (pt) * 2013-10-16 2021-02-23 Fujifilm Corporation sal de ácido carboxílico ou um sal de ácido mineral, cristal de succinato, cristal de fumarato e composição farmacêutica
WO2015095444A1 (en) 2013-12-20 2015-06-25 Merck Sharp & Dohme Corp. Thiazole-substituted aminoheteroaryls as spleen tyrosine kinase inhibitors
US9415049B2 (en) 2013-12-20 2016-08-16 Celgene Avilomics Research, Inc. Heteroaryl compounds and uses thereof
EP3082807B1 (en) 2013-12-20 2018-07-04 Merck Sharp & Dohme Corp. Thiazole-substituted aminoheteroaryls as spleen tyrosine kinase inhibitors
EP3083559B1 (en) 2013-12-20 2021-03-10 Merck Sharp & Dohme Corp. Thiazole-substituted aminoheteroaryls as spleen tyrosine kinase inhibitors
US10793571B2 (en) 2014-01-31 2020-10-06 Dana-Farber Cancer Institute, Inc. Uses of diazepane derivatives
CN106029653A (zh) 2014-01-31 2016-10-12 达纳-法伯癌症研究所股份有限公司 二氨基嘧啶苯砜衍生物及其用途
US9775839B2 (en) 2014-03-13 2017-10-03 Merck Sharp & Dohme Corp. 2-pyrazine carboxamides as spleen tyrosine kinase inhibitors
US9498467B2 (en) 2014-05-30 2016-11-22 Incyte Corporation Treatment of chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML) by inhibitors of JAK1
CN106715437A (zh) 2014-08-08 2017-05-24 达纳-法伯癌症研究所股份有限公司 二氮杂环庚烷衍生物及其用途
WO2016025561A1 (en) 2014-08-13 2016-02-18 Celgene Avilomics Research, Inc. Forms and compositions of an erk inhibitor
WO2016027904A1 (ja) 2014-08-22 2016-02-25 富士フイルム株式会社 Ｆｌｔ３変異陽性癌を処置するための医薬組成物、変異型ｆｌｔ３阻害剤およびそれらの応用
CA2986441A1 (en) 2015-06-12 2016-12-15 Dana-Farber Cancer Institute, Inc. Combination therapy of transcription inhibitors and kinase inhibitors
JP6412471B2 (ja) 2015-07-15 2018-10-24 富士フイルム株式会社 含窒素複素環化合物の製造方法およびその中間体
WO2017044792A1 (en) 2015-09-11 2017-03-16 Dana-Farber Cancer Institute, Inc. Acetamide thienotriazoldiazepines and uses thereof
JP2018526421A (ja) 2015-09-11 2018-09-13 ダナ−ファーバー キャンサー インスティテュート， インコーポレイテッド シアノチエノトリアゾロジアゼピンおよびこれらの使用
MX2018006499A (es) 2015-11-25 2018-08-01 Dana Farber Cancer Inst Inc Inhibidores de bromodominio bivalentes y usos de los mismos.
US11001570B2 (en) * 2016-12-13 2021-05-11 Boehringer Ingelheim International Gmbh 6-amino-quinolinone compounds and derivatives as BCL6 inhibitors
KR20190043437A (ko) 2017-10-18 2019-04-26 씨제이헬스케어 주식회사 단백질 키나제 억제제로서의 헤테로고리 화합물
CN107805212B (zh) * 2017-11-03 2021-08-20 宿迁德威化工股份有限公司 一种2-甲基-5-氨基苯磺酰胺的制备方法
WO2019113487A1 (en) 2017-12-08 2019-06-13 Incyte Corporation Low dose combination therapy for treatment of myeloproliferative neoplasms
AU2019213665B2 (en) 2018-01-30 2024-06-13 Incyte Corporation Processes for preparing (1 -(3-fluoro-2-(trifluoromethyl)isonicotinyl)piperidine-4-one)
SG11202009441PA (en) 2018-03-30 2020-10-29 Incyte Corp Treatment of hidradenitis suppurativa using jak inhibitors
KR102195348B1 (ko) 2018-11-15 2020-12-24 에이치케이이노엔 주식회사 단백질 키나제 억제제로서의 신규 화합물 및 이를 포함하는 약제학적 조성물
EP4009974A1 (en) 2019-08-08 2022-06-15 Rigel Pharmaceuticals, Inc. Compounds and method for treating cytokine release syndrome
CN112824420B (zh) * 2019-11-21 2022-04-26 浙江同源康医药股份有限公司 用作egfr激酶抑制剂的化合物及其应用
US11833155B2 (en) 2020-06-03 2023-12-05 Incyte Corporation Combination therapy for treatment of myeloproliferative neoplasms
CN116444512A (zh) * 2023-04-13 2023-07-18 常州英诺升康生物医药科技有限公司 一种苯磺酰胺化合物的制备方法
US11773084B1 (en) * 2023-04-14 2023-10-03 King Faisal University 4-arylamino-2-(6-indolylamino)pyrimidine compounds as antibacterial agents

Family Cites Families (169)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4166452A (en) 1976-05-03 1979-09-04 Generales Constantine D J Jr Apparatus for testing human responses to stimuli
US4256108A (en) 1977-04-07 1981-03-17 Alza Corporation Microporous-semipermeable laminated osmotic system
US4166542A (en) * 1977-12-05 1979-09-04 Bryan John F Jr Telescoping lattice boom crane
US4265874A (en) 1980-04-25 1981-05-05 Alza Corporation Method of delivering drug with aid of effervescent activity generated in environment of use
CN87210811U (zh) 1987-07-25 1988-04-20 徐正斌 方便投药盒
US5728536A (en) 1993-07-29 1998-03-17 St. Jude Children's Research Hospital Jak kinases and regulation of Cytokine signal transduction
SK47096A3 (en) 1993-10-12 1996-10-02 Du Pont Merck Pharma 1n-alkyl-n-arylpyrimidinamines and derivatives thereof
US5700904A (en) 1995-06-07 1997-12-23 Eli Lilly And Company Preparation of an acylated protein powder
US6316635B1 (en) 1995-06-07 2001-11-13 Sugen, Inc. 2-indolinone derivatives as modulators of protein kinase activity
GB9523675D0 (en) 1995-11-20 1996-01-24 Celltech Therapeutics Ltd Chemical compounds
US6696448B2 (en) 1996-06-05 2004-02-24 Sugen, Inc. 3-(piperazinylbenzylidenyl)-2-indolinone compounds and derivatives as protein tyrosine kinase inhibitors
JPH10271051A (ja) 1997-03-11 1998-10-09 Alcatel Alsthom Co General Electricite 双方向等化を伴う送／受信装置
US6316429B1 (en) 1997-05-07 2001-11-13 Sugen, Inc. Bicyclic protein kinase inhibitors
US6486185B1 (en) 1997-05-07 2002-11-26 Sugen, Inc. 3-heteroarylidene-2-indolinone protein kinase inhibitors
GB9718913D0 (en) 1997-09-05 1997-11-12 Glaxo Group Ltd Substituted oxindole derivatives
US6133305A (en) 1997-09-26 2000-10-17 Sugen, Inc. 3-(substituted)-2-indolinones compounds and use thereof as inhibitors of protein kinase activity
BR9908004A (pt) 1998-02-17 2001-12-18 Tularik Inc Composto, composição e método para prevençãoou supressão de uma infecção viral
WO2000000202A1 (en) 1998-06-30 2000-01-06 Parker Hughes Institute Method for inhibiting c-jun expression using jak-3 inhibitors
KR20010089171A (ko) 1998-08-21 2001-09-29 추후제출 퀴나졸린 유도체
ATE342892T1 (de) 1998-08-29 2006-11-15 Astrazeneca Ab Pyrimidine verbindungen
EE05086B1 (et) 1998-11-10 2008-10-15 Janssen Pharmaceutica N.V. Primidiini derivaadid, nende valmistamismeetod ja kasutamine, farmatseutiline kompositsioon ja selle valmistamismeetod, kombinatsioon ning saadus
GB9828511D0 (en) 1998-12-24 1999-02-17 Zeneca Ltd Chemical compounds
US6841567B1 (en) 1999-02-12 2005-01-11 Cephalon, Inc. Cyclic substituted fused pyrrolocarbazoles and isoindolones
GB9904995D0 (en) 1999-03-04 1999-04-28 Glaxo Group Ltd Substituted aza-oxindole derivatives
US6624171B1 (en) 1999-03-04 2003-09-23 Smithkline Beecham Corporation Substituted aza-oxindole derivatives
US6080747A (en) 1999-03-05 2000-06-27 Hughes Institute JAK-3 inhibitors for treating allergic disorders
US7125875B2 (en) 1999-04-15 2006-10-24 Bristol-Myers Squibb Company Cyclic protein tyrosine kinase inhibitors
GB9914258D0 (en) 1999-06-18 1999-08-18 Celltech Therapeutics Ltd Chemical compounds
WO2001045641A2 (en) 1999-11-30 2001-06-28 Parker Hughes Institute Inhibitors of thrombin induced platelet aggregation
HU229671B1 (en) 1999-12-10 2014-04-28 Pfizer Prod Inc Pyrrolo[2,3-d]pirimidine compounds
ES2245955T3 (es) 1999-12-21 2006-02-01 Sugen, Inc. 7-aza-indolin-2-onas 4-sustituidas y su utilizacion como inhibidores de proteina-quinasa.
ATE449764T1 (de) 1999-12-28 2009-12-15 Pharmacopeia Inc Cytokine, insbesondere tnf-alpha, hemmer
US20020065270A1 (en) 1999-12-28 2002-05-30 Moriarty Kevin Joseph N-heterocyclic inhibitors of TNF-alpha expression
AU2968701A (en) 2000-01-24 2001-07-31 Genzyme Corporation Jak/stat pathway inhibitors and the uses thereof
DE10003668B4 (de) 2000-01-28 2005-09-15 Xion Gmbh Flexibles Endoskop
EP1196390A2 (en) 2000-02-05 2002-04-17 Vertex Pharmaceuticals Incorporated Pyrazole compositions useful as inhibitors of erk
SK14082001A3 (sk) 2000-02-05 2002-03-05 Vertex Pharmaceuticals Incorporated Deriváty pyrazolu ako inhibítory ERK a farmaceutická kompozícia, ktorá ich obsahuje
WO2001060816A1 (en) 2000-02-17 2001-08-23 Amgen Inc. Kinase inhibitors
GB0004887D0 (en) 2000-03-01 2000-04-19 Astrazeneca Uk Ltd Chemical compounds
GB0004888D0 (en) * 2000-03-01 2000-04-19 Astrazeneca Uk Ltd Chemical compounds
GB0004886D0 (en) 2000-03-01 2000-04-19 Astrazeneca Uk Ltd Chemical compounds
GB0004890D0 (en) 2000-03-01 2000-04-19 Astrazeneca Uk Ltd Chemical compounds
US6608048B2 (en) 2000-03-28 2003-08-19 Wyeth Holdings Tricyclic protein kinase inhibitors
AR028261A1 (es) 2000-03-28 2003-04-30 Wyeth Corp Inhibidores triciclicos de la proteina quinasa
WO2001085700A2 (en) 2000-05-08 2001-11-15 Janssen Pharmaceutica N.V. Hiv replication inhibiting pyrimidines and triazines
CA2407754C (en) 2000-05-08 2009-09-15 Janssen Pharmaceutica N.V. Prodrugs of hiv replication inhibiting pyrimidines
KR100516419B1 (ko) 2000-06-26 2005-09-23 화이자 프로덕츠 인크. 면역억제제로서 피롤로[2,3-ｄ]피리미딘 화합물
GB0016877D0 (en) 2000-07-11 2000-08-30 Astrazeneca Ab Chemical compounds
AU2001229722A1 (en) 2000-11-29 2002-06-11 Parker Hughes Institute Inhibitors of thrombin induced platelet aggregation
US20020115173A1 (en) 2000-12-11 2002-08-22 Children's Medical Center Corporation Short peptides from the 'A-region' of protein kinases which selectively modulate protein kinase activity
AR035721A1 (es) 2000-12-20 2004-07-07 Sugen Inc Indolinonas 4-aril sustituidas; sus composiciones farmaceuticas y metodo para modular la actividad catalitica de una proteina quinasa
HUP0400908A3 (en) 2000-12-21 2010-03-29 Vertex Pharma Pyrazole compounds useful as protein kinase inhibitors, their use and pharmaceutical compositions containing them
CA2432000C (en) 2000-12-21 2011-03-15 Glaxo Group Limited Pyrimidineamines as angiogenesis modulators
AUPR279101A0 (en) 2001-01-30 2001-02-22 Cytopia Pty Ltd Protein kinase signalling
EP1363702A4 (en) 2001-01-30 2007-08-22 Cytopia Pty Ltd PROCESS FOR INHIBITING KINASES
GB0103926D0 (en) 2001-02-17 2001-04-04 Astrazeneca Ab Chemical compounds
US7078410B2 (en) 2001-02-20 2006-07-18 Astrazeneca Ab 2-arylamino-pyrimidines for the treatment of GSK3-related disorders
RS94703A (en) * 2001-05-29 2007-02-05 Schering Aktiengesellschaft, Cdk inhibiting pyrimidines, production thereof and their use as medicaments
US7301023B2 (en) 2001-05-31 2007-11-27 Pfizer Inc. Chiral salt resolution
CA2450769A1 (en) 2001-06-15 2002-12-27 Vertex Pharmaceuticals Incorporated 5-(2-aminopyrimidin-4-yl) benzisoxazoles as protein kinase inhibitors
WO2002102313A2 (en) 2001-06-19 2002-12-27 Bristol-Myers Squibb Company Pyrimidine inhibitors of phosphodiesterase (pde) 7
EP1408978A4 (en) 2001-06-21 2005-07-13 Ariad Pharma Inc NOVEL PHENYLAMINO-PYRIMIDINES AND THEIR USE
JO3429B1 (ar) 2001-08-13 2019-10-20 Janssen Pharmaceutica Nv مشتقات برميدينات مثبطة فيروس الايدز
US7115617B2 (en) 2001-08-22 2006-10-03 Amgen Inc. Amino-substituted pyrimidinyl derivatives and methods of use
US6939874B2 (en) 2001-08-22 2005-09-06 Amgen Inc. Substituted pyrimidinyl derivatives and methods of use
US6433018B1 (en) 2001-08-31 2002-08-13 The Research Foundation Of State University Of New York Method for reducing hypertrophy and ischemia
WO2003020698A2 (en) 2001-09-06 2003-03-13 Prochon Biotech Ltd. Protein tyrosine kinase inhibitors
BR0212435A (pt) 2001-09-10 2004-08-17 Sugen Inc Derivados de 3-(4,5,6,7-tetraidroindol-2-ilmetilideno)-2-indolinona como inibidores de cinase
WO2003030909A1 (en) 2001-09-25 2003-04-17 Bayer Pharmaceuticals Corporation 2- and 4-aminopyrimidines n-substtituded by a bicyclic ring for use as kinase inhibitors in the treatment of cancer
WO2003026664A1 (en) 2001-09-26 2003-04-03 Bayer Corporation 2-phenylamino-4- (5-pyrazolylamino) -pyramidine derivatives as kinase inhibitors, in particular, src kinase inhibitors
WO2003032994A2 (de) 2001-10-17 2003-04-24 Boehringer Ingelheim Pharma Gmbh & Co. Kg 5-substituierte 4-amino-2-phenylamino-pyrimidinderivate und ihre verwendung als beta-amyloid modulatoren
EP1438053B1 (de) 2001-10-17 2008-09-10 Boehringer Ingelheim Pharma GmbH & Co.KG Pyrimidinderivate, arzneimittel enthaltend diese verbindungen, deren verwendung und verfahren zu ihrer herstellung
GT200200234A (es) 2001-12-06 2003-06-27 Compuestos cristalinos novedosos
SE0104140D0 (sv) 2001-12-07 2001-12-07 Astrazeneca Ab Novel Compounds
TWI329105B (en) 2002-02-01 2010-08-21 Rigel Pharmaceuticals Inc 2,4-pyrimidinediamine compounds and their uses
US6998391B2 (en) 2002-02-07 2006-02-14 Supergen.Inc. Method for treating diseases associated with abnormal kinase activity
AU2003209077A1 (en) 2002-02-08 2003-09-02 Smithkline Beecham Corporation Pyrimidine compounds
ES2290479T3 (es) 2002-03-01 2008-02-16 Smithkline Beecham Corporation Diamino-pirimidinas y su uso como inhibidores de la angiogenesis.
US7288547B2 (en) 2002-03-11 2007-10-30 Schering Ag CDK-inhibitory 2-heteroaryl-pyrimidines, their production and use as pharmaceutical agents
EP1483260A1 (de) * 2002-03-11 2004-12-08 Schering Aktiengesellschaft Cdk inhibitorische 2-heteroaryl-pyrimidine, deren herstellung und verwendung als arzneimittel
GB0206215D0 (en) * 2002-03-15 2002-05-01 Novartis Ag Organic compounds
WO2004058753A1 (en) 2002-05-06 2004-07-15 Vertex Pharmaceuticals Incorporated Thiadiazoles or oxadiazoles and their use as inhibitors of jak protein kinase
AU2003231231A1 (en) * 2002-05-06 2003-11-11 Bayer Pharmaceuticals Corporation Pyridinyl amino pyrimidine derivatives useful for treating hyper-proliferative disorders
AR039540A1 (es) 2002-05-13 2005-02-23 Tibotec Pharm Ltd Compuestos microbicidas con contenido de pirimidina o triazina
JP2005528443A (ja) 2002-05-30 2005-09-22 バーテックス　ファーマシューティカルズ　インコーポレイテッド Ｊａｋキナーゼおよびｃｄｋ２プロテインキナーゼのインヒビター
IL165286A0 (en) 2002-06-17 2005-12-18 Smithkline Beecham Corp Chemical process
ATE530530T1 (de) 2002-06-28 2011-11-15 Astellas Pharma Inc Diaminopyrimidincarbonsäureamidderivat
EP1522558A4 (en) 2002-07-17 2005-11-16 Mitsubishi Chem Corp WATER SOLUBLE COMPLEX, RECORDING LIQUID, AND RECORDING METHOD
DK1534286T3 (da) 2002-07-29 2010-04-26 Rigel Pharmaceuticals Inc Fremgangsmåder til behandling eller forebyggelse af autoimmune sygdomme med 2,4-pyrimidindiamin-forbindelser
MXPA05001804A (es) 2002-08-14 2005-05-27 Vertex Pharma Inhibidores de proteinas cinasas y usos de los mismos.
EP1501824B1 (en) * 2002-08-21 2007-10-10 Teva Pharmaceutical Industries Ltd A method for the purification of lansoprazole
CA2497977A1 (en) 2002-09-20 2004-04-01 Alcon, Inc. Use of cytokine synthesis inhibitors for the treatment of dry eye disorders
WO2004041789A1 (en) * 2002-11-01 2004-05-21 Vertex Pharmaceuticals Incorporated Compositions useful as inhibitors of jak and other protein kinases
ES2289349T3 (es) 2002-11-04 2008-02-01 Vertex Pharmaceuticals Incorporated Derivados de heteroaril-pirimidina como inhibidores de jak.
AU2003286895A1 (en) * 2002-11-05 2004-06-07 Vertex Pharmaceuticals Incorporated Compounds useful as inhibitors of jak and other protein kinases
KR100481130B1 (ko) 2002-11-08 2005-04-07 주식회사 웨어밸리 데이터베이스 시스템에 접속하지 않고 데이터베이스시스템을 모니터링하는 방법
GB0226582D0 (en) 2002-11-14 2002-12-18 Cyclacel Ltd Anti-viral compounds
GB0226583D0 (en) 2002-11-14 2002-12-18 Cyclacel Ltd Compounds
AR042052A1 (es) 2002-11-15 2005-06-08 Vertex Pharma Diaminotriazoles utiles como inhibidores de proteinquinasas
CA2506016C (en) 2002-11-21 2009-03-17 Pfizer Products Inc. 3-amino-piperidine derivatives and processes for their preparation
CN1717236A (zh) 2002-11-26 2006-01-04 辉瑞产品公司 治疗移植排斥的方法
WO2004058749A1 (en) 2002-12-18 2004-07-15 Vertex Pharmaceuticals Incorporated Benzisoxazole derivatives useful as inhibitors of protein kinases
PL227577B1 (pl) 2003-02-07 2017-12-29 Janssen Pharmaceutica Nv Zastosowanie pochodnych pirymidyny do wytwarzania leku do zapobiegania zakażeniu wirusem HIV oraz kompozycja farmaceutyczna
CL2004000306A1 (es) 2003-02-20 2005-04-08 Tibotec Pharm Ltd Compuestos derivados de pirimidina sustituidas con indano; proceso para su preparacion; composicion farmaceutica que lo comprende; combinacion farmaceutica; y su uso para el tratamiento o profilaxis de una enfermedad infecciosa.
GB2398582A (en) 2003-02-20 2004-08-25 Schlumberger Holdings System and method for maintaining zonal isolation in a wellbore
US7514446B2 (en) 2003-02-20 2009-04-07 Smithkline Beecham Corporation Pyrimidine compounds
GB0305929D0 (en) 2003-03-14 2003-04-23 Novartis Ag Organic compounds
CA2522595A1 (en) 2003-04-03 2004-10-28 Vertex Pharmaceuticals Incorporated Compositions useful as inhibitors of protein kinases
EP1618094B1 (en) 2003-04-30 2007-09-05 The Institutes for Pharmaceutical Discovery, LLC Substituted heteroaryls as inhibitors of protein tyrosine phosphatases
GB0311276D0 (en) 2003-05-16 2003-06-18 Astrazeneca Ab Chemical compounds
GB0311274D0 (en) 2003-05-16 2003-06-18 Astrazeneca Ab Chemical compounds
WO2005007621A2 (en) 2003-05-30 2005-01-27 Rigel Pharmaceuticals, Inc. Ubiquitin ligase inhibitors
US7979448B2 (en) 2003-06-25 2011-07-12 International Business Machines Corporation Mail and calendar tool and method
AU2004257260A1 (en) 2003-07-10 2005-01-27 Neurogen Corporation Substituted heterocyclic diarylamine analogues
JP2007526894A (ja) 2003-07-16 2007-09-20 ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ グリコーゲンシンターゼキナーゼ３インヒビターとしてのトリアゾロピリミジン誘導体
NZ545058A (en) * 2003-07-16 2008-05-30 Janssen Pharmaceutica Nv Triazolopyrimidine derivatives as glycogen synthase kinase 3 inhibitors
US20070161637A1 (en) 2003-07-22 2007-07-12 Neurogen Corporation Substituted pyridin-2-ylamine analogues
WO2005009957A1 (en) 2003-07-24 2005-02-03 Merck & Co., Inc. Tyrosine kinase inhibitors
JP2007500179A (ja) 2003-07-30 2007-01-11 サイクラセル・リミテッド キナーゼ阻害剤としての２−アミノフェニル−４−フェニルピリミジン
RS53109B (en) 2003-07-30 2014-06-30 Rigel Pharmaceuticals Inc. 2,4 PIRIMIDINDIAMINE COMPOUNDS FOR USE IN TREATMENT OR PREVENTION OF AUTOIMMUNE DISEASES
DK1663242T3 (da) 2003-08-07 2011-08-01 Rigel Pharmaceuticals Inc 2,4-Pyrimidindiamin-forbindelser og anvendelse som antiproliferative midler
WO2005016344A1 (en) 2003-08-14 2005-02-24 Pfizer Limited Piperazine derivatives for the treatment of hiv infections
CA2533320A1 (en) 2003-08-15 2006-02-24 Novartis Ag 2, 4-pyrimidinediamines useful in the treatment of neoplastic diseases, inflammatory and immune system disorders
TWI339206B (en) 2003-09-04 2011-03-21 Vertex Pharma Compositions useful as inhibitors of protein kinases
US7223759B2 (en) 2003-09-15 2007-05-29 Anadys Pharmaceuticals, Inc. Antibacterial 3,5-diaminopiperidine-substituted aromatic and heteroaromatic compounds
GB0321710D0 (en) 2003-09-16 2003-10-15 Novartis Ag Organic compounds
CA2538413A1 (en) * 2003-09-18 2005-03-24 Novartis Ag 2,4-di (phenylamino) pyrimidines useful in the treatment of proliferative disorders
BRPI0414791A (pt) 2003-09-25 2006-11-21 Janssen Pharmaceutica Nv derivados de purina inibidores da replicação do hiv
EP1682545B1 (en) 2003-10-03 2007-12-12 Pfizer Limited Imidazopyridine substituted tropane derivatives with ccr5 receptor antagonist activity for the treatment of hiv and inflammation
DE10349423A1 (de) 2003-10-16 2005-06-16 Schering Ag Sulfoximinsubstituierte Parimidine als CDK- und/oder VEGF-Inhibitoren, deren Herstellung und Verwendung als Arzneimittel
US20080312192A1 (en) 2003-11-28 2008-12-18 Guido Bold Diaryl Urea Derivatives in the Treatment of Protein Kinase Dependent Diseases
MY141255A (en) 2003-12-11 2010-03-31 Memory Pharm Corp Phosphodiesterase 4 inhibitors, including n-substituted diarylamine analogs
WO2005063722A1 (en) 2003-12-19 2005-07-14 Rigel Pharmaceuticals, Inc. Stereoisomers and stereoisomeric mixtures of 1-(2,4-pyrimidinediamino)-2-cyclopentanecarboxamide synthetic intermediates
GB2432834A (en) 2004-01-12 2007-06-06 Cytopia Res Pty Ltd Selective Kinase Inhibitors
GB0402653D0 (en) 2004-02-06 2004-03-10 Cyclacel Ltd Compounds
KR100645040B1 (ko) 2004-02-09 2006-11-10 삼성전자주식회사 소오스 스트래핑을 갖는 플래시 메모리 소자의 셀 어레이
US7968557B2 (en) 2004-02-14 2011-06-28 Novartis Ag Substituted pyrrolo[2,3-2]pyrimidines as protein kinase inhibitors
WO2005107760A1 (en) 2004-04-30 2005-11-17 Irm Llc Compounds and compositions as inducers of keratinocyte differentiation
JP4812763B2 (ja) 2004-05-18 2011-11-09 ライジェル ファーマシューティカルズ， インコーポレイテッド シクロアルキル置換ピリミジンジアミン化合物およびそれらの用途
US7268012B2 (en) 2004-08-31 2007-09-11 Micron Technology, Inc. Methods for fabrication of thin semiconductor assemblies including redistribution layers and packages and assemblies formed thereby
EP1786783A1 (en) 2004-09-01 2007-05-23 Rigel Pharmaceuticals, Inc. Synthesis of 2,4-pyrimidinediamine compounds
EP1794134A1 (de) 2004-09-29 2007-06-13 Bayer Schering Pharma Aktiengesellschaft Substituierte 2-anilinopyrimidine als zellzyklus -kinase oder rezeptortyrosin-kinase inhibitoren, deren herstellung und verwendung als arzneimittel
ATE520672T1 (de) 2004-09-30 2011-09-15 Tibotec Pharm Ltd Hiv-hemmende 5-carbo- oder heterozyklisch substituierte pyrimidine
WO2006068770A1 (en) 2004-11-24 2006-06-29 Rigel Pharmaceuticals, Inc. Spiro-2, 4-pyrimidinediamine compounds and their uses
JP5208516B2 (ja) * 2004-12-30 2013-06-12 エグゼリクシス， インコーポレイテッド キナーゼモジュレーターとしてのピリミジン誘導体および使用方法
PT1856135E (pt) 2005-01-19 2010-02-26 Rigel Pharmaceuticals Inc Pró-fármacos de compostos 2,4-pirimidinodiamina e suas utilizações
EP1883302A4 (en) 2005-05-03 2009-05-20 Rigel Pharmaceuticals Inc JAK KINASE HEMMER AND ITS USE
WO2006129100A1 (en) * 2005-06-03 2006-12-07 Glaxo Group Limited Novel compounds
US20070203161A1 (en) 2006-02-24 2007-08-30 Rigel Pharmaceuticals, Inc. Compositions and methods for inhibition of the jak pathway
ES2651349T3 (es) 2005-06-08 2018-01-25 Rigel Pharmaceuticals, Inc. Composiciones y métodos para la inhibición de la ruta JAK
US7576053B2 (en) 2005-06-13 2009-08-18 Rigel Pharmaceuticals, Inc. Methods and compositions for treating degenerative bone disorders
WO2007006926A2 (fr) 2005-07-11 2007-01-18 Sanofi-Aventis Nouveaux derives de 2,4-dianilinopyrimidines, leur preparation, a titre de medicaments, compositions pharmaceutiques et notamment comme inhibiteurs de ikk
US8321953B2 (en) 2005-07-14 2012-11-27 Imation Corp. Secure storage device with offline code entry
CA2627242A1 (en) 2005-10-31 2007-05-10 Rigel Pharmaceuticals, Inc. Compositions and methods for treating inflammatory disorders
WO2007053452A1 (en) 2005-11-01 2007-05-10 Targegen, Inc. Bi-aryl meta-pyrimidine inhibitors of kinases
US7713987B2 (en) 2005-12-06 2010-05-11 Rigel Pharmaceuticals, Inc. Pyrimidine-2,4-diamines and their uses
US7962290B1 (en) * 2006-01-09 2011-06-14 Rigel Pharmaceuticals, Inc. Identification of pharmacophores from co-crystals of spleen tyrosine kinase (SYK) and SYK ligands
WO2007085540A1 (en) 2006-01-27 2007-08-02 Glaxo Group Limited 1h-indaz0l-4-yl-2 , 4-pyrimidinediamine derivatives
US7659280B2 (en) 2006-02-17 2010-02-09 Rigel Pharmaceuticals, Inc. 2,4-pyrimidinediamine compounds for treating or preventing autoimmune diseases
WO2007098507A2 (en) 2006-02-24 2007-08-30 Rigel Pharmaceuticals, Inc. Compositions and methods for inhibition of the jak pathway
GB0605691D0 (en) 2006-03-21 2006-05-03 Novartis Ag Organic Compounds
ATE497496T1 (de) 2006-10-19 2011-02-15 Rigel Pharmaceuticals Inc 2,4-pyridimediamon-derivate als hemmer von jak- kinasen zur behandlung von autoimmunerkrankungen
DK2078026T3 (da) 2006-11-21 2012-04-30 Rigel Pharmaceuticals Inc Prodrug-salte af 2, 4-pyrimidinediamine-forbindelser og anvendelser deraf
WO2008118822A1 (en) 2007-03-23 2008-10-02 Rigel Pharmaceuticals, Inc. Compositions and methods for inhibition of the jak pathway
US7834024B2 (en) 2007-03-26 2010-11-16 Rigel Pharmaceuticals, Inc. Compositions and methods for inhibition of the JAK pathway
WO2009003136A1 (en) 2007-06-26 2008-12-31 Rigel Pharmaceuticals, Inc. Substituted pyrimidine-2, 4 -diamines for treating cell proliferative disorders
US8541426B2 (en) 2007-07-11 2013-09-24 Pfizer Inc. Pharmaceutical compositions and methods of treating dry eye disorders
BRPI0814432A2 (pt) 2007-07-17 2017-05-09 Rigel Pharmaceuticals Inc pirimidinadiaminas substituídas por amina cíclica como inibidores de pkc
HUE026315T2 (en) * 2009-01-23 2016-06-28 Rigel Pharmaceuticals Inc Preparations and methods for inhibiting the JAK pathway

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