SK2072003A3 - Process for making N-aryl-anthranilic acids and their derivatives - Google Patents

Process for making N-aryl-anthranilic acids and their derivatives Download PDF

Info

Publication number: SK2072003A3
Authority: SK; Slovakia
Prior art keywords: compound; formula; alkyl; hydrogen; aryl
Prior art date: 2000-08-25

Application number

SK207-2003A

Other languages

English (en)

Slovak (sk)

Inventor

Michael Huai Gu Chen

Edward Mark Davis

Javier Magano

Thomas Norman Nanninga

Derick Dale Winkle

Original Assignee

Warner Lambert Co

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

2000-08-25

Filing date

2001-07-20

Publication date

2004-01-08

2001-07-20 Application filed by Warner Lambert Co filed Critical Warner Lambert Co

2004-01-08 Publication of SK2072003A3 publication Critical patent/SK2072003A3/sk

Links

238000000034 method Methods 0.000 title claims abstract description 358
230000008569 process Effects 0.000 title claims abstract description 140
239000002253 acid Substances 0.000 title claims abstract description 62
150000007513 acids Chemical class 0.000 title abstract description 16
150000001408 amides Chemical class 0.000 claims abstract description 50
150000001875 compounds Chemical class 0.000 claims description 322
-1 alkaline earth metal cation Chemical class 0.000 claims description 279
229910052739 hydrogen Inorganic materials 0.000 claims description 253
125000000217 alkyl group Chemical group 0.000 claims description 241
239000001257 hydrogen Substances 0.000 claims description 221
125000000623 heterocyclic group Chemical group 0.000 claims description 153
125000004432 carbon atom Chemical group C* 0.000 claims description 150
150000002431 hydrogen Chemical class 0.000 claims description 143
229910052757 nitrogen Inorganic materials 0.000 claims description 143
239000002585 base Substances 0.000 claims description 136
150000003839 salts Chemical class 0.000 claims description 134
125000003118 aryl group Chemical group 0.000 claims description 131
125000004433 nitrogen atom Chemical group N* 0.000 claims description 121
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 106
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 105
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 90
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 86
125000003342 alkenyl group Chemical group 0.000 claims description 84
229910052784 alkaline earth metal Inorganic materials 0.000 claims description 81
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 79
PIGFYZPCRLYGLF-UHFFFAOYSA-N Aluminum nitride Chemical compound [Al]#N PIGFYZPCRLYGLF-UHFFFAOYSA-N 0.000 claims description 73
125000005842 heteroatom Chemical group 0.000 claims description 70
229910052760 oxygen Inorganic materials 0.000 claims description 67
229910052717 sulfur Inorganic materials 0.000 claims description 63
229910052736 halogen Inorganic materials 0.000 claims description 60
150000002367 halogens Chemical class 0.000 claims description 60
229910052783 alkali metal Inorganic materials 0.000 claims description 58
UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 58
125000001424 substituent group Chemical group 0.000 claims description 58
239000000203 mixture Substances 0.000 claims description 52
125000000896 monocarboxylic acid group Chemical group 0.000 claims description 48
125000004665 trialkylsilyl group Chemical group 0.000 claims description 48
229910052799 carbon Inorganic materials 0.000 claims description 46
125000000304 alkynyl group Chemical group 0.000 claims description 45
125000003545 alkoxy group Chemical group 0.000 claims description 44
238000006243 chemical reaction Methods 0.000 claims description 44
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 claims description 44
150000001340 alkali metals Chemical class 0.000 claims description 43
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 39
239000011541 reaction mixture Substances 0.000 claims description 38
239000002904 solvent Substances 0.000 claims description 37
239000000460 chlorine Substances 0.000 claims description 33
PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 31
125000001072 heteroaryl group Chemical group 0.000 claims description 30
150000001342 alkaline earth metals Chemical class 0.000 claims description 29
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 28
125000000753 cycloalkyl group Chemical group 0.000 claims description 28
AFRJJFRNGGLMDW-UHFFFAOYSA-N lithium amide Chemical compound [Li+].[NH2-] AFRJJFRNGGLMDW-UHFFFAOYSA-N 0.000 claims description 28
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 26
125000001246 bromo group Chemical group Br* 0.000 claims description 21
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 21
229910052794 bromium Inorganic materials 0.000 claims description 19
125000001188 haloalkyl group Chemical group 0.000 claims description 19
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 19
229910052740 iodine Inorganic materials 0.000 claims description 19
125000002346 iodo group Chemical group I* 0.000 claims description 19
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 18
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 18
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 18
229910000103 lithium hydride Inorganic materials 0.000 claims description 18
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 18
125000006413 ring segment Chemical group 0.000 claims description 18
125000001153 fluoro group Chemical group F* 0.000 claims description 17
238000003786 synthesis reaction Methods 0.000 claims description 17
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 16
239000003513 alkali Substances 0.000 claims description 16
230000015572 biosynthetic process Effects 0.000 claims description 16
150000001721 carbon Chemical group 0.000 claims description 16
239000011630 iodine Substances 0.000 claims description 16
239000011734 sodium Substances 0.000 claims description 16
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-Ethyl-3-(3-dimethylaminopropyl)carbodiimide Substances CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims description 13
230000003213 activating effect Effects 0.000 claims description 13
239000003795 chemical substances by application Substances 0.000 claims description 13
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 12
150000001412 amines Chemical class 0.000 claims description 12
229910052801 chlorine Inorganic materials 0.000 claims description 12
239000011737 fluorine Substances 0.000 claims description 12
229910052731 fluorine Inorganic materials 0.000 claims description 12
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 11
239000000543 intermediate Substances 0.000 claims description 11
229910052744 lithium Inorganic materials 0.000 claims description 11
ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 claims description 10
ZFFBIQMNKOJDJE-UHFFFAOYSA-N 2-bromo-1,2-diphenylethanone Chemical compound C=1C=CC=CC=1C(Br)C(=O)C1=CC=CC=C1 ZFFBIQMNKOJDJE-UHFFFAOYSA-N 0.000 claims description 9
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 9
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 9
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 9
YHNRUSMOYCDMJS-UHFFFAOYSA-N o-(cyclopropylmethyl)hydroxylamine Chemical compound NOCC1CC1 YHNRUSMOYCDMJS-UHFFFAOYSA-N 0.000 claims description 9
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 9
239000000376 reactant Substances 0.000 claims description 9
229910052708 sodium Inorganic materials 0.000 claims description 9
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 9
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 8
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 claims description 8
229910052700 potassium Inorganic materials 0.000 claims description 8
239000011591 potassium Substances 0.000 claims description 8
230000002194 synthesizing effect Effects 0.000 claims description 8
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 7
229910000102 alkali metal hydride Inorganic materials 0.000 claims description 7
150000008046 alkali metal hydrides Chemical class 0.000 claims description 7
125000004429 atom Chemical group 0.000 claims description 7
125000001309 chloro group Chemical group Cl* 0.000 claims description 7
NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 claims description 7
229910000105 potassium hydride Inorganic materials 0.000 claims description 7
229910000104 sodium hydride Inorganic materials 0.000 claims description 7
239000012312 sodium hydride Substances 0.000 claims description 7
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims description 6
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 6
230000003247 decreasing effect Effects 0.000 claims description 6
150000007522 mineralic acids Chemical class 0.000 claims description 6
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 5
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 5
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 5
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 5
LZDKZFUFMNSQCJ-UHFFFAOYSA-N 1,2-diethoxyethane Chemical compound CCOCCOCC LZDKZFUFMNSQCJ-UHFFFAOYSA-N 0.000 claims description 4
LEEANUDEDHYDTG-UHFFFAOYSA-N 1,2-dimethoxypropane Chemical compound COCC(C)OC LEEANUDEDHYDTG-UHFFFAOYSA-N 0.000 claims description 4
HEWZVZIVELJPQZ-UHFFFAOYSA-N 2,2-dimethoxypropane Chemical compound COC(C)(C)OC HEWZVZIVELJPQZ-UHFFFAOYSA-N 0.000 claims description 4
FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 claims description 4
RVDLHGSZWAELAU-UHFFFAOYSA-N 5-tert-butylthiophene-2-carbonyl chloride Chemical compound CC(C)(C)C1=CC=C(C(Cl)=O)S1 RVDLHGSZWAELAU-UHFFFAOYSA-N 0.000 claims description 4
HBBGRARXTFLTSG-UHFFFAOYSA-N Lithium ion Chemical compound [Li+] HBBGRARXTFLTSG-UHFFFAOYSA-N 0.000 claims description 4
125000004423 acyloxy group Chemical group 0.000 claims description 4
125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 claims description 4
229940006487 lithium cation Drugs 0.000 claims description 4
230000000269 nucleophilic effect Effects 0.000 claims description 4
YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 claims description 4
125000006432 1-methyl cyclopropyl group Chemical group [H]C([H])([H])C1(*)C([H])([H])C1([H])[H] 0.000 claims description 3
CSDQQAQKBAQLLE-UHFFFAOYSA-N 4-(4-chlorophenyl)-4,5,6,7-tetrahydrothieno[3,2-c]pyridine Chemical compound C1=CC(Cl)=CC=C1C1C(C=CS2)=C2CCN1 CSDQQAQKBAQLLE-UHFFFAOYSA-N 0.000 claims description 3
NPYPAHLBTDXSSS-UHFFFAOYSA-N Potassium ion Chemical compound [K+] NPYPAHLBTDXSSS-UHFFFAOYSA-N 0.000 claims description 3
FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 claims description 3
125000005279 aryl sulfonyloxy group Chemical group 0.000 claims description 3
125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 claims description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
230000007062 hydrolysis Effects 0.000 claims description 2
238000006460 hydrolysis reaction Methods 0.000 claims description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
235000011149 sulphuric acid Nutrition 0.000 claims description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 2
ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 claims description 2
150000001735 carboxylic acids Chemical class 0.000 claims 5
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 2
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims 1
125000006187 phenyl benzyl group Chemical group 0.000 claims 1
230000035484 reaction time Effects 0.000 claims 1
238000002360 preparation method Methods 0.000 abstract description 26
NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical class C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 abstract description 12
150000002148 esters Chemical class 0.000 abstract description 9
239000000243 solution Substances 0.000 description 45
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 38
239000000047 product Substances 0.000 description 33
239000007787 solid Substances 0.000 description 28
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 26
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 24
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 20
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 19
229910000041 hydrogen chloride Inorganic materials 0.000 description 19
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 description 18
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical group [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 17
102000043136 MAP kinase family Human genes 0.000 description 16
108091054455 MAP kinase family Proteins 0.000 description 16
125000006578 monocyclic heterocycloalkyl group Chemical group 0.000 description 16
XCNBGWKQXRQKSA-UHFFFAOYSA-N 2-(2-chloro-4-iodoanilino)-3,4-difluorobenzoic acid Chemical compound OC(=O)C1=CC=C(F)C(F)=C1NC1=CC=C(I)C=C1Cl XCNBGWKQXRQKSA-UHFFFAOYSA-N 0.000 description 13
239000000010 aprotic solvent Substances 0.000 description 12
125000002950 monocyclic group Chemical group 0.000 description 12
239000012044 organic layer Substances 0.000 description 12
108091000080 Phosphotransferase Proteins 0.000 description 11
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 11
102000020233 phosphotransferase Human genes 0.000 description 11
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 11
102000004232 Mitogen-Activated Protein Kinase Kinases Human genes 0.000 description 10
108090000744 Mitogen-Activated Protein Kinase Kinases Proteins 0.000 description 10
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 10
150000001732 carboxylic acid derivatives Chemical class 0.000 description 10
239000003054 catalyst Substances 0.000 description 10
150000001768 cations Chemical class 0.000 description 10
102000016914 ras Proteins Human genes 0.000 description 10
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
230000004913 activation Effects 0.000 description 9
210000004027 cell Anatomy 0.000 description 9
239000010410 layer Substances 0.000 description 9
MYDAOWXYGPEPJT-UHFFFAOYSA-N 2-chloro-4-iodoaniline Chemical compound NC1=CC=C(I)C=C1Cl MYDAOWXYGPEPJT-UHFFFAOYSA-N 0.000 description 8
125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 8
PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 8
125000006580 bicyclic heterocycloalkyl group Chemical group 0.000 description 8
229910002091 carbon monoxide Inorganic materials 0.000 description 8
238000001914 filtration Methods 0.000 description 8
230000026731 phosphorylation Effects 0.000 description 8
238000006366 phosphorylation reaction Methods 0.000 description 8
125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 7
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
125000002947 alkylene group Chemical group 0.000 description 7
239000012267 brine Substances 0.000 description 7
239000011575 calcium Substances 0.000 description 7
235000019439 ethyl acetate Nutrition 0.000 description 7
125000000524 functional group Chemical group 0.000 description 7
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 7
125000004043 oxo group Chemical group O=* 0.000 description 7
239000001301 oxygen Substances 0.000 description 7
239000008188 pellet Substances 0.000 description 7
108090000623 proteins and genes Proteins 0.000 description 7
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
239000007858 starting material Substances 0.000 description 7
WEPXLRANFJEOFZ-UHFFFAOYSA-N 2,3,4-trifluorobenzoic acid Chemical compound OC(=O)C1=CC=C(F)C(F)=C1F WEPXLRANFJEOFZ-UHFFFAOYSA-N 0.000 description 6
NSTREUWFTAOOKS-UHFFFAOYSA-N 2-fluorobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1F NSTREUWFTAOOKS-UHFFFAOYSA-N 0.000 description 6
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 6
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 6
239000003153 chemical reaction reagent Substances 0.000 description 6
238000001816 cooling Methods 0.000 description 6
239000012458 free base Substances 0.000 description 6
150000002430 hydrocarbons Chemical group 0.000 description 6
239000011777 magnesium Substances 0.000 description 6
125000006239 protecting group Chemical group 0.000 description 6
102000004169 proteins and genes Human genes 0.000 description 6
239000002002 slurry Substances 0.000 description 6
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125000005098 aryl alkoxy carbonyl group Chemical group 0.000 description 1
230000003305 autocrine Effects 0.000 description 1
125000004069 aziridinyl group Chemical group 0.000 description 1
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SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical class OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
125000005605 benzo group Chemical group 0.000 description 1
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125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
150000001558 benzoic acid derivatives Chemical class 0.000 description 1
RROBIDXNTUAHFW-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 RROBIDXNTUAHFW-UHFFFAOYSA-N 0.000 description 1
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
229910052790 beryllium Inorganic materials 0.000 description 1
125000002618 bicyclic heterocycle group Chemical group 0.000 description 1
XGIUDIMNNMKGDE-UHFFFAOYSA-N bis(trimethylsilyl)azanide Chemical compound C[Si](C)(C)[N-][Si](C)(C)C XGIUDIMNNMKGDE-UHFFFAOYSA-N 0.000 description 1
150000001649 bromium compounds Chemical class 0.000 description 1
125000001589 carboacyl group Chemical group 0.000 description 1
150000001718 carbodiimides Chemical class 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
150000001734 carboxylic acid salts Chemical class 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
230000010307 cell transformation Effects 0.000 description 1
238000005119 centrifugation Methods 0.000 description 1
230000008859 change Effects 0.000 description 1
239000003610 charcoal Substances 0.000 description 1
239000007806 chemical reaction intermediate Substances 0.000 description 1
239000007805 chemical reaction reactant Substances 0.000 description 1
150000001805 chlorine compounds Chemical class 0.000 description 1
VDANGULDQQJODZ-UHFFFAOYSA-N chloroprocaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1Cl VDANGULDQQJODZ-UHFFFAOYSA-N 0.000 description 1
229960002023 chloroprocaine Drugs 0.000 description 1
OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
229960001231 choline Drugs 0.000 description 1
150000001860 citric acid derivatives Chemical class 0.000 description 1
238000004140 cleaning Methods 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
238000011109 contamination Methods 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
230000008878 coupling Effects 0.000 description 1
239000007822 coupling agent Substances 0.000 description 1
238000010168 coupling process Methods 0.000 description 1
239000012043 crude product Substances 0.000 description 1
238000002425 crystallisation Methods 0.000 description 1
230000008025 crystallization Effects 0.000 description 1
MGNCLNQXLYJVJD-UHFFFAOYSA-N cyanuric chloride Chemical compound ClC1=NC(Cl)=NC(Cl)=N1 MGNCLNQXLYJVJD-UHFFFAOYSA-N 0.000 description 1
125000002993 cycloalkylene group Chemical group 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000002933 cyclohexyloxy group Chemical group C1(CCCCC1)O* 0.000 description 1
125000006547 cyclononyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
125000006638 cyclopentyl carbonyl group Chemical group 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
238000001514 detection method Methods 0.000 description 1
150000001991 dicarboxylic acids Chemical class 0.000 description 1
SPWVRYZQLGQKGK-UHFFFAOYSA-N dichloromethane;hexane Chemical compound ClCCl.CCCCCC SPWVRYZQLGQKGK-UHFFFAOYSA-N 0.000 description 1
QVQGTNFYPJQJNM-UHFFFAOYSA-N dicyclohexylmethanamine Chemical compound C1CCCCC1C(N)C1CCCCC1 QVQGTNFYPJQJNM-UHFFFAOYSA-N 0.000 description 1
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
229940043237 diethanolamine Drugs 0.000 description 1
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
VFNGKCDDZUSWLR-UHFFFAOYSA-N disulfuric acid Chemical class OS(=O)(=O)OS(O)(=O)=O VFNGKCDDZUSWLR-UHFFFAOYSA-N 0.000 description 1
238000001035 drying Methods 0.000 description 1
230000009977 dual effect Effects 0.000 description 1
238000005837 enolization reaction Methods 0.000 description 1
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
CGAJYBUEWWHRDO-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate;triphenylphosphane Chemical compound CCOC(=O)N=NC(=O)OCC.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 CGAJYBUEWWHRDO-UHFFFAOYSA-N 0.000 description 1
125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
239000000284 extract Substances 0.000 description 1
238000000605 extraction Methods 0.000 description 1
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
238000001640 fractional crystallisation Methods 0.000 description 1
238000004817 gas chromatography Methods 0.000 description 1
238000007429 general method Methods 0.000 description 1
229940050410 gluconate Drugs 0.000 description 1
125000000350 glycoloyl group Chemical group O=C([*])C([H])([H])O[H] 0.000 description 1
239000003102 growth factor Substances 0.000 description 1
125000005155 haloalkylene group Chemical group 0.000 description 1
JYGYEBCBALMPDC-UHFFFAOYSA-N heptane;propan-2-one Chemical compound CC(C)=O.CCCCCCC JYGYEBCBALMPDC-UHFFFAOYSA-N 0.000 description 1
238000011141 high resolution liquid chromatography Methods 0.000 description 1
239000012456 homogeneous solution Substances 0.000 description 1
DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 1
BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
238000005984 hydrogenation reaction Methods 0.000 description 1
238000007327 hydrogenolysis reaction Methods 0.000 description 1
125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
125000002249 indol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([*])=C([H])C2=C1[H] 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
230000003993 interaction Effects 0.000 description 1
230000004068 intracellular signaling Effects 0.000 description 1
150000004694 iodide salts Chemical class 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
238000004255 ion exchange chromatography Methods 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
KQNPFQTWMSNSAP-UHFFFAOYSA-N isobutyric acid Chemical class CC(C)C(O)=O KQNPFQTWMSNSAP-UHFFFAOYSA-N 0.000 description 1
125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
238000002955 isolation Methods 0.000 description 1
125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
125000001786 isothiazolyl group Chemical group 0.000 description 1
125000004284 isoxazol-3-yl group Chemical group [H]C1=C([H])C(*)=NO1 0.000 description 1
150000003893 lactate salts Chemical class 0.000 description 1
150000007517 lewis acids Chemical class 0.000 description 1
SIAPCJWMELPYOE-UHFFFAOYSA-N lithium hydride Chemical compound [LiH] SIAPCJWMELPYOE-UHFFFAOYSA-N 0.000 description 1
JILPJDVXYVTZDQ-UHFFFAOYSA-N lithium methoxide Chemical compound [Li+].[O-]C JILPJDVXYVTZDQ-UHFFFAOYSA-N 0.000 description 1
AHNJTQYTRPXLLG-UHFFFAOYSA-N lithium;diethylazanide Chemical compound [Li+].CC[N-]CC AHNJTQYTRPXLLG-UHFFFAOYSA-N 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
QWDJLDTYWNBUKE-UHFFFAOYSA-L magnesium bicarbonate Chemical group [Mg+2].OC([O-])=O.OC([O-])=O QWDJLDTYWNBUKE-UHFFFAOYSA-L 0.000 description 1
229940096405 magnesium cation Drugs 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
WYPTZCBYSQFOQS-UHFFFAOYSA-N magnesium;bis(trimethylsilyl)azanide Chemical group [Mg+2].C[Si](C)(C)[N-][Si](C)(C)C.C[Si](C)(C)[N-][Si](C)(C)C WYPTZCBYSQFOQS-UHFFFAOYSA-N 0.000 description 1
229940049920 malate Drugs 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
AFVFQIVMOAPDHO-UHFFFAOYSA-M methanesulfonate group Chemical class CS(=O)(=O)[O-] AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
229940098779 methanesulfonic acid Drugs 0.000 description 1
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical class COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 1
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
239000002829 mitogen activated protein kinase inhibitor Substances 0.000 description 1
238000002156 mixing Methods 0.000 description 1
125000002911 monocyclic heterocycle group Chemical group 0.000 description 1
125000005322 morpholin-1-yl group Chemical group 0.000 description 1
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
125000002757 morpholinyl group Chemical group 0.000 description 1
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
150000002823 nitrates Chemical class 0.000 description 1
LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
125000006574 non-aromatic ring group Chemical group 0.000 description 1
239000012038 nucleophile Substances 0.000 description 1
238000007339 nucleophilic aromatic substitution reaction Methods 0.000 description 1
WWZKQHOCKIZLMA-UHFFFAOYSA-M octanoate Chemical class CCCCCCCC([O-])=O WWZKQHOCKIZLMA-UHFFFAOYSA-M 0.000 description 1
231100000590 oncogenic Toxicity 0.000 description 1
230000002246 oncogenic effect Effects 0.000 description 1
238000005580 one pot reaction Methods 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
239000013110 organic ligand Substances 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
125000004287 oxazol-2-yl group Chemical group [H]C1=C([H])N=C(*)O1 0.000 description 1
YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
239000002245 particle Substances 0.000 description 1
239000008177 pharmaceutical agent Substances 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
125000001791 phenazinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3N=C12)* 0.000 description 1
125000001484 phenothiazinyl group Chemical group C1(=CC=CC=2SC3=CC=CC=C3NC12)* 0.000 description 1
125000001644 phenoxazinyl group Chemical group C1(=CC=CC=2OC3=CC=CC=C3NC12)* 0.000 description 1
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical class OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
235000021317 phosphate Nutrition 0.000 description 1
150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
125000005498 phthalate group Chemical class 0.000 description 1
125000004592 phthalazinyl group Chemical group C1(=NN=CC2=CC=CC=C12)* 0.000 description 1
125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
125000004193 piperazinyl group Chemical group 0.000 description 1
125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 1
125000003386 piperidinyl group Chemical group 0.000 description 1
IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 1
CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
229910000343 potassium bisulfate Inorganic materials 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
229960004919 procaine Drugs 0.000 description 1
102000004196 processed proteins & peptides Human genes 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
108060006633 protein kinase Proteins 0.000 description 1
125000001042 pteridinyl group Chemical group N1=C(N=CC2=NC=CN=C12)* 0.000 description 1
125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
125000004289 pyrazol-3-yl group Chemical group [H]N1N=C(*)C([H])=C1[H] 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 description 1
125000002098 pyridazinyl group Chemical group 0.000 description 1
125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
238000010791 quenching Methods 0.000 description 1
230000000171 quenching effect Effects 0.000 description 1
VBCVBVXRDBPFIL-UHFFFAOYSA-N quinazoline-4-carbonitrile Chemical compound C1=CC=C2C(C#N)=NC=NC2=C1 VBCVBVXRDBPFIL-UHFFFAOYSA-N 0.000 description 1
125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
125000004159 quinolin-2-yl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C([H])C(*)=NC2=C1[H] 0.000 description 1
125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
102000009929 raf Kinases Human genes 0.000 description 1
108010077182 raf Kinases Proteins 0.000 description 1
238000006894 reductive elimination reaction Methods 0.000 description 1
230000001105 regulatory effect Effects 0.000 description 1
208000037803 restenosis Diseases 0.000 description 1
238000004366 reverse phase liquid chromatography Methods 0.000 description 1
238000002390 rotary evaporation Methods 0.000 description 1
150000003335 secondary amines Chemical group 0.000 description 1
125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
102000034285 signal transducing proteins Human genes 0.000 description 1
108091006024 signal transducing proteins Proteins 0.000 description 1
230000011664 signaling Effects 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
229910052712 strontium Inorganic materials 0.000 description 1
125000005017 substituted alkenyl group Chemical group 0.000 description 1
125000004426 substituted alkynyl group Chemical group 0.000 description 1
125000005346 substituted cycloalkyl group Chemical group 0.000 description 1
239000000758 substrate Substances 0.000 description 1
150000003890 succinate salts Chemical class 0.000 description 1
LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical class [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
125000004434 sulfur atom Chemical group 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
125000004523 tetrazol-1-yl group Chemical group N1(N=NN=C1)* 0.000 description 1
WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
125000004495 thiazol-4-yl group Chemical group S1C=NC(=C1)* 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
LBLYYCQCTBFVLH-UHFFFAOYSA-M toluenesulfonate group Chemical group C=1(C(=CC=CC1)S(=O)(=O)[O-])C LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
238000005292 vacuum distillation Methods 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
229910052725 zinc Inorganic materials 0.000 description 1
239000011701 zinc Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
- C07C259/04—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids
- C07C259/10—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to carbon atoms of six-membered aromatic rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/08—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions not involving the formation of amino groups, hydroxy groups or etherified or esterified hydroxy groups
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C221/00—Preparation of compounds containing amino groups and doubly-bound oxygen atoms bound to the same carbon skeleton
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/04—Formation of amino groups in compounds containing carboxyl groups
- C07C227/06—Formation of amino groups in compounds containing carboxyl groups by addition or substitution reactions, without increasing the number of carbon atoms in the carbon skeleton of the acid
- C07C227/08—Formation of amino groups in compounds containing carboxyl groups by addition or substitution reactions, without increasing the number of carbon atoms in the carbon skeleton of the acid by reaction of ammonia or amines with acids containing functional groups
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/08—Indoles; Hydrogenated indoles with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to carbon atoms of the hetero ring
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Chemical Kinetics & Catalysis (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Indole Compounds (AREA)
Pyridine Compounds (AREA)

SK207-2003A 2000-08-25 2001-07-20 Process for making N-aryl-anthranilic acids and their derivatives SK2072003A3 (en)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US22820600P	2000-08-25	2000-08-25
PCT/US2001/022948 WO2002018319A1 (fr)	2000-08-25	2001-07-20	Procede de fabrication d'acides n-aryle-anthraniliques et de leurs derives

Publications (1)

Publication Number	Publication Date
SK2072003A3 true SK2072003A3 (en)	2004-01-08

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ID=22856235

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Application Number	Title	Priority Date	Filing Date
SK207-2003A SK2072003A3 (en)	2000-08-25	2001-07-20	Process for making N-aryl-anthranilic acids and their derivatives

Country Status (31)

Country	Link
EP (1)	EP1313694A1 (fr)
JP (1)	JP2004507518A (fr)
KR (1)	KR20030059115A (fr)
CN (1)	CN1458921A (fr)
AP (1)	AP2001002249A0 (fr)
AR (1)	AR032175A1 (fr)
AU (1)	AU2001277044A1 (fr)
BG (1)	BG107635A (fr)
BR (1)	BR0113520A (fr)
CA (1)	CA2420003A1 (fr)
CZ (1)	CZ2003477A3 (fr)
DO (1)	DOP2001000238A (fr)
EA (1)	EA200300187A1 (fr)
GT (1)	GT200100174A (fr)
HN (1)	HN2001000216A (fr)
HU (1)	HUP0300828A2 (fr)
IL (1)	IL154507A0 (fr)
IS (1)	IS6724A (fr)
MA (1)	MA26949A1 (fr)
MX (1)	MXPA03001654A (fr)
NO (1)	NO20030844L (fr)
PA (1)	PA8526501A1 (fr)
PE (1)	PE20020393A1 (fr)
PL (1)	PL360699A1 (fr)
SK (1)	SK2072003A3 (fr)
SV (1)	SV2002000601A (fr)
TN (1)	TNSN01127A1 (fr)
UY (1)	UY26908A1 (fr)
WO (1)	WO2002018319A1 (fr)
YU (1)	YU14303A (fr)
ZA (1)	ZA200301182B (fr)

Families Citing this family (37)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US7235537B2 (en)	2002-03-13	2007-06-26	Array Biopharma, Inc.	N3 alkylated benzimidazole derivatives as MEK inhibitors
PT2130537E (pt)	2002-03-13	2012-12-20	Array Biopharma Inc	Derivados de benzimidazole n3 alquilado como inibidores de mek
US7144907B2 (en)	2003-09-03	2006-12-05	Array Biopharma Inc.	Heterocyclic inhibitors of MEK and methods of use thereof
US7538120B2 (en)	2003-09-03	2009-05-26	Array Biopharma Inc.	Method of treating inflammatory diseases
CA2542210A1 (fr)	2003-10-21	2005-05-06	Warner-Lambert Company Llc	Forme polymorphe du n-[(r)-2,3-dihydroxy-propoxy]-3,4-difluoro-2-fluoro-4-iodophenylamino)-benzamide
PL1689233T3 (pl)	2003-11-19	2012-11-30	Array Biopharma Inc	Bicykliczne inhibitory MEK
US7517994B2 (en)	2003-11-19	2009-04-14	Array Biopharma Inc.	Heterocyclic inhibitors of MEK and methods of use thereof
US7732616B2 (en)	2003-11-19	2010-06-08	Array Biopharma Inc.	Dihydropyridine and dihydropyridazine derivatives as inhibitors of MEK and methods of use thereof
CN102786482A (zh)	2003-11-21	2012-11-21	阿雷生物药品公司	Akt蛋白激酶抑制剂
UA89035C2 (ru) *	2003-12-03	2009-12-25	Лео Фарма А/С	Эфиры гидроксамовых кислот и их фармацевтическое применение
DK2332909T3 (da)	2005-04-13	2014-11-10	Astex Therapeutics Ltd	Hydroxybenzamidderivater og deres anvendelse som inhibitorer af hsp90
ES2405785T3 (es)	2005-05-18	2013-06-03	Array Biopharma Inc.	Inhibidores heterocíclicos de MEK y métodos de uso de los mismos
US7754725B2 (en)	2006-03-01	2010-07-13	Astex Therapeutics Ltd.	Dihydroxyphenyl isoindolymethanones
US8063050B2 (en)	2006-07-06	2011-11-22	Array Biopharma Inc.	Hydroxylated and methoxylated pyrimidyl cyclopentanes as AKT protein kinase inhibitors
CN101631778B (zh)	2006-07-06	2013-05-08	阵列生物制药公司	作为akt蛋白激酶抑制剂的环戊二烯并[d]嘧啶
US9303040B2 (en)	2006-07-06	2016-04-05	Array Biopharma Inc.	Substituted piperazines as AKT inhibitors
DE602007011628D1 (de)	2006-07-06	2011-02-10	Array Biopharma Inc	Dihydrofuropyrimidine als akt-proteinkinaseinhibitoren
EP2073802A1 (fr)	2006-10-12	2009-07-01	Astex Therapeutics Limited	Combinaisons pharmaceutiques
JP5518478B2 (ja)	2006-10-12	2014-06-11	アステックス、セラピューティックス、リミテッド	医薬化合物
GB0620259D0 (en)	2006-10-12	2006-11-22	Astex Therapeutics Ltd	Pharmaceutical compounds
JP5410285B2 (ja)	2006-10-12	2014-02-05	アステックス、セラピューティックス、リミテッド	医薬化合物
JP5528806B2 (ja)	2006-10-12	2014-06-25	アステックス、セラピューティックス、リミテッド	複合薬剤
JP5528807B2 (ja)	2006-10-12	2014-06-25	アステックス、セラピューティックス、リミテッド	複合薬剤
KR101650956B1 (ko)	2007-07-05	2016-08-24	어레이 바이오파마 인크.	Ａｋｔ 단백질 키나제 억제제로서의 피리미딜 시클로펜탄
US9409886B2 (en)	2007-07-05	2016-08-09	Array Biopharma Inc.	Pyrimidyl cyclopentanes as AKT protein kinase inhibitors
US8846683B2 (en)	2007-07-05	2014-09-30	Array Biopharma, Inc.	Pyrimidyl cyclopentanes as Akt protein kinase inhibitors
KR101624361B1 (ko)	2007-07-05	2016-05-25	어레이 바이오파마 인크.	Ａｋｔ 단백질 키나제 억제제로서의 피리미딜 시클로펜탄
AU2009204019B2 (en)	2008-01-09	2014-02-20	Array Biopharma Inc.	Hydroxylated pyrimidyl cyclopentane as AKT protein kinase inhibitor
ES2422733T3 (es)	2008-01-09	2013-09-13	Array Biopharma Inc	Pirimidilciclopentanos hidroxilados como inhibidores de proteínas cinasas AKT
GB0806527D0 (en)	2008-04-11	2008-05-14	Astex Therapeutics Ltd	Pharmaceutical compounds
CN101985428B (zh) *	2009-07-29	2014-02-12	杭州民生药业有限公司	邻苯胺基苯甲酸衍生物或其药学上可接受的盐、其制备方法及其用途
US20120316337A1 (en) *	2010-02-19	2012-12-13	Universite Du Maine	Method for preparing chemical compounds of interest by nucleophilic aromatic substitution of aromatic carboxylic acid derivatives supporting at least one electro-attractive group
CA2789373A1 (fr) *	2010-02-19	2011-08-25	Centre National De La Recherche Scientifique	Processus de preparation de composes chimiques d'interet par substitution nucleophile aromatique de derives d'acides carboxyliques aromatiques soutenant au moins un groupe attirant les electrons
CA2844699C (fr)	2011-04-01	2019-05-07	Genentech, Inc.	Combinaisons de composes inhibiteurs d'akt et d'abiraterone et procedes d'utilisation
CN103841976A (zh)	2011-04-01	2014-06-04	基因泰克公司	Akt和mek抑制剂化合物的组合及其使用方法
WO2014059422A1 (fr) *	2012-10-12	2014-04-17	Exelixis, Inc.	Nouveau procédé pour la production de composés à utiliser dans le traitement du cancer
CN112745237B (zh) *	2019-10-29	2023-06-20	中国科学院上海药物研究所	2-芳基胺类化合物及其制备方法和应用

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3138636A (en) *	1960-06-23	1964-06-23	Parke Davis & Co	Anthranilic acid derivatives
WO1998037881A1 (fr) *	1997-02-28	1998-09-03	Warner Lambert Company	Methode de traitement ou de prevention du choc septique par administration d'un inhibiteur mek
ES2274572T3 (es) *	1997-07-01	2007-05-16	Warner-Lambert Company Llc	Derivados de acido 2-(4-bromo- o 4-yodo-fenilamino) benzoico y su uso como inhibidor de mek.
CA2290506C (fr) *	1997-07-01	2005-12-27	Warner-Lambert Company	Derives d'acide benzhydroxamique phenylamino 4-bromo ou 4-iodo et utilisation de ces derniers en tant qu'inhibiteurs de mek
CA2348236A1 (fr) *	1999-01-13	2000-07-20	Stephen Douglas Barrett	4-arylamino, 4-aryloxy, et 4-arylthio diarylamines et leurs derives comme inhibiteurs selectifs de mek
EP1171418B1 (fr) *	1999-04-21	2004-12-29	Warner-Lambert Company LLC	Procede de preparation d'acides 2-(n-phenylalmino)benzoiques

2001
- 2001-07-20 JP JP2002523437A patent/JP2004507518A/ja active Pending
- 2001-07-20 SK SK207-2003A patent/SK2072003A3/sk unknown
- 2001-07-20 CZ CZ2003477A patent/CZ2003477A3/cs unknown
- 2001-07-20 AP APAP/P/2001/002249A patent/AP2001002249A0/en unknown
- 2001-07-20 EP EP01954824A patent/EP1313694A1/fr not_active Withdrawn
- 2001-07-20 IL IL15450701A patent/IL154507A0/xx unknown
- 2001-07-20 MX MXPA03001654A patent/MXPA03001654A/es unknown
- 2001-07-20 CN CN01815869A patent/CN1458921A/zh active Pending
- 2001-07-20 EA EA200300187A patent/EA200300187A1/ru unknown
- 2001-07-20 KR KR10-2003-7002675A patent/KR20030059115A/ko not_active Application Discontinuation
- 2001-07-20 HU HU0300828A patent/HUP0300828A2/hu unknown
- 2001-07-20 AU AU2001277044A patent/AU2001277044A1/en not_active Abandoned
- 2001-07-20 CA CA002420003A patent/CA2420003A1/fr not_active Abandoned
- 2001-07-20 WO PCT/US2001/022948 patent/WO2002018319A1/fr not_active Application Discontinuation
- 2001-07-20 BR BR0113520-1A patent/BR0113520A/pt not_active Application Discontinuation
- 2001-07-20 YU YU14303A patent/YU14303A/sh unknown
- 2001-07-20 PL PL36069901A patent/PL360699A1/xx unknown
- 2001-08-15 SV SV2001000601A patent/SV2002000601A/es not_active Application Discontinuation
- 2001-08-22 TN TNTNSN01127A patent/TNSN01127A1/en unknown
- 2001-08-23 PA PA20018526501A patent/PA8526501A1/es unknown
- 2001-08-24 DO DO2001000238A patent/DOP2001000238A/es unknown
- 2001-08-24 AR ARP010104047A patent/AR032175A1/es unknown
- 2001-08-24 GT GT200100174A patent/GT200100174A/es unknown
- 2001-08-24 PE PE2001000853A patent/PE20020393A1/es not_active Application Discontinuation
- 2001-08-24 UY UY26908A patent/UY26908A1/es not_active Application Discontinuation
- 2001-09-26 HN HN2001000216A patent/HN2001000216A/es unknown
2003
- 2003-02-12 ZA ZA200301182A patent/ZA200301182B/en unknown
- 2003-02-20 IS IS6724A patent/IS6724A/is unknown
- 2003-02-24 NO NO20030844A patent/NO20030844L/no not_active Application Discontinuation
- 2003-03-13 BG BG107635A patent/BG107635A/bg unknown
- 2003-03-14 MA MA27069A patent/MA26949A1/fr unknown

Also Published As

Publication number	Publication date
PA8526501A1 (es)	2002-07-30
IS6724A (is)	2003-02-20
KR20030059115A (ko)	2003-07-07
YU14303A (sh)	2006-08-17
IL154507A0 (en)	2003-09-17
PE20020393A1 (es)	2002-05-09
EP1313694A1 (fr)	2003-05-28
BG107635A (bg)	2004-09-30
NO20030844D0 (no)	2003-02-24
UY26908A1 (es)	2001-11-30
GT200100174A (es)	2002-07-18
CA2420003A1 (fr)	2002-03-07
MA26949A1 (fr)	2004-12-20
AP2001002249A0 (en)	2001-09-30
ZA200301182B (en)	2004-05-12
AU2001277044A1 (en)	2002-03-13
CZ2003477A3 (cs)	2003-10-15
PL360699A1 (en)	2004-09-20
SV2002000601A (es)	2002-04-03
AR032175A1 (es)	2003-10-29
TNSN01127A1 (en)	2005-11-10
DOP2001000238A (es)	2003-01-31
JP2004507518A (ja)	2004-03-11
HN2001000216A (es)	2002-05-22
HUP0300828A2 (hu)	2003-09-29
CN1458921A (zh)	2003-11-26
NO20030844L (no)	2003-02-25
EA200300187A1 (ru)	2003-08-28
BR0113520A (pt)	2003-06-24
MXPA03001654A (es)	2004-09-10
WO2002018319A1 (fr)	2002-03-07

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