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WO1989001333A1 - IMIDAZO[1,2-b]PYRIDAZINES - Google Patents

IMIDAZO[1,2-b]PYRIDAZINES Download PDF

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Publication number
WO1989001333A1
WO1989001333A1 PCT/AU1988/000290 AU8800290W WO8901333A1 WO 1989001333 A1 WO1989001333 A1 WO 1989001333A1 AU 8800290 W AU8800290 W AU 8800290W WO 8901333 A1 WO8901333 A1 WO 8901333A1
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Prior art keywords
substituted
compound
ome
phenyl
formula
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PCT/AU1988/000290
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English (en)
Inventor
Gordon Bruce Barlin
Leslie Philip Davies
Stephen James Ireland
Maria Mee Leng Ngu
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The Australian National University
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Publication of WO1989001333A1 publication Critical patent/WO1989001333A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/50—Pyridazines; Hydrogenated pyridazines

Definitions

  • This invention relates to imidazo[1,2-b]- pyridazine compounds, and in particular it relates to a group of imidazo[1,2-b]pyridazines bearing substituents in the 2-, 3- and 6- positions which have been found to interact with the receptors in the central nervous system which mediate the anxiolytic, anticonvulsant, muscle-relaxant, hypnotic and other activities of the benzodiazepine class of drugs.
  • a method for the treatment of anxiety syndromes, epilepsy, insomnia or skeletal muscle tension, or for the reversal of the sedative effects of the benzodiazepine class of drugs which comprises administration of an effective amount of compound of the general formula V:
  • X is a halogen atom, or a group of the formula
  • R 1 is selected from alkyl or substituted alkyl, alkenyl or substituted alkenyl, alkynyl or substituted alkynyl, aryl or substituted-aryl (including phenyl or substituted phenyl), arylalkyl or substituted-arylalkyl (including phenylalkyl or substituted phenylalkyl), arylalkenyl or substituted-arylalkenyl (including phenylalkenyl or substituted phenylalkenyl), arylalkynyl or substituted-arylalkynyl (including phenylalkenyl or substituted phenylalkenyl), heteroaryl or substituted-heteroaryl, heteroarylalkyl or substituted-heteroarylalkyl, heteroarylalkenyl or
  • Y is a group of the formula OR 2 ,
  • R 2 , R 4 and R 6 and R 7 (which may be the same or different) is selected from alkyl
  • Z is selected from aryl or substituted-aryl (including phenyl or substituted-phenyl), arylalkyl or substituted-arylalkyl, (including phenylalkyl and substituted phenylalkyl) heteroaryl or substituted-heteroaryl, heteroarylalkyl or substituted-heteroarylalkyl, cycloalkyl or substituted-cycloalkyl, cycloalkylalkyl or (substituted-cycloalkyl) alkyl, heterocyclo or substituted-heterocyclo, or heterocycloalkyl or substituted-heterocycloalkyl; with the proviso that X is not a group of the formula -OAr or -SCH 2 Ar (where Ar is aryl or substituted aryl) when Y is a group of the formula -OAlkyl and Z is aryl or substituted aryl, or heteroaryl or substituted heteroaryl.
  • Preferred aryl groups represented by X, Y and Z are phenyl and ⁇ - and ⁇ -naphthyl groups, however other aryl groups are encompassed within the scope of this invention.
  • Preferred heteroaryl groups represented by X and Z are ⁇ -, ß and ⁇ -pyridyl, and ⁇ - and ⁇ -thienyl groups, however other heteroaryl groups are also encompassed within the scope of this invention.
  • Preferred optional substituents on the groups represented by X and Z include one or more alkyl (particularly methyl), alkoxy (particularly methoxy), alkylthio (particularly methylthio), halo (particularly fluoro, chloro or bromo), trifluoromethyl, dialkylamino (particularly dimethylamino), nitro or amino groups.
  • One group of preferred compounds of the general formula V are compounds wherein:
  • X is a halogen atom, or is selected from alkoxy, alkylthio, phenylalkoxy or substituted- phenylalkoxy, phenylthio or substituted- phenylthio, anilino, phenylalkylamino or substituted phenylalkylamino, ⁇ -, ⁇ - or ⁇ -picolythio, ß-picolylamino, or benzthiazol-2-ylthio; Y is selected from methoxy or ethoxy; and
  • Z is selected from phenyl or substituted-phenyl, ⁇ - or ß-naphthyl, ⁇ -, ß- or ⁇ -pyridyl, or ⁇ - or ß-thienyl.
  • a second group of preferred compounds of the general formula V are compounds wherein:
  • X is a halogen atom, or is selected from alkoxy, alkylthio, phenoxy or substituted phenoxy, phenylalkoxy or substituted phenylalkoxy, phenylthio or substituted phenylthio, or phenylalkylthio or substituted phenylalkylthio;
  • Y is selected from -CH 2 NHCOMe, -CH 2 NHCOPh, and -CH 2 NMe 2 ; and Z is selected from phenyl or substituted phenyl.
  • the present invention provides a pharmaceutical composition for use in treatment of anxiety syndromes, epilepsy, insomnia or skeletal muscle tension, or for the reversal of the sedative effects of the benzodiazepine class of drugs, which comprises a compound of the general formula V as broadly described above, in association with a pharmaceutically acceptable carrier or diluent.
  • substituent X is a halogen atom, particularly a chlorine atom
  • this substituent may be readily replaced by other substituents represented by X, such as alkoxy or alkylthio groups, by methods well known in the art.
  • the starting materials for the reaction schemes as set out above may be prepared from 3,6-dichloropyridazine as follows:
  • Specific tests performed to investigate this biological activity include: (i) a test for displacement of H-diazepam from rat brain membranes; and (ii) a rat conflict test for anxiolytic effects.
  • 6-Chloro-3-methoxy-2-(2'-methoxyphenyl)imidazo[1,2-b]pyridazine A mixture of 6-chloropyridazin-3-amine (0.2 g), 2-methoxy- phenylglyoxal (0.28 g) (prepared by selenium dioxide oxidation of 2-methoxyacetophenone for 48 h by a method similar to that used for phenylglyoxal), ethanol (8 ml) and concentrated hydrochloric acid (0.2 ml) was refluxed for 8 h. The solvent was evaporated under reduced pressure, the residue was diluted with water, and the red precipitate (0.25 g) was filtered off, washed with water and dried.
  • Portion (0.15 g) of this product was stirred with ethereal diazomethane (from 1.3 g nitrosomethylurea) in ice and then at 20° overnight. It was evaporated to dryness and the product subjected to t.l.c. (alumina; chloroform) and recrystallised from cyclohexane to give yellow crystals of 6-chloro-3-methoxy- 2-(2 '-methoxyphenyl)imidazo[1,2-b]pyridazine (0.070 g), m.p. 147-150° (Found, for sample dried at 40° amd 0.1 mm Hg for 6 h: C, 58.3; H, 4.1; N, 14.5.
  • 6-Chloro-3-methoxy-2-(3'-nitrophenyl)imidazo[1,2-b]pyridazine A mixture of 6-chloropyridazin-3-amine (0.2 g), m- nitrophenylglyoxal (0.35 g), concentrated hydrochloric acid (0.12 ml) and ethanol (8.0 ml) was refluxed in an oil bath at 85° for 8 h. After cooling, the red precipitate (0.28 g) was collected and washed with cold water and ether.
  • [1,2-b]pyridazine (0.1 g) in methanol (30 ml) was added dropwise to a rapidly stirred mixture of iron powder (0.45 g, freshly washed with dilute acid), methanol (15.0 ml), water (6.0 ml) and concentrated hydrochloric acid (0.6 ml) at 80-85° and then maintained at that temperature for 2 h.
  • the residual solid was filtered off and washed with hot methanol.
  • the combined filtrates were evaporated, the residue diluted with water (10.0 ml) and adjusted with M sodium hydroxide to pH 6-7. This solution was extracted with chloroform and the extract washed with water and dried (Na 2 SO 4 ).
  • 6-Fluoro-3-methoxy-2-(4'-methylphenyl)imidazo[1,2-b]pyridazine 6-Fluoropyridazin-3-amine 0.5 g, Barlin, Aust. J. Chem., 1986, 39, 1803
  • 4-methylphenylglyoxal hydrate 0.74 g
  • concentrated hydrochloric acid 0.5 ml
  • ethanol 10 ml
  • 6-Propylthiopyridazin-3-amine 6-Chloropyridazin-3-amine (1.942 g) and aqueous sodium propanethiolate (prepared from 1.2 g sodium hydroxide in 25 ml water with 2.28 g propanethiol) were heated at 140° for 17 h. After cooling the solid was filtered off, washed with 1 M sodium hydroxide, dried, and recrystallised from cyclohexane to give white crystals of 6-prop ⁇ lthiop ⁇ ridazin-3-amine (1.7 g), m.p. 77-78° (Found, for sample dried at 50° for 4.5 h: C, 49.3; H, 6.5; N, 24.4.
  • 6-Chloropyridazin-3-amine (5.0 g) was added to a solution of thiophenol (10.0 ml) in 1.7 M sodium hydroxide (50 ml) and the mixture heated at 130° for 18 h. After cooling the white solid was filtered off washed with 1 M sodium hydroxide and water and dried at the pump. It was divided into two parts and chromatographed separately in chloroform over a column of alumina (12 cm x 4 cm diameter) and recrystallised from benzene to give white crystals of 6-phenylthiopyridazin-3-amine (4.2 g), m.p. 139-140° (lit. 136°).
  • Example 14 6-Benzyloxy-3-methoxy-2-(4'-methylphenylimidazo[1,2-b]pyridazine
  • a mixture of 6-benzyloxypyridazin-3-amine (0.2 g), p-methylphenyl glyoxal monohydrate (0.18 g), ethanol (17 ml) and concentrated hydrochloric acid (0.2 ml) was refluxed for 10 h, then the solvent evaporated under reduced pressure, the residue was methylated with etheral diazomethane and the product subjected to t.l.c. (alumina; chloroform) to give a yellow residue which was recrystallised from light petroleum (b.p.
  • 6-(2'-Methoxybenzyloxy)pyridazin-3-amine 2-oxide (0.28 g) and phenacyl bromide (0.24 g) in ethanol (6 ml) were refluxed with stirring for 1.5 h.
  • Ethanol was removed under reduced pressure to give a dark residue which was stirred with ethereal diazomethane at 0°, then at 20° overnight.
  • the crude product was subjected to t.l.c. (alumina; chloroform then toluene) to give an orange solid which was recrystallised from light petroleum (b.p. 60-80°) to give the title compound (0.04 g), m.p.
  • This compound was prepared from 3-methoxybenzyl alcohol (6.0 g) and 6-chloropyridazin-3-amine 2-oxide (0.65) as for the isomer above.
  • 6-Chlorcpyridazin-3-amine 2-oxide (0.2 g) and benzylamine (2.0 g) were heated in a screw top reaction vessel at 160° for 20 h. After cooling, chloroform (2 ml) was added to the brown residue and the mixture subjected to column chromatography
  • This compound was prepared from 6-chloropyridazin-3-amine 2-oxide and 2-methoxybenzylamine as for the benzylamino- analogue.
  • the product was subjected to column chromatography
  • 6-(2'-Methoxybenzylamino)pyridazin-3-amine 2-oxide (0.20 g) and phenacylbromide (0.18 g) in ethanol (9.0 ml) were refluxed for 2.5 h and then methylated as above.
  • the crude product was subjected to t.l.c. (alumina; chloroform) and recrystallised from a mixture of chloroform and cyclohexane to give the title compound (0.100 g), m.p. 132-134° (Found, for a sample dried at 100° and 0.1mmHg for 4 h: C, 69.9; H, 5.7; N, 15.4.
  • This product was prepared as for its 6-(2'- methoxybenzylamino)-isomer above and purified by column chromatography (alumina; chloroform, and eluted with ethanol) and recrystallisation from a mixture of n-propanol and acetone to give the title compound, m.p. 161-163° (Found: C, 58.7; H,
  • CD 3 SOCD 3 (CD 3 SOCD 3 ): ⁇ 3.75, s, MeO; 5.23, s, CH 2 ; 5.9, b, NH 2 ; 6.85, d, 6.93, d, J 4 5 9 Hz, H4 and 5; 6.95, d, 7.40, d, J 2',3 ' 9 Hz, H2' ,3' ,5' ,6'.
  • 6-Chloropyridazin-3-amine 2-oxide (0.5 g) and ethanolamine (2.0 g) were heated in a screw top reaction vessel at 160° for 16 h. This mixture was dissolved in methanol and applied to a column of alumina (20 cm x 2.5 cm) packed with chloroform. It was then elute with chloroform containing increasing amounts of methanol. Ethanolamine was eluted first, followed by the product (0.34 g) which was recrystallised from cyclohexane to give the title compound, m.p. 166-168° (Found: C, 42.6; H, 6.0; N, 32.6.
  • 6-Aminopyridazine-3-thiol (0.44 g) in 0.5 M sodium hydroxide (15 ml) was shaken with pyrid-2-ylmethyl chloride hydrochloride (0.58 g) for 4 h.
  • the aqueous solution was extracted with chloroform, the extract washed with water and dried (Na 2 SO 4 ). Evaporation of the solvent gave a white solid (0.72 g) which was recrystallised from toluene to give the title compound (0.6 g), m.p. 124-126° (Found: C, 55.3; H, 4.6; N, 25.5.
  • C 10 H 10 N 4 S requires C, 55.0; H, 4.6; N, 25.7%).
  • 6-Chloropyridazin-3-amine 2-oxide (0.4 g) and pyrid-3- ylmethylamine (3.0 g) were heated at 160° for 16 h.
  • the reaction mixture was dissolved in ethanol (3.0 ml) and applied to a column of alumina (22 cm) and washed with n-propanol/acetone (lsl) to remove excess pyridylmethylamine.
  • the product was eluted with methanol and precipitated from chloroform with ether. It was recrystallised from n-propanol/ethylacetate to give yellow crystals of the title compound (0.25 g), m.p.
  • aliquots of the membrane suspension (approx.0.6-0.8mg protein) were incubated with tritiated diazepam (86.6 Ci/mmol, 0.70 + - 0.05 nM final concentration) and 3 to 5 separate concentrations of the test compounds, in a final volume of 2 ml of 50 mM Tris-HCl buffer. Assays were conducted on ice for an incubation period of 35 min. Unless otherwise stated, assays also contained 100 ⁇ M GABA to stimulate the binding of the ligand to the benzodiazepine receptors in the plasma membranes. Nonspecific binding was determined in separate tubes by the addition of a large excess (10 ⁇ M) of unlabelled diazepam.
  • Membranes were collected by filtration under vacuum on glass-fibre filters (Whatman GF/B, 2.4 cir.) and washed with 12 ml of ice-cold buffer. Filters were placed in scintillation vials with 1 ml of water and 8 ml of toluene/triton X-100 scintillation fluid; bound radioactivity was determined using conventional techniques. Test compounds (imidazo[l, 2-b]pyridazines) were routinely tested at 4 separate concentrations; within each experiment all assays were performed in triplicate.

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Abstract

Les composés d'imidazo[1,2-b]pyridazine décrits qui sont substitués aux positions 2, 3 et 6, sont utiles dans le traitement des syndromes d'angoisse, de l'épilepsie, de l'insomnie ou des tensions musculaires transosseuses ou pour inverser les effets sédatifs de médicaments appartenant à la classe des benzodiazépines.
PCT/AU1988/000290 1987-08-07 1988-08-05 IMIDAZO[1,2-b]PYRIDAZINES WO1989001333A1 (fr)

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Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0305093B1 (fr) * 1987-08-15 1994-04-06 The Wellcome Foundation Limited Dérivés de l'imidazo[1,2-b]pyridazine
US6369060B1 (en) 1996-06-20 2002-04-09 Smithkline Beecham P.L.C. Indoline derivatives useful as 5-HT-2C receptor antagonists
WO2003006471A1 (fr) * 2001-07-13 2003-01-23 Neurogen Corporation Composes heteroaryles bicycliques fondus a substitution heteroaryle utilises comme ligands des recepteurs gabaa
WO2007110437A1 (fr) * 2006-03-29 2007-10-04 Ferrer Internacional, S.A. Imidazo [1, 2-b] pyridazines, leurs procédés de préparation et leur utilisation en tant que ligands du récepteur gaba
FR2918986A1 (fr) * 2007-07-19 2009-01-23 Sanofi Aventis Sa Derives de 6-cycloamino-3-(pyridazin-4-yl)imidazo[1,2-b]- pyridazine, leur preparation et leur application en therapeutique
WO2010070237A1 (fr) * 2008-12-19 2010-06-24 Sanofi-Aventis DÉRIVÉS DE 6-CYCLOAMINO-2-THIENYL-3-(PYRIDIN-4-YL)IMIDAZO[1,2-b]-PYRIDAZINE ET 6-CYCLOAMINO-2-FURANYL-3-(PYRIDIN-4-YL)IMIDAZO[1,2-b]-PYRIDAZINE, LEUR PRÉPARATION ET LEUR APPLICATION EN THÉRAPEUTIQUE
WO2010070238A1 (fr) * 2008-12-19 2010-06-24 Sanofi-Aventis DÉRIVÉS DE 6-CYCLOAMINO-2,3-DI-PYRIDINYL-IMIDAZO[1,2-b]-PYRIDAZINE, LEUR PRÉPARATION ET LEUR APPLICATION EN THÉRAPEUTIQUE
US8034812B2 (en) 2006-08-04 2011-10-11 Takeda Pharmaceutical Company Limited Imidazopyridazine derivative having kinase inhibitory activity and pharmaceutical agent thereof
JP2015180633A (ja) * 2008-05-19 2015-10-15 サノビオン ファーマシューティカルズ インクＳｕｎｏｖｉｏｎ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃ． イミダゾ［１，２−ａ］ピリジン化合物
RU2598385C2 (ru) * 2010-12-22 2016-09-27 ХЕНГРУЙ (ЮЭсЭй), ЛТД. ПРОИЗВОДНЫЕ 2-АРИЛИМИДАЗО[1,2-b]ПИРИДАЗИНА, 2-ФЕНИЛИМИДАЗО[1,2-a]ПИРИДИНА И 2-ФЕНИЛИМИДАЗО[1,2-a]ПИРАЗИНА
JP2018509416A (ja) * 2015-03-12 2018-04-05 イー・アイ・デュポン・ドウ・ヌムール・アンド・カンパニーＥ．Ｉ．Ｄｕ Ｐｏｎｔ Ｄｅ Ｎｅｍｏｕｒｓ Ａｎｄ Ｃｏｍｐａｎｙ 複素環置換二環式アゾール殺有害生物剤

Citations (1)

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US4464372A (en) * 1982-08-16 1984-08-07 Schering Corporation Imidazo[1,2-b]pyridazines

Non-Patent Citations (3)

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Title
AUST. J. CHEM., Volume 36, issued June 1983, G.B. BARLIN ET AL.," Imidazo(1,2-b)pyridazines and an Imidazo(1,2-a)pyrazine from Pyridazin- and pyrazin-amines", pages 1215-20. *
AUST. J. CHEM., Volume 39, issued November 1986, G.B. BARLIN, "Imidazol(1,2-b)pyridazines I Some 3-Alkoxy-6-halogeno-2-phenyl- (and 4'-substituted phenyl) imidazo(1,2-b)pyridazines and 3-Methoxy-2,6-diphenylimidazo(1,2-b)pyridazines", pages 1803-9. *
AUST. J. CHEM., Volume 40, issued August 1987, G.B. BARLIN et al., "Imidazo(1,2-b)pyridazines II 6-Alkylthio- and 6-Arylthio-3-methoxy-2-phenyl-imidazo(1,2-b)pyridazines", pages 1491-7. *

Cited By (30)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0305093B1 (fr) * 1987-08-15 1994-04-06 The Wellcome Foundation Limited Dérivés de l'imidazo[1,2-b]pyridazine
US6369060B1 (en) 1996-06-20 2002-04-09 Smithkline Beecham P.L.C. Indoline derivatives useful as 5-HT-2C receptor antagonists
EP0912554B1 (fr) * 1996-06-20 2002-11-27 SmithKline Beecham plc Derives de l'indoline utiles comme antagonistes des recepteurs 5ht-2c
CN100369912C (zh) * 2001-07-13 2008-02-20 神经原公司 用作gabaa受体配体的杂芳基取代的稠合双环杂芳基化合物
WO2003006471A1 (fr) * 2001-07-13 2003-01-23 Neurogen Corporation Composes heteroaryles bicycliques fondus a substitution heteroaryle utilises comme ligands des recepteurs gabaa
EP1845098A1 (fr) * 2006-03-29 2007-10-17 Ferrer Internacional, S.A. Imidazo[1,2-b]pyridazines, leur procédés de préparation et leur utilisation comme ligands du recepteur GABA
US8153789B2 (en) 2006-03-29 2012-04-10 Ferrer Internacional, S.A. Imidazo[1,2-b]pyridazines, processes, uses, intermediates and compositions
WO2007110438A1 (fr) * 2006-03-29 2007-10-04 Ferrer Internacional, S.A. Imidazo [1,2 -b] pyridazines, leurs processus de préparation et leur utilisation en tant que ligands du récepteur gaba
US8993562B2 (en) 2006-03-29 2015-03-31 Ferrer Internacional, S.A. Imidazo[1,2-b]pyridazines, processes, uses, intermediates and compositions
TWI403512B (zh) * 2006-03-29 2013-08-01 Ferrer Int 咪唑并〔１，２-ｂ〕嗒類、製法、用途、中間物及組成物
RU2486188C2 (ru) * 2006-03-29 2013-06-27 Феррер Интернасионал, С.А. СОЕДИНЕНИЯ ИМИДАЗО-[1,2-b]-ПИРИДАЗИНА (ВАРИАНТЫ), СПОСОБ ПОЛУЧЕНИЯ СОЕДИНЕНИЙ ИМИДАЗО-[1,2-b]-ПИРИДАЗИНА (ВАРИАНТЫ), ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ И ЛЕКАРСТВЕННОЕ СРЕДСТВО ДЛЯ ЛЕЧЕНИЯ И/ИЛИ ПРЕДУПРЕЖДЕНИЯ ЗАБОЛЕВАНИЙ, СВЯЗАННЫХ С ИНГИБИРОВАНИЕМ ГАМКА РЕЦЕПТОРОВ
JP2009531384A (ja) * 2006-03-29 2009-09-03 フエルレル インターナショナル，ソシエダッド アノニマ イミダゾ［１，２−ｂ］ピリダジン、その調製方法及びＧＡＢＡ受容体リガンドとしてのその使用
WO2007110437A1 (fr) * 2006-03-29 2007-10-04 Ferrer Internacional, S.A. Imidazo [1, 2-b] pyridazines, leurs procédés de préparation et leur utilisation en tant que ligands du récepteur gaba
US8273741B2 (en) 2006-08-04 2012-09-25 Takeda Pharmaceutical Company Limited Imidazo-pyridazinyl compounds and uses thereof
US8034812B2 (en) 2006-08-04 2011-10-11 Takeda Pharmaceutical Company Limited Imidazopyridazine derivative having kinase inhibitory activity and pharmaceutical agent thereof
US8044049B2 (en) 2006-08-04 2011-10-25 Takeda Pharmaceutical Company Limited Fused heterocyclic derivative and use thereof
US9108971B2 (en) 2007-07-19 2015-08-18 Sanofi 6-cycloamino-3-(pyridazin-4-yl)imidazo[1,2-b]-pyridazine and derivatives thereof preparation and therapeutic application thereof
WO2009037394A3 (fr) * 2007-07-19 2009-06-18 Sanofi Aventis DERIVES DE 6-CYCLOAMINO-S-(PYRIDAZIN-YL)IMIDAZO[1,2-b]-PYRIDAZINE, LEUR PREPARATION ET LEUR APPLICATION EN THERAPEUTIQUE.
FR2918986A1 (fr) * 2007-07-19 2009-01-23 Sanofi Aventis Sa Derives de 6-cycloamino-3-(pyridazin-4-yl)imidazo[1,2-b]- pyridazine, leur preparation et leur application en therapeutique
WO2009037394A2 (fr) * 2007-07-19 2009-03-26 Sanofi-Aventis DERIVES DE 6-CYCLOAMINO-S-(PYRIDAZIN-YL)IMIDAZO[1,2-b]-PYRIDAZINE, LEUR PREPARATION ET LEUR APPLICATION EN THERAPEUTIQUE.
EA016376B1 (ru) * 2007-07-19 2012-04-30 Санофи-Авентис ПРОИЗВОДНЫЕ 6-ЦИКЛОАМИНО-3-(ПИРИДАЗИН-4-ИЛ)ИМИДАЗО[1,2-b]ПИРИДАЗИНА, ИХ ПОЛУЧЕНИЕ И ИХ ПРИМЕНЕНИЕ В ТЕРАПИИ
US8455491B2 (en) 2007-07-19 2013-06-04 Sanofi 6-cycloamino-3-(pyridazin-4-yl)imidazo[1,2-b]pyridazine and derivatives and pharmaceutical compositions comprising the same
JP2015180633A (ja) * 2008-05-19 2015-10-15 サノビオン ファーマシューティカルズ インクＳｕｎｏｖｉｏｎ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ Ｉｎｃ． イミダゾ［１，２−ａ］ピリジン化合物
WO2010070237A1 (fr) * 2008-12-19 2010-06-24 Sanofi-Aventis DÉRIVÉS DE 6-CYCLOAMINO-2-THIENYL-3-(PYRIDIN-4-YL)IMIDAZO[1,2-b]-PYRIDAZINE ET 6-CYCLOAMINO-2-FURANYL-3-(PYRIDIN-4-YL)IMIDAZO[1,2-b]-PYRIDAZINE, LEUR PRÉPARATION ET LEUR APPLICATION EN THÉRAPEUTIQUE
FR2940285A1 (fr) * 2008-12-19 2010-06-25 Sanofi Aventis Derives de 6-cycloamino-2-thienyl-3-(pyridin-4-yl)imidazo °1,2-b!-pyridazine et 6-cycloamino-2-furanyl-3- (pyridin-4-yl)imidazo°1,2-b!-pyridazine, leur preparation et leur application en therapeutique
WO2010070238A1 (fr) * 2008-12-19 2010-06-24 Sanofi-Aventis DÉRIVÉS DE 6-CYCLOAMINO-2,3-DI-PYRIDINYL-IMIDAZO[1,2-b]-PYRIDAZINE, LEUR PRÉPARATION ET LEUR APPLICATION EN THÉRAPEUTIQUE
CN102325773A (zh) * 2008-12-19 2012-01-18 赛诺菲 6-环氨基-2,3-二吡啶基咪唑并[1,2-b]-哒嗪衍生物及其制备和治疗应用
FR2940284A1 (fr) * 2008-12-19 2010-06-25 Sanofi Aventis Derives de 6-cycloamino-2,3-di-pyridinyl-imidazo°1,2-b!- pyridazine,leur preparation et leur application en therapeutique
RU2598385C2 (ru) * 2010-12-22 2016-09-27 ХЕНГРУЙ (ЮЭсЭй), ЛТД. ПРОИЗВОДНЫЕ 2-АРИЛИМИДАЗО[1,2-b]ПИРИДАЗИНА, 2-ФЕНИЛИМИДАЗО[1,2-a]ПИРИДИНА И 2-ФЕНИЛИМИДАЗО[1,2-a]ПИРАЗИНА
JP2018509416A (ja) * 2015-03-12 2018-04-05 イー・アイ・デュポン・ドウ・ヌムール・アンド・カンパニーＥ．Ｉ．Ｄｕ Ｐｏｎｔ Ｄｅ Ｎｅｍｏｕｒｓ Ａｎｄ Ｃｏｍｐａｎｙ 複素環置換二環式アゾール殺有害生物剤

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