Fused heterocyclic derivative and use thereofThe present invention provides a fused heterocyclic derivative having a potent kinase inhibitory activity and use thereof. A compound represented by the formula (I): wherein each symbol is as defined in the specification, except a particular compound, or a salt thereof, and a pharmaceutical agent containing the compound or a prodrug thereof, which is a kinase (VEGFR, VEGFR2, PDGFR, Raf) inhibitor, an angiogenesis inhibitor, an agent for the prophylaxis or treatment of cancer, a cancer growth inhibitor or a cancer metastasis suppressor.The compound or its salt shown in the formula (i):in the formularing y is the optional cyclic group that replaces;x is-o-,-s-,-s (o)-,-s (o) 2-or-nr-(wherein r is hydrogen atom or substituting group); r 1be hydrogen atom or substituting group; r 2be hydrogen atom or substituting group; r 3be hydrogen atom or substituting group; r 4be hydrogen atom or substituting group; condition iswork as r 1when not being optional replace amino, ring y is the cyclic group that the amino that is optionally substituted replaces, and wherein this cyclic group is optional is further replaced, and gets rid of following compounds: [6-(thiophenyl) imidazo [1,2-b] pyridazine-2-yl] urethylane,[6-(phenyl sulfinyl) imidazo [1,2-b] pyridazine-2-yl] urethylane,6-(4-kharophen phenoxy group) imidazo [1,2-b] pyridazine-2-carboxylic acid, ethyl ester,6-[4-(4-ethanoyl piperazine-1-yl) phenoxy group] imidazo [1,2-b] pyridazine-2-carboxylic acid, ethyl ester,n-[1-(imidazo [1,2-b] pyridazine-6-base is amino)-2,5-dioxo-1,2,5,6,7,8-six hydrogen quinoline-3-yl] benzamide,n-[1-(imidazo [1,2-b] pyridazine-6-base is amino)-7,7-dimethyl-2,5-dioxo-1,2,5,6,7,8-six hydrogen quinoline-3-yl] benzamide,n-[1-(imidazo [1,2-b] pyridazine-6-base is amino)-2,5-dioxo-2,5,6,7-tetrahydrochysene-1h-cyclopenta [b] pyridin-3-yl] benzamide,n-[1-(imidazo [1,2-b] pyridazine-6-base is amino)-7-methyl-2,5-dioxo-1,2,5,6,7,8-six hydrogen quinoline-3-yl] benzamide,n-[(5e)-and 5-(imidazo [1,2-b] pyridazine-6-base hydrazono-)-7-methyl-2-oxo-4a, 5,6,7,8,8a-six hydrogen-2h-chromene-3-yl] benzamide,(6r, 7r)-3-(imidazo [1,2-b] pyridazine-6-base sulfenyl)-8-oxo-7-[(phenyl acetyl) amino]-5-thia-1-azabicyclic [4.2.0] oct-2-ene-2-carboxylic acid 4-methoxy benzyl ester,4-[(3-methoxyl group-2-phenylimidazole is [1,2-b] pyridazine-6-yl also) sulfenyl]-n, accelerine,3-methoxyl group-6-(3-nitro-phenoxy)-2-phenylimidazole is [1,2-b] pyridazine also,3-[(3-methoxyl group-2-phenylimidazole is [1,2-b] pyridazine-6-yl also) the oxygen base] aniline, and3-[(3-methoxyl group-2-phenylimidazole is [1,2-b] pyridazine-6-yl also) the oxygen base]-n, accelerine.
융합 헤테로시클릭 유도체 및 이의 용도본 발명은 강력한 키나아제 저해 활성을 가진 융합 헤테로시클릭 유도체 및 이의 용도를 제공한다. 특정 화합물을 제외한, 하기 화학식 (I) 로 표시되는 화합물 (식 중, 각 기호는 본 명세서에 정의된 바와 같음), 또는 이의 염, 및 키나아제 (VEGFR, VEGFR2, PDGFR, Raf) 저해제, 혈관신생 저해제, 암 예방 또는 치료제, 암 성장 저해제 또는 암 전이 억제제인, 상기 화합물 또는 이의 전구약물을 함유하는 약학적 작용제: 하기 화학식 (I) 로 표시되는 화합물 또는 이의 염: [이미지] [식 중, 고리 Y 는 임의 치환된 시클릭기이고; X 는 -O-, -S-, -S(O)-, -S(O)2- 또는 -NR- (이 때, R 은 수소 원자 또는 치환기임) 이고; R1 은 수소 원자 또는 치환기이고; R2 는 수소 원자 또는 치환기이고; R3 은 수소 원자 또는 치환기이고; R4 는 수소 원자 또는 치환기이고; 단, R1 이 임의 치환된 아미노가 아닌 경우, 고리 Y 는 임의 치환된 아미노로 치환된 시클릭기이고, 이 때, 상기 시클릭기는 임의로 추가 치환되고, 하기는 제외됨: 메틸 [6-(페닐티오)이미다조[1,2-b]피리다진-2-일]카르바메이트, 메틸 [6-(페닐술피닐)이미다조[1,2-b]피리다진-2-일]카르바메이트, 에틸 6-(4-아세트아미도페녹시)이미다조[1,2-b]피리다진-2-카르복실레이트, 에틸 6-[4-(4-아세틸피페라진-1-일)페녹시]이미다조[1,2-b]피리다진-2-카르복실레이트, N-[1-(이미다조[1,2-b]피리다진-6-일아미노)-2,5-디옥소-1,2,5,6,7,8-헥사히드로퀴놀린-3-일]벤즈아미드, N-[1-(이미다조[1,2-b]피리다진-6-일아미노)-7,7-디메틸-2,5-디옥소-1,2,5,6,7,8-헥사히드로퀴놀린-3-일]벤즈아미드, N-[1-(이미다조[1,2-b]피리다진-6-일아미노)-2,5-디옥소-2,5,6,7-테트라히드로-1H-시클로펜타[b]피리딘-3-일]벤즈아미드, N-[1-(이미다조[1,2-b]피리다진-6-일아미노)-7-메틸-2,5-디옥소-1,2,5,6,7,8-헥사히드로퀴놀린-3-일]벤즈아미드, N-[(5E)-5-(이미다조[1,2-b]피리다진-6-일히드라조노)-7-메틸-2-옥소-4a,5,6,7,8,8a-헥사히드로-2H-크로멘-3-일]벤즈아미드, 4-메톡시벤질 (6R,7R)-3-(이미다조[1,2-b]피리다진-6-일티오)-8-옥소-7-[(페닐아세틸)아미노]-5-티아-1-아자비시클로[4.2.0]옥트-2-엔-2-카르복실레이트, 4-[(3-메톡시-2-페닐이미다조[1,2-b]피리다진-6-일)티오]-N,N-디메틸아닐린, 3-메톡시-6-(3-니트로페녹시)-2-페닐이미다조[1,2-b]피리다진, 3-[(3-메톡시-2-페닐이미다조[1,2-b]피리다진-6-일)옥시]아닐린, 및 3-[(3-메톡시-2-페닐이미다조[1,2-b]피리다진-6-일)옥시]-N,N-디메틸아닐린]. 