THIENOPYRIMIDINE COMPOUND, PREPARATION METHOD THEREFOR, PHARMACEUTICAL COMPOSITION, AND APPLICATIONSThe present invention relates to thienopyrimidine compound, preparation method thereof, pharmaceutical composition and use thereof, and in particular to a type of compounds having ALK and/or c-Met selective inhibitory activity, a method for the preparation thereof, a pharmaceutical composition comprising the same, and use of these compounds in the manufacture of a medicament for preventing or treating a disease associated with anaplastic lymphoma kinase in vivo, and in the manufacture of a medicament for preventing or treating a disease associated with angiogenesis or cancer metastasis, in particular in the manufacture of a medicament for preventing or treating tumor growth and metastasis. A compound of Formula I wherein: R' is H, Cl or Br; preferably R' is H; R1 is selected from: 1) C1-C6 alkyl, 2-N,N-dimethylaminoethyl, 2-hydroxyethyl, 2-N,N-diethylaminoethyl, 2-N,N-diisopropylaminoethyl, 2-morpholinylethyl, 2-(4-methylpiperazinyl)ethyl, 3-N,N-dimethylaminopropyl, 3-N,N-diethylaminopropyl, 3-N,N-diisopropylaminopropyl, 3-morpholinylpropyl, 3-(4-methylpiperazinyl)propyl, C3-C6 cycloalkyl, 4-N,N-dimethylaminocyclohexyl, 4-N,N-diethylaminocyclohexyl, N-methyl-4-piperidinyl, N-ethyl-4-piperidinyl, N-isopropyl-4-piperidinyl, 1,3-dimethyl-5-pyrazolyl, 1-methyl-4-pyrazolyl, 3-methyl-5-isoxazolinyl, 1-(N-methyl-4-piperidinyl)-4-pyrazolyl, 1-(N-t-butoxycarbonyl-4-piperidinyl)-4-pyrazolyl; 2)  wherein Z1, Z2, Z3, Z4, Z5 each are independently selected from: (1) H, F, Cl, Br, I, nitro, cyano, (2) C1-C6 alkyl, C1-C6 alkoxy, C1-C6 oxygen-containing alkyl, C1-C6 fluorine-containing alkyl, C1-C6 fluorine-containing alkoxy, N-methyl-4-piperidinyl, (3) N,N-dimethylamino, N,N-diethylamino, N,N-diisopropylamino, 2-N,N-dimethylaminoethylamino, 2-morpholinylethylamino, 2-(4-methylpiperazinyl)ethylamino, 3-N,N-dimethylaminopropylamino, 3-N,N-diethylaminopropylamino, 3-N,N-diisopropylaminopropylamino, 3-morpholinylpropylamino, 3-(4-methylpiperazinyl)propylamino, N-methylpiperidinyl-4-amino, N-ethylpiperidinyl-4-amino, N-isopropylpiperidinyl-4-amino, (4) 2-N,N-dimethylaminoethoxy, 2-N,N-diethylaminoethoxy, 2-N,N-diisopropylaminoethoxy, 2-(4-methylpiperazinyl)ethoxy, 2-(4-acetylpiperazinyl)ethoxy, 2-morpholinylethoxy, 2-thiomorpholinylethoxy, 2-piperidinylethoxy, 3-N,N-dimethylaminopropoxy, 3-N,N-diethylaminopropoxy, 3-N,N-diisopropylaminopropoxy, 3-(4-methylpiperazinyl)propoxy, 3-(4-acetylpiperazinyl)propoxy, 3-morpholinylpropoxy, 3-thiomorpholinylpropoxy, 3-piperidinylpropoxy, pyridin-2-ylmethoxy, pyridin-3-ylmethoxy, pyridin-4-ylmethoxy, phenylmethoxy, monohalo-substituted phenylmethoxy, gem-dihalo-substituted phenylmethoxy, hetero-dihalo-substituted phenylmethoxy, (5) piperidinyl, 4-N,N-dimethylaminopiperidinyl, 4-N,N-diethylaminopiperidinyl, 4-N,N-diisopropylaminopiperidinyl, 4-hydroxypiperidinyl, morpholinyl, 3,5-dimethylmorpholinyl, thiomorpholinyl, tetrahydropyrrolyl, 3-N,N-dimethylaminotetrahydropyrrolyl, 3-N,N-diethylaminotetrahydropyrrolyl, 4-methylpiperazinyl, 4-ethylpiperazinyl, 4-isopropylpiperazinyl, 4-acetylpiperazinyl, 4-t-butoxycarbonylpiperazinyl, 4-methylsulfonylpiperazinyl, 4-(2-hydroxyethyl)piperazinyl, 4-(2-cyanoethyl)piperazinyl, 4-(3-hydroxypropyl)piperazinyl, 4-(2-N,N-dimethylaminoethyl)piperazinyl, 4-(2-N,N-diethylaminoethyl)piperazinyl, 4-(3-N,N-dimethylaminopropyl)piperazinyl, 4-(3-N,N-diethylaminopropyl)piperazinyl, 2-oxo-piperazin-4-yl, imidazolyl, 4-methylimidazolyl, (6) 4-(4-methylpiperazinyl)piperidinyl, 4-(4-ethylpiperazinyl)piperidinyl, 4-(4-isopropylpiperazinyl)piperidinyl, 4-(4-acetylpiperazinyl)piperidinyl, 4-(4-t-butoxycarbonylpiperazinyl)piperidinyl, 4-(4-methylsulfonylpiperazinyl)piperidinyl, 4-(4-(2-hydroxyethyl)piperazinyl)piperidinyl, 4-(4-(2-cyanoethyl)piperazinyl)piperidinyl, 4-(4-(3-hydroxypropyl)piperazinyl)piperidinyl, 4-(4-(2-N,N-dimethylaminoethyl)piperazinyl)piperidinyl, 4-(4-(2-N,N-diethylaminoethyl)piperazinyl)piperidinyl, 4-(4-(3-N,N-dimethylaminopropyl)piperazinyl)piperidinyl, 4-(4-(3-N,N-diethylaminopropyl)piperazinyl)piperidinyl, 4-(tetrahydropyrrolyl)piperidinyl, 4-(3-N,N-dimethylaminotetrahydropyrrolyl)piperidinyl, 4-(N-methyl-4-piperidinyl)piperazinyl, 4-(N-ethyl-4-piperidinyl)piperazinyl, (7) hydroxysulfonyl, aminosulfonyl, methylaminosulfonyl, ethylaminosulfonyl, propylaminosulfonyl, isopropylaminosulfonyl, cyclopropylaminosulfonyl, cyclobutylaminosulfonyl, cyclopentylaminosulfonyl, piperidin-1-ylsulfonyl, 4-hydroxypiperidin-1-ylsulfonyl, 4-N,N-dimethylaminopiperidin-1-ylsulfonyl, 4-N,N-diethylaminopiperidin-1-ylsulfonyl, tetrahydropyrrolyl-1-sulfonyl, 3-N,N-dimethylaminotetrahydropyrrolyl-1-sulfonyl, 3-N,N-diethylaminotetrahydropyrrolyl-1-sulfonyl, 4-methylpiperazin-1-ylsulfonyl, 4-ethylpiperazin-1-ylsulfonyl, 4-acetylpiperazin-1-ylsulfonyl, 4-t-butoxycarbonylpiperazin-1-ylsulfonyl, 4-(2-hydroxyethyl)piperazin-1-ylsulfonyl, 4-(2-cyanoethyl)piperazin-1-ylsulfonyl, 4-(2-N,N-dimethylaminoethyl)piperazin-1-ylsulfonyl, 4-(2-N,N-diethylethyl)piperazin-1-ylsulfonyl, 4-(3-hydroxypropyl)piperazin-1-ylsulfonyl, 4-(3-N,N-dimethylaminopropyl)piperazin-1-ylsulfonyl, 4-(3-N,N-diethylaminopropyl)piperazin-1-ylsulfonyl, morpholin-1-ylsulfonyl, 3,5-dimethylmorpholin-1-ylsulfonyl, 4-(tetrahydropyrrolyl)piperidin-1-ylsulfonyl, 4-(4-methyl-piperazin-1-yl)piperidin-1-ylsulfonyl, 4-(4-ethylpiperazin-1-yl)piperidin-1-ylsulfonyl, 4-(4-acetyl-1-piperazinyl)piperidin-1-ylsulfonyl, 4-(N-methyl-4-piperidinyl)piperazin-1-ylsulfonyl, (8) hydroxycarbonyl, aminocarbonyl, methylaminocarbonyl, ethylaminocarbonyl, propylaminocarbonyl, isopropylaminocarbonyl, cyclopropylaminocarbonyl, cyclobutylaminocarbonyl, cyclopentylaminocarbonyl, piperidinyl-1-carbonyl, 4-hydroxypiper...
티에노피리미딘 화합물, 그의 제조 방법, 약학 조성물 및 용도본 발명은 티에노피리미딘 화합물, 그의 제조 방법, 약학 조성물 및 용도에 관한 것이다. 구체적으로, 본 발명은 ALK 및/또는 c-Met 선택성 억제 활성을 갖는 화합물, 상기 화합물의 제조 방법, 상기 화합물을 포함하는 약학 조성물, 유기체 중에서 역형성 림프종 키나제와 관련된 질병의 예방 또는 치료에 사용되는 약물의 제조에서 상기 화합물의 용도, 및 혈관형성 또는 암 전이와 관련된 질병의 예방 또는 치료에 사용되는 약물의 제조에서 상기 화합물의 용도, 특히 종양 성장 및 전이의 예방 또는 치료에 사용되는 약물의 제조에서 상기 화합물의 용도에 관한 것이다.하기 화학식 I의 화합물 또는 그의 입체 이성질체, 그의 전구약물, 그의 약학적으로 허용 가능한 염 또는 그의 약학적으로 허용 가능한 용매화물:상기 식에서,R'는 H, Cl 또는 Br이고; 바람직하게 R' 는 H이고;R1은 하기 중에서 선택되고: 1) C1-C6 알킬, 2-N,N-디메틸아미노에틸, 2-하이드록시에틸, 2-N,N-디에틸아미노에틸, 2-N,N-디이소프로필아미노에틸, 2-모르폴리닐에틸, 2-(4-메틸피페라지닐)에틸, 3-N,N-디메틸아미노프로필, 3-N,N-디에틸아미노프로필, 3-N,N-디이소프로필아미노프로필, 3-모르폴리닐프로필, 3-(4-메틸피페라지닐)프로필, C3-C6 사이클로알킬, 4-N,N-디메틸아미노사이클로헥실, 4-N,N-디에틸아미노사이클로헥실, N-메틸-4-피페리디닐, N-에틸-4-피페리디닐, N-이소프로필-4-피페리디닐, 1,3-디메틸-5-피라졸릴, 1-메틸-4-피라졸릴, 3-메틸-5-이속사졸리닐, 1-(N-메틸-4-피페리디닐)-4-피라졸릴, 1-(N-t-부톡시카보닐-4-피페리디닐)-4-피라졸릴; 2) , 여기에서 Z1, Z2, Z3, Z4, Z5 는 각각 독립적으로 하기 중에서 선택되고:(1) H, F, Cl, Br, I, 니트로, 시아노, (2) C1-C6 알킬, C1-C6 알콕시, C1-C6 산소-함유 알킬, C1-C6 불소-함유 알킬, C1-C6 불소-함유 알콕시, N-메틸-4-피페리디닐, (3) N,N-디메틸아미노, N,N-디에틸아미노, N,N-디이소프로필아미노, 2-N,N-디메틸아미노에틸아미노, 2-모르폴리닐에틸아미노, 2-(4-메틸피페라지닐)에틸아미노, 3-N,N-디메틸아미노프로필아미노, 3-N,N-디에틸아미노프로필아미노, 3-N,N-디이소프로필아미노프로필아미노, 3-모르폴리닐프로필아미노, 3-(4-메틸피페라지닐)프로필아미노, N-메틸피페리디닐-4-아미노, N-에틸피페리디닐-4-아미노, N-이소프로필피페리디닐-4-아미노, (4) 2-N,N-디메틸아미노에톡시, 2-N,N-디에틸아미노에톡시, 2-N,N-디이소프로필아미노에톡시, 2-(4-메틸피페라지닐)에톡시, 2-(4-아세틸피페라지닐)에톡시, 2-모르폴리닐에톡시, 2-티오모르폴리닐에톡시, 2-피페리디닐에톡시, 3-N,N-디메틸아미노프로폭시, 3-N,N-디에틸아미노프로폭시, 3-N,N-디이소프로필아미노프로폭시, 3-(4-메틸피페라지닐)프로폭시, 3-(4-아세틸피페라지닐)프로폭시, 3-모르폴리닐프로폭시, 3-티오모르폴리닐프로폭시, 3-피페리디닐프로폭시, 피리딘-2-일메톡시, 피리딘-3-일메톡시, 피리딘-4-일메톡시, 페닐메톡시, 모노할로-치환된 페닐메톡시, 젬-디할로-치환된 페닐메톡시, 헤테로-디할로-치환된 페닐메톡시, (5) 피페리디닐, 4-N,N-디메틸아미노피페리디닐, 4-N,N-디에틸아미노피페리디닐, 4-N,N-디이소프로필아미노피페리디닐, 4-하이드록시피페리디닐, 모르폴리닐, 3,5-디메틸모르폴리닐, 티오모르폴리닐, 테트라하이드로피롤릴, 3-N,N-디메틸아미노테트라하이드로피롤릴, 3-N,N-디에틸아미노테트라하이드로피롤릴, 4-메틸피페라지닐, 4-에틸피페라지닐, 4-이소프로필피페라지닐, 4-아세틸피페라지닐, 4-t-부톡시카보닐피페라지닐, 4-메틸설포닐피페라지닐, 4-(2-하이드록시에틸)피페라지닐, 4-(2-시아노에틸)피페라지닐, 4-(3-하이드록시프로필)피페라지닐, 4-(2-N,N-디메틸아미노에틸)피페라지닐, 4-(2-N,N-디에틸아미노에틸)피페라지닐, 4-(3-N,N-디메틸아미노프로필)피페라지닐, 4-(3-N,N-디에틸아미노프로필)피페라지닐, 2-옥소-피페라진-4-일, 이미다졸릴, 4-메틸이미다졸릴, (6) 4-(4-메틸피페라지닐)피페리디닐, 4-(4-에틸피페라지닐)피페리디닐, 4-(4-이소프로필피페라지닐)피페리디닐, 4-(4-아세틸피페라지닐)피페리디닐, 4-(4-t-부톡시카보닐피페라지닐)피페리디닐, 4-(4-메틸설포닐피페라지닐)피페리디닐, 4-(4-(2-하이드록시에틸)피페라지닐)피페리디닐, 4-(4-(2-시아노에틸)피페라지닐)피페리디닐, 4-(4-(3-하이드록시프로필)피페라지닐)피페리디닐, 4-(4-(2-N,N-디메틸아미노에틸)피페라지닐)피페리디닐, 4-(4-(2-N,N-디에틸아미노에틸)피페라지닐)피페리디닐, 4-(4-(3-N,N-디메틸아미노프로필)피페라지닐)피페리디닐, 4-(4-(3-N,N-디에틸아미노프로필)피페라지닐)피페리디닐, 4-(테트라하이드로피롤릴)피페리디닐, 4-(3-N,N-디메틸아미노테트라하이드로피롤릴)피페리디닐, 4-(N-메틸-4-피페리디닐)피페라지닐, 4-(N-에틸-4-피페리디닐)피페라지닐, (7) 하이드록시설포닐, 아미노설포닐, 메틸아미노설포닐, 에틸아미노설포닐, 프로필아미노설포닐, 이소프로필아미노설포닐, 사이클로프로필아미노설포닐, 사이클로부틸아미노설포닐, 사이클로펜틸아미노설포닐, 피페리딘-1-일설포닐, 4-하이드록시피페리딘-1-일설포닐, 4-N,N-디메틸아미노피페리딘-1-일설포닐, 4-N,N-디에틸아미노피페리딘-1-일설포닐, 테트라하이드로피롤릴-1-설포닐, 3-N,N-디메틸아미노테트라하이드로피롤릴-1-설포닐, 3-N,N-디에틸아미노테트라하이드로피롤릴-1-설포닐, 4-메틸피페라진-1-일설포닐, 4-에틸피페라진-1-일설포닐, 4-아세틸피페라진-1-일설포닐, 4-t-부톡시카보닐피페라진-1-일설포닐, 4-(2-하이드록시에틸)피페라진-1-일설포닐, 4-(2-시아노에틸)피페라진-1-일설포닐, 4-(2-N,N-디메틸아미노에틸)피페라진-1-일설포닐, 4-(2-N,N-디에틸에틸)피페라진-1-일설포닐, 4-(3-하이드록시프로필)피페라진-1-일설포닐, 4-(3-N,N-디메틸아미노프로필)피페라진-1-일설포닐, 4-(3-N,N-디에틸아미노프로필)피페라진-1-일설포닐, 모르폴린-1-일설포닐, 3,5-디메틸모르폴린-1-일설포닐, 4-(테트라하이드로피롤릴)피페리딘-1-일설포닐, 4-(4-메틸-피페라진-1-일)피페리딘-1-일설포닐, 4-(4-에틸피페라진-1-일)피페리딘-1-일설포닐, 4-(4-아세틸-1-피페라지닐)피페리딘-1-일설포닐, 4-(N-메틸-4-피페리디닐)피페라진-1-일설포닐, (8) 하이드록시카보닐, 아미노카보닐, 메틸아미노카보닐, 에틸아미노카보닐, 프로필아미노카보닐, 이소프로필아미노카보닐, 사이클로프로필아미노카보닐, 사이클로부틸아미노카보닐, 사이클로펜틸아미노카보닐, 피페리디닐-1-카보닐, 4-하이드록시피페리디닐-1-카보닐, 4-N,N-디메틸아미노피페리디닐-1-카보닐, 4-N,N-디에틸아미노피페리디닐-1-카보닐, 4-(테트라하이드로피롤릴)피페리디닐-1-카보닐, 테트라하이드로피롤릴-1-카보닐, 3-N,N-디메틸아미노테트라하이드로피롤릴-1-카보닐, 3-N,N-디에틸아미노테트라하이드로피롤릴-1-카보닐, 4-메틸피페라진-1-일카보닐, 4-에틸피페라지닐-1-카보닐, 4-아세틸피페라지닐-1-카보닐, 4-t-부톡시카보닐피페라지닐-1-카보닐, 4-(2-하이드록시에틸)피페라지닐-1-카보닐, 4-(2-시아노에틸)피페라지닐-1-카보닐, 4-(2-N,N-디메틸아미노에틸)피페라진-1-일카보닐, 4-(2-N,N-디에틸아미노에틸)피페라진-1-일카보닐, 4-(3-하이드록시프로필)피페라진-1-일카보닐, 4-(3-N,N-디메틸아미노프로필)피페라진-1-일카보닐, 4-(3-N,N-디에틸아미노프로필)피페라진-1-일카보닐, 모르폴리닐-1-카보닐, 3,5-디메틸모르폴리닐-1-카보닐, 4-(4-메틸-피페라진-1-일)피페리딘-1-일카보닐, 4-(4-에틸-1-피페라지닐)피페리디닐-1-카보닐, 4-(4-아세틸-피페라진-1-일)피페리디닐-1-카보닐, 4-(N-메틸-4-피페리디닐)피페라진-1-일카보닐, (9) 메톡시카보닐, 에톡시카보닐, 프로폭시카보닐, 이소프로폭시카보닐, n-부톡시카보닐, 이소부톡시카보닐, 3급-부톡시카보닐, (10) 아미노포름아미도, 메틸아미노포름아미도, 에틸아미노포름아미도, 프로필아미노포름아미도, 이소프로필아미노포름아미도, 사이클로프로필아미노포름아미도, 사이클로부틸아미노포름아미도, 사이클로펜틸아미노포름아미도, 피페리디닐-1-포름아미도, 4-하이드록시피페리디닐-1-포름아미도, 4-N,N-디메틸아미노피페리디닐-1-포름아미도, 4-N,N-디에틸아미노피페리디닐-1-포름아미도, 테트라하이드로피롤릴-1-포름아미도, 3-N,N-디메틸아미노테트라하이드로피롤릴-1-포름아미도, 3-N,N-디에틸아미노테트라하이드로피롤릴-1-포름아미도, 4-메틸피페라진-1-일포름아미도, 4-에틸피페라진-1-일포름아미도, 4-아세틸피페라진-1-일포름아미도, 4-t-부톡시카보닐피페라진-1-일포름아미도, 4-(2-하이드록시에틸)피페라진-1-일포름아미도, 4-(2-시아노에틸)피페라진-1-일포름아미도, 4-(2-N,N-디메틸아미노에틸)피페라진-1-일포름아미도, 4-(2-N,N-디에틸아미노에틸)피페라진-1-일포름아미도, 4-(3-하이드록시프로필)피페라진-1-일포름아미도, 4-(3-N,N-디메틸아미노프로필)피페라진-1-일포름아미도, 4-(3-N,N-디에틸아미노프로필)피페라진-1-일포름아미도, 모르폴린-1-일포름아미도, 3,5-디메틸모르폴린-1-일포름아미도, 4-(테트라하이드로피롤릴)피페리딘-1-일포름아미도, 4-(4-메틸-피페라진-1-일)피페리딘-1-일포름아미도, 4-(4-에틸피페라진-1-일)피페리딘-1-일포름아미도, 4-(4-아세틸-피페라진-1-일)피페리딘-1-일포름아미도, 4-(N-메틸-4-피페리디닐)피페라진-1-일포름아미도; 또는(11) 아미노아세트아미도, 2-디메틸아미노아세트아미도, N-t-부톡시카보닐아세트아미도, N-아세틸아미노아세트아미도, 아크릴아미도, 사이클로프로피온아미도, 클로로아세트아미도, 피페리디닐아세트아미도, 4-하이드록시피페리디닐아세트아미도, 4-N,N-디메틸아미노피페리디닐아세트아미도, 4-N,N-디에틸아미노피페리디닐아세트아미도, 테트라하이드로피롤릴아세트아미도, 3-N,N-디메틸아미노테트라하이드로피롤릴아세트아미도, 3-N,N-디에틸아미노테트라하이드로피롤릴아세트아미도, 4-메틸피페라지닐아세트아미도, 4-에틸피페라지닐아세트아미도, 4-아세틸피페라지닐아세트아미도, 4-t-부톡시카보닐피페라지닐아세트아미도, 4-(2-하이드록시에틸)피페라지닐아세트아미도, 4-(2-시아노에틸)피페라지닐아세트아미도, 4-(2-N,N-디메틸아미노에틸)피페라지닐아세트아미도, 4-(2-N,N-디에틸아미노에틸)피페라지닐아세트아미도, 4-(3-하이드록시프로필)피페라지닐...