Inhibitors of tyrosine kinases and uses thereofDisclosed herein are compounds that inhibit the activity of particular tyrosine kinases. Methods for the preparation of such compounds are disclosed. Also disclosed are pharmaceutical compositions that include the compounds. Methods of using the compounds disclosed, alone or in combination with other therapeutic agents, for the treatment of tyrosine kinase-rnediated diseases or conditions or tyrosine, kinase-dependent diseases or conditions are provided.The compound of formula (iii):wherein:r aand r bbe selected from h, halogen, `cn, no independently of one another 2, c 1-c 4alkyl, c 1-c 4haloalkyl and c 1-c 4alkoxyl group; t is 1,6-dimethyl-9-oxo-8,9-dihydro-1h-imidazo [4,5-h] isoquinoline 99.9-2,7-subunit or 1,7-dimethyl-9-oxo-8,9-dihydro-1h-imidazo [4,5-h] isoquinoline 99.9-2,6-subunit;l is-x 250a-y 250-or-y 250-x 250a-, wherein x 250abe to replace or unsubstituted c 1-c 6alkyl, replacement or unsubstituted c 1-c 6haloalkyl, replacement or unsubstituted c 3-c 8cycloalkyl, replacement or unsubstituted c 5-c 8cycloalkenyl group, replacement or unsubstituted c 2-c 6thiazolinyl, replacement or unsubstituted c 2-c 6haloalkenyl group, replacement or unsubstituted c 2-c 6alkynyl or replacement or unsubstituted c 2-c 6the halo alkynyl; y 250be valence link ,-o-,-s (=o)-,-s (=o) 2-,-c (=o)-,-nr 45-,-nh-,-nhc (=o)-,-nr 45c (=o)-,-nr 45c (=o) nr 45-,-c (=o) nh-,-c (=o) nr 45-,-oc (=o)-,-c (=o) o-,-nhso 2-,-nr 45so 2-,-so 2nh-,-so 2nr 45-,-c (r 45)=no-,-ch=no-,-on=ch-, heteroaryl, aryl ,-nhc (=o) o-,-oc (=o) nh-,-nr 45c (=o) o-or-oc (=o) nr 45-; each r wherein 45be independently selected from hydrogen, replacement or unsubstituted c 1-c 6alkyl, replacement or unsubstituted c 3-c 8cycloalkyl, replacement or unsubstituted c 2-c 6thiazolinyl, replacement or unsubstituted c 2-c 6alkynyl; m is n or ch;w is or e is oxygen or sulphur;r 100be halogen ,-oh or be selected from following optional substituted group: c 1-c 6alkyl, c 2-c 6thiazolinyl, c 2-c 6alkynyl, phenyl, c 1-c 4alkyl (phenyl), c 3-c 8cycloalkyl, c 1-c 4alkyl (c 3-c 8cycloalkyl), c 2-c 8heterocyclylalkyl, c 1-c 4alkyl (c 2-c 8heterocyclylalkyl), heteroaryl, c 1-c 4alkyl (heteroaryl), c 1-c 6alkoxyl group, c 1-c 6alkene oxygen base, c 1-c 6alkynyloxy group or-nr 102ar 102br 102aand r 102bbe hydrogen independently or be selected from following optional substituted group: c 1-c 6alkyl, c 2-c 6thiazolinyl, c 2-c 6alkynyl, aryl, aralkyl, heteroaryl, heteroaralkyl, c 3-c 8cycloalkyl, c 1-c 4alkyl (c 3-c 8cycloalkyl), c 2-c 8heterocyclylalkyl and c 1-c 4alkyl (c 2-c 8heterocyclylalkyl); r 200be to be selected from following optional substituted group: c 2-c 10acyl group, c 2-c 6thiazolinyl, c 2-c 6alkynyl, c 3-c 6cycloalkyl, c 1-c 4alkyl (c 3-c 6cycloalkyl), aryl, heteroaryl, heteroaralkyl, c 1-c 6alkyl sulphonyl, c 2-c 6thiazolinyl alkylsulfonyl, aryl sulfonyl, heteroarylsulfonyl, c 1-c 10alkoxy carbonyl, amino-sulfonyl, c 1-c 6alkyl amino sulfonyl, two (c 1-c 6alkyl) amino-sulfonyl and c 1-c 6alkyl sulfonyl-amino; r 350abe hydrogen, replacement or unsubstituted c 1-c 6alkyl, replacement or unsubstituted c 2-c 6thiazolinyl, replacement or unsubstituted c 2-c 6alkynyl, replacement or unsubstituted c 1-c 6haloalkyl, replacement or unsubstituted c 2-c 6haloalkenyl group or replacement or unsubstituted c 2-c 6the halo alkynyl; n is 0,1 or 2; withits pharmaceutically active metabolite, pharmaceutically acceptable solvate, pharmacy acceptable salt or pharmaceutically acceptable prodrug.
티로신 키나제 억제제 및 이의 용도본원 발명에 특정 티로신 키나제의 활성을 억제하는 화합물이 기술된다. 이러한 화합물의 제조방법이 기술된다. 당해 화합물을 포함하는 약제학적 조성물도 또한 기술된다. 티로신 키나제 매개된 질환 또는 상태, 또는 티로신 키나제 의존성 질환 또는 상태를 치료하기 위해 기술된 화합물을 단독으로 또는 기타 치료제와 함께 사용하는 방법이 제공된다. 화학식 III의 화합물, 및 이의 약제학적으로 활성인 대사산물, 약제학적으로 허용되는 용매화물, 약제학적으로 허용되는 염 또는 약제학적으로 허용되는 프로드럭. 화학식 III [이미지] 상기 화학식 III에서, Ra 및 Rb는 각각 독립적으로 H, 할로겐, CN, NO2, C1-C4알킬, C1-C4할로알킬, 및 C1-C4알콕시로부터 선택되고; T는 1,6-디메틸-9-옥소-8,9-디하이드로-1H-이미다조[4,5-h]이소퀴놀린-2,7-일렌 또는 1,7-디메틸-9-옥소-8,9-디하이드로-1H-이미다조[4,5-h]이소퀴놀린-2,6-일렌이고; L은 -X250a-Y25O- 또는 -Y250-X250a이고, 여기서 X250a는 치환되거나 치환되지 않은 C1-C6알킬, 치환되거나 치환되지 않은 C1-C6할로알킬, 치환되거나 치환되지 않은 C3-C8사이클로알킬, 치환되거나 치환되지 않은 C5-C8사이클로알케닐, 치환되거나 치환되지 않은 C2-C6알케닐, 치환되거나 치환되지 않은 C2-C6할로알케닐, 치환되거나 치환되지 않은 C2-C6알키닐 또는 치환되거나 치환되지 않은 C2-C6할로알키닐이고, Y250은 결합, -O-, -S(=O)-, -S(=O)2-, -C(=O)-, -NR45-, -NH-, -NHC(=O)-, -NR45C(=O)-, -NR45C(=O)NR45-, -C(=O)NH-, -C(=O)NR45-, -OC(=O)-, -C(=O)O-, -NHSO2-, -NR45SO2-, -SO2NH-, -SO2NR45-, -C(R45)=NO-; -CH=NO-, -ON=CH-, 헤테로아릴, 아릴, -NHC(=O)O-, -OC(=O)NH-, -NR45C(=O)O- 또는 -OC(=O)NR45-이고, 여기서, R45는 각각 독립적으로 수소, 치환되거나 치환되지 않은 C1-C6알킬, 치환되거나 치환되지 않은 C3-C8사이클로알킬, 치환되거나 치환되지 않은 C2-C6알케닐 및 치환되거나 치환되지 않은 C2-C6알키닐로부터 선택되고; M은 N 또는 CH이고; W는 [이미지]이고; E는 산소 또는 황이고; R100은 할로겐, -OH, 또는 C1-C6알킬, C2-C6알케닐, C2-C6알키닐, 페닐, C1-C4알킬(페닐), C3-C8사이클로알킬, C1-C4알킬(C3-C8사이클로알킬), C2-C8헤테로사이클로알킬, C1-C4알킬(C2-C8헤테로사이클로알킬), 헤테로아릴, C1-C4알킬(헤테로아릴), C1-C6알콕시, C1-C6알케닐옥시, C1-C6알키닐옥시 및 -NR102aR102b로부터 선택된 치환될 수 있는 그룹이고; Rl02a 및 Rl02b는 독립적으로 수소, 또는 C1-C6알킬, C2-C6알케닐, C2-C6알키닐, 아릴, 아르알킬, 헤테로아릴, 헤테로아르알킬, C3-C8사이클로알킬, C1-C4알킬(C3-C8사이클로알킬), C2-C8헤테로사이클로알킬 및 C1-C4알킬(C2-C8헤테로사이클로알킬)로부터 선택된 치환될 수 있는 그룹이고; R200은 C2-C10아실, C2-C6알케닐, C2-C6알키닐, C3-C6사이클로알킬, C1-C4알킬(C3-C6사이클로알킬), 아릴, 헤테로아릴, 헤테로아르알킬, C1-C6알킬설포닐, C2-C6알케닐설포닐, 아릴설포닐, 헤테로아릴설포닐, C1-C10알콕시카보닐, 아미노설포닐, C1-C6알킬아미노설포닐, 디(C1-C6알킬)아미노설포닐 및 C1-C6알킬설포닐아미노로부터 선택된 치환될 수 있는 그룹이고; R350a는 수소, 치환되거나 치환되지 않은 C1-C6알킬, 치환되거나 치환되지 않은 C2-C6알케닐, 치환되거나 치환되지 않은 C2-C6알키닐, 치환되거나 치환되지 않은 C1-C6할로알킬, 치환되거나 치환되지 않은 C2-C6할로알케닐 또는 치환되거나 치환되지 않은 C2-C6할로알키닐이고; n은 0, 1 또는 2이다.