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1. 发明申请

WO2007076092A2 NITROGEN-CONTAINING BICYCLIC HETEROARYL COMPOUNDS AND METHODS OF USE 审中-公开
标题翻译：含氮的双环杂环化合物及其使用方法
公开(公告)号：WO2007076092A2
公开(公告)日：2007-07-05
申请号：PCT/US2006049187
申请日：2006-12-22
申请人： AMGEN INC , DE MORIN FRENEL F , CHEN JIAN J , DOHERTY ELIZABETH M , HITCHCOCK STEPHEN , HUANG QI , KIM JOSEPH L , LIU GANG , NIXEY THOMAS , PARAS NICK A , PETKUS JEFFREY , RETZ DANIEL M , SMITH ADRIAN L , TASKER ANDREW , ZHU JIAWANG
发明人： DE MORIN FRENEL F , CHEN JIAN J , DOHERTY ELIZABETH M , HITCHCOCK STEPHEN , HUANG QI , KIM JOSEPH L , LIU GANG , NIXEY THOMAS , PARAS NICK A , PETKUS JEFFREY , RETZ DANIEL M , SMITH ADRIAN L , TASKER ANDREW , ZHU JIAWANG
IPC分类号： C07D239/84 , C07D239/95 , C07D401/04 , C07D401/14
CPC分类号： C07D401/14 , C07D239/84 , C07D239/95 , C07D401/04 , C07D403/04 , C07D403/14 , C07D405/14 , C07D409/14 , C07D413/04 , C07D413/14 , C07D417/14 , C07D471/04 , C07D487/04 , C07D495/04
摘要： The present invention comprises a new class of compounds capable of modulating Raf kinase and, accordingly, useful for treatment of Raf kinase mediated diseases, including melanomas, tumors and other cancer-related conditions. The compounds have Formula (I) wherein R 1 is Formula (II), (III) or (IV) and A 1 , A 2 , A 3 , A 4 , X, Z, Z', R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are defined herein. The invention further comprises pharmaceutical compositions, methods for treatment of Raf kinase mediated diseases, and intermediates and processes useful for the preparation of compounds of the invention.
摘要翻译：本发明包括能够调节Raf激酶的新一类化合物，因此可用于治疗Raf激酶介导的疾病，包括黑素瘤，肿瘤和其它癌症相关病症。化合物具有式（I）其中R 1为式（II），（III）或（IV）和A 1，A 2，，A 4，A 4，X，Z，Z'，R 1，R 2，R 2， SUP 3，R 4，R 5和R 6在本文中定义。本发明还包括药物组合物，用于治疗Raf激酶介导的疾病的方法，以及可用于制备本发明化合物的中间体和方法。

2. 发明专利

ES2392673T3 Compuestos de heteroarilo bicíclicos que contienen nitrógeno para el tratamiento de enfermedades mediadas por proteína cinasa raf 未知
公开(公告)号：ES2392673T3
公开(公告)日：2012-12-12
申请号：ES06848110
申请日：2006-12-22
申请人： AMGEN INC
发明人： DE MORIN FRENEL , CHEN JIAN J , DOHERTY ELIZABETH M , HITCHCOCK STEPHEN , HUANG QI , KIM JOSEPH , LIU GANG , NIXEY THOMAS , PARAS NICK , PETKUS JEFFREY , RETZ DANIEL , SMITH ADRIAN , TASKER ANDREW , ZHU JIAWANG
IPC分类号： C07D239/84 , A61K31/435 , A61K31/495 , A61K31/55 , C07D239/95 , C07D401/04 , C07D401/14 , C07D403/04 , C07D403/14 , C07D405/14 , C07D409/14 , C07D413/04 , C07D413/14 , C07D417/14 , C07D471/04 , C07D487/04 , C07D495/04
摘要： Un compuesto de Fórmula 1: **Fórmula**o un estereoisómero, tautómero, sOlvato, o sal farmacéuticamente aceptable del mismo, en el que Z es:**Fórmula** l' es un anillo de átomos de carbono aromático de 5 ó 6 miembros que comprende opcionalmente 1-3 heteroátomos seleccionados de N, O o S, de modo que l y l' tomados conjuntamente forman un anillo heterocíclico o de heteroarilo de 8, 9 ó 10 miembros condensado; **Fórmula**es en el que cada uno de Al, A2 Y A3es, independientemente, CR6 o N; R es halo, haloal~uilo, N02, CN, R, NRR, NRR, OR, SR, OR, SR, C (O) R, OC (O) R, COOR, C (O~R8, OC (O) R8, COOR, C (O) NR7R7, C (S) NR7R7, NR7C (O) R7, NRC (S) R7, NR7C (O) NR R7, NRC (S) NR R7, NRt (COOR\ OC (O) NR7R7, C (O) NR7R8, C (S) NR7R8 N R7C (O) R8, NR"C (S) R8 NR7C (O) NRR8, NRC (S) NR7R8, NR (COOR8) OC (O) NRR8, S (O) 2R, S (O) 2NRR, NRS (O) 2NRR7, NRS (O) 2R, S (O) 2R, S (O) 2NR7R8, NRS (OhNR7R8º NRS (O) 2R8; es H, halo, haloalquilo, N~, CN, OR7, SR7, NRR7, NRR8, C (O) R7, COOR7, C (O) NRR, C (O) NR7R8, NRC (O) NRR, NRC (O) NRR, OC (O) NRR8, S (O) 2R, S (O) 2NRR7, S (O) 2NRR8, NRS (O) 2R7, NRS (O) 2R8, alquilo-CHO, alquenilo-C2-l0, alquinilo-C2-l0, cicloalquilo-C3-lo o cicloalquenilo-C4-lo, cada uno de alquilo-Cl -l0, alquenilo-C2-l0, alquinilo-C2-l0, cicloalquilo-C3-l0 y cicloalquenilo-C4-lo comprendiendo opcionalmente 1-4 heteroátomos seleccionados de N, O o S y opcionalmente sustituido con uno o más sustituyentes de R8 o R9; cada R6 es, independientemente, H, halo, haloalquiloN~, CN, NRR7, NR7R8, OR7, SR, C (O) R, OC (O~R7, COOR7 C (O) NR7R7 C (O) NR7R, N R7C (O) R7, NR C (O) R8, NR8C (O) NR7R8, NR7 (COOR\ OC (O) NR R8, S (O) 2R, S (O) 2NR R, NRS (O) 2NR7R, NRS (O) 2R, NRS (O) 2R7, alquilo-Cl -l0, alquenilo-C2-l0, alquinilo-C2-lo, cicloalquilo-C3-lo o cicloalquenilo C4-l0, cada uno de alquilo-Cl-l0, alquenilo-C2-l0, alquinilo-C2-l0, cicloalquilo-C3_l0 y cicloalquenilo-C4-l0 comprendiendo opcionalmente 1-4 heteroátomos seleccionados de N, O o S y opcionalmente sustituido con uno o más sustituyentes de R8 o R9; Res halo, haloalquilo, N02, CN, NRR, OR7, SR, C (O) R7, S (O) 2R7, alquilo-Cl-l0 o cicloalquilo-C3-1O; R3 es NR10Rll, NR10C (O) Rll, NR1°C (S) Rll, NR1°C (O) NR10Rll, NR10 (COORll), NR10S (O) 2NR10Rll o es H, alquilo-Cl-10, alquenilo-C2-l0, alquinilo-C2-l0, cicloalquilo-C3-l0 o cicloalquenilo-C4-l0, cada uno de alquilo-Cl_l0, alquenilo-C2-l0, alquinilo-C2-l0, cicloalquilo-C3-l0 y cicloalquenilo-C4-l0 comprendiendo opcionalmente 1-4 heteroátomos seleccionados de N, O o S y opcionalmente sustituido con uno o más sustituyentes de NR8R9, NR9R9, OR8, SR8, OR9, SR9, C (O) R8, OC (O) R8, COOR8, C (O) R9, OC (O) R9, COOR9, C (O) NR8R9, C (O) NR9R9, NR9C (O) R8, NR9C (O) R9, NR9C (O) NR8R9, NR6C (O) NR9R9, NR9 (COOR8), NR9 (COOR\ OC (O) NR8R9, OC (O) NR9R9, S (O) 2R8, S (O) 2NR8R9, S (O) 2R9, S (O) 2NR9R9, NR9S (O) 2NR8R9, NR9S (O) 2NR9 R6, NR~S (O) 2R8, NR9S (O) 2R9 o R9.

4. 发明专利

CA2753405A1 NITROGEN-CONTAINING BICYCLIC HETEROARYL COMPOUNDS AND METHODS OF USE 未知
公开(公告)号：CA2753405A1
公开(公告)日：2007-07-05
申请号：CA2753405
申请日：2006-12-22
申请人： AMGEN INC
发明人： DE MORIN FRENEL F , CHEN JIAN J , DOHERTY ELIZABETH M , HITCHCOCK STEPHEN , HUANG QI , KIM JOSEPH L , LIU GANG , NIXEY THOMAS , PARAS NICK A , PETKUS JEFFREY , RETZ DANIEL MARTIN , SMITH ADRIAN LEONARD , TASKER ANDREW , ZHU JIAWANG
IPC分类号： C07D401/14 , A61K31/506 , A61P35/00

6. 发明专利

AU2012204048A1 Nitrogen-containing bicyclic hetroaryl compounds for the treatment of RAF protein kinase-mediated diseases 未知
公开(公告)号：AU2012204048A1
公开(公告)日：2012-07-26
申请号：AU2012204048
申请日：2012-07-09
申请人： AMGEN INC
发明人： DE MORIN FRENEL F , CHEN JIAN J , DOHERTY ELIZABETH M , HITCHCOCK STEPHEN , HUANG QI , KIM JOSEPH L , LIU GANG , NIXEY THOMAS , PARAS NICK A , PETKUS JEFFREY , RETZ DANIEL M , SMITH ADRIAN L , TASKER ANDREW , ZHU JIAWANG
IPC分类号： C07D239/84 , A61K31/435 , C07D239/95 , C07D401/04 , C07D401/14 , C07D403/04 , C07D403/14 , C07D405/14 , C07D409/14 , C07D413/04 , C07D413/14 , C07D417/14 , C07D471/04 , C07D487/04 , C07D495/04
摘要： Abstract The present invention comprises a new class of compounds capable of modulating Raf kinase and, accordingly, useful for treatment of Raf kinase mediated diseases, including melanomas, tumors and other cancer-related conditions. The compounds have 5 Formula (I) wherein R' is formula (II), (III), or (IV) and A , A2, A', A4, X, Z, Z', R', R2, R3, R4, R5 and R6 are defined herein. The invention further comprises pharmaceutical compositions, methods for treatment of Raf kinase mediated diseases, and intermediates and processes useful for the preparation of compounds of the invention.

7. 发明专利

PE20071328A1 COMPUESTOS DE HETEROARILO BICICLICO QUE CONTIENEN NITROGENO Y METODOS DE USO 未知
公开(公告)号：PE20071328A1
公开(公告)日：2008-02-09
申请号：PE2006001704
申请日：2006-12-26
申请人： AMGEN INC
发明人： DE MORIN FRENEL F , CHEN JIAN J , DOHERTY ELIZABETH M , HITCHCOCK STEPHEN , HUANG QI , KIM JOSEPH L , LIU GANG , NIXEY THOMAS , PARAS NICK A , PETKUS JEFFREY , RETZ DANIEL MARTIN , SMITH ADRIAN LEONARD , TASKER ANDREW , ZHU JIAWANG
IPC分类号： A61K31/5377 , A61K31/541 , C07D403/02 , C07D417/02
摘要： SE REFIERE A UN COMPUESTO DE FORMULA I, DONDE Z ES A, B, ENTRE OTROS; Z' ES UN ANILLO AROMATICO DE 5-6 MIEMBROS QUE OPCIONALMENTE COMPRENDEN 1-3 HETEROATOMOS SELECCIONADOS DE N, O Y S; R1 ES 1,2, ENTRE OTROS; A1,A1a,A2,A3 Y A4 SON CADA UNO CR6, N; X ES CR6R6, CO, NR6, ENTRE OTROS; R5 ES H, HALO, HALOALQUILO, NO2, CN, ENTRE OTROS; R6 ES H, HALO, HALOALQUILO, NO2, ENTRE OTROS; R2 ES HALO, HALOALQUILO, NO2, CN, ENTRE OTROS; R3 ES NH2, OH, SH, ENTRE OTROS; R17 ES H, HALO, HALOALQUILO, CN, OH, NH2, ACETILO, ENTRE OTROS. SON COMPUESTOS PREFERIDOS: 6-METIL-N5-(3-(4-PIRIMIDINIL)-2-PIRIDINI)N1-(3-(TRIFLUOROMETIL)FENIL)-1,5-ISOQUINOLINEDIAMINA; N1-(3-(DIETILAMIN)FENIL-6-METIL-N5-(3-(4-PIRIMIDINIL)-1,5-ISOQUINOLINEDIAMINA; ENTRE OTROS. DICHOS COMPUESTOS SON MODULADORES DE QUINASA RAF UTILES EN EL TRATAMIENTO DE MELANOMAS, TUMORES Y OTRAS CONDICIONES RELACIONADAS CON EL CANCER

8. 发明专利

PE13282007A1 COMPUESTOS DE HETEROARILO BICICLICO QUE CONTIENEN NITROGENO Y METODOS DE USO 未知
公开(公告)号：PE13282007A1
公开(公告)日：2008-02-09
申请号：PE0017042006
申请日：2006-12-26
申请人： AMGEN INC
发明人： DE MORIN FRENEL F , CHEN JIAN J , DOHERTY ELIZABETH M , HITCHCOCK STEPHEN , HUANG QI , KIM JOSEPH L , LIU GANG , NIXEY THOMAS , PARAS NICK A , PETKUS JEFFREY , RETZ DANIEL MARTIN , SMITH ADRIAN LEONARD , TASKER ANDREW , ZHU JIAWANG
IPC分类号： A61K31/5377 , A61K31/541 , C07D403/02 , C07D417/02
CPC分类号： C07D401/14 , C07D239/84 , C07D239/95 , C07D401/04 , C07D403/04 , C07D403/14 , C07D405/14 , C07D409/14 , C07D413/04 , C07D413/14 , C07D417/14 , C07D471/04 , C07D487/04 , C07D495/04
摘要： SE REFIERE A UN COMPUESTO DE FORMULA I, DONDE Z ES A, B, ENTRE OTROS; Z' ES UN ANILLO AROMATICO DE 5-6 MIEMBROS QUE OPCIONALMENTE COMPRENDEN 1-3 HETEROATOMOS SELECCIONADOS DE N, O Y S; R1 ES 1,2, ENTRE OTROS; A1,A1a,A2,A3 Y A4 SON CADA UNO CR6, N; X ES CR6R6, CO, NR6, ENTRE OTROS; R5 ES H, HALO, HALOALQUILO, NO2, CN, ENTRE OTROS; R6 ES H, HALO, HALOALQUILO, NO2, ENTRE OTROS; R2 ES HALO, HALOALQUILO, NO2, CN, ENTRE OTROS; R3 ES NH2, OH, SH, ENTRE OTROS; R17 ES H, HALO, HALOALQUILO, CN, OH, NH2, ACETILO, ENTRE OTROS. SON COMPUESTOS PREFERIDOS: 6-METIL-N5-(3-(4-PIRIMIDINIL)-2-PIRIDINI)N1-(3-(TRIFLUOROMETIL)FENIL)-1,5-ISOQUINOLINEDIAMINA; N1-(3-(DIETILAMIN)FENIL-6-METIL-N5-(3-(4-PIRIMIDINIL)-1,5-ISOQUINOLINEDIAMINA; ENTRE OTROS. DICHOS COMPUESTOS SON MODULADORES DE QUINASA RAF UTILES EN EL TRATAMIENTO DE MELANOMAS, TUMORES Y OTRAS CONDICIONES RELACIONADAS CON EL CANCER

9. 发明专利

AU2006330888B2 Nitrogen- containing bicyclic hetroaryl compounds for the treatment of Raf protein kinase-mediated diseases 未知
公开(公告)号：AU2006330888B2
公开(公告)日：2011-07-28
申请号：AU2006330888
申请日：2006-12-22
申请人： AMGEN INC
发明人： RETZ DANIEL M , PETKUS JEFFREY , ZHU JIAWANG , TASKER ANDREW , CHEN JIAN J , NIXEY THOMAS , DOHERTY ELIZABETH M , LIU GANG , SMITH ADRIAN L , HUANG QI , DE MORIN FRENEL F , HITCHCOCK STEPHEN , PARAS NICK A , KIM JOSEPH L
IPC分类号： C07D239/84 , A61K31/435 , C07D239/95 , C07D401/04 , C07D401/14 , C07D403/04 , C07D403/14 , C07D405/14 , C07D409/14 , C07D413/04 , C07D413/14 , C07D417/14 , C07D471/04 , C07D487/04 , C07D495/04
摘要： The present invention comprises a new class of compounds capable of modulating Raf kinase and, accordingly, useful for treatment of Raf kinase mediated diseases, including melanomas, tumors and other cancer-related conditions. The compounds have Formula (I) wherein R is Formula (II), (III) or (IV) and A, A, A, A, X, Z, Z', R, R, R, R, R and R are defined herein. The invention further comprises pharmaceutical compositions, methods for treatment of Raf kinase mediated diseases, and intermediates and processes useful for the preparation of compounds of the invention.

10. 发明专利

AU2011211423B2 Nitrogen-containing bicyclic hetroaryl compounds for the treatment of RAF protein kinase-mediated diseases 未知
公开(公告)号：AU2011211423B2
公开(公告)日：2014-02-20
申请号：AU2011211423
申请日：2011-08-12
申请人： AMGEN INC
发明人： DE MORIN FRENEL F , CHEN JIAN J , DOHERTY ELIZABETH M , HITCHCOCK STEPHEN , HUANG QI , KIM JOSEPH L , LIU GANG , NIXEY THOMAS , PARAS NICK A , PETKUS JEFFREY , RETZ DANIEL M , SMITH ADRIAN L , TASKER ANDREW , ZHU JIAWANG
IPC分类号： C07D239/84 , A61K31/435 , C07D239/95 , C07D401/04 , C07D401/14 , C07D403/04 , C07D403/14 , C07D405/14 , C07D409/14 , C07D413/04 , C07D413/14 , C07D417/14 , C07D471/04 , C07D487/04 , C07D495/04
摘要： Abstract The present invention comprises a new class of compounds capable of modulating Raf kinase and, accordingly, useful for treatment of Raf kinase mediated diseases, including melanomas, tumors and other cancer-related conditions. The compounds have 5 Formula (I) wherein R' is formula (II), (III), or (IV) and A1 , A2 , A3, A4 , X, Z, Z', R', R2, R3, R4 , R5 and R6 are defined herein. The invention further comprises pharmaceutical compositions, methods for treatment of Raf kinase mediated diseases, and intermediates and processes useful for the preparation of compounds of the invention.

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