公开(公告)号：US08163906B2

公开(公告)日：2012-04-24

申请号：US12152432

申请日：2008-05-14

申请人： Sarah C. Abbot ,  Geneviève N. Boice ,  Bernd Buettelmann ,  David Michael Goldstein ,  Leyi Gong ,  Joan Heather Hogg ,  Pravin Iyer ,  Kristen Lynn McCaleb ,  Yun-chou Tan

发明人： Sarah C. Abbot ,  Geneviève N. Boice ,  Bernd Buettelmann ,  David Michael Goldstein ,  Leyi Gong ,  Joan Heather Hogg ,  Pravin Iyer ,  Kristen Lynn McCaleb ,  Yun-chou Tan

IPC分类号： C07D471/04

CPC分类号： C07D215/48 ,  C07D401/06 ,  C07D401/12 ,  C07D405/06 ,  C07D405/12 ,  C07D413/04 ,  C07D471/04

摘要： Compounds of formula I are effective modulators of JNK: wherein X is CR11 or N; Y is —C(O)R3, 5-membered heteroaryl, or 5-membered heterocyclyl; Z is phenyl, cycloalkyl, heterocyclyl or heteroaryl, and is substituted with R1 and R2; R1 and R2 are each independently H, halo, CN, lower alkyl, or —Y1—Y2—Y3—R8, or R1 and R2 together form —O(CH2)nO—, where n is 1 or 2; Y1 is —O—, —C(O)—, —C(O)O—, —C(O)NR9—, —NR9C(O)—, —S—, —SO2—, or a bond; Y2 is cycloalkylene, heterocycloalkylene, lower alkylene or a bond; Y3 is —O—, —C(O)—, —C(O)O—, —C(O)NR9—, —NR9C(O)—, —SO2—, or a bond; R8 is H, lower alkyl, lower alkoxy, cycloalkyl, heterocycloalkyl, or —NR9R10, wherein R8 other than H is optionally substituted with lower alkyl, halo, —CF3, or —OH; R9 and R10 are each independently H or lower alkyl; R3 is OH, lower alkyl, lower alkoxy, (lower alkoxy)-lower alkoxy, or —NR9R10; R4 is lower alkyl, phenyl, heterocyclyl, cycloalkyl, heterocycloalkyl, or heteroaryl, and is optionally substituted with lower alkyl, hydroxy, lower alkoxy, halo, nitro, amino, cyano, or halo-lower alkyl; R5 and R6 are each independently H, halo, cyano, lower alkyl, —CF3, lower alkoxy, —OCHF2, —NO2, or —NR9R10; R7 is H, F, Cl, methyl, or OH; R11 is H, lower alkyl, lower cycloalkyl, or phenyl; or a pharmaceutically acceptable salt thereof.

摘要翻译： 式I化合物是JNK的有效调节剂：其中X是CR11或N; Y是-C（O）R 3，5元杂芳基或5元杂环基; Z是苯基，环烷基，杂环基或杂芳基，并被R1和R2取代; R1和R2各自独立地为H，卤素，CN，低级烷基或-Y1-Y2-Y3-R8，或R1和R2一起形成-O（CH 2）n O-，其中n为1或2; Y1是-O - ， - C（O） - ， - C（O）O - ， - C（O）NR 9 - ， - NR 9 C（O） - ， - S - ， - SO 2 - 或键; Y2是亚环烷基，杂环亚烷基，低级亚烷基或键; Y 3是-O - ， - C（O） - ， - C（O）O-，-C（O）NR 9 - ， - NR 9 C（O） - ， - SO 2 - 或键; R8是H，低级烷基，低级烷氧基，环烷基，杂环烷基或-NR9R10，其中R8以外的R8任选被低级烷基，卤素，-CF 3或-OH取代; R9和R10各自独立地为H或低级烷基; R3是OH，低级烷基，低级烷氧基，（低级烷氧基） - 低级烷氧基或-NR9R10; R 4是低级烷基，苯基，杂环基，环烷基，杂环烷基或杂芳基，并且任选被低级烷基，羟基，低级烷氧基，卤素，硝基，氨基，氰基或卤代低级烷基取代。 R 5和R 6各自独立地为H，卤素，氰基，低级烷基，-CF 3，低级烷氧基，-OCHF 2，-NO 2或-NR 9 R 10; R7是H，F，Cl，甲基或OH; R11是H，低级烷基，低级环烷基或苯基; 或其药学上可接受的盐。

公开(公告)号：US20080287458A1

公开(公告)日：2008-11-20

申请号：US12152432

申请日：2008-05-14

申请人： Sarah C. Abbot ,  Genevieve N. Boice ,  Bernd Buettelmann ,  David Michael Goldstein ,  Leyi Gong ,  Joan Heather Hogg ,  Pravin Iyer ,  Kristen Lynn McCaleb ,  Yun-chou Tan

发明人： Sarah C. Abbot ,  Genevieve N. Boice ,  Bernd Buettelmann ,  David Michael Goldstein ,  Leyi Gong ,  Joan Heather Hogg ,  Pravin Iyer ,  Kristen Lynn McCaleb ,  Yun-chou Tan

IPC分类号： A61K31/496 ,  C07D471/04 ,  A61P19/02 ,  A61K31/4375

CPC分类号： C07D215/48 ,  C07D401/06 ,  C07D401/12 ,  C07D405/06 ,  C07D405/12 ,  C07D413/04 ,  C07D471/04

摘要： Compounds of formula I are effective modulators of JNK: wherein X is CR11 or N; Y is —C(O)R3, 5-membered heteroaryl, or 5-membered heterocyclyl; Z is phenyl, cycloalkyl, heterocyclyl or heteroaryl, and is substituted with R1 and R2; R1 and R2 are each independently H, halo, CN, lower alkyl, or —Y1—Y2—Y3—R8, or R1 and R2 together form —O(CH2)nO—, where n is 1 or 2; Y1 is —O—, —C(O)—, —C(O)O—, —C(O)NR9—, —NR9C(O)—, —S—, —SO2—, or a bond; Y2 is cycloalkylene, heterocycloalkylene, lower alkylene or a bond; Y3 is —O—, —C(O)—, —C(O)O—, —C(O)NR9—, —NR9C(O)—, —SO2—, or a bond; R8 is H, lower alkyl, lower alkoxy, cycloalkyl, heterocycloalkyl, or —NR9R10, wherein R8 other than H is optionally substituted with lower alkyl, halo, —CF3, or —OH; R9 and R10 are each independently H or lower alkyl; R3 is OH, lower alkyl, lower alkoxy, (lower alkoxy)-lower alkoxy, or —NR9R10; R4 is lower alkyl, phenyl, heterocyclyl, cycloalkyl, heterocycloalkyl, or heteroaryl, and is optionally substituted with lower alkyl, hydroxy, lower alkoxy, halo, nitro, amino, cyano, or halo-lower alkyl; R5 and R6 are each independently H, halo, cyano, lower alkyl, —CF3, lower alkoxy, —OCHF2, —NO2, or —NR9R10; R7 is H, F, Cl, methyl, or OH; R11 is H, lower alkyl, lower cycloalkyl, or phenyl; or a pharmaceutically acceptable salt thereof.

公开(公告)号：US20070123527A1

公开(公告)日：2007-05-31

申请号：US11605528

申请日：2006-11-29

申请人： Pravin Iyer ,  Matthew Lucas ,  Ryan Schoenfeld ,  Marzia Villa ,  Robert Weikert

发明人： Pravin Iyer ,  Matthew Lucas ,  Ryan Schoenfeld ,  Marzia Villa ,  Robert Weikert

IPC分类号： A61K31/538 ,  A61K31/498 ,  A61K31/506 ,  A61K31/501 ,  A61K31/4745 ,  A61K31/428 ,  A61K31/423 ,  C07D413/02 ,  C07D417/02 ,  C07D403/02

CPC分类号： C07D209/12 ,  C07D209/08 ,  C07D209/14 ,  C07D209/30 ,  C07D209/32 ,  C07D209/40 ,  C07D209/42 ,  C07D231/56 ,  C07D235/06 ,  C07D235/24 ,  C07D235/26 ,  C07D307/79 ,  C07D311/04 ,  C07D333/52 ,  C07D333/58 ,  C07D401/06 ,  C07D401/10 ,  C07D403/06 ,  C07D409/06 ,  C07D413/06 ,  C07D417/10 ,  C07D471/04

摘要： The present invention provides compounds of the formula: or pharmaceutically acceptable salts, solvates or prodrugs thereof, wherein p, Ar, R1, R2, R3, Ra, Rb, Rc, Rd and Re are defined herein. Also provided are pharmaceutical compositions, methods of using, and methods of preparing the compounds.

摘要翻译： 本发明提供下式的化合物或其药学上可接受的盐，溶剂合物或前药，其中p，Ar，R 1，R 2，R 3， R SUP，R，B，R，C，R，D， / SUP>。 还提供药物组合物，使用方法和制备化合物的方法。