Patent number: 8183254
Abstract: The invention relates to prodrugs of JNK inhibitors and corresponding methods, formulations, and compositions for inhibiting JNK and treating JNK-mediated disorders. The application discloses prodrugs of JNK inhibitors, as described below in formula I: wherein m, n, p, q, Q, r, R1, R2, R3, X, X1, X2, X3, X4, X5, Y1, Y2, Z1 and Z2 are as defined herein. The compounds and compositions disclosed herein are useful to modulate the activity of JNK and treat diseases associated with JNK activity. Disclosed are methods and formulations for inhibiting JNK and treating JNK-mediated disorders, and the like, with the compounds, and processes for making said compounds, and corresponding compositions, disclosed herein.
Type:
Grant
Filed:
May 14, 2009
Date of Patent:
May 22, 2012
Assignee:
Roche Palo Alto LLC
Inventors:
Humberto Bartolome Arzeno, James Patrick Dunn, David Michael Goldstein, Leyi Gong, Xiaochun Han, Joan Heather Hogg, Alam Jahangir, Wylie Solang Palmer, Deborah Carol Reuter, Tania Silva, Parcharee Tivitmahaisoon, Teresa Alejandra Trejo-Martin, Shao-Yong Wu
Patent number: 8163906
Abstract: 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, hydro
Type:
Grant
Filed:
May 14, 2008
Date of Patent:
April 24, 2012
Assignee:
Roche Palo Alto, LLC
Inventors:
Sarah C. Abbot, Geneviève N. Boice, Bernd Buettelmann, David Michael Goldstein, Leyi Gong, Joan Heather Hogg, Pravin Iyer, Kristen Lynn McCaleb, Yun-chou Tan