Pyrimidine derivatives as kinase modulators and method of use

US8211929B2 · kind B2 · utility

Assignee

• Exelixis, Inc. · US

Inventors

• Jeff Chen · San Francisco, US
• Lisa Esther Dalrymple Meyr · San Leandro, US
• Sergey Epshteyn · Fremont, US
• Timothy Patrick Forsyth · Hayward, US
• Tai Phat Huynh · Oakland, US
• Mohamed Abdulkader Ibrahim · Mountain View, US
• James William Leahy · San Leandro, US
• Gary L. Lewis · San Francisco, US
• Grace Mann · Brisbane, US
• Larry W. Mann · Redwood City, US
• Robin Tammie Noguchi · San Bruno, US
• Brian Hugh Ridgway · Belmont, US
• Joan C. Sangalang · San Francisco, US
• Kevin Luke Schnepp · Elk Grove, US
• Xian Shi · San Bruno, US
• Craig Stacy Takeuchi · Burlingame, US
• Matthew A. Williams · Foster City, US
• John M. Nuss · Danville, US
• Atwood Kim CHEUNG · Arlington, US

Key dates

• Filing date: Dec 28, 2005
• Grant date: Jul 3, 2012
• Expiry date: Jan 10, 2029

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D487/04
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

The invention provides compounds and methods for inhibition of kinases, more specifically IGF 1 R kinases. The invention also provides compounds and methods for inhibition of wildtype Abl. The invention provides compounds for modulating protein kinase enzymatic activity for modulating cellular activities such as proliferation, differentiation, programmed cell death, migration and chemoinvasion. Compounds of the invention inhibit, regulate and/or modulate kinase receptor signal transduction pathways related to the changes in cellular activities as mentioned above, and the invention includes compositions which contain these compounds, and methods of using them to treat kinase-dependent diseases and conditions. A compound of formula (I), or a pharmaceutically acceptable salt, hydrate, or prodrug thereof, wherein, V is NR1R1a, or O—R1, wherein X is H, halo, C1-C6 alkyl, NO2, mono-, di-, or tri-halo substituted methyl, NR13R,14. C(O)O—C1-C6 alkyl, or N(R13)—C(O)—C1-C6 alkyl; Y is H, halo, OH, C1-C6 alkyl, C0-C6alkyl-NR,15R16, NR15R,6, C1-C6 alkoxy, —N(R13)—(CH2)n-NR15R16, —C(O)O—C1-C6 alkyl, —O—(CH2)n—NR15R16, —C(O)—C1-C6 alkyl, —C0-C6-alkyl-R21, —O—R21, —C(O)—R21, —O—(CH2)n—R21, —C(O)—…