The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same.
本发明提供了化合物、药学上可接受的组合物以及使用它们的方法。
KRAS G12C INHIBITORS
申请人:Mirati Therapeutics, Inc.
公开号:US20190144444A1
公开(公告)日:2019-05-16
The present invention relates to compounds that inhibit KRas G12C. In particular, the present invention relates to compounds that irreversibly inhibit the activity of KRas G12C, pharmaceutical compositions comprising the compounds and methods of use therefor.
The invention is an algorithm and method for designing an inhibitor that covalently binds a target polypeptide. The algorithm and method can be used to rapidly and efficiently convert reversible inhibitors into irreversible inhibitors.
Provided are compounds represented by Formula I, wherein R3, A, A1, A2, A3, E, E1, E2, L, Q, Z, and (aa) are as defined in the specification, and the pharmaceutically acceptable salts and solvates thereof. Compounds of Formula (I) are KRAS inhibitors and are thus useful to treat cancer and other diseases.