2-substituted quinazoline compounds comprising a substituted heterocyclic group and methods of use thereof

US10414757B2 · kind B2 · utility

Assignee

• Araxes Pharma LLC · US

Inventors

• Liansheng Li · San Diego, US
• Jun Feng · San Diego, US
• Yun Oliver Long · San Diego, US
• Yuan Liu · Billerica, US
• Tao Wu · Carlsbad, US
• Pingda Ren · San Diego, US
• Yi Liu · San Diego, US

Key dates

• Filing date: Nov 16, 2016
• Grant date: Sep 17, 2019
• Expiry date: Nov 16, 2036

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07D491/10
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

Compounds having activity as inhibitors of G12C mutant KRAS protein are provided. The compounds have the following structure (I): or a pharmaceutically acceptable salt, stereoisomer or prodrug thereof, wherein R1, R2a, R2b, R2c, R3a, R3b, R4a, R4b, R5a, R5b, R6, A, G1, G2, L1, L2, m1, m2, n, X and E are as defined herein and, wherein at least one of R3a, R3b, R4a or R4b is not H. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of G12C mutant KRAS protein for treatment of disorders, such as cancer, are also provided.