Merck Sharp + Dohme Corp.

Merck Sharp & Dohme LLC

Xiaoshen Ma

Anandan Palani

Yongxin Han

David L Sloman

Thomas H Graham

Ryan D Otte

Timothy J Henderson

Mihir Mandal

Indu T Bharathan

Elisabeth Hennessy

Symon Gathiaka

Andrew J Hoover

Zahid Hussain

The disclosure provides compounds of Formula (I) or a pharmaceutically acceptable salt thereof, wherein W, W, Y, Z, M, L, C, C, R, R, R, R, R, R, R, and the subscripts m, n, q, and r are as described herein. The compounds or their pharmaceutically acceptable salts can inhibit the G12C mutant of Kirsten rat sarcoma (KRAS) protein and are expected to have utility as therapeutic agents, for example, for treating cancer. The disclosure also provides pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. The disclosure also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of cancer and for preparing pharmaceuticals for this purpose.

Small molecule inhibitors of KRAS G12C mutant

The disclosure provides compounds of Formula (I) or a pharmaceutically acceptable salt thereof, wherein W, W, Y, Z, M, L, C, C, R, R, R, R, R, R, Rand the subscripts m, n, q, and r are as described herein. The compounds or their pharmaceutically acceptable salts can inhibit the G12C mutant of Kirsten rat sarcoma (KRAS) protein and are expected to have utility as therapeutic agents, for example, for treating cancer. The disclosure also provides pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. The disclosure also relates to methods for use of the compounds or their pharmaceutically acceptable salts in the therapy and prophylaxis of cancer and for preparing pharmaceuticals for this purpose.

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Boston, MA, United States of America

Xiaoshen Ma