公开(公告)号：US20220267376A1

公开(公告)日：2022-08-25

申请号：US17618751

申请日：2020-06-16

申请人： Tomi K. SAWYER ,  Pietro ARONICA ,  Christopher J. BROWN ,  Fernando J. FERRER ,  Charles W. JOHANNES ,  Srinivasaraghavan KANNAN ,  David P. LANE ,  Anthony W. PARTRIDGE ,  Yaw Sing TAN ,  Chandra S. VERMA ,  Tsz Ying YUEN ,  Merck Sharp & Dohme Corp. ,  Agency for Science, Technology and Research ,  MSD International GMBH (Singapore Branch)

发明人： Pietro Aronica ,  Christopher J. Brown ,  Fernando J. Ferrer ,  Charles W. Johannes ,  Srinivasaraghavan Kannan ,  David P. Lane ,  Anthony W. Partridge ,  Tomi K. Sawyer ,  Yaw Sing Tan ,  Chandra S. Verma ,  Tsz Ying Yuen

IPC分类号： C07K7/08 ,  A61K45/06 ,  C07K7/06 ,  A61P35/00

摘要： Peptidomimetic macrocycles that comprise all-D configuration ?-amino acids and bind mouse double minute 2 (MDM2 aka E3 ubiquitin-protein ligase) and MDMX (aka MDM4) are described. These all-D configuration α-amino acid peptidomimetic macrocycles are protease resistant, cell permeable without inducing membrane disruption, and intracellularly activate p53 by binding MDM2 and MDMX thereby antagonizing MDM2 and MDMX binding to p53. These peptidomimetic macrocycles may be useful in anticancer therapies, particularly in combination with chemotherapy or radiation therapy.

公开(公告)号：US20230083431A1

公开(公告)日：2023-03-16

申请号：US17783224

申请日：2020-12-15

申请人： Nicolas C. BOYER ,  Michael B. GARRIGOU ,  Sookhee Nicole HA ,  Chunhui HUANG ,  Anthony W. PARTRIDGE ,  Tomi K. SAWYER ,  Pietro ARONICA ,  Charles W. JOHANNES ,  Srinivasaraghavan KANNAN ,  Chandra S. VERMA ,  Tsz Ying YUEN ,  Merck Sharp & Dohme LLC ,  MSD International GMBH (Singapore Branch) ,  Agency for Science, Technology and Research

发明人： Nicolas C. Boyer ,  Michael B. Garrigou ,  Sookhee Nicole Ha ,  Chunhui Huang ,  Anthony W. Partridge ,  Tomi K. Sawyer ,  Pietro Aronica ,  Charles W. Johannes ,  Srinivasaraghavan Kannan ,  Chandra S. Verma ,  Tsz Ying Yuen

IPC分类号： A61K38/12 ,  A61P35/00 ,  C07K7/52

摘要： The invention provides compounds of the Formula (I) or pharmaceutically acceptable salts thereof, wherein the variables are as described herein. The compounds or their pharmaceutically acceptable salts can inhibit the G12D mutant of Kirsten rat sarcoma (K-Ras) protein and are expected to have utility as therapeutic agents, for example, for treating cancer. The invention also provides pharmaceutical compositions which comprise compounds of Formula (I) or pharmaceutically acceptable salts thereof. The invention 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.