Hoffmann-la Roche Inc.

Pmv Pharmaceuticals, Inc.

F. Hoffmann-la Roche Ag

Hoffmann-le Roche Inc.

Binh Vu

Romyr Dominique

Hongju Li

Xin-Jie Chu

Norman Kong

Gregory Jay Haley

David Joseph Bartkovitz

Emily Aijun Liu

Bruce Fahr

Stephen Evan Webber

Nader Fotouhi

Allen John Lovey

Klaus B Simonsen

Andrew Charles Good

Peter Michael Wovkulich

Qingjie Ding

Chunlin Zhao

Yi Heng Chen

Jin-Jun Liu

Nan Jiang

John Anthony Moliterni

John Guilfoyle Mullin, Jr

Sung-Sau So

Robert Alan Goodnow, Jr

Giacomo Pizzolato

Bradford Graves

Qi Qiao

Jianping Cai

John Lawson Roberts

George Kenneth Ehrlich

Daniel Vincent Fishlock

Hanspeter Michel

Mutations in oncogenes and tumor suppressors contribute to the development and progression of cancer. The present disclosure describes compounds and methods to recover wild-type function to p53 mutants. The compounds of the present invention can bind to mutant p53 and restore the ability of the p53 mutant to bind DNA and activate downstream effectors involved in tumor suppression. The disclosed compounds can be used to reduce the progression of cancers that contain a p53 mutation.

Methods and compounds for restoring mutant p53 function

The compounds of the current disclosure include propynyl substituted indoles, where one or more hydrido radicals is substituted with a deuterium atom, wherein the compound binds a mutant p53 protein and increases wild-type p53 activity of the mutant p53 protein.

Deuterated compounds for restoring mutant p53 function

Mutations in oncogenes and tumor suppressors contribute to the development and progression of cancer. The present disclosure describes compounds and methods that restore DNA binding affinity of p53 mutants. The compounds of the present disclosure can bind to mutant p53 and restore the ability of the p53 mutant to bind DNA and activate downstream effectors involved in tumor suppression. The disclosed compounds can be used to reduce the progression of cancers that contain a p53 mutation.

Mutations in oncogenes and tumor suppressors contribute to the development and progression of cancer. The present disclosure describes compounds and methods to recover wild-type function to p53 mutants. The compounds of the present disclosure can bind to mutant p53 and restore the ability of the p53 mutant to bind DNA and activate downstream effectors involved in tumor suppression. The disclosed compounds can be used to reduce the progression of cancers that contain a p53 mutation.

There are provided compounds of the formula wherein X, Y, Z, R, Rand Rare as described hereinand enantiomers and pharmaceutically acceptable salts and esters thereof. The compounds are useful as anticancer agents.

Substituted pyrrolidine-2-carboxamides

There are provided compounds of the formula wherein X, Y, Z, R, R, Rand Rare as described hereinand enantiomers and pharmaceutically acceptable salts and esters thereof. The compounds are useful as anticancer agents.

There are provided compounds of the formula or the pharmaceutically acceptable salts thereof, wherein X, Y, Z, V, V, R, R, R, Rand Rare herein described. These compounds are useful as anticancer agents.

Chiral cis-imidazolines

and the pharmaceutically acceptable salts and esters thereof, wherein X, X, X, Y, Yand R are described herein inhibit the interaction of MDM2 protein with a p53-like peptide and hence have anti proliferative activity.

The present invention relates to compounds of the formula and the pharmaceutically acceptable salts and esters thereof, a process for their manufacture, medicaments containing them as well as the use of these compounds as pharmaceutically active agents. The compounds show antiproliferative activity and may be especially useful for the treatment of cancer.

CIS-imidazolines

There is provided a compound of formula I and the pharmaceutically acceptable salts and esters thereofwherein X, X, R, R, R, R, Rand Rare herein described. The compounds exhibit activity as anticancer agents.

4,4,5,5, tetrasubstituted imidazolines

Growing community of inventors

North Caldwell, NJ, United States of America

Binh Vu