N-(3-(2-(4-CHLOROPHENOXY)ACETAMIDO)BICYCLO[1.1.1]PENTAN-1-YL)-2-CYCLOBUTANE-1-CARBOXAMIDE DERIVATIVES AND RELATED COMPOUNDS AS ATF4 INHIBITORS FOR TREATING CANCER AND OTHER DISEASES

• Main Authors: KALITA, Biswajit, CHEUNG, Mui, DEMARTINO, Michael P
• Format: Patent
• Language: English; French
• Published: 10.01.2019
• Subjects: ACYCLIC OR CARBOCYCLIC COMPOUNDS; CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS ORMEDICINAL PREPARATIONS

The invention is directed to substituted bridged cycloalkane derivatives. Specifically, the invention is directed to compounds according to Formula (I) wherein X, a, b, C, D, L2, L3, Y1, Y2, R2, R4, R5, R6, z2, z4, z5, and z6 are as defined herein, and salts thereof. The invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to compounds for use in methods of inhibiting the ATF4 (activating transcription factor 4) pathway and treatment of disorders associated therewith, such as e.g. cancer, neurodegenerative diseases and many other diseases, using a compound of the invention or a pharmaceutical composition comprising a compound of the invention. Preferred compounds of the invention are N-(3-(2-(4-chlorophenoxy) acetamido)bicyclo[1.1.1]pentan-l-yl)-2-cyclobutane-l-carboxamide derivatives and related compounds. L'invention concerne des dérivés de cycloalcanes pontés substitués. L'invention concerne particulièrement des composés de formule (II), dans laquelle X, a, b, C, D, L2, L3, Y1, Y2, R2, R4, R5, R6, z2, z4, z5 et z6 sont tels que définis dans la description; l'invention concerne également des sels de ces composés. L'invention concerne en outre des compositions pharmaceutiques comprenant un composé selon l'invention. L'invention concerne en outre des composés destinés à être utilisés dans des procédés d'inhibition de la voie ATF4 (facteur 4 d'activation de la transcription) et dans le traitement de troubles associés à celle-ci, comme par exemple le cancer, des maladies neurodégénératives et d'autres maladies, à l'aide d'un composé de l'invention ou d'une composition pharmaceutique comprenant un composé de l'invention. Les composés préférés selon l'invention sont des dérivés de N-(3-(2-(4-chlorophénoxy)acétamido)bicyclo [1.1.1]pentan-l-yl)-2-cyclobutane-l-carboxamide et des composés apparentés.