Chemical compounds

Patent metadata

Field	Value
Publication number	US-11547704-B2
Application number	US-202016898667-A
Country	US
Kind code	B2
Filing date	Jun 11, 2020
Priority date	Jun 8, 2016
Publication date	Jan 10, 2023
Grant date	Jan 10, 2023

Abstract

The invention is directed to substituted piperidine derivatives. Specifically, the invention is directed to compounds according to Formula IIII:

wherein A, B, X, Y, L 1 , L 2 , L 3 , R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 9 , z 2 , z 4 , z 5 , and z 6 are as defined herein, and salts thereof.

The compounds of the invention are inhibitors of the ATF4 pathway and can be useful in the treatment of cancer, pre-cancerous syndromes and diseases associated with activated unfolded protein response pathways, such as Alzheimer's disease, spinal cord injury, traumatic brain injury, ischemic stroke, stroke, diabetes, Parkinson disease, Huntington's disease, Creutzfeldt-Jakob Disease, and related prion diseases, progressive supranuclear palsy, amyotrophic lateral sclerosis, myocardial infarction, cardiovascular disease, inflammation, fibrosis, chronic and acute diseases of the liver, chronic and acute diseases of the lung, chronic and acute diseases of the kidney, chronic traumatic encephalopathy (CTE), neurodegeneration, dementia, cognitive impairment, atherosclerosis, ocular diseases, arrhythmias, in organ transplantation and in the transportation of organs for transplantation. Accordingly, the invention is further directed to pharmaceutical compositions comprising a compound of the invention. The invention is still further directed to methods of inhibiting the ATF4 pathway and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

First claim

What is claimed is:

1. A compound which is

or a pharmaceutically acceptable salt thereof.

2. A pharmaceutical combination comprising:
a) a compound as described in claim 1 or a pharmaceutically acceptable salt thereof; and
b) at least one anti-neoplastic agent.

3. A pharmaceutical composition comprising a compound according to claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient.

4. The compound of claim 1 which is a hydrochloride salt thereof.

Assignees

• Glaxosmithkline Ip Dev Ltd

Inventors

• Axten Jeffrey Michael
• Cheung Mui
• Demartino Michael P
• Eidam Hilary Schenck
• Kethiri Raghava Reddy
• Kalita Biswajit

Classifications

• A61K31/439

  the ring forming part of a bridged ring system, e.g. quinuclidine (8-azabicyclo [3.2.1] octanes A61K31/46) · CPC title

• C07D405/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D471/08

  Bridged systems · CPC title

• C07D209/52

  condensed with a ring other than six-membered · CPC title

• C07D498/10

  Spiro-condensed systems · CPC title