Glaxo Group Limited

Glaxosmithkline Intellectual Property Development Limited

Anthony William Dean

Michael David Barker

Brian Evans

Michael David Woodrow

Stuart Holman

Mui Cheung

Julie Nicole Hamblin

Paul Spencer Jones

Colin David Eldred

Stephen Barry Guntrip

Hilary Schenck Eidam

Raghava Reddy Kethiri

Jeffrey Michael Axten

Alison Judith Redgrave

Christopher James Lunniss

Michael P DeMartino

Ian Robert Baldwin

Biswajit Kalita

John Edward Robinson

Rajendra Kristam

Sharon Lisa Gough

Mika Kristian Lindvall

Tracy Jane Redfern

The invention is directed to substituted pyrrolidine derivatives. Specifically, the invention is directed to compounds according to Formula III: wherein A, B, L, L, L, R, R, R, R, R, R, R, R, R, Y, Y, z, z, z, and zare 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.

Chemical compounds

There are provided according to the invention novel compounds of formula (I) or pharmaceutically acceptable salts thereof, wherein R1, R2, R19, R20, and R34 are as described in the specification, processes for preparing them, formulations containing them and their use in therapy for the treatment of inflammatory diseases.

Quinoline derivatives as phosphodiesterase inhibitors

There are provided according to the invention novel compounds of formula (I)  or pharmaceutically acceptable salts thereof, wherein R, RRRand Rare as described in the specification, processes for preparing them, formulations containing them and their use in therapy for the treatment of inflammatory diseases.

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Stevenage, United Kingdom

Anthony William Dean