Glaxosmithkline Intellectual Property Development Limited

Smithkline Beecham Corporation

Glaxosmithkline LLC

Cancer Research Technology Limited

Glaxosmithkline Intellectual Property (no.2) Limited

Andrew B Benowitz

Kelly M Aubart

Siegfried B Christensen, Iv

Joseph M Karpinski

Stuart Paul Romeril

Domingos J Silva

Bryan Wayne King

Jinhwa Lee

David T Fosbenner

William Henry Miller

Juan I Luengo

Allan Michael Jordan

Nicholas D Adams

Bohdan Waszkowycz

Donghui Qin

James B Hoffman

Xiangmin Liao

Dongchuan Shi

Stanley J Schmidt

Alexander Joseph Reif

Mei Li

Karen Anderson Evans

Jared T Spletstoser

Yuhong Fang

Andrew Nicholson Knox

Ali Raoof

Christopher S Kershaw

Kristin M Goldberg

Roger J Butlin

María Lourdes Rueda Benede

Jason Christopher Dreabit

Nicholas David Adams

Juan Ignacio Luengo

Siegfried Benjamin Iv Christensen

Beth Norton

The invention relates to substituted pyridine derivatives that are inhibitors of the activity of DNA methyltransferase 1 (DNMT1). The invention also relates to pharmaceutical compositions comprising such compounds and methods of using such compounds in the treatment of cancer, pre-cancerous syndromes, beta haemoglobinopathy disorders, and other diseases associated with inappropriate DNMT1 activity.

Substituted pyridines as DNMT1 inhibitors

The invention is directed to substituted pyridine derivatives. Specifically, the invention is directed to compounds according to Formula (Iar): wherein Y, X, X, R, R, R, Rand Rare as defined herein; or a pharmaceutically acceptable salt or prodrug thereof. The compounds of the invention are selective inhibitors of DNMT1 and can be useful in the treatment of cancer, pre-cancerous syndromes, beta hemoglobinopathy disorders, sickle cell disease, sickle cell anemia, and beta thalassemia, and diseases associated with DNMT1 inhibition. 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 DNMT1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

Substituted pyridines as inhibitors of DNMT1

The present invention relates to a compound of Formula (I): ora pharmaceutically acceptable salt thereof, corresponding pharmaceutical compositions, compound preparation and treatment methods directed to bacterial infections and inhibition of bacterial peptide deformylase (PDF) activity.

Peptide deformylase inhibitors

Novel PDF inhibitors and novel methods for their use are provided.

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Collegeville, PA, United States of America

Andrew B Benowitz