Glaxosmithkline LLC

Glaxo Group Limited

Smithkline Beecham Corporation

Glaxosmithkline Intellectual Property Development Limited

Jeffrey Michael Axten

William Henry Miller

Timothy Francis Gallagher

Mui Cheung

Mark Andrew Seefeld

Neil David Pearson

Michael P DeMartino

Graham Elgin Jones

David Thomas Davies

Hilary Schenck Eidam

Raghava Reddy Kethiri

Domingos J Silva

Stuart Paul Romeril

Jun Tang

Israil Pendrak

Robert A Daines

Seth Wilson Grant

Biswajit Kalita

Jesus Raul Medina

Jerry Leroy Adams

Kenneth Allen Newlander

Dashyant Dhanak

Chengde Wu

Vipulkumar Kantibhai Patel

Dirk Andries Heerding

Neil W Johnson

Xinrong Tian

Jiri Kasparec

Christopher Roland Wellaway

Nicholas D Adams

Deborah Lynne Bryan

Cynthia A Parrish

David Harold Drewry

Huiping Amy Guan

Donghui Qin

Guy Marguerite Marie Gerard Nadler

Zhiliu Zhang

Francis Louis Atkinson

Martha A Sarpong

Yan Hu

Charles William Blackledge, Jr

Anthony William Dean

Thomas H Faitg

Yanhong Feng

Amita M Chaudhari

Michael Lee Moore

Jeffrey M Ralph

Toshihiro Hamajima

Catherine Genevieve Yvette Dartois

Rajendra Kristam

Aaron Bayne Miller

Xiaojuan Lin

Jesus Rual Medina

Gerald Patrick Brady, Jr

Maria Cichy-Knight

Allison K Dunn

Mark Antony Seefeld

Mark Anthony Seefeld

Jesus R Medina

Vipulkumar Kantibhai Patei

Jesus Rahul Medina

Yanhoug G Feng

This invention relates to novel compounds according to Formula (I) which are inhibitors of furin, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy for the treatment of fibrotic diseases, including pulmonary fibrosis, renal fibrosis, liver fibrosis, skin fibrosis, ocular fibrosis, cardiac fibrosis, and other miscellaneous fibrotic conditions. The disclosed compounds may also be useful for treating other furin-mediated conditions, including but not limited to, hypertension, cancer, infectious diseases, and genetic disorders (e.g., cystic fibrosis (CF)), and neurodegenerative disorders.

Furin inhibitors

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, L, L, R, R, R, R, R, R, R, 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

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.

The invention is directed to 6-(4-pyrimidinyl)-1H-indazole derivatives. Specifically, the invention is directed to compounds according to Formula (I) wherein R-Rare defined herein. The compounds of the invention axe inhibitors of PDK1 and can be useful in the treatment of immune and metabolic diseases and disorders characterized by constitutively activated ACG kinases such as cancer and more specifically cancers of the breast, colon, and lung. 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 PDK1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

The invention is directed to substituted indoline derivatives. Specifically, the invention is directed to compounds according to Formula I: wherein R, R, and Rare defined herein. The compounds of the invention are inhibitors of PERK and can be useful in the treatment of cancer, ocular diseases, and diseases associated with activated unfolded protein response pathways, such as Alzheimer's disease, stroke, Type 1 diabetes Parkinson disease, Huntington's disease, amyotrophic lateral sclerosis, myocardial infarction, cardiovascular disease, atherosclerosis, and arrhythmias, and more specifically cancers of the breast, colon, pancreatic, and lung. 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 PERK activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

The invention is directed to pyrido[4,3-d]pyrimidin-5(6H)-one derivatives. Specifically, the invention is directed to compounds according to Formula I: wherein R, R, R, and Rare defined below. The compounds of the invention are inhibitors of PDK1 and can be useful in the treatment of disorders characterized by constitutively activated ACG kinases such as cancer and more specifically cancers of the breast, colon, and lung. 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 PDK1 activity and treatment of disorders associated therewith using a compound of the invention or a pharmaceutical composition comprising a compound of the invention.

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

Peptide deformylase inhibitors

The present invention relates to a compound represented by the following formula: or a pharmaceutically acceptable salt thereof;

Anthranilamide inhibitors of aurora kinase

Naphthalene, quinoline, quinoxaline and naphthyridine derivatives useful in the treatment of bacterial infections in mammals, particularly humans, are disclosed herein.

Antibacterial agents

Cyclohexane and cyclohexene derivatives and pharmaceutically acceptable derivatives thereof useful in methods of treatment of bacterial infections in mammals, particularly man.

Antibacterial compounds

Quinoline and naphthyridine derivatives useful in the treatment of bacterial infections in mammals, particularly humans.

Piperidine derivatives and pharmaceutically acceptable derivatives thereof useful in methods of treatment of bacterial infections in mammals, particularly in man. The piperidine derivatives include compounds of formula (I): wherein R, AB, n, R, Rand Rare defined herein. For example, Ris an optionally substituted bicyclic carbocyclic or heterocyclic ring system, and Ris a group U-Rin which Ris an optionally substituted bicyclic heterocyclic ring system as defined herein (e.g. optionally substituted pyrido [3,2, -b][1,4] thiazin-yl).

Compounds

The present invention relates to a compound represented by Formula (I): and pharmaceutically acceptable salts. Compounds of the present invention inhibit Aurora kinase, making them especially suitable for the treatment of a number of diseases, including solid tumor cancers and hematological cancers.

Azaindole inhibitors of aurora kinases

Quinoline and naphthridine derivatives useful in the treatment of bacterial infections in mammals, particularly humans.

Quinolines and nitrogenated derivatives thereof and their use as antibacterial agents

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Collegeville, PA, United States of America

Jeffrey Michael Axten