Smithkline Beecham Corporation

Glaxosmithkline LLC

Glaxosmithkline Intellectual Property Development Limited

Glaxosmithkline Intellectual Property (no.2) Limited

Sitari Pharma, Inc.

Glaxosmithkline Intellectual Property Limited

Mui Cheung

Hilary Schenck Eidam

Raghuram Tangirala

Philip Anthony Harris

James Marvin Veal

Chengde Wu

Robert Anthony Mook

Huiping Amy Guan

Donghui Qin

Kyle Allen Emmitte

Brian Alvin Johns

Amogh Boloor

Stanley Dawes Chamberlain

Kristjan S Gudmundsson

Krista B Goodman

Carl A Brooks

Michael Robert Peel

Zhiliu Zhang

James Michael Salovich

Kevin Hinkle

Jeffery Alan Stafford

David Kendall Jung

Jeffrey Michael Axten

Zhen Gong

Michael P DeMartino

Guosen Ye

Mark A Hilfiker

Kevin Kuntz

Marlys Hammond

Raghava Reddy Kethiri

Ryan Michael Fox

Michael John Alberti

Jaclyn R Patterson

Biswajit Kalita

Douglas McCord Sammond

Jeffrey Alan Stafford

Alex Gregory Waterson

Mark Andrew Pobanz

Neil W Johnson

Scott Howard Dickerson

Nigel Paul King

Robert Neil Hunter, Iii

Joseph Wendell Wilson

Tara Renae Rheault

David Edward Uehling

Hideyuki Sato

John Brad Shotwell

Robert Dale Hubbard

Hemant Joshi

Kristen Elizabeth Nailor

Haiying Yang

Haiyu Yu

Patrick Stoy

Michael P Demartino

Brian Wilson

Sridhar Reddy Bethi

Ronda Davis

Jennifer Badiang Stanford

Eric Steven Manas

Stephon Cornell Smith

Kirk Stevens

Gregory Pacofsky

Jennifer Gabriel Badiang

Yan Hu

Tram H Hoang

Keith Hornberger

Dai-Shi Su

Anthony William Dean

Masaichi Hasegawa

Holly Kathleen Emerson

Yoshiaki Washio

Satoru Ida

Marcus Semones

F Leslie Boyd

David Campbell

Justin Chapman

Thomas R Diraimondo

Sergio G Duron

Matthew Lee Brown

Kimberly Petrov

Naohiko Nishigaki

Rajendra Kristam

Hamilton Dickson

Raghuram S Tangirala

Kazuya Kano

Rob I West

Kaushik Raha

Cassandra Gauthier

Connie Jo Sexton

Michael Jonathan Bury

Aaron Bayne Miller

Xiaojuan Lin

Anish Bandyopadhyay

Erich W Baum

Ganesh Moorthy

Ronda Gayle Davis-Ward

Christopher P Lauderman

Mariko Yamabe

Ganesh S Moorthy

Described herein are compounds and pharmaceutical compositions containing such compounds which inhibit transglutaminase 2 (TG2). Also described herein are methods for using such TG2 inhibitors, alone or in combination with other compounds, for treating diseases or conditions that would benefit from TG2 inhibition.

Transglutaminase 2 (TG2) inhibitors

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

This invention relates to novel compounds according to Formula (I) which are inhibitors of ghrelin O-acyltransferase (GOAT), to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy for the treatment of metabolic disorders (e.g. Prader-Willi syndrome, metabolic syndrome, insulin resistance, impaired glucose tolerance, prediabetes, diabetes mellitus (e.g., type II diabetes mellitus), dysglycemia (e.g., hyperglycemia), obesity (e.g., obesity caused by Prader-Willi syndrome), increased adiposity, poor glycemic control, hyperphagia, impaired satiety, dyslipidemia (e.g., atherogenic dyslipidemia), hepatic steatosis (e.g., non-alcoholic fatty liver disease (e.g., non-alcoholic steatohepatitis))), psychiatric disorders (e.g., eating disorders (e.g., bulimia nervosa, binge eating disorder, night-time eating syndrome), substance related disorders (e.g., addiction disorders (e.g., alcohol, smoking, overeating, or use of illicit drugs))), as well as disorders related to or complications of metabolic or psychiatric disorders (e.g., cardiovascular diseases (e.g., diabetic heart disease (e.g., diabetic cardiomyopathy), heart failure, or hypertension), ischemia (e.g., myocardial ischemia, cerebral ischemia, ischemic stroke), or BMI-related cancers (e.g., pancreatic cancer, gallbladder cancer, esophageal cancer, colorectal cancer, breast cancer etc.). 

Ghrelin O-acyltransferase inhibitors

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.

This invention relates to methods for the preparation of a compound which is an inhibitor of acyl coenzyme A: diacylglycerol acyltransferase 1 (DGAT-1).

Compounds as diacylglycerol acyltransferase inhibitors

This invention relates to novel compounds which are inhibitors of the Rearranged during Transfection (RET) kinase, to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy, alone or in combination, for the normalization of gastrointestinal sensitivity, motility and/or secretion and/or abdominal disorders or diseases and/or treatment related to diseases related to RET dysfunction or where modulation of RET activity may have therapeutic benefit including but not limited to all classifications of irritable bowel syndrome (IBS) including diarrhea-predominant, constipation-predominant or alternating stool pattern, functional bloating, functional constipation, functional diarrhea, unspecified functional bowel disorder, functional abdominal pain syndrome, chronic idiopathic constipation, functional esophageal disorders, functional gastroduodenal disorders, functional anorectal pain, inflammatory bowel disease, proliferative diseases such as non-small cell lung cancer, hepatocellular carcinoma, colorectal cancer, medullary thyroid cancer, follicular thyroid cancer, anaplastic thyroid cancer, papillary thyroid cancer, brain tumors, peritoneal cavity cancer, solid tumors, other lung cancer, head and neck cancer, gliomas, neuroblastomas, Von Hippel-Lindau Syndrome and kidney tumors, breast cancer, fallopian tube cancer, ovarian cancer, transitional cell cancer, prostate cancer, cancer of the esophagus and gastroesophageal junction, biliary cancer, adenocarcinoma, and any malignancy with increased RET kinase activity.

Compounds as rearranged during transfection (RET) inhibitors

This invention relates to important intermediates in the preparation of a compound which is an inhibitor of acyl coenzyme A: diacylglycerol acyltransferase 1 (DGAT-1).

This invention relates to novel compounds which are inhibitors of acyl coenzyme A: diacylglycerol acyltransferase 1 (DGAT-1), to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy, alone or in combination with weight management therapies or other triglyceride lowering therapy for the prevention or treatment of diseases related to DGAT-1 dysfunction or where modulation of DGAT-1 activity may have therapeutic benefit including but not limited to obesity, obesity related disorders, genetic (Type 1, Type 5 hyperlipidemia) and acquired forms of hypertriglyceridemia or hyperlipoproteinemia-related disorders, caused by but not limited to lipodystrophy, hypothyroidism, medications (beta blockers, thiazides, estrogen, glucocorticoids, transplant) and other factors (pregnancy, alcohol intake), hyperlipoproteinemia, chylomicronemia, dyslipidemia, non-alcoholic steatohepatitis, diabetes, insulin resistance, metabolic syndrome, cardiovascular outcomes, angina, excess hair growth (including syndromes associated with hirsutism), nephrotic syndrome, fibrosis such as myocardial, renal and liver fibrosis, hepatitis C virus infection and acne or other skin disorders.

Compounds of Formula (I) are inhibitors of acyl coenzyme A: diacylglycerol acyltransferase 1 (DGAT-1), useful in the treatment of obesity, obesity related disorders, genetic (Type 1, Type 5 hyperlipidemia) and acquired forms of hypertriglyceridemia or hyperlipoproteinemia-related disorders, caused by but not limited to lipodystrophy, hypothyroidism, medications (beta blockers, thiazides, estrogen, glucocorticoids, transplant) and other factors (pregnancy, alcohol intake), hyperlipoproteinemia, chylomicronemia, dyslipidemia, non-alcoholic steatohepatitis, diabetes, insulin resistance, metabolic syndrome, cardiovascular outcomes, angina, excess hair growth (including syndromes associated with hirsutism), nephrotic syndrome, fibrosis such as mycocardial, renal and liver fibrosis, hepatitis C virus infection and acne or other skin disorders. 

This invention relates to novel compounds which are inhibitors of acyl coenzymeA: diacylglycerol acyltransferase 1 (DGAT-1), to pharmaceutical compositions containing them, to processes for their preparation, and to their use in therapy for the prevention or treatment of diseases related to DGAT-1 dysfunction or where modulation of DGAT-1 activity may have therapeutic benefit including but not limited to obesity, obesity related disorders, hypertriglyceridemia, hyperlipoproteinemia, chylomicronemia, dyslipidemia, non-alcoholic steatohepatitis, diabetes, insulin resistance, metabolic syndrome, hepatitis C virus infection and acne or other skin disorders.

The present invention relates to spirocarbamate analogs, pharmaceutical compositions containing them and their use as TRPV4 antagonists.

TRPV4 antagonists

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King of Prussia, PA, United States of America

Mui Cheung