Glaxosmithkline Intellectual Property Development Limited

Glaxosmithkline Intellectual Property (No.2) Limited

Glaxo Group Limited

Glaxosmithkline LLC

Hilary Schenck Eidam

Mui Cheung

Chengde Wu

Krista B Goodman

Huiping Amy Guan

Guosen Ye

Ryan Michael Fox

Mark A Hilfiker

Zhen Gong

Carl A Brooks

Zhiliu Zhang

Marlys Hammond

Haiyu Yu

Haiying Yang

Raghava Reddy Kethiri

Jeffrey Michael Axten

Clark A Sehon

Michael P DeMartino

Pamela A Haile

Donghui Qin

Jaclyn R Patterson

Biswajit Kalita

Patrick Stoy

Michael P Demartino

Tram H Hoang

Eric Steven Manas

Terry Vincent Hughes

Gren Z Wang

Andrew Q Viet

Brian W Budzik

Lara Kallander

Brian Griffin Lawhorn

Hemant Joshi

Ronggang Liu

Dai-Shi Su

Anthony William Dean

Rajendra Kristam

David G Washburn

Joanne Philp

Jing Zhang

Anish Bandyopadhyay

Tamara Ann Miskowski

Nathan A Miller

Dimitar B Gotchev

Michael Jonathan Bury

Kaushik Raha

Sharada Manns

Mark Elban

Sarah E Dowdell

Carl Brooks

Jeffrey Axten

Amy Huiping Guan

Krista Goodman

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.

Disclosed are compounds having the formula: wherein R1, R2 and R3 are as defined herein, and methods of making and using the same, including use as inhibitors of BMP1, TLL1 and/or TLL2 and in treatment of diseases associated with BMP1, TLL1 and/or TLL2 activity.

Hydroxy formamide derivatives and their use

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

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

TRPV4 antagonists

Pyridine derivatives as rearranged during transfection (RET) kinase inhibitors

The present invention relates to spirocarbamate compounds of Formula (I) in which R1, (R2)Y, R3, R4, X and A have the meanings given in the specification. The invention further provides pharmaceutical compositions containing the compounds or pharmaceutically acceptable salts thereof and relates to their use of these compounds as TRPV4 antagonists in treating or preventing conditions associated with TRPV4 imbalance.

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

The present invention relates to diazabicyclo[2.2.1]hept-2-yl analogs, pharmaceutical compositions containing them and their use as TRPV4 antagonists.

The present invention relates to a compound of the following formula: where R-R, R, Y, n, m, p, and q are as defined herein. Compounds and compositions of the present invention are useful for the treatment of diseases associated with the overexpression of CCR2.

Spiroindolines as modulators of chemokine receptors

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King of Prussia, PA, United States of America

Hilary Schenck Eidam