Metabasis Therapeutics, Inc.

Dart Neuroscience, LLC

Merck Sharp + Dohme Corp.

Vertex Pharmaceuticals, Inc.

Dart Neuroscience, (cayman) Ltd.

Gensia Sicor Inc.

Brett C Bookser

Nicholas Brian Raffaele

Mark D Erion

Qun Dang

K Raja Reddy

Scott J Hecker

Venkat Reddy Mali

Serge H Boyer

Andrew Richard Hudson

Joe Anh Tran

Jeff Stebbins

Feng Tian

Lino J Valdez

DeMichael Chung

Wenyu Li

G Sridhar Prasad

Mark Thomas Miller

Jinglan Zhou

Sara Sabina Hadida Ruah

Jianming Bao

F Anthony Romero

Jinlong Jiang

Iyassu Sebhat

Thomas Cleveland

Brian Dyck

Mi Chen

Michel Gallant

Timothy Richard Coon

Claudio F Sturino

Prasuna Paraselli

Jeremy J Clemens

Aaron Craig Burns

Thumkunta Jagadeeswar Reddy

Ahmet Kekec

Dariusz Wodka

Yeeman K Ramtohul

Benjamin Pratt

Michael I Weinhouse

Ping Lan

Joel Renick

Hongjian Jiang

Marco Peters

Jillian Basinger

Pablo Garcia-Reynaga

Tony Gibson

Vincent Santora

Iriny Botrous

Huagang Lu

Minson Baek

Margaret McCarrick

Gergely M Makara

Mali Venkat Reddy

De Michael Chung

Dange Vijay Kumar

Andy Kassick

James Na

Julie Laterreur

William Schulz Bechara

Jillian Basinger Thompson

Scott Burley

Aaron Thompson

Andrew Kleinke

David Wilson

David Bernard Smith

Harry E Gruber

Peter Diederik Jan Grootenhuis

Peter Grootenhuis

Alan P Kaplan

Srinivas Rao Kasibhatla

Zhili Sun

Varsha Gupta

Vito Melillo

Lino Valdez

Margaret Mccarrick

Michael Weinhouse

Joe Tran

Thompson Jillian Basinger

Demichael Chung

Claudio Sturino

This disclosure provides modulators of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), pharmaceutical compositions containing at least one such modulator, methods of treatment of cystic fibrosis using such modulators and pharmaceutical compositions, and processes for making such modulators.

Modulators of cystic fibrosis transmembrane conductance regulator

Substituted furanopyrimidine chemical entities of Formula (I): wherein Rhas any of the values described herein, and compositions comprising such chemical entities; methods of making them; and their use in a wide range of methods, including metabolic and reaction kinetic studies; detection and imaging techniques; radioactive therapies; modulating and treating disorders mediated by PDE1 activity or dopaminergic signaling; treating neurological disorders, CNS disorders, dementia, neurodegenerative diseases, and trauma-dependent losses of function; treating stroke, including cognitive and motor deficits during stroke rehabilitation; facilitating neuroprotection and neurorecovery; enhancing the efficiency of cognitive and motor training, including animal skill training protocols; and treating peripheral disorders, including cardiovascular, renal, hematological, gastroenterological, liver, cancer, fertility, and metabolic disorders.

Substituted furanopyrimidine compounds as PDE1 inhibitors

Substituted cyclohexyl chemical entities of Formula (I):

Substituted cyclohexyl compounds as NOP inhibitors

Substituted furanopyrimidine chemical entities of Formula (I): wherein Rhas any of the values described herein, and compositions comprising such chemical entities; methods of making them; and their use in a wide range of methods, including metabolic and reaction kinetic studies; detection and imaging techniques; radioactive therapies; modulating and treating disorders mediated by PDE1 activity or dopaminergic signaling; treating neurological disorders, CNS disorders, dementia, neurodegenerative diseases, and trauma-dependent losses of function; treating stroke, including cognitive and motor deficits during stroke rehabilitation; facilitating neuroprotection and neurorecovery; enhancing the efficiency of cognitive and motor training, including animal skill training protocols; and treating peripheral disorders, including cardiovascular, renal, hematological, gastroenterological, liver, cancer, fertility, and metabolic disorders. 

Substituted cyclohexyl chemical entities of Formula (I): wherein R, G, and Rhave any of the values described herein, and compositions comprising such chemical entities; methods of making them; and their use in a wide range of methods, including metabolic and reaction kinetic studies; detection and imaging techniques; radioactive therapies; modulating and treating disorders mediated by nociceptin activity or dopamine signaling; treating neurological disorders, neurodegenerative diseases, depression, and schizophrenia; enhancing the efficiency of cognitive and motor training; and treating peripheral disorders, including renal, respiratory, gastrointestinal, liver, genitourinary, metabolic, and inflammatory disorders. 

Substituted cyclohexyl compounds as NOP inhibiiors

This invention pertains to the use of fused bicycle heterocyclic adducts of thiohydroxy pyridines or pyrimidines as diacylglycerol O-acyltransferase 1 (DGAT-1) inhibitors to treat hyperlipidiemias and various diseases and disorders associated therewith. Other conditions also be ameliorated or avoided, such as high postprandial triglycerides or diet-related hypertriglyceridemia, cardiovascular risk associated with excessive triglycerides, and insulin resistance/glucose intolerance in overweight patients, those with diabetes or other glucose metabolic disorders such as Syndrome X and/or polycystic ovary disease.

Inhibitors of diacylglycerol O-acyltransferase 1 (DGAT-1) and uses thereof

The present invention provides for novel compounds of Formulas I and II and pharmaceutically acceptable salts and co-crystals thereof which have glucokinsae activator activity. The present invention further provides for pharmaceutical compositions comprising the same as well as methods of treating, preventing, delaying the time to onset or reducing the risk for the development or progression of a disease or condition for which one or more glucokinase activator is indicated, including Type 1 and 2 diabetes, impaired glucose tolerance, insulin resistance and hyperglycemia. The present invention also provides for processes of making the compounds of Formulas I and II, including salts and co-crystals thereof, and pharmaceutical compositions comprising the same.

Activators of glucokinase

The invention provides a chemical entity of Formula (I) wherein R, R, R, R, X, and Y have any of the values described herein, and compositions comprising such chemical entities; methods of making them; and their use in a wide range of methods, including metabolic and reaction kinetic studies; detection and imaging techniques; radioactive treatments; modulating and treating disorders mediated by GlyT1 activity; treating neurological disorders, CNS disorders, dementia, neurodegenerative diseases, and trauma-dependent losses of function; treating stroke, including cognitive and motor deficits during stroke rehabilitation; facilitating neuroprotection and neurorecovery; enhancing the efficiency of cognitive and motor training, including animal skill training; and treating other disorders, including pain and alcohol-dependence. 

Substituted azetidinyl compounds as GlyT1 inhibitors

The invention pertains to the use of compounds represented by the formula, Q-G-G-G-G-Z, where Q is  The compounds can be used as diacylglycerol O-acyltransferase 1 (DGAT-1) inhibitors to treat hyperlipidiemias and various diseases and disorders associated therewith. Other conditions also can be ameliorated or avoided, such as high postprandial triglycerides or diet-related hypertriglyceridemia, cardiovascular risk associated with excessive triglycerides, and insulin resistance/glucose intolerance in overweight patients, those with diabetes or other glucose metabolic disorders such as Syndrome X and/or polycystic ovary disease.

The invention provides a chemical entity of Formula (I), wherein R, R, R, R, Rand X have any of the values described herein, and compositions comprising such chemical entities; methods of making them; and their use in a wide range of methods, including metabolic and reaction kinetic studies; detection and imaging techniques; radioactive treatments; modulating and treating disorders mediated by GlyT1 activity; treating neurological disorders, CNS disorders, dementia, neurodegenerative diseases, and trauma-dependent losses of function; treating stroke, including cognitive and motor deficits during stroke rehabilitation; facilitating neuroprotection and neurorecovery; enhancing the efficiency of cognitive and motor training, including animal skill training; and treating other disorders, including pain and alcohol-dependence. 

Substituted 2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole and 4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridine compounds as GlyT1 inhibitors

The invention pertains to the use of fused bicyclo heterocyclic adducts of thiohydroxy pyridines or pyrimidines as diacylglycerol O-acyltransferase 1 (DGAT-1) inhibitors to treat hyperlipidiemias and various diseases and disorders associated therewith. Other conditions also can be ameliorated or avoided, such as high postprandial triglycerides or diet-related hypertriglyceridemia, cardiovascular risk associated with excessive triglycerides, and insulin resistance/glucose intolerance in overweight patients, those with diabetes or other glucose metabolic disorders such as Syndrome X and/or polycystic ovary disease.

The invention pertains to the use of fused bicyclo heterocyclic adducts of thiohdroxy pridines or primidines as diacylglycerol O-acyltransferase 1 DGAT-1 inhibitors to treat hyperlipidiemias and various diseases and disorders associated therewith. Other conditions also can be ameliorated or avoided, such as high postprandial triglycerides or diet-related hypertriglyceridemia, cardiovascular risk associated with excessive triglycerides, and insulin resistance/glucose intolerance in overweight patients, those with diabetes or other glucose metabolic disorders such as Syndrome X and/or polycystic ovary disease.

The present invention provides for novel compounds of Formulas I and II and pharmaceutically acceptable salts and co-crystals thereof which have glucokinase activator activity. The present invention further provides for pharmaceutical compositions comprising the same as well as methods of treating, preventing, delaying the time to onset or reducing the risk for the development or progression of a disease or condition for which one or more glucokinase activator is indicated, including Type 1 and 2 diabetes, impaired glucose tolerance, insulin resistance and hyperglycemia. The present invention also provides for processes of making the compounds of Formulas I and II, including salts and co-crystals thereof, and pharmaceutical compositions comprising the same.

Growing community of inventors

San Diego, CA, United States of America

Brett C Bookser