Amgen Inc.

Teijin Pharma Limited

Daniel B Horne

Matthew R Kaller

Ning Chen

Nobuko Nishimura

Xiaoqi Chen

Holger Monenschein

Thomas T Nguyen

Jeffrey Thomas Mihalic

Zhihua Ma

David John Kopecky

Zice Fu

Ted Charles Judd

Xiaodong Wang

Julie Anne Heath

Julio Cesar Medina

Jonathan B Houze

Xiaohui Du

Kevin Chao Yang

Paul John Dransfield

Vatee Pattaropong

Richard V Connors

Jeffrey Deignan

Steven H Olson

Su-Jen Lai

Lawrence R McGee

Mikkel V Debenedetto

Simon J Hedley

Wenge Zhong

Alan C Cheng

Gayathri Swaminath

Robert P Farrell

Frank Kayser

Scott S Harried

Wen-Chen Yeh

Aarif Yusuf Khakoo

Yinhong Chen

Jian Jeffrey Chen

Matthew M Weiss

Vinod Francis Patel

Stephen A Hitchcock

Patricia Lopez

Qiufen May Xue

Vu Van Ma

Charles Kreiman

Bryant Yang

Michael D Croghan

Vijay Keshav Gore

Jennifer Rebecca Allen

Robert Michael Rzasa

James A Brown

Thomas Dineen

Andreas Reichelt

Essa Hu Harrington

Qingyian Liu

Yuan Cheng

Michael D Bartberger

Russell Graceffa

Lewis D Pennington

Kaustav Biswas

Kelvin C Sham

Craig E Masse

Brian K Albrecht

Mark Henry Norman

Ryan D White

Michael J Frohn

Nuria A Tamayo

Alexander J Pickrell

Angel Guzman-Perez

Laurie B Schenkel

Daniel La

Chester Chenguang Yuan

Paul E Harrington

James Richard Falsey

Kevin Yang

Thomas Nixey

Randall W Hungate

Shannon Rumfelt

Stuart C Chaffee

Lars V Heumann

David Joseph St Jean, Jr

James S Harvey

Roxanne Kay Kunz

Zihao Hua

Yunxin Y Bo

Frank Chavez

Guomin Yao

John Stellwagen

Nagasree Chakka

Benjamin Charles Milgram

Frenel Fils De Morin

Jane Panteleev

Ryan Brown

Malgorzata Wanska

Daniel C H Lin

Hua Gao

Wei Zhao

Dean Hickman

Matthew Walker

The present invention relates to inhibitors of Transient Receptor Potential Channel 6 (TRPC6) protein activity. The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof, pharmaceutical compositions comprising a compound of the invention, a method for manufacturing compounds of the invention and therapeutic uses thereof. 

Benzimidazole derivatives and their uses

Compounds of Formula (I) and Formula (II), pharmaceutically acceptable salt thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and may have use in treating cardiovascular and other conditions. Compounds of Formula I and Formula II have the following structures: where the definitions of the variables are provided herein.

Heteroaryl-substituted triazoles as APJ receptor agonists

Compounds of Formula I and Formula II, pharmaceutically acceptable salt thereof, stereoisomers of any of the foregoing, or mixtures thereof are agonists of the APJ Receptor and have use in treating cardiovascular and other conditions. Compounds of Formula I and Formula II have the following structures: where the definitions of the variables are provided herein.

Triazole agonists of the APJ receptor

Methods of treating heart failure include administering to a subject having heart failure an effective amount of a triazole compound that is an agonist of the APJ receptor, a pharmaceutically acceptable salt of the compound, or a mixture thereof. Compounds particularly useful in such methods are provided herein.

Methods of treating heart failure

Compounds of Formula VII, salts thereof, tautomers thereof, and salts of the tautomers are useful intermediates in the synthesis of agonists of the APJ Receptor. Compounds of Formula VII have the following structure: where the definitions of the variables are provided herein.

Intermediates for preparing triazole agonists of the APJ receptor

Methods of preparing compounds of Formula VI, salts thereof, tautomers thereof, or salts of the tautomers include cyclizing compounds of Formula V, salts thereof, tautomers thereof, or salts of the tautomers. Compounds of Formula VI and Formula V have the following structures: where the definitions of the variables are provided herein.

Methods for preparing triazole agonists of the APJ receptor

Compounds of Formula V, salts thereof, tautomers thereof, and salts of the tautomers are useful intermediates in the synthesis of agonists of the APJ Receptor. Compounds of Formula V have the following structure: where the definitions of the variables are provided herein.

Heteroaryloxyheterocyclyl compounds, and compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, non-insulin dependent diabetes, schizophrenia, Huntington's Disease, bipolar disorder, obsessive-compulsive disorder, and the like.

Heteroaryloxyheterocyclyl compounds as PDE10 inhibitors

Compounds of Formula I are useful as antagonists of TRPM8. Such compounds are useful in treating a number of TRPM8 mediated disorders and conditions and may be used to prepare medicaments and pharmaceutical compositions useful for treating such disorders and conditions. Examples of such disorders include, but are not limited to, migraines and neuropathic pain. Compounds of Formula I have the following structure: where the definitions of the variables are provided herein.

TRPM8 antagonists and their use in treatments

Chroman compounds and derivatives of Formula I are useful inhibitors of TRPM8. Such compounds are useful in treating a number of TRPM8 mediated disorders and conditions and may be used to prepare medicaments and pharmaceutical compositions useful for treating such disorders and conditions. Examples of such disorders include, but are not limited to, migraines and neuropathic pain. Compounds of Formula I have the following structure: where the definitions of the variables are provided herein.

Chroman derivatives as TRPM8 inhibitors

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Natick, MA, United States of America

Daniel B Horne