Amgen Inc.

Gayathri Swaminath

Jonathan B Houze

Zhihua Ma

Paul John Dransfield

Vatee Pattaropong

Wen-Chen Yeh

Julie Anne Heath

Nobuko Nishimura

David John Kopecky

Zice Fu

Ning Chen

Xiaoqi Chen

Xiaodong Wang

Alan C Cheng

Mikkel V Debenedetto

Julio Cesar Medina

Xiaohui Du

Jeffrey Thomas Mihalic

Richard V Connors

Steven H Olson

Frank Kayser

Matthew R Kaller

Daniel B Horne

Jeffrey Deignan

Kevin Chao Yang

Ted Charles Judd

Lawrence R McGee

Anthony B Reed

Michael J Frohn

Brian Alan Lanman

Alexander J Pickrell

Leslie Phillip Miranda

Aaron C Siegmund

John Gordon Allen

Bryant Yang

Charles Kreiman

Wang Shen

Matthew Irvine Brown

Lewis D Pennington

Liusheng Zhu

Jian Luo

Ming Yu

Jiwen Liu

Sean P Brown

Thomas Nixey

Yingcai Wang

Kevin Yang

Su-Jen Lai

Aarif Yusuf Khakoo

Yinhong Chen

James S Harvey

Simon J Hedley

Robert P Farrell

Lars V Heumann

Jerry Ryan Holder

Malgorzata Wanska

Philip Dean Ramsden

Ankit Sharma

An-Rong Li

Todd J Kohn

Jie Zhang

Marc Vimolratana

David C Moebius

YuMei Xiong

Xian Yun Jiao

Yongli Su

SuJen Lai

Yong-Jae Kim

Margrit Schwarz

Jeffrey D Reagan

Qiong Cao

Daniel Lin

Li Yang

Matthew Brown

Sujen Lai

Ted C Judd

Jonathan Houze

Julio C Medina

Jeffrey T Mihalic

Lawrence R Mcgee

Jennifer Aral

The invention provides modified apelin polypeptides having increased stability, circulating half-life, and/or potency relative to the native apelin-13 polypeptide. Compositions comprising the modified apelin polypeptides and methods of using the polypeptides for treating cardiac disorders, such as heart failure, are also disclosed.

Apelin polypeptides

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: (I), (II) where the definitions of the variables are provided herein. 

Alkyl substituted triazole compounds as agonists of the APJ Receptor

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 may have use in treating cardiovascular and other conditions. Compounds of Formula I and Formula II have the following structures: (I) (II) where the definitions of the variables are provided herein. 

Cycloalkyl substituted triazole compounds as agonists of the APJ receptor

Triazole phenyl compounds as agonists of the APJ receptor

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: (I); (II). Intermediates (V) are also claimed. 

Triazole furan compounds as agonists of the APJ receptor

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 structures where the definitions of the variables are provided herein. 

Triazole pyridyl compounds as agonists of the APJ receptor

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 I and Formula II, pharmaceutically acceptable salts 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.

Heterocyclic triazole compounds as agonists of the APJ receptor

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Brisbane, CA, United States of America

Gayathri Swaminath