Amgen Inc.

Matthew R Kaller

Christopher Michael Tegley

Thomas T Nguyen

Daniel B Horne

Wenge Zhong

Ning Chen

Holger Monenschein

Nobuko Nishimura

Ted Charles Judd

Xiaoqi Chen

Robert Michael Rzasa

Jeffrey Thomas Mihalic

Zhihua Ma

David John Kopecky

Zice Fu

Xiaodong Wang

Julie Anne Heath

Julio Cesar Medina

Jonathan B Houze

Xiaohui Du

Kevin Chao Yang

Alexander J Pickrell

Paul John Dransfield

Vatee Pattaropong

Richard V Connors

Jeffrey Deignan

Steven H Olson

Su-Jen Lai

Jian Jeffrey Chen

Lawrence R McGee

Jennifer Rebecca Allen

Qiufen May Xue

Scott S Harried

Mikkel V Debenedetto

Simon J Hedley

Vinod Francis Patel

Patricia Lopez

Michael J Frohn

Alan C Cheng

Gayathri Swaminath

Robert P Farrell

Frank Kayser

Stephen A Hitchcock

Paul E Harrington

James A Brown

Wen-Chen Yeh

Charles Kreiman

Bryant Yang

Michael D Croghan

Yinhong Chen

Aarif Yusuf Khakoo

Matthew M Weiss

Qingyian Liu

Yuan Cheng

Daniel La

Russell Graceffa

Lewis D Pennington

Andreas Reichelt

Essa Hu Harrington

Craig E Masse

Brian K Albrecht

Vu Van Ma

Michael D Bartberger

Kexue Li

Thomas Nixey

Randall W Hungate

Stuart C Chaffee

Kelvin C Sham

Vijay Keshav Gore

Mark Henry Norman

Brian Alan Lanman

Ana Elena Minatti

Nuria A Tamayo

Jonathan Dante Low

Sean P Brown

Wenyuan Qian

Markian Myroslaw Stec

James Richard Falsey

Shannon Rumfelt

Kaustav Biswas

Todd J Kohn

Yunxiao Li

Roxanne Kay Kunz

Guomin Yao

Joshua Taygerly

Kate Ashton

John Gordon Allen

Hui-Ling Wang

Thomas Dineen

Frank Chavez

Aaron C Siegmund

Chester Chenguang Yuan

Qi Huang

Matthew Paul Bourbeau

Kevin Yang

Lei Jia

David Joseph St Jean, Jr

Lars V Heumann

James S Harvey

The present invention relates to chemical compounds having a general formula (I), as defined herein, and synthetic intermediates thereof, which are capable of modulating KIF18A protein thereby influencing the process of cell cycle and cell proliferation to treat cancer and cancer-related diseases. The invention also includes pharmaceutical compositions, including the compounds, and methods of treating disease states related to the activity of KIF18A.

KIF18A inhibitors

Compounds of formula (I): as defined herein, and synthetic intermediates thereof, which are capable of modulating KIF18A protein thereby influencing the process of cell cycle and cell proliferation to treat cancer and cancer-related diseases. The invention also includes pharmaceutical compositions, including the compounds, and methods of treating disease states related to the activity of KIF18A.

Provided herein are myeloid cell leukemia 1 protein (Mcl-1) inhibitors, methods of their preparation, related pharmaceutical compositions, and methods of using the same. For example, provided herein are compounds of Formula I, or a stereoisomer thereof; and pharmaceutically acceptable salts thereof and pharmaceutical compositions containing the compounds. The compounds and compositions provided herein may be used, for example, in the treatment of diseases or conditions, such as cancer.

Compounds that inhibits MCL-1 protein

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 that inhibit Mcl-1 protein

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.

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Ventura, CA, United States of America

Matthew R Kaller