2. Academic Validation
  3. Discovery and in vivo evaluation of (S)-N-(1-(7-fluoro-2-(pyridin-2-yl)quinolin-3-yl)ethyl)-9H-purin-6-amine (AMG319) and related PI3Kδ inhibitors for inflammation and autoimmune disease

Discovery and in vivo evaluation of (S)-N-(1-(7-fluoro-2-(pyridin-2-yl)quinolin-3-yl)ethyl)-9H-purin-6-amine (AMG319) and related PI3Kδ inhibitors for inflammation and autoimmune disease

  • J Med Chem. 2015 Jan 8;58(1):480-511. doi: 10.1021/jm501624r.
Timothy D Cushing 1,  Xiaolin Hao,  Youngsook Shin,  Kristin Andrews,  Matthew Brown,  Mario Cardozo,  Yi Chen,  Jason Duquette,  Ben Fisher,  Felix Gonzalez-Lopez de Turiso,  Xiao He,  Kirk R Henne,  Yi-Ling Hu,  Randall Hungate,  Michael G Johnson,  Ron C Kelly,  Brian Lucas,  John D McCarter,  Lawrence R McGee,  Julio C Medina,  Tisha San Miguel,  Deanna Mohn,  Vatee Pattaropong,  Liping H Pettus,  Andreas Reichelt,  Robert M Rzasa,  Jennifer Seganish,  Andrew S Tasker,  Robert C Wahl,  Sharon Wannberg,  Douglas A Whittington,  John Whoriskey,  Gang Yu,  Leeanne Zalameda,  Dawei Zhang,  Daniela P Metz
Affiliations

Affiliation

  • 1 Department of Therapeutic Discovery, ‡Department of Pharmacokinetics and Drug Metabolism, and §Department of Pharmaceutics Research and Development, Amgen Inc. , 1120 Veterans Boulevard, South San Francisco, California 94080, United States.
PMID: 25469863 DOI: 10.1021/jm501624r
Abstract

The development and optimization of a series of quinolinylpurines as potent and selective PI3Kδ kinase inhibitors with excellent physicochemical properties are described. This medicinal chemistry effort led to the identification of 1 (AMG319), a compound with an IC50 of 16 nM in a human whole blood assay (HWB), excellent selectivity over a large panel of protein kinases, and a high level of in vivo efficacy as measured by two rodent disease models of inflammation.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-12948
    98.27%, PI3Kδ Inhibitor