2. Academic Validation
  3. Discovery of Orally Efficacious Phosphoinositide 3-Kinase δ Inhibitors with Improved Metabolic Stability

Discovery of Orally Efficacious Phosphoinositide 3-Kinase δ Inhibitors with Improved Metabolic Stability

  • J Med Chem. 2016 Oct 13;59(19):9228-9242. doi: 10.1021/acs.jmedchem.6b01169.
Leena Patel 1,  Jayaraman Chandrasekhar 1,  Jerry Evarts 1,  Kristen Forseth 1,  Aaron C Haran 1,  Carmen Ip 1,  Adam Kashishian 1,  Musong Kim 1,  David Koditek 1,  Sandy Koppenol 1,  Latesh Lad 1,  Eve-Irene Lepist 1,  Mary E McGrath 1,  Stephane Perreault 1,  Kamal D Puri 1,  Armando G Villaseñor 1,  John R Somoza 1,  Bart H Steiner 1,  Joseph Therrien 1,  Jennifer Treiberg 1,  Gary Phillips 1
Affiliations

Affiliation

  • 1 Gilead Sciences, Inc. , 333 Lakeside Drive, Foster City, California 94404, United States.
PMID: 27660855 DOI: 10.1021/acs.jmedchem.6b01169
Abstract

Aberrant signaling of phosphoinositide 3-kinase δ (PI3Kδ) has been implicated in numerous pathologies including hematological malignancies and rheumatoid arthritis. Described in this manuscript are the discovery, optimization, and in vivo evaluation of a novel series of pyridine-containing PI3Kδ inhibitors. This work led to the discovery of 35, a highly selective inhibitor of PI3Kδ which displays an excellent pharmacokinetic profile and is efficacious in a rodent model of rheumatoid arthritis.

Figures
Products