Discovery of N-substituted 7-azaindoles as Pan-PIM kinases inhibitors - Lead optimization - Part III

  • Bioorg Med Chem Lett. 2019 Feb 1;29(3):491-495. doi: 10.1016/j.bmcl.2018.12.015.
Claude Barberis  1 ,  James Pribish  2 ,  Elina Tserlin  2 ,  Alexandre Gross  2 ,  Mark Czekaj  2 ,  Matthieu Barragué  2 ,  Paul Erdman  2 ,  Sachin Maniar  2 ,  John Jiang  2 ,  Luke Fire  2 ,  Vinod Patel  2 ,  Andrew Hebert  3 ,  Mikhail Levit  3 ,  Anlai Wang  4 ,  Frank Sun  5 ,  Shih-Min A Huang  4
Affiliations
  • 1. IDD Medicinal Chemistry, Sanofi, 153 Second Avenue, Waltham MA 02451, United States. Electronic address: [email protected].
  • 2. IDD Medicinal Chemistry, Sanofi, 153 Second Avenue, Waltham MA 02451, United States.
  • 3. Oncology Biochemistry, Sanofi, 270 Albany Street, Cambridge MA 02139, United States.
  • 4. Oncology Biology, Sanofi, 270 Albany Street, Cambridge MA 02139, United States.
  • 5. Oncology Pharmacology, Sanofi, 640 Memorial Drive, Cambridge MA 02139, United States.
PMID: 30553737 DOI: 10.1016/j.bmcl.2018.12.015
Abstract

N-substituted azaindoles were discovered as promising pan-PIM inhibitors. Lead optimization is described en route toward the identification of a clinical candidate. Modulation of physico-chemical properties allowed to solve inherent hERG and permeability liabilities. Compound 17 showed tumor growth inhibition in a KG1 tumor-bearing mouse model.

Keywords
AML; Cancer; Lead; PK/PD; Pan-PIM kinases; Tumor growth inhibition.
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-183198
    PIM-IN-5
    PIM Kinase Inhibitor
    target: Pim
    Research Areas: Cancer