2. Academic Validation
  3. Discovery of N-substituted 7-azaindoles as Pan-PIM kinases inhibitors - Lead optimization - Part III

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

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.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-183198
    PIM Kinase Inhibitor
    Pim