Discovery of 5-(1H-indol-5-yl)-1,3,4-thiadiazol-2-amines as potent PIM inhibitors

Bioorg Med Chem Lett. 2015 Feb 15;25(4):775-80. doi: 10.1016/j.bmcl.2014.12.091. Epub 2015 Jan 7.

Abstract

PIM kinases are a family of Ser/Thr kinases that are implicated in tumorigenesis. The discovery of a new class of PIM inhibitors, 5-(1H-indol-5-yl)-1,3,4-thiadiazol-2-amines, is discussed with optimized compounds showing excellent potency against all three PIM isoforms.

Keywords: 1,3,4-Thiadiazol-2-amines; Kinase inhibitors; Lead optimization; PIM kinases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemical synthesis
  • Amines / chemistry*
  • Amines / pharmacology*
  • Carbolines / chemical synthesis
  • Carbolines / chemistry
  • Carbolines / pharmacology
  • Cell Line, Tumor
  • Drug Discovery
  • Humans
  • Models, Molecular
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology*
  • Proto-Oncogene Proteins c-pim-1 / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-pim-1 / chemistry
  • Structure-Activity Relationship

Substances

  • Amines
  • Carbolines
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins c-pim-1
  • proto-oncogene proteins pim
  • diazoline