Design, synthesis, structure-activity relationships, and docking studies of pyrazole-containing derivatives as a novel series of potent glucagon receptor antagonists

Bioorg Med Chem. 2016 Jun 15;24(12):2852-63. doi: 10.1016/j.bmc.2016.04.053. Epub 2016 Apr 26.

Abstract

Glucagon receptor antagonists possess a great potential for treatment of type 2 diabetes mellitus. A series of pyrazole-containing derivatives were designed, synthesized and evaluated by biological assays as glucagon receptor antagonists. Most of the compounds exhibited good in vitro efficacy. Two of them, compounds 17f and 17k, displayed relatively potent antagonist effects on glucagon receptors with IC50 values of 3.9 and 3.6μM, respectively. The possible binding modes of 17f and 17k with the cognate receptor were explored by molecular docking simulation.

Keywords: Antagonist; Glucagon receptor; Molecular docking; Pyrazole; Type 2 diabetes mellitus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / metabolism
  • Drug Design
  • Humans
  • Molecular Docking Simulation
  • Pyrazoles / chemical synthesis
  • Pyrazoles / chemistry*
  • Pyrazoles / pharmacology*
  • Receptors, Glucagon / antagonists & inhibitors*
  • Receptors, Glucagon / metabolism
  • Structure-Activity Relationship

Substances

  • Pyrazoles
  • Receptors, Glucagon