Synthesis of Triazolo- and Oxadiazolopiperazines by Gold(I)-Catalyzed Domino Cyclization: Application to the Design of a Mitogen Activated Protein (MAP) Kinase Inhibitor

Org Lett. 2019 Jan 18;21(2):373-377. doi: 10.1021/acs.orglett.8b03500. Epub 2018 Dec 31.

Abstract

An efficient method for the synthesis of [1,2,4]triazolo[4,3- a]piperazine derivatives was established based on a gold(I)-catalyzed domino cyclization of an amidrazone substrate with a terminal alkyne. The amidoxime congeners were converted into [1,2,4]oxadiazolo[4,5- a]piperazine derivatives in the presence of a gold catalyst. The oxadiazolopiperazine is a promising scaffold for the design of novel inhibitors against p38 mitogen activated protein kinase (MAP kinase).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aza Compounds / chemical synthesis*
  • Aza Compounds / chemistry
  • Aza Compounds / pharmacology
  • Catalysis
  • Cyclization
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Gold / chemistry*
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • Mitogen-Activated Protein Kinases / chemistry
  • Protein Kinase Inhibitors / chemical synthesis*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology
  • Triazoles / chemical synthesis*
  • Triazoles / chemistry
  • Triazoles / pharmacology

Substances

  • Aza Compounds
  • Enzyme Inhibitors
  • Protein Kinase Inhibitors
  • Triazoles
  • Gold
  • Mitogen-Activated Protein Kinases