Microwave-assisted synthesis of N-pyrazole ureas and the p38alpha inhibitor BIRB 796 for study into accelerated cell ageing

Org Biomol Chem. 2006 Nov 21;4(22):4158-64. doi: 10.1039/b611493h.

Abstract

Microwave irradiation of substituted hydrazines and beta-ketoesters gives 5-aminopyrazoles in excellent yield, which can be transformed to the corresponding N-carbonyl derivatives by treatment with an isocyanate or chloroformate. Derivatization of 4-nitronaphth-1-ol using predominantly microwave heating methods and reaction with an N-pyrazole carbamate provides a rapid route to the N-pyrazole urea BIRB 796 in high purity, as a potent and selective inhibitor of p38alpha mitogen-activated protein kinase for the study of accelerated ageing in Werner syndrome cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cellular Senescence / drug effects*
  • Enzyme Inhibitors* / chemical synthesis
  • Enzyme Inhibitors* / pharmacology
  • Enzyme Inhibitors* / radiation effects
  • Humans
  • Microwaves*
  • Mitogen-Activated Protein Kinase 14 / antagonists & inhibitors*
  • Molecular Structure
  • Naphthalenes* / chemical synthesis
  • Naphthalenes* / pharmacology
  • Naphthalenes* / radiation effects
  • Pyrazoles* / chemical synthesis
  • Pyrazoles* / pharmacology
  • Pyrazoles* / radiation effects
  • Stereoisomerism
  • Structure-Activity Relationship
  • Werner Syndrome / enzymology

Substances

  • Enzyme Inhibitors
  • Naphthalenes
  • Pyrazoles
  • Mitogen-Activated Protein Kinase 14
  • doramapimod