Role of the hydrogen bonding heteroatom-Lys53 interaction between the p38alpha mitogen-activated protein (MAP) kinase and pyridinyl-substituted 5-membered heterocyclic ring inhibitors

J Med Chem. 2009 Apr 23;52(8):2613-7. doi: 10.1021/jm801467h.

Abstract

In the framework of investigating the role of heteroatoms in pyridinyl-substituted 5-membered (hetero)cycles as potential p38alpha MAP kinase inhibitor scaffolds, cyclopentene, pyrrole, furan, and imidazole analogues were synthesized and tested with respect to their ability to inhibit p38alpha MAP kinase. The vicinal pyridine/4-fluorophenyl pharmacophore was conserved, such as in the prototypical imidazole inhibitor SB203580. The strength of the HB interaction was calculated and compared to the biological data.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cyclopentanes / chemical synthesis
  • Cyclopentanes / chemistry
  • Furans / chemical synthesis
  • Furans / chemistry
  • Hydrogen Bonding
  • Imidazoles / chemical synthesis
  • Imidazoles / chemistry
  • Mitogen-Activated Protein Kinase 14 / antagonists & inhibitors*
  • Mitogen-Activated Protein Kinase 14 / chemistry
  • Pyridines / chemical synthesis*
  • Pyridines / chemistry
  • Pyrroles / chemical synthesis
  • Pyrroles / chemistry
  • Structure-Activity Relationship
  • Thermodynamics

Substances

  • Cyclopentanes
  • Furans
  • Imidazoles
  • Pyridines
  • Pyrroles
  • Mitogen-Activated Protein Kinase 14