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

Bassam Abu Thaher; Pierre Koch; Verena Schattel; Stefan Laufer

doi:10.1021/jm801467h

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.

Authors

Bassam Abu Thaher¹, Pierre Koch, Verena Schattel, Stefan Laufer

Affiliation

¹ Faculty of Science, Chemistry Department, Islamic University of Gaza, Gaza Strip, Palestine, Germany.

PMID: 19301816
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