title: Discovery and design of benzimidazolone based inhibitors of p38 MAP kinase.
abstract: A new class of benzimidazolone p38 MAP kinase inhibitors was discovered through high-throughput screening. X-ray crystallographic data of the lead molecule with p38 were used to design analogues with improved binding affinity and potency in a cell assay of LPS-induced TNFalpha production. Herein, we report the SAR of this new class of p38 inhibitors.
authors.affiliation: Department of Medicinal Chemistry, Boehringer Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, CT 06877, USA.
authors.forename: Abdelhakim
authors.initials: A
authors.lastname: Hammach
authors.forename: Antonio
authors.initials: A
authors.lastname: Barbosa
authors.forename: Faith Corbo
authors.initials: FC
authors.lastname: Gaenzler
authors.forename: Tazmeen
authors.initials: T
authors.lastname: Fadra
authors.forename: Daniel
authors.initials: D
authors.lastname: Goldberg
authors.forename: Ming-Hong
authors.initials: MH
authors.lastname: Hao
authors.forename: Rachel R
authors.initials: RR
authors.lastname: Kroe
authors.forename: Pingrong
authors.initials: P
authors.lastname: Liu
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Qian
authors.forename: Mark
authors.initials: M
authors.lastname: Ralph
authors.forename: Christopher
authors.initials: C
authors.lastname: Sarko
authors.forename: Fariba
authors.initials: F
authors.lastname: Soleymanzadeh
authors.forename: Neil
authors.initials: N
authors.lastname: Moss
mesh_terms: D001562:Benzimidazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D008958:Models, Molecular; D008968:Molecular Conformation; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry*
chemical_list: D001562:Benzimidazoles; D004791:Enzyme Inhibitors; C031000:benzimidazole; D048051:p38 Mitogen-Activated Protein Kinases