title: New modifications to the area of pyrazole-naphthyl urea based p38 MAP kinase inhibitors that bind to the adenine/ATP site.
abstract: Discovery of the pyrazole-naphthyl urea class of p38 MAP kinase inhibitors typified by the clinical candidate BIRB 796 has encouraged further exploration of this particular scaffold. Modification to the part of the inhibitor that occupies the adenine/ATP binding site has resulted in a new way to obtain potent inhibitors that possess favorable in vitro and in vivo properties.
authors.affiliation: Department of Medicinal Chemistry, Boehringer Ingelheim Pharmaceutical, Inc., 900 Ridgebury Road, Ridgefield, CT 0687, USA. nmoss@rdg.boehringeringleheim.com
authors.forename: Neil
authors.initials: N
authors.lastname: Moss
authors.forename: Steffen
authors.initials: S
authors.lastname: Breitfelder
authors.forename: Raj
authors.initials: R
authors.lastname: Betageri
authors.forename: Pier F
authors.initials: PF
authors.lastname: Cirillo
authors.forename: Tazmeen
authors.initials: T
authors.lastname: Fadra
authors.forename: Eugene R
authors.initials: ER
authors.lastname: Hickey
authors.forename: Thomas
authors.initials: T
authors.lastname: Kirrane
authors.forename: Rachel R
authors.initials: RR
authors.lastname: Kroe
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Madwed
authors.forename: Richard M
authors.initials: RM
authors.lastname: Nelson
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Pargellis
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Qian
authors.forename: John
authors.initials: J
authors.lastname: Regan
authors.forename: Alan
authors.initials: A
authors.lastname: Swinamer
authors.forename: Carol
authors.initials: C
authors.lastname: Torcellini
mesh_terms: D000225:Adenine / Q000378:metabolism*; D001665:Binding Sites; D006801:Humans; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D047428:Protein Kinase Inhibitors; D048051:p38 Mitogen-Activated Protein Kinases; D000225:Adenine