title: Enhanced selectivity profile of pyrazole-urea based DFG-out p38alpha inhibitors.
abstract: By targeting an extended region of the conventional 'DFG-out' pocket of p38alpha, while minimizing interactions with the specificity pocket and eliminating interactions with the adenine binding site, we are able to design and synthesize a number of pyrazole-urea based DFG-out p38alpha inhibitors with good potencies, and excellent selectivity.
authors.affiliation: Department of Chemistry, Cambridge South Laboratories, Pfizer Inc., 620 Memorial Drive, Cambridge, MA 02139, USA. hu.liu@pfizer.com
authors.forename: Hu
authors.initials: H
authors.lastname: Liu
authors.forename: Cyrille
authors.initials: C
authors.lastname: Kuhn
authors.forename: Frederic
authors.initials: F
authors.lastname: Feru
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Jacques
authors.forename: Gayatri D
authors.initials: GD
authors.lastname: Deshmukh
authors.forename: Ping
authors.initials: P
authors.lastname: Ye
authors.forename: Glen R
authors.initials: GR
authors.lastname: Rennie
authors.forename: Theresa
authors.initials: T
authors.lastname: Johnson
authors.forename: Steven
authors.initials: S
authors.lastname: Kazmirski
authors.forename: Simon
authors.initials: S
authors.lastname: Low
authors.forename: Rocco
authors.initials: R
authors.lastname: Coli
authors.forename: Yuan-hua
authors.initials: YH
authors.lastname: Ding
authors.forename: Alan C
authors.initials: AC
authors.lastname: Cheng
authors.forename: Haile
authors.initials: H
authors.lastname: Tecle
authors.forename: Jessie M
authors.initials: JM
authors.lastname: English
authors.forename: Robert
authors.initials: R
authors.lastname: Stanton
authors.forename: Joe C
authors.initials: JC
authors.lastname: Wu
mesh_terms: D000225:Adenine / Q000378:metabolism; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001665:Binding Sites; D006801:Humans; D008861:Microsomes / Q000378:metabolism; D048308:Mitogen-Activated Protein Kinase 14 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010671:Phenylurea Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D048308:Mitogen-Activated Protein Kinase 14; D000225:Adenine