title: Potent and selective thiophene urea-templated inhibitors of S6K.
abstract: S6K1 (p70 S6 kinase-1) is thought to play a critical role in the development of obesity and insulin resistance, thus making it an attractive target in developing medicines for the treatment of these disorders. We describe a novel thiophene urea class of S6K inhibitors. The lead matter for the development of these inhibitors came from mining the literature for reports of weak off-target S6K activity. These optimized inhibitors exhibit good potency and excellent selectivity for S6K over a panel of 43 kinases.
authors.affiliation: Cambridge South Laboratory, Pfizer Inc., 620 Memorial Drive, Cambridge, MA 02139, United States.
authors.forename: Ping
authors.initials: P
authors.lastname: Ye
authors.forename: Cyrille
authors.initials: C
authors.lastname: Kuhn
authors.forename: Miret
authors.initials: M
authors.lastname: Juan
authors.forename: Rahul
authors.initials: R
authors.lastname: Sharma
authors.forename: Brendan
authors.initials: B
authors.lastname: Connolly
authors.forename: Gordon
authors.initials: G
authors.lastname: Alton
authors.forename: Hu
authors.initials: H
authors.lastname: Liu
authors.forename: Robert
authors.initials: R
authors.lastname: Stanton
authors.forename: Natasha M
authors.initials: NM
authors.lastname: Kablaoui
mesh_terms: D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013876:Thiophenes / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D014508:Urea / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
chemical_list: D047428:Protein Kinase Inhibitors; D013876:Thiophenes; D014508:Urea; D038762:Ribosomal Protein S6 Kinases, 70-kDa