title: Application of a 3,3-diphenylpentane skeleton as a multi-template for creation of HMG-CoA reductase inhibitors.
abstract: Based on our hypothesis that the 3,3-diphenylpentane (DPP) skeleton is useful as a multi-template for creation of various biologically active compounds and acts as a steroid skeleton substitute, we designed and synthesized novel HMG-CoA reductase inhibitors with a DPP skeleton. Among them, sodium (E,3R,5S)-7-(2-(4-fluorophenyl)-4-(3-phenylpentan-3-yl)phenyl)-3,5-dihydroxy-hept-6-enoate showed potent HMG-CoA reductase-inhibitory activity comparable with that of clinically useful mevastatin.
authors.affiliation: Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-0032, Japan.
authors.forename: Shinnosuke
authors.initials: S
authors.lastname: Hosoda
authors.forename: Daisuke
authors.initials: D
authors.lastname: Matsuda
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tomoda
authors.forename: Mariko
authors.initials: M
authors.lastname: Hashimoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Aoyama
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Hashimoto
mesh_terms: D000728:Androgens / Q000737:chemistry; D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008148:Lovastatin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology; D008956:Models, Chemical; D015394:Molecular Structure; D010420:Pentanes / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: C524325:3,3-diphenylpentane; D000728:Androgens; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010420:Pentanes; C012258:mevastatin; D008148:Lovastatin