Application of a 3,3-diphenylpentane skeleton as a multi-template for creation of HMG-CoA reductase inhibitors

• Published in: Bioorganic & medicinal chemistry letters Vol. 19; no. 15; pp. 4228 - 4231
• Main Authors: Hosoda, Shinnosuke, Matsuda, Daisuke, Tomoda, Hiroshi, Hashimoto, Mariko, Aoyama, Hiroshi, Hashimoto, Yuichi
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 01.08.2009; Elsevier
• Subjects: 3,3-Diphenylpentane; Androgens - chemistry; Animals; Biological and medical sciences; Chemistry, Pharmaceutical - methods; DPP skeleton; Drug Design; General and cellular metabolism. Vitamins; HMG-CoA reductase; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - chemical synthesis; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology; Inhibitory Concentration 50; Lovastatin - analogs & derivatives; Lovastatin - chemical synthesis; Lovastatin - pharmacology; Medical sciences; Models, Chemical; Molecular Structure; Pentanes - chemical synthesis; Pentanes - pharmacology; Pharmacology. Drug treatments; Rats; Statin; Structure-Activity Relationship; Statin; 3,3-Diphenylpentane; DPP skeleton; HMG-CoA reductase; Diol; Enzyme; Aliphatic compound; Benzene derivatives; Enzyme inhibitor; Statin derivative; In vitro; Sodium Compounds; Structure activity relation; Biphenyl derivatives; Organic salt; Carboxylate; Hydroxymethylglutaryl-CoA reductase; Fluorine Organic compounds; Oxidoreductases; Secondary alcohol; Chemical synthesis; Ethylenic compound; Antilipemic agent
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2009.05.100

HMG-CoA reductase inhibitors with a 3,3-diphenylpentane skeleton were prepared. 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.