title: (1-Benzylindole-3-yl)alkanoic acids; novel nonsteroidal inhibitors of steroid 5 alpha-reductase (I).
abstract: A novel series of indole-3-alkanoic acids with varied N-benzyl substituents were synthesized as nonsteroidal inhibitors of steroid 5 alpha-reductase. The structure-activity relationships in this series were studied and the optimum carboxylic acid side chain was butyric acid. Furthermore, compounds with a diaryl substituent at the 1-position of the indole ring displayed strong inhibitory activities in vitro. Amongst these derivatives, 4-[1-(6,6-dimethyl-6H-dibenzo[b,d]pyran-3-yl)methylindol-3-yl]b uty ric acid (FR119680) displayed very high inhibitory activity in vitro against rat prostatic 5 alpha-reductase (IC50 = 5.0 nM) and good in vivo activity in the castrated young rat model.
authors.affiliation: Exploratory Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Tsukuba, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Sawada
authors.forename: H
authors.initials: H
authors.lastname: Hirai
authors.forename: P
authors.initials: P
authors.lastname: Golden
authors.forename: S
authors.initials: S
authors.lastname: Okada
authors.forename: Y
authors.initials: Y
authors.lastname: Sawada
authors.forename: M
authors.initials: M
authors.lastname: Hashimoto
authors.forename: H
authors.initials: H
authors.lastname: Tanaka
mesh_terms: D058891:5-alpha Reductase Inhibitors; D000818:Animals; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D011467:Prostate / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D058891:5-alpha Reductase Inhibitors; D002264:Carboxylic Acids; D004791:Enzyme Inhibitors; D007211:Indoles