(1-Benzylindole-3-yl)alkanoic acids; novel nonsteroidal inhibitors of steroid 5 alpha-reductase (I).
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.
Sawada
K
K
Exploratory Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Tsukuba, Japan.
Hirai
H
H
Golden
P
P
Okada
S
S
Sawada
Y
Y
Hashimoto
M
M
Tanaka
H
H
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
D058891:5-alpha Reductase Inhibitors; D002264:Carboxylic Acids; D004791:Enzyme Inhibitors; D007211:Indoles