A novel class of inhibitors for human steroid 5alpha-reductase: synthesis and biological evaluation of indole derivatives. II.
In a search for novel nonsteroidal inhibitors of human prostatic 5alpha-reductase, we found a new series of indole derivatives that showed potent inhibitory activities for the human enzyme. Among them, 4-[(1-benzyl-1H-indol-5-yl)oxyl-3-chlorobenzoic acid (2d, YM-32906) showed more potent inhibitory activity than finasteride with an IC50 value of 0.44 nM. 3-Chloro-4-[[1-(4-phenoxybenzyl)-1H-indol-5-yl]oxy]benzoic acid (2m) showed inhibitory activities for both human and rat prostatic 5alpha-reductase with IC50 values of 2.1 and 73 nM, respectively. The synthesis and structure-activity relationships of these indole derivatives are presented.
Igarashi
S
S
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Tsukuba, Ibaraki, Japan.
Inami
H
H
Hara
H
H
Fujii
M
M
Koutoku
H
H
Oritani
H
H
Mase
T
T
D058891:5-alpha Reductase Inhibitors; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D011467:Prostate / Q000201:enzymology; D051381:Rats; D017208:Rats, Wistar; D013329:Structure-Activity Relationship
D058891:5-alpha Reductase Inhibitors; D004791:Enzyme Inhibitors; D007211:Indoles