A novel class of inhibitors for human and rat steroid 5alpha-reductases: synthesis and biological evaluation of indoline and aniline derivatives. III.
While searching for novel nonsteroidal inhibitors of human and rat prostatic 5alpha-reductases, we found a new series of indoline and aniline derivatives that showed potent inhibitory activities for both enzymes. Among them, 3-chloro-4-¿[1-(4-phenoxybenzyl)indolin-5-yl]oxylbenzoic acid (2e, YM-36117) showed a more potent inhibitory activity for the human enzyme than ONO-3805 with an IC50 value of 5.3 nM and a reduced rat prostatic dihydrotestosterone (DHT) concentration by oral administration. The synthesis and the structure-activity relationships of these indoline and aniline derivatives are presented.
Igarashi
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S
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co, Ltd, Tsukuba, Ibaraki, Japan. igara@yamanouchi.co.jp
Inami
H
H
Hara
H
H
Koutoku
H
H
Oritani
H
H
Mase
T
T
D058891:5-alpha Reductase Inhibitors; D000814:Aniline Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology; D008297:Male; D011467:Prostate / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar
D058891:5-alpha Reductase Inhibitors; D000814:Aniline Compounds; D004791:Enzyme Inhibitors; D007211:Indoles