Synthesis and testosterone 5 alpha-reductase-inhibitory activity of 4-aza-5 alpha-androstane-17-carboxamide compound with an aromatic moiety in the C-17 carbamoyl group.
A series of 4-aza-5 alpha-androstane compounds with one or two aromatic moieties in the carbamoyl group at the C-17 position were synthesized and their inhibitory activities for rat and human prostatic testosterone 5 alpha-reductase were tested in vitro. Compounds with one aromatic moiety in the carbamoyl group showed high inhibitory activity for rat 5 alpha-reductase, but little for human prostatic 5 alpha-reductase. On the other hand, compounds with two aromatic moieties had potent inhibitory activities for both rat and human 5 alpha-reductase. The structural requirements for potent inhibition for both enzymes are discussed in relation to the spatial arrangement of the C-17 carbamoyl group.
Kurata
H
H
Medicinal Chemistry Research Laboratories, Sankyo Co., Ltd, Tokyo, Japan.
Ishibashi
K
K
Saito
S
S
Hamada
T
T
Horikoshi
H
H
Furukawa
Y
Y
Kojima
K
K
D058891:5-alpha Reductase Inhibitors; D000731:Androstanes / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D001372:Aza Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D008297:Male; D011467:Prostate / Q000201:enzymology; D051381:Rats; D013045:Species Specificity; D013329:Structure-Activity Relationship
D058891:5-alpha Reductase Inhibitors; D000731:Androstanes; D001372:Aza Compounds; D004791:Enzyme Inhibitors