Steroselective synthesis of some steroidal oxazolines, as novel potential inhibitors of 17alpha-hydroxylase-C17,20-lyase.
17beta-Oxazolinyl steroids 7a-g and 8a-g were synthesized. The Lewis acid-catalysed reactions of (20R)-3beta-acetoxy-21-azidomethyl-20-hydroxypregn-5-ene with substituted aromatic aldehydes led to the formation of 3beta-acetoxyandrost-5-enes substituted in position 17beta with oxazolinyl residues (7a-g). Oppenauer oxidation of the 3beta-hydroxy-exo-heterocyclic steroids yielded the corresponding Delta(4)-3-ketosteroids. The inhibitory effects (IC(50)) of both 3-hydroxy compounds 7a-g and their Delta(4)-3-keto counterparts 8a-g on rat testicular C(17,20)-lyase were investigated with an in vitro radioligand incubation technique. The 3-chlorophenyl- (8d), and the 4-bromophenyl-17beta-(2-oxazolin-5-yl)androst-4-en-3-one derivatives (8f) were found to be modest inhibitors (IC(50)=4.8 and 5.0 microM, respectively).
Ondré
Dóra
D
Department of Organic Chemistry, University of Szeged, Dóm tér 8, Szeged, Hungary.
Wölfling
János
J
Tóth
István
I
Szécsi
Mihály
M
Julesz
János
J
Schneider
Gyula
G
D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008190:Lyases / Q000037:antagonists & inhibitors*; D008297:Male; D010080:Oxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013237:Stereoisomerism; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors*; D013256:Steroids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013737:Testis / Q000187:drug effects / Q000201:enzymology
D004791:Enzyme Inhibitors; D010080:Oxazoles; D013256:Steroids; D013254:Steroid 17-alpha-Hydroxylase; D008190:Lyases