Synthesis of regioisomeric 17beta-N-phenylpyrazolyl steroid derivatives and their inhibitory effect on 17alpha-hydroxylase/C(17,20)-lyase.
The reaction of 3beta-hydroxy-21-hydroxymethylidenepregn-5-en-3beta-ol-20-one (1) with phenylhydrazine (2a) affords two regioisomers, 17beta-(1-phenyl-3-pyrazolyl)androst-3-en-3beta-ol (5a) and 17beta-(1-phenyl-5-pyrazolyl)androst-5-en-3beta-ol (6a). The direction of the ring-closure reactions of 1 with p-substituted phenylhydrazines (2b-e) depends strongly on the electronic features of the substituents. Oppenauer oxidation of 3beta-hydroxy-17beta-exo-heterocyclic steroids 5a-e and 6a-e yielded the corresponding Delta(4)-3-ketosteroids 9a-e and 10a-e. The inhibitory effects (IC(50)) of these compounds on rat testicular C(17,20)-lyase were investigated by means of an in vitro radioligand incubation technique.
Iványi
Zoltán
Z
Department of Organic Chemistry, University of Szeged, Dóm tér 8, H-6720 Szeged, Hungary.
Wölfling
János
J
Görbe
Tamás
T
Szécsi
Mihály
M
Wittmann
Tibor
T
Schneider
Gyula
G
D000818:Animals; D006834:Hydrazines / Q000737:chemistry; D008297:Male; D015394:Molecular Structure; D051381:Rats; D013237:Stereoisomerism; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013256:Steroids / Q000138:chemical synthesis; D013737:Testis / Q000201:enzymology
D006834:Hydrazines; D013256:Steroids; C029424:hydrazine; D013254:Steroid 17-alpha-Hydroxylase