Novel series of 17β-pyrazolylandrosta-5,16-diene derivatives and their inhibitory effect on 17α-hydroxylase/C(17,20)-lyase.
The Claisen condensation of 3β-acetoxypregna-5,16-dien-20-one (1) with ethyl formate in the presence of sodium methylate in pyridine is known to lead to 3β-hydroxy-21-hydroxymethylidenepregna-5,16-dien-20-one (2) in good yield. With the methods described for the preparation of the saturated D-ring pyrazolyl series, the reactions of 2 with phenylhydrazine and its p-substituted derivatives in acetic acid resulted in mixtures of two steroidal regioisomers, the 1'-aryl-3'-pyrazolyl-(4a-e) and 1'-aryl-5'-pyrazolyl (5a-e) steroids. Compounds 4a-e are unknown in the literature. The arylpyrazoles produced were tested against 17α-hydroxylase/C(17,20)-lyase (P450(17α)) in vitro and neither of the regioisomers exerted efficient inhibition.
Department of Organic Chemistry, University of Szeged, Dóm tér 8, H-6720 Szeged, Hungary.
Zoltán
Z
Iványi
Nikoletta
N
Szabó
János
J
Wölfling
Mihály
M
Szécsi
János
J
Julesz
Gyula
G
Schneider
D000730:Androstadienes / Q000138:chemical synthesis*; D018931:Antineoplastic Agents, Hormonal / Q000138:chemical synthesis*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis*; D012996:Solutions; D013237:Stereoisomerism; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors / Q000737:chemistry*; D013329:Structure-Activity Relationship
D000730:Androstadienes; D018931:Antineoplastic Agents, Hormonal; D011720:Pyrazoles; D012996:Solutions; D013254:Steroid 17-alpha-Hydroxylase