Inhibition of steroid C17(20) lyase with C-17-heteroaryl steroids

Steroids bearing a heteroaromatic substituent at C-17 were designed as inhibitors of C17(20) lyase. The thiazoles, furans, and thiophenes appended to the steroid nucleus were positioned on the alpha-face and the beta-face of the steroid, and conjugated with a 16,17-olefin, to test their ability to c...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry 1996-09, Vol.4 (9), p.1411-1420
Main Authors: Burkhart, J P, Gates, C A, Laughlin, M E, Resvick, R J, Peet, N P
Format: Article
Language:English
Subjects:
Animals
Enzyme Inhibitors - chemistry
Macaca fascicularis
Male
Steroid 17-alpha-Hydroxylase - antagonists & inhibitors
Steroids - chemistry
Testis - enzymology
Thiazoles - chemistry
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Summary:Steroids bearing a heteroaromatic substituent at C-17 were designed as inhibitors of C17(20) lyase. The thiazoles, furans, and thiophenes appended to the steroid nucleus were positioned on the alpha-face and the beta-face of the steroid, and conjugated with a 16,17-olefin, to test their ability to coordinate the heme iron of the P450 enzyme complex. The position of the heterocycle with respect to the steroid skeleton was determined to be important for optimum affinity and, in general, compounds with the heterocycle attached to a trigonal center at C-17, had the best affinity for C17(20) lyase. Simple molecular models were used to compare the three types of heterocyclic-substituted steroids.
ISSN:0968-0896
DOI:10.1016/0968-0896(96)00135-6