Studies on biotransformation of STS 557.

Transformation of STS 557 (17 alpha-cyanomethyl-17 beta-hydroxy-estra-4, 9-dien-3-one) by female rat liver microsomes demonstrates a lower transformation rate in comparison with the analogous compound without 9-double bond: 17 alpha-cyanomethyl-19-nortestosterone, and the basic substance: 19-nortestosterone. 17 alpha-Cyanomethyl-estra-1, 3, 5(10), 9(11)-tetraene-3, 17 beta-diol, 17 alpha-cyanomethyl-11 beta, 17 beta-dihydroxy-estra-4, 9-dien-3-one, and tentatively 17 alpha-cyanomethyl-6 alpha, 17 beta-dihydroxy-estra-4, 9-dien-3-one were identified as metabolites. Microbial model investigations with species known to hydrogenate the 4-double bond in 4-en-3-oxo steroids stereospecifically to 5 alpha H- or 5 beta H-metabolites indicate 5 alpha-hydrogenation to be prevented in STS 557 by the 9-double bond, whereas 5 beta-hydrogenation is not affected. Isolation and characterization of metabolites from beagle dog and rat urine following administration of 3H-STS 557 revealed the following pathways of biotransformation: Hydroxylation in different positions of the steroid molecule, aromatization of ring A, hydrogenation of a double bond, simultaneous hydroxylation and hydrogenation, and alteration of the 17 alpha-side chain with loss of nitrogen.