Novel 17 Substituted Pregnadiene Derivatives as 5α-Reductase Inhibitors and Their Binding Affinity for the Androgen Receptor

概要

論文の詳細を見る
The in vitro antiandrogenic activity of four new progesterone derivatives : 4, 5, 6 and 7 (8 is a known compound) was determined. These compounds were evaluated as 5α-reductase inhibitors as well as by their capacity to bind to the androgen receptor in gonadectomized hamster prostate. The IC_<50> value was determined using increasing concentrations of 4, 5, 6, 7 and 8 in the presence of [^3H]T and the microsomal fraction of the hamster prostate containing the 5α-reductase enzyme. In this paper we also demonstrated the effect of increasing concentrations of the novel steroids upon [^3H]DHT binding to the androgen receptors from hamster prostate which produces competition for the androgen receptor sites. The in vitro studies showed that steroids 4, 5, 6, 7 and 8 had an inhibitory activity for the 5α-reductase with IC_<50> of : 4 (0.17μM), 5 (0.19μM), 6 (1μM), 7 (4.2μM), and 8 (2.7μM). On the other hand, the IC_<50> value for compounds 4, 5, 6, 7, 8 and DHT showed the following order of affinity for the androgen receptor : 6>7>5>DHT. Surprisingly compounds 4 and 8 did not bind to the androgen receptor. The overall data indicate that all synthesized compounds are inhibitors for the enzyme 5α-reductase present in the hamster prostate. In contrast, compounds 5, 6 and 7, which have a cyclohexyl group in the side chain showed a high affinity for the androgen receptor.
公益社団法人日本薬学会の論文
2004-05-01