Synthesis and 5α-reductase inhibitory activity of C₂₁ steroids having 1,4-diene or 4,6-diene 20-ones and 4-azasteroid 20-oximes.
The synthesis and evaluation of 5α-reductase inhibitory activity of some 4-azasteroid-20-ones and 20-oximes and 3β-hydroxy-, 3β-acetoxy-, or epoxy-substituted C₂₁ steroidal 20-ones and 20-oximes having double bonds in the A and/or B ring are described. Inhibitory activity of synthesized compounds was assessed using 5α-reductase enzyme and [1,2,6,7-³H]testosterone as substrate. All synthesized compounds were less active than finasteride (IC₅₀: 1.2 nM). Three 4-azasteroid-2-oximes (compounds 4, 6 and 8) showed good inhibitory activity (IC₅₀: 26, 10 and 11 nM) and were more active than corresponding 4-azasteroid 20-ones (compounds 3, 5 and 7). 3β-Hydroxy-, 3β-acetoxy- and 1α,2α-, 5α,6α- or 6α,7α-epoxysteroid-20-one and -20-oxime derivatives having double bonds in the A and/or B ring showed no inhibition of 5α-reductase enzyme.
College of Pharmacy, Catholic University of Daegu, Hayang 712-702, Korea.
Sujeong
S
Kim
Yong-ung
YU
Kim
Eunsook
E
Ma
D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000737:chemistry; D058891:5-alpha Reductase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D015195:Drug Design; D006801:Humans; D010091:Oximes / Q000138:chemical synthesis* / Q000737:chemistry; D011278:Pregnanes / Q000138:chemical synthesis* / Q000737:chemistry
D058891:5-alpha Reductase Inhibitors; D010091:Oximes; D011278:Pregnanes; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase