Synthesis and biological activity of some amino-4'-substituted phenyl(pyridine)androst-4-en-3-one candidates

Abstract

A series of substituted androstanopyridine derivatives 2–5 were synthesized using 17-acetyl- 1,7,8,10,11,12,13,15,16,17-decahydro-10,13-dimethyl-2H-cyclopenta[a]-phenanthren-3(6H,9H,14H)-one (progesterone, 1) as a starting material. Reaction of 1a–1d with malononitrile and aldehydes in the presence of ammonium acetate gave the corresponding amino cyanopyridine derivatives 2a–2d. The same compounds 1a–1d reacted with cyanoacetamide and aldehydes in the presence of ammonium acetate to give a mixture of 3a–3d and 4a–4d, that was separated chromatographically. The reaction of compounds 1a–1d with ethyl cyanoacetate and aldehydes led to products 5a–5d. Structures of the newly synthesized compounds were elucidated by physical and spectral methods. The synthesized compounds were tested as 5α-reductase inhibitors and anti-prostate cancer agents.