Synthesis and testosterone 5α-reductase inhibitory activity of 11-substituted 4-aza-5α-androstane compounds

Article abstract of DOI:10.1016/0223-5234(96)85876-4

11α-Acetoxy-, 11α-hydroxy-, 11β-hydroxy-, and 11-oxo-4-aza-5α-androstane compounds with an N-diphenylmethylcarbamoyl moiety at the C-17 position were synthesized and their inhibitory activities against rat and human testosterone 5α-reductase were tested.Introduction of the 11α-acetoxy, 11α-hydroxy, 11β-hydroxy and 11-oxo groups into 4-aza-5α-androstane compounds reduced the inhibitory activity against rat and human 5α-reductase.The 11α-acetoxy-4-aza-5α-androstane compound in particular lost almost all its activity.However, several compounds with an 11β-hydroxy or 11-oxo group showed inhibitory activities comparable to MK-906.The 4-methyl-11β-hydroxy-4-aza-5α-androstane derivative showed the most potent inhibitory activity against rat and human enzyme, and was more active than MK-906. - Keywords: testosterone 5α-reductase inhibitor; synthesis; 4-aza-5α-androstane; steroid; prostatic hypertrophy