Synthesis of N-substituted piperidine-4-(benzylidene-4-carboxylic acids) and evaluation as inhibitors of steroid-5α-reductase type 1 and 2 Original Research Article

The synthesis of N-substituted piperidine-4-(benzylidene-4-carboxylic acids) is described [benzoyl (), benzyl (), adamantanoyl (), cyclohexanoyl (), cyclohexylacetyl (), diphenylacetyl (), dicyclohexylacetyl (), 2-propylpentanoyl (), diphenylcarbamoyl (), trimethylacetyl (), 3,3-dimethylacryloyl (), dicyclohexylacetyl derivative of the benzyl compound ()]. Compounds were tested for inhibitory activity toward 5α-reductase isozymes 1 and 2 in human and rat. The test compounds inhibited 5α-reductase, showing a broad range of inhibitory potencies. In rat, compounds (IC50=3.44 and 0.37 μM for type 1 and 2, respectively) and (IC50=0.54 and 0.69 μM for type 1 and 2, respectively) displayed the best inhibition toward both isozymes. Compound showed a strong inhibition toward type 2 human and rat enzyme (IC50=60 and 80 nM) but only a moderate activity versus type 1 enzyme (IC50 approximately 10 μM for rat and human enzyme). In vivo, selected compounds reduced prostate weights in castrated testosterone treated rats.