S. Igarashi et al., A novel class of inhibitors for human steroid 5 alpha-reductase: Phenoxybenzoic acid derivatives. I, CHEM PHARM, 47(8), 1999, pp. 1073-1080
In a search for novel nonsteroidal inhibitors of human prostatic 5 alpha-re
ductase, we found a new series of phenoxybenzoic acid derivatives to be pot
ent human prostatic 5 alpha-reductase inhibitors. Among them, 4-(biphenyl-4
-yloxy)benzoic acid derivatives (2n, YM-31758), 2o and 2s showed more poten
t inhibitory activities than finasteride with IC50 values of 0.87, 0.67 and
0.56 nM, respectively. The optimized structures for the phenoxybenzoic aci
d derivatives 2d-2i were calculated by molecular modeling analysis, and the
favorable distance between the carbon of the carboxyl group and the centro
id of the phenyl group (benzene ring C) was found to be in the 9-11 Angstro
m range.