Picard Franck, Hartmann Rolf W
8.5 Pharmaceutical and Medicinal Chemistry, Saarland University, Saarbrücken, Germany.
J Enzyme Inhib Med Chem. 2002 Jun;17(3):187-96. doi: 10.1080/1475636021000003156.
In search of non-steroidal inhibitors of human prostatic 5alpha-reductase, we recently described N-substituted 4'-biphenyl-4-carboxylic acids. Here, we report the optimisation of this series of compounds by increasing the conformational flexibility using an ether linker between the steroidal A-C ring mimetics. Ten new compounds were synthesised and tested against human and rat isozymes 1 and 2. The substances showed a broad range of activity from 36% inhibition at a concentration of 10 microM to an IC50 value of 60 nM for compounds 22 and 29 respectively. The most potent compound 26 showed an IC50 value improved by a factor of 5 from 1.9 microM to 0.38 microM in comparison with the parent biphenyl compound 15.
