Discovery of orteronel (TAK-700), a naphthylmethylimidazole derivative, as a highly selective 17, 20-lyase inhibitor with potential utility in the treatment of prostate …
T Kaku, T Hitaka, A Ojida, N Matsunaga… - Bioorganic & medicinal …, 2011 - Elsevier
T Kaku, T Hitaka, A Ojida, N Matsunaga, M Adachi, T Tanaka, T Hara, M Yamaoka…
Bioorganic & medicinal chemistry, 2011•ElsevierA novel naphthylmethylimidazole derivative 1 and its related compounds were identified as
17, 20-lyase inhibitors. Based on the structure–activity relationship around the naphthalene
scaffold and the results of a docking study of 1a in the homology model of 17, 20-lyase, the
6, 7-dihydro-5H-pyrrolo [1, 2-c] imidazole derivative (+)-3c was synthesized and identified as
a potent and highly selective 17, 20-lyase inhibitor. Biological evaluation of (+)-3c at a dose
of 1mg/kg in a male monkey model revealed marked reductions in both serum testosterone …
17, 20-lyase inhibitors. Based on the structure–activity relationship around the naphthalene
scaffold and the results of a docking study of 1a in the homology model of 17, 20-lyase, the
6, 7-dihydro-5H-pyrrolo [1, 2-c] imidazole derivative (+)-3c was synthesized and identified as
a potent and highly selective 17, 20-lyase inhibitor. Biological evaluation of (+)-3c at a dose
of 1mg/kg in a male monkey model revealed marked reductions in both serum testosterone …
A novel naphthylmethylimidazole derivative 1 and its related compounds were identified as 17,20-lyase inhibitors. Based on the structure–activity relationship around the naphthalene scaffold and the results of a docking study of 1a in the homology model of 17,20-lyase, the 6,7-dihydro-5H-pyrrolo[1,2-c]imidazole derivative (+)-3c was synthesized and identified as a potent and highly selective 17,20-lyase inhibitor. Biological evaluation of (+)-3c at a dose of 1mg/kg in a male monkey model revealed marked reductions in both serum testosterone and dehydroepiandrosterone concentrations. Therefore, (+)-3c (termed orteronel [TAK-700]) was selected as a candidate for clinical evaluation and is currently in phase III clinical trials for the treatment of castration-resistant prostate cancer.
Elsevier