Author/Authors :
Kazutaka Tachibana، نويسنده , , Ikuhiro Imaoka، نويسنده , , Hitoshi Yoshino، نويسنده , , Nobuaki Kato، نويسنده , , Mitsuaki Nakamura، نويسنده , , Masateru Ohta، نويسنده , , Hiromitsu Kawata، نويسنده , , Kenji Taniguchi and Kenichi Nakashi ، نويسنده , , Nobuyuki Ishikura، نويسنده , , Masahiro Nagamuta، نويسنده , , Etsuro Onuma، نويسنده , , Haruhiko Sato، نويسنده ,
Abstract :
Lead optimization of CH4892280 (4), an androgen receptor (AR) pure antagonist, was investigated. Compounds 6 and 7, which have a carboxylic acid at the end of the side chain at the position 7α of dihydrotestosterone (DHT), showed partial agonistic activities in reporter gene assay (RGA). Conversion of the steroidal core structure to 17α-methyltestosterone gave compound 14, which showed weak pure antagonistic activity. Optimization of the side chain by the insertion of a phenyl ring led to compounds 22 and 28–30, which showed pure antagonistic activities at submicromolar concentrations. The structure–activity relationships were clarified.
