Details

Autor(en) / Beteiligte

• Tachibana, Kazutaka
• Imaoka, Ikuhiro
• Yoshino, Hitoshi
• Emura, Takashi
• Kodama, Hirohumi
• Furuta, Yoshiyuki
• Kato, Nobuaki
• Nakamura, Mitsuaki
• Ohta, Masateru
• Taniguchi, Kenji
• Ishikura, Nobuyuki
• Nagamuta, Masahiro
• Onuma, Etsuro
• Sato, Haruhiko

Titel

Discovery of 7α-substituted dihydrotestosterones as androgen receptor pure antagonists and their structure–activity relationships

Ist Teil von

• Bioorganic & medicinal chemistry, 2007, Vol.15 (1), p.174-185

Ort / Verlag

Elsevier Ltd

Erscheinungsjahr

2007

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• CH4892280 and others were synthesized and showed AR antagonistic activities without agonistic activities in reporter gene assay. SARs of the compounds are also presented in this report. A series of 7α-substituted dihydrotestosterone derivatives were synthesized and evaluated for androgen receptor (AR) pure antagonistic activity. From reporter gene assay (RGA), the compound with a side chain containing N- n-butyl- N-methyl amide ( 19a) showed pure antagonistic activity (IC 50 = 340 nM, FI 5 > 10,000 nM), whereas known AR antagonists showed partial agonistic activities. The optimization of 19a led to compound 23 ( CH4892280), which showed more potent pure antagonistic activity (IC 50 = 190 nM, FI 5 > 10,000 nM). The SARs of tested compounds suggested that the length of the side chain and the substituents on the amide nitrogen are important for pure antagonistic activities.