Novel non-steroidal/non-anilide type androgen antagonists effective toward mutated androgen receptor

MEDI 80

Aya Tanatani, aya@iam.u-tokyo.ac.jp, Ken-ichi Wakabayashi, Hiroyuki Miyachi, and Yuichi Hashimoto. Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-0032, Japan
Androgen receptor (AR) is a member of the nuclear receptor superfamily and is a key molecular target in the etiology such as the progression of prostate cancer. AR antagonists are useful for the treatment of androgen-dependent prostate cancer. However, the prostate cancer often advances to a hormone-refractory state in which the disease progressed in the presence of continued androgen ablation or antagonist therapy. AR mutation is considered to be one possible reason for hormone-refractory. For example, the known AR antagonists, hydroxyflutamide and bicartamide show agonistic activity in some AR mutants. In order to overcome the resistance, we designed and synthesized 4-substituted pyrrole-2-carboxamide derivatives as the novel non-steroidal/non-anilide type AR antagonists. Some pyrrole-2-carboxamides inhibited the growth of prostate cancer cells with mutated AR.
 

General Poster Session
7:00 PM-9:00 PM, Sunday, 10 September 2006 Moscone Center -- Hall D, Poster

Sci-Mix
8:00 PM-10:00 PM, Monday, 11 September 2006 Moscone Center -- Hall D, Sci-Mix

Division of Medicinal Chemistry

The 232nd ACS National Meeting, San Francisco, CA, September 10-14, 2006