Novel retinoid antagonists bearing trifluoromethyl groups

MEDI 81

Hiroyuki Kagechika, kage.omc@tmd.ac.jp1, Michimasa Maeda1, Tomoya Hirano1, Emiko Kawachi1, and Yuichi Hashimoto2. (1) School of Biomedical Science, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo, 101-0062, Japan, (2) Institute of Molecular and Cellular Biosciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-0032, Japan
Retinoids have potent biological activities, being involved in the control of cell proliferation, differentiation, and morphogenesis in vertebrates, mediated by the activation of heterodimer of two nuclear receptors, RAR (retinoic acid receptor) and RXR (retinoid X receptor). In order to develop novel synthetic retinoid agonists and antagonists with unique biological activities, we examined the virtual screening method using databases of commercially available molecules, and obtained a trifluoromethylated aromatic compound as an RAR ligand candidate. The introduction of trifluoromenthyl groups into retinoid structures resulted in the retinoid antagonistic activities. The conventional retinoid antagonists have bulky substituents at the hydrophobic region, which disturb the proper folding of AF-2 (helix 12) of the retinoid nuclear receptors. Therefore, the retinoid antagonists with smaller trifluoromethyl group at the hydrophobic region would have unique biological properties in retinoid functions.
 

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

Division of Medicinal Chemistry

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