synthesis of novel nitro-substituted triaryl pyrazole derivatives as potential estrogen receptor ligands合成新型nitro-substituted triaryl吡唑衍生物作为潜在的雌激素受体配体.pdf

Molecules 2007, 12, 1259-1273 molecules ISSN 1420-3049 © 2007 by MDPI /molecules Full Paper Synthesis of Novel Nitro-substituted Triaryl Pyrazole Derivatives as Potential Estrogen Receptor Ligands Fotini Naoum 1, Konstantinos M. Kasiotis 1, Prokopios Magiatis 2 and Serkos A. Haroutounian 1,* 1 Chemistry Laboratory, Agricultural University of Athens, Iera odos 75, Athens 11855, Greece 2 Faculty of Pharmacy, Laboratory of Pharmacognosy and Natural Products Chemistry, University of Athens, Panepistimiopolis Zografou, Athens 15771, Greece * Author to whom correspondence should be addressed. E-mail: sehar@aua.gr Received: 11 June 2007; in revised form: 29 June 2007 / Accepted: 29 June 2007 / Published: 2 July 2007 Abstract: Novel tetrasubstituted pyrazole derivatives bearing a nitro substituent on their A-phenol ring were synthesized and their binding affinity towards the estrogen receptor (ER) subtypes ERα and ERβ was determined. Among compounds tested, the 2-nitrophenol derivative 5c was found to bind satisfactorily to both estrogen receptor subtypes (RBAα=5.17 and RBAβ=3.27). In general, the introduction of a nitro group into the A ring of these compounds was found to benefit their ERβ binding abilities. Keywords: Pyrazoles, SERMs, Estrogen Receptor Binding Affinity. Introduction The estrogen receptor (ER) displays a considerable capacity for binding with a wide range of steroidal and nonsteroidal ligands. [1] Particularly, the nonster