title: Development of 2,3,5-triaryl-1H-pyrroles as estrogen receptor α selective ligands.
abstract: 1-Alkyl-2,3,5-triaryl-1H-pyrroles (for which alkyl=methyl, ethyl, n-propyl, or 2-methylpropyl) were tested for stability, estrogen receptor (ER) binding, and inhibition of tumor cell growth. These pyrroles (type B) showed higher stability in aqueous solution than their 1,2,4-triaryl-1H-pyrrole congeners (type A pyrroles), exclusive ERα binding (no ERβ interaction), and a hormonal profile of partial agonists at ERα. The most potent compound, 1-(2-methylpropyl)-2,3,5-tris(4-hydroxyphenyl)-1H-pyrrole (5 d), was less active than the lead structure 1,3,5-tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole (PPT) in MCF-7 cells stably transfected with the plasmid EREwtcluc (MCF-7/2a), but more potent in U2-OS/α cells. Furthermore, 5 d showed weak anti-estrogenic properties (IC50=310 nM). An additional propyl chain at C4 decreased the stability and pharmacological effects.
authors: Institut für Pharmazie, Freie Universität Berlin, Königin-Luise-Str. 2+4, 14195 Berlin, Germany.
authors: Anja
authors: A
authors: Schäfer
authors: Anja
authors: A
authors: Wellner
authors: Martin
authors: M
authors: Strauss
authors: Gerhard
authors: G
authors: Wolber
authors: Ronald
authors: R
authors: Gust
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D004353:Drug Evaluation, Preclinical; D004355:Drug Stability; D004965:Estrogen Antagonists / Q000737:chemistry / Q000494:pharmacology; D020847:Estrogen Receptor Modulators / Q000737:chemistry* / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D005260:Female; D006801:Humans; D008958:Models, Molecular; D010636:Phenols; D011720:Pyrazoles; D011758:Pyrroles / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D004965:Estrogen Antagonists; D020847:Estrogen Receptor Modulators; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D010636:Phenols; D011720:Pyrazoles; D011758:Pyrroles; C486184:4,4',4''-(4-propyl-((1)H)-pyrazole-1,3,5-triyl) tris-phenol