title: Amide derivatives of 2,3-diarylacrylophenone as estrogen receptor binding ligands.
abstract: Substituted amidoalkyl derivatives of 2,3-diarylacrylophenones carrying the amide chain on the 3-aryl residue have been prepared by reacting corresponding phenolic 2,3-diarylacrylophenones with haloalkyl carboxylic acid esters, their hydrolysis and subsequent treatment with different alkyl amines. Compounds thus prepared were evaluated for their relative binding affinity (RBA) towards estrogen receptors (ER), estrogen agonistic and antagonistic activities. Out of eleven amide derivatives thus prepared, compounds 7, 13, 15-19, 23, 24 showed significant estrogen antagonistic activity. Interestingly the phenolic compound 7 and the acid ester 18 also exhibited estrogen inhibiting property. Majority of the dimethoxy derivatives (R = OCH(3)) showed significantly high estrogenic activity. In order to throw light on their SAR, In silico docking of the acrylophenone derivatives in the ligand binding site of the ERalpha and their comparison with pure steroidal estrogen antagonist ICI-164,384 and the non-steroidal antiestrogen raloxifene, was carried out. Crystal structure of compound 6 revealed relative trans-geometry of the 2(B) and 3(C) phenyl rings.
authors.affiliation: Medicinal and Process Chemistry, Central Drug Research Institute, Lucknow, India. atisky2001@yahoo.co.in
authors.forename: Atul
authors.initials: A
authors.lastname: Gupta
authors.forename: Resmi
authors.initials: R
authors.lastname: Raghunandan
authors.forename: Atul
authors.initials: A
authors.lastname: Kumar
authors.forename: Prakash R
authors.initials: PR
authors.lastname: Maulik
authors.forename: Anila
authors.initials: A
authors.lastname: Dwivedy
authors.forename: Govind
authors.initials: G
authors.lastname: Keshri
authors.forename: Man Mohan
authors.initials: MM
authors.lastname: Singh
authors.forename: Suprabhat
authors.initials: S
authors.lastname: Ray
mesh_terms: D000577:Amides / Q000737:chemistry*; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D004965:Estrogen Antagonists / Q000737:chemistry; D020847:Estrogen Receptor Modulators / Q000737:chemistry*; D006841:Hydrocarbons, Aromatic / Q000737:chemistry*; D008024:Ligands; D010636:Phenols / Q000737:chemistry; D011485:Protein Binding; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D004965:Estrogen Antagonists; D020847:Estrogen Receptor Modulators; D006841:Hydrocarbons, Aromatic; D008024:Ligands; D010636:Phenols; D011960:Receptors, Estrogen