title: Rapid synthesis of 4-benzylidene and 4-[bis-(4-methoxyphenyl)-methylene-2-substituted phenyl-benzopyrans as potential selective estrogen receptor modulators (SERMs) using McMurry coupling reaction.
abstract: 7-Methoxy-4-(4-methoxybenzylidene)-2-substituted phenyl-benzopyrans I and 4-[bis-(4-methoxyphenyl)-methylene-2-substituted phenyl-benzopyrans II carrying different alkylamino residues, designed as estrogen receptor (ER) binding ligands, were successfully synthesized through the McMurry coupling reaction of substituted benzaldehyde/substituted benzophenones and 2-hydroxyphenyl-7-methoxy-chroman-4-one in presence of lithium aluminum hydride and titanium (IV) chloride (LAH-TiCl(4)). Self-coupling of carbonyl reactants led to the formation of several side products. The prototypes were evaluated for their relative binding affinity (RBA), as well as their estrogenic and antiestrogenic activities. High order of estrogenic activity (>50% gain) observed with compounds 3, 7a, 7b, 7c, 8, and 10a and also their partial estrogen antagonistic activity (> or =15%) at the uterine level points toward successful designing of the compounds. Compounds 4, 7a, 7b, 7c, and 10a also possessed significant anticancer activity against human adenocarcinoma cell line (MCF-7 cell line) that may be related to their estrogen-dependent action.
authors.affiliation: Medicinal and Process Chemistry Division, Central Drug Research Institute, Lucknow 226001, India. atisky2001@yahoo.co.in <atisky2001@yahoo.co.in>
authors.forename: Atul
authors.initials: A
authors.lastname: Gupta
authors.forename: Anila
authors.initials: A
authors.lastname: Dwivedy
authors.forename: Govind
authors.initials: G
authors.lastname: Keshri
authors.forename: Ramesh
authors.initials: R
authors.lastname: Sharma
authors.forename: Anil Kumar
authors.initials: AK
authors.lastname: Balapure
authors.forename: Man Mohan
authors.initials: MM
authors.lastname: Singh
authors.forename: Suprabhat
authors.initials: S
authors.lastname: Ray
mesh_terms: D001597:Benzylidene Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004967:Estrogens / Q000819:agonists / Q000378:metabolism; D005419:Flavonoids / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008745:Methylation; D015394:Molecular Structure; D020845:Selective Estrogen Receptor Modulators / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013997:Time Factors
chemical_list: D001597:Benzylidene Compounds; D004967:Estrogens; D005419:Flavonoids; D020845:Selective Estrogen Receptor Modulators