Synthesis of 3-phenyl-4-phenylvinyl benzopyranones and the corresponding 2,2-dimethyl-benzopyrans with structural similarity to estradiol, as estrogen receptor ligands.
7-Methoxy-3-phenyl-4-phenylvinyl benzopyran-2-ones and the corresponding 2,2-dimethyl-benzopyrans, substituted with different alkylamino residues were synthesized. Except compound 13e, all compounds showed high level of estrogen agonistic activity (>81 %) whereas, compounds 13 b-e and 15a showed significant estrogen antagonistic activity (>20 %). X-Ray analysis of a 7-methoxy-3-phenyl-4-phenylvinyl benzopyran-2-one derivative 13d showed its structural resemblance to endogenous estrogen, 17beta-estradiol. Estrogenic and antiestrogenic activities of these derivatives demonstrate their estrogen receptor (ER) binding ability. The lack of hydroxyl groups at appropriate positions resulted in poor Relative Binding Affinity (RBA).
Gupta
Atul
A
Medicinal and Process Chemistry Division, Central Drug Research Institute, Lucknow, India. atisky2001@yahoo.co.in
Raghunandan
Resmi
R
Kumar
Atul
A
Maulik
Prakash R
PR
Dwivedyc
Anila
A
Keshri
Govind
G
Singh
Man Mohan
MM
Ray
Suprabhat
S
D001578:Benzopyrans / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D004958:Estradiol / Q000737:chemistry* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D011960:Receptors, Estrogen / Q000378:metabolism*; D013055:Spectrophotometry, Infrared
D001578:Benzopyrans; D011960:Receptors, Estrogen; D004958:Estradiol