Structure-activity relationship of antiestrogens. Studies on 2,3-diaryl-1-benzopyrans.
A series of 2,3-diaryl-1-benzopyran analogues substituted at position 4 of 2-phenyl with a hydroxy or pyrrolidinoethoxy residue were synthesized as models for (E)-triarylpropenones constrained in the s-trans conformation. The prototypes, belonging to five chemical series, were evaluated for their estrogen receptor affinity and for estrogen agonist-antagonist activities. The 4H-1-benzopyran-4-one, the 2,3-dihydro-4H-1-benzopyran-4-one, the 4H-1-benzopyran, and the 2,3-dihydro-1-benzopyran derivatives were found to be inactive or only marginally activate as receptor ligands or estrogen agonists-antagonists. In the 2H-1-benzopyran category the parent phenol was also inactive whereas the basic ethers 16 and 26 were modest receptor ligands while being quite active as antiestrogens. In a comparative study the benzopyran 16 was found to be more effective antiestrogen than tamoxifen while being as effective as LY-117018. The benzopyrans have thus emerged as a new class of potent antiestrogens.
Saeed
A
A
Medicinal Chemistry Division, Central Drug Research Institute, Lucknow, India.
Sharma
A P
AP
Durani
N
N
Jain
R
R
Durani
S
S
Kapil
R S
RS
D000818:Animals; D001578:Benzopyrans / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D001681:Biological Assay; D055598:Chemical Phenomena; D002621:Chemistry; D003600:Cytosol / Q000378:metabolism; D004965:Estrogen Antagonists / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D015394:Molecular Structure; D009929:Organ Size / Q000187:drug effects; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011960:Receptors, Estrogen / Q000378:metabolism; D013329:Structure-Activity Relationship; D013629:Tamoxifen / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology; D014599:Uterus / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism
D001578:Benzopyrans; D004965:Estrogen Antagonists; D011759:Pyrrolidines; D011960:Receptors, Estrogen; D013876:Thiophenes; D013629:Tamoxifen; C066623:2-(4-(2-pyrrolidinoethoxy)phenyl)-3-phenyl-2H-1-benzopyran; C025430:LY 117018