Document Report Card

ID: ALA1123662

Journal: J Med Chem

Title: Preparation, receptor binding, and fluorescence properties of hexestrol-fluorophore conjugates: evaluation of site of attachment, fluorophore structure, and fluorophore-ligand spacing.

Authors: Fevig TL, Lloyd JE, Zablocki JA, Katzenellenbogen JA.

Abstract: We have undertaken a staged development of certain estrogen-fluorophore conjugates, in order to prepare a fluorescent estrogen suitable for determination of the estrogen receptor content of individual cells. Since non-steroidal estrogens with bulky substituents are often more readily bound by receptor than their steroidal counterparts, we have investigated fluorophore conjugates with derivatives of the non-steroidal estrogen hexestrol [3R*, 4S*)-3,4-bis(4-hydroxyphenyl)hexane). On the basis of the receptor-binding affinity of model compounds, we prepared a prototypical set of three ring- and side-chain-substituted fluorescent hexestrol derivatives, whose binding and fluorescence properties ultimately led to the preparation of a series of side-chain-substituted nitrobenzoxadiazole derivatives. The compounds prepared have binding affinities for the estrogen receptors that range from ca. 1% to 5% that of estradiol, and they have very favorable fluorescence characteristics, similar to those of fluorescein.

CiteXplore: 3027331

DOI: 10.1021/jm00384a026