2,3-Diarylindenes and 2,3-diarylindenones: synthesis, molecular structure, photochemistry, estrogen receptor binding affinity, and comparisons with related triarylethylenes.
Two 2,3-diphenylindene and -indenone systems, with potential fluorescent and photofluorogenic properties, were prepared and studied as ligands for the estrogen receptor. The indene systems were prepared by Friedel-Crafts cyclization of appropriate alpha-benzyl desoxybenzoin systems, and the indenones either by oxidation of the indenes, by cyclization of alpha-benzoyl desoxybenzoins, or by acylium ion attack on tolan. Crystallographic analysis of the 2,3-diphenylindene and -indenone systems shows the phenyl substituents twisted out of the plane of the indene/indenone systems, with both torsional angles greater in the indenone than indene system; the phenyl attachment to the five-membered ring allows these systems to be considerably more planar than the related 1,2-diphenyl-3,4-dihydronaphthalene and the triarylethylene nonsteroidal estrogens. In contrast to the diphenyldihydronaphthalenes, the diarylindene and -indenone systems undergo photocyclization to phenanthrenes inefficiently. The estrogen receptor binding affinity of these systems is reasonably high (9-59% relative to estradiol), with the indenone systems having higher affinity than the indenes; additional hydroxyl substitution raises the affinity of the indenes but lowers that of the indenones. These trends can be rationalized by considering differences in molecular volumes or surface areas (related to torsional angles) and specific polar interactions.
Anstead
G M
GM
Department of Chemistry, University of Illinois, Urbana 61801.
Altenbach
R J
RJ
Wilson
S R
SR
Katzenellenbogen
J A
JA
D001667:Binding, Competitive; D055598:Chemical Phenomena; D002621:Chemistry; D007192:Indenes / Q000138:chemical synthesis* / Q000378:metabolism; D008968:Molecular Conformation; D010777:Photochemistry; D011960:Receptors, Estrogen / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship; D014961:X-Ray Diffraction
D007192:Indenes; D011960:Receptors, Estrogen