Diaryl-dialkyl-substituted pyrazoles: regioselective synthesis and binding affinity for the estrogen receptor.
We have developed two novel series of tetrasubstituted pyrazoles, embodying 1,3-diaryl-4,5-dialkyl or 3,5-diaryl-1,4-dialkyl substitution patterns. The scope of a regioselective method, developed by us earlier, was expanded to allow the synthesis of the first series of these tetrasubstituted pyrazoles directly from alpha,beta-unsaturated ketones. The binding affinity of some of these pyrazoles for the estrogen receptor (ER) subtypes ERalpha and ERbeta is very high, and the overall affinity pattern suggests the importance of three phenol substituents for high affinity, ERalpha-selective binding.
Nishiguchi
Gisele A
GA
Department of Chemistry, University of Illinois, Urbana 61801, USA.
Rodriguez
Alice L
AL
Katzenellenbogen
John A
JA
D001665:Binding Sites; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D006801:Humans; D008024:Ligands; D011485:Protein Binding; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000378:metabolism*; D013237:Stereoisomerism
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D008024:Ligands; D011720:Pyrazoles; D011960:Receptors, Estrogen