Development of Novel Subtype Selective Ligands for the Estrogen Receptor: I. 5,6-Diakyl-5,6,11,12-Tetrahydrochrysenes as Estrogen Receptor-Beta Selective Antagonists. II. Diarylpropionitriles as Estrogen Receptor-Beta Potency Selective Agonists

A series of ERbeta selective DPN analogs were prepared where the both the ligand core and the aromatic rings were modified by the repositioning of phenolic hydroxy groups and by the addition of alkyl substituents and nitrile groups. Another series of DPN analogs were synthesized where the nitrile functionality was replaced with acetylene groups or polar groups to mimic the linear geometry or the polarity of the nitrile. All of the analogs are affinity selective for ERbeta to varying degrees, but many are not potency selective. meso- and dl-2,3-bis(4-hydroxyphenyl)succinonitrile are among the highest ERbeta affinity selective ligands and have somewhat greater ERbeta potency selectivity than DPN. The nitrile functionality was found to be critical to ERbeta selectivity as it is the optimal combination of linear geometry and polarity. Furthermore, the addition of another nitrile group beta to the nitrile or ortho methylation of the aromatic ring increases the affinity and selectivity of these compounds for ERbeta.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Chemistry

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Meyers, Marvin Jay

Contributors dc:contributor

• Katzenellenbogen, John A.

• Chemistry, Biochemistry

Language dc:language

eng

Identifier

(MiAaPQ)AAI9990083

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/84488