Novel Core Scaffolds for the Development of Subtype Selective Estrogen Receptor Ligands

We have explored many novel core scaffolds, heterocyclic and acyclic, in our search for subtype selective ligands. During our studies we discovered ligands containing new pharmacological profiles for estrogens. The pyrazolo[1,5-a]pyrimidine ligands provided us with two new pharmacological classes of ligands: (1) ERbeta potency selective antagonists and (2) ERbeta potency and efficacy selective antagonists. These ligands provide researchers with the ability to selectively antagonize ERbeta allowing for them to study the effects of ERbeta inhibition in cells, in the presence of ERalpha. Although these are interesting ligands we desired to develop an ERbeta potency selective agonist. An ERbeta selective agonist will allow researchers to study the role of ERbeta when activated. To aid in the development of ERbeta selective agonists we described a pharmacophore model that we believed would aid in ligand design. Using this model we developed a series of ERbeta potency and efficacy selective agonists. The new pharmacological profiles of estrogens that we have developed will provide researchers with additional tools to study and elucidate the role of the estrogen receptor.

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

• Compton, Dennis Ray

Contributors dc:contributor

• Katzenellenbogen, John A.

• Chemistry, Organic

Language dc:language

eng

Identifier

(MiAaPQ)AAI3182441

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/84178