Design and synthesis of benzofused heterocyclic RXR modulators

D L Gernert; D A Neel; M F Boehm; M D Leibowitz; D A Mais; P Y Michellys; D Rungta; A Reifel-Miller; T A Grese

doi:10.1016/j.bmcl.2004.03.073

Design and synthesis of benzofused heterocyclic RXR modulators

Bioorg Med Chem Lett. 2004 Jun 7;14(11):2759-63. doi: 10.1016/j.bmcl.2004.03.073.

Authors

D L Gernert¹, D A Neel, M F Boehm, M D Leibowitz, D A Mais, P Y Michellys, D Rungta, A Reifel-Miller, T A Grese

Affiliation

¹ Discovery Chemistry Research, Lilly Research Laboratories, Indianapolis, IN 46285, USA. dgernert@lilly.com

PMID: 15125928
DOI: 10.1016/j.bmcl.2004.03.073

Abstract

Benzofused heterocyclic analogs of the RXR selective modulator 1 (LG101506) were synthesized, and tested for their ability to bind RXRalpha and activate RXR homo and heterodimers. Potency and efficacy were observed to be dependent upon the choice of heterocycle as well as the sidechain employed.

MeSH terms

Animals
Benzene / chemistry
Cell Line
Chlorocebus aethiops
Drug Design
Heterocyclic Compounds, 3-Ring / chemical synthesis*
Heterocyclic Compounds, 3-Ring / pharmacology*
Humans
PPAR gamma
Protein Binding
Retinoid X Receptor alpha / agonists
Retinoid X Receptor alpha / antagonists & inhibitors
Retinoid X Receptor alpha / chemistry
Retinoid X Receptor gamma / agonists
Retinoid X Receptor gamma / antagonists & inhibitors
Retinoid X Receptor gamma / chemistry
Retinoid X Receptors / agonists
Retinoid X Receptors / antagonists & inhibitors
Retinoid X Receptors / chemistry*
Structure-Activity Relationship
Transcriptional Activation / drug effects

Substances

Heterocyclic Compounds, 3-Ring
PPAR gamma
Retinoid X Receptor alpha
Retinoid X Receptor gamma
Retinoid X Receptors
Benzene