Synthesis of small molecule inhibitors of the orphan nuclear receptor steroidogenic factor-1 (NR5A1) based on isoquinolinone scaffolds

Joshua Roth; Franck Madoux; Peter Hodder; William R Roush

doi:10.1016/j.bmcl.2008.03.027

Synthesis of small molecule inhibitors of the orphan nuclear receptor steroidogenic factor-1 (NR5A1) based on isoquinolinone scaffolds

Bioorg Med Chem Lett. 2008 Apr 15;18(8):2628-32. doi: 10.1016/j.bmcl.2008.03.027. Epub 2008 Mar 14.

Authors

Joshua Roth¹, Franck Madoux, Peter Hodder, William R Roush

Affiliation

¹ Department of Chemistry, Scripps Florida, 5353 Parkside Drive, RE-2, Jupiter, FL 33458, USA.

Abstract

Three synthetic routes were developed for structure-activity relationship (SAR) studies of HTS-derived isoquinolinone inhibitor probes for the orphan nuclear receptor steroidogenic factor-1 (NR5A1). Among the new analogs reported herein, 31 and 32 have improved potency, lower cellular toxicity, and improved selectivity compared to the initial HTS-derived leads 1 and 2.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Molecular Structure
Quinolines / chemical synthesis*
Quinolines / chemistry
Quinolines / pharmacology*
Steroidogenic Factor 1 / antagonists & inhibitors*
Steroidogenic Factor 1 / metabolism*
Structure-Activity Relationship
Titrimetry

Substances

Quinolines
Steroidogenic Factor 1
quinoline

Abstract

Publication types

MeSH terms

Substances

Grants and funding