Synthesis of small molecule inhibitors of the orphan nuclear receptor steroidogenic factor-1 (NR5A1) based on isoquinolinone scaffolds.
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.
Roth
Joshua
J
Department of Chemistry, Scripps Florida, 5353 Parkside Drive, RE-2, Jupiter, FL 33458, USA.
Madoux
Franck
F
Hodder
Peter
P
Roush
William R
WR
D015394:Molecular Structure; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D054339:Steroidogenic Factor 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D013329:Structure-Activity Relationship; D017186:Titrimetry
D011804:Quinolines; D054339:Steroidogenic Factor 1; C037219:quinoline