Discovery of 1-arylcarbonyl-6, 7-dimethoxyisoquinoline derivatives as glutamine fructose-6-phosphate amidotransferase (GFAT) inhibitors

…, S Tannu, K Conde-Knape, J Kochan, D Bolin

Index: Qian, Yimin; Ahmad, Mushtaq; Chen, Shaoqing; Gillespie, Paul; Le, Nam; Mennona, Frank; Mischke, Steven; So, Sung-Sau; Wang, Hong; Burghardt Charles; Tannu, Shahid; Conde-Knape, Karin; Kochan, Jarema; Bolin, David Bioorganic and Medicinal Chemistry Letters, 2011 , vol. 21, # 21 p. 6264 - 6269

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Citation Number: 3

Abstract

Through high throughput screening and subsequent hit identification and optimization, we synthesized a series of 1-arylcarbonyl-6, 7-dimethoxyisoquinoline derivatives as the first reported potent and reversible GFAT inhibitors. SAR studies of this class of compounds indicated significant impact on GFAT inhibition potency by substitutions on the A-ring and C- ring. The ketone group was found to be necessary for high potency. Compound 28 ( ...