Publications by authors named "Louise H Foley"
New modifications on the C-8 4-aminobenzyl unit of the previously reported 3-alkyl-1,8-dibenzylxanthine inhibitors of cPEPCK are presented. The most active compound reported here is the 5-chloro-1,3-dimethyl-1H-pyrazole-4-sulfonic acid amide derivative 2 with an IC(50) of 0.29+/-0.
View Article and Find Full Text PDFThe analysis of the X-ray structures of two xanthine inhibitors bound to PEPCK and a comparison to the X-ray structure of GTP bound to PEPCK are reported. The SAR at N-1, N-7 and developing SAR at C-8 are consistent with information gained from the X-ray structures of compounds 1 and 2 bound to PEPCK. Representative N-3 modifications of compound 2 that led to the discovery of 3-cyclopropylmethyl and its carboxy analogue as optimal N-3 groups are presented.
View Article and Find Full Text PDFArticle Synopsis
- Researchers have identified the first non-substrate-like inhibitors for the enzyme PEPCK, which compete with GTP.
- The focus is on finding oral drugs to help manage glucose levels in Type 2 diabetes by reversibly inhibiting PEPCK.
- The compound 1-allyl-3-butyl-8-methylxanthine was modified, resulting in a 100-fold improvement in its effectiveness, contributing to the development of structure-activity relationship (SAR) insights for these inhibitors.