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- Title
5-((3-Amidobenzyl)oxy)nicotinamides as SIRT2 Inhibitors: A Study of Constrained Analogs.
- Authors
Ai, Teng; Wilson, Daniel J.; Chen, Liqiang
- Abstract
SIRT2 is a member of NAD+-dependent sirtuins and its inhibition has been proposed as a promising therapeutic approach for treating human diseases, including neurodegenerative diseases, cancer, and infections. Expanding SIRT2 inhibitors based on the 3-aminobenzyloxy nicotinamide core structure, we have synthesized and evaluated constrained analogs and selected stereoisomers. Our structure-activity relationship (SAR) study has revealed that 2,3-constrained (S)-isomers possess enhanced in vitro enzymatic inhibitory activity against SIRT2 and retain excellent selectivity over SIRT1 and SIRT3, provided that a suitable ring A is used. This current study further explores SIRT2 inhibitors based on the 3-aminobenzyloxy nicotinamide scaffold and contributes to the discovery of potent, selective SIRT2 inhibitors that have been actively pursued for their potential therapeutic applications.
- Subjects
SIRTUINS; NICOTINAMIDE; NAD (Coenzyme); STRUCTURE-activity relationships; NEURODEGENERATION; STEREOISOMERS
- Publication
Molecules, 2023, Vol 28, Issue 22, p7655
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules28227655