Synthesis, biological evaluation, and structure activity relationship (SAR) study of pyrrolidine amide derivatives as N-acylethanolamine acid amidase (NAAA) inhibitors.

ABSTRACT: N-Acylethanolamine acid amidase (NAAA) is one of the key enzymes involved in the degradation of fatty acid ethanolamides (FAEs), especially for palmitoylethanolamide (PEA). Pharmacological blockage of NAAA restores PEA levels, providing therapeutic benefits in the management of inflammation and pain. In the current work, we showed the structure-activity relationship (SAR) studies for pyrrolidine amide derivatives as NAAA inhibitors. A series of aromatic replacements or substituents for the terminal phenyl group of pyrrolidine amides were examined. SAR data showed that small lipophilic 3-phenyl substituents were preferable for optimal potency. The conformationally flexible linkers increased the inhibitory potency of pyrrolidine amide derivatives but reduced their selectivity toward f

SUBMITTER: Zhou P 

PROVIDER: S-EPMC6399680 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature