SAR study on Novel truxillic acid monoester-Based inhibitors of fatty acid binding proteins as Next-Generation antinociceptive agents.

ABSTRACT: Fatty acid binding protein 5 (FABP5) is a highly promising target for the development of analgesics as its inhibition is devoid of CB₁R-dependent side-effects. The design and discovery of highly potent and FABP5-selective truxillic acid (TA) monoesters (TAMEs) is the primary aim of the present study. On the basis of molecular docking analysis, ca. 2,000 TAMEs were designed and screened in silico, to funnel down to 55 new TAMEs, which were synthesized and assayed for their affinity (Ki) to FABP5, 3 and 7. The SAR study revealed that the introduction of H-bond acceptors to the far end of the 1,1'-biphenyl-3-yl and 1,1'-biphenyl-2-yl ester moieties improved the affinity of α-TAMEs to FABP5. Compound γ-3 is the first γ-TAME, demonstrating a high affinity to FABP5 and competing with

SUBMITTER: Wang H 

PROVIDER: S-EPMC11323223 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature