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ID: ALA5143693

Journal: Bioorg Med Chem Lett

Title: Design and synthesis of endocannabinoid enzyme inhibitors for ocular indications.

Authors: Fulp A, Bingham S, Fisler B, Kho F, Kim J, Kim SJ, Martin T, Mims B, Reji Thomas K, Roe G, Spiotta J, Young J, Lazenka M.

Abstract: A small library of FAAH and dual FAAH/MAGL inhibitors designed for peripheral selectivity were targeted. Of these compounds, three were identified to have desirable FAAH inhibition and reduced permeability in a PAMPA assay. Those three compounds were advanced into a MAGL inhibitor assay and one was found to be a relative selective FAAH inhibitor, FAAH to MAGL IC50 ratio of 1:27, and one was found to be more characteristic of a true dual enzyme inhibitor, FAAH to MAGL IC50 ratio of 1:4. Both compounds showed activity in an ABPP assay, blockage of TAMRA-FP labeling of FAAH and MAGL in rat eye homogenate.

CiteXplore: 35500728

DOI: 10.1016/j.bmcl.2022.128763