A 4-aminobenzoic acid derivative as novel lead for selective inhibitors of multidrug resistance-associated proteins

Bioorganic & Medicinal Chemistry Letters
Stefan LeyersMichael Wiese

Abstract

We present a novel lead for inhibitors of multidrug resistance-associated proteins (MRPs). Compound 1 (4-[(5,6,7,8-tetrahydro-4-oxo-4H-[1]benzothieno[2,3-d][1,3]thiazin-2-yl)amino]benzoic acid) was about six times more potent than the known inhibitor MK571 at MRP1, while at MRP2 its effect was similar to that of MK571. Structural analogs were also evaluated. Among them, compound 2, sharing the 4-aminobenzoic acid substructure with 1, also inhibited MRP1. Both derivatives were inactive against P-gp. It can be concluded that their carboxyl group is needed for inhibition of MRPs and accounts for the selectivity of these compounds.

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Citations

Jan 20, 2010·Drug Metabolism Reviews·Katalin JemnitzPeter Krajcsi
Mar 5, 2016·Journal of Medicinal Chemistry·Sven Marcel SchmittMichael Wiese
Jul 19, 2014·Chemistry & Biology·Anna-Lena SchmitzEvi Kostenis
Nov 5, 2016·Biochimica Et Biophysica Acta. Biomembranes·Sven Marcel SchmittMichael Wiese
Feb 4, 2011·Archiv der Pharmazie·Umasankar KulandaiveluVenkatesan Jayaprakash
Feb 13, 2020·Molecular Diversity·Minh-Tri LeKhac-Minh Thai
Aug 5, 2018·Journal of Medicinal Chemistry·Michael K KrapfMichael Wiese

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