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Triazolopyrimidines identified as reversible myeloperoxidase inhibitors.

ABSTRACT: Myeloperoxidase, a mammalian peroxidase involved in the immune system as an anti-microbial first responder, can produce hypochlorous acid in response to invading pathogens. Myeloperoxidase has been implicated in several chronic pathological diseases due to the chronic production of hypochlorous acid, as well as other reactive radical species. A high throughput screen and triaging protocol was developed to identify a reversible inhibitor of myeloperoxidase toward the potential treatment of chronic diseases such as atherosclerosis. The identification and characterization of a reversible myeloperoxidase inhibitor, 7-(benzyloxy)-3H-[1,2,3]triazolo[4,5-d]pyrimidin-5-amine is described.

SUBMITTER: Duclos F

PROVIDER: S-EPMC6071758 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Triazolopyrimidines identified as reversible myeloperoxidase inhibitors.

Duclos Franck F Abell Lynn M LM Harden David G DG Pike Kristen K Nowak Kimberly K Locke Gregory A GA Duke Gerald J GJ Liu Xiaoqin X Fernando Gayani G Shaw Scott A SA Vokits Benjamin P BP Wurtz Nicholas R NR Viet Andrew A Valente Meriah N MN Stachura Sylwia S Sleph Paul P Khan Javed A JA Gao Ji J Dongre Ashok R AR Zhao Lei L Wexler Ruth R RR Gordon David A DA Kick Ellen K EK

MedChemComm 20171026 11

Myeloperoxidase, a mammalian peroxidase involved in the immune system as an anti-microbial first responder, can produce hypochlorous acid in response to invading pathogens. Myeloperoxidase has been implicated in several chronic pathological diseases due to the chronic production of hypochlorous acid, as well as other reactive radical species. A high throughput screen and triaging protocol was developed to identify a reversible inhibitor of myeloperoxidase toward the potential treatment of chroni ...[more]

PMID: 30108726

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Methoxyphenol derivatives as reversible inhibitors of myeloperoxidase as potential antiatherosclerotic agents.

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| S-EPMC7333589 | biostudies-literature

From Dynamic Combinatorial Chemistry to <i>in Vivo</i> Evaluation of Reversible and Irreversible Myeloperoxidase Inhibitors.

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| S-EPMC1184209 | biostudies-other

Reversible inhibitors of regulators of G-protein signaling identified in a high-throughput cell-based calcium signaling assay.

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| S-EPMC3848259 | biostudies-literature

Thioxo-dihydroquinazolin-one Compounds as Novel Inhibitors of Myeloperoxidase.

Project description:Myeloperoxidase (MPO) is a key antimicrobial enzyme, playing a normal role in host defense, but also contributing to inflammatory conditions including neuroinflammatory diseases such as Parkinson's and Alzheimer's. We synthesized and characterized more than 50 quinazolin-4(1H)-one derivatives and showed that this class of compounds inhibits MPO with IC50 values as low as 100 nM. Representative compounds showed partially reversible inhibition that was competitive with respect to Amplex Red substrate and did not result in the accumulation of MPO Compound II. Members of this group show promise for therapeutic development for the treatment of diseases in which inflammation plays a pathogenic role.

| S-EPMC4601060 | biostudies-literature

Reversible covalent direct thrombin inhibitors.

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| S-EPMC6072017 | biostudies-literature

New trifluoromethyl triazolopyrimidines as anti-Plasmodium falciparum agents.

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| S-EPMC6268855 | biostudies-literature

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