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SAR Development of Lysine-Based Irreversible Inhibitors of Transglutaminase 2 for Huntington's Disease.

ABSTRACT: We report a series of irreversible transglutaminase 2 inhibitors starting from a known lysine dipeptide bearing an acrylamide warhead. We established new SARs resulting in compounds demonstrating improved potency and better physical and calculated properties. Transglutaminase selectivity profiling and in vitro ADME properties of selected compounds are also reported.

SUBMITTER: Wityak J

PROVIDER: S-EPMC4025666 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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SAR Development of Lysine-Based Irreversible Inhibitors of Transglutaminase 2 for Huntington's Disease.

Wityak John J Prime Michael E ME Brookfield Frederick A FA Courtney Stephen M SM Erfan Sayeh S Johnsen Siw S Johnson Peter D PD Li Marie M Marston Richard W RW Reed Laura L Vaidya Darshan D Schaertl Sabine S Pedret-Dunn Anna A Beconi Maria M Macdonald Douglas D Muñoz-Sanjuan Ignacio I Dominguez Celia C

ACS medicinal chemistry letters 20121004 12

We report a series of irreversible transglutaminase 2 inhibitors starting from a known lysine dipeptide bearing an acrylamide warhead. We established new SARs resulting in compounds demonstrating improved potency and better physical and calculated properties. Transglutaminase selectivity profiling and in vitro ADME properties of selected compounds are also reported. ...[more]

PMID: 24900424

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