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

Authors :
Wityak J
Prime ME
Brookfield FA
Courtney SM
Erfan S
Johnsen S
Johnson PD
Li M
Marston RW
Reed L
Vaidya D
Schaertl S
Pedret-Dunn A
Beconi M
Macdonald D
Muñoz-Sanjuan I
Dominguez C
Source :
ACS medicinal chemistry letters [ACS Med Chem Lett] 2012 Oct 04; Vol. 3 (12), pp. 1024-8. Date of Electronic Publication: 2012 Oct 04 (Print Publication: 2012).
Publication Year :
2012

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.

Details

Language :
English
ISSN :
1948-5875
Volume :
3
Issue :
12
Database :
MEDLINE
Journal :
ACS medicinal chemistry letters
Publication Type :
Academic Journal
Accession number :
24900424
Full Text :
https://doi.org/10.1021/ml300241m