Structure-based design, synthesis, and antimicrobial activity of purine derived SAH/MTA nucleosidase inhibitors

Martina E Tedder; Zhe Nie; Stephen Margosiak; Shaosong Chu; Victoria A Feher; Robert Almassy; Krzysztof Appelt; Kraig M Yager

doi:10.1016/j.bmcl.2004.04.006

Structure-based design, synthesis, and antimicrobial activity of purine derived SAH/MTA nucleosidase inhibitors

Bioorg Med Chem Lett. 2004 Jun 21;14(12):3165-8. doi: 10.1016/j.bmcl.2004.04.006.

Authors

Martina E Tedder¹, Zhe Nie, Stephen Margosiak, Shaosong Chu, Victoria A Feher, Robert Almassy, Krzysztof Appelt, Kraig M Yager

Affiliation

¹ Department of Medicinal Chemistry, Quorex Pharmaceuticals, Carlsbad, CA 92008, USA.

PMID: 15149667
DOI: 10.1016/j.bmcl.2004.04.006

Abstract

The structure-based design, synthesis, and biological activity of novel inhibitors of S-adenosyl homocysteine/methylthioadenosine (SAH/MTA) nucleosidase are described. Using 6-substituted purine and deaza purines as the core scaffolds, a systematic and structure guided series of modifications provided low nM inhibitors with broad-spectrum antimicrobial activity.

MeSH terms

Anti-Bacterial Agents / chemical synthesis*
Anti-Bacterial Agents / pharmacology
Drug Design*
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / pharmacology
Homocysteine / antagonists & inhibitors
Homocysteine / metabolism
N-Glycosyl Hydrolases / antagonists & inhibitors*
N-Glycosyl Hydrolases / metabolism
Purine-Nucleoside Phosphorylase / antagonists & inhibitors
Purine-Nucleoside Phosphorylase / metabolism
Purines / chemical synthesis
Purines / pharmacology
Structure-Activity Relationship

Substances

Anti-Bacterial Agents
Enzyme Inhibitors
Purines
Homocysteine
Purine-Nucleoside Phosphorylase
5'-methylthioadenosine phosphorylase
N-Glycosyl Hydrolases