4,7-Dichloro benzothien-2-yl sulfonylaminomethyl boronic acid: first boronic acid-derived beta-lactamase inhibitor with class A, C, and D activity

Qiang Tan; Aimie M Ogawa; Ronald E Painter; Young-Whan Park; Katherine Young; Frank P DiNinno

doi:10.1016/j.bmcl.2010.02.065

4,7-Dichloro benzothien-2-yl sulfonylaminomethyl boronic acid: first boronic acid-derived beta-lactamase inhibitor with class A, C, and D activity

Bioorg Med Chem Lett. 2010 Apr 15;20(8):2622-4. doi: 10.1016/j.bmcl.2010.02.065. Epub 2010 Feb 19.

Authors

Qiang Tan¹, Aimie M Ogawa, Ronald E Painter, Young-Whan Park, Katherine Young, Frank P DiNinno

Affiliation

¹ Department of Medicinal Chemistry, Merck & Co., Inc., Rahway, NJ 07065, USA. [email protected]

PMID: 20299220
DOI: 10.1016/j.bmcl.2010.02.065

Abstract

4,7-Dichloro-1-benzothien-2-yl sulfonylaminomethyl boronic acid (DSABA, Compound I) was discovered as the first boronic acid-based class D beta-lactamase inhibitor. It exhibited an IC(50) of 5.6 microM against OXA-40. The compound also inhibited class A and C beta-lactamases with sub to low microM IC(50), and synergized with imipenem against Acinetobacter baumannii.

MeSH terms

Acinetobacter baumannii / drug effects
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology*
Boronic Acids / chemistry
Boronic Acids / pharmacology*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology*
Inhibitory Concentration 50
Microbial Sensitivity Tests
beta-Lactamase Inhibitors*

Substances

Anti-Bacterial Agents
Boronic Acids
Enzyme Inhibitors
beta-Lactamase Inhibitors