Preparation of novel anthranilic acids as antibacterial agents: extensive evaluation of structural and physical properties on antibacterial activity and human serum albumin affinity

Bioorg Med Chem Lett. 2007 Jun 1;17(11):3113-6. doi: 10.1016/j.bmcl.2007.03.036. Epub 2007 Mar 15.

Abstract

In the past few years a significant effort has been devoted by Pharmacia toward the discovery of novel antibiotics. We have recently described the identification of an anthranilic acid lead 1 and the optimization resulting in the advanced lead 2. In this report, we describe the preparation of several selected analogs to probe the dependency of this template for antibacterial activity and the affinity these compounds have for human serum albumin (HSA). These analogs illustrate that decreased affinity for HSA can be achieved while retaining relevant antibacterial activity. The most important factor for reduced HSA affinity is decrease in logP rather than a structural change.

MeSH terms

  • Anti-Bacterial Agents / chemical synthesis
  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology*
  • Bacteria / drug effects*
  • Humans
  • Serum Albumin / chemistry*
  • Structure-Activity Relationship
  • ortho-Aminobenzoates / chemical synthesis
  • ortho-Aminobenzoates / chemistry*
  • ortho-Aminobenzoates / pharmacology*

Substances

  • Anti-Bacterial Agents
  • Serum Albumin
  • ortho-Aminobenzoates