title: Preparation of novel anthranilic acids as antibacterial agents: extensive evaluation of structural and physical properties on antibacterial activity and human serum albumin affinity.
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.
authors.affiliation: Medicinal Chemistry and Infectious Diseases Biology, Pharmacia Corporation, 301 Henrietta Street, Kalamazoo, MI 49001, USA. atli.thorarensen@pfizer.com
authors.forename: Atli
authors.initials: A
authors.lastname: Thorarensen
authors.forename: Jianke
authors.initials: J
authors.lastname: Li
authors.forename: Brian D
authors.initials: BD
authors.lastname: Wakefield
authors.forename: Donna L
authors.initials: DL
authors.lastname: Romero
authors.forename: Keith R
authors.initials: KR
authors.lastname: Marotti
authors.forename: Michael T
authors.initials: MT
authors.lastname: Sweeney
authors.forename: Gary E
authors.initials: GE
authors.lastname: Zurenko
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Sarver
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D006801:Humans; D012709:Serum Albumin / Q000737:chemistry*; D013329:Structure-Activity Relationship; D062367:ortho-Aminobenzoates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D012709:Serum Albumin; D062367:ortho-Aminobenzoates