Preparation of novel antibacterial agents. Replacement of the central aromatic ring with heterocycles.
Discovery of novel antibacterial agents is a significant challenge. We have recently reported on our discovery of novel antibacterial agents in which we have rapidly optimized potency utilizing a parallel chemistry approach. These advanced leads suffer from high affinity for human serum albumin (HSA). In an effort to decrease the affinity for HSA we have prepared a series of heterocyclic analogs, which retained antibacterial activity and demonstrated reduced affinity for HSA.
Li
Jianke
J
Medicinal Chemistry and Infectious Diseases Biology, Pharmacia Corporation, 301 Henrietta Street, Kalamazoo, MI 49001, USA.
Wakefield
Brian D
BD
Ruble
J Craig
JC
Stiff
Cory M
CM
Romero
Donna L
DL
Marotti
Keith R
KR
Sweeney
Michael T
MT
Zurenko
Gary E
GE
Rohrer
Douglas C
DC
Thorarensen
Atli
A
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D001419:Bacteria / Q000187:drug effects; D006571:Heterocyclic Compounds; D006801:Humans; D008826:Microbial Sensitivity Tests; D011485:Protein Binding; D012709:Serum Albumin / Q000378:metabolism; D013329:Structure-Activity Relationship; D062367:ortho-Aminobenzoates
D000900:Anti-Bacterial Agents; D006571:Heterocyclic Compounds; D012709:Serum Albumin; D062367:ortho-Aminobenzoates; C031385:anthranilic acid