The discovery and structure-activity relationships leading to CE-156811, a difluorophenyl cyclopropyl fluoroether: a novel potent antibacterial analog derived from hygromycin A

Phuong T Le; Steven J Brickner; Sarah K Wade; Katherine Brighty; Rhonda Monahan; Gregory G Stone; Dennis Girard; Steve Finegan; Joan Duignan; John Schafer; Meghan Maloney; Richard P Zaniewski; Ann G Connolly; Jennifer Liras; Jon Bordner; Ivan Samardjiev

doi:10.1016/j.bmcl.2010.11.022

The discovery and structure-activity relationships leading to CE-156811, a difluorophenyl cyclopropyl fluoroether: a novel potent antibacterial analog derived from hygromycin A

Bioorg Med Chem Lett. 2011 Jan 1;21(1):276-9. doi: 10.1016/j.bmcl.2010.11.022. Epub 2010 Nov 10.

Authors

Phuong T Le¹, Steven J Brickner, Sarah K Wade, Katherine Brighty, Rhonda Monahan, Gregory G Stone, Dennis Girard, Steve Finegan, Joan Duignan, John Schafer, Meghan Maloney, Richard P Zaniewski, Ann G Connolly, Jennifer Liras, Jon Bordner, Ivan Samardjiev

Affiliation

¹ Pfizer Worldwide Research & Development, La Jolla Laboratories, Pfizer Inc, La Jolla, CA 92121, United States. phuong.le@pfizer.com

PMID: 21115249
DOI: 10.1016/j.bmcl.2010.11.022

Abstract

SAR studies and optimization of various modified Hygromycin A fluoroalkyl ethers, which led to the discovery of the highly potent 4'-(2-cyclopropyl-2-fluoroethyl ether) antibacterial CE-156811 (1) derived from truncation of the ribose ring and difluorination of the phenyl found in Hygromycin A, are discussed.

MeSH terms

Administration, Oral
Animals
Anti-Bacterial Agents / chemical synthesis
Anti-Bacterial Agents / chemistry*
Anti-Bacterial Agents / pharmacokinetics
Cinnamates / chemistry*
Dioxoles / chemistry*
Dogs
Drug Evaluation, Preclinical
Haplorhini
Hygromycin B / analogs & derivatives*
Hygromycin B / chemistry
Mice
Microbial Sensitivity Tests
Rats
Structure-Activity Relationship

Substances

Anti-Bacterial Agents
CE 156811
Cinnamates
Dioxoles
Hygromycin B
hygromycin A