The discovery and structure-activity relationships leading to CE-156811, a difluorophenyl cyclopropyl fluoroether: a novel potent antibacterial analog derived from hygromycin A.
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.
Pfizer Worldwide Research & Development, La Jolla Laboratories, Pfizer Inc, La Jolla, CA 92121, United States. phuong.le@pfizer.com
Phuong T
PT
Le
Steven J
SJ
Brickner
Sarah K
SK
Wade
Katherine
K
Brighty
Rhonda
R
Monahan
Gregory G
GG
Stone
Dennis
D
Girard
Steve
S
Finegan
Joan
J
Duignan
John
J
Schafer
Meghan
M
Maloney
Richard P
RP
Zaniewski
Ann G
AG
Connolly
Jennifer
J
Liras
Jon
J
Bordner
Ivan
I
Samardjiev
D000284:Administration, Oral; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics; D002934:Cinnamates / Q000737:chemistry*; D004149:Dioxoles / Q000737:chemistry*; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D000882:Haplorhini; D006921:Hygromycin B / Q000031:analogs & derivatives* / Q000737:chemistry; D051379:Mice; D008826:Microbial Sensitivity Tests; D051381:Rats; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; C531326:CE 156811; D002934:Cinnamates; D004149:Dioxoles; D006921:Hygromycin B; C026273:hygromycin A