The synthesis and antibacterial activity of 1,3,4-thiadiazole phenyl oxazolidinone analogues.
Replacement of the morpholine C-ring of linezolid 1 with a 1,3,4-thiadiazolyl ring leads to oxazolidinone analogues 5 having potent antibacterial activity against both gram-positive and gram-negative organisms. Conversion of the C5 acetamide group to a thioacetamide further increases the potency of these compounds.
Thomasco
Lisa M
LM
Discovery-Chemistry and Discovery-Infectious Diseases, Pharmacia Corporation, 7000 Portage Road, Kalamazoo, MI 49001, USA. lisa.m.thomasco@pfizer.com
Gadwood
Robert C
RC
Weaver
Elizabeth A
EA
Ochoada
Jason M
JM
Ford
Charles W
CW
Zurenko
Gary E
GE
Hamel
Judith C
JC
Stapert
Douglas
D
Moerman
Judy K
JK
Schaadt
Ronda D
RD
Yagi
Betty H
BH
D000081:Acetamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D000069349:Linezolid; D008826:Microbial Sensitivity Tests; D023303:Oxazolidinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D010636:Phenols / Q000737:chemistry*; D051381:Rats; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000737:chemistry*; D013853:Thioacetamide / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D000081:Acetamides; D000900:Anti-Bacterial Agents; D023303:Oxazolidinones; D010636:Phenols; D013830:Thiadiazoles; D013853:Thioacetamide; D000069349:Linezolid