Novel antibacterial azetidine lincosamides.
The synthesis and evaluation of novel azetidine lincosamides 1 are described. Eleven new (3-trans-alkyl)azetidine-2-carboxylic acids were synthesized via alkylation of N-TBS-4-oxo-azetidine-2-carboxylic acid and subsequent elaboration then coupled to 7-chloro-1-methylthio-lincosamine. The resulting lincosamides differ from the drug clindamycin in both the size of the ring and the position/structure of the alkyl side-chain. SAR within the series was explored with attention to alkyl variants in positions 1 and 3 of the azetidine ring.
O'Dowd
Hardwin
H
Pfizer Global Research & Development, Fremont, Formerly Vicuron Pharmaceuticals, Inc., CA 94555, USA. hardwin@hotmail.com
Lewis
Jason G
JG
Trias
Joaquim
J
Asano
Rumi
R
Blais
Johanne
J
Lopez
Sara L
SL
Park
Craig K
CK
Wu
Charlotte
C
Wang
Wen
W
Gordeev
Mikhail F
MF
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001384:Azetidines / Q000737:chemistry*; D055231:Lincosamides; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D050296:Microbial Viability / Q000187:drug effects; D015394:Molecular Structure; D014176:Protein Biosynthesis / Q000187:drug effects / Q000235:genetics; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics
D000900:Anti-Bacterial Agents; D001384:Azetidines; D055231:Lincosamides; D018942:Macrolides; C082735:azetidine