Studies on the synthesis and structure-activity relationships of 2-(2-functionalized pyrrolidin-4-ylthio)-1 beta-methylcarbapenems.
A series of new carbapenem derivatives, which have a pyrrolidin-4-ylthio group substituted with a hydroxyalkyl or carbamoyl group at the 2' position as the C-2 side chain, have been prepared. The antibacterial activity and the stability to renal dehydropeptidase-I of these compounds were investigated, and the structure-activity relationships were studied. Among these new carbapenems, (1R,5S,6S)-2-[(2S,4S)-2-¿(2-hydroxy)ethylmercaptomethyl¿pyrroli din-4 -ylthio]-6-[(1R)-I-hydroxyethyl]-1-methyl-1-carbapen-2-em-3- carboxylic acid (1a) showed the most potent and well balanced activity and was selected as a candidate for further evaluation.
Lee
H W
HW
Research Institute, Chong Kun Dang Corp., Seoul, Korea.
Kim
E N
EN
Son
H J
HJ
Ahn
S K
SK
Chung
K H
KH
Kim
J W
JW
Lee
C R
CR
D000818:Animals; D015780:Carbapenems / Q000138:chemical synthesis / Q000737:chemistry*; D002855:Chromatography, Thin Layer; D004150:Dipeptidases / Q000378:metabolism*; D007668:Kidney / Q000201:enzymology; D013058:Mass Spectrometry; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013329:Structure-Activity Relationship
D015780:Carbapenems; D004150:Dipeptidases; C038937:dipeptidase