Synthesis and activity of 2-(sulfonamido)methyl-carbapenems: discovery of a novel, anti-MRSA 1,8-naphthosultam pharmacophore.
A series of 1beta-methyl carbapenems substituted at the 2-position with lipophilic, acyclic and cyclic (sulfonamido)methyl groups was prepared and evaluated for activity against resistant gram-positive bacteria. From these studies, the 1,8-naphthosultamyl group emerged as a novel, PBP2a-binding, anti-MRSA pharmacophore worthy of further exploration.
Wilkening
R R
RR
Department of Medicinal Chemistry, Merck Research Laboratories, Merck & Co., Inc., Rahway, New Jersey 07065-0900, USA.
Ratcliffe
R W
RW
Wildonger
K J
KJ
Cama
L D
LD
Dykstra
K D
KD
DiNinno
F P
FP
Blizzard
T A
TA
Hammond
M L
ML
Heck
J V
JV
Dorso
K L
KL
St Rose
E
E
Kohler
J
J
Hammond
G G
GG
D001426:Bacterial Proteins; D015780:Carbapenems / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism; D004352:Drug Resistance, Microbial; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D006602:Hexosyltransferases; D008826:Microbial Sensitivity Tests; D002267:Muramoylpentapeptide Carboxypeptidase / Q000187:drug effects / Q000378:metabolism; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases
D001426:Bacterial Proteins; D015780:Carbapenems; D002352:Carrier Proteins; D046915:Penicillin-Binding Proteins; D010458:Peptidyl Transferases; D006602:Hexosyltransferases; D002267:Muramoylpentapeptide Carboxypeptidase