Synthesis and activity of 2-(sulfonamido)methyl-carbapenems: discovery of a novel, anti-MRSA 1,8-naphthosultam pharmacophore

R R Wilkening; R W Ratcliffe; K J Wildonger; L D Cama; K D Dykstra; F P DiNinno; T A Blizzard; M L Hammond; J V Heck; K L Dorso; E St Rose; J Kohler; G G Hammond

doi:10.1016/s0960-894x(99)00070-0

Synthesis and activity of 2-(sulfonamido)methyl-carbapenems: discovery of a novel, anti-MRSA 1,8-naphthosultam pharmacophore

Bioorg Med Chem Lett. 1999 Mar 8;9(5):673-8. doi: 10.1016/s0960-894x(99)00070-0.

Authors

R R Wilkening¹, R W Ratcliffe, K J Wildonger, L D Cama, K D Dykstra, F P DiNinno, T A Blizzard, M L Hammond, J V Heck, K L Dorso, E St Rose, J Kohler, G G Hammond

Affiliation

¹ Department of Medicinal Chemistry, Merck Research Laboratories, Merck & Co., Inc., Rahway, New Jersey 07065-0900, USA.

PMID: 10201827
DOI: 10.1016/s0960-894x(99)00070-0

Abstract

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.

MeSH terms

Bacterial Proteins*
Carbapenems / chemical synthesis*
Carbapenems / chemistry
Carbapenems / pharmacology
Carrier Proteins / drug effects
Carrier Proteins / metabolism
Drug Resistance, Microbial
Gram-Positive Bacteria / drug effects*
Hexosyltransferases*
Microbial Sensitivity Tests
Muramoylpentapeptide Carboxypeptidase / drug effects
Muramoylpentapeptide Carboxypeptidase / metabolism
Penicillin-Binding Proteins
Peptidyl Transferases*

Substances

Bacterial Proteins
Carbapenems
Carrier Proteins
Penicillin-Binding Proteins
Peptidyl Transferases
Hexosyltransferases
Muramoylpentapeptide Carboxypeptidase