Download MendeleyDiscovery of MK-7655, a beta-lactamase inhibitor for combination with Primaxin().
Blizzard, T.A., Chen, H., Kim, S., Wu, J., Bodner, R., Gude, C., Imbriglio, J., Young, K., Park, Y.W., Ogawa, A., Raghoobar, S., Hairston, N., Painter, R.E., Wisniewski, D., Scapin, G., Fitzgerald, P., Sharma, N., Lu, J., Ha, S., Hermes, J., Hammond, M.L.(2014) Bioorg Med Chem Lett 24: 780-785
- PubMed: 24433862
- DOI: https://doi.org/10.1016/j.bmcl.2013.12.101
- Primary Citation of Related Structures:
4NK3 - PubMed Abstract:
β-Lactamase inhibitors with a bicyclic urea core and a variety of heterocyclic side chains were prepared and evaluated as potential partners for combination with imipenem to overcome class A and C β-lactamase mediated antibiotic resistance. The piperidine analog 3 (MK-7655) inhibited both class A and C β-lactamases in vitro. It effectively restored imipenem's activity against imipenem-resistant Pseudomonas and Klebsiella strains at clinically achievable concentrations. A combination of MK-7655 and Primaxin® is currently in phase II clinical trials for the treatment of Gram-negative bacterial infections.
Organizational Affiliation:
Department of Medicinal Chemistry, Merck Research Labs, Rahway, NJ 07065, USA. Electronic address: [email protected].
