Discovery of MK-7655, a 尾-lactamase inhibitor for combination with Primaxin庐
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- 作者：Timothy A. Blizzard ; Helen Chen ; Seongkon Kim ; Jane Wu ; Rena Bodner ; C ; ido Gude ; Jason Imbriglio ; Katherine Young ; Young-Whan Park ; Aimie Ogawa ; Susan Raghoobar ; Nichelle Hairston ; Ronald E. Painter ; Doug Wisniewski ; Giovanna Scapin ; Paula Fitzgerald ; N ; ini Sharma ; Jun Lu ; Sookhee Ha ; Jeff Hermes ; Milton L. Hammond ; et al.
- 关键词：尾-Lactamase inhibitor ; MK-7655 ; Antibacterial ; Imipenem ; Antibiotic
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：1 February, 2014
- 年：2014
- 卷：24
- 期：3
- 页码：780-785
- 全文大小：2678 K
文摘
尾-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 尾-lactamase mediated antibiotic resistance. The piperidine analog 3 (MK-7655) inhibited both class A and C 尾-lactamases in vitro. It effectively restored imipenem鈥檚 activity against imipenem-resistant Pseudomonas and Klebsiella strains at clinically achievable concentrations. A combination of MK-7655 and Primaxin庐 is currently in phase II clinical trials for the treatment of Gram-negative bacterial infections.