作为金属β-内酰胺酶抑制剂的卡托普利类似物
Captopril analogues as metallo-β-lactamase inhibitors.
作者信息
Yusof Yusralina, Tan Daniel T C, Arjomandi Omid Khalili, Schenk Gerhard, McGeary Ross P
机构信息
School of Chemistry and Molecular Biosciences, The University of Queensland, Queensland 4072, Australia.
School of Chemistry and Molecular Biosciences, The University of Queensland, Queensland 4072, Australia.
出版信息
Bioorg Med Chem Lett. 2016 Mar 15;26(6):1589-1593. doi: 10.1016/j.bmcl.2016.02.007. Epub 2016 Feb 4.
A number of captopril analogues were synthesised and tested as inhibitors of the metallo-β-lactamase IMP-1. Structure-activity studies showed that the methyl group was unimportant for activity, and that the potencies of these inhibitors could be best improved by shortening the length of the mercaptoalkanoyl side-chain. Replacing the thiol group with a carboxylic acid led to complete loss of activity, and extending the length of the carboxylate group led to decreased potency. Good activity could be maintained by substituting the proline ring with pipecolic acid.
合成了多种卡托普利类似物，并将其作为金属β-内酰胺酶IMP-1的抑制剂进行测试。构效关系研究表明，甲基对活性并不重要，缩短巯基烷酰基侧链的长度能最好地提高这些抑制剂的效力。用羧酸取代硫醇基团会导致活性完全丧失，延长羧酸盐基团的长度会导致效力降低。用哌啶酸取代脯氨酸环可维持良好的活性。
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