细菌 NAD+-依赖性 DNA 连接酶抑制剂的发现：抗菌活性的优化。
Discovery of bacterial NAD+-dependent DNA ligase inhibitors: optimization of antibacterial activity.
机构信息
Infection Innovative Medicines Unit, AstraZeneca R&D Boston, Waltham, MA 02451, USA.
出版信息
Bioorg Med Chem Lett. 2011 Aug 1;21(15):4556-60. doi: 10.1016/j.bmcl.2011.05.128. Epub 2011 Jun 12.
PMID:21719282
Abstract
Optimization of adenosine analog inhibitors of bacterial NAD(+)-dependent DNA ligase is discussed. Antibacterial activity against Streptococcus pneumoniae and Staphylococcus aureus was improved by modification of the 2-position substituent on the adenine ring and 3'- and 5'-substituents on the ribose. Compounds with logD values 1.5-2.5 maximized potency and maintained drug-like physical properties.
摘要
讨论了细菌 NAD（+）依赖性 DNA 连接酶的腺苷类似物抑制剂的优化。通过修饰腺嘌呤环上的 2-位取代基以及核糖上的 3′和 5′取代基，提高了对肺炎链球菌和金黄色葡萄球菌的抗菌活性。具有 1.5-2.5 的 logD 值的化合物最大限度地提高了效力并保持了类药性的物理性质。
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