Breen David, Kennedy Alan R, Suckling Colin J
WestCHEM, Department of Pure & Applied Chemistry, University of Strathclyde, 296 Cathedral Street, Glasgow, G1 1XL, Scotland.
Org Biomol Chem. 2009 Jan 7;7(1):178-86. doi: 10.1039/b814452d. Epub 2008 Nov 7.
A new synthesis of polyamide minor groove binders in which diversity is introduced by the nucleophilic substitution of a 2-sulfido-1,3,2-diazaphospholidinyloxy substituent by volatile secondary amine nucleophiles is described. Such a method has potential value for economically investigating structure-activity relationships in this important class of compounds through library synthesis. As an example using this method are prepared two new minor groove binders with pyrrolidinyl or piperidinyl tail groups that are close relatives of highly active antibacterial minor groove binders with morpholinyl tail groups. The antibacterial activity found against Staphylococcus aureus and Mycobacterium spp. indicates that the pK(a) of this set of compounds is not the dominant factor in determining the antibacterial activity.
描述了一种聚酰胺小沟结合剂的新合成方法，其中通过挥发性仲胺亲核试剂对2-硫代-1,3,2-二氮杂磷环烷氧基取代基进行亲核取代来引入多样性。这种方法对于通过文库合成经济地研究这类重要化合物的构效关系具有潜在价值。作为使用该方法的一个例子，制备了两种具有吡咯烷基或哌啶基尾基的新型小沟结合剂，它们是具有吗啉基尾基的高活性抗菌小沟结合剂的近亲。对金黄色葡萄球菌和分枝杆菌属的抗菌活性表明，这组化合物的pK(a)不是决定抗菌活性的主要因素。
