Dipartimento di Chimica G. Ciamician, Università of Bologna, Via Selmi 2, 40126 Bologna, Italy.
ChemMedChem. 2009 Dec;4(12):1991-2001. doi: 10.1002/cmdc.200900309.
2-Azetidinones, commonly known as beta-lactams, are well-known heterocyclic compounds. Herein we described the synthesis and biological evaluation of a series of novel beta-lactams. In vitro inhibition assays against HDAC isoforms showed an interesting isoform-selectivity of these compounds towards HDAC6 and HDAC8. The isoform selectivity changed in response to modification of the azetidinone-ring nitrogen atom substituent. The presence of an N-thiomethyl group is a prerequisite for the activity of these compounds in the micromolar range towards HDAC8.
2-氮杂环丁酮，通常被称为β-内酰胺，是一种众所周知的杂环化合物。在此，我们描述了一系列新型β-内酰胺的合成和生物学评价。对 HDAC 同工酶的体外抑制实验表明，这些化合物对 HDAC6 和 HDAC8 具有有趣的同工酶选择性。氮杂环丁酮环氮原子取代基的修饰会改变同工酶选择性。这些化合物在微摩尔范围内对 HDAC8 的活性需要 N-硫甲基的存在。
