Medicinal Chemistry Research Division, Vaagdevi College of Pharmacy, Hanamkonda, Warangal 506 001, Andhra Pradesh, India.
Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi 835 215, Jharkhand, India.
Bioorg Chem. 2014 Dec;57:116-120. doi: 10.1016/j.bioorg.2014.08.005. Epub 2014 Sep 3.
A series of hydroxamates (4a-4l) were prepared from p-aminobenzoic acid to inhibit HDAC8. The idea is to substitute rigid aromatic ring in place of less rigid piperazine ring of hydroxamates reported earlier by our group. It is expected to increase potency retaining the selectivity. Result obtained suggested that the modifications carried out retained the selectivity towards HDAC8 isoform and increasing the potency in very few cases. Increase in potency is also associated with variation in cap aryl region. Two compounds (4f &4l) were found to inhibit HDAC8 at concentrations (IC50) less than 20μM.
我们从对氨基苯甲酸出发，制备了一系列的羟肟酸类化合物（4a-4l）来抑制 HDAC8。我们的想法是用刚性芳香环取代之前报道的羟肟酸类化合物中不太稳定的哌嗪环，以此来增加化合物的活性并保持对 HDAC8 同型酶的选择性。结果表明，所进行的修饰在大多数情况下保留了对 HDAC8 同型酶的选择性，同时在少数情况下增加了化合物的活性。活性的增加也与帽芳基区域的变化有关。有两个化合物（4f 和 4l）被发现能够在低于 20μM 的浓度下抑制 HDAC8。
