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分别以1,3,5-三苯甲酰基-α-D-核糖、3,5-二苯甲酰基-2-脱氧-2,2-二氟戊呋喃糖-1-酮和D-木糖为原料,经由烟酰胺核苷及烟酰胺核苷酸中间体,合成了系列糖环经氟原子取代的烟酰胺腺嘌呤二核苷酸(NAD)类CD38抑制剂.基于对CD38的水解抑制能力的考察,评价了所合成氟代NAD类似物的活性.结果表明,糖环上氟原子取代的数目和位置对抑制剂活性的影响十分明显,烟酰胺核苷的端基构型对活性的影响较大.2个化合物均显示出非常好的CD38抑制活性,其中化合物2a的抑制活性高出阳性对照物阿糖型氟代烟酰胺腺嘌呤二核苷酸2个数量级.
1,3,5-tribenzoyl-α-D-ribose, 3,5-dibenzoyl-2-deoxy-2,2-difluoropentafuranos-1-one and D-xylose As a starting material, nicotinamide adenine dinucleotide (NAD) CD38 inhibitor with a series of sugar ring substituted by fluorine atoms was synthesized via nicotinamide nucleoside and nicotinamide nucleotide intermediates.Based on the ability of inhibiting the hydrolysis of CD38 The results showed that the effect of the number and position of fluorine atoms on the sugar ring on the activity of the inhibitor was very obvious. The effect of terminal configuration of nicotinamide nucleosides on the activity The larger two compounds all showed very good CD38 inhibitory activity, with the inhibitory activity of compound 2a being two orders of magnitude higher than that of the positive control, arabinofluoronicotinamide adenine dinucleotide.