PDF(Pubmed)
Abstract：
A small library of 79 substituted phenylsulfonamidoalkyl sulfamates, 1b-79b, was synthesized starting from arylsulfonyl chlorides and amino alcohols with different numbers of methylene groups between the hydroxyl and amino moieties yielding intermediates 1a-79a, followed by the reaction of the latter with sulfamoyl chloride. All compounds were screened for their inhibitory activity on bovine carbonic anhydrase II. Compounds 1a-79a showed no inhibition of the enzyme, in contrast to sulfamates 1b-79b. Thus, the inhibitory potential of compounds 1b-79b towards this enzyme depends on the substituent and the substitution pattern of the phenyl group as well as the length of the spacer. Bulkier substituents in the para position proved to be better for inhibiting CAII than compounds with the same substituent in the meta or ortho position. For many substitution patterns, compounds with shorter spacer lengths were superior to those with long chain spacers. Compounds with shorter spacer lengths performed better than those with longer chain spacers for a variety of substitution patterns. The most active compound held inhibition constant as low as Ki = 0.67 μM (for 49b) and a tert-butyl substituent in para position and acted as a competitive inhibitor of the enzyme.
摘要：
79个取代的苯基磺酰氨基烷基氨基磺酸盐的小文库，1b-79b,从芳基磺酰氯和氨基醇开始合成，在羟基和氨基部分之间具有不同数量的亚甲基基团，产生中间体1a-79a，然后后者与氨磺酰氯反应。筛选所有化合物对牛碳酸酐酶II的抑制活性。化合物1a-79a对酶没有抑制作用，与氨基磺酸盐1b-79b相反。因此，化合物1b-79b对该酶的抑制潜力取决于苯基的取代基和取代模式以及间隔基的长度。与在间位或邻位具有相同取代基的化合物相比，在对位的较大取代基对抑制CAII更好。对于许多替代模式，间隔区长度较短的化合物优于具有长链间隔区的化合物。对于各种取代模式,具有较短间隔区长度的化合物比具有较长链间隔区的化合物表现更好。最具活性的化合物保持的抑制常数低至Ki=0.67μM（对于49b），对位有叔丁基取代基，并充当该酶的竞争性抑制剂。
