Synthesis and biological evaluation of novel N,N′-diaryl cyanoguanidines acting as potent and selective carbonic anhydrase II inhibitors
Synthesis and biological evaluation of novel N,N′-diaryl cyanoguanidines acting as potent and selective carbonic anhydrase II inhibitors
复制标题
DOI：
10.1016/j.bioorg.2018.01.022
复制
发表时间：
2018-04-01
影响因子：
5.1
通讯作者：
Supuran, Claudiu T.
中科院分区：
文献类型：
--
作者：
Akocak, Suleyman;Lolak, Nabih;Supuran, Claudiu T.
以二苯基N-氰基碳酰咪酯与磺胺反应，再用取代芳胺处理得到N，N " -二苯基氰脲，合成了一系列新型N，N " -二苯基氰胍。新制备的N，N”-二硝基氰胍对四种人类碳酸酐酶（CA, EC 4.2.1.1）亚型，hCA I和hCA II（胞质），hCA IV（膜结合）和hCA IX（跨膜）具有非常有趣的抑制作用。这些化合物对hCA II亚型均有较强的抑制作用，抑制常数在低纳摩尔范围内，对hCA II的选择性高于hCA I、IV和IX。由于hCA II是抗青光眼药物的重要靶点，这些异构体选择性抑制剂可能被认为是进一步医学/药理学研究的兴趣。(C) 2018爱思唯尔公司版权所有。
A series of novel N,N ''-diaryl cyanoguanidines were synthesized by reacting diphenyl N-cyanocarbonimidate with sulfanilamide followed by treatment of the obtained cyano-O-phenylisourea with substituted aromatic amines. The newly prepared N,N ''-diaryl cyanoguanidines showed a very interesting inhibition profile against four selected human carbonic anhydrase (CA, EC 4.2.1.1) isoforms, hCA I and hCA II (cytosolic), hCA IV (membrane-bound), and hCA IX (transmembrane). All these compounds showed a potent inhibition against isoform hCA II,with inhibition constants in the low nanomolar range, as well as a high selectivity for hCA II over hCA I, IV and IX. Since hCA II is an important drug target for antiglaucoma agents, these isoform-selective inhibitors may be considered of interest for further medicinal/pharmacologic studies. (C) 2018 Elsevier Inc. All rights reserved.