Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Adiyaman University, 02040 Adiyaman, Turkey.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Adiyaman University, 02040 Adiyaman, Turkey.
Bioorg Chem. 2018 Apr;77:542-547. doi: 10.1016/j.bioorg.2018.02.015. Epub 2018 Feb 15.
A series of novel 1,3-diaryltriazene-substituted sulfonamides was synthesized by reaction of diazonium salt of 4-amino benzenesulfonamide with substituted aromatic amines. The obtained 1,3-diaryltriazene-substituted sulfonamides were investigated as inhibitors of four selected human carbonic anhydrase (CA, EC 4.2.1.1) isoforms (hCA I, hCA II, hCA VII and hCA IX) are involved in various diseases such as glaucoma, epilepsy, retinitis pigmentosa, cancer, obesity, etc. All these sulfonamides were found to be potent inhibitors of the cytosolic isoform hCA II with low nanomolar to sub-nanomolar Ks in the range of 0.2-21.5 nM, as well as a moderate selectivity against other cytosolic isoforms hCA I and hCA VII, and great selectivity against membrane-bound isoform hCA IX was observed. Since hCA II is an important drug target for antiglaucoma agents and diuretics, these isoform-selective inhibitors may be considered of interest as tools for the development of new candidates for these conditions.
通过将 4-氨基苯磺酰胺的重氮盐与取代的芳族胺反应，合成了一系列新型 1,3-二芳基三嗪取代的磺酰胺。所得到的 1,3-二芳基三嗪取代的磺酰胺被用作四种选定的人碳酸酐酶（CA，EC 4.2.1.1）同工酶（hCA I、hCA II、hCA VII 和 hCA IX）的抑制剂，这些同工酶与各种疾病有关，如青光眼、癫痫、视网膜色素变性、癌症、肥胖症等。所有这些磺酰胺都被发现是细胞溶质同工酶 hCA II 的有效抑制剂，其在 0.2-21.5 nM 的范围内对 hCA II 的 Ks 值低至亚纳摩尔，对其他细胞溶质同工酶 hCA I 和 hCA VII 具有中等选择性，对膜结合同工酶 hCA IX 具有很大选择性。由于 hCA II 是抗青光眼药物和利尿剂的重要药物靶标，因此这些同工酶选择性抑制剂可能被认为是开发这些疾病新候选药物的有用工具。
