Altug Cevher, Güneş Hanife, Nocentini Alessio, Monti Simona Maria, Buonanno Martina, Supuran Claudiu T
Department of Chemistry, Abant Izzet Baysal University, TR-14280 Bolu, Turkey.
Department of Chemistry, Abant Izzet Baysal University, TR-14280 Bolu, Turkey.
Bioorg Med Chem. 2017 Feb 15;25(4):1456-1464. doi: 10.1016/j.bmc.2017.01.008. Epub 2017 Jan 11.
Two series of benzenesulfonamide containing isoxazole compounds were prepared by using conventional and microwave (MW) methods. 5-Amino-3-aryl-N-(4-sulfamoylphenyl)isoxazole-4-carboxamide derivatives were synthesized by the reaction of hydroxymoyl chlorides with 2-cyano-N-(4-sulfamoylphenyl)acetamide in the presence of triethylamine. The synthesized 5-amino isoxazoles were reacted with various benzoyl chlorides in order to obtain 5-amidoisoxazoles. The novel compounds were screened in vitro as inhibitors of four human (h) isoforms of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1): hCA I, hCA II, hCA IV and hCA VII. The derivatives of the first series were shown to possess excellent inhibitory activity against the cytosolic isoform hCA II, an antiglaucoma drug target, with Ks in the range of 0.5-49.3nM and hCA VII, a recently validated anti-neuropathic pain target with Ks in the range of 4.3-51.9nM.
采用常规方法和微波（MW）方法制备了两系列含异恶唑的苯磺酰胺化合物。通过羟基甲酰氯与2-氰基-N-(4-氨磺酰基苯基)乙酰胺在三乙胺存在下反应，合成了5-氨基-3-芳基-N-(4-氨磺酰基苯基)异恶唑-4-甲酰胺衍生物。为了得到5-酰胺基异恶唑，使合成的5-氨基异恶唑与各种苯甲酰氯反应。对这些新型化合物进行了体外筛选，以检测它们作为金属酶碳酸酐酶（CA，EC 4.2.1.1）的四种人类（h）同工型抑制剂的活性：hCA I、hCA II、hCA IV和hCA VII。结果表明，第一系列衍生物对胞质同工型hCA II（一种抗青光眼药物靶点，Ks范围为0.5-49.3 nM）和hCA VII（一种最近被证实的抗神经性疼痛靶点，Ks范围为4.3-51.9 nM）具有优异的抑制活性。
