Synthesis of isoxazole-containing sulfonamides with potent carbonic anhydrase II and VII inhibitory properties

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• 作者：Cevher Altug^a ; ^{caltug@gmail.com} ; Hanife Gü ; neş^a ; Alessio Nocentini^b ; Simona Maria Monti^c ; Martina Buonanno^c ; Claudiu T. Supuran^b ; ^{claudiu.supuran@unifi.it}
• 关键词：5-Amino isoxazole ; 5-Amidoisoxazole ; Carbonic anhydrase ; Sulfonamide ; Amide
• 刊名：Bioorganic & Medicinal Chemistry
• 出版年：2017
• 出版时间：15 February 2017
• 年：2017
• 卷：25
• 期：4
• 页码：1456-1464
• 全文大小：2103 K
• 卷排序：25

文摘

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 KIs in the range of 0.5–49.3 nM and hCA VII, a recently validated anti-neuropathic pain target with KIs in the range of 4.3–51.9 nM.