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

Publication date: Available online 11 January 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Cevher Altug, Hanife Güneş, Alessio Nocentini, Simona Maria Monti, Martina Buonanno, Claudiu T. Supuran
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.



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