title: Synthesis of isoxazole-containing sulfonamides with potent carbonic anhydrase II and VII inhibitory properties.
abstract: 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 0.5-49.3nM and hCA VII, a recently validated anti-neuropathic pain target with KIs in the range of 4.3-51.9nM.
authors.affiliation: Department of Chemistry, Abant Izzet Baysal University, TR-14280 Bolu, Turkey. Electronic address: caltug@gmail.com.
authors.forename: Cevher
authors.initials: C
authors.lastname: Altug
authors.affiliation: Department of Chemistry, Abant Izzet Baysal University, TR-14280 Bolu, Turkey.
authors.forename: Hanife
authors.initials: H
authors.lastname: Güneş
authors.affiliation: Università degli Studi di Firenze, NEUROFARBA Dept., Sezione di Scienze Farmaceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Florence, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Nocentini
authors.affiliation: Istituto di Biostrutture e Bioimmagini-CNR, via Mezzocannone 16, 80134 Napoli, Italy.
authors.forename: Simona Maria
authors.initials: SM
authors.lastname: Monti
authors.affiliation: Istituto di Biostrutture e Bioimmagini-CNR, via Mezzocannone 16, 80134 Napoli, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Buonanno
authors.affiliation: Università degli Studi di Firenze, NEUROFARBA Dept., Sezione di Scienze Farmaceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Florence, Italy. Electronic address: claudiu.supuran@unifi.it.
authors.forename: Claudiu T
authors.initials: CT
authors.lastname: Supuran
mesh_terms: D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007555:Isoxazoles / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D007555:Isoxazoles; D013449:Sulfonamides; D024402:Carbonic Anhydrase II; D002256:Carbonic Anhydrases; C477051:carbonic anhydrase VI
keywords: 5-Amidoisoxazole; 5-Amino isoxazole; Amide; Carbonic anhydrase; Sulfonamide