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Bioorg Med Chem. 2017 Feb 15;25(4):1456-1464. doi: 10.1016/j.bmc.2017.01.008. Epub 2017 Jan 11.

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

Author information

1
Department of Chemistry, Abant Izzet Baysal University, TR-14280 Bolu, Turkey. Electronic address: caltug@gmail.com.
2
Department of Chemistry, Abant Izzet Baysal University, TR-14280 Bolu, Turkey.
3
Università degli Studi di Firenze, NEUROFARBA Dept., Sezione di Scienze Farmaceutiche, Via Ugo Schiff 6, 50019 Sesto Fiorentino, Florence, Italy.
4
Istituto di Biostrutture e Bioimmagini-CNR, via Mezzocannone 16, 80134 Napoli, Italy.
5
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.

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.

KEYWORDS:

5-Amidoisoxazole; 5-Amino isoxazole; Amide; Carbonic anhydrase; Sulfonamide

PMID:
28111158
DOI:
10.1016/j.bmc.2017.01.008
[Indexed for MEDLINE]

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