New Dihydrothiazole Benzensulfonamides: Looking for Selectivity toward Carbonic Anhydrase Isoforms I, II, IX, and XII

  • ACS Med Chem Lett. 2020 Feb 13;11(5):852-856. doi: 10.1021/acsmedchemlett.9b00644.
Rita Meleddu  1 ,  Simona Distinto  1 ,  Filippo Cottiglia  1 ,  Rossella Angius  2 ,  Pierluigi Caboni  1 ,  Andrea Angeli  3 ,  Claudia Melis  1 ,  Serenella Deplano  1 ,  Stefano Alcaro  4 ,  Francesco Ortuso  4 ,  Claudiu T Supuran  3 ,  Elias Maccioni  1
Affiliations
  • 1. Department of Life and Environmental Sciences, University of Cagliari, Via Ospedale 72, 09124 Cagliari, Italy.
  • 2. Laboratorio NMR e Tecnologie Bioanalitiche, Sardegna Ricerche, 09010 Pula, CA, Italy.
  • 3. Dipartimento NEUROFARBA, Sezione di Scienze Farmaceutiche, Università degli Studi di Firenze, Sesto Fiorentino, 50139 Florence, Italy.
  • 4. Dipartimento di Scienze della Salute, Università Magna Graecia di Catanzaro, Campus "S. Venuta", Viale Europa, 88100 Catanzaro, Italy.
PMID: 32435395 DOI: 10.1021/acsmedchemlett.9b00644
Abstract

In the present study we investigated the structure-activity relationships of a new series of 4-[(3-ethyl-4-aryl-2,3-dihydro-1,3-thiazol-2-ylidene)amino]benzene-1-sulfonamides (EMAC10101a-m). All synthesized compounds, with the exception of compound EMAC10101k, preferentially inhibit off-target hCA II isoform. Within the series, compound EMAC10101d, bearing a 2,4-dichorophenyl substituent in position 4 of the dihydrothiazole ring, was the most potent and selective toward hCA II with an inhibitory activity in the low nanomolar range.

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