{"abstract": "We investigated the inhibitory activity of several 1,3,4-thiadiazole-sulfonamides against all catalytically active CA (EC 4.2.1.1), CA I-XV. The tail derivatizing the 5-position in the 1,3,4-thiadiazole-2-sulfonamide scaffold was observed to be critical as an inhibitory determinant of these compounds. The high resolution X-ray crystal structure of hCA II in complex with 5-(1-adamantylcarboxamido)-1,3,4-thiadiazole-2-sulfonamide, showed the adamantyl moiety of the inhibitor residing in a less utilized binding pocket than that of most hydrophobic inhibitors, lined by the amino acid residues Ile91, Val121 and Phe131. This binding site may explain the diverse inhibition profiles of 5-carboxamide- and sufonamide-derivatized 1,3,4-thiadiazole-2-sulfonamides and offers a hot spot for designing isoform selective inhibitors, considering that residues 91 and 131 are highly variable among the 13 catalytically active isoforms.", "authors": "Avvaru BS, Wagner JM, Maresca A, Scozzafava A, Robbins AH, Supuran CT, McKenna R.", "chembl_release": {"chembl_release": "CHEMBL_9", "creation_date": "2011-01-20"}, "contact": null, "doc_type": "PUBLICATION", "document_chembl_id": "CHEMBL1208748", "doi": "10.1016/j.bmcl.2010.06.082", "doi_chembl": null, "first_page": "4376", "issue": "15", "journal": "Bioorg Med Chem Lett", "journal_full_title": "Bioorganic & medicinal chemistry letters.", "last_page": "4381", "patent_id": null, "pubmed_id": 20605094, "src_id": 1, "title": "Carbonic anhydrase inhibitors. The X-ray crystal structure of human isoform II in adduct with an adamantyl analogue of acetazolamide resides in a less utilized binding pocket than most hydrophobic inhibitors.", "volume": "20", "year": 2010}