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These compounds can be regarded as reduced\u2010flexibility analogues of histamine and histidine, two well\u2010known CA activators. Their activating properties were evaluated against human CA I, II, VA, VII, and XIII. Activity was observed exclusively on CA VA and CA XIII, with\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>A<\/jats:sub>\n                    values in the medium and low micromolar range, respectively. Among the tested molecules, compound (\n                    <jats:italic>R<\/jats:italic>\n                    )\u2010\n                    <jats:bold>2<\/jats:bold>\n                    emerged as a promising lead compound for the development of selective CA XIII activators. Conversely, introduction of a 4\u2010sulfamoylbenzoyl group on the piperazine nitrogen atom switched the activity from activation to inhibition, yielding compound\n                    <jats:bold>6<\/jats:bold>\n                    as a potent inhibitor of hCA II.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.70353","type":"journal-article","created":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T03:48:31Z","timestamp":1783136911000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Piperazine Derivatives Carrying an Imidazole Ring as Selective Modulators of Human Carbonic Anhydrase Isozymes"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9529-7107","authenticated-orcid":false,"given":"Alessio","family":"Gabellini","sequence":"first","affiliation":[{"name":"Department NEUROFARBA Section of Pharmaceutical and Nutraceutical Sciences University of Florence  Sesto Fiorentino 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