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Herein, we report the inhibition properties of isomeric families of sulfonamidopropyl\u2010dicarba\u2010<jats:italic>closo<\/jats:italic>\u2010dodecaboranes group(s) prepared using a new direct five\u2010step synthesis from the corresponding parent cages. The protocol offers a reliable solution for synthesis of singly and doubly substituted dicarba\u2010<jats:italic>closo<\/jats:italic>\u2010dodecaboranes with a different geometric position of carbon atoms. The <jats:italic>closo<\/jats:italic>\u2010compounds from the <jats:italic>ortho<\/jats:italic>\u2010 and <jats:italic>meta<\/jats:italic>\u2010series were then degraded to corresponding 11\u2010vertex dicarba\u2010<jats:italic>nido<\/jats:italic>\u2010undecaborate(1\u2212) anions. All compounds show in vitro enzymatic activity against CA IX in the low nanomolar or subnanomolar range. This is accompanied by clear isomer dependence of the inhibition constant (<jats:italic>K<\/jats:italic><jats:sub>i<\/jats:sub>) and selectivity towards CA IX. Decreasing trends in <jats:italic>K<\/jats:italic><jats:sub>i<\/jats:sub> and selectivity index (<jats:italic>S<\/jats:italic><jats:sub>I<\/jats:sub>) values are observed with increasing separation of the cage carbon atoms. Interactions of compounds with the active sites of CA IX were explored with X\u2010ray crystallography, and eight high\u2010resolution crystal structures uncovered the structural basis of inhibition potency and selectivity.<\/jats:p>","DOI":"10.1002\/chem.202002809","type":"journal-article","created":{"date-parts":[[2020,8,5]],"date-time":"2020-08-05T09:06:57Z","timestamp":1596618417000},"page":"16541-16553","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Direct Introduction of an Alkylsulfonamido Group on C\u2010sites of Isomeric Dicarba\u2010<i>closo<\/i>\u2010dodecaboranes: The Influence of Stereochemistry on Inhibitory Activity against the Cancer\u2010Associated Carbonic Anhydrase IX Isoenzyme"],"prefix":"10.1002","volume":"26","author":[{"given":"Jan","family":"Nekvinda","sequence":"first","affiliation":[{"name":"Department of Synthesis Institute of Inorganic Chemistry of, the Czech Academy of Sciences  25068 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