Journal of Medicinal Chemistry · 1987 · 110 citations · 0 references
PharmacyMedicinal ChemistryPharmacologyDrug DesignDrug DiscoveryStructure-activity RelationshipsEnzyme InhibitionPotency OptimizationSolubility EnhancementSolubility OptimizationStructure-activity Relationship AnalysisSulfur ChemistryAntiglaucoma TherapyAqueous Solubility ImprovementAqueous Solubility OptimizationAqueous Solubility PredictionCarbonic Anhydrase FunctionCarbonic Anhydrase InhibitorsChemical Structure-activity RelationshipsSolubility
An attempt to develop a water-soluble carbonic anhydrase inhibitor focused on exploring structure-activity relationships in the thienothiopyransulfonamide class. The strategy to influence water solubility while retaining carbonic anhydrase activity involved the introduction of a hydroxyl moiety and adjusting the oxidation state of the sulfur on the thiopyran portion of the molecule. Compounds 4 and 17 best fit the criteria of aqueous solubility and inhibitory potency vs. human carbonic anhydrase II and are candidates for evaluation as topically effective antiglaucoma agents.