Preparation and Characterization of Inclusion Complexes of N-Substituted-benzenesulfonyl Heterocycles with Cyclodextrins

Abstract

As part of our ongoing drug discovery program we have prepared a library of N-substituted-benzenesulfonyl hetero cycles. Both the heterocyclic and the benzenesulfonyl moiety are considered privileged structures. The insolubility of these compounds has hampered the study of their biological properties. We have prepared and studied the inclusion complexes of representative N-benzenesulfonyl hetero cycles with α-, β-, and γ-cyclodextrins. The complexes have been characterized by spectroscopic (1H-NMR, IR, UV and Raman) and chromatographic methods (HPLC/MS), as well as phase solubility techniques. Molecular modeling techniques have been correlated with the experimental results in order to have a predictive tool to include in the development of novel compounds. The results show that the benzenesulfonyl moiety interacts with the hydrophobic pocket of the cyclodextrin molecule. The phase-solubility diagrams show that complexation with cyclodextrins, in particular β-cyclodextrin can significantly increase the apparent aqueous solubility of the N-benzenesulfonyl heterocycles.