Carbaboranes as pharmacophores: similarities and differences between aspirin and asborin

Abstract

In medicinal chemistry carbaboranes have been used almost exclusively as boron carriers for boron neutron capture therapy (BNCT). Recent developments extended the carrier approach and use carbaboranes as scaffolds for radiodiagnostic or therapeutic agents. Most recent studies, however, focus on carbaboranes as modern hydrophobic pharmacophores. This research employs preferably meta- and para-carbaborane, because these isomers are extremely hydrophobic and very stable. In this paper we therefore investigated the pharmacophoric behavior of the ortho isomer as putative phenyl mimetic by comparing aspirin to asborin, its ortho-carbaborane analogue. Special emphasis is placed on the impact of the cluster properties on the pharmacological profile. Subjects under study are the mode of cyclooxygenase (COX) inhibition, stability, and toxicity. The straightforward syntheses of the corresponding nido compounds as well as their contribution to the pharmacology of the closo precursors will be highlighted. Finally, proof will be given that the ortho-carbaborane core of asborin merits the designation "pharmacophore" by definition and is a multifunctional group rather than just a hydrophobic, bulky spectator.