IntroductionTetrazoles and 1,2,4-oxadiazol-5-ones are heterocyclic acids that have attracted a lot of interest in medicinal chemistry. The 1,2,4-oxadiazol-5-one heterocycle is a relative newcomer among binding groups in modern drug design. It has already become a promising bioisosteric 1replacement for carboxylic acids, for example, in non-peptide angiotensin II receptor antagonists 2(for lowering blood pressure) and in cholecystokinin antagonists 3(for the treatment of certain neuropsychiatric disorders). While pKavalues Two structurally related antihypertension drugs, one with a 1,2,4-oxadiazol-5-one and another with a tetrazole group, were reported to have pKavalues of 6.1 and 5.3, respectively.6a,btend to be comparable, tetrazoles and 1,2,4-oxadiazol-5-ones are more lipophilic than carboxylic acids.1The change in water solubility, binding affinity, metabolic rate and bioavailability become important in the optimisation of pharmacological properties during the development of new drugs.Their effectiveness as ligands should make acidic heterocycles promising binding groups in supramolecular chemistry, too. While studying non-covalent complexes with amidine bases, we have recently been able to demonstrate that the replacement of carboxylic acids by tetrazoles in complexes with heterocyclic amidine1causes subtle changes in the binding mode that affect the properties of the complexes both in the solid and solution phase.4Following a preliminary report on the complexation of other acidic heterocycles,5we now describe details of the synthesis, crystal structure and solution binding studies of non-covalent complexes between several 1,2,4-oxadiazol-5-ones and the relatively simple trisimidazoline receptor1.