Synthesis of a new series of 2,8-disubstituted-2,8-diazaspiro[4,5]decan-1-ones as potential muscarinic agonists

A new series of 2,8-disubstituted-2,8-diazaspiro[4,5]decan-1-ones 2 has been synthesized and tested for affinity towards muscarinic receptors by binding studies in comparison with the model RS-86. The membrane phosphatidylinositol turnover in the presence or absence of carbachol has also been investigated. In both experiments all the new derivatives 2 were found to be less active than the model; only 5g, which retains the imidic moiety, could approach it in potency. A possible explanation for the lack of activity of this class of compounds is given in terms of the computed interaction energies of the minimized ligand-m₁ receptor complex.