Synthesis, Characterization and NO Synthase Inhibition Testing of 2‐Aryl‐5‐aroyl‐3,4,5,6‐tetrahydropyrimidinium Chlorides

Abstract

Aryl methyl ketones can be easily converted to 1‐aryl‐2‐dimethylaminomethylpropenones that are known as interesting lead structures for drug development. By reaction of these enone Mannich bases with benzamidines, a series of new 2‐aryl‐5‐aroyl‐3,4,5,6‐tetrahydopyrimidines were synthesized. These structures were characterized according to their lipophilicity. Thirty five tetrahydropyrimidines were evaluated as nitric oxide synthase (NOS) inhibitors in usual screening assays. Some interesting members of this class of compounds were forwarded to more detailed tests determining mechanism of inhibition and inhibition of NADH consumption. The investigated structures showed modest activity of NOS inhibition. However, some new tetrahydropyrimidines bearing extended aromatic substituents such as the naphthyloyl or biphenyloyl residue displayed some activity of neuronal NOS and endothelial NOS inhibition but without selectivity for an isoform and should be of interest for further modifications.