Synthesis,Characterization and NO Synthase Inhibition Testing of 2‐Aryl‐5‐aroyl‐3,4,5,6‐tetrahydropyrimidinium Chlorides |
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| Authors: | Ullvi Bluhm Jean‐Luc Boucher Bernd Clement Ulrich Girreser Dieter Heber Booma Ramassamy Ulrich Wolschendorf |
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| Institution: | 1. Pharmaceutical Institute, Department of Pharmaceutical Chemistry, Christian‐Albrechts–University of Kiel, Kiel, Germany;2. Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, UMR 8601, University Paris Descartes, Paris, Cedex 06, France |
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| 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. |
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