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Abstract
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Diamondoids are cage hydrocarbon molecules that can be described as fully hydrogen-terminated nanometer-sized diamonds.1 Adamantane molecule, corresponding to C10H16 formula, is the smallest Diamondoid. Derivatives of adamantane have found numerous applications in medicinal chemistry. The adamantyl group is present in eight compounds in current clinical use for the treatment of neurodegenerative disorders, viral infections and type-2 diabetes. Having the “lipophilic bullet” (adamantane is often viewed as providing the critical lipophilicity) readily available as an “add-on” for known pharmacophors, it was used in the modification of drugs. The adamantane modifications were chosen to enhance lipophilicity and stability of the drugs, thereby improving their pharmacokinetics.2
Dihydropyrimidinones (DHPMs) have widespread pharmacological activities, and are regarded as one of the most important groups of drug-like scaffolds.3 The Biginelli reaction is ranked as one of the most powerful tools for the facile synthesis of these scaffolds.
In this work, novel diamondoid-modified pyrimidines were synthesized in two steps. Firstly adamantly-containing active methylene compound 1 was synthesized by the reaction of amantadine (1-aminoadamantane) with ethyl acetoacetate. Then Biginelli reaction of 1 with thiourea 2 and benzaldehyde derivatives 3 afforded pyrimidines 4a-h. All synthesized compounds were completely characterized by FT-IR, 1H and 13C NMR spectroscopy.
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