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QSAR based synthesis of novel primaquine ureidoamides

Novel ureidoamides 5a-g, bearing primaquine (PQ) and amino acid moieties, were designed and prepared after a detailed QSAR study. QSAR model was developed based on the results of antimalarial screening of our previously synthesized compounds against the er ythrocytic stages of Plasmodium falciparum strain [1]. Compounds 5a-g were prepared by the aminolysis of N-(1-benzotriazolecarbonyl) - amino acid amides 4a-g with PQ, while amides 4 were obtained from N-(1-benzotriazolecarbonyl) - amino acid chlorides 3a-c and the corresponding amines or hydrazones. Three amino acids (L-leucine, D-phenylglycine, DL-p-chlorophenylglycine), four amines (p-bromoaniline, diphenylmethanamine, (4-chlorophenyl)(phenyl)methanamine)), N-methyl-1, 1, diphenylmethanamine and one hydrazone (4-methoxybenzophenone hydrazone) were used. The synthesis of similar ureidoamides was described by our group in several papers [2, 3], as well as the synthesis of starting N-(1-benzotriazolecarbonyl) - amino acids 2a-c, their chlorides 3a-c [4] and 1-benzotriazole carboxylic acid chloride (BtcCl, 1) [5]. Scheme outlines the general route leading to compounds 5a-g and their synthetic precursors. The structures of newly prepared compounds 5a-g was confirmed by IR, 1H, 13C NMR and MS spectroscopy. The evaluation of their biological (antimalarial, antiproliferative, antioxidative and antimicrobial) activity is in progress.

primaquine ; ureidoamides ; QSAR ; synthesis ; antimalarial activity

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