Synthesis and in vitro cytotoxicity evaluation of some N-substituted α-amino acid derivatives containing a hexahydropyrimidine moiety

Synthesis and Cytotoxic Activity of 5-Benzoylhexahydropyrimidine Derivatives

“…Compounds containing a hexahydropyrimidine frag ment exhibit high biological activity, in particular those possessing antitumor [1], cytotoxic [2][3][4], antibacterial [5,6], antimalarial [7], antiviral [8], and nootropic [9] properties have been reported. Chemical modification of a pyrimidine ring via variation of initial components of the classical Mannich reaction [10][11][12] could change pharmacological properties and give rise to new potentially biologically active pyrimidine derivatives.…”

“…Chemical modification of a pyrimidine ring via variation of initial components of the classical Mannich reaction [10][11][12] could change pharmacological properties and give rise to new potentially biologically active pyrimidine derivatives. We previously reported cytotoxic activity of hexahydropyrimidine derivatives containing an amino acid moiety [3]. It was found that derivatives with aryl groups in the substituents on N 1 and N 3 of the hexahydropyrimidine ring exhibit enhanced cytotoxicity [3].…”

“…We previously reported cytotoxic activity of hexahydropyrimidine derivatives containing an amino acid moiety [3]. It was found that derivatives with aryl groups in the substituents on N 1 and N 3 of the hexahydropyrimidine ring exhibit enhanced cytotoxicity [3].…”

“…In continuation of our studies in the field of design of biologically active hexahydropyrimidine derivatives [3,4], herein we describe the synthesis of a series of 5-benzoyl-substituted hexahydropyrimidines with amino acid residues at positions 1 and 3 by the Mannich reaction of ethyl benzoylacetate (1). The amine components in the Mannich reaction were glycine, L-alanine, L-valine, L-leucine, and L-tyrosine ester hydrochlorides 2a-2e.…”

“…The amine components in the Mannich reaction were glycine, L-alanine, L-valine, L-leucine, and L-tyrosine ester hydrochlorides 2a-2e. The reactant ratio 1-CH 2 O-2 was 1:15:2, and the reactions were carried out in acetate buffer (AcONa/AcOH, pH 4.0) at room temperature according to the procedure proposed by us previously [3]. This procedure is advantageous due to the lack of epimerization and formation of diastereoisomerically pure products, as shown in [13].…”