Synthesis and antitumor activity of the 6-p-alkoxyphenyl derivatives of hexahydropyrimidine-2,4-diones

Abstract

In continuation of our previous investigation into the relationship between the structure of the cyclic compounds containing --CO-NH-CO-NH-groups and their biological activity [1], we have synthesized new 6-p-alkoxyphenyl derivatives of hexahydropyrimidine-2,4-diones (Ia-Ii, IIc, IIe, IIf). Our interest in these compounds as inspired by the data indicating that hexahydropyrimidine-2,4-diones can be potential antitumor preparations [2][3][4]]. An unsubstituted 6-phenylhexahydropyrimidine-2,4-dione (Ia) [5] and a series of its alkoxy derivatives (Ib-Ii) were synthesized in order to establish the relationship between their antitumor activity and the nature of substituents, while compounds IIc, He, and IIf were obtained in order to elucidate the role of the second substituent in position 6 of the pyfimidine ring.Compounds Ib-Ii were synthesized using a simplified variant of the conventional method [6] based on a singlestage condensation of substituted 13-phenyI-13-alanines with urea:

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“…In terms of physiology, an increase in bioavailability and selectivity with respect to the pharmacological target are achieved. 3 Hexahydropyrimidines belong to an important class of biologically active heterocycles with a broad range of physiological activity: antitumoral, 4,5 cytotoxic, 3,6 antibacterial, 7 antimicrobial, 8 antiarrhythmic 9 and antiviral (against hepatitis C). 10 5,5-Disubstituted hexahydropyrimidines are efficient against Ehrlich carcinoma and Staphylococcus aureus.…”