Abstract
The title compounds were synthesized via N-benzylmalonamic acid methyl ester (3). As the key intermediate, 3 was prepared from methyl malonyl chloride and benzylamine. Then, compound 3 was reacted with dimethyl-formamide dimethyl acetal yielding vinylogue amides 4 and 5. Isomers 4 and 5 were respectively treated with amidine and guanidine to afford the title compounds 2-substituted pyrimidinone-5-carboxylic acid benzylamides 6 and 7. All of the new compounds were characterized by 1H-NMR (nuclear magnetic resonance), 13C-NMR, MS and High Resolution Mass Spectrometer (HRMS). The antitumor activities of the compounds were tested in vitro against LoVo cells and Hep3B cells. Both compounds 6 and 7 show activity against these two cell lines.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Zheng H, ed. Medicinal Chemistry. 5th edition. Beijing: People’s Medical Publishing House, 2004, 219–226 (in Chinese)
Wang Z M, ed. Current structured drugs (Volume I, II). Beijing: Beijing Press of Science and Technology, 1993, 704–706, 1092–1095 (in Chinese)
Lee J Y, Brune M E, Warner R B, Buckner S B, Winn M, De B, Zydowsky T M, Opgenorth T J, Kerkman D J, Debernardis J F. Antihypertensive activity of ABBOTT-81282, a nonpeptide angiotensin II antagonist, in the renal hypertensive rat. Pharmacology, 1993, 47(3): 176–187
Singh S K, Covind A N M, Hynes J B. Synthesis of 5-(trifluoromethyl)-5,8-dideazafolic acid and 5-(trifluoromethyl)-5,8-dideazaisofolic acid. J Heterocyclic Chem, 1990, 27: 2101–2105
Grout R J, Partridge M W. Cyclic amidines. (X). 2-Aminoquinazoline derivatives. J Chem Soc, 1960, 3540–3545
Fu N Y, Pang M L, Yu Y F, Wang J T. A novel one-pot synthesis of 3, 4-dihydropyrimidine-2-(1H)-ones catalyzed by indium tribromide. Chem J Chin Univ, 2003, 24(1): 79–81 (in Chinese)
Chen W M, Zhang J J, Wan S H, Wu S G. The synthetic processes of 2-amino-quinazolin-4-ones. CN Pat, 1335307A, 2002
Abdulla R F, Brinkmeyer R S. The chemistry of formamide acetals. Tetrahedron, 1979, 35: 1675–1735
Zhang N, Vozzolo J. Novel C-C bond cleavage under mild, neutral conditions: conversion of electron-deficient aryl alkyl ketones to aryl carboxylic esters. Journal of Organic Chemistry, 2002, 67: 1703–1704
Tu H Y, Chen W M. Synergistic anticancer effect of DNA methyltransferase inhibitor combined with thymidylate synthase inhibitor in vitro. Life Science Research, 2005, 9(4): 366–370 (in Chinese)
Domagala J M, Lee H T, Ramharack R R, Roth B D, Sawyer T, Sliskovic D R. Preparation of isothiazolones for lowering plasma levels of lipoprotein(a). US Pat, 5668162, 1997
Bolton G L, Domagala J M, Elslager E F, Gogliott R D, Purchase T S, Sanchez J P, TrivediI B K. Preparation of isothiazolones as anti-retroviral, anti-inflammatory and anti-atherosclerotic agents. WO Pat, 9638144, 1996
Author information
Authors and Affiliations
Corresponding author
Additional information
Translated from Huaxue Tongbao (Chemistry), 2006, 69(8): 623–626 (in Chinese)
About this article
Cite this article
Chen, W., Feng, J. & Tu, H. Synthesis and antitumor activities of novel 2-substituted pyrimidinone-5-carboxylic acid benzylamides. Front. Chem. China 2, 127–130 (2007). https://doi.org/10.1007/s11458-007-0026-4
Issue Date:
DOI: https://doi.org/10.1007/s11458-007-0026-4