PMID: 2502632Aug 1, 1989Paper

2,4-Diamino-5-benzylpyrimidines and analogues as antibacterial agents. 10. 2,4-Diamino-5-(6-quinolylmethyl)- and -[(tetrahydro-6-quinolyl)methyl]pyrimidine derivatives. Further specificity studies

Journal of Medicinal Chemistry
B S RauckmanB Roth

Abstract

A series of 18 2,4-diamino-5-[(1,2,3,4-tetrahydro-6-quinolyl)methyl]pyrimidines has been prepared by the condensation of 2,4-diamino-5-(hydroxymethyl)pyrimidine with 1,2,3,4-tetrahydroquinolines in acidic medium. Several derivatives were catalytically aromatized; others were synthesized from these by routine aromatic substitution or by condensations of (anilinomethyl)pyrimidines to give quinolinylmethyl analogues. Compounds with 4-methyl-8-methoxy substitution are closely related to trimethoprim (1a) in structure and are excellent inhibitors of bacterial dihydrofolate reductase, with activity at least equivalent to that of 1a. The highest degree of inhibition was achieved with the rigid aromatic series, but greater specificity was accomplished among the tetrahydroquinoline derivatives. This was directly related to N-1 substitution of 4-methyl-8-methoxy derivatives. The spatial relationships around N-1 and protonation at this site may both affect selectivity. Such compounds also had excellent broad-spectrum in vitro antibacterial activity.

Citations

Nov 3, 2010·Foodborne Pathogens and Disease·Javier RúaMaría Rosario García-Armesto
May 23, 2009·Journal of Medicinal Food·F J NaldoniM H Dos Santos
Apr 23, 2009·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Milan MladenovićSlavica Solujić
May 13, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·João Paulo L DamascenoRodrigo R Kitagawa
Jun 17, 2005·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·K Ferrazzoli DevienneW Vilegas
May 12, 2018·Molecular Nutrition & Food Research·Jing-Jing Zhu, Jian-Guo Jiang
May 12, 2019·Plant & Cell Physiology·Ioannis A StringlisCornï M J Pieterse
Dec 26, 2001·Chemical Reviews·S Kobayashi, H Ishitani
Feb 1, 2005·Journal of Natural Products·Eleni MelliouIoanna Chinou

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