Pyridopyrimidines. 14. Conformational Studies of 5,6,7,8-Tetrahydropyridopyrimidines. Potential Multisubstrate Analogue Inhibitors of Thymidylate Synthetase

Article abstract of DOI:10.1021/jo00144a001

The synthesis of 5-<(2,4-dioxo-6-methyl-5,6,7,8-tetrahydropyrido<3,2-d>pyrimidin-5-yl)methyl>-2'deoxyuridine and a number of related compounds as models of potent inhibitors of thymidylate synthetase has been accomplished.The 1H and 13C NMR spectra of certain of these molecules show unusual and remarkably stable conformational effects.A partial conformational analysis was undertaken in order to determine the origins of these effects.These studies revealed that the presence of a diastereomeric center at C-6 is responsible for the observed phenomena.