C‐2 Arylamino substituted purine ara‐carbocyclic nucleosides as potential anti‐cytomegalovirus agents

Abstract

There are reports in the literature that placement of an arylamino side chain at the C‐2 position of purine nucleosides produces compounds capable of inhibiting DNA polymerase. To evaluate the potential of this class of compounds as antiviral agents that act by inhibiting viral DNA polymerase, ara‐carbocyclic purine nucleosides possessing a 4‐(l‐butyl)phenylamino and a 3,5‐dichlorophenylamino substituent at C‐2 were chosen as the prototype structures and have been prepared from 2,4,6‐trichloropyrimidine in 6 steps. For the antiviral analysis, human cytomegalovirus served as the principal virus since it expresses a virally specific DNA polymerase. None of the compounds showed activity towards this virus, but they were found to display some toxicity towards one or more cell lines.

Unusual radical addition on a heteroaromatic nitrogen. A convenient access to new pyrimidine derivatives

“…Substitution of one chlorine with allylamine furnished an easily separable 1 : 2 mixture of the desired 2-N-allylamino-4,6-dichloropyridine 6a and its regioisomer 6b (Scheme 2). 3 Acetylation of the former gave 7a and radical addition with a number of xanthates 8a-g afforded the expected adducts 9a-g in generally good yield (Table 1). 4 We were pleased to find that treatment of these xanthates with stoichiometric amounts of lauroyl peroxide in ethyl acetate resulted indeed in cyclisation on the nitrogen atom, giving rise to the various pyrimidinones 10a-g displayed in Table 1.…”