SYNTHESIS AND ANTI-HIV-1 ACTIVITIES OF 6-ARYLTHIO AND 6-ARYLSELENOACYCLONUCLEOSIDES

6-Arylthio and 6-arylselenoacyclonucleosides was synthesized and teste d for the ability to inhibit replication of HIV-1. Lithiation of acycl onucleosides with LDA followed by reaction with the electrophiles phen yl disulfide, diphenyl diselenide, 2,2'-dipyrdyl disulfide or 2,2'-dip yridyl diselenide afforded 6-(arylthio or arylseleno)acyclonucleosides 5a-c, 6, 7, 9, 15a-c, 17a-c. Compounds 19a-c and 20a-c were obtained by deprotection of corresponding TBDMS derivatives. Dehydrated product s 16a, and 18a-c were also formed during the reactions. 5-Ethyl-6-(alp ha-pyridylthio or alpha-pyridylseleno) disubstituted acyclouracils 6 a nd 7 were more active against HIV-1 in both MT-2 and CEM-IW cell lines than AZT, DDC, DDI or D4T. The EC50 of 6 against HIV-1 in CEM-IW cell was in the nanomolar range with a therapeutic index of 1100.