3'-OXIMINO-2',3'-DIDEOXYNUCLEOSIDES AND DERIVATIVES OF THE SAME

摘要

The present invention relates to new 3'-oximino-2',3'-dideoxynucleoside derivatives corresponding to formula (I) where B is substituted or unsubstituted thymin-1-yl, uracyl-1-yl, cytosin-1-yl, adenin-9-yl or guanin-9-yl and R is C1-C6 alkyl or C1-C6 acyl. This invention may be used to produce substances of this class having an increased activity. The 3'-oximino-2',3'-dideoxynucleosides are synthesised from naturally occurring nucleosides that contain a 2-deoxyribofuranose as their hydrocarbon compound. The position 5' of said 2-deoxyribofuranose is protected by a monomethoxytrityl, dimethoxytrityl or tributyldimethylsilyl group. The hydroxyl group is then oxidised at position 3' in the keto-group using an oxidiser such as pyridine dichromate or a Dess-Martin reagent, and further oximised in situ (hydroxylamine hydrochloride in pyridine) before suppressing the protecting group at position 5', the yield ranging from 30 to 70 %. Virological tests showed that 3'-oximino-2',3'-dideoxynucleosides and more precisely 3'-oximino-2',3'-dideoxythymidine are active against the human immunodeficiency virus (HIV), the B hepatitis virus and the herpes simplex virus (HSV). These compounds show anti-HIV activity in cells deficient in thymidinekynase, as well as an activity against HSV strains deficient in thymidinekynase.