Zalcitabine dideoxycytidine, ddC

At present there are seven NRTIs, which have been formally approved for the treatment of AIDS 3 -azido-2, 3 -dideoxythymidine (AZT, zidovudine), 2, 3 -dideoxyinosine (ddl, didanosine), 2, 3 -dideoxycytidine (ddC, zalcitabine), 2, 3 -didehydro-2, 3 -dideoxythymidine (d4T, stavudine), (—)-L-3 -thia-2, 3 -dideoxycytidine (3TC, lamivudine), cyclopentenyl V -cyclopropylaminopurine (abacavir, ABC), and (—)-L-5-fluoro-3 -thia-2, 3 -dideoxycytidine ((—)FTC, emtricitabine) (De Clercq 2004a) (Fig. 3). 

The present NRTIs available for the treatment of HIV are zidovudine (azidothymidine, AZT), stavu-dine (d4T), didanosine (ddl), lamivudine (3TC), dideoxycytidine (ddC, zalcitabine) and abacavir, emtricitabine and tenofovir disoproxil. Combination formulations are abcavir combined with zidovudine and lamivudine and the abacavir-lamivudine combination. 

Dideoxycytidine (DDC, zalcitabine), a nucleoside analogue that also inhibits reverse transcriptase, is more active than zidovudine in vitro, and (unlike zidovudine) does not suppress erythro-poiesis. DDC is not without toxicity, however, and a severe peripheral neurotoxicity, which is dose-related, has been reported. The chemical structures of DDC and of another analogue with similar properties, 2 3 -dideoxyinosine (DDI, didanosine), are presented in Fig. 10.25 (G, H, respectively). 

Zalcitabine (2, 3 dideoxycytidine ddC) is a synthetic cytosine analog reverse-transcriptase inhibitor. It is active against HIV-I, HIV-2, and hepatitis B virus (HBV). The in vitro ICjo of zalcitabine against HIV-1 ranges from 2 nM in monocytes-macrophage cell lines to 0.5 pM in human peripheral blood mononuclear cells. Zalcitabine has considerably more antiretroviral activity in monocytes-macrophage cell lines than other nucleoside analogs, but the potential clinical utility of this observation is uncertain. 

Several 2, 3 -dideoxynucleosides are given to patients with HIV. These analogs include 3 -azido-2, 3 -dideoxythymidine (zidovudine, AZT), 2, 3 -dideoxycytidine (zalcitabine, ddC), 2, 3 -dideoxyinosine (didanosine, ddl), 2, 3 -didehydro-3 -deoxythymidine (stavudine, d4T), and (-)-2 -deoxy-3 -thiacytidine (lamivudine, 3TC). A related molecule is abacavir (ABC), which contains a cyclopentene-methanol moiety instead of the dideoxyribose moiety of the above-mentioned... 

Didanosine (DDi, 2, 3 -dideoxyinosine) and zalcitabine (DDC, 2, 3 -dideoxycytidine) are two other nucleoside analogs that are now used to treat... 

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