text: Carbocyclic analogues of dideoxyadenosine were investigated for their anti-HIV activity. Minimal activity was first observed. Many nucleoside analogues were prepared and examined but only one had significant activity and satisfied the requirements for clinical use. That was 2´,3´-didehydro analogue of dideoxyadenosine. Insertion of a cyclopropyl group on its 6-amino nitrogen of the adenine ring increased lipophilicity and thus enhanced brain penetration. The resulting compound is known as abacavir (see table 3). Abacavir  was approved by the FDA for use in therapy of HIV-1 infections in December 1998.
  This drug is the only approved antiretroviral that is active as a guanosine analogue in vivo. First it is monophosphorylated  by adenosine phosphotransferase and then the monophosphate is converted to carbovir 3´-monophosphate. Subsequently, it is fully phosphorylated and the carbovir is incorporated by the RT into the DNA chain and acts as a chain terminator. Carbovir is a related guanosine analogue that had poor oral bioavailability and thus was withdrawn from clinical development.