ABSTRACT
Abacavir sulfate (also known as 1592U89) is a carbocyclic nucleotide analog that received US Food and Drug Administration (FDA) approval in 1998 for the treatment of HIV infections (Huff, 1999). Abacavir was developed from the compound carbovir (NSC 614846), by the addition of a 6-cyclopropylamino moiety at the 6-position of the purine ring (Daluge et al., 1997; Figure 230.1). Although carbovir was initially found to have potent in vitro anti-HIV activity (Vince et al., 1988; Coates et al., 1991) and was intensively researched as a potential antiretroviral drug target, its poor oral bioavailability in animal studies (Yeom et al., 1989; Huang et al., 1991), unfavorable toxicology profile, and limited brain penetration (Daluge et al., 1997) precluded further clinical development. The 6-cyclopropylamino modifications to carbovir overcame these pharmacokinetic and toxicologic limitations (Good et al., 1995) while retaining its potent antiviral activity (Daluge et al., 1995) In addition, this modified carbovir compound retained the improved in vivo stability conventionally associated with this structure compared with the other 2′,3′-dideoxynucleotides such as zidovudine, didanosine, zalcitabine, and stavudine (Daluge et al., 1997). The structure of (a) abacavir and (b) carbovir. https://s3-euw1-ap-pe-df-pch-content-public-p.s3.eu-west-1.amazonaws.com/9781315152110/08d8042d-9481-4a8d-8c27-9bd589f6de6b/content/fig230_1.tif" xmlns:xlink="https://www.w3.org/1999/xlink"/>
