4 -Azido-3 -deoxythymidine

P-(P -D-aiabinofuianosyl)-9ff-puiin-6-amine] [5536-17 ], an antineoplastic and antiviral compound known by a number of trade names, and AZT (3 -azido-3 -deoxythymidine [30516-87-1]) an antiviral compound also known by a variety of trade names (see Antiviral agents). 

H. hth, R. Tocklu, K. Welten, G. J. de Jong, U. A. Th Brinkman and R. W. Frei (1989), Trace-level determination of 3 -azido-3 -deoxythymidine in human plasma by precon-centi ation on a silver (I)-tliiol stationary phase with on-line reversed-phase liigh-perfor-mance liquid chromatography , J. Chromatogr. 491 321-330 (1989). 

Azido-3 -deoxythymidine 5 -[(methyl 5-acetamido-3,5-dideoxy-D-g/ycero-a-D-ga/acto-non-2-ulopyranosylonate) phosphonate]... 

Patel BA, Boudinot FD, Schinazi RF, Gallo JM, Chu CK (1990) Comparative pharmacokinetics and interspecies scaling of 3 -azido-3 -deoxythymidine (AZT) in several mammalian species. J Pharmacobiodyn 13 206-211... 

Arion D, Kaushik N, McCormick S, Borkow G, Parniak MA (1998) Phenotypic mechanism of HIV-1 resistance to 3 -azido-3 -deoxythymidine (AZT) increased polymerization processivity and enhanced sensitivity to pyrophosphate of the mutant viral reverse transcriptase, Biochem 37 15908-15917... 

The Zn-N3imide interaction has been used to selectively extract imide-containing nucleosides and nucleotides into lipophilic media (39). Hexadecyl-derivatized Zn2+-cyclen was shown to extract dT from an aqueous solution containing a mixture of C, A, and G nucleobases. The antiviral agent AZT (3 azido-3 deoxythymidine) could also be extracted into CHCI3 from neutral aqueous solutions. Transport across a lipophilic layer was also shown, using acidic conditions, to promote the release of dT and AZT (Fig. 9). 

AIDS is associated with aberrant lymphocyte production and it has been proposed that Li+ may have a potential role in reversing this. Additionally, 3 -azido-3"deoxythymidine (AZT, zidovudine), an effective inhibitor of viral reverse transcriptase that reduces mortality in AIDS patients, induces hematopoietic suppression in patients resulting in anemia, neutropenia, and overall bone-marrow failure [220]. In murine AIDS, the coadministration of Li+ effectively moderates this toxicity of AZT in vivo [221,222]. There are several case reports where Li+ has been administered to help reduce the hematopoietic suppression in HIV-infected patients taking AZT (for example, see ref. 223). To date, the use of Li+ has been limited to a few weeks of treatment, and varying degrees of success have been achieved nevertheless the outlook in this field is quite hopeful. 

Schwendener RA, et al. New lipophilic acyl/alkyl dinucleoside phosphates as derivatives of 3 -azido-3 -deoxythymidine Inhibition of HIV-1 replication in vitro and antiviral activity against Rauscher leukemia virus infected mice with delayed treatment regimens. Antivir Res 1994 24 79. 

Zidovudine is 3 -azido-3 -deoxythymidine, and is a derivative of deoxythymidine in which an azide group replaces the 3 -hydroxyl. It is better... 

Purine and pyrimidine nucleosides of AZT (Zidovudine, 3 -azido-3 -deoxythymidine) with [RuO ] (from RuClj/K S O/aq. M KOH) gave l-((3-azido-2,3-dideoxy-P-D-eryf/tro-pentafuranosyl-5-uronic acid)-thymine (Fig. 2.11) [335]. 

The acquired immune deficiency syndrome (AIDS) has become a serious public health problem around the world, and commands much concern in medical and lay circles alike. Its causative agent is a human T-cell lymphotropic virus (HIV) that destroys helper/inducer T cells (discussed in chapter 6) of the immune system and causes mortality by allowing opportunistic infections and malignancies. A compound designed along traditional lines, 3 -azido-3 -deoxythymidine (9.16, AZT), emerged as one of the first useful therapeutics. However, since that time many other drugs have been devised. 

Yarchoan R, Brouwers P, Spitzer AR, et al. Response of human-immunodeficiency associated neurological disease to 3 -azido-3 -deoxythymidine. Lancet 1987 1 132-135. 

Diwan BA, Riggs CW, Logsdon D, Haines DC, Olivero OA, Rice JM, Yuspa SH, Poirier MC, Anderson LM (1999) Multiorgan transplacental and neonatal carcinogenicity of 3 -azido-3 -deoxythymidine in mice. Toxicol Appl Pharmacol, 161(1) 82-99. 

Lacey SF, Reardon JE, Furfine ES, Kunkel , Bebenek K, Eckert KA, et al. Biochemical studies on the reverse transcriptase and RNase H activities from human immunodeficiency virus strains resistant to 3 -azido-3 -deoxythymidine. JBiol Chem 1992 267 15789-15794. 

Larder BA. 3 -Azido-3 -deoxythymidine resistance suppressed by a mutation conferring human immunodeficiency virus type 1 resistance to nonnucleoside... 

Buckheit RW Jr., White EL, Germany-Decker J, Allen LB, Ross LJ, Shannon WM, et al. Cell-based and biochemical analysis of the anti-HIV activity of combinations of 3 -azido-3 -deoxythymidine and analogues of TIBO. Antiviral Chem Chemother 1994 5 35 12. 

Chong K-T, Pagano PJ, Hinshaw RR. Bis(heteroacyl)piperazine reverse transcriptase inhibitor in combination with 3 -azido-3 -deoxythymidine or 2, 3 -dideoxycytidine synergistically inhibits human immunodeficiency virus type 1 replication in vitro. Antimicrob Agents Chemother 1994 38 288-293. 

Johnson VA, Walker BD, Barlow MA, Paradis TJ, Chou T-C, Hirsch MS. Synergistic inhibition of human immunodeficiency virus type 1 and type 2 replication in vitro by castanospermine and 3 -azido-3 -deoxythymidine. Antimicrob Agents Chemother 1989 33 53-57. 

Azido-3 -deoxythymidine, or AZT, is a nucleoside analog approved for use to treat AIDS. Its metabolites, the mono-, di- and triphosphate forms, accu-... 

The 3 -azido-3 -deoxythymidine 656 was converted to the tetrazolo [l,5-c]pyrimidinone nucleoside 657 by treatment with POCl3/LiN3 in MeCN. Reaction of 657 with NH3/MeOH gave 658 (92BBR1545) (Scheme 133). 

Furman PA, Fyfe JA, St. Clair MH, Weinhold K, et al. 1986. Phosphorylation of 3-azido-3 deoxythymidine and selective interaction of the 5 triphosphate with human immunodeficiency virus reverse transcriptase. Proc Natl Acad Sci USA. 83 8333-8337. 

Anhydrothymidine (25 g 0.1115 mol) and NaN3 (29 g 0.446 mol) was suspended in a mixture of 250 mL DMF and 38 mL H20. The reaction was refluxed for 5 hours at which time it was poured into 1 liter of H20. This aqueous solution was extracted with ethyl acetate (EtOAc) (3x700 ml). The EtOAc was dried over Na2S04, filtered, and then EtOAc was removed in vacuo to yield a viscous oil. This oil was stirred with 200 mL water resulting in a solid, 3 -azido-3 -deoxythymidine, 9.15 g (0.0342 mol) 30.7% melting point 116°-118°C. 

---