3 -Azido-3 -deoxy thymidine

Huang P, Farquhar D, Plunkett W. Selective action of 3 -azido-3 -deoxy-thymidine 5 -triphosphate on viral reverse transcriptases and human DNA polymerases. J Biol Chem 1990 265 11914-11918. 

An interesting idea was to use a monolith column to perform dual functions of online SPE and chromatographic separation. Because of the porous structure of a monolith column and its very low backpressure, plasma or diluted plasma can be directly injected. Plumb et al. (2001) used this approach to quantitate an isoquinoline drug and 3 -azido-3 -deoxy thymidine (AZT). Diluted plasma samples (plasma water 1 1) were injected directly into a Chromolith Speed ROD RP-18e column... 

The Step 3 product (0.02 mmol) was dissolved in 2 ml of DMF and treated with 3 -azido-3 -deoxy-thymidine (0.04 mmol), 1-hydroxybenzotriazole (0.04 mmol), 4-dimethyla-minopyridine (0.042 mmol), and dicyclohexylcarbodiimide (0.046 mmol) and stirred overnight at ambient temperature. The mixture was filtered, concentrated, precipitated in 2-propanol/diethyl ether, 1 1, and 0.17 g product was isolated. 

The S-pivaloyl-2-thioethyl 5-fluorophosphate derivative of 3 -azido-3 -deoxy-thymidine (24) was synthesised by Perigaud and evaluated for anti-HIV activity in an attempt to improve the biological activity of the mononucleoside 5 -fluorophosphate parent. The fluorophosphotriester was obtained by treating the H-phosphonate diester in pyridine with iodine and triethylamine trihydrofluor-ide. ... 

Terasaki T, Pardridge WM. 1988. Restricted transport of 3 -azido-3 -deoxy-thymidine and dideoxynucleosides through the blood-brain barrier. J. Infect. Dis. 158 630-32... 

Among the 3 -azido analogues of pyrimidine deoxyribonucleosides, 3 -azido-3 -deoxy-thymidine (2, AZT) was the most active against HIV-1 in vitro with an EC50 value of 0.002 jaM. Conversely, 3 -azido-3 -deoxy-6-azathymidine (37) was practically inactive (EC50 >100 aM). The 3 -azido derivatives of 3 -deoxy-3-(3-oxo-l-propenyl)thymidine (36), 2 -deoxyuridine (1), 5-bromo-2 -deoxyuridine (5), 2 -deoxy-5-fluorocytidine (8), 2 -deoxy-5-iodouridine (6), 2 -deoxycytidine (7), 2 -deoxy-5-fluorouridine (4), 2 -deoxy-5-thio-... 

Therapeutic Function Antiviral, Antineoplastic Chemical Name Thymidine, 3 -azido-3 -deoxy-... 

Wang reported the synthesis of dinucleosides, dinucleotides and oligodeoxynucleotides containing 3 -amino-3 -deoxy-3 -N,5 -(i )-C-ethylenethymidine. The bicyclothymidine was prepared from 3 -azido-3 -deoxythymidine and condensed with 5 -0-(H-phosphonyl)thymidine in the presence of triethylamine and 5 -0-(p-nitrophenoxycarbonyl)thymidine derivatives... 

The interesting analogue 77 of 5-adenosylmethionine has been made by a process in which 5 -deoxy-2, 3 -0-isopropylidene-5-methylaminoadenosine was first prepared, and then linked to a side-chain unit derived from L-glutamic acid. Thymidine analogues with a hydroxyalkylammonium moiety, such as 78, and 5 -amino- and 5 -azido-2, 5 -dideoxynucleosides of thieno[2,3-[Pg.278]

Imanishi has reported the synthesis and properties of a bridged nucleic acid analogue which contained a N3 P5 phosphoramidate linkage. " The heterodimer containing 3 -amino-2, 4 -BNA thymine monomer and thymine and methylcytosine monomers of 3 -amino-2, 4 -BNA and their 5 -phosphoramidites [34a-c] were synthesised from the intermediate 3 -azido 3 -deoxy-2, 4 -bicyclic thymidine. 

Azido and 3 -amino analogues of 2 -deoxy-5-substituted uridine and cytidine, together with 3 -amino-5 -fluoro-thymidine, have been prepared by standard procedures using 3 -0-mesyl ester intermediates the most active anti-cancer compounds were the 3 -amino-5-fluoro analogues of 2 -deoxyuridine and 2 -deoxycytidine cuid the 3 -amino analogue of 2 -deoxycytidine.An alternative doubleinversion sequence at C-3 using a 3 -chloro-3 -deoxyxylo-nucleo-side intermediate has been described for the preparation of 3 -... 

D-arablnofuranosyl-2-cyanomethyl-lH-pyrrole-3-carboxylate,° 3-benzoyloxy-l-3-D-ribofuranosyl-pyrazole-4-carboxyllc acid, l-(2,3,5-tri-0-benzoyl-3-D-ribofuranosyl) derivatives of tetrahydro-2H-1,3-diazepine-2,4(3H)-dione and 6,7-dihydro-2H-1,3-diazepine-2(3H)-one, cis-(5R,6R)-5,6-dlhydroxy-5,6-dlhydrothymldlne (a radiation product of thymidine), " 3 -azido-3 -deoxy-thymidlne, ... 

Replacement of the C-3 hydroxyl group of D-ribonucleosides (or ribonucleotides) with azido or amino groups forms 3 -azidothymidine (AZT) or 3 -amino-3 -deoxythymidine, both of which are used in the treatment of AIDS and cancer. These compounds are synthesized by the mesylation of l-(2 -deoxy-5 -0-trityl-p-D-lyxofuranosyl)-thymidine [100]. The mesyl group is displaced by reaction with lithium azide in DMF at 100°C. The azide can then be catalytically hydrogenated to give the 3 -amino analog (reaction 4.94). 

Another contrast with the 2, 3 -dideoxynucleoside family of HIV inhibitors is elucidated by the data in Table 3. Potent activity among the 4 -derivatives is maintained even when a nonpolar substituent (e.g., methyl) is present. While in the case of 2, 3 -dideoxynucleosides, in order to maintain activity, the 3 a position must be hydrogen or certain electronegative groups like azido, fiuoro, or thiol. For example, 3 -deoxy-3 -methylthymidine and 3 -(propyl-2-ene)-2, 3 -dideoxyuridine are known to be inactive against HIV. Furthermore, while 3 -cyano-3 -deoxythymidine is inactive, 4 -cyano-thymidine is among the most potent nucleoside inhibitors known. Thus, the activity elicited by a substituent at the 3 -position of thymidine is not at all predictive of the activity to be expected when the same substituent resides at the 4 -position. 

Replacement of the hydroxyl group on the 5 -carbon of thymidine by an azido gave a moderately active compound (5 -Az-5 -deoxy-T) whereas replacement by an amino gave an inactive one (5 -NH2-5 -deoxy-T). Insertion of a methylene unit between the 4 - and 5 -carbons of AZT (5 -CH20H-5 -deoxy-AZT) eliminated the antiviral activity of ACT. 

The following symbols are used throughout all tables =data converted to fiM from literature values in /xg/ml --=data not reported in reference ara=arabinosyl Az=azido C=cytidine d=2 -deoxy dd=2 ,3 -dideoxy d4=2 ,3 -didehydro-2 ,3 -dideoxy Et=ethyl Me=methyi NA=not active Pr=propyl T=thymidine U=uridine. 

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