Azido thymidine

Zidovudine. 3 -Azido-3 -deoxythymidine azido-thymidine AZT BW A509U Retrovir. mol... 

We have recently reported the potent in vitro HIV inhibitory activity of 4 -azido-thymidine. This compound is unique among all other nucleoside inhibitors because it retains the 3 -hydroxyl group. However, in spite of the presence of a 3 -hydroxyl group, it too can act as a chain terminator besides being a potent reverse transcriptase inhibitor. In order to delineate the breadth of activity as it extends over other 4 -substituted nucleosides, we have synthesized a series of analogues. In this series, we have varied the base while an azido group remained at the 4 -position, we have made substitutions at the 3 -position of 4 -azidothymidine, and we have examined the effect of other substituents at the 4 -position of thymidine. From these studies some general trends in structure—activity relationships are evident. 

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... 

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

ADP adenosine diphosphate, ANP atrial natriuretic peptide, AP5DTPT(5 -adenosyl)P5-(5 -thymidyl)pentaphosphate, ATP adenosine triphosphate, AZTMP 3 -azido-3 -deoxythymidine monophosphate, dGMP deoxyguanosine monophosphate, P 4-(2-hydroxyethyl)-l-piperazine ethanesulfonic acid, HMD hymenialdisine, TMP thymidine monophosphate... 

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. ... 

Following conversion to the triphosphate, the role of the azido substituent of AZT in the interaction of the drug with viral RT is also uncertain. Enzyme inhibition studies have demonstrated that HIV RT has a of 2.8 for the natural substrate thymidine-5 -triphosphate, whereas... 

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... 

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... 

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