Purine nucleoside analogues used

Structure of some of the purine nucleoside analogues used as antiviral agents. 

Purine nucleosides, syntheses using transglycosylation 81YGK205. Pyrimidine and purine nucleosides and their analogues, silyl methods of... 

Vidarabine is a purine nucleoside analogue active against herpes viruses, influenza viruses, and some RNA viruses. Use of vidarabine for treatment of herpes simplex and varicella-zoster infections has largely been supplanted by acyclovir because of the superior efficacy, fewer adverse effects, and easier administration of the latter agent. Vidarabine has been associated with significant gastrointestinal, neurologic, and hematopoietic toxicities. Patients with renal insuffi-... 

Pun KT. Baines BS, Lawrence GC. Isolation, immobilisation and use of adenosine deaminase in the synthesis of f-J-carbovir, a purine nucleoside analogue. Fifth European Congress on Biotechnology, Copenhagen, 1990 Abstract TUP 111, p. 292. 

Pradere et al. described the synthesis of bis(pivaloylo g methyl) prodrugs of (F)-[4 -phosphonobut-2 -en-l -yl]purine nucleosides (55) using a one-step Mitsunobu reaction. The authors evaluated these compounds for their antiviral activities against a number of DNA and RNA viruses and some of the compounds showed submicromolar activity. Modification of the side chain or base in these analogues may lead to the discovery of new antiviral agents. 

Monaharan has developed a versatile synthetic route for the synthesis of 2 -0-[(N, iV-dimethylamino)-oxyethyl] modified purine and pyrimidine nucleoside phosphoramidites (63a-d) to be used as antisense oligonucleotide building blocks. In the syntheses of the purine-based analogues, the (iV, N-dimethylamino)-oxyethyl group was introduced via a 2 -allyloxy nucleoside intermediate, while the pyrimidine-based nucleosides were obtained from the TBDMS-protected 2,2 -anhydro-5-methyluridine via ring opening reaction in the presence of borane and ethylene glycol. The aminoxy derivatives were... 

Purine nucleoside phosphorylase (PNP). In contrast to lU-NH, PNP appears to use extensive contacts with the purine ring to promote catalysis and relatively few contacts with the ribosyl ring. The crystal structure of PNP has been determined in a complex with an iminosugar inhibitor, immucillin H, which was developed based on TS analyses of PNP-catalyzed hydrolysis and arsenolysis reactions. TS analysis revealed that the enzyme catalyzes a dissociative A Dn mechanism. The crystal structure was compared with the structures determined by Ealick and coworkers ° of PNP in a Michaelis complex analogue, PNP-inosine-sulfate, and a product complex, PNP-a-D-ribose-l-phosphate-hypoxanthine. 

In clinical practice, HIV antiretroviral regimens usually require a pair of nucleoside reverse transcriptase inhibitors in the regimen. It is of paramount importance that combinations of like nucleosides analogues (i.e., two thymidines, two cytosines, etc.) are not used together, because they have displayed antagonism and reduced viral load suppression. Nonnucleoside reverse transcriptase inhibitors are not structurally related to nucleic purines and pyrimidines therefore, they do not act as substrates of the target enzyme. 

Numerous syntheses have also been reported for arabinofuranosyl nucleoside analogues, prepared either conventionally from arabinofuranosyl derivatives or via 2,2-anhydro-nucleosides obtained from appropriate ribonucleosides. 5-Aza-cytosine-D-arabinoside has been synthesized and found to show similar antiviral activity to Ara-C(arabinosyl-cytosine). 7-a-, 7-<3-, 9-0 -, and 9- 3-arabino-furanosyl derivatives of 3-deazaguanine have also been prepared, but none showed any anti-tumour activity. 9-(o -D-Arabinofuranosyl)-8-aza[2- C]-adenine, 7-(/3-D-arabinofuranosyl)-pyrrolo[2,3-d]pyrimidine-4(3//)-one (15)," l-(a-D-arabinofuranosyl)- and l-(/3-D-xylofuranosyl)-4-nitropyrazole, and Ot-arabino-nucleosides of 5-fluoro-cytosine and -uracil derivatives have also been prepared. An improved synthesis of 9-(/3-D-arabinofuranosyl)-2-fluoro-adenine has been reported. The ratio of o to 3 anomers obtained by phase-transfer reaction of 2,3,5-tri-O-benzyl-D-arabinofuranosyl bromide with 6-chloro-2-thiomethyl-7-deazapurine varied with the quaternary ammonium salt used as a catalyst, although the jU-anomer predominated in every case. 2,2-Anhydro-nucleosides have been used to prepare l-j3-D-arabinofiiranosyl derivatives of 5-alkylthio-uracils, 5-ethyl-cytosine, and 5-ethyl-uracil, 8-alkylamino-purines, and 2-aralkylamino-l,4-dihydro-4-imino-pyrimidine hydrochlorides (16). ... 

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