3-deaza adenosine

The Merck compound MK-0608 is a 2 -C-Me-7-deaza-adenosine analog, which has recently been reported to show a 5.7 log drop in viral load in HCV-infected chimpanzees after dosing QD at 2mg/kg (Olsen 2006). An efQcient and practical process for preparing kilogram quantities has been described (Bio et al. 2004). The 12-step synthesis provides an impressive 35% overall yield and starts from the inexpensive diacetone-D-glucose. The synthesis features a novel acyl migration in route to prepare the key crystalline furanose diol intermediate (Fig. 5). The conditions... 

Fluoroadenine, 2-chloroadenine, 2-aminoadenine, 2- and 8-aza-adenines, 4-aminopyra7.olo[3, 4-d] pyrimidine and 6-methylpurine are converted to their ribonucleosidesby adenosine phosphoribosyltransferase,and their ribonucleosides are converted to the ribonucleotides by adenosine kinase most of the ribonucleotides are then converted to the di- and triphosphates. A -Aminoadenine, A -hydroxyadenine, A -methyladenine, purine, 7-deaza-adenine, and 7-amino-pyrazolo[4, 3-d] pyrimidine are either not substrates or are very poor substrates for the phosphoribosyltransferase, but their ribonucleosides are excellent substrates for the kinase. The ribonucleotides of purine, 7-deaza-adenine and... 

Another promising approach to 2 -deoxyribonucleosides with only a slightly modified purine which shows selective base pairing with 2 -deoxythymidinc (dT) and can be incorporated into DNA is represented by compounds of type 10. Here, position 7 of a 7-deazapurine heterocycle is substituted by an alkynyl side chain. Such nucleosides, e.g. 7-deaza-2 -deoxy-7-hex-l-ynyl-adenosine, exhibit strong fluorescence = 275 nm, = 405 nm). ... 

A few deaza- and aza-dA analogues are reported. 3 -Deaza-dA has been used to probe minor groove recognition contacts,as well as its interactions in DNA curvature at A-tracts. 1-Deaza-adenosine, tubercidin, purine and 4-methylindole deoxyribosides have all been used to probe for an essential... 

The effects of bromo and iodo substituents in the major groove of DNA have been investigated using 7-halo-7-deaza-8-aza-adenosine and 5-halo-dU derivatives. The incorporation of bromo or iodo groups onto the purine derivative always gave higher stability compared to dA or 7-deaza-8-aza-adenosine. However, there was little effect on substitution of dU. The N -linked 8-aza-7-deaza-... 

FIGURE 14.9 Plasma concentration of 7-deaza-2 -C-[14C]methyl-adenosine (Compound A) (ng/mL open circle) and total 14C levels (ng Eq/mL filled circle) after oral administration of 0.02mg/kg (-100 nCi) 14C-Compound A to dogs (n = 2). (Adapted from Sandhu, P. et al., Drug Metab. Dispos., 32, 1254, 2004. With permission.)... 

Nucleoside Acyclic Phosphates - It is well established that most nucleoside analogues become biologically active as a result of cellular conversion to phosphomonoesters. For this reason there has been increasing interest in the synthesis of nucleoside phosphotriesters and in some cases, i osphodiesters which might act as membrane soluble pro-drugs of the bioactive nucleotides. The diethyl-, dipropyl- and dibutyl-phosphates (1) of 2, 3 -dideoxy-3-deaza-adenosine have been synthesis and shown to possess anti-HIV-1 activity at non-cytotoxic doses. Phosphate triester derivatives of the anti-leukaemic nucleoside nmbi/io-cytidine have... 

Cyclic adenosine 5 -diphosphate ribose (cADP-ribose), 3-deaza-cADP-ribose, Ryanodine derivatives, BODIPY FL thapsigargin etc. 

Tubercidin (7-deaza-adenosine) has been synthesized by conventional procedures from 4-chloro-5,7-diazaindoline and tetra-acetyl ribofuranose," and the a-anomer was also prepared." A series of glycosyl naphtha [2,3-c]pyrazole-4,9-dione derivatives have been prepared from glycals and the parent heterocycle (26), giving either 1-N- or 2-A-substituted compounds the former show cytostatic activity against HeLa cells, irrespective of the particular pyranosyl substituent, whereas the 2-A-substituted compounds were inactive. ... 

Schneider, K. and Chait, B.T. (1995) Increased stabiUty of nucleic acids containing 7-deaza-guanosine and 7-deaza-adenosine may enable rapid DNA sequencing by matrix-assisted laser desorption mass spectrometry. Nucleic Acids Res., 23 (9), 1570-1575. 

Tubereidin 6-amino-9-p-D-ribofuranosyl-7-deaza-purine, M, 266.25, m.p. 247-248 °C (d.), [a] j -67° (c = 1, 50% acetic acid), a purine antibiotic (see Nucleoside antibiotics) from Streptomyces tubercidicus, and one of the group of 7-deaza-adenine-nucleoside analogs. The N7 of adenine is replaced by a methylene group. T. is biosynthesized from adenosine (Fig.) the C-atoms of the pyrrole ring are derived from a ribose moiety, which is introduced from 5-phosphoribosyl 1-pyrophosphate. As an antimetabolite of adenosine, T. interferes with purine metabolism. T. can also be eonverted into nicotinamide-dea-za-adenine dinucleotide, which inhibits glycolysis. T. is particularly active against Mycobacterium tuberculosis and Candida albicans. 

Tubercidin (7-deaza-adenosine) (535) has been converted, via treatment of its 2, 3 -0-methoxyethylidene derivative with pivaloyl chloride in refluxing pyridine, into A -epi-, 3 -deoxy-, and 2, 3 -dideoxy-tubercidin. 2, 3 -Anhydrotubercidin was also prepared and converted into its 2, 3 -anhydro-jS-D-lyxofuranosyl analogue. These epoxides were then used to prepare D-xylo and D-arabino analogues [(536) and (537), respectively] of tubercidin. 7-Methyltubercidin (538) and its a-anomer have been prepared from the products obtained on condensation of 2,3,5-tri-O-benzyl-D-ribofuranosyl bromide and an appropriately protected 7-methylpyrrolo[2,3-d] pyrimidine. ... 

An analogue of adenosylhomocysteine, 5 -deoxy-5 -isobutylthio-3-deaza-adenosine, has been prepared and its biological and biochemical properties... 

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