78582-17-9Relevant academic research and scientific papers
Synthesis and Anti-herpetic Activity of Phosphoramidate ProTides
Maiti, Munmun,Persoons, Leentje,Andrei, Graciela,Snoeck, Robert,Balzarini, Jan,Herdewijn, Piet
, p. 985 - 993 (2013/07/27)
Among the many prodrug approaches aimed at delivering nucleoside monophosphates into cells, the phosphoramidate ProTide approach is one that has shown success, which has made it possible for some of the phosphoramidates to enter into clinical trials. Herein, we report the synthesis and antiviral activity of a series of phosphoramidate ProTides designed to bypass the thymidine kinase (TK) dependence of the parent nucleoside analogues. Phosphoramidate derivatives of (E)-5-(2-bromovinyl)-2′-deoxyuridine (BVDU) that contain L-alanine or pivaloyloxymethyl iminodiacetate (IDA-POM) exhibit anti-HSV-1 and anti-VZV activity in cell cultures, but they largely lost antiviral potency against TK-deficient virus strains. Among deazapurine nucleosides and their phosphoramidate derivatives, the 7-deazaadenine containing nucleosides and their phosphoramidate triester derivatives showed weak antiviral activity against VZV. Apparently, intracellular nucleotide delivery with these phosphoramidates is partly successful. However, none of the compound prodrugs showed superior activity to their parent drugs. Copyright
Nucleosides and nucleotides. 143. Synthesis of 5-amino-4- imidazolecarboxamide (AICA) deoxyribosides from deoxyinosines and their conversion into 3-deazapurine derivatives
Minakawa,Sasabuchi,Kiyosue,Kojima,Matsuda
, p. 288 - 295 (2007/10/03)
An efficient and large scale chemical synthesis of 5-aminoimidazole-4- carboxamide (AICA) 2'-deoxyriboside (5a) and its 3'-deoxyriboside 5b is described. Treatment of 3',5'-di-O-acetyl-N1-triphenylmethyl-2'-deoxyinosine (3a) with 5N NaOH in EtOH, followed by anhydrous trifluoroacetic acid gave 5a in 59% yield from 2'-deoxyinosine (1a). AICA 3'-deoxyriboside (5b) was also obtained in a similar manner as for 5a in 73% yield from 3'-deoxyinosine (1b). Conversion of these AICA derivatives (5a, b) into 3-deazapurine derivatives (9a, b, 15a, b, 20a, b) is also described.
SYNTHESIS OF 2-DEOXY-β-D-RIBONUCLEOSIDES AND2,3-DIDEOXY.β-D-PENTOFURANOSIDES ON IMMOBILIZED BACTERIAL CELLS
Votruba, Ivan,Holy, Antonin,Dvorakova, Hana,Guenter, Jaroslav,Hockova, Dana,et al.
, p. 2303 - 2330 (2007/10/02)
Alginate gel-entrapped cells of auxotrophic thymine-dependent strain of E. coli catalyze the transfer of 2-deoxy-D-ribofuranosyl moiety of 2'-deoxyuridine to purine and pyrimidine bases as well as their aza and deaza analogs.All experiments invariably gave β-anomers; in most cases, the reaction was regiospecific, affording N9-isomers in the purine and N1-isomers in the pyrimidine series.Also a 2,3-dideoxynucleoside can serve as donor of the glycosyl moiety.The acceptor activity of purine bases depends only little on substitution, the only condition being the presence of N7-nitrogen atom.On the other hand, in the pyrimidine series the activity is limited to only a narrow choice of mostly short 5-alkyl and 5-halogeno uracil derivatives.Heterocyclic bases containing amino groups are deaminated; this can be avoided by conversion of the base to the corresponding N-dimethylaminomethylene derivative which is then ammonolyzed.The method was verified by isolation of 9-(2-deoxy-β-D-ribofuranosyl) derivatives of adenine, guanine, 2-chloroadenine, 6-methylpurine, 8-azaadenine, 8-azaguanine, 1-deazaadenine, 3-deazaadenine, 1-(2-deoxy-β-D-ribofuranosyl) derivatives of 5-ethyluracil, 5-fluorouracil, and 9-(2,3-deoxy-β-D-pentofuranosyl)hypoxanthine, 9-(2,3-deoxy-β-D-pentofuranosyl)-6-methylpurine, and other nucleosides.
3-Deaza-2'-deoxyadenosine: Synthesis via 4-(Methylthio)-1H-imidazopyridine 2'-Deoxyribonucleosides and Properties of Oligonucleotides
Seela, Frank,Grein, Thomas,Samnick, Samuel
, p. 1639 - 1650 (2007/10/02)
The synthesis of 4-(methylthio)-1H-imidazopyridine 2'-deoxy-β-D-ribonucleosides 2 and 9 and the conversion of the N1-isomer 2 into the 2',3'-didehydro-2',3'-dideoxyribonucleoside 3a or (via 7) 3-deaza-2'-deoxyadenosine (1) is described.P
Imidazo[4,5-c]pyridines (3-deazapurines) and their nucleosides as immunosuppressive and antiinflammatory agents
Krenitsky,Rideout,Chao,Koszalka,Gurney,Crouch,Cohn,Wolberg,Vinegar
, p. 138 - 143 (2007/10/02)
A variety of imidazo[4,5-c]pyridines (3-deazapurines) were synthesized. With use of these aglycons as pentosyl acceptors, the corresponding ribonucleosides and 2'-deoxyribonucleosides were prepared by an enzymatic method involving transfer of the pentosyl moiety from appropriate pyrimidine nucleosides. With most of the imidazo[4,5-c]pyridines, the products obtained from the enzyme-catalyzed reactions were pentosylated exclusively in the 1-position. However, some 3-pentosylation occurred with aglycons that had H or N3 in the 4-position. In addition to the 2'-deoxy congener of the ribonucleoside of 4-amino-1H-imidazo[4,5-c]pyridine, the 5'-deoxy and 2',5'-dideoxy congeners were synthesized. All of the aglycons and their nucleosides were tested for toxicity to mammalian cells in culture. None were markedly cytotoxic. These compounds were also evaluated for their ability to inhibit lymphocyte-mediated cytolysis in vitro. 3-Deazaadenosine and its 2'-deoxy congener were the most potent inhibitors (ED50 = 20 μM). In addition to these two in vitro tests, in vivo inhibition of the inflammatory response in the rat carrageenan pleurisy model was determined. 3-Deazaadenosine was the most potent compound (ED50 = 3 mg/kg) in this in vivo test.
Anti-inflammatory deoxyribosides
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, (2008/06/13)
The novel compounds 3-deaza-2'-deoxyadenosine and certain of its derivatives and their pharmaceutically acceptable salts have anti-inflammatory activity as well as immune response suppression activity. 3-Deaza-2'-deoxyadenosine and certain of its intermed
