550-33-4Relevant articles and documents
Antiviral, metabolic, and pharmacokinetic properties of the isomeric dideoxynucleoside 4(S)-(6-amino-9H-purin-9-yl)tetrahydro-2(S)-furanmethanol
Nair,St. Clair,Reardon,Krasny,Hazen,Paff Lawrence,Boone,Tisdale,Najera,Dornsife,Averett,Borroto-Esoda,Yale,Zimmerman,Rideout
, p. 1993 - 1999 (1995)
4(S)-(6-Amino-9H-purin-9-yl)tetrahydro-2(s)-furanmethanol (IsoddA) is the most antivirally active member of a novel class of optically active isomeric dideoxynucleosides in which the base has been transposed from the natural 1' position to the 2' position and the absolute configuration is (S,S). IsoddA was active against human immunodeficiency virus type 1 (HIV-1) (strain IIIB), HIV-2 (strain ZY), and HIV-1 clinical isolates. Combinations of the compound with zidovudine (3'-azido-3'-deoxythymidine), 2',3'-dideoxyinosine, or 5- fluoro-2'-deoxy-3'-thiacytidine showed synergistic inhibition of HIV. A moderate reduction of activity was observed with clinical isolates resistant to zidovudine. An IsoddA-resistant virus (eightfold-increased 50% inhibitory concentration) was selected in vitro by repeated passage of HIV-1 (HXB2) in the presence of increasing concentrations of IsoddA. The reverse transcriptase-coding region of the mutant virus contained a single base change resulting in a change at codon 184 from Met to Val. IsoddA was also active against hepatitis B virus (HBV) in vitro; however, it lacked substantial selective activity in an in vivo HBV model. IsoddA was inefficiently phosphorylated in CEM cells; however, the half-life of the triphosphate was 9.4 h, and IsoddATP was a potent inhibitor of HIV-1 reverse transcriptase, with a K(i) of 16 nM. The cytotoxicity 50% inhibitory concentrations of IsoddA were greater than 100 μM for CEM, MOLT-4, IM9, and the HepG2-derived HBV-infected 2.2.15 (subclone P5A) cell lines but were 12 and 11 μM for human granulocyte-macrophage (CFU-GM) and erythroid (BFU-E) progenitor cells, respectively. When given orally to rats and mice, the compound was very well absorbed and rapidly eliminated. However, there was no detectable brain penetration by IsoddA in rats. Catabolic metabolites were not detected, and this is consistent with the observed resistance of the compound to metabolic degradation by adenosine deaminase.
The synthesis of nebularine and its analogs via oxidative desulfuration in aqueous nitric acid
Xia, Ran,Sun, Li-Ping,Qu, Gui-Rong
supporting information, p. 88 - 91 (2016/12/24)
The synthesis of nebularine and its analogs has been achieved via oxidative desulfuration in H2O for the first time. With 50% HNO3as an oxidant and solvent, 18 products were obtained in good yields (70%–94%). The oxidative desulfuration system could tolerate different functional groups including fluoro, chloro, amino, alkyl, allyl, ribosyl, deoxyribosyl, and arabinofuranosyl groups.More importantly, the drug nebularine could be obtained successfully on a 20 g scale, which made this route more attractive for industrial applications.
High-throughput five minute microwave accelerated glycosylation approach to the synthesis of nucleoside libraries
Bookser, Brett C.,Raffaele, Nicholas B.
, p. 173 - 179 (2007/10/03)
The Vorbrueggen glycosylation reaction was adapted into a one-step 5 min/130 °C microwave assisted reaction. Triethanolamine in acetontrile containing 2% water was determined to be optimal for the neutralization of trimethylsilyl inflate allowing for direct MPLC purification of the reaction mixture. When coupled with a NH3/methanol deprotection reaction, a high-throughput method of nucleoside library synthesis was enabled. The method was demonstrated by examining the ribosylation of 48 nitrogen containing heteroaromatic bases that included 25 purines, four pyrazolopyrimidines, two 8-azapurines, one 2-azapurine, two imidazopyridines, two benzimidazoles, three imidazoles, three 1,2,4-triazoles, two pyrimidines, two 3-deazapyrimidines, one quinazolinedione, and one alloxazine. Of these, 32 yielded single regioisomer products, and six resulted in separable mixtures. Seven examples provided inseparable regioisomer mixtures of -two to three compounds (16 nucleosides), and three examples failed to yield isolable products. For the 45 single isomers isolated, the average two-step overall yield ± SD was 26 ± 16%, and the average purity ± SD was 95 ± 6%. A total of 58 different nucleosides were prepared of which 15 had not previously been accessed directly from glycosylation/deprotection of a readily available base.
