Nucleosides analogs

Although the term nucleoside was once limited to the compounds in Table 28.2 and a few others, cunent use is more permissive. Pyrimidine derivatives of D-arabinose, for exfflnple, occur in the free state in certain sponges and are called spongonticleosides. The powerful antiviral drug ribavirin, used to treat hepatitis C and Lassa fever, is a synthetic nucleoside analog in which the base, rather than being a pyrimidine or purine, is a triazole. 

Aminopyrazolo[4,3-d]pyrimidine moiety (47) is present in several nucleosides of both biological and synthetic origins. Among them, formycin (47, R = 3/3-D-ribofuranozyl) is of particular interest as a C-nucleoside analog of adenosine. 

Syntheses of isoxazolinyl and isoxazolidinyl nucleoside analogs 98T6587. 

Nucleoside analog 56 treated with sodium methoxide yielded a mixture, which after acetylation and chromatographic purification provided 27% of triacetate of the starting compound and 32% of diacetate 57 (Eq. 9) (78JOC4784). 

Azacitidine (5-aza-cytidine, Fig. 8) is a pyrimidine nucleoside analog of cytidine. The structural formula is... 

Tli is immunosuppressive drug, which is only marketed in Japan, is a nucleoside analog. Its phosphorylated form, mizoribine-5-phosphate, is a potent inhibitor of IMPDH activity. 

Nucleoside analogs substituted at the C-5 position of the pyrimidine base have been identified as anfiviral and anticancer agents, hi this context new... 

De Clercq E, Descamps J, De Somer P, Holy A (1978) (S)-9-(2,3-Dihydroxypropyl)adenine an ahphatic nucleoside analog with broad-spectrum antiviral activity. Science 5 563-565 De Clercq E, Holy, A (2005) Acyclic nucleoside phosphonates a key class of antiviral drugs. Nature reviews 4 928-940... 

F%. 4 Important nucleoside analogs that have undergone clinical trials for treatment of HC V. Both PSI-6130 (R7128) and R1479 were administered to humans as prodrugs... 

Although nucleoside analogs are not substrates for P-gp or CYP3A4, most protease inhibitors and NNl are substrates for both the P-gp efflux pump (Aungst 1999 ... 

Carroll SS, Olsen DB (2006) Nucleoside analog inhibitors of hepatitis C vims rephcation. Infect Disord Dmg Targets (Formerly Current Drag Targets - Infectious) 6 17-29 CasteU JV, lover R, Martinez-Jimenez CP, Gomez-Lechon MJ (2006) Hepatocyte cell lines their use, scope and limitations in dmg metabolism studies. Expert Opin Drag Metab Toxicol 2 183-212... 

There are currently six major antiretroviral drug families (Table 5). Nucleoside reverse transcriptase inhibitors (NRTI) are nucleoside analogs (discussed in more detail in chapter by De Clercq and Neyts, this volume) and were the first approved antiretroviral agents. They include drugs such as AZT, didanosine (ddl), stavudine (d4T), abacavir (ABC), and lamivudine (3TC), the latest used at doses of 300 mg daily as anti-HIV agent (lOOmg/day is the dosing approved for treatment of HBV... 

Chen CH, Vazquez-Padua M et al (1991) Effect of anti-human immunodeficiency virus nucleoside analogs on mitochondrial DNA and its implication for delayed toxicity. Mol Pharmacol 39(5) 625-628... 

Cui L, Locatelli L et al (1997) Effect of nucleoside analogs on neurite regeneration and mitochondrial DNA synthesis in PC-12 cells. J Pharmacol Exp Ther 280(3) 1228-1234 Dal Pan GJ, Glass JD et al (1994) Clinicopathologic correlations of HIV-l-associated vacuolar myelopathy an autopsy-based case-control study. Neurology 44(11) 2159-2164 Dalakas MC (2001) Peripheral neuropathy and antiretroviral drugs. J Peripher Nerv Syst 6(l) 14-20 Dalakas MC, Semino-Mora C et al (2001) Mitochondrial alterations with mitochondrial DNA depletion in the nerves of AIDS patients with peripheral neuropathy induced by 2 3 -dideoxycytidine (ddC). Lab Invest 81(11) 1537-1544... 

Gaied NB, Glasser N, Ramalanjaona N, Beltz H, Wolff P, Marquet R, Burger A, Mly Y (2005) 8-vinyl-deoxyadenosine, an alternative fluorescent nucleoside analog to 2 -deoxyribosyl-2-aminopurine with improved properties. Nucl Acids Res 33 1031-1039... 

Various kinds of chiral acyclic nitrones have been devised, and they have been used extensively in 1,3-dipolar cycloaddition reactions, which are documented in recent reviews.63 Typical chiral acyclic nitrones that have been used in asymmetric cycloadditions are illustrated in Scheme 8.15. Several recent applications of these chiral nitrones to organic synthesis are presented here. For example, the addition of the sodium enolate of methyl acetate to IV-benzyl nitrone derived from D-glyceraldehyde affords the 3-substituted isoxazolin-5-one with a high syn selectivity. Further elaboration leads to the preparation of the isoxazolidine nucleoside analog in enantiomerically pure form (Eq. 8.52).78... 

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