阿糖腺苷, Vidarabine

9-(b-D-Arabinofuranosyl)adenine

9-(b-D-Arabinofuranosyl)adenine is a nucleoside that is used as an antiviral agent. It binds to viral RNA and inhibits viral replication. 9-(b-D-Arabinofuranosyl)adenine has been shown to have potent side-effect profiles, including myocardial infarct, neuronal death, and immunological reactions. These effects are due to its ability to inhibit the synthesis of guanine nucleotides in the heart and brain cells, which are essential for energy production and neurotransmitter release respectively. 9-(b-D-Arabinofuranosyl)adenine also binds to toll-like receptors (TLRs), which are proteins found on the surface of cells that recognize invading microbes or foreign substances. This binding leads to activation of immune response pathways.

Title: Vidarabine

CAS Registry Number: 5536-17-4

CAS Name: 9-b-D-Arabinofuranosyl-9H-purine-6-amine monohydrate

Additional Names: 9-b-D-arabinofuranosyladenine monohydrate; arabinosyladenine; adenine arabinoside; spongoadenosine; ara-A

Manufacturers' Codes: CI-673

Trademarks: Arasena-A (Mochida); Vira-A (Warner-Lambert)

Molecular Formula: C10H13N5O4.H2O

Molecular Weight: 285.26

Percent Composition: C 42.10%, H 5.30%, N 24.55%, O 28.04%

Literature References: Purine nucleoside first synthesized as a potential anticancer agent: Lee et al., J. Am. Chem. Soc. 82, 2648 (1960); Reist et al., J. Org. Chem. 27, 3274 (1962); Glaudemans, Fletcher, ibid. 28, 3004 (1963); Reist et al., ibid. 29, 3725 (1964). Fermentation process using a strain of Streptomyces antibioticus: GB 1159290; J. D. Howells, A. Ryder, US 3616208 (1969, 1971 both to Parke, Davis). Crystal and molecular structure: Bunick, Voet, Acta Crystallogr. 30B, 1641 (1974). Series of articles on antiviral activity: Antimicrob. Agents Chemother. 1968, 136-179. Toxicity study: S. M. Kurtz et al., ibid. 180. HPLC determn in plasma and urine: W. P. McCann et al., ibid. 28, 265 (1985). Clinical trial in immunocompromised patients: R. J. Whitley et al., J. Infect. Dis. 165, 450 (1992). Book: Adenine Arabinoside: An Antiviral Agent, D. Paven-Langston et al., Eds. (Raven Press, New York, 1975) xviii + 425 pp. Review of pharmacology and clinical experience: R. A. Buchanan, F. Hess, Pharmacol. Ther. 8, 143-171 (1980). Comprehensive description: W. Hong et al., Anal. Profiles Drug Subs. 15, 647-672 (1986).

Properties: Crystals from water, mp 257.0-257.5° (0.4 H2O). [a]D27 -5° (c = 0.25). uv max (pH 1): 257.5 nm (e 12700); pH 7: 259 nm (e 13400); pH 13: 259 nm (e 14000). LD50 in mice (mg/kg): 4677 i.p.; >7950 orally (Kurtz).

Melting point: mp 257.0-257.5° (0.4 H2O)

Optical Rotation: [a]D27 -5° (c = 0.25)

Absorption maximum: uv max (pH 1): 257.5 nm (e 12700); pH 7: 259 nm (e 13400); pH 13: 259 nm (e 14000)

Toxicity data: LD50 in mice (mg/kg): 4677 i.p.; >7950 orally (Kurtz)

Therap-Cat: Antiviral.

Keywords: Antiviral; Purines/Pyrimidinones.