Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1987-03-23
1989-09-19
Rollins, John W.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
514934, A61K 3170
Patent
active
048681628
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
This invention relates to an antiviral agent. More particularly this invention relates to an antiviral agent which displays a high level of antiviral effect with small doses and yet its toxicity to normal cells is low.
BACKGROUND ART
The replication of a viral DNA in a viral infected cell is conducted independently of the DNA replication cycle of the host cell, and it proceeds at much higher level in both speed and volume as compared with the replication of DNA which takes place in a normal cell. In view of this fact, reports have been made and published on several kinds of compounds which inhibit the DNA formation of a virus based on the difference in the process of DNA replication between a normal cell and a virus infected cell such as (E)-5-(2-bromovinyl)-2'-deoxyuridine [Nucleic Acid Research, 10, 6051 (1982), European Patent Publication No. 61283], 2'-nor-2'-deoxyguanosine [Biochemical and Biophysical Research Communications, 116, 360 (1983)], 9-(2-hydroxy-3-nonyl) adenine [Biochemical Pharmacology, 32, 3541 (1983)], 9-(2-hydroxyethoxymethyl)guanine [Chemotherapy, 25, 279 (1979), Journal of Biological Chemistry, 253, 8721 (1978)], 9-.beta.-D-Arabinofuranosyladenine [British Medical Journal, 2, 531 (1978)], etc.
Besides the aforementioned ones, it is reported that 5-halogenated pyrimidinenucleoside strongly inhibits the DNA formation in a virus infected and normal eucaryotic cell [Biochemical and Biophysical Research Communications, 86, 112 (1979), Pharmacology Review, 29, 249 (1977), Biochemica et Biophysica Acta, 518, 31 (1978), Proceedings of the Society for Experimental Biology and Medicine, 154, 439 (1977), Cancer Research, 36, 4480 (1976)]. However, 5-halogenated pyrimidinenucleoside in its original condition is too strong in its function to inhibit the DNA formation in an animal cell and 5-iodo-2'-deoxyuridine has a limited use as an antiviral agent only for herpetic keratitis. Also, 5-fluoro-2'-deoxyuridine is efficacious as an antitumor drug [Cancer Research, 38, 3784 (1978)], and it is also reported that its ester derivatives have an antitumor activity [Cancer Chemotherapy and Pharmacology, 6, 19 (1981), Chemical and Pharmaceutical Bulletin, 33, 1652 (1985)]; however, nothing has yet been made known about its antiviral activity.
DISCLOSURE OF THE INVENTION
As the result of an intensive research conducted on masked type compounds obtained by modifying the hydroxyl group of 5-halogenated-2'-deoxyuridine with various substituents with the purpose of obtaining a drug of low toxicity for normal animal cell while inhibiting the proliferation of virus even when taken in small dosage by inducing a compound, which is inhibitive of the DNA formation, into derivatives, the present inventors have come to find that various compounds obtained by esterifying the hydroxyl group of 5-halogenated-2'-deoxyuridine with an aliphatic or aromatic acyl group not only display the effect of inhibiting the proliferation of virus at high level when taken in very small dosage but also show a high therapeutic index while having a low toxicity against normal cells, thus completing the present invention.
The present invention relates to an antiviral agent characterized by containing as an active ingredient an esterified derivative of 5-halogenated-2'-deoxyuridine expressed by the following formula (I) ##STR2## wherein X represents any one of F, Cl and Br; R.sup.1 and R.sup.2 may be identical or different from each other, each representing an aliphatic acyl group comprising two or more carbon atoms, or an aromatic acyl group comprising seven or more carbon atoms.
BEST MODE OF CARRYING OUT THE INVENTION
In the formula (I) of this invention, X represents F, Cl or Br, of which F and Cl are preferable.
R.sup.1 and R.sup.2 are identical or different from each other, each representing a hydrogen atom, or an aliphatic acyl group comprising two or more carbon atoms, or an aromatic acyl group comprising six or more carbon atoms.
As the aliphatic acyl group of this type, acetyl, butyryl, hexanoyl, octanoyl, d
REFERENCES:
patent: 3323994 (1967-06-01), Grotsch
patent: 3352849 (1987-11-01), Shen et al.
Kanzawa et al., the Chemical Abstracts, 95:197203j (1981).
Kawaguchi et al., the Chemical Abstracts, 103:31965t (1985).
Supplementary European Search Report.
Fujinaga Shigeki
Kawaguchi Takeo
Suzuki Yoshiki
Rollins John W.
Teijin Limited
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