Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Patent
1996-09-20
1997-12-23
Kight, John
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
536 172, 536 41, 536 62, 514 27, C07H 504
Patent
active
057009180
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
The present invention relates to a novel moranoline derivative which is of use in the medicinal field, for example as an antiinflammatory agent or an antiviral agent.
BACKGROUND TECHNOLOGY
The sugar chains of sialic acid-containing glycolipids and glycoproteins have receptor functions for hormones, bacterial toxins, viruses, etc. and are closely associated with the fundamental and dynamic vital phenomena such as the recognition, differentiation, proliferation, adhesion, cancerization, immunity, and senescence of cells, thus being current subjects of interest.
For example, their application as antiviral agents has been reported in JP Kokai S63-139193 and JP Kokai H3-251593 and as immunomodulators in JP Kokai S61-243074 and JP Kokai S62-209094. Furthermore, their application to cancer diagnosis and therapy has been described in JP Kokai S61-63700.
These sialic acid derivatives exist as traces in the natural kingdom and, therefore, it has been considerably difficult to isolate such compounds as pure singular entities from biological materials. For this reason, explorations into sialic acid derivatives for exploitation as medicines constitute a new domain of research with good promises of clinical application.
The inventors of the present invention explored into a varies of sugar-chain epitope derivatives, discovered novel sialyl Lewis sugar-chain epitope derivatives including moranoline having medicinally meritorious pharmacologic actions, and perfected the invention disclosed in PCT/JP 93/00106 (WO 93/15098).
The tetrasaccharide sialyl Lewis epitope sugar-chain derivative according to said PCT/JP 93/00106 was found to be a substance possessing meritorious pharmacological features but because its synthesis required many steps and complicated procedures, the compounds could hardly be synthesized economically and efficiently so that the technology was not fully satisfactory for production on a commercial scale.
According to recent studies, like sialyl tetrasaccharide Lewis sugar-chain epitope derivatives, non-sialic acid-containing trisaccharide hydroxysulfonyl Lewis sugar-chain epitope derivatives also have antagonistic activity against selectins which are associated with cell adhesion (Glycobiology, Vol. 3, no. 6, pp. 633-639, 1993).
DISCLOSURE OF THE INVENTION
The present invention has for its object to provide a trisaccharide hydroxysulfonyl Lewis epitope moranoline derivative which is structurally simpler than the known sugar-chain epitope derivatives and can be easily produced.
The inventors of the present invention did further research and found that available upon substitution of a sulfate group for the sialic acid residue of the compounds disclosed in said PCT/JP93/00106 meets the above object. They have accordingly perfected the present invention. ##STR2## wherein R.sup.1 represents hydrogen or lower alkyl; R.sup.2 and R.sup.3 are dissimilar and each represents galactopyranosyl which may be optionally substituted by hydroxysulfonyl or a metal salt thereof, or fucopyranosyl.
Compared with the process required for production of the compounds of said PCT/JP93/00106, the production process for the compounds of the present invention employs hydroxysulfonyl in lieu of sialyl and, as such, represents marked improvements in process parameters, time, and other economic factors. not only novel compounds not heretofore documented but are substances possessing very meritorious pharmacologic actions as described hereinafter. preferably a straight-chain or branched-chain alkyl group of 1-7 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, n-pentyl, isopentyl, n-hexyl, isohexyl, n-heptyl, and isoheptyl.
The preferred alkali metal salt of the hydroxysulfonyl residue in the compounds of the present invention includes salts with lithium, sodium, and potassium, and the preferred alkaline earth metal salt includes salts with magnesium, calcium, and barium.
The compounds of the present invention includes the following species in addition to those described in the
REFERENCES:
patent: 5498604 (1996-03-01), Hasegawa et al.
Makoto et al., Synthetic Studies on Gialo-glycoconjugates 45:Synthesis of 1-Deoxynojinimycin-Containing Oligosacchinides Related to the Cancer-Associated Sialyl-Lewis a Antigen Recognized by LEC-CAMS (Selectins), J. Canbohydrate Chem. 1993, 12, 673-677.
Makoto et al, Synthetic Studies on Sialylglycoconjugates. Part 62. Systematic Synthesis of N-Methyl-1-Deoxyjinimycin-Containing, Lex, Lea, Sialyl-Lex and Sialyl-Lea Epitopes Recognized by Selectins, Bioorg. Med. Chem. 1994, 2, 1295-1308.
Hasegawa Akira
Kiso Makato
Yoshikuni Yoshiaki
Burnett Friedrich N.
Kight John
Nippon Shinyaku Co. Ltd.
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