Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1995-08-30
1998-06-09
Fonda, Kathleen K.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
514 54, 514 61, 514 62, 536 41, 536 172, 536 185, 536 186, 536 187, 536 55, 536 551, 536 552, 536 553, 5361231, 536124, A61K 3170, C07H 1500, C07H 1700
Patent
active
057634130
DESCRIPTION:
BRIEF SUMMARY
This application is filed under 35 U.S.C. .sctn.371 from International Patent Application No. PCT/JP94/00352, filed Mar. 4, 1994.
FIELD OF THE INVENTION
The present invention relates to the method for preparing Lewis-related compounds, especially Lewis x (Le.sup.x) and Lewis a (Le.sup.a) as well as the anti-inflammatory agents containing said Lewis-related compounds as the active ingredients.
BACKGROUND OF THE INVENTION
Lewis x (Le.sup.x) and Lewis a (Le.sup.a) belong to a family of oligosaccharide in which fucose is linked to Type II and Type I lactosamine in a .alpha.(1.fwdarw.3) or .alpha.(1.fwdarw.4) linkage. Furthermore, the saccharide chain extended by linking sialic acid as the constituent sugar to the non-reducing end of Le.sup.x and Le.sup.a are called sialyl Le.sup.x and sialyl Le.sup.a, respectively. Glycolipids and glycoproteins comprising Le.sup.x, Le.sup.a, sialyl Le.sup.x and sialyl Le.sup.a in their structure have been reported to widely occur as the embryonal antigen or carcinoembryonic antigen (tumor antigen) on the cellular membrane of the animal and play an important role in the intercellular information transport and cell recognition.
Recently, the carbohydrate chain containing such structure as described above, especially sialyl Le.sup.x has been reported to be closely involved in the adhesion of leukocytes to endothelial cells and platelets. In addition, sialyl dimeric Le.sup.x, a structural dimer thereof, has been reported to appear as the tumor cell surface antigen and be involved in the metastasis mechanism. Also sulfated Le.sup.x and Le.sup.a wherein the position to which sialic acid residue is linked is substituted with sulfate residue have been found in a cancer tissue.
References cited below disclose the background related arts of the present invention:
1. J. Am. Chem. Soc. 114: 9283-9298 (1992),
2. Biochemistry 31: 9126-9131 (1992),
3. Proc. Natl. Acad. Sci. USA 88: 6224-6228 (1991),
4. J. Am. Chem. Soc. 114: 3126-3128 (1992),
5. Biochem. Biophys. Res. Commun. 188: 244-251 (1992),
6. Carbohydrate Research 209: c1-c4 (1991),
7. Bioorganic & Medicinal Chemistry Letters Vol. 1 (No. 8): 425-428 (1991), and
8. JP-A-2-174696.
Noticing Le.sup.x and Le.sup.a with such a variety of biological functions, the present inventors have achieved the present invention by synthesizing sugar chain derivatives related thereto and further discovering the useful biological activity of said synthesized compounds.
SUMMARY OF THE INVENTION
The present invention aims to provide the method for preparing the Lewis-related compounds, especially Le.sup.x, Le.sup.a and related compounds thereof and also the anti-inflammatory agents containing said compounds as the active ingredients.
The present invention is to provide the Lewis-related compounds represented by the following general structural formulas (I), (II), (III), (IV), (V) or (VI): ##STR2## Wherein
R.sup.1 represents hydrogen atom, SO.sub.3 M, CH.sub.2 COOM (M represents hydrogen atom, alkali metal (sodium, potassium, lithium, and so on) or lower alkyl group (methyl group, ethyl group, propyl group, and so on).), acetyl group, pivaloyl group or levulinoyl group;
R.sup.2 represents hydrogen atom, SO.sub.3 M, CH.sub.2 COOM (M represents hydrogen atom, alkali metal (sodium, potassium, lithium, and so on) or lower alkyl group (methyl group, ethyl group, propyl group, and so on).), acethyl group, levulinoyl group or sialic acid residue;
R.sup.3 represents hydrogen atom, SO.sub.3 M, CH.sub.2 COOM (M represents hydrogen atom, alkali metal (sodium, potassium, lithium, and so on) or lower alkyl group (methyl group, ethyl group, propyl group, and so on).), acetyl group or levulinoyl group;
R.sup.2 and R.sup.3 may corporate to form benzylidene group;
R.sup.4 represents hydrogen atom, acetyl group, benzyl group or pivaloyl group;
R.sup.5 represents O-lower alkyl group, O-lower alkenyl group, O-1-imino-2,2,2-trichloroethyl group, fluorine atom, O-aryl group (e.g., p-methoxyphenyl group), O-ceramide residue, O-mannose residue, O-galactose residue or O-la
REFERENCES:
patent: 5211937 (1993-05-01), Brandley et al.
patent: 5296594 (1994-03-01), Ratcliffe et al.
Hasegawa et al., "Steroecontrolled synthesis of sialyl Lewis X ceramide consisting of a pentasaccharide recognized by the selectin family", Carbohydrate Research, 230 (1992) pp. C1-C5.
Nicolaou et al., "Total Synthesis of Sulfated Le.sup..times. and Le.sup.a -Type Oligosaccharide Selectin Ligands", J. Am. Chem. Soc., vol. 115, No. 19, 1993, pp. 8843-8844.
Nakano et al., "Synthesis of sulfated glucuronyl glycosphingolipids; carbohydrate epitopes of neural cell-adhesion molecules", Carbohydrate Research, vol. 243, No. 1, 1993, pp. 43-69.
Lubineau et al., "First Synthesis of the 3'-Sulfated Lewis.sup.a Trisaccharide, Putative Ligand for the Leucocyte Homing Receptor", J. Chem. Soc., Chem. Commun., 1993, pp. 1419-1420.
Kitagawa et al. J. Biol. Chem. Mar. 1990, 265(9), 4859-4862.
Yuen et al. J. Biol. Chem. Jan. 21, 1994, 269(3), 1595-1598.
"Synthesis and Structural Analysis Using 2-D NMR of Sialyl Lewis X (SLe.sup..times.) and Lewis X (Le.sup..times.) Oligosaccharides: Ligands Society (Jun. 1992) vol. 114, No. 13, pp. 5449-5451.
"Total Synthesis of the Tumor-Associated Le.sup..times. Family of Glycosphingolipids", Journal of American Chemical Society (Apr. 1990) vol. 112, No. 9, pp. 3693-3695.
"Synthesis of a Dimeric Lewis X Hexasaccharide Derivative Corresponding to a Tumor-Associated Glycolipid", Carbohydrate Research (1988) vol. 183, No. 1, pp. 71-82.
"Chemical-Enzymatic Synthesis and Conformational Analysis of Sialyl Lewis x and Derivatives", Journal of American Chemical Society (1992) vol. 114, pp. 9283-9298.
"Novel Sulfated Ligands for the Cell Adhesion Molecule E-Selection Revealed by the Neoglycolipid Technology among O-Linked Oligosaccharides on an Ovarian Cystadenoma Glycoprotein", Journal of American Chemical Society (1992) vol. 31, pp. 9126-9131.
"CD62 and endothelial cell-leukocyte adhesion molecule 1 (ELAM-1) recognize the same carbohydrate ligand, sialyl-Lewis X", Proc. Natl. Acad. Sci, USA (Jul. 1991) vol. 88, pp. 6224-6228.
"Total Synthesis of Sialyl Dimeric Le", Journal of American Chemical Society (1992) vol. 114, pp. 3126-3128.
"High Affinity Binding of the Leucocyte Adhesion Molecule L-Selectin to 3'-Sulphated' Le.sup.a and Le.sup..times. Oligosaccharides and the Predominance of Sulphate in this Interaction Demonstrated by Binding Studies with a Series of Lipid-Linked Oligosaccharides", Biochemical and Biophysical Research Communications (Oct. 1992) vol. 188, No. 1, pp. 244-251.
"Preliminary Communication", Carbohydrate Research (1991) vol. 209, pp. c1-c4.
"Enzymatic Synthesis of Sialyl Le.sup..times. and Derivatives Based on a Recombinant Fucosyltransferase", Bioorganic & Medicinal Chemistry Letters (1991) vol. 1, No. 8, pp. 425-428.
Endo Akira
Fujita Masamichi
Fujita Shuji
Iida Masami
Ishii Takayuki
Fonda Kathleen K.
Mect Corporation
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