Sialic acid/fucose based medicaments

Details Sialic acid/fucose based medicaments Sialic acid/fucose based medicaments

1993-06-16

1998-05-12

Fonda, Kathleen K.

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Carbohydrate doai

514 24, 514 53, 514 54, 536 41, 536 172, 536 175, 536 176, 536 179, 5361231, 53612313, A61K 3170, C07H 1500

Patent

active

057505080

ABSTRACT:
Compounds that are synthetically inexpensive to make relative to the naturally occurring selectin ligands and that retain selectin binding activity are described that have a three-dimensionally stable configuration for sialic acid and fucose, or analogs or derivatives of these groups, such that sialic acid and fucose are separated by a non-carbohydrate linker that permits binding between those groups and the selectins, such compounds being represented by the following general structure formula I(a): ##STR1## wherein m and n are independently an integer of from 1 to 5, Y and Z are independently a connecting moiety selected from the group consisting of --CH.sub.2 --, --O--, --S--, --NR'and --NR'R"--(wherein R' and R" are independently H or an alkyl containing 1 to 4 carbon atoms); X is a connecting moiety which is selected from the group consisting of --O--, --S-- and --N--; and --R" may be --R'" or any moiety which does not interfere with the three-dimensional configuration of A or B so as to interfere with selectin binding and is preferably a moiety selected from the group consisting of --OR", --SR", --I, --N.sub.3, and --NR'R", and A is selected from the group consisting of .alpha. and .beta. forms of sialic acid, Kemp's acid. Quinic acid, Glyceric acid, Lactic acid and acetic acid, and esters thereof and B is selected from the group consisting of .alpha. and .beta. forms of L-Fucose and esters and substituted forms thereof wherein one or more of the --OH groups is independently --F, or --NR.sup.IV, R.sup.V wherein R.sup.IV and R.sup.V are independently an alkyl contain 1 to 5 carbons.

REFERENCES:
patent: 5143712 (1992-09-01), Brandley et al.
patent: 5211937 (1993-05-01), Brandley et al.
Z. Szurmai et al., "Diethylene and Triethylene Glycol Spacers for the Preparation of Neoglycoproteins," Acta Chim., Hungarica, vol. 126, pp. 259-269 (Mar.-Apr. 1989).
T. Sugawara, "Synthesis of Omega-(Methoxycarbonyl) Alkyl and 9-(Methoxycarbonyl)-3,6-Dioxynonyl Glycopyranosides for the Preparation of Carbohydrate-Protein Conjugates," Carbohydr. Res., vol. 230, pp. 117-149 (Jun. 4, 1992).
N.M. Allanson et al., "A Novel Mimic of the Sialyl Lewis X Determinant," Tetrahedr. Lett., vol. 34, pp. 3945-3948 (1993) month not available.
F. Dasgupta et al., "Anti-Adhesive Therapeutics," Expert Opinion on Investigational Drugs, vol. 3, No. 7, pp. 709-724 (Jul. 1994).
Levy et al., "Cell Adhesion and Carbohydrates," Annual Reports in Medicinal Chemistry, 29:215-224 (1994) month not available.
Mulligan et al., "Protective effects of oligosacchardies in P-selectin-dependent lung injury," Nature, 364:149-1441 (Jul. 1993).
Gundel et al., "Endothelial Leukocyte Adhesion Molecule-1 Mediates Antigen-induced Acute Airway Inflammation and Late-phase Airway Obstruction in Monkeys," J. Clin. Invest., 88:1407-1411 (Oct. 1991).
Mulligan et al., "Role of Endothelial-Leukocyte Adhesion Molecule 1 (ELAM-1) in Neutrophil-mediated Lung injury in Rats," J. Clin. Invest., 88:1396-1406 (Oct. 1991).
Science, vol. 250, pp. 1130-1132, Phillips et al. (1990) month not available.
PNAS, vol. B8 No. 22 pp. 10372-10376, Liprell et al. (1991) month not available.
JACS, vol. 114 No. 13 5449-5451, Ball et al (1992) month not available.
J. Cell Biol; vol. 120, No. 5 1227-1235 Erbe et al. (1993) month not available.

Affiliated with

Also associated with

Rating

Sialic acid/fucose based medicaments does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Sialic acid/fucose based medicaments, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Sialic acid/fucose based medicaments will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-979122