Glycomimetics, Inc.

Universitat Basel

Ciba-geigy Corporation

Novartis Ag

Universitaet Basel

Beat Ernst

John L Magnani

Arun K Sarkar

John Tinsman Patton, Jr

Sergei A Svarovsky

Andreas Steck

Ruben Herrendorff

Fan Yang

Andreas Hafner

Rudolf Duthaler

Gebhard Thoma

Michael Heneghan

Hélène Pfister

Giulio Navarra

Céline E Weckerle

Jonas K Egger

Daniel Schwizer

John T Patton

Brian Cutting

Sachin V Shelke

The invention relates to carbohydrate ligands presenting the minimal Human Natural Killer-1 (HNK-1) epitope that bind to anti-MAG (myelin-associated glycoprotein) IgM antibodies, and their use in diagnosis as well as for the treatment of anti-MAG neuropathy. In particular, the invention relates to disaccharides of formula (I) and (II) wherein Z is optionally substituted phenyl, heteroaryl, arylcarbonyl, or heteroarylmethyl, and to therapeutically acceptable polymers comprising a multitude of substituents of formula (I) and/or formula (II), wherein Z is a bifunctional linker connecting the disaccharides to the polymer backbone. 

Carbohydrate ligands that bind to IgM antibodies against myelin-associated glycoprotein

The invention relates to carbohydrate ligands and moieties, respectively, mimicking glycoepitopes comprised by glycosphingolipids of the nervous system, particularly glycoepitopes comprised by glycosphingolipids of the cerebroside, the globoside-, the ganglioside- and the sulfoglucuronyl paragloboside type, which are bound by anti-glycan antibodies associated with neurological diseases. The invention further relates to the use of these carbohydrate ligands/moieties, in diagnosis as well as for the treatment of neurological diseases associated with anti-glycan antibodies. In particular, the invention relates to compounds of formula (I) and (II) and to therapeutically acceptable polymers comprising a multitude of these compounds, including polymers with loading of one compound of formula (I) or (II) or combinations of several compounds of formula (I), and/or (II). The compounds of formula (I) are defined as: whereinRis Z or whereinRis H, SOH, or whereinRis H or whereinRis H or whereinRand Rare independently H or whereinRis H or and compounds of formula (II) are defined as: whereinRis Z or whereinRis Z or wherein Z is &#x2014;N(R)&#x2014;A&#x2014;B&#x2014;CH&#x2014;(CH)&#x2014;SH, whereinRis H, C-C-alky, C-Calkoxy, CHCH, CHCHCH, OCHCH, or OCHCHCH;A is C-C-alkylene, C-C-alkoxy, C-C-alkyl&#x2014;(OCHCH)O&#x2014;C-C-alkyl, or C-C-alkoxy-R, wherein Ris an optionally substituted aryl or an optionally substituted heteroaryl, and wherein p is 0 to 6, preferably p is 1, 2 or 3, and further preferably p is 1;B is NHC(O), S or CH;q is 0 to 6, preferably q is 1, 2, 3 or 4, and further preferably q is 1 or 2.

Carbohydrate ligands that bind to antibodies against glycoepitopes of glycosphingolipids

The invention relates to carbohydrate ligands presenting the minimal Human Natural Killer-1 (HNK-1) epitope that bind to anti-MAG (myelin-associated glycoprotein) IgM antibodies, and their use in diagnosis as well as for the treatment of anti-MAG neuropathy. In particular, the invention relates to disaccharides of formula (I) and (II) wherein Z is optionally substituted phenyl, heteroaryl, arylcarbonyl, or heteroarylmethyl, and to therapeutically acceptable polymers comprising a multitude of substitutents of formula (I) and/or formula (II), wherein Z is a bifunctional linker connecting the disaccharides to the polymer backbone. 

Carbohydrate ligands that bind to IGM antibodies against myelin-associated glycoprotein

Compounds, compositions and methods are provided for inhibiting in vitro and in vivo processes mediated by E-selectin binding. More specifically, particular glycomimetic compounds are described, wherein the compounds are E-selectin antagonists.

E-selectin antagonists

Compounds and methods are provided for modulating in vitro and in vivo processes mediated by selectin binding. More specifically, selectin modulators and their use are described, wherein the selectin modulators that modulate (e.g., inhibit or enhance) a selectin-mediated function comprise particular glycomimetics alone or linked to a member of a class of compounds termed BASAs (Benzyl Amino Sulfonic Acids) or a member of a class of compounds termed BACAs (Benzyl Amino Carboxylic Acids).

Heterobifunctional pan-selectin inhibitors

Compounds and methods are provided for obtaining oligosaccharide mimics. More specifically, compounds and methods are described wherein oligosaccharide mimics are obtained by incorporating or substituting in a cyclohexane derivative.

Glycomimetic replacements for hexoses and N-acetyl hexosamines

The present invention provides biologically active linear polypeptides that possess a plurality of biologically active groups, methods employing such peptides to target molecules to cells, and methods employing such peptides for inhibiting the binding of cells to each other.

Multivalent polymers, processes for their preparation, and their use for preparing biologically active compounds

The invention relates to a process for the preparation of glycosides by reacting protected sugars carrying an anomeric hydroxyl group with an aglycon selected from the group consisting of alcohol, thiol and a protected sugar carrying a non-anomeric hydroxyl group, in an inert solvent, in the preferred temperature range from -20.degree. to +250.degree. C., in the presence of catalytic amounts of metal complex salts. The glycosides are obtained in high yield. Often an excess of the .alpha.- or .beta.-form is obtained and even the pure .alpha.- oder .beta.-forms are obtainable.

Process for the preparation of glycosides

The reaction of protected monosaccharides or oligosaccharides or protected monosaccharide and oligosaccharide derivatives containing an anomeric hydroxyl group with secondary .alpha.-haloenamines affords high yields of protected glycosyl halides, which are valuable intermediates for the introduction of sugar groups in the synthesis of oligosaccharides, glycolipids or glycopeptides.

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Magden, Switzerland

Beat Ernst