The invention describes novel conjugates of formula (I) of a pharmaceutical agent and a moiety capable of binding to a glucose sensing protein allowing a reversible release of the pharmaceutical agent depending on the glucose concentration.

The invention relates to methods, compounds, compositions and vehicles for delivering 3-amino-1-propanesulfonic acid (3APS) in a subject, preferably a human subject. The invention encompasses compound that will yield or generate 3APS, either in vitro or in vivo. Preferred compounds include amino acid prodrugs of 3APS for use, including but not limited to the prevention and treatment of Alzheimer's disease

The invention relates to methods, compounds, compositions and vehicles for delivering 3-amino-1-propanesulfonic acid (3APS) in a subject, preferably a human subject. The invention encompasses compound that will yield or generate 3APS, either in vitro or in vivo. Preferred compounds include amino acid prodrugs of 3APS for use, including but not limited to the prevention and treatment of Alzheimer's disease

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:

##STR00001##

wherein
R.sup.I1 is Z or

##STR00002##

wherein
R.sup.I2 is H, SO.sub.3H, or

##STR00003## ##STR00004##

wherein
R.sup.I3 is H or

##STR00005##

wherein
R.sup.I4 is H or

##STR00006##

wherein
R.sup.I5 and R.sup.I6 are independently H or

##STR00007##

wherein
R.sup.I7 is H or

##STR00008##

and compounds of formula (II) are defined as:

##STR00009##

wherein
R.sup.II1 is Z or

##STR00010##

wherein
R.sup.II2 is Z or

##STR00011##

wherein Z is —N(R.sup.a)-A-B—CH.sub.2—(CH.sub.2).sub.q—SH, wherein
R.sup.a is H, C, Ca alkyl, C.sub.1-C.sub.4-alkoxy, CH.sub.2C.sub.6H.sub.5, CH.sub.2CH.sub.2C.sub.6H.sub.5, OCH.sub.2C.sub.6H.sub.5, or OCH.sub.2CH.sub.2C.sub.6H.sub.5;
A is C.sub.1-C.sub.7-alkylene, C.sub.1-C.sub.7-alkoxy, C.sub.1-C.sub.4-alkyl-(OCH.sub.2CH.sub.2).sub.pO—C.sub.1-C.sub.4-alkyl, or
C.sub.1-C.sub.7-alkoxy-R.sup.b, wherein R.sup.b is 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.sub.2;
q is 0 to 6, preferably q is 1, 2, 3 or 4, and further preferably q is 1 or 2.

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:

##STR00001##

wherein
R.sup.I1 is Z or

##STR00002##

wherein
R.sup.I2 is H, SO.sub.3H, or

##STR00003## ##STR00004##

wherein
R.sup.I3 is H or

##STR00005##

wherein
R.sup.I4 is H or

##STR00006##

wherein
R.sup.I5 and R.sup.I6 are independently H or

##STR00007##

wherein
R.sup.I7 is H or

##STR00008##

and compounds of formula (II) are defined as:

##STR00009##

wherein
R.sup.II1 is Z or

##STR00010##

wherein
R.sup.II2 is Z or

##STR00011##

wherein Z is —N(R.sup.a)-A-B—CH.sub.2—(CH.sub.2).sub.q—SH, wherein
R.sup.a is H, C, Ca alkyl, C.sub.1-C.sub.4-alkoxy, CH.sub.2C.sub.6H.sub.5, CH.sub.2CH.sub.2C.sub.6H.sub.5, OCH.sub.2C.sub.6H.sub.5, or OCH.sub.2CH.sub.2C.sub.6H.sub.5;
A is C.sub.1-C.sub.7-alkylene, C.sub.1-C.sub.7-alkoxy, C.sub.1-C.sub.4-alkyl-(OCH.sub.2CH.sub.2).sub.pO—C.sub.1-C.sub.4-alkyl, or
C.sub.1-C.sub.7-alkoxy-R.sup.b, wherein R.sup.b is 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.sub.2;
q is 0 to 6, preferably q is 1, 2, 3 or 4, and further preferably q is 1 or 2.

The current invention concerns methods for the synthesis of 6-azido-6-deoxy-2-N-acetyl-monosaccharide-nucleoside diphosphate, in particular 6-azido-6-deoxy-2-N-acetyl-D-galactosamine-nucleoside diphosphate or 6-azido-6-deoxy-2-N-acetyl-D-glucosamine-nucleoside diphosphate. The synthesis method according to the invention is characterized by being highly efficient and high yielding. Also part of the present invention are key intermediates of this process.

The current invention concerns methods for the synthesis of 6-azido-6-deoxy-2-N-acetyl-monosaccharide-nucleoside diphosphate, in particular 6-azido-6-deoxy-2-N-acetyl-D-galactosamine-nucleoside diphosphate or 6-azido-6-deoxy-2-N-acetyl-D-glucosamine-nucleoside diphosphate. The synthesis method according to the invention is characterized by being highly efficient and high yielding. Also part of the present invention are key intermediates of this process.

There are provided compounds of Formula (A) and pharmaceutically acceptable salts and esters thereof, and pharmaceutical compositions thereof, used for the prevention or treatment in a mammal of joint and bone disorders such as arthritis and osteoporosis. ##STR00001##

There are provided compounds of Formula (A) and pharmaceutically acceptable salts and esters thereof, and pharmaceutical compositions thereof, used for the prevention or treatment in a mammal of joint and bone disorders such as arthritis and osteoporosis. ##STR00001##

This disclosure features chemical entities (e.g., a compound or a pharmaceutically acceptable salt, and/or hydrate, and/or cocrystal, and/or drug combination of the compound) that comprise one or more ligand moieties for an asialoglycoprotein receptor (ASGPR). Exemplary chemical entities can further comprise an oligonucleotide. Said chemical entities are useful, e.g., in the targeted delivery of oligonucleotides to liver cells (e.g., liver parenchymal cells). The chemical entities are useful e.g., in the treatment of conditions or diseases caused by the expression (e.g., abnormal expression) of one or more genes in liver cells This disclosure also features compositions containing the same as well as methods of using and making the same.