1374768-24-7

Upstream product

• 1374768-23-6 (3aR,5R,6S,7R,7aR)-6,7-bis(benzyloxy)-5-(benzyloxymethyl)-N,N-dimethyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-2-amine 
• 1374768-25-8 C₂₅H₃₀N₂O₅S 
• 108-24-7 acetic anhydride 
• 4704-18-1 (2S,3R,4R,5S,6R)-(6-(acetoxymethyl)-3-isothiocyanatotetrahydro-2H-pyran-2,4,5-triyl)triacetate 
• 14131-63-6 D-glucosamine hydrochloride 
• 5432-46-2 1,3,4,6-tetra-O-acetyl-D-glucosamine hydrochloride 
• 51471-40-0 6-(hydroxymethyl)-3-[4-methoxybenzylideneamino]tetrahydropyran-2,4,5-triol 
• 1395832-70-8 (3aR,5R,6S,7R,7aR)-6,7-bis(benzyloxy)-5-(((tert-butyldimethylsilyl)oxy)methyl)-N,N-dimethyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-2-amine 
• 1374661-46-7 (3aR,5R,6S,7R,7aR)-5-(((tert-butyldimethylsilyl)oxy)methyl)-2-(dimethylamino)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazole-6,7-diol 
• 100-39-0 benzyl bromide 
• 1374966-46-7 (3R,4R,5S,6R)-6-(acetoxymethyl)-3-isothiocyanato-tetrahydro-2H-pyran-2,4,5-triyl triacetate 
• 191281-31-9 (3aR,5R,6S,7R,7aR)-(5-(acetoxymethyl)-2-(dimethylamino)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazole-6,7-diyl)diacetate 

Downstream Products

• 1374768-41-8 ((3aR,5R,6S,7R,7aR)-6,7-bis(benzyloxy)-2-(dimethylamino)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-5-yl)methyl methanesulfonate 
• 1374768-26-9 (3aR,5S,6S,7R,7aR)-6,7-bis(benzyloxy)-2-(dimethylamino)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazole-5-carbaldehyde 
• 1374768-28-1 ((3aR,5R,6S,7R,7aR)-6,7-bis(benzyloxy)-2-(dimethylamino)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-5-yl)(1,3-dithian-2-yl)methanol 
• 1374768-27-0 (R)-((3aR,5R,6S,7R,7aR)-6,7-bis(benzyloxy)-2-(dimethylamino)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-5-yl)(1,3-dithian-2-yl)methanol 
• 1374768-42-9 2-((3aR,5R,6R,7R,7aR)-6,7-bis(benzyloxy)-2-(dimethylamino)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-5-yl)acetonitrile 
• 1374768-43-0 2-((3aR,5R,6R,7R,7aR)-6,7-bis(benzyloxy)-2-(dimethylamino)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-5-yl)ethanol 
• 1374768-44-1 (3aR,5R,6R,7R,7aR)-6,7-bis(benzyloxy)-5-(2-fluoroethyl)-N,N-dimethyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-2-amine 
• 1374768-46-3 (3aR,5R,6R,7R,7aR)-6,7-bis(benzyloxy)-5-(2,2-difluoroethyl)-N,N-dimethyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-2-amine 
• 1374768-50-9 (3aR,5R,6R,7R,7aR)-6,7-bis(benzyloxy)-N,N-dimethyl-5-(2,2,2-trifluoroethyl)-5,6,7,7a tetrahydro-3aH-pyrano[3,2-d]thiazol-2-amine 
• 1374768-29-2 (3aR,5S,6S,7R,7aR)-6,7-bis(benzyloxy)-5-((R)-benzyloxy(1,3-dithian-2-yl)methyl)-N,N-dimethyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-2-amine 
• 1374768-30-5 (R)-2-(benzyloxy)-2-((3aR,5S,6S,7R,7aR)-6,7-bis(benzyloxy)-2-(dimethylamino)-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-5-yl)acetaldehyde 
• 1374768-31-6 (3aR,5S,6S,7R,7aR)-6,7-bis(benzyloxy)-5-((R)-1-(benzyloxy)-2,2-difluoroethyl)-N,N-dimethyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-2-amine 
• 1395832-71-9 (3aR,5S,6S,7-R,7aR)-6,7-bis(benzyloxy)-5-(fluoromethyl)-N,N-dimethyl-5,6,7,7a-tetrahydro-3aH-pyrano[3,2-d]thiazol-2-amine 

Relevant academic research and scientific papers

Discovery of MK-8719, a Potent O-GlcNAcase Inhibitor as a Potential Treatment for Tauopathies

Inhibition of O-GlcNAcase (OGA) has emerged as a promising therapeutic approach to treat tau pathology in neurodegenerative diseases such as Alzheimer's disease and progressive supranuclear palsy. Beginning with carbohydrate-based lead molecules, we pursued an optimization strategy of reducing polar surface area to align the desired drug-like properties of potency, selectivity, high central nervous system (CNS) exposure, metabolic stability, favorable pharmacokinetics, and robust in vivo pharmacodynamic response. Herein, we describe the medicinal chemistry and pharmacological studies that led to the identification of (3aR,5S,6S,7R,7aR)-5-(difluoromethyl)-2-(ethylamino)-3a,6,7,7a-tetrahydro-5H-pyrano[3,2-d]thiazole-6,7-diol 42 (MK-8719), a highly potent and selective OGA inhibitor with excellent CNS penetration that has been advanced to first-in-human phase I clinical trials.

PERMEABLE GLYCOSIDASE INHIBITORS AND USES THEREOF

Disclosed are compounds of Formula (I), wherein each substituent of Formula (I) is defined as in the specification, pharmaceutical formulations comprising these compounds which are useful as 0-linked N-acetylglucosaminidase (O-GlcNAcase) inhibitors, and thus are useful for the treatment of certain disorders such as Alzheimer' s disease including reducing NFTs and/or hyperphosphorylated tau. Also disclosed is the use of the compounds as O-GlcNAcase imaging agents.

PERMEABLE GLYCOSIDASE INHIBITORS AND USES THEREOF

The present invention is directed to compounds and pharmaceutical formulations comprising these compounds which are useful as O-linked N-acetylglucosaminidase (O-GlcNAcase) inhibitors, and thus may be useful for the treatment of certain disorders such as Alzheimer's disease including reducing NFTs and/or hyperphosphorylated tau. The invention is also directed to use of the compounds as O-GlcNAcase imaging agents.

SELECTIVE GLYCOSIDASE INHIBITORS AND USES THEREOF

The invention is directed to compounds for selectively inhibiting glycosidases, uses of the compounds and pharmaceutical compositions including the compounds, and methods of treating diseases and disorders related to deficiency or overexpression of O-GlcNAcase, and/or accumulation or deficiency of O-GlcNAc.

PYRANO[3,2-D]THIAZOL DERIVATIVES AND USES THEREOF AS SELECTIVE GLYCOSIDASE INHIBITORS

Pyrano[3,2-d]thiazol derivatives of formula (I) for selectively inhibiting glycosidases, uses of the compounds and pharmaceutical compositions including the compounds are disclosed. Methods of treating diseases and disorders related to deficiency or overexpression of O-GlcNAcase, accumulation or deficiency of O-GlcNAc are also provided.

SELECTIVE GLYCOSIDASE INHIBITORS AND USES THEREOF

The invention provides compounds with enhanced permeability for selectively inhibiting glycosidases, prodrugs of the compounds, and pharmaceutical compositions including the compounds or prodrugs of the compounds. The invention also provides methods of treating diseases and disorders related to deficiency or overexpression of O-GlcNAcase, accumulation or deficiency of O-GlcNAc.

SELECTIVE GLYCOSIDASE INHIBITORS AND USES THEREOF

The invention provides compounds for selectively inhibiting glycosidases, prodrugs of the compounds, and pharmaceutical compositions including the compounds or prodrugs of the compounds. The invention also provides methods of treating diseases and disorders related to deficiency or overexpression of O-Glc NAcase, accumulation or deficiency of O-Glc NAc.