1309832-49-2

Upstream product

• 2265-90-9 2-hydroxy-1,5-dinitro-3-fluorobenzene 
• 1309832-48-1 2-bromo-1-fluoro-3,5-dinitrobenzene 
• 367-12-4 2-fluorophenol 

Downstream Products

• 1309832-50-5 2-cyclopropyl-3-fluoro-5-nitroaniline 
• 1309832-51-6 2-Cyclopropyl-3-fluoro-5-nitrophenylisocyanate 
• 1309832-52-7 1-(2-cyclopropyl-3-fluoro-5-nitrophenyl)-4,5-dihydro-5H-tetrazol-5-one 
• 1309832-53-8 1-(2-Cyclopropyl-3-fluoro-5-nitrophenyl)-4-methyl-5H-tetrazol-5-one 
• 1309832-54-9 1-(5-Amino-2-cyclopropyl-3-fluorophenyl)-4-methyl-5H-tetrazol-5-one 
• 1356493-32-7 2-(4-cyclopropyl-3-fluoro-5-(1H-tetrazol-1-yl)phenylamino)-4-(2,2,6,6-tetramethylpiperidin-4-ylamino)pyrimidine-5-carbonitrile 
• 1356493-33-8 N₂-(4-cyclopropyl-3-fluoro-5-(1H-tetrazol-1-yl)phenyl)-5-fluoro-N₄-(2,2,6,6-tetramethylpiperidin-4-yl)pyrimidine-2,4-diamine 
• 1356493-52-1 1-(2-cyclopropyl-3-fluoro-5-nitrophenyl)-1H-tetrazole 
• 1356493-53-2 4-cyclopropyl-3-fluoro-5-(1H-tetrazol-1-yl)benzenamine 

Relevant academic research and scientific papers

Small-compound enhancers for functional O-mannosylation of alpha-dystroglycan, and uses thereof

The present invention provides compounds that can enhance functional O-mannosylation of proteins including alpha-dystroglycan. Also provided are methods of preparation of the compounds defined by the formula I. Also provided are the methods of using the compounds or the pharmaceutical acceptable salts or prodrugs thereof in treating and preventing subjects suffering from the diseases including muscular dystrophies and cancers.

Small molecules enhance functional O-mannosylation of Alpha-dystroglycan

Alpha-dystroglycan (α-DG), a highly glycosylated receptor for extracellular matrix proteins, plays a critical role in many biological processes. Hypoglycosylation of α-DG results in various types of muscular dystrophies and is also highly associated with progression of majority of cancers. Currently, there are no effective treatments for those devastating diseases. Enhancing functional O-mannosyl glycans (FOG) of α-DG on the cell surfaces is a potential approach to address this unmet challenge. Based on the hypothesis that the cells can up-regulate FOG of α-DG in response to certain chemical stimuli, we developed a cell-based high-throughput screening (HTS) platform for searching chemical enhancers of FOG of α-DG from a large chemical library with 364,168 compounds. Sequential validation of the hits from a primary screening campaign and chemical works led to identification of a cluster of compounds that positively modulate FOG of α-DG on various cell surfaces including patient-derived myoblasts. These compounds enhance FOG of α-DG by almost ten folds, which provide us powerful tools for O-mannosylation studies and potential starting points for the development of drug to treat dystroglycanopathy.

PROTEIN KINASE C INHIBITORS AND USES THEREOF

This disclosure concerns compounds which are useful as inhibitors of protein kinase C (PKC) and are thus useful for treating a variety of diseases and disorders that are mediated or sustained through the activity of PKC. This disclosure also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.

PROTEIN KINASE C INHIBITORS AND USES THEREOF

This disclosure concerns compounds which are useful as inhibitors of protein kinase C (PKC) and are thus useful for treating a variety of diseases and disorders that are mediated or sustained through the activity of PKC. This disclosure also relates to pharmaceutical compositions comprising these compounds, methods of using these compounds in the treatment of various diseases and disorders, processes for preparing these compounds and intermediates useful in these processes.