1361218-24-7

Upstream product

• 1239766-85-8 2-(4-bromophenyl)-2-(trifluoromethyl)oxirane 
• 136476-20-5 1-bromo-4-(3,3,3-trifluoroprop-1-en-2-yl)benzene 
• 7529-22-8 4-methylmorpholine N-oxide 
• 16184-89-7 4'-bromo-2,2,2-trifluoroacetophenone 

Downstream Products

• 1361218-83-8 3,3,3-trifluoro-2-(4-((2S)-2-(((3S)-3-methyl-4-morpholinyl)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,2-propanediol 
• 1361218-85-0 (2R)-3,3,3-trifluoro-2-(4-((2S)-2-(((3S)-3-methyl-4-morpholinyl)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,2-propanediol 
• 1361218-84-9 (2S)-3,3,3-trifluoro-2-(4-((2S)-2-(((3S)-3-methyl-4-morpholinyl)methyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,2-propanediol 
• 1361218-23-6 2-(4-((2S)-2-methyl-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-3,3,3-trifluoro-1,2-propanediol 
• 1572928-69-8 tert-butyl (5-(((3S)-4-(4-(1-hydroxy-1-(trifluoromethyl)-3-butyn-1-yl)phenyl)-3-(1-propyn-1-yl)-1-piperazinyl)-sulfonyl)-2-pyridinyl)carbamate 
• 1572927-85-5 (2R)-2-(4-((2S)-4-((6-amino-3-pyridinyl)sulfonyl)-2-(1-propyn-1-yl)-1-piperazinyl)phenyl)-1,1,1-trifluoro-4-pentyn-2-ol 
• 1572927-86-6 (2S)-2-(4-((2S)-4-((6-amino-3-pyridinyl)sulfonyl)-2-(1-propyn-1-yl)-1-piperazinyl)phenyl)-1,1,1-trifluoro-4-pentyn-2-ol 
• 1572928-70-1 tert-butyl (5-(((3S)-4-(4-(1-hydroxy-1-(trifluoromethyl)-3-pentyn-1-yl)phenyl)-3-(1-propyn-1-yl)-1-piperazinyl)sulfonyl)-2-pyridinyl)carbamate 
• 1572927-87-7 (2R)-2-(4-((2S)-4-((6-amino-3-pyridinyl)sulfonyl)-2-(1-propyn-1-yl)-1-piperazinyl)phenyl)-1,1,1-trifluoro-4-hexyn-2-ol 
• 1572927-88-8 (2S)-2-(4-((2S)-4-((6-amino-3-pyridinyl)sulfonyl)-2-(1-propyn-1-yl)-1-piperazinyl)phenyl)-1,1,1-trifluoro-4-hexyn-2-ol 
• 1572928-71-2 tert-butyl (5-(((3S)-4-(4-(1-(azidomethyl)-2,2,2-trifluoro-1-hydroxyethyl)phenyl)-3-(1-propyn-1-yl)-1-piperazinyl)sulfonyl)-2-pyridinyl)carbamate 
• 1572927-89-9 (2S)-2-(4-((2S)-4-((6-amino-3-pyridinyl)sulfonyl)-2-(1-propyn-1-yl)-1-piperazinyl)phenyl)-3-azido-1,1,1-trifluoro-2-propanol 
• 1572927-90-2 (2R)-2-(4-((2S)-4-((6-amino-3-pyridinyl)sulfonyl)-2-(1-propyn-1-yl)-1-piperazinyl)phenyl)-3-azido-1,1,1-trifluoro-2-propanol 
• 1572928-72-3 tert-butyl (5-(((3S)-3-(1-propyn-1-yl)-4-(4-(2,2,2-trifluoro-1-hydroxy-1-(methoxymethyl)ethyl)phenyl)-1-piperazinyl)sulfonyl)-2-pyridinyl)carbamate 

Relevant academic research and scientific papers

Small molecule disruptors of the glucokinase-glucokinase regulatory protein interaction: 3. Structure-activity relationships within the aryl carbinol region of the N-arylsulfonamido-N′-arylpiperazine series

We have recently reported a novel approach to increase cytosolic glucokinase (GK) levels through the binding of a small molecule to its endogenous inhibitor, glucokinase regulatory protein (GKRP) these initial investigations culminated in the identification of 2-(4-((2S)-4-((6-amino-3- pyridinyl)sulfonyl)-2-(1-propyn-1-yl)-1-piperazinyl)phenyl)-1,1,1,3,3, 3-hexafluoro-2-propanol (1, AMG-3969), a compound that effectively enhanced GK translocation and reduced blood glucose levels in diabetic animals. Herein we report the results of our expanded SAR investigations that focused on modifications to the aryl carbinol group of this series. Guided by the X-ray cocrystal structure of compound 1 bound to hGKRP, we identified several potent GK-GKRP disruptors bearing a diverse set of functionalities in the aryl carbinol region. Among them, sulfoximine and pyridinyl derivatives 24 and 29 possessed excellent potency as well as favorable PK properties. When dosed orally in db/db mice, both compounds significantly lowered fed blood glucose levels (up to 58%).

TRICYCLIC ALKYNES THAT INTERACT WITH GLUCOKINASE REGULATORY PROTEIN

The present invention relates to tricyclic alkyne compounds of formula I that interact with glucokinase regulatory protein. In addition, the present invention relates to methods of treating type 2 diabetes, and other diseases and/or conditions where gluco

SULFONYL COMPOUNDS THAT INTERACT WITH GLUCOKINASE REGULATORY PROTEIN

The present invention relates to sulfonyl compounds that interact with glucokinase regulatory protein. In addition, the present invention relates to methods of treating type 2 diabetes, and other diseases and/or conditions where glucokinase regulatory protein is involved using the compounds, or pharmaceutically acceptable salts thereof, and pharmaceutical compositions that contain the compounds, or pharmaceutically acceptable salts thereof.

SULFONYLPIPERAZINE DERIVATIVES THAT INTERACT WITH GLUCOKINASE REGULATORY PROTEIN FOR THE TREATMENT OF DIABETES

The present invention relates to compounds of Formula I, or pharmaceutically acceptable salts thereof, that interact with glucokinase regulatory protein. In addition, the present invention relates to methods of treating type 2 diabetes, and other diseases and/or conditions where glucokinase regulatory protein is involved using the compounds, or pharmaceutically acceptable salts thereof, and pharmaceutical compositions that contain the compounds, or pharmaceutically acceptable salts thereof.