577757-11-0

Upstream product

• 10449-07-7 (2-chlorophenyl)hydrazine 
• 64096-89-5 5-amino-1-(2-chlorophenyl)-1H-pyrazole-4-carbonitrile 
• 792953-14-1 5-amino-1-(2-chloro-phenyl)-1H-pyrazole-4-carboxylic acid amide 
• 26530-39-2 2-bromo-N-(4-methylthiazol-2-yl)acetamide 
• 1082528-89-9 1-(2-chlorophenyl)-1H-pyrazolo[3,4-d]pyrimidine-4-thiol 
• 1006597-09-6 1-(2-chloro-phenyl)-1,5-dihydro-pyrazolo[3,4-d]pyrimidin-4-one 

Relevant academic research and scientific papers

The discovery of a novel series of glucokinase activators based on a pyrazolopyrimidine scaffold

Glucokinase is a key enzyme in glucose homeostasis since it phosphorylates glucose to give glucose-6-phosphate, which is the first step in glycolysis. GK activators have been proven to lower blood-glucose, and therefore have potential as treatments for type 2 diabetes. Here the discovery of pyrazolopyrimidine GKAs is reported. An original singleton hit from a high-throughput screen with micromolar levels of potency was optimised to give compounds with nanomolar activities. Key steps in this success were the introduction of an extra side-chain, which increased potency, and changing the linking functionality from a thioether to an ether, which led to improved potency and lipophilic ligand efficiency. This also led to more stable compounds with improved profiles in biological assays.