1224883-47-9

Upstream product

• 38533-61-8 2-chloro-6-methoxy-3-nitropyridine 
• 1224883-38-8 2-(2-bromo-4-methyl-1H-imidazol-1-yl)-6-methoxy-3-nitropyridine 
• 1224883-39-9 2-(2-bromo-4-methyl-1H-imidazol-1-yl)-6-methoxypyridin-3-amine 
• 1224883-40-2 9-bromo-2-methoxy-7-methylimidazo[5,1-c]pyrido[2,3-e][1,2,4]triazine 
• 849062-30-2 (2-fluoro-5-isopropoxyphenyl)boronic acid 

Relevant academic research and scientific papers

Novel triazines as potent and selective phosphodiesterase 10A inhibitors

The identification of highly potent and orally active triazines for the inhibition of PDE10A is reported. The new analogs exhibit low-nanomolar potency for PDE10A, demonstrate high selectivity against all other members of the PDE family, and show desired drug-like properties. Employing structure-based drug design approaches, we investigated the selectivity of PDE10A inhibitors against other known PDE isoforms, by methodically exploring the various sub-regions of the PDE10A ligand binding pocket. A systematic assessment of the ADME and pharmacokinetic properties of the newly synthesized compounds has led to the design of drug-like candidates with good brain permeability and desirable drug kinetics (t1/2, bioavailability, clearance). Compound 66 was highly potent for PDE10A (IC50 = 1.4 nM), demonstrated high selectivity (>200×) for the other PDEs, and was efficacious in animal models of psychoses; reversal of MK-801 induced hyperactivity (MED = 0.1 mg/kg) and conditioned avoidance responding (CAR; ID50 = 0.2 mg/kg).

Triazine derivatives as inhibitors of phosphodiesterases

The invention relates to triazine derivatives of formula (I): which are inhibitors of phosphodiesterase 2 or 10, useful in treating central nervous system diseases such as psychosis and also in treating, for example, obesity, type 2 diabetes, metabolic syndrome, glucose intolerance, and pain.