1206970-13-9

Upstream product

• 104-92-7 1-bromo-4-methoxy-benzene 
• 504-29-0 2-aminopyridine 
• 78644-78-7 N-(4-methoxyphenyl)pyridin-2-amine 
• 4858-85-9 2,3-dichloropyrazine 
• 82564-29-2 4-(N-pyridin-2-ylamino)phenol 

Downstream Products

• 1231923-31-1 N-(4-(3-benzylpyrazin-2-yloxy)phenyl)pyridin-2-amine 
• 1231921-28-0 2-(1-(3-(4-(pyridin-2-ylamino)phenoxy)pyrazin-2-yl)pyrrolidin-3-yl)propan-2-ol 
• 1231921-26-8 1-(3-(4-(Pyridin-2-ylamino)phenoxy)pyrazin-2-yl)piperidine-4-carbonitrile 
• 1231921-30-4 2-(1-(3-(4-(pyridin-2-ylamino)phenoxy)pyrazin-2-yl)piperidin-4-yl)propan-2-ol 
• 1231922-89-6 N-(4-(3-(2-methylpyridin-4-yl)pyrazin-2-yloxy)phenyl)pyridin-2-amine 
• 1231922-90-9 C₂₅H₁₆N₆O 
• 1231921-88-2 N-(4-((3-(4-morpholinyl)-2-pyrazinyl)oxy)phenyl)-2-pyridinamine 

Relevant academic research and scientific papers

Design, optimization, and biological evaluation of novel keto-benzimidazoles as potent and selective inhibitors of phosphodiesterase 10A (PDE10A)

Our development of PDE10A inhibitors began with an HTS screening hit (1) that exhibited both high p-glycoprotein (P-gp) efflux ratios in rat and human and poor metabolic stability. On the basis of cocrystal structure of 1 in human PDE10A enzyme, we designed a novel keto-benzimidazole 26 with comparable PDE10A potency devoid of efflux liabilities. On target in vivo coverage of PDE10A in rat brain was assessed using our previously reported LC-MS/MS receptor occupancy (RO) technology. Compound 26 achieved 55% RO of PDE10A at 30 mg/kg po and covered PDE10A receptors in rat brain in a dose-dependent manner. Cocrystal structure of 26 in PDE10A confirmed the binding mode of the novel scaffold. Further optimization resulted in the identification of keto-benzimidazole 34, which showed an increased in vivo efficacy of 57% RO in rats at 10 mg/kg po and an improved in vivo rat clearance and oral bioavailability.

AMINOPYRIDINE AND CARBOXYPYRIDINE COMPOUNDS AS PHOSPHODIESTERASE 10 INHIBITORS

Pyridine and pyrimidine compounds: or a pharmaceutically acceptable salt thereof, wherein m, n, R1, R2, R3, R4, R5, R6, R7, X1, X2, X3, X4, X5, X6, X7, X8, and Y are as defined in the specification; or a pharmaceutically acceptable salt thereof, wherein ring A, m, n, y, R2, R3, R4, R5, R6, R7, R8, R9, X1, X2, and ring A are as defined in the specification; and or a pharmaceutically acceptable salt thereof, wherein m, n, y, R2, R3, R4, R5, R6, R7, R9, X1, X2, and ring A are as defined in the specification; compositions containing them, and processes for preparing such compounds. Provided herein also are methods of treating disorders or diseases treatable by inhibition of PDE10, such as obesity, non-insulin dependent diabetes, schizophrenia, bipolar disorder, obsessive-compulsive disorder, and the like.