1412913-71-3

Upstream product

• 64858-67-9 1-(4-methylphenyl)-1H-1,2,3-triazolo[4,5-c]pyridine 
• 35488-10-9 N-(4-methylphenyl)pyridin-4-amine 
• 626-64-2 pyridin-4-ol 
• 5435-54-1 4-hydroxy-3-nitropyridine 
• 13091-23-1 4-chloro-3-nitropyridine 
• 54696-69-4 4-(4-methylphenyl)amino-3-nitropyridine 
• 1038315-36-4 3-amino-4-(4-methylphenyl)aminopyridine 
• 19524-06-2 4-bromopyridine hydrochloride 
• 89-62-3 4-methyl-2-nitroaniline 
• 5326-34-1 4-Bromo-3-nitrotoluene 
• 504-24-5 4-aminopyridine 

Downstream Products

• 35488-10-9 N-(4-methylphenyl)pyridin-4-amine 
• 1412913-72-4 4-(4-methyl-2,6-dinitrophenyl)aminopyridine 

Relevant academic research and scientific papers

Benzimidazole derivatives as well as preparation method and application thereof

The invention discloses a benzimidazole compound as well as a preparation method and application thereof. The compound has a structure as shown in a formula (I); wherein the X and Y are each independently C or N, R1, R2, R3, R4, A and B are different substituents. The compound is novel in structure and has excellent inhibition effect on the phosphodiesterase 10 type, can effectively selectively suppress the phosphodiesterase 10 type and is free of or is very weak in inhibition effect on other subtype phosphodiesterase; therefore, the compound disclosed by the invention can be used as a phosphodiesterase 10 type inhibitor to be prepared into a medicine for treating and/or preventing related diseases caused by phosphodiesterase 10 type, such as pulmonary hypertension, pulmonary fibrosis, schizophrenia and the like; meanwhile, the benzimidazole compound or the pharmaceutically acceptable salt thereof can be used as a fluorescent probe; for example, the benzimidazole compound or the pharmaceutically acceptable salt thereof can be applied to the aspects of cell imaging, tissue imaging, living body imaging and the like.

Discovery and Optimization of Chromone Derivatives as Novel Selective Phosphodiesterase 10 Inhibitors

Phosphodiesterase 10 (PDE10) inhibitors have received much attention as promising therapeutic agents for central nervous system (CNS) disorders such as schizophrenia and Huntington's disease. Recently, a hit compound 1 with a novel chromone scaffold has shown moderate inhibitory activity against PDE10A (IC50 = 500 nM). Hit-to-lead optimization has resulted in compound 3e with an improved inhibitory activity (IC50 = 6.5 nM), remarkable selectivity (>95-fold over other PDEs), and good metabolic stability (RLM t1/2 = 105 min) by using an integrated strategy (molecular modeling, chemical synthesis, bioassay, and cocrystal structure). The cocrystal structural information provides insights into the binding pattern of 3e in the PDE10A catalytic domain to highlight the key role of the halogen and hydrogen bonds toward Tyr524 and Tyr693, respectively, thereby resulting in high selectivity against other PDEs. These new observations are of benefit for the rational design of the next generation PDE10 inhibitors for CNS disorders.

Validation of Phosphodiesterase-10 as a Novel Target for Pulmonary Arterial Hypertension via Highly Selective and Subnanomolar Inhibitors

Pulmonary arterial hypertension (PAH) causes pathological increase in pulmonary vascular resistance, leading to right-heart failure and eventual death. Previously, phosphodiesterase-10 (PDE10) was reported to be a promising target for PAH based on the studies with a nonselective PDE inhibitor papaverine, but little progress has been made to confirm the practical application of PDE10 inhibitors. To validate whether PAH is ameliorated by PDE10 inhibition rather than other PDE isoforms, here we report an integrated strategy to discover highly selective PDE10 inhibitors as chemical probes. Structural optimization resulted in a PDE10 inhibitor 2b with subnanomolar affinity and good selectivity of >45 000-fold against other PDEs. The cocrystal structure of the PDE10-2b complex revealed an important H-bond interaction between 2b and Tyr693. Finally, compound 2b significantly decreased the arterial pressure in PAH rats and thus validated the potential of PDE10 as a novel anti-PAH target. These findings suggest that PDE10 inhibition may be a viable treatment option for PAH.

Use of the graebe-ullmann reaction in the synthesis of 8-methyl-γ- carboline and isomeric aromatic aza-γ-carbolines

Two variants of the Graebe-Ullmann reaction were used to obtain 8-methyl-5H-pyrido[4,3-b]indole (8-methyl-γ-carboline) and the conditions for this reaction were optimized. The feasibility of using this method was studied for the synthesis of a series of isomeric aromatic aza-γ- carbolines from the corresponding 1-(pyridyl)-1H-1,2,3-triazolo[4,5-c]pyridines under thermal and microwave irradiation conditions.