16588-32-2

Upstream product

• 108-86-1 bromobenzene 
• 89-62-3 4-methyl-2-nitroaniline 
• 5326-34-1 4-Bromo-3-nitrotoluene 
• 62-53-3 aniline 
• 446-11-7 4-fluoro-3-nitrotoluene 
• 89-60-1 1-chloro-4-methyl-2-nitro-benzene 
• 103-70-8 Formanilid 

Downstream Products

• 68765-54-8 4-methyl-N¹-phenylbenzene-1,2-diamine 
• 1393176-26-5 (S)-1-(5-methyl-1-phenyl-1H-benzoimidazol-2-yl)ethylamine 
• 1393176-27-6 [(S)-1-(5-methyl-1-phenyl-1H-benzoimidazol-2-yl)ethyl]carbamic acid tert-butyl ester 
• 1393180-53-4 (S)-N-(1-(5-methyl-1-phenyl-1H-benzo[d]imidazol-2-yl)ethyl)-9H-purin-6-amine 

Relevant academic research and scientific papers

Ni-Catalyzed Dual C-H Annulation of Benzimidazoles with Alkynes for Synthesis of π-Extended Heteroarenes

Transition metal catalyzed dual C-H activation and annulation with alkynes was an attractive protocol to construct polycyclic π-extended structures. However, most of them were dominated by noble metal catalysts. Disclosed herein was the study of base-metal Ni-catalysis for dual C-H annulation of N-aromatic imidazole, which produced a range of desired polycyclic aza-quinolines in 48-95% yields. The use of bifunctional phosphine oxide ligand proved to be critical for success.

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.

Construction of Druglike 2-Amido Benzo[ d]imidazole Analogues via Desulfurative Cyclization of Thiourea Intermediate Resin on Solid-Phase

A 2-amido benzo[d]imidazole library has been constructed by solid-phase synthesis. The key step of this solid-phase synthesis involves the preparation of polymer-bound 2-amino benzo[d]imidazole resin through desulfurative cyclization of thiourea resin using 2-chloro-1,3-dimethylimidazolinium chloride and N,N-diisopropylethylamine in dichloromethane (DCM), and the resin is then functionalized by acylation at the 2-amine position to afford 2-amidobenzo[d]imidazole resin. In the case of 2-amidobenzo[d]imidazole resin having a p-I or m-NO2, the resin was further functionalized by Suzuki/Sonogashira-coupling (p-I) and reduction to the primary amine (m-NO2) followed by acylation. Finally, the functionalized 2-amido-benzo[d]imidazole resin was cleaved from the polymer support by treatment with a cocktail of trifluoroacetic acid and DCM. As a result, we obtained 2-amidobenzo[d]imidazole analogues in high yield and good purities.

Novel benzimidazole derivatives as phosphodiesterase 10A (PDE10A) inhibitors with improved metabolic stability

In this study, we report the identification of potent benzimidazoles as PDE10A inhibitors. We first identified imidazopyridine 1 as a high-throughput screening hit compound from an in-house library. Next, optimization of the imidazopyridine moiety to improve inhibitory activity gave imidazopyridinone 10b. Following further structure-activity relationship development by reducing lipophilicity and introducing substituents, we acquired 35, which exhibited both improved metabolic stability and reduced CYP3A4 time-dependent inhibition.

HETEROCYCLIC COMPOUNDS AND METHODS OF USE

Formula I compounds, including stereoisomers, geometric isomers, tautomers, metabolites and pharmaceutically acceptable salts thereof, are useful for inhibiting the delta isoform of PI3K, and for treating disorders mediated by lipid kinases such as inflammation, immunological disorders, and cancer. Methods of using compounds of Formula I for in vitro, in situ, and in vivo diagnosis, prevention or treatment of such disorders in mammalian cells, or associated pathological conditions, are disclosed.

ARYL SULFAMIDE DERIVATIVES AND METHODS OF THEIR USE

The present invention is directed to aryl sulfamide derivatives of formula (I): or a pharmaceutically acceptable salt, stereoisomer or tautomer thereof, which are monoamine reuptake inhibitors, compositions containing these derivatives, and methods of their use for the prevention and treatment of conditions, including, inter alia, vasomotor symptoms, sexual dysfunction, gastrointestinal disorders and genitourinary disorder, depression disorders, endogenous behavioral disorders, cognitive disorders, diabetic neuropathy, pain, and other diseases or disorders.