22019-66-5

Upstream product

• 100-44-7 benzyl chloride 
• 89-62-3 4-methyl-2-nitroaniline 
• 100-39-0 benzyl bromide 
• 100-52-7 benzaldehyde 
• 446-11-7 4-fluoro-3-nitrotoluene 
• 100-46-9 benzylamine 
• 5326-34-1 4-Bromo-3-nitrotoluene 
• 5405-15-2 N-benzyl-N-(4-methylphenyl)amine 
• 128691-92-9 4-methyl-2-nitrotrifluoroacetanilide 

Downstream Products

• 39235-93-3 N¹-benzyl-4-methylbenzene-1,2-diamine 
• 39235-95-5 1-benzyl-5-methyl-2-phenyl-1H-1,3-benzimidazole 
• 53811-77-1 1-benzyl-5-methyl-2-(4-methylphenyl)-1H-benzimidazole 
• 1415650-62-2 1-benzyl-2-(4-(benzyloxy)phenyl)-5-methyl-1H-benzimidazole 
• 1415650-67-7 1-benzyl-2-cyclohexyl-5-methyl-1H-benzimidazole 
• 28643-35-8 1-benzyl-5-methyl-1,3-dihydro-2H-benzo[d]imidazol-2-one 
• 55415-32-2 1-benzyl-2-chloro-5-methyl-1H-benzoimidazole 

Relevant academic research and scientific papers

MRGX Receptor Antagonists

The invention relates to a method for preventing or treating a disease or disorder that is associated with the MrgX2 receptor. The invention also relates to MrgX2 antagonists and physiologically acceptable salts thereof. The invention also relates to pharmaceutical compositions and dosage forms comprising an MrgX2 antagonist.

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.

Regioselective Nitration of N-Alkyl Anilines using tert-Butyl Nitrite under Mild Condition

Regioselective ring nitration of N-alkyl anilines is reported using tert-butyl nitrite. The reactions proceed efficiently with a wide range of substrates providing synthetically useful N-nitroso N-alkyl nitroanilines in excellent yields which can be easily converted into N-alkyl phenylenediamines and N-alkyl nitroanilines using Zn-AcOH and HCl/MeOH, respectively.

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.

Phenylquinoxalinone CFTR activator as potential prosecretory therapy for constipation

Constipation is a common condition for which current treatments can have limited efficacy. By high-throughput screening, we recently identified a phenylquinoxalinone activator of the cystic fibrosis transmembrane conductance regulator (CFTR) chloride chan

"All-water" one-pot diverse synthesis of 1,2-disubstituted benzimidazoles: Hydrogen bond driven 'synergistic electrophile-nucleophile dual activation' by water

A new "all-water" tandem arylaminoarylation/arylaminoalkylation- reduction-cyclisation route is reported for one-pot diversity oriented synthesis of regiodefined 1,2-disubstituted benzimidazoles. Water plays a crucial and indispensable role through hydrogen bond driven 'synergistic electrophile-nucleophile dual activation' in the formation of N-mono-aryl/aryl alkyl/alkyl/cycloalkyl o-nitroanilines under metal and base-free conditions to replace the transition metal-based C-N bond formation (aryl amination) chemistry and underlines the origin of regiodefined installation of the diverse selection of aryl, aryl alkyl, and alkyl/cycloalkyl groups as substituents on the benzimidazole scaffold to form the 1,2-disubstituted benzimidazoles. The influence of the hydrogen bond effect of water in promoting the arylaminoarylation reaction under base and metal-free conditions has been realized through observation of inferior yields in D2O compared to that obtained in water during the reaction of o-fluoronitrobenzene with aniline separately performed in water and D2O under similar experimental conditions. Water also provides assistance in promoting the subsequent nitro reduction and in the final cyclocondensation steps. The role of water in promoting the cyclocondensation reaction through hydrogen bonds is realized by the differential product yields during the reaction of mono-N-phenyl-o- phenylenediamine with benzaldehyde performed separately in water and D 2O. The better hydrogen bond donor and hydrogen bond acceptor abilities of water compared to those of the organic solvents are the contributing/deciding factors for making the new water-assisted tandem arylaminoarylation/arylaminoalkylation-reduction-cyclisation strategy for the diversified synthesis of the regiodefined 1,2-disubstituted benzimidazoles effective in an aqueous medium, making it represent a true "all-water chemistry."

"All-water" chemistry of tandem N-alkylation-reduction- condensation for synthesis of N-arylmethyl-2-substituted benzimidazoles

A water-assisted tandem N-alkylation-reduction-condensation process has been devised as a new synthetic route for the one-pot synthesis of N-arylmethyl-2-substituted benzimidazoles. Water plays the crucial and indispensable role through hydrogen bond mediated 'electrophile-nucleophile dual activation' in promoting selective N-monobenzylation of o-nitroanilines as an alternative to the transition metal-based chemistry for C-N bond formation (amination) and forms the basis of disposing the substituents on the benzimidazole moiety in regiodefined manner. Water also exerts a beneficial effect in the condensation of N-monobenzylated o-phenylenediamines with aldehydes. The water-assisted C-N bond formation chemistry led to metal/base-free synthesis of N-monobenzylated o-nitroanilines and N-monobenzylated o-phenylenediamines. The indispensable/advantageous role of water in the various stage of the N-alkylation-reduction-condensation process exemplifies an 'all-water' chemistry for the synthesis of N-arylmethyl-2- substituted benzimidazoles.

Novel benzo[d]imidazole-2(3H)-thiones as potent inhibitors of the α-melanocyte stimulating hormone induced melanogenesis in melanoma B16 cells

In order to determine the optimum size of heterocycle of lead compound 1 (6-methyl-3-phenethyl-3,4-dihydro-1H-quinoline-2-thione; IC50=0.8 μM) for inhibition of melanogenesis, we have synthesized and evaluated some benzimdazole-2(3H)-thiones 5a

Indole and benzimidazole derivatives

The present invention relates to new indole and benzimidazole compounds and pharmaceutically acceptable salts, esters or prodrugs thereof, compositions of the new compounds together with pharmaceutically acceptable carriers, and uses of the new compounds. The compounds of the invention have the following general formula:

New 2-piperazinylbenzimidazole derivatives as 5-HT3 antagonists. Synthesis and pharmacological evaluation

A series of 2-piperazinylbenzimidazole derivatives were prepared and evaluated as 5-HT3 receptor antagonists. Their 5-HT3 receptor affinities were evaluated by radioligand binding assays, and their abilities to inhibit the 5-HT-induced Bezold-Jarisch reflex in anesthetized rats were determined. Compound 7e (lerisetron, pK(i) = 9.2) exhibited higher affinity for the 5- HT3 receptor than did tropisetron and granisetron, while compound 7q (pK(i) = 7.5) had very low affinity for this receptor, showing that substitution on the N1 atom of the benzimidazole ring is essential for affinity and activity. The effect of substitution on the aromatic ring of benzimidazole by several substituents in different positions is also discussed. A strong correlation between the 5-HT3 antagonistic activity of the studied compounds and the position of substitution on the aromatic ring was established. Thus, while the 4-methoxy derivative 7m showed weak affinity for the 5-HT3 receptor (pK(i) = 6.7), the 7-methoxy derivative 7n exhibited the highest affinity (pK(i) = 9.4). Compounds 7e and 7n are now under further investigation as drugs for the treatment of nausea and emesis evoked by cancer chemotherapy and radiation.