27099-22-5

Usage

Structure

A derivative of benzimidazole with a nitrile functional group and a methyl substituent at the 5-position of the benzimidazole ring.

Functional groups

Nitrile (C≡N) and methyl (-CH3)

Application

Commonly used as a building block in the synthesis of pharmaceuticals and agrochemicals.

Biological activity

Potential biological activity, being studied for its pharmacological properties.

Research status

Further research is necessary to determine its full range of applications and potential uses in various industries.

InChI:InChI=1/C10H9N3/c1-7-2-3-8-9(6-7)13-10(12-8)4-5-11/h2-3,6H,4H2,1H3,(H,12,13)

Upstream product

• 496-72-0 4-methyl-1,2-diaminobenzene 
• 105-56-6 ethyl 2-cyanoacetate 

Downstream Products

• 712293-81-7 C₁₇H₁₂BrN₃ 
• 1427518-87-3 1-amino-3-[5-(4-chlorophenoxy)-3-methyl-1-(4-methylphenyl)-1H-pyrazol-4-yl]-7-methylpyrido[1,2-a]benzimidazole-2,4-dicarbonitrile 
• 1427518-86-2 1-amino-3-[5-(4-methoxyphenoxy)-3-methyl-1-(4-methylphenyl)-1H-pyrazol-4-yl]-7-methylpyrido[1,2-a]benzimidazole-2,4-dicarbonitrile 
• 1427518-85-1 1-amino-3-[3-methyl-5-(4-methylphenoxy)-1-(4-methylphenyl)-1H-pyrazol-4-yl]-7-methylpyrido[1,2-a]benzimidazole-2,4-dicarbonitrile 
• 1427518-84-0 1-amino-3-[3-methyl-1-(4-methylphenyl)-5-phenoxy-1H-pyrazol-4-yl]-7-methylpyrido[1,2-a]benzimidazole-2,4-dicarbonitrile 
• 1427518-83-9 1-amino-3-[5-(4-chlorophenoxy)-3-methyl-1-phenyl-1H-pyrazol-4-yl]-7-methylpyrido[1,2-a]benzimidazole-2,4-dicarbonitrile 

Relevant academic research and scientific papers

Structure-Guided Discovery of Antitubercular Agents That Target the Gyrase ATPase Domain

In this study we explored the pharmaceutically underexploited ATPase domain of DNA gyrase (GyrB) as a potential platform for developing novel agents that target Mycobacterium tuberculosis. In this effort a combination of ligand- and structure-based pharmacophore modeling was used to identify structurally diverse small-molecule inhibitors of the mycobacterial GyrB domain based on the crystal structure of the enzyme with a pyrrolamide inhibitor (PDB ID: 4BAE). Pharmacophore modeling and subsequent in vitro screening resulted in an initial hit compound 5 [(E)-5-(5-(2-(1H-benzo[d]imidazol-2-yl)-2-cyanovinyl)furan-2-yl)isophthalic acid; IC50=4.6±0.1 μm], which was subsequently tailored through a combination of molecular modeling and synthetic chemistry to yield the optimized lead compound 24 [(E)-3-(5-(2-cyano-2-(5-methyl-1H-benzo[d]imidazol-2-yl)vinyl)thiophen-2-yl)benzoic acid; IC50=0.3±0.2 μm], which was found to display considerable in vitro efficacy against the purified GyrB enzyme and potency against the H37Rv strain of M. tuberculosis. Structural handles were also identified that will provide a suitable foundation for further optimization of these potent analogues.

Regioselective transmonocyanoacetylation of o-phenylenediamine derivatives: simple and efficient synthesis of 2-cyanomethylbenzimidazole derivatives

A simple and efficient method for the regioselective transmonocyanoacetylation of o-phenylenediamine derivatives was developed using 1-cyanoacetyl-3,5-dimethylpyrazole as a cyanoacetylating agent. This method provided operationally simple and efficient access to a series of N-(2-aminophenyl)-2-cyanoacetamide derivatives under mild conditions with short reaction time. Also, 2-cyanomethylbenzimidazole derivatives have been synthesized through the cyclocondensation of N-(2-aminophenyl)-2-cyanoacetamide derivatives. In all cases, high yield of products was obtained and reaction times were significantly reduced with relation to similar reactions.

Design, synthesis and biological evaluation of 5-amino-4-(1H-benzoimidazol-2-yl)-phenyl-1,2-dihydro-pyrrol-3-ones as inhibitors of protein kinase FGFR1

Fibroblast growth factor receptor 1 (FGFR1) plays an important role in tumorigenesis and is therefore an attractive target for anticancer therapy. Using molecular docking approach we have identified inhibitor of FGFR1 belonging to 5-amino-4-(1H-benzoimidazol-2-yl)-phenyl-1,2-dihydro-pyrrol-3-ones with IC50 value of 3.5 μM. A series of derivatives of this chemical scaffold has been synthesized and evaluated for inhibition of FGFR1 kinase activity. It was revealed that the most promising compounds 5-amino-1-(3-hydroxy-phenyl)-4-(6-methyl-1H-benzoimidazol-2-yl)-1,2-dihydro-pyrrol-3-one and 5-amino-4-(1H-benzoimidazol-2-yl)-1-(3-hydroxy-phenyl)-1,2-dihydro-pyrrol-3-one inhibit FGFR1 with IC50 values of 0.63 and 0.32 μM, respectively, and posses antiproliferative activity against KG1 myeloma cell line with IC50 values of 5.6 and 9.3 μM. Structure-activity relationships have been studied and binding mode of this chemical class has been proposed.

Discovery of a benzimidazole series of ADAMTS-5 (aggrecanase-2) inhibitors by scaffold hopping

We describe a medicinal chemistry approach to generate a series of benzimidazoles bearing thiazolidin-4-one using scaffold hopping from thiazole 1, our previously described thiazole. Our goal was to discover a potent and permeable small-molecule ADAMTS-5 inhibitor. The results suggest that small compound 22 shows promise as a potent small-molecule ADAMTS-5 inhibitor with good permeability.