670749-91-4

Upstream product

• 860469-26-7 1-(dimethoxymethyl)-1H-benzo[d]imidazol 
• 4192-77-2 ethyl cinnamate 
• 51-17-2 benzoimidazole 
• 100-52-7 benzaldehyde 
• 939-70-8 2-acetylbenzimidazole 
• 16414-04-3 1-benzimidazol-2-ylethanol 
• 95-54-5 1,2-diamino-benzene 

Downstream Products

• 76115-82-7 4,6-diphenyl-2-(benzimidazol-2-yl)pyridine 
• 670750-03-5 1-(1-benzyl-1H-benzoimidazol-2-yl)-3-phenyl-propenone 
• 630102-56-6 4-(1H-benzoimidazol-2-yl)-2-phenyl-2,3-dihydro-benzo[b][1,4]thiazepine 
• 132308-69-1 4-(benzimidazol-2-yl)-6-phenylpyrimidin-2-amine 
• 58035-20-4 2-(1,5-diphenyl-4,5-dihydro-1H-3-pyrazolyl)-1H-benzimidazole 
• 63330-81-4 2-(5-phenyl-4,5-dihydroisoxazol-3-yl)benzimidazole 
• 132308-52-2 2-(5-phenyl-4,5-dihydro-1H-3-pyrazolyl)-1H-benzimidazole 
• 1417372-97-4 5-[(2E)-1-(1H-benzimidazol-2-yl)-3-phenylprop-2-en-1-ylidene]pyrimidine-2,4,6-(1H,3H,5H)-trione 
• 630102-68-0 4-(1-methyl-1H-benzoimidazol-2-yl)-2-phenyl-2,3-dihydro-benzo[b][1,4]thiazepine 
• 630102-60-2 4-(1H-benzoimidazol-2-yl)-2-phenyl-benzo[b][1,4]thiazepine 
• 670749-99-2 (E)-1-(1-methyl-1H-benzimidazol-2-yl)-3-phenyl-2-propen-1-one 

Relevant academic research and scientific papers

Design, synthesis, and in vitro biological evaluation of novel benzimidazole tethered allylidenehydrazinylmethylthiazole derivatives as potent inhibitors of Mycobacterium tuberculosis

Tuberculosis (TB) has become one of the most significant public health problems in recent years. Antibiotic therapy remains the mainstay of TB control strategies, but the increasing resistance of mycobacterial species has heightened alarm, requiring the development of novel drugs in order to improve treatment outcomes. Here, as an effort to identify novel and effective antitubercular agents, we designed and synthesized a series of novel substituted benzimidazolallylidenehydrazinylmethylthiazole derivatives via a multi-component molecular hybridization approach with single molecular architecture. Our design strategy involved assembling the antitubercular pharmacophoric fragments benzimidazole, 2-aminothiazole and substituted α,β-unsaturated ketones via condensation reactions. All the newly synthesized compounds were fully characterized via NMR and mass spectral data and evaluated for in vitro biological activity against the H37Ra strain of Mycobacterium tuberculosis. From the biological evaluation data, we identified some effective compounds, of which 8g and 7e were the most active ones (both having MIC values of 2.5 μg mL?1). In addition, compound 8g exhibited a lower cytotoxicity profile. We conceive that compound 8g may serve as a chemical probe of interest for further lead optimization studies with the general aim of developing novel and effective antitubercular agents.

Design and synthesis of benzimidazole-chalcone derivatives as potential anticancer agents

Numerous reports have shown that conjugated benzimidazole derivatives possess various kinds of biological activities, including anticancer properties. In this report, we designed and synthesized 24 new molecules comprising a benzimidazole ring, arene, and alkyl chain-bearing cyclic moieties. The results showed that the N-substituted benzimidazole derivatives bearing an alkyl chain and a nitrogen-containing 5- or 6-membered ring enhanced the cytotoxic effects on human breast adenocarcinoma (MCF-7) and human ovarian carcinoma (OVCAR-3) cell lines. Among the 24 synthesized compounds, (2E)-1-(1-(3-morpholinopropyl)-1H-benzimidazol-2 -yl)-3-phenyl-2-propen-1-one) (23a) reduced the proliferation of MCF-7 and OVCAR-3 cell lines demonstrating superior outcomes to those of cisplatin.

Treatment with low-dose sorafenib in combination with a novel benzimidazole derivative bearing a pyrolidine side chain provides synergistic anti-proliferative effects against human liver cancer

Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies and deadliest cancers in the world. Currently, sorafenib is the only drug that has been approved by the U.S. FDA for patients with advanced HCC. However, its improvement on patient outcomes is modest, and the median survival time is only prolonged 2-3 months. In addition, the application of sorafenib is limited because of its high cost and severe adverse side-effects. Therefore, developing more effective novel agents and reducing the dosage of sorafenib are urgently needed for HCC therapy. Here, a novel benzimidazole derivative (4a) bearing a pyrolidine side chain (9a) was synthesized. The treatments of compounds 4a, 9a and sorafenib either alone or in combination on the inhibition of liver cancer cells proliferation were measured using alamarBlue cell viability and trypan blue staining assay. Intracellular signaling pathway activities were assessed by Western blot, Q-PCR and IHC staining. The HuH7 xenograft model was used to examine antitumor activity in vivo. Adverse effects (e.g., changes in body weight, serum parameters, liver function and pathology) of mice treated with 9a were also evaluated. Compound 9a significantly inhibited HCC cell proliferation compared with 4a. In addition, 9a strongly synergized with a low dose of sorafenib in suppressing HCC cell proliferation. Regarding the activities of the signaling pathways, sorafenib did not suppress AKT signaling; however, 9a inhibited AKT and its downstream phosphorylation of p70S6K. In addition, treatment with either 9a alone or in combination with sorafenib led to the inhibition of JNK phosphorylation. However, there were no effects on the inhibition of apoptosis. The in vivo HuH7 xenograft model showed that the administration of 9a plus a low dose of sorafenib significantly decreased expression of the HCC markers α-fetoprotein, glypican-3 and survivin as well as suppressed tumor growth. Finally, there were no adverse effects in mice treated with 9a. In conclusion, co-treatment with a novel benzimidazole derivative bearing a pyrolidine side chain in combination with a low dose of sorafenib exerted significant antitumor activity in preclinical HCC models, which potentially suggests its use as a novel therapeutic strategy for patients with HCC.

Design, synthesis and biological evaluation of novel benzimidazole-2-substituted phenyl or pyridine propyl ketene derivatives as antitumour agents

A series of novel benzimidazole-2-subsituted phenyl or pyridine propyl ketene derivatives were designed and synthesized. The biological activities of these derivatives were then evaluated as potential antitumour agents. These compounds were assayed for growth-inhibitory activity against HCT116, MCF-7 and HepG2 cell lines in vitro. The IC50 values of compounds A1 and A7 against the cancer cells were 0.06e3.64 mM and 0.04e9.80 mM, respectively. Their antiproliferative activities were significantly better than that of 5-Fluorouracil (IC50: 56.96e174.50 mM) and were close to that of Paclitaxel (IC50: 0.026 e1.53 μ M). The activity of these derivatives was over 100 times more effective than other reported structures of chalcone analogues (licochalcone A). A preliminary mechanistic study suggested that these compounds inhibit p53-MDM2 binding. Compounds A1, A7 and A9 effectively inhibited tumour growth in BALB/c mice with colon carcinoma HCT116 cells. The group administered 200 mg/kg of compound A7 showed a 74.6% tumour growth inhibition with no signs of toxicity at high doses that was similar to the inhibition achieved with the 12.5 mg/kg irinotecan positive control (70.2%). Therefore, this class of benzimidazole-2-subsituted phenyl or pyridine propyl ketene derivatives represents a promising lead structure for the development of possible p53-MDM2 inhibitors as new antitumour agents.

Ultrasound accelerated synthesis of novel benzimidazole derived chalcones as glucosidases inhibitor and antimicrobial agents

A novel series of 3-substituted-1-[1-(toluene-4-sulfonyl)-1H-benzoimidazol-2-yl]-propen-1-one 3a-m have been synthesized by tosylation of benzimidazole chalcones 2a-m using ultrasound in lesser time with higher yields. All the synthesized compounds have been characterized by IR, 1H and 13C NMR, mass and elemental analysis in full accordance with their depicted structure. Biological evaluation of the compounds 3a-m reveals that compound 3f shows moderate inhibition of glucoamylase and compound 3i exhibits compelling inhibition of α-amylase. Compound 3k and 3d display excellent antibacterial activity against all tested strains and admirable antifungal activity against Candida albicans respectively in comparison to the standards. The results of biological study show that introduction of tosyl group in benzimidazole chalcones enhances the inhibition of glycosidases and microorganism in comparison to parent compounds.

Microwave assisted synthesis, physico-chemical properties and antioxidant activity of α,β-unsaturated benzimidazole derivatives incorporated with baritone moiety

A series of (2E)-1-(H-benzimidazol-2-yl)-3-substituted phenyl 2-propen-1-one linked with barbitone (5a-g) are synthesized by both conventional method and microwave assisted method. The benzimidazole chalcones (4a-g) were prepared from the condensation of 2-acetyl benzimidazole (3a) with different aromatic aldehydes. These chalcones on reaction with barbituric acid in presence of acetic acid medium gave the a,b-unsaturated benzimidazole derivatives. The structures of the all the final compounds were established on the basis of IR, 1H NMR, mass spectra and elemental analysis. The druglikeness and physicochemical properties of the derivatives were determined by actelion, molsoft, molinspiration and ACD ChemDraw Ultra 11.0 software. The final products possess a favourable drug likeness and drug score. All the final synthesized compounds were screened for their antioxidant properties like free radical scavenging by DPPH method. Among the synthesized compounds (5f), (5c) and (5d) were exhibited a good antioxidant activity and all the other derivatives showed a moderate activity.

Antitumour activity of 5-[(2E)-1-(1H-benzimidazol-2-yl)-3-substituted phenylprop-2-en-1-ylidene] pyrimidine-2,4,6(1H,3H,5H)-triones against Dalton's ascitic lymphoma in mice

A new series of novel benzimidazole derivatives containing barbitone moiety (5a-f) was synthesized by a Knoevenagel condensation of (2E)-1-(1H- benzimidazol-2-yl)-3-phenylprop-2-en-1-ones (4a-f) and barbituric acid in the presence of catalytic amount of acetic acid medium. All the final structures were assigned on the basis of IR, 1H NMR and mass spectra analysis. Acute toxicity studies were performed initially to determine the safety of titled derivatives and the ED 50 value was calculated 50 mg/kg. All the final derivatives were screened for antitumour activity against Dalton's ascitic lymphoma in mice. All the new candidates at a dose of 50 mg/kg showed a good antitumour activity against DLA-bearing mice when compared to the standard 5-fluro uracil. Among the final derivatives (5e), 5-[(2E)-1-(1H-benzimidazol-2- yl)-3-(3-nitrophenyl) prop-2-en-1-ylidene] pyrimidine-2,4,6(1H,3H,5H)-trione was found to be most potent antitumour in nature.

Pyrazoline bearing benzimidazoles: Search for anticancer agent

2-acetyl benzimidazole was allowed to react with substituted aromatic aldehydes to get desired intermediate chalcones (2a-g), the cyclocondensation of these intermediates with hydrazine hydrate and phenyl hydrazine in two separate reactions yielded pyrazoline derivatives (3a-g & 4a-g respectively). Among the synthesize compounds, six compounds were granted NSC code and screened at National Cancer Institute (NCI), USA for anticancer activity at a single high dose (10-5 M) in full NCI 60 cell panel. Among the selected compounds, (4f) 2-[5-(3,4-dimethoxyphenyl)-1-phenyl-4,5-dihydro-1H-3-pyrazolyl]-1H-benzimidazole (NSC 748326) was found to be the most active candidate of the series and selected for further evaluation at five dose level screening.

Facile synthesis of alkoxyphthalimide derivatized benzimidazole assembled pyrazoles, pyrimidines and isoxazoles, via common intermediate chalcone

In the present investigation, synthesis of 2-(3-aryl-2-phenyl-3,4- dihydropyrazol-5-yl)-1-N-alkoxyphthalimidobenzimidazole 9a-h, 4-(1-N-alkoxyphthalimidobenzimidazol-2-yl)-6-arylpyrimidin-2-amine 10a-h and 2-(5-aryl-4,5-dihydroisoxazol-3-yl)-1-N-alkoxyphthalimidobenzimidazole 11a-h are described. Mild dichromate oxidation of 1-benzimidazol-2-yl-ethanol 1 gives 1-benzimidazol-2-yl-ethanone 2 which on Clasien condensation with various aromatic aldehydes yields the corresponding 3-aryl-1-(benzimidazol-2-yl)-prop-2- en-1-one 3a-d derivatives. Compound 3a-d act as key intermediates for all the three series of final compounds. In one pathway 3a-d is converted to its alkoxyphthalimide derivatives 5a-h by condensation with ω- bromoalkoxyphthalimides 4a-b, which cyclize with PhNHNH2/pyridine, guanidine nitrate/10% NaOH and hydroxylamine hydrochloride/CH3COOH to give 9a-h, 10a-h and 11a-h respectively. In an alternative route, reaction of 3a-d with all the three reagents affords 2-(3-aryl-2-phenyl-3,4-dihydropyrazol- 5-yl)benzimidazole 6a-d, 4-(benzimidazol-2-yl)-6-arylpyrimidin-2-amine 7a-d and 2-(5-aryl-4,5-dihydroisoxazol-3-yl)benzimidazole 8a-d which on condensation with co-bromoalkoxyphthalimides 4a-b give the final compounds 9a-h, 10a-h and 11a-h. Structure elucidations of all the compounds have been accomplished by elemental analysis, IR, 1H NMR and mass spectral data.

Why are benzimidazoles efficiently acylated with esters? Identification of a tetrahedral hemiacetal alkoxide intermediate

2-Lithio benzimidazoles were acylated with esters, lactones, and lactams. The tetrahedral hemiacetal intermediates responsible for the efficient conversion were characterized by low temperature NMR.