2033-29-6

Usage

Uses

Used in Oncology:
5,6-Dichloro-1H-benzo[d]imidazol-2(3H)-one is used as an anticancer agent for its capacity to impede the proliferation of cancer cells. It targets the cell cycle, leading to cell cycle arrest, and induces apoptosis, thereby contributing to the reduction of tumor size and potentially enhancing the effectiveness of cancer treatments.
Used in Drug-Resistant Cancer Treatment:
In the field of oncology, 5,6-Dichloro-1H-benzo[d]imidazol-2(3H)-one is utilized for its potential to combat drug-resistant cancers. Its activity against a range of cancer types suggests that DCBIO could be instrumental in overcoming resistance mechanisms that traditional chemotherapy drugs may not address, thereby improving patient outcomes in refractory cancer cases.
Used in Preclinical Cancer Research:
5,6-Dichloro-1H-benzo[d]imidazol-2(3H)-one is employed in preclinical studies to evaluate its efficacy and safety as a potential therapeutic agent for various types of cancer. These studies are crucial for understanding the compound's mechanism of action, side effects, and optimal dosages before it can be considered for clinical trials and eventual use in cancer treatment regimens.
Used in Pharmaceutical Development:
Within the pharmaceutical industry, 5,6-Dichloro-1H-benzo[d]imidazol-2(3H)-one serves as a key compound in the development of new anticancer drugs. Its unique properties and demonstrated effects on cancer cells make it a valuable asset in the creation of novel therapeutics aimed at improving cancer treatment options and patient survival rates.

Upstream product

• 5348-42-5 4,5-Dichloro-1,2-phenylenediamine 
• 57-13-6 urea 
• 64269-79-0 Carbonyldiimidazole 
• 530-62-1 1,1'-carbonyldiimidazole 
• 615-16-7 1,3-dihydro-2H-benzimidazol-2-one 

Downstream Products

• 142372-26-7 1-benzyl-2,5,6-trichlorobenzimidazole 
• 1268713-06-9 N-(cyclohexylmethyl)-1-(5,6-dichloro-1H-benzo[d]imidazol-2-yl)piperidine-4-carboxamide 
• 1268709-74-5 N-cyclopentyl-1-(5,6-dichloro-1-phenyl-1H-benzo[d]imidazol-2-yl)piperidine-4-carboxamide 
• 1268709-65-4 N-cyclopentyl-1-(5,6-dichloro-1-(1-phenylethyl)-1H-benzo[d]imidazol-2-yl)piperidine-4-carboxamide 
• 1268712-25-9 (R)-1-(5,6-dichloro-1-p-tolyl-1H-benzo[d]imidazol-2-yl)-N-(tetrahydrofuran-3-yl)piperidine-4-carboxamide 
• 1268710-95-7 (R)-1-(5,6-dichloro-1-(3-methoxyphenyl)-1H-benzo[d]imidazol-2-yl)-N-(tetrahydrofuran-3-yl)piperidine-4-carboxamide 
• 1268710-29-7 1-(1-(4-(1H-1,2,4-triazol-1-yl)benzyl)-5,6-dichloro-1H-benzo[d]imidazol-2-yl)-N-cyclopentylpiperidine-4-carboxamide 
• 161468-75-3 5,6-Dichloro-2,3-dihydro-2-oxo-3-(phenylmethyl)-1H-benzimidazole-1-carboxylic acid ethyl ester 
• 1026027-09-7 5,6-Dichloro-3-cyclohexylmethyl-2-oxo-2,3-dihydro-benzoimidazole-1-carboxylic acid ethyl ester 
• 16865-11-5 2,5,6-trichloro-1H-benzo[d]imidazole 

Relevant academic research and scientific papers

Synthesis of novel halogenated heterocycles based on o‐phenylenediamine and their interactions with the catalytic subunit of protein kinase ck2

Protein kinase CK2 is a highly pleiotropic protein kinase capable of phosphorylating hundreds of protein substrates. It is involved in numerous cellular functions, including cell viability, apoptosis, cell proliferation and survival, angiogenesis, or ER‐stress response. As CK2 activity is found perturbed in many pathological states, including cancers, it becomes an attractive target for the pharma. A large number of low‐mass ATP‐competitive inhibitors have already been developed, the majority of them halogenated. We tested the binding of six series of halogenated heterocyclic ligands derived from the commercially available 4,5‐dihalo‐benzene‐1,2‐diamines. These ligand series were selected to enable the separation of the scaffold effect from the hydrophobic interactions attributed directly to the presence of halogen atoms. In silico molecular docking was initially applied to test the capability of each ligand for binding at the ATP‐binding site of CK2. HPLC‐derived ligand hydrophobicity data are compared with the binding affinity assessed by low‐volume differential scanning fluorimetry (nanoDSF). We identified three promising ligand scaffolds, two of which have not yet been described as CK2 inhibitors but may lead to potent CK2 kinase inhibitors. The inhibitory activity against CK2α and toxicity against four reference cell lines have been determined for eight compounds identified as the most promising in nanoDSF assay.

Disrupting the Conserved Salt Bridge in the Trimerization of Influenza A Nucleoprotein

Antiviral drug resistance in influenza infections has been a major threat to public health. To develop a broad-spectrum inhibitor of influenza to combat the problem of drug resistance, we previously identified the highly conserved E339?R416 salt bridge of the nucleoprotein trimer as a target and compound 1 as an inhibitor disrupting the salt bridge with an EC50 = 2.7 μM against influenza A (A/WSN/1933). We have further modified this compound via a structure-based approach and performed antiviral activity screening to identify compounds 29 and 30 with EC50 values of 110 and 120 nM, respectively, and without measurable host cell cytotoxicity. Compared to the clinically used neuraminidase inhibitors, these two compounds showed better activity profiles against drug-resistant influenza A strains, as well as influenza B, and improved survival of influenza-infected mice.

Discovery of a Selective Aurora A Kinase Inhibitor by Virtual Screening

Here we report the discovery of a selective inhibitor of Aurora A, a key regulator of cell division and potential anticancer target. We used the atom category extended ligand overlap score (xLOS), a 3D ligand-based virtual screening method recently developed in our group, to select 437 shape and pharmacophore analogs of reference kinase inhibitors. Biochemical screening uncovered two inhibitor series with scaffolds unprecedented among kinase inhibitors. One of them was successfully optimized by structure-based design to a potent Aurora A inhibitor (IC50 = 2 nM) with very high kinome selectivity for Aurora kinases. This inhibitor locks Aurora A in an inactive conformation and disrupts binding to its activator protein TPX2, which impairs Aurora A localization at the mitotic spindle and induces cell division defects. This phenotype can be rescued by inhibitor-resistant Aurora A mutants. The inhibitor furthermore does not induce Aurora B specific effects in cells.

Rational Design, Pharmacomodulation, and Synthesis of Dual 5-Hydroxytryptamine 7 (5-HT7)/5-Hydroxytryptamine 2A (5-HT2A) Receptor Antagonists and Evaluation by [18F]-PET Imaging in a Primate Brain

We report the synthesis of 46 tertiary amine-bearing N-alkylated benzo[d]imidazol-2(3H)-ones, imidazo[4,5-b]pyridin-2(3H)-ones, imidazo[4,5-c]pyridin-2(3H)-ones, benzo[d]oxazol-2(3H)-ones, oxazolo[4,5-b]pyridin-2(3H)-ones and N,N′-dialkylated benzo[d]imidazol-2(3H)-ones. These compounds were evaluated against 5-HT7R, 5-HT2AR, 5-HT1AR, and 5-HT6R as potent dual 5-HT7/5-HT2A serotonin receptors ligands. A thorough study of the structure-activity relationship of the aromatic rings and their substituents, the alkyl chain length and the tertiary amine was conducted. 1-(4-(4-(4-Fluorobenzoyl)piperidin-1-yl)butyl)-1H-benzo[d]imidazol-2(3H)-one (79) and 1-(6-(4-(4-fluorobenzoyl)piperidin-1-yl)hexyl)-1H-benzo[d]imidazol-2(3H)-one (81) were identified as full antagonist ligands on cyclic adenosine monophosphate (cAMP, KB = 4.9 and 5.9 nM, respectively) and inositol monophosphate (IP1, KB = 0.6 and 16 nM, respectively) signaling pathways of 5-HT7R and 5-HT2AR. Both antagonists crossed the blood-brain barrier as evaluated with [18F] radiolabeled compounds [18F]79 and [18F]81 in a primate's central nervous system using positron emission tomography. Both radioligands showed standard uptake values ranging from 0.8 to 1.1, a good plasmatic stability, and a distribution consistent with 5-HT7R and 5-HT2AR in the CNS.

MEGLUMINE SALT FORMULATIONS OF 1-(5,6-DICHLORO-1H-BENZO[D]IMIDAZOL-2-YL)-1H-PYRAZOLE-4-CARBOXYLIC ACID

The meglumine salt of 1-(5,6-dichloro-1H-benzo[d]imidazol-2-yl)-1H-pyrazole-4-carboxylic acid (compound (1)) and pharmaceutically acceptable formulations thereof are described. Such compounds may be used in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by prolyl hydroxylase activity.

PIPERIDINYL BENZOIMIDAZOLE DERIVATIVES AS MPGES-1 INIHIBITORS

A compound of formula (I) as well as pharmaceutically acceptable salts thereof, and a pharmaceutical composition comprising the compound. The compound is useful for the treatment of disorder selected from inflammatory diseases, pain, auto-immune disease, breathing disorders, fever, cancer, inflammation related anorexia, overactive bladder, familial adenomatous polyposis (FAP) condition, neurodegenerative diseases, bone diseases and cardiovascular diseases.

MICROSOMAL PROSTAGLANDIN E SYNTHASE-1 (MPGES1) INHIBITORS

A compound of formula (I): as well as pharmaceutically acceptable salts thereof, and a pharmaceutical composition comprising the compound. The compound is useful for the treatment of disorder selected from inflammatory diseases, nociceptive pain, auto-imm

BENZOIMIDAZOLES AS PROLYL HYDROXYLASE INHIBITORS

The present invention is directed to benzoimidazole compounds of the formula (1) and enantiomers, diastereomers, racemates, and pharmaceutically acceptable salts thereof. Compounds of the present invention are useful in pharmaceutical compositions and met

Synthesis and in vitro antimicrobial activity of some novel substituted benzimidazole derivatives having potent activity against MRSA

The novel benzimidazole derivatives (3, 5, 8, 9, 12-14, 18-41) were prepared in this paper and the antimicrobial activities of these compounds against Staphylococcus aureus, methicillin-resistant S. aureus (MRSA, standard and clinical isolates), Bacillus subtilis, Escherichia coli and Candida albicans were evaluated. Compounds 24-26 which have no substitution of N-1 position displayed better antibacterial activities than those of standards (ciprofloxacin, ampicillin and sultamicillin) against both the drug-resistant bacteria (MRSA, standard and clinical isolates). These derivatives (24-26), 2,5,6-trihalogenobenzimidazole analogues (8, 12), 5,6-dichloro-2-amino derivative (13), and 5-chloro-2-(4-benzyloxyphenyl)benzimidazole (35) exhibited the most potent antibacterial activity with MIC 3.12 μg/ml against S. aureus.

SUBSTITUTED BENZIMIDAZOLONE DERIVATIVES, MEDICAMENTS COMPRISING THEM AND THEIR USE

The present invention relates to novel benzimidazolone derivatives of the general formula (I) in which the substituents R1, R2, R3, A1, A2, and B are as defined in claim 1, medicaments comprising these, and the use thereof for the prophylaxis and/or treatment of vasopressin-dependent diseases.