155198-10-0

Upstream product

• 54997-99-8 2-nitro-5-piperidin-1-yl-phenylamine 
• 74628-25-4 2-nitro-5-(1-piperidinyl)aniline 
• 364-53-4 4-fluoro-1,2-dinitro-benzene 
• 27429-80-7 spiro[2H-benzimidazole-2,1'-cyclohexane] 
• 3190-03-2 1,3-dihydrospiro[2H-benzimidazole-2,1'-cyclohexane] 
• 110-89-4 piperidine 
• 1635-61-6 5-chloro-2-nitroaniline 
• 63953-55-9 5-piperidino-2H-benzimidazole-2-spirocyclohexane 
• 2369-11-1 5-fluoro-2-nitroaniline 

Downstream Products

• 54998-26-4 2-amino-4-<5'-(piperidin-1''-yl)benzimidazol-2'-yl>aniline 
• 158667-55-1 4-dimethylamino-1-{5'-[5''-(piperidin-1''-yl)-1H-benzimidazol-2'-yl]-3H-benzimidazol-2'-yl}benzene 

Relevant academic research and scientific papers

Discovery of 1-(5-(1H-benzo[d]imidazole-2-yl)-2,4-dimethyl-1H-pyrrol-3-yl)ethan-1-one derivatives as novel and potent bromodomain and extra-terminal (BET) inhibitors with anticancer efficacy

As epigenetic readers, bromodomain and extra-terminal domain (BET) family proteins bind to acetylated-lysine residues in histones and recruit protein complexes to promote transcription initiation and elongation. Inhibition of BET bromodomains by small molecule inhibitors has emerged as a promising therapeutic strategy for cancer. Herein, we describe our efforts toward the discovery of a novel series of 1-(5-(1H-benzo[d]imidazole-2-yl)-2,4-dimethyl-1H-pyrrol-3-yl)ethan-1-one derivatives as BET inhibitors. Intensive structural modifications led to the identification of compound 35f as the most active inhibitor of BET BRD4 with selectivity against BET family proteins. Further biological studies revealed that compound 35f can arrest the cell cycle in G0/G1 phase and induce apoptosis via decreasing the expression of c-Myc and other proteins related to cell cycle and apoptosis. More importantly, compound 35f showed favorable pharmacokinetic properties and antitumor efficacy in MV4-11 mouse xenograft model with acceptable tolerability. These results indicated that BET inhibitors could be potentially used to treat hematologic malignancies and some solid tumors.

Discovery of 3-(5′-Substituted)-Benzimidazole-5-(1-(3,5-dichloropyridin-4-yl)ethoxy)-1H-indazoles as Potent Fibroblast Growth Factor Receptor Inhibitors: Design, Synthesis, and Biological Evaluation

Fibroblast growth factor receptor (FGFR) represents an attractive oncology target for cancer therapy in view of its critical role in promoting cancer formation and progression, as well as causing resistance to approved therapies. In this article, we describe the identification of the potent pan-FGFR inhibitor (R)-21c (FGFR1-4 IC50 values of 0.9, 2.0, 2.0, and 6.1 nM, respectively). Compound (R)-21c exhibited excellent in vitro inhibitory activity against a panel of FGFR-amplified cell lines. Western blot analysis demonstrated that (R)-21c suppressed FGF/FGFR and downstream signaling pathways at nanomolar concentrations. Moreover, (R)-21c provided nearly complete inhibition of tumor growth (96.9% TGI) in NCI-H1581 (FGFR1-amplified) xenograft mice model at the dose of 10 mg/kg/qd via oral administration.

Quantitative structure-activity relationships on 5-substituted terbenzimidazoles as topoisomerase I poisons and antitumor agents

Several 5-substituted terbenzimidazoles were synthesized and evaluated as mammalian topoisomerase I poisons and for cytotoxicity against a human lymphoblastoma cell line, RPMI-8402. No correlation was observed between topoisomerase I poisoning activity and the Hansch π value or the σ(meta) and σ(para) values associated with each substituent. These data suggest that electronic effects and relative lipophilicity of substituents at the 5-position of these terbenzimidazoles do not have a significant effect upon intrinsic topoisomerase I poisoning activity. There was, however, a good correlation between the relative π values for the various subtituents evaluated and cytotoxic activity. Experimentally determined log P values did not correlate well with either cytotoxicity or π values. Capacity factors (log k') as determined by high pressure liquid chromatography did correlate well with the π values of varied substituents and cytotoxicity. These data indicate that the relative lipophilic activity of substituents at the 5-position of these terbenzimidazoles can strongly influence relative cytotoxic activity.

2H-benzimidazoles (isobenzimidazoles). Part 10. Synthesis of polysubstituted o-phenylenediamines and their conversion into heterocycles, particularly 2-substituted benzimidazoles with known or potential anthelminthic activity

Polysubstituted o-phenylenediamines were synthesised in moderate to high yield by reductive cleavage of the corresponding 2H-benzimidazole-2-spirocyclohexane with sodium dithionite in aqueous ethanol and converted into methyl benzimidazole-2-carbamates and 2-methylthio- and 2-trifluoro-methylbenzimidazoles with known or potential anthelminthic activity. 5-(Pyrimidin-2-ylthio)-benzimidazole and 11-(pyridin-2-ylthio)dibenzo[a,c]phenazine were synthesized too. Attempts to oxidise 1,3-dihydro-2H-4,9-diazanaphth[2,3-d]imidazole, prepared by condensation of 2,3-diaminoquinoxaline with cyclohexanone, to an analogue of the title system failed.

DNA Binding Compounds. V. Synthesis and Characterization of Boron-Containing Bibenzimidazoles Related to the DNA Minor Groove Binder, Hoechst 33258

The synthesis and characterization of four novel boron-containing bibenzimidazoles related to the DNA minor groove binder Hoechst 33258 are reported.Such compounds, particularly their 10B-enriched forms, have potential as agents for boron neutron capture therapy which is used in the treatment of cancers.

Umpolung of o-Phenylenediamines by Conversion into Izobenzimidazole. An Expedient Approach to Heterocycles with Nucleophilic Substituents

Isobenzimidazole-2-spirocyclohexane (1) can be made to react with nitrogen, oxygen, sulphur, and carbon nucleophiles to give mono- and di-substituted derivatives.On reductive ring-opening the correspondingly substituted o-phenylenediamine is obtained.The scope of this synthetic principle has been studied and the reaction used to prepare various heterocycles with substituents that are difficult to introduce by conventional methods.Selenadiazole or its 4-chloro and 4,5-dichloro derivatives were found to be unsuitable alternatives to (1).