119421-28-2

Upstream product

• 54998-00-4 5-morpholino-2-nitroaniline 
• 63953-56-0 5-morpholin-4-yl-spiro[benzoimidazole-2,1'-cyclohexane] 
• 1635-61-6 5-chloro-2-nitroaniline 
• 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] 

Downstream Products

• 1187383-55-6 7-methoxy-8-{5-[2-[(4-(benzyloxy)phenyl)-6-morpholino]benzimidazol-1-yl]pentyl}oxy-(11aS)-1,2,3,11a-tetrahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one 
• 1187383-66-9 (2S)-N-{4-(5-[2-[(4-(benzyloxy)phenyl)-6-morpholino]benzimidazol-1-yl]pentyl)oxy-5-methoxy-2-aminobenzoyl}pyrrolidine-2-carboxaldehyde diethyl thioacetal 
• 1187383-65-8 (2S)-N-{4-(5-[2-[(4-(benzyloxy)phenyl)-6-morpholino]benzimidazol-1-yl]pentyl)oxy-5-methoxy-2-nitrobenzoyl}pyrrolidine-2-carboxaldehyde diethyl thioacetal 
• 1187383-72-7 4-{2-[4-(benzyloxy)phenyl]benzimidazol-6-yl}morpholine 
• 1339045-88-3 4-(5'-morpholino-benzimidazol-2'-yl)-2-nitroaniline 
• 402948-33-8 ethyl 2-(5-morpholin-4-ylbenzimidazol-2-yl)acetate 
• 948834-65-9 C₁₇H₁₇N₆O₂Br 
• 111861-06-4 5⁽⁶⁾-Morpholino-2-(4-nitrophenyl)benzimidazole 
• 136415-11-7 2,6-Di-tert-butyl-4-[2-(5-morpholin-4-yl-1H-benzoimidazol-2-yl)-ethyl]-phenol 
• 136415-10-6 2,6-Di-tert-butyl-4-(5-morpholin-4-yl-1H-benzoimidazol-2-ylmethyl)-phenol 
• 120423-37-2 5⁽⁶⁾-Morpholino-2-(3,5-di-tert-butyl-4-hydroxyphenyl)benzimidazole 

Relevant academic research and scientific papers

Fragment-based design, synthesis, biological evaluation, and SAR of 1H-benzo[d]imidazol-2-yl)-1H-indazol derivatives as potent PDK1 inhibitors

In this work, we describe the use of the rule of 3 fragment-based strategies from biochemical screening data of 1100 in-house, small, low molecular weight fragments. The sequential combination of in silico fragment hopping and fragment linking based on S1

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.

SUBSTITUTED BENZIMIDAZOLE CARBOXAMIDES AND THEIR USE IN THE TREATMENT OF MEDICAL DISORDERS

The invention provides substituted benzimidazole carboxamides and related compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat a medical disorder, e.g., cancer, lysosomal storage disorder, neurodegenerative disorder, inflammatory disorder, in a patient.

Pyrrole derivative as well as preparation method and application thereof

The invention belongs to the field of medical chemistry, and relates to a pyrrole derivativex as well as a preparation method and application thereof. A compound with a structure shown as a general formula (I), or one or a mixture of more of a tautomer, a

NEW QUINOLINONE COMPOUNDS

Provided are new quinolinone compounds, pharmaceutical compositions comprising said compounds, processes for the preparation of said compounds and the use of said compounds as FGFR inhibitors and their use in the treatment of diseases, e.g. cancer.

Targeting G-quadruplex DNA structures in the telomere and oncogene promoter regions by benzimidazole?carbazole ligands

Recent studies support the idea that G-quadruplex structures in the promoter regions of oncogenes and telomere DNA can serve as potential therapeutic targets in the treatment of cancer. Accordingly, several different types of organic small molecules that stabilize G-quadruplex structures and inhibit telomerase activity have been discerned. Here, we describe the binding of benzimidazole-carbazole ligands to G-quadruplex structures formed in G-rich DNA sequences containing the promoter regions of human c-MYC, c-KIT1, c-KIT2, VEGF and BCL2 proto-oncogenes. The fluorescence spectroscopic data indicate that benzimidazole-carbazole ligands bind and stabilize the G-quadruplexes in the promoter region of oncogenes. The molecular docking studies provide insights into the mode and extent of binding of this class of ligands to the G-quadruplexes formed in oncogene promoters. The high stability of these G-quadruplex structures was validated by thermal denaturation and telomerase-catalyzed extension of the 3' end. Notably, benzimidazole-carbazole ligands suppress the expression of oncogenes in cancer cells in a dose-dependent manner. We anticipate that benzimidazole-carbazole ligands, by virtue of their ability to stabilize G-quadruplex structures in the promoter regions of oncogenes, might reduce the risk of cancer through the loss of function in the proteins encoded by these genes.

Preparation method and purpose of pyrrolone BRD4 protein inhibitor

The invention relates to the field of medicinal chemistry, in particular to pyrrolone derivatives, a preparation method of the pyrrolone derivatives, a pharmaceutical composition containing the compounds and medical purposes of the pharmaceutical composition, particularly an antitumor purpose of the pharmaceutical composition as a BRD4 protein inhibitor.

Hybrid pharmacophore design and synthesis of naphthalimide-benzimidazole conjugates as potential anticancer agents

Naphthalimide-benzimidazole conjugates were prepared using two different types of spacer units; either a simple alkane chain or a substituted piperazine moiety with variable alkyl side chains. Each set of conjugates was evaluated for their in vitro antica

N-aryl-2-aminobenzimidazoles: Novel, efficacious, antimalarial lead compounds

From the phenotypic screening of the AstraZeneca corporate compound collection, N-aryl-2-aminobenzimidazoles have emerged as novel hits against the asexual blood stage of Plasmodium falciparum (Pf). Medicinal chemistry optimization of the potency against Pf and ADME properties resulted in the identification of 12 as a lead molecule. Compound 12 was efficacious in the P. berghei (Pb) model of malaria. This compound displayed an excellent pharmacokinetic profile with a long half-life (19 h) in rat blood. This profile led to an extended survival of animals for over 30 days following a dose of 50 mg/kg in the Pb malaria model. Compound 12 retains its potency against a panel of Pf isolates with known mechanisms of resistance. The fast killing observed in the in vitro parasite reduction ratio (PRR) assay coupled with the extended survival highlights the promise of this novel chemical class for the treatment of malaria.

Design and synthesis of new benzimidazole-carbazole conjugates for the stabilization of human telomeric DNA, telomerase inhibition, and their selective action on cancer cells

Cell-permeable small molecules that enhance the stability of the G-quadruplex (G4) DNA structures are currently among the most intensively pursued ligands for inhibition of the telomerase activity. Herein we report the design and syntheses of four novel benzimidazole-carbazole conjugates and demonstrate their high binding affinity to G4 DNA. S1 nuclease assay confirmed the ligand mediated G-quadruplex DNA protection. Additional evidence from Telomeric Repeat Amplification Protocol (TRAP-LIG) assay demonstrated efficient telomerase inhibition activity by the ligands. Two of the ligands showed IC 50 values in the sub-micromolar range in the TRAP-LIG assay, which are the best among the benzimidazole derivatives reported so far. The ligands also exhibited cancer cell selective nuclear internalization, nuclear condensation, fragmentation, and eventually antiproliferative activity in long-term cell viability assays. Annexin V-FITC/PI staining assays confirm that the cell death induced by the ligands follows an apoptotic pathway. An insight into the mode of ligand binding was obtained from the molecular dynamics simulations.