43156-08-7

Upstream product

• 43155-80-2 5-(2-chlorophenoxy)-2-nitroaniline 
• 1635-61-6 5-chloro-2-nitroaniline 
• 2369-11-1 5-fluoro-2-nitroaniline 

Downstream Products

• 43155-41-5 methyl 5-<(o-chloro)phenoxy>-2-benzimidazolecarbamate 
• 1430719-92-8 1-(5-(2-chlorophenoxy)-1H-benzo[d]imidazol-2-yl)-3-ethylurea 
• 1430719-92-8 C₁₆H₁₅ClN₄O₂ 

Relevant academic research and scientific papers

5 - [...] -2 alkyl substituted [...] and imidazole compound and use thereof

The present invention discloses a 5-aryl phenol-2 alkyl substituted urea benzimidazole compound and applications thereof, wherein the compound has a structure represented by a formula (I). According to the present invention, the 5-aryl phenol-2 alkyl subs

New benzimidazole-2-urea derivates as tubulin inhibitors

Emerging drug resistance and other drawbacks limit tubulin inhibitors' therapeutic applications and developing novel tubulin inhibitors still attracts intensive efforts. We describe the discovery and structure-activity relationship study of a series of benzimidazole-2-urea derivatives as novel β tubulin inhibitors. The representative compound 6o potently suppressed the proliferation of a panel of human cancer cells (NCI-H460, Colo205, K562, A431, HepG2, Hela, MDA-MB-435S) with IC50 values of 0.040, 0.050, 0.006, 0.026, 1.774, 0.452 and 0.052 μM, respectively. Compound 6o obviously inhibited NCI-H460 spindles formation and induced cell cycle arrest at G2/M phase at 0.10 μM. Computational study suggested that 6o interacts with β tubulin in a novel binding mode. Our results suggested that benzimidazole-2-urea derivatives might be promising tubulin inhibitors with novel binding mode for further development.

Discovery of picomolar ABL kinase inhibitors equipotent for wild type and T315I mutant via structure-based de novo design

Although the constitutively activated break-point cluster region-Abelson (ABL) tyrosine kinase is known to cause chronic myelogenous leukemia (CML), the prevalence of drug-resistant ABL mutants has made it difficult to develop effective anti-CML drugs. With the aim to identify new lead compounds for anti-CML drugs, we carried out a structure-based de novo design using the scoring function improved by implementing an accurate solvation free energy term. This approach led to the identification of ABL inhibitors equipotent for the wild type and the most drug-resistant T315I mutant of ABL at the picomolar level. Decomposition analysis of the binding free energy showed that a decrease in the desolvation cost for binding in the ATP-binding site could be as important as the strengthening of enzyme-inhibitor interaction to enhance the potency of an ABL inhibitor with structural modifications. A similar energetic feature was also observed in free energy perturbation (FEP) calculations. Consistent with the previous experimental and computational studies, the hydrogen bond interactions with the backbone groups of Met318 proved to be the most significant binding forces to stabilize the inhibitors in the ATP-binding sites of the wild type and T315I mutant. The results of molecular dynamics simulations indicated that the dynamic stabilities of the hydrogen bonds between the inhibitors and Met318 should also be considered in designing the potent common inhibitors of the wild-type and T315I mutant of ABL.

Discovery of new benzothiazole-based inhibitors of breakpoint cluster region-abelson kinase including the T315i mutant

The existence of drug resistance caused by mutations in the break-point cluster region-Abelson tyrosine kinase (Bcr-Abl) kinase domain remains a clinical challenge due to limited effective treatment options for chronic myeloid leukemia (CML). Herein we report a novel series of benzothiazole-based inhibitors that are effective against wild-type and T315I mutant Bcr-Abl kinases. The original hit compound, nocodazole, was extensively modified through a structure-based drug design strategy, especially by varying the groups at the C2 and C6 positions of the scaffold. In addition, the introduction of water-solubilizing groups at the terminal ethyl group resulted in enhanced physicochemical properties and potency in cellular inhibition. Several compounds inhibited the kinase activity of both wild-type Bcr-Abl and the T315I mutant with IC50 values in the picomolar range and exhibited good antiproliferative effects on Ba/F3 cell lines transformed with either wild-type or T315I mutant Bcr-Abl.

Synthesis and spectral properties of methyl 5-[(o-, m-, and p-r)- phenoxy]-2-benzimidazolecarbamate

The preparation of eleven novel methyl 5-[(o-, m-, p-R)-phenoxy-2- benzimidazolecarbamates with possible pharmacological activity as anthelmintics is described. The structure of all products was corroborated by it, 1H-nmr, 13C-nmr and mass spectra.