82357-48-0

Usage

Chemical Properties

White solid

InChI:InChI=1/C8H7ClN2O3/c1-10-6-3-2-5(8(9)12)4-7(6)11(13)14/h2-4,10H,1H3

Upstream product

• 41263-74-5 4-(methylamino)-3-nitrobenzoic acid 
• 1187067-71-5 4-(methylamine)-3-nitrobenzoic acid hydrochloride 
• 96-99-1 4-chloro-3-nitrobenzoate 
• 453-71-4 3-nitro-4-fluorobenzoic acid 

Downstream Products

• 429658-94-6 [(4-methylamino-3-nitro-benzoyl)phenyl-amino]acetic acid ethyl ester 
• 429659-01-8 ethyl 3-{[{1-(methylamino)-2-nitrophen-4-yl}carbonyl](pyridyn-2-yl)amino}propanoate 
• 429659-00-7 4-[(4-methylamino-3-nitro-benzoyl)-phenyl-amino]-butyric acid ethyl ester 
• 41263-66-5 4-Methylamino-3-nitro-benzamid 
• 1187067-68-0 ethyl 3-[[4-(methylamino)-3-nitrobenzoyl](pyridin-2-yl)amino]propanoate hydrochloride 
• 211915-06-9 dabigatran etexilate 
• 872728-81-9 N-[[2-[[[4-[[[(hexyloxy)carbonyl]amino]iminomethyl]phenyl] amino]methyl]-1-methyl-1H-benzimidazol-5-yl]carbonyl]-N-(2-pyridinyl)-β-alanine ethyl ester methanesulfonate 
• 1315605-50-5 3-[(4-Methylamino-3-nitro-benzoyl)-phenyl-amino]-propionic acid methyl ester 

Relevant academic research and scientific papers

Novel potent benzimidazole-based microsomal prostaglandin E2 synthase-1 (mPGES-1) inhibitors derived from BRP-201 that also inhibit leukotriene C4 synthase

Microsomal prostaglandin E2 synthase-1 (mPGES-1) is recognized as a promising therapeutic target for next-generation anti-inflammatory drugs to treat inflammatory diseases. In this study, we report the identification of new, potent and selectiv

Design, synthesis and biological activity evaluation of novel methyl substituted benzimidazole derivatives

Ten new dabigatran derivatives (7a–j) with high docking scoring were designed, synthesised and biologically evaluated. The inhibitory in vitro activity of these compounds on thrombin was evaluated on the basis of preliminary activity screening results. The IC50 values of compounds 7a, 7d and 7j were 1.92, 2.17 and 1.54 nM, respectively, and are equivalent to the dabigatran (IC50 = 1.20 nM). Therefore, the most active compound, 7j, was selected to further investigate the anticoagulant activity in rats. Compound 7j presented excellent in vivo inhibitory effects on arteriovenous thrombosis, and the inhibition rate was (84.19 ± 1.14) %. The anticoagulant activity of compound 7k synthesised in the previous work was evaluated in vivo, and its inhibition rate was (85.58 ± 2.89) %. This rate was nearly equivalent to that of dabigatran (85.07 ± 0.61) %. Results indicated that compounds 7a, 7d, 7j and 7k can be further studied as novel antithrombin drug candidates.

Computer-aid drug design, synthesis, and anticoagulant activity evaluation of novel dabigatran derivatives as thrombin inhibitors

In this study, computer-aided drug design techniques were adopted to explore the structural and chemical features for dabigatran and design novel derivatives. The built 3D-QSAR models demonstrated significant statistical quality and excellent predictive ability by internal and external validation. Based on QSAR information, 11 novel dabigatran derivatives (12a–12k) were designed and predicted, then ADME prediction and molecular docking were performed. Furthermore, all designed compounds were synthesized and characterized by 1H NMR, 13C NMR and HR-MS. Finally, they were evaluated for anticoagulant activity in vitro. The activity results showed that the 10 obtained compounds exhibited comparable activity to the reference dabigatran (IC50 = 9.99 ± 1.48 nM), except for compound 12i. Further analysis on molecular docking was performed on three compounds (12a, 12c and 12g) with better activity (IC50 = 11.19 ± 1.70 nM, IC50 = 10.94 ± 1.85 nM and IC50 = 11.19 ± 1.70 nM). MD simulations (10 ns) were carried out, and their binding free energies were calculated, which showed strong hydrogen bond and pi–pi stacking interactions with key residues Gly219, Asp189 and Trp60D. The 10 novel dabigatran derivatives obtained can be further studied as anticoagulant candidate compounds.

Benzimidazole derivative and pharmaceutical purposes thereof

The invention discloses a benzimidazole derivative and pharmaceutical purposes thereof, and particularly discloses a benzimidazole derivative shown in a formula I and purposes of the benzimidazole derivative to preparation of drugs for treating and/or pre

Synthesis, Crystal Structure, and Anti-Gastric Cancer Activity of Ethyl 3-(3-Amino-4-(Methylamino)-N-(Pyridin-2-Yl) Benzamido)Propanoate

A new heterocyclic compound ethyl 3-(3-amino-4-(methylamino)-N-(pyridin-2-yl)benzamido)propanoate (1), designed using 4-(methylamino)-3-nitrobenzoic acid (2) as a starting material is successfully obtained via a multiple synthesis route and finally characterized by IR, 1H NMR, and single crystal X-ray crystallography. In addition, the in vitro anti-cancer activity of newly synthesized complex 1 is emulated against three human gastric cancer cell lines SGC-790, MKN-4, and MKN45.

Molecular modeling studies, synthesis and biological evaluation of dabigatran analogues as thrombin inhibitors

In this work, 48 thrombin inhibitors based on the structural scaffold of dabigatran were analyzed using a combination of molecular modeling techniques. We generated three-dimensional quantitative structure-activity relationship (3D-QSAR) models based on three alignments for both comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) to highlight the structural requirements for thrombin protein inhibition. In addition to the 3D-QSAR study, Topomer CoMFA model also was established with a higher leave-one-out cross-validation q2 and a non-cross-validation r2, which suggest that the three models have good predictive ability. The results indicated that the steric, hydrophobic and electrostatic fields play key roles in QSAR model. Furthermore, we employed molecular docking and re-docking simulation explored the binding relationship of the ligand and the receptor protein in detail. Molecular docking simulations identified several key interactions that were also indicated through 3D-QSAR analysis. On the basis of the obtained results, two compounds were designed and predicted by three models, the biological evaluation in vitro (IC50) demonstrated that these molecular models were effective for the development of novel potent thrombin inhibitors.

Design, synthesis, biological evaluation and molecular docking studies of dabigatran analogs as potential thrombin inhibitors

A series of fluorinated dabigatran analogs were designed and synthesized. All the target compounds were characterized by 1H NMR, 13C NMR, and FT-ICR-MS. The thrombin inhibitory activities of the new synthesized compounds were also evaluated in vitro. The results show that compound 12a has the highest IC50 of thrombin inhibition (IC50 = 5.41 nM). Moreover, molecular docking simulation was carried out to elucidate the conformations of the compounds and key amino acid residues at the active site of thrombin protein. The results show there is an appropriate relationship between IC50 and the docking scores for compounds 12a-e. We suggest that the hydrogen bond interaction between Asp189, Gly219 of thrombin and the compounds appear to play major role in thrombin inhibition.

Synthesis and biological evaluation of novel dabigatran derivatives as thrombin inhibitors

A novel series of 3-[{2-[(4-carbamimidoylphenylamino)methyl]-1-substituted-1H-benzoimidazole-5-carbonyl}(3-chloro-4-fluorophenyl)amino]propionic derivatives of dabigatran was synthesized. The structures of the compounds were characterized by 1H NMR, 13C NMR, HRMS, and elemental analysis. The compounds were screened for in vitro thrombin inhibitory activity. The results indicated that the compounds had low to moderate inhibitory activity. The compounds with N-methyl and N-ethyl side chains had much greater inhibitory activity against thrombin than those with other side chains.

Multi-substituted 4-methyl ester derivative of amino benzonitrile trunk and its preparation and use

The invention provides new ester derivatives with a general formula (I) shown in the specification of multi-substituted 4-methylamino-benzamidine or pharmaceutically acceptable salts, wherein A1, A2, A3 and A4 in the formula are as defined in the specification. The compounds have an anticoagulant effect and can be used for preparing medicaments for preventing and treating thromboembolic diseases.

A PROCESS FOR PREPARATION OF DABIGATRAN ETEXILATE MESYLATE AND INTERMEDIATES THEREOF

The present invention relates to an improved process for the preparation of Dabigatran etexilate and its acid addition salts thereof, wherein the said process substantially eliminates the potential impurities. The present invention also relates to an intermediate of Dabigatran etexilate and process for preparation thereof.