42288-26-6Relevant articles and documents
Computer-aid drug design, synthesis, and anticoagulant activity evaluation of novel dabigatran derivatives as thrombin inhibitors
Huang, Shanshan,Ren,Peng, Xiuxiu,Qian, Pingping,Meng, Lingwei
, (2019/07/05)
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.
Mechanosynthesis of sydnone-containing coordination complexes
Pétry, Nicolas,Vanderbeeken, Thibaut,Malher, Astrid,Bringer, Yoan,Retailleau, Pascal,Bantreil, Xavier,Lamaty, Frédéric
supporting information, p. 9495 - 9498 (2019/08/15)
N-Phenyl-4-(2-pyridinyl) sydnone was shown to act as a four-electron donor N,O-ligand in unprecedented coordination complexes featuring three different metallic centers (Co, Cu, and Zn). Starting with various anilines, the use of a ball-mill efficiently enabled the synthesis of N-arylglycines, subsequent nitrosylation and cyclization into sydnones, and further metalation.
Design, synthesis, anticoagulant activity evaluation and molecular docking studies of a class of N -ethyl dabigatran derivatives
Ren, Weixin,Ren, Yujie,Wang, Shuai
, p. 148 - 159 (2016/05/24)
A class of N-ethyl dabigatran derivatives was designed based on pharmacological strategies for inhibition of thrombin activity and the structure-activity relationship studies of the previous dabigatran derivatives. Activities of these novel compounds were predicted based on CoMFA model, and most of the compounds had comparable predicted activity with dabigatran. All of screened compounds were synthesized and characterized by 1HNMR13C NMR and HRMS. Subsequently, these compounds were evaluated inhibitory activity on thrombin. Among these compounds, 9a-9e, 9h, 9l-9n and 9p exhibited comparable inhibitory activity to dabigatran (IC50 Combining double low line 1.20 nM), additionally, compound 9p (IC50 Combining double low line 0.96 nM) exhibited better inhibitory activity than dabigatran. Moreover, compound 9p also exhibited a fairly good inhibitory activity for arteriovenous thrombosis with inhibition rate of (85.35 ± 0.72) %, which was comparable to that of dabigatran (85.07 ± 0.61) %. These results, along with related molecular docking studies, could provide an important basis for further development of compound 9p as a potent thrombin inhibitor.
Multi-substituted 4-methyl ester derivative of amino benzonitrile trunk and its preparation and use
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Paragraph 0096; 0102-0104, (2018/01/19)
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.
N-(1-Oxy-2-picolyl)oxalamic Acid as an Efficient Ligand for Copper-Catalyzed Amination of Aryl Iodides at Room Temperature
Wang, Yongbin,Ling, Jing,Zhang, Yu,Zhang, Ao,Yao, Qizheng
, p. 4153 - 4161 (2015/07/01)
N-(1-Oxy-pyridin-2-ylmethyl)oxalamic acid was identified as efficient ligand for CuI-catalyzed amination of aryl halides at room temperature. In our catalytic system, N-arylation of cyclic secondary amines, primary amines, amino acids, and ammonia proceeded with moderate to excellent yields and high functional group tolerance.
Process For The Preparation Of Benzimidazole Derivatives And Salts Thereof
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Paragraph 0227-0228, (2015/03/31)
Provided are novel salts of benzimidazole derivatives, preferably salts of benzimidazole derivatives which are useful intermediates in the synthesis of pure 1-methyl-2-[N-[4-(N-n-hexyloxycarbonylamidino)phenyl]aminomethyl]benzimidazol-5-yl-carboxylicacid-N-(2-pyridyl)-N-(2-ethoxycarbonylethyl)amide and its salts.
PROCESS FOR THE PREPARATION OF DABIGATRAN ETEXILATE MESYLATE AND POLYMORPHS OF INTERMEDIATES THEREOF
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Paragraph 0121-0122, (2015/02/18)
The present invention provides crystalline form of intermediates of Formula 2A, The present invention also provides process for the preparation of dabigatran etexilate mesylate; polymorph of intermediates thereof; particularly processes for the preparation of crystalline form of intermediates. The present invention also relates to the use of crystalline intermediates for the preparation of dabigatran etexilate mesylate.
PROCESS FOR THE PREPARATION OF BENZIMIDAZOLE DERIVATIVES AND ITS SALTS
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Paragraph 0258, (2014/06/11)
An dabigatran etexilate intermediate of Formula-6a, and the use in the preparation of dabigatran etexilate thereof.
One-pot synthesis of 1,4-disubstituted pyrazoles from arylglycines via copper-catalyzed sydnone-alkyne cycloaddition reaction
Specklin, Simon,Decuypere, Elodie,Plougastel, Lucie,Aliani, Soifia,Taran, Frédéric
, p. 7772 - 7777 (2014/10/15)
A robust method for constructing 1,4-pyrazoles from arylglycines was developed using the copper-catalyzed sydnone-alkyne cycloaddition reaction. The procedure offers a straightforward and general route to the pyrazole heterocycle through a three-step one-pot procedure.
PROCESS FOR THE PREPARATION OF DABIGATRAN ETEXILATE MESYLATE AND POLYMORPHS OF INTERMEDIATES THEREOF
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Page/Page column 18, (2013/08/15)
The present invention provides crystalline form of intermediates of Formula 2A, Formula 2B and Formula E. The present invention also provides process for the preparation of dabigatran etexilate mesylate; polymorph of intermediates thereof; particularly processes for the preparation of crystalline form of intermediates. The present invention also relates to the use of crystalline intermediates for the preparation of dabigatran etexilate mesylate.
