3951-92-6Relevant articles and documents
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)
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.
Synthesis and biological evaluation of some new 2,5-Substituted 1-Ethyl-1H-benzoimidazole fluorinated derivatives as direct thrombin Inhibitors
Li, Meilin,Ren, Yujie
, p. 353 - 365 (2015/05/13)
A new series of fluorinated 2,5-substituted 1-ethyl-1H-benzimidazole derivatives were synthesized from starting compounds 3a-i, which were prepared from acrylic acid ethyl ester and the appropriate amines using trifluoromethanesulfonic acid as a catalyst. A total of 9 novel derivatives were synthesized through 9 steps. All of them were evaluated for thrombin inhibition activity in vitro for the first time. We have altered their structures using different substituents on the amines to assess their structure-activity relationships as direct thrombin inhibitors. All the compounds were effective thrombin inhibitors, with IC50 values ranging from 3.39 to 23.30nM. Among the compounds synthesized, compounds 14a, 14b, 14d, 14e, and 14h exhibited greater anticoagulant activity than argatroban (IC50=9.36nM). Furthermore, compound 14h synthesized starting with 2-amino-pyridine was the most potent thrombin inhibitor with an IC50 value of 3.39nM. Molecular modeling studies were performed to determine the probable interactions of the most potent compounds 14a, 14e, and 14h with their protein receptor (PDB ID: 1KTS). Docking data show that the active compounds inhibit thrombin in a similar mode to that of the potent anticoagulant dabigatran. A new series of fluorinated derivatives were evaluated for their in vitro thrombin inhibition activities. 3-({2-[(4-Carbamimidoyl-2-fluoro-phenylamino)-methyl]-1-ethyl-1H-benzoimidazole-5-carbonyl}-pyridin-2-yl-amino)-propionic acid 14h shows the most potent antithrombin activity (IC50=3.39nM). Molecular docking revealed that its inhibition mode was similar to that of dabigatran.
Cerium(IV) ammonium nitrate (CAN) catalyzed aza-Michael addition of amines to α,β-unsaturated electrophiles
Duan, Zheng,Xuan, Xuejie,Li, Ting,Yang, Chenfei,Wu, Yangjie
, p. 5433 - 5436 (2007/10/03)
Cerium(IV) ammonium nitrate (CAN) catalyzed facile and efficient aza-Michael addition of aromatic and aliphatic amines with α,β-unsaturated electrophiles in the absence of solvent under ultrasound irradiation.
