101971-72-6Relevant articles and documents
Synthesis and in Vitro and in Vivo anticoagulant and antiplatelet activities of amidino- and non-amidinobenzamides
Lee, Soo Hyun,Lee, Wonhwa,Bae, Jong-Sup,Ma, Eunsook
, (2016/07/06)
Three amidino- and ten non-amidinobenzamides were synthesized as 3-aminobenzoic acid scaffold-based anticoagulant and antiplatelet compounds. The anticoagulant activities of thirteen synthesized compounds 1-13, and 2b and 3b as prodrugs were preliminary evaluated by screening the prolongation of activated partial thromboplastin time (aPTT) and prothrombin time (PT) in vitro. From the aPTT results obtained, two amidinobenzamides, N-(3′-amidinophenyl)-3-(thiophen-2″-ylcarbonylamino) benzamide (1, 33.2 ± 0.7 s) and N-(4′-amidinophenyl)-3-(thiophen-2″-ylcarbonylamino) benzamide (2, 43.5 ± 0.6 s) were selected to investigate the further anticoagulant and antiplatelet activities. The aPTT results of 1 (33.2± 0.7 s) and 2 (43.5 ± 0.6 s) were compared with heparin (62.5 ± 0.8 s) in vitro at 30 μM. We investigated the effect of 1 and 2 on blood anticoagulant activity (ex vivo) and on tail bleeding time (in vivo) on mice. A tail cutting/bleeding time assay revealed that both 1 and 2 prolonged bleeding time in mice at a dose of 24.1 g/mouse and above. Compounds 1 and 2 dose-dependently inhibited thrombin-catalyzed fibrin polymerization and platelet aggregation. In addition, 1 and 2 were evaluated on the inhibitory activities of thrombin and FXa as well as the generation of thrombin and FXa in human umbilical vein endothelial cells (HUVECs). Collectively, 1 and 2 possess some antiplatelet and anticoagulant activities and offer a basis for development of a novel antithrombotic product.
Design, synthesis and structure-activity relationship of new HSL inhibitors guided by pharmacophore models
Al-Shawabkeh, Jumana D.,Al-Nadaf, Afaf H.,Dahabiyeh, Lina A.,Taha, Mutasem O.
, p. 127 - 145 (2014/03/21)
Hormone-sensitive lipase (HSL) is a critical enzyme involved in the hormonally regulated release of fatty acids and glycerol from adipocyte lipid stores. Its inhibition may improve insulin sensitivity and blood glucose handling in type 2 diabetes. Accordingly, many small-molecule HSL inhibitors have recently been identified. In continuation of our efforts for discovery of new HSL inhibitors, we prepared a variety of esters, amides, sulfonamides and sulfonate esters capable of fitting two pharmacophore models that we developed and published earlier. The tested compounds were synthesized via coupling reactions of aroyl chlorides or sulfonyl chlorides with phenols, amines and related derivatives. Our efforts led to the identification of interesting compounds of low micromolar anti-HSL bioactivities, which have potential to be developed into effective antidiabetic agents.
An efficient and convenient synthesis of ethyl 1-(4-Methoxyphenyl)-5- phenyl-1H-1,2,3-triazole-4-carboxylate
Chen, Jung-Hsuan,Liu, Shuan-Ru,Chen, Kwunmin
experimental part, p. 328 - 333 (2010/07/05)
The "click chemistry" of using organic azides and terminal alkynes is arguably the most efficient and straightforward route to the synthesis of 1,2,3-triazoles. In this paper, an alternative and direct access to ethyl 1-(4-methoxyphenyl)-5-phenyl-1H-1,2,3