109139-47-1Relevant articles and documents
Synthesis, in vitro cytotoxicity and biological evaluation of twenty novel 1,3-benzenedisulfonyl piperazines as antiplatelet agents
Liu, Xiu-jie,Wang, Yan,Wang, Xiao,Zhang, Zhi-hao
, (2021)
In order to discover antiplatelet drug with novel structure and expand our research scope, total twenty 1,3-benzenedisulfonyl piperazines, were designed and synthesized. These target compounds were divided into two series, namely 4-methoxy-1,3-benzenedisulfonyl piperazines of series 1 and 4-ethoxy-1,3-benzenedisulfonyl piperazines of series 2. With adenosine diphosphate (ADP), arachidonic acid (AA) and collagen as inducers, respectively, the Born turbidimetric method was used to screen the antiplatelet activity in vitro of all target compounds at a concentration of 1.3 μM, with aspirin and picotamide as positive control drugs. And of which, the activities of five compounds for collagen were higher than both picotamide and aspirin. In ADP or AA channel, compounds with an inhibition rate greater than 33% were selected, and their corresponding IC50 values were obtained. According to the IC50, the in vitro activity of one compound for ADP was higher than picotamide, and for AA, two compounds were higher than two positive control drugs and other two compounds only higher than or equal to aspirin. The preliminary analysis of the structure-activity relationship of the target compounds involved in this study was completed. Further, eight compounds exhibiting higher activity in one or two test channels, were subjected to cytotoxicity test on mouse fibroblasts (L929) by CCK-8 method. The in vitro cytotoxicity of most test compounds showed less than or same to control drug picotamide at 10 μM, but at the higher concentration of 100 μM, merely two compounds exhibited higher cell survival rate than that of picotamide. In addition, compound N1,N3-di(4-ethoxy-1,3-phenylenedisulfonyl)bis(1-(m-tolyl)piperazine), which is delivery activity in the three test channels, and another compound N1,N3–di(4-methoxy-1,3-phenylenedisulfonyl)bis(1-(m-tolyl)piperazine), which has the lowest cytotoxic in vitro compound among series 1 and series 2, respectively, are found and selected for simulation analysis as two most likely to dock with the receptor P2Y12. Each of synthesized compounds in silico molecular property and ADME (absorption, distribution, metabolism and excretion) are predicted by using Molinspiration property engine v2018.10 and PreADMET online servers, respectively. Compared with other series of compounds in the previous stage, the two series compounds obtained after the introduction of piperazinyl have a similar in vitro activity.
Synthesis and in vitro activities on anti-platelet aggregation of N,N′-di(2-substituted-phenyl)-4-methoxy isophthalamides and benzene-1,3-disulfonamides
Liu, Xiu Jie,He, Xin,Shi, Cheng Ling,Meng, Jie,Shao, Ying Lu,Si, Hong Qiang,Hu, Tao
scheme or table, p. 1139 - 1142 (2012/01/06)
On the propose of searching for the SAR and obtaining novel antiplatelet aggregating drugs, we have described the synthesis procedure and the activities in vitro on antiplatelet aggregation of two series of derivatives, which contain both 18 N,N′-di(2-substitutedphenyl)-4-methoxyisophthalamides (2a-2r) of the 2 series and nine N,N′-di(2-substitutedphenyl)-4-methoxybenzene-1,3- disulfonamides (3a-3i) of the 3 series. The results showed that three compounds 2e, 2i and 3g emerged as significant activities of antiplatelet aggregation, superior to two reference drugs picotamide and aspirin, and eight compounds 2j, 2k, 2l, 2o, 2p, 2q, 2r and 3i merely superior to picotamide. The preliminary SAR shows that it is favorable for the 2 series to increase the activities via the steric hindrance substituents attached to the two side chain benzene rings at 2-positions. And the arylamides of the 2 series have better the activity values than the arylsulfonamides of the 3 series respective except for 3b and 3g. On the contrary, electrostatic factors would not contribute evidently to the activities of the two series. The structures of 15 compounds newly synthesized have been established by MS and 1H NMR and been first reported in this paper.
