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...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,21,2o,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.展开更多
设计、合成香豆素-3-羧酸-烟酸前药并研究其抗血小板聚集活性,以发现活性更高的新型抗血小板聚集剂。利用拼合原理,以不同的连接桥将香豆素-3-羧酸和烟酸偶联,合成目标化合物。通过体外抗血小板聚集试验对目标化合物进行抗血小板聚集活...设计、合成香豆素-3-羧酸-烟酸前药并研究其抗血小板聚集活性,以发现活性更高的新型抗血小板聚集剂。利用拼合原理,以不同的连接桥将香豆素-3-羧酸和烟酸偶联,合成目标化合物。通过体外抗血小板聚集试验对目标化合物进行抗血小板聚集活性评价。设计、合成了5个新的目标化合物,其结构经ESI-MS、IR及1 H NMR确证。体外抗血小板聚集活性结果表明,目标化合物的抗血小板聚集活性均强于阳性对照药阿司匹林,其中化合物6a的活性最强,值得进一步研究。展开更多
以9-乙酰氧基乙基-2-丙硫基-6-氯嘌呤化合物为原料,经烷胺化和玻沃-布兰还原制得2-(6-烷氨基-2-丙硫基-9 H-嘌呤-9-基)乙醇(2a^2d);2a^2d与二苄基磷酰氯反应制得2-(6-烷氨基-2-丙硫基-9 H-嘌呤-9-基)乙基二苄基磷酸酯(3a^3d);3a^3d与三...以9-乙酰氧基乙基-2-丙硫基-6-氯嘌呤化合物为原料,经烷胺化和玻沃-布兰还原制得2-(6-烷氨基-2-丙硫基-9 H-嘌呤-9-基)乙醇(2a^2d);2a^2d与二苄基磷酰氯反应制得2-(6-烷氨基-2-丙硫基-9 H-嘌呤-9-基)乙基二苄基磷酸酯(3a^3d);3a^3d与三甲基溴硅烷反应合成了2-(6-烷氨基-2-丙硫基-9 H-嘌呤-9-基)乙基磷酸二氢酯化合物(4a^4d),化合物3与化合物4均为新化合物,其结构经1 H NMR,13 C NMR,31 P NMR,IR和HR-MS(ESI)表征。研究了3a^3d,4a^4d的抗血小板凝集活性。结果表明:含有磷酸基团的嘌呤化合物活性明显优于不含磷酸基团嘌呤化合物的活性,其中4b活性最好,抗血小板凝集活性为17.79%。展开更多
基金the Committee of Science and Technology of Tianjin of China for the financial support from the Prop Up Research Project(No.10ZCKFSH00500)
文摘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,21,2o,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.
文摘设计、合成香豆素-3-羧酸-烟酸前药并研究其抗血小板聚集活性,以发现活性更高的新型抗血小板聚集剂。利用拼合原理,以不同的连接桥将香豆素-3-羧酸和烟酸偶联,合成目标化合物。通过体外抗血小板聚集试验对目标化合物进行抗血小板聚集活性评价。设计、合成了5个新的目标化合物,其结构经ESI-MS、IR及1 H NMR确证。体外抗血小板聚集活性结果表明,目标化合物的抗血小板聚集活性均强于阳性对照药阿司匹林,其中化合物6a的活性最强,值得进一步研究。
文摘以9-乙酰氧基乙基-2-丙硫基-6-氯嘌呤化合物为原料,经烷胺化和玻沃-布兰还原制得2-(6-烷氨基-2-丙硫基-9 H-嘌呤-9-基)乙醇(2a^2d);2a^2d与二苄基磷酰氯反应制得2-(6-烷氨基-2-丙硫基-9 H-嘌呤-9-基)乙基二苄基磷酸酯(3a^3d);3a^3d与三甲基溴硅烷反应合成了2-(6-烷氨基-2-丙硫基-9 H-嘌呤-9-基)乙基磷酸二氢酯化合物(4a^4d),化合物3与化合物4均为新化合物,其结构经1 H NMR,13 C NMR,31 P NMR,IR和HR-MS(ESI)表征。研究了3a^3d,4a^4d的抗血小板凝集活性。结果表明:含有磷酸基团的嘌呤化合物活性明显优于不含磷酸基团嘌呤化合物的活性,其中4b活性最好,抗血小板凝集活性为17.79%。
