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本文报道了22个7-三氟甲基和2-甲基-7-三氟甲基氨酚喹类似物的合成。用伯氏疟原虫(plasmodium berghei)ANKA正常株感染小鼠作抑制性治疗试验,在剂量为(10 mg/kg)/d×4和(20 mg/kg)/d×4时,有11个化合物(Ⅰ1~9,Ⅱ3和Ⅱ6)对疟原虫完全抑制。其中3个化合物(Ⅰ2,Ⅰ6和Ⅰ7)在剂量为(5 mg/kg)/d×4时,就能对原虫完全抑制。12个化合物(Ⅰ1~10,Ⅱ3和Ⅱ6)用伯氏疟原虫ANKA抗氯喹株感染小鼠作治疗试验,剂量为(20 mg/kg)/d×4,2个化合物(Ⅰ4和Ⅱ3)在受试的5只小鼠中,原虫完全被抑制的鼠分别为3和4只,用相同剂量的对照药物盐酸氨酚喹治疗,原虫仍为阳性。 相似文献
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6-(4′-取代酰胺基苯基)-4,5-二氢-3(2H)-哒嗪酮类化合物的合成及其抑制血小板聚集作用 总被引:1,自引:0,他引:1
目的:6-(4′-取代苯基)-4,5-二氢-3(2H)-哒嗪酮类化合物的合成及抗血小板聚集活性的研究。方法:通过付-克反应、碳链延长、水解和环合反应得到两个关键中间体,然后通过酰化反应制得各种酰胺化合物;参考Born比浊法测定目标化合物的抗血小板聚集活性。结果:设计合成了24个6-(4′-取代酰胺基苯基)-4,5-二氢-3(2H)-哒嗪酮类化合物,22个为首次报道;所有化合物在体外对ADP诱导的兔血小板聚集均有不同程度的抑制作用,第II类化合物的抑制作用强于第I类化合物,其中I1,I3,II1,II3,II4,II6和II9的抑制作用均强于对照药CI-930,其中II1和II3的抑制作用最强,其IC50约为CI-930的1/10。结论:其中一些化合物显示较强的抗血小板聚集活性,值得进一步研究。 相似文献
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黄花乌头中Hetisine型生物碱的高速逆流色谱分离与结构鉴定 总被引:13,自引:0,他引:13
目的研究黄花乌头块根的化学成分,寻找更多天然活性物质。方法采用高速逆流色谱法分离纯化黄花乌头块根中的生物碱类化学成分,根据理化性质、波谱学分析鉴定化合物的结构。结果高速逆流色谱的两相溶剂分离系统采用氯仿-甲醇-0.2 mol·L-1 HCl(体积比为10∶3∶3),从黄花乌头块根中一次性分离得到8个化合物,分别鉴定为2α-propionyl-11α,13β-diacetyl-14-hydroxyhetisine (I)、关附巳素(II)、关附庚素(III)、关附己素(IV)、关附Z素(V)、关附辰素(VI)、关附甲素(VII)、关附壬素(VIII)。结论化合物I为新化合物,命名为关附未素(Guanfu base R)。 相似文献
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关附甲素对实验性心律失常和心肌收缩性的影响 总被引:21,自引:0,他引:21
关附甲素(GFA)浓度为20~3oμg·ml-1时,可以降低无K+高Ca2+液灌流离体大鼠心脏诱发VT和VF的发生率。清醒大鼠ivGFA2.5~10mg·kg-1,可依剂量性显著增加北草乌头碱引起室性早搏的用量。清醒犬ivGFA10mg·kg-1,可逆转哇巴因引起VT,并对麻醉犬(10~20mg·kg-1),由ACh诱发房颤有明显的抑制作用。GFA10mg·kg-1iv可明显减慢麻醉犬或清醒犬心率,对心肌收缩性(Vmax和Vpm)只有轻度而短暂的抑制,但对左室收缩压,心搏量和心输出量无明显影响。 相似文献
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《Expert opinion on therapeutic patents》2013,23(12):1443-1456
Atrial fibrillation is the most common cardiac arrhythmia associated with heart failure, stroke and mortality. Existing treatment of atrial fibrillation with class I or class III antiarrhythmic agents produces negative feedback on the ventricular repolarisations, which is widely considered as a critical risk factor of Torsades de pointes. The serious side effects hinder the appropriate usage and fair evaluation of these antiarrhythmic agents in clinical trials. Specifically existing in the ventricular, the ultra-rapid delayed rectifier potassium current (IKur), encoded by the Kv1.5 gene, is a crucial determinant of Phase I repolarisation during action potential duration. All evidence suggests that the Kv1.5 gene would be a potent target for the treatment of atrial fibrillation. This review describes the progress of Kv1.5 inhibitors in up-to-date literatures and awarded patents, and the latest information in clinical and preclinical trials. 相似文献
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De-Zai Dai Lu-Fan An You-Qun Wang Jun Huang Hua Zhang Dong Dai Feng Yu Meng-Hui Zhang Zhen-Ya Huang Si-Xun Peng 《Drug development research》1996,39(2):184-190
Protection by CPU 86017 against reperfusion-induced arrhythmias was studied in Langendorff perfused hearts and anesthetized rats. Inhibition of arrhythmias induced by ouabain and aconitine was observed, and the influence of CPU 86017 on ventricular fibrillation threshold (VFT) was determined. CPU 86017 exerted a dose-dependent antiarrhythmic effect in animal models. In Langendorff's perfused hearts, CPU 86017 significantly reduced the incidence and duration of ventricular fibrillation and ventricular tachycardia, as well as arrhythmic scores in a dose-dependent manner. The approximate ED50 of CPU 86017 against ventricular fibrillation was 2.10 μM. The antiarrhythmic effect of CPU 86017 against arrhythmia persisted for more than 6 h. In anaesthetized rats, CPU 86017 provided potent antiarrhythmic and antifibrillatory effects by po or iv routes. CPU 86017 was similar in potency to propafenone by the po route, and 10 times more potent than lidocaine by the iv route. CPU 86017 significantly attenuated the exaggerated arrhythmia and ventricular fibrillation in hypertrophic hearts induced by 1-thyroxine. Against ouabain-induced arrhythmias CPU 86017 exerted a dose-dependent inhibitory effect, which was 6.5-fold more potent than berberine. CPU 86017 significantly reduced ventricular fibrillation incidence and prevented the further deterioration of ventricular arrhythmias induced by aconitine. In conclusion, CPU 86017 is a potent antiarrhythmic agent with multiple mechanisms of action. Drug Dev. Res. 39:184–190. © 1997 Wiley-Liss, Inc. 相似文献
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Trapidil and some selected derivatives of trapidil were investigated in ouabain induced arrhythmia in guinea-pigs and in aconitine induced arrhythmia in rats. In both models trapidil exerted a marked antiarrhythmic effect. Investigations on ouabain induced arrhythmia showed that three derivatives were more effective than trapidil concerning the threshold for premature ventricular beats and flutter. One derivative only was able to decrease the sensitivity for fibrillation in the same order of magnitude as trapidil. On aconitine induced arrhythmia all derivatives of trapidil were less effective in elevating the threshold of arrhythmia than trapidil itself, but three derivatives showed antiarrhythmic properties. 相似文献
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山莨菪碱(anisodamine,简称Ani)有阻断M受体和α受体等作用。近年来,有人报道Ani有钙拮抗作用,这可能与茛菪碱类药物用于治疗心律失常有关。本文采用七种实验动物模型,观察了Ani的抗心律失常作用。 相似文献
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Na Zhao Qian Yang Yue‐Miao Yin Xiao‐Yong Le Xiang Guo Min‐Hui Wang Hao Zhong Qi‐Dong You 《Drug development research》2012,73(4):214-221
Strategy, Management and Health Policy | ||||
Enabling Technology, Genomics, Proteomics | Preclinical Research | Preclinical Development Toxicology, Formulation Drug Delivery, Pharmacokinetics | Clinical Development Phases I‐III Regulatory, Quality, Manufacturing | Postmarketing Phase IV |
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去葡萄糖竹节参皂苷Ⅳa抗实验性心律失常作用 总被引:2,自引:0,他引:2
目的研究去葡萄糖竹节参皂苷Ⅳa(DCⅣa)是否具有抗实验性心律失常的作用。方法采用氯化钡、乌头碱、毒毛花苷G及结扎左冠状动脉前降支诱发大鼠或豚鼠心律失常模型,八道生理记录仪观察并记录Ⅱ导联心电图,观察DCⅣa对实验性心律失常的预防作用。结果DCⅣa能缩短氯化钡和乌头碱诱发大鼠心律失常的持续时间,增加恢复正常心律的动物数;增加诱发豚鼠心律失常的毒毛花苷G用量;延长冠脉结扎致大鼠心律失常发生的潜伏期,缩短心律失常的持续时间,降低室颤发生的百分率。结论DCⅣa具有明显的抗心律失常作用。 相似文献
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《Expert opinion on investigational drugs》2013,22(4):399-416
Atrial fibrillation (AF) is the most common sustained arrhythmia. Anti-arrhythmic drugs remain the mainstay of therapy, but the available class I and III anti-arrhythmic drugs are only moderately effective in long-term restoring/maintaining sinus rhythm (SR) and can produce potentially fatal ventricular pro-arrhythmia. In an attempt to identify safer and more effective anti-arrhythmic drugs, drug discovery efforts have focused on ‘atrial selective drugs’ that target cardiac ion channel(s) that are exclusively or predominantly expressed in the atria. The ultra-rapid activating delayed rectifier K+ current (IKur), carried by Kv1.5 channels, is a major repolarizing current in human atria, but seems to play no role in the ventricle. This finding offers the possibility of developing selective IKur blockers to restore and maintain SR without a risk of ventricular pro-arrhythmia. Several IKur blockers are now being developed but clinical data are still limited, so the precise role of these agents in the treatment of AF remains to be defined. In this review we analyze the possible advantages and disadvantages of the developmental IKur blockers as they represent the first step for the development of potential atrial selective drugs for a more effective and safer treatment and prevention of AF. 相似文献