Avanafil, a potent new selective phosphodiesterase type 5 （PDE5） inhibitor, has been developed for the treatment of erectile dysfunction （ED）. We carried out a systematic review and meta-analysis to assess the eff...Avanafil, a potent new selective phosphodiesterase type 5 （PDE5） inhibitor, has been developed for the treatment of erectile dysfunction （ED）. We carried out a systematic review and meta-analysis to assess the efficacy and safety of this drug for the treatment of ED. A literature review was performed to identify all published randomized, double-blind, placebo-controlled trials of avanafil for the treatment of ED. The search included the following databases： MEDLINE, EMBASE and the Cochrane Controlled Trials Register. The reference lists of the retrieved studies were also investigated. Four publications, involving a total of 1381 patients, were used in the analysis, including four randomized controlled trials （RCTs） that compared avanafU with a placebo. Among the co-primary efficacy end points indicating that avanafil 100 mg was more effective than a placebo were successful vaginal penetration （SEP2） （the odds ratio （OR） =5.06, 95% confidence interval （CI） =3.29-7.78, P〈 0.00001） and successful intercourse （SEP3） （OR = 3.99, 95% CI = 2.80-5.67, P 〈 0.00001）. Men randomized to receive avanafil were less likely than those receiving the placebo to drop out due to an adverse event （AE） （OR = 1.48, 95% CI = 0.54-4.08, P = 0.44）. Specific AEs with avanafil included headache and flushing, which were significantly less likely to occur with placebo. This meta-analysis indicates that avanafil 100 or 200 mg is an effective and well-tolerated treatment for ED. Compared with avanafil 100 mg, patients who take avanafil 200 mg are more likely to experience headaches.展开更多
目的对阿伐那非合成工艺中具有警示结构的潜在有关物质进行致突变性评价研究,为阿伐那非有关物质的分类分级提供指导和依据。方法通过化学方法定向合成阿伐那非含警示结构的潜在遗传毒性杂质E(impurity E,Imp-E),按照国际人用药品注册...目的对阿伐那非合成工艺中具有警示结构的潜在有关物质进行致突变性评价研究,为阿伐那非有关物质的分类分级提供指导和依据。方法通过化学方法定向合成阿伐那非含警示结构的潜在遗传毒性杂质E(impurity E,Imp-E),按照国际人用药品注册技术协调会(The InternationalCouncil for Harmonisation of Technical Requirementsfor Pharmaceuticals for Human Use,ICH)M7指导原则对其进行评价和分类。分别采用基于专家规则和统计学原理的2种互补的定量构效关系(quantitative structure-activity relationship,QSAR)评价系统(Derek和Sarah)对Imp-E的遗传毒性进行初步预测,并展开Ames试验对Imp-E进一步验证。结果Imp-E的Derek预测结果为阳性,依据ICH M7指导原则的分类为第3类。在Ames验证试验中,受试物剂量为每皿62.5~1000μg时,无论S9存在与否的情况下,回复突变菌落数均未超过溶剂对照组菌落数的2倍且不呈剂量-反应关系,试验结果显阴性。结论Imp-E的致突变性为阴性,推翻了Derek预测的阳性结果,依据ICH M7中的第5类即非突变性杂质进行控制。展开更多
以4-(3-氯-4-甲氧基苄基氨基)-2-[(2S)-2-羟甲基-1-吡咯烷基]-5-嘧啶羧酸乙酯为原料,合成了4-(3-氯-4-甲氧基苄基氨基)-2-[(2S)-2-羟甲基-1-吡咯烷基]-N-(2-吡啶甲基)-5-嘧啶甲酰胺,研究了此种阿伐那非类似物的合成条件优化,考察了投料...以4-(3-氯-4-甲氧基苄基氨基)-2-[(2S)-2-羟甲基-1-吡咯烷基]-5-嘧啶羧酸乙酯为原料,合成了4-(3-氯-4-甲氧基苄基氨基)-2-[(2S)-2-羟甲基-1-吡咯烷基]-N-(2-吡啶甲基)-5-嘧啶甲酰胺,研究了此种阿伐那非类似物的合成条件优化,考察了投料比、反应温度、反应时间等因素对产率的影响.获得较高产率的反应条件为n(C6H8N2)∶n(C18H21ClN4O4)∶n(EDCI)∶n(HOBt)∶n(Et3N)=1.2∶1∶1.2∶1.2∶2,在搅拌下,60℃反应6h,经过后处理,柱层析纯化,得到类白色固体产物,产率为84.3%.所合成的产物经FT-IR、1 H NMR、13 C NMR、ESI-MS得到验证.展开更多
文摘Avanafil, a potent new selective phosphodiesterase type 5 （PDE5） inhibitor, has been developed for the treatment of erectile dysfunction （ED）. We carried out a systematic review and meta-analysis to assess the efficacy and safety of this drug for the treatment of ED. A literature review was performed to identify all published randomized, double-blind, placebo-controlled trials of avanafil for the treatment of ED. The search included the following databases： MEDLINE, EMBASE and the Cochrane Controlled Trials Register. The reference lists of the retrieved studies were also investigated. Four publications, involving a total of 1381 patients, were used in the analysis, including four randomized controlled trials （RCTs） that compared avanafU with a placebo. Among the co-primary efficacy end points indicating that avanafil 100 mg was more effective than a placebo were successful vaginal penetration （SEP2） （the odds ratio （OR） =5.06, 95% confidence interval （CI） =3.29-7.78, P〈 0.00001） and successful intercourse （SEP3） （OR = 3.99, 95% CI = 2.80-5.67, P 〈 0.00001）. Men randomized to receive avanafil were less likely than those receiving the placebo to drop out due to an adverse event （AE） （OR = 1.48, 95% CI = 0.54-4.08, P = 0.44）. Specific AEs with avanafil included headache and flushing, which were significantly less likely to occur with placebo. This meta-analysis indicates that avanafil 100 or 200 mg is an effective and well-tolerated treatment for ED. Compared with avanafil 100 mg, patients who take avanafil 200 mg are more likely to experience headaches.
文摘目的对阿伐那非合成工艺中具有警示结构的潜在有关物质进行致突变性评价研究,为阿伐那非有关物质的分类分级提供指导和依据。方法通过化学方法定向合成阿伐那非含警示结构的潜在遗传毒性杂质E(impurity E,Imp-E),按照国际人用药品注册技术协调会(The InternationalCouncil for Harmonisation of Technical Requirementsfor Pharmaceuticals for Human Use,ICH)M7指导原则对其进行评价和分类。分别采用基于专家规则和统计学原理的2种互补的定量构效关系(quantitative structure-activity relationship,QSAR)评价系统(Derek和Sarah)对Imp-E的遗传毒性进行初步预测,并展开Ames试验对Imp-E进一步验证。结果Imp-E的Derek预测结果为阳性,依据ICH M7指导原则的分类为第3类。在Ames验证试验中,受试物剂量为每皿62.5~1000μg时,无论S9存在与否的情况下,回复突变菌落数均未超过溶剂对照组菌落数的2倍且不呈剂量-反应关系,试验结果显阴性。结论Imp-E的致突变性为阴性,推翻了Derek预测的阳性结果,依据ICH M7中的第5类即非突变性杂质进行控制。
文摘以4-(3-氯-4-甲氧基苄基氨基)-2-[(2S)-2-羟甲基-1-吡咯烷基]-5-嘧啶羧酸乙酯为原料,合成了4-(3-氯-4-甲氧基苄基氨基)-2-[(2S)-2-羟甲基-1-吡咯烷基]-N-(2-吡啶甲基)-5-嘧啶甲酰胺,研究了此种阿伐那非类似物的合成条件优化,考察了投料比、反应温度、反应时间等因素对产率的影响.获得较高产率的反应条件为n(C6H8N2)∶n(C18H21ClN4O4)∶n(EDCI)∶n(HOBt)∶n(Et3N)=1.2∶1∶1.2∶1.2∶2,在搅拌下,60℃反应6h,经过后处理,柱层析纯化,得到类白色固体产物,产率为84.3%.所合成的产物经FT-IR、1 H NMR、13 C NMR、ESI-MS得到验证.
