共查询到19条相似文献,搜索用时 109 毫秒
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磷酸二酯酶5(PDE5)是磷酸二酯酶家族中的一员,以水解和环磷酸鸟苷为主,广泛分布于血管平滑肌和气管平滑肌,在血小板、肾脏以及阴茎海绵体也有分布。临床试验证明,PDE5抑制剂具有降低肺动脉高压、抗血栓、治疗心绞痛和勃起功能障碍等作用。综述PDE5的分子结构、调节机制以及PDE5抑制剂的构效关系和临床应用。 相似文献
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《中国药物化学杂志》2017,(5):400-407
磷酸二酯酶5(PDE5)属超家族酶,催化第二信使c GMP转化为GMP。磷酸二酯酶5抑制剂主要用于治疗勃起功能障碍,目前已有多种药物(西地那非、伐地那非等)上市,此外,PDE5抑制剂亦可用于治疗高血压、冠心病和前列腺增生等疾病。本文重点介绍已上市、处于临床试验阶段以及文献报道的PDE5抑制剂,并对其活性及构效关系进行综述。 相似文献
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磷酸二酯酶5抑制剂的进展与评价 总被引:4,自引:0,他引:4
目的:评价磷酸二酯酶5抑制剂的进展与临床合理应用.方法:采用近期国内、外相关文献进行综述.结果与结论:伴随社会的发展,性健康逐渐引起人们的认识.20世纪90年代一项药物研究的突破,促使药物的性质由治疗转向提高生活质量.磷酸二酯酶抑制剂可使环磷酸鸟苷酸的水平增高,促使男性阴茎勃起,受得了临床和患者的青睐.西地那非的上市为男性勃起功能障碍的治疗提供了全新的效果,标志着一个新的里程的开始. 相似文献
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磷酸二酯酶5抑制剂可选择性阻断cGMP的酶水解,最终引起血管平滑肌的松驰。这一作用靶目前主要用于人类勃起功能障碍的治疗。本文综述了其作用机制,磷酸二酯酶的生物学生物化学特点,新的磷酸二酯酶5抑制剂的构效关系以及其他药理学活性。 相似文献
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选择性磷酸二酯酶Ⅳ抑制剂的研究 总被引:3,自引:0,他引:3
磷酸二酯酶Ⅳ(PDE-4)主要分布于各类炎性细胞,能专一性水解环腺苷酸(cAMP),促进炎症的发展。PDE-4抑制剂通过选择性抑制PDE-4、使胞内cAMP水平升高,在抗炎和抗哮喘方面显示了广阔的应用前景。将PDE-4抑制剂分为儿茶酚醚类、苯甲酰胺类、喹唑啉二酮类、黄嘌呤类、苯并呋喃类等,分别综述其构效关系研究和临床开发应用。 相似文献
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磷酸二酯酶5抑制剂研究进展 总被引:2,自引:1,他引:2
男性勃起功能障碍(ED),是临床上较为常见的一种性功能障碍疾病。磷酸二酯酶5(PDE5)是存在于平滑肌、血小板等组织中一种有特定结构和功能的磷酸二酯酶亚型。口服PED5抑制剂使环磷酸鸟苷酸水平升高,促使血管平滑肌扩张,能达到治疗男性ED的作用。目前除了西地那非以外,还有一些结构不同的化合物具有PED5抑制作用,他们有可能成为更具疗效及选择性的ED治疗药物。 相似文献
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目的综述磷酸二酯酶-4(phosphodiesterase-4,PDE-4)的生理活性及其抑制剂的研究进展。方法查阅近年来国内外相关文献31篇,对其进行归纳、总结和分析。结果 PDE-4抑制剂通过对PDE-4的抑制作用,阻止环磷酸腺苷的水解,在哮喘和慢性阻塞性肺炎等炎症疾病方面作用显著。目前,罗氟司特已经通过美国FDA批准上市,许多活性较强、不良反应较少的PDE-4抑制剂相继进入了临床阶段。结论 PDE-4作为重要的炎症靶点之一得到了深入的研究,其抑制剂发展迅速,具有良好的开发前景。 相似文献
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磷酸二酯酶9及其抑制剂的研究进展 总被引:1,自引:0,他引:1
目的为磷酸二酯酶9(phosphodiesterase 9,PDE 9)的研究与开发提供参考。方法查阅PDE 9及其抑制剂的研究开发现状的多篇相关文献,进行整理和归纳。结果大多数PDE9抑制剂都能选择性地在体外和体内抑制PDE 9,并取得较好的药理活性。结论PDE 9将成为药物治疗的新一代靶点,其抑制剂的研究与开发具有广阔的发展前景。 相似文献
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《中国药理学通报》2014,(2)
磷酸二酯酶(PDEs)是一类可水解细胞内第二信使环磷酸腺苷(cyclic adenosine monophosphate,cAMP)和环磷酸鸟苷(cyclic guanosine monophosphate,cGMP)的酶类,可调节细胞内的多种信号传递和生理活动。PDEs由11种不同的家族组成,且各家族包含不同的亚型,各个亚型在细胞内分布、表达、调节方式以及对抑制剂的敏感性均不同,参与了炎症、哮喘、抑郁、勃起功能障碍等多种病理过程的发生发展,这些特点使得PDE作为新的药物靶点得到了越来越多的关注。该文将从PDE各家族生物学特点、生理病理学意义及其抑制剂的应用作一简单综述。 相似文献
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Phosphodiesterase 5 inhibitors, such as sildenafil, vardenafil and tadalafil, are now approved for the treatment of erectile dysfunction. They inhibit the cGMP-specific isoform 5 of phosphodiesterase, resulting in cGMP accumulation, which, for example in smooth muscle cells, reduces muscular tone. In the cardiovascular system, they slightly reduce arterial systemic blood pressure. This moderate effect was also shown in combination with many antihypertensive drugs. But the important contraindication is the concomitant use of PDE 5 inhibitors with any drug serving as a nitric oxide donor, as this combination can lead to significant arterial hypotension. Caution is needed in patients on alpha-blocking agents. In general, this class of drugs was not shown to exhibit direct deleterious effects on the myocardium or promote arrhythmias. Furthermore, statistical evaluations did not demonstrate an increased risk for patients taking PDE 5 inhibitors in comparison with an adequate control population. Many patients suffering from erectile dysfunction may be characterized by multiple cardiovascular risk factors or even ischemic heart disease, suggesting an increased baseline risk. While in many forms of erectile dysfunction, these agents seem to be very effective, it becomes clear that endothelial dysfunction is an attractive target of PDE 5 inhibitors and may also be the underlying cause in many types of erectile dysfunction. In addition, these agents seem to be very effective in lowering pulmonary arterial pressure, which might provide the opportunity to treat primary and some forms of secondary pulmonary hypertension, perhaps in combination with inhaled nitric oxide or other pulmonary arterial vasodilators. Sildenafil was approved for treatment of primary arterial hypertension in the U.S. in June 2005. Recently, direct cardioprotective effects were described in animal research, resembling preconditioning-like effects, which may, under certain conditions, also be applicable in clinical research. 相似文献
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近年来质子泵抑制剂的研究进展 总被引:74,自引:6,他引:74
概述了质子泵抑制剂(PPIs)作为临床应用最广泛的抗酸药物的作用机制,以及各种不同PPIs包括奥美拉唑、兰索拉唑、泮托拉唑、雷贝拉唑、莱米诺拉唑和吡帕拉唑等的临床应用特点。 相似文献
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The clinical significance of phosphodiesterase 5 (PDE5) inhibition is increasingly understood following the pioneering work with sildenafil, and the continuing development programmes for both sildenafil and other marketed inhibitors. Since the initial launch of sildenafil for male erectile dysfunction (MED), approval has now been granted for treatment of pulmonary hypertension, whilst ongoing studies have indicated the potential of PDE5 inhibition for the treatment of a range of additional indications including cardioprotection, memory retention and diabetes. Many of these additional indications are best suited to chronic oral dosing and emphasise the need for highly selective inhibitors with extended duration of action. This article will focus on a research programme aimed at the discovery of improved second-generation PDE5 inhibitors. Essential features of these new PDE5 inhibitors would be enhanced selectivity across the whole PDE family and pharmacokinetics compatible with once daily dosing. Key elements used in this programme are high throughput screening (HTS), exploitation of co-crystal structural information for bound inhibitor in the PDE5 active site, and employment of parallel chemistry to speed progress. Under the guidance of co-crystal structural information, a non-selective HTS hit with poor physicochemistry was initially modified using parallel chemistry to give a lead compound (3) that established a new PDE5 inhibitor series. Notably, (3) displayed physicochemistry compatible with a long plasma half-life, and wide chemical scope. Subsequent optimisation of (3) using crystal structure information to guide design, led rapidly to highly potent and selective PDE5 inhibitors (47, 50). Continued focus on physical properties through ligand efficiency evaluation and lipophilicity (cLogP), maintained the inherently desirable physicochemistry of the initial lead. 相似文献