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关注:1 2013-05-23 12:21

求翻译:Targeting phosphodiesterase IV (PDE-IV) with small-molecule inhibitors as a therapeutic for chronic inflammatory disorders has been an active area of research interest for many years. The major drawback, however, has been to develop pharmacophores that would differentiate between targeting isoforms of PDE-IV associated with inflammation, as opposed to those that cause emesis, a major side effect associated with PDE-IV inhibition. Several different approaches have been employed, including designing subtype selective PDE-IV inhibitors. A recent approach has been to develop chemotypes that target PDE-VII, a cAMP-specific PDE, expressed widely in immune and pro-inflammatory cells. It is hypothesized that dual inhibitors, which function to inhibit both PDE-IV and VII, may achieve a higher therapeutic index and thereby exhibit a lower propensity to cause adverse side effects that are characteristic when targeting PDE-IV alone. This review focuses on the major classes of compounds that are presently being studied for their potential to inhibit PDE-VII and discusses the available data in the development of dual PDE-IV and -VII inhibitors, their biologic activity and their scope as a therapeutic choice in chronic inflammatory diseases.是什么意思?

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Targeting phosphodiesterase IV (PDE-IV) with small-molecule inhibitors as a therapeutic for chronic inflammatory disorders has been an active area of research interest for many years. The major drawback, however, has been to develop pharmacophores that would differentiate between targeting isoforms of PDE-IV associated with inflammation, as opposed to those that cause emesis, a major side effect associated with PDE-IV inhibition. Several different approaches have been employed, including designing subtype selective PDE-IV inhibitors. A recent approach has been to develop chemotypes that target PDE-VII, a cAMP-specific PDE, expressed widely in immune and pro-inflammatory cells. It is hypothesized that dual inhibitors, which function to inhibit both PDE-IV and VII, may achieve a higher therapeutic index and thereby exhibit a lower propensity to cause adverse side effects that are characteristic when targeting PDE-IV alone. This review focuses on the major classes of compounds that are presently being studied for their potential to inhibit PDE-VII and discusses the available data in the development of dual PDE-IV and -VII inhibitors, their biologic activity and their scope as a therapeutic choice in chronic inflammatory diseases.
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  • 匿名
2013-05-23 12:26:38
针对磷酸二酯酶四 (PDE IV) 与小分子抑制剂治疗慢性炎症疾病多年来一直积极研究感兴趣的领域。主要的缺点,但是,已发展会区分针对偏微分方程四亚型的 pharmacophores 与相关炎症,相对于那些该原因呕吐,与偏微分方程四抑制相关联的主要副作用。已采用了几种不同的方法,包括设计亚型选择性偏微分方程-IV 抑制剂。最近的做法一直发展目标偏微分方程-七营特定偏微分方程免疫和炎症细胞表达广泛的 chemotypes。这被假设,双重抑制剂的作用是抑制偏微分方程第四和第七,可实现更高的治疗指数,从而表现出较低的倾向会针对偏微分方程四单时特性的不良副作用。这项审查重点是目前正在研究的潜能,抑制偏微分方程七,并讨论了双偏微分方程四-七抑制剂,其生物活性和它们的范围在慢性炎症疾病的治疗选择作为发展中的可用数据的化合物的主要类。
 
 
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