四氢异喹啉衍生物作为PDE4抑制剂的设计、合成及生物活性研究
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- 英文论文题名：Design,Synthesis and Biological Evaluation of Novel Tetrahydroisoquinoline Derivatives as PDE4 Inhibitors
- 论文作者：李俊骅 ; 蔡乃峻 ; 廖奕贤 ; 梁兆基 ; 崔紫宁 ; 宋高鹏
- 英文论文作者：Junhua Li ; Naijun Cai ; Yixian Liao ; Zhaoji Liang ; Zi-Ning Cui ; Gaopeng Song ; College of Materials and Energy ; South China Agricultural University ; Guangdong Province Key Lab of Microbial Signals and Disease Control ; Research Centre of Quorum Sensing ; South China Agricultural University
- 年：2016
- 作者机构：材料与能源学院华南农业大学;广东省微生物信号与作物病害防控重点实验室群体微生物研究中心华南农业大学;
- 论文关键词：PDE4抑制剂 ; 药物合成 ; 构效关系 ; 先导化合物
- 会议召开时间：2016-07-01
- 会议录名称：中国化学会第30届学术年会摘要集-第二十八分会：化学生物学
- 语种：中文
- 分类号：TQ463.5
- 学会代码：ZGHY
- 会议名称：中国化学会第30届学术年会-第二十八分会 ; 化学生物学
- 会议地点：中国辽宁大连
- 主办单位：中国化学会
- 学会名称：中国化学会
- 页数：1
- 文件大小：243k
- 原文格式：D
- 会议级别：全国
摘要
支气管哮喘和慢性阻塞性肺疾病(COPD)是常见的呼吸系统疾病,但是现在尚无有效的治疗药物~([1,2])。儿茶酚醚类衍生物作为最早的磷酸二酯酶IV抑制剂被广泛应用,但是经典的PDE4抑制剂rolipram等会引起呕吐、恶心等副作用~([3])。本课题组以rolipram等为先导化合物,借助计算机辅助药物设计等手段建立了该类化合物的药效团,然后利用生物电子等排体原理及构象限制等药物设计的基本方法进行骨架越迁,设计合成了系列以四氢异喹啉为骨架的新型选择性PDE4抑制剂。初步构效关系表明酰胺键为活性必需基团,芳香环有助于提高生物活性。
Nowadays asthma and chronic obstructive pulmonary diseases(COPD) known as the kind of chronic obstructive lung disease have been a major public health burden worldwide.But there is no effective drug for treating asthma and COPD.The diether derivative of catechol class as the important type of selective PDE4 inhibitors such as rolipram is one of the earliest and most extensively studied PDE4 inhibitors.Our focus was placed on the design and synthesis of 7-(cyclopentyloxy)-6-methoxyl,2,3,4-tetrahydroisoquinoline derivatives based on scaffold hopping through bioisosteres and conformational restriction theories.A primary structure-activity relationship study showed that carbonyl group and aromatic ring in the molecule were favored to the bioactivity.
Nowadays asthma and chronic obstructive pulmonary diseases(COPD) known as the kind of chronic obstructive lung disease have been a major public health burden worldwide.But there is no effective drug for treating asthma and COPD.The diether derivative of catechol class as the important type of selective PDE4 inhibitors such as rolipram is one of the earliest and most extensively studied PDE4 inhibitors.Our focus was placed on the design and synthesis of 7-(cyclopentyloxy)-6-methoxyl,2,3,4-tetrahydroisoquinoline derivatives based on scaffold hopping through bioisosteres and conformational restriction theories.A primary structure-activity relationship study showed that carbonyl group and aromatic ring in the molecule were favored to the bioactivity.
引文
[1]Rodrigo,G.J.;Plaza,V.Chest.2014,146:309.
[2]Raghavan,N.;Webb,K.;Amomputtisathaporn,N.;O'Donnell,D.E.Curr.Opin.Pharmacol.2010,26:1051.
[3]Song,G.P.;Zhao,D.S.;Hu,D.K.;Li,Y.S.;Jin,H.W.;Cui,Z.N.Bioorg.Med.Chem.Lett.2015,25:4610.
[2]Raghavan,N.;Webb,K.;Amomputtisathaporn,N.;O'Donnell,D.E.Curr.Opin.Pharmacol.2010,26:1051.
[3]Song,G.P.;Zhao,D.S.;Hu,D.K.;Li,Y.S.;Jin,H.W.;Cui,Z.N.Bioorg.Med.Chem.Lett.2015,25:4610.