D-607

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: D-607
• 英文别名: (6S)-6-N-propyl-6-N-[2-[4-(6-pyridin-2-ylpyridin-3-yl)piperazin-1-yl]ethyl]-4,5,6,7-tetrahydro-1,3-benzothiazole-2,6-diamine
• 化学式: C₂₆H₃₅N₇S
• 分子量: 477.677
• InChiKey: WQTLRHZZRMRHMI-FQEVSTJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  三正丁基2-吡啶基锌 在 四(三苯基膦)钯 、 四丁基氟化铵 、 palladium diacetate 、 三氧化硫吡啶 、 三乙酰氧基硼氢化钠 、 caesium carbonate 、 R-(+)-1,1'-联萘-2,2'-双二苯膦 、 三乙胺 作用下， 以 四氢呋喃 、 5,5-dimethyl-1,3-cyclohexadiene 、 二氯甲烷 、 二甲基亚砜 、 甲苯 为溶剂， 反应 87.5h， 生成 D-607
  参考文献：
  名称：

  A Novel Iron(II) Preferring Dopamine Agonist Chelator as Potential Symptomatic and Neuroprotective Therapeutic Agent for Parkinson’s Disease

  摘要：

  parkinson's disease (PD) is a progressive neurodegenerative disorder, and development of disease-modifying treatment is still an 'unmet medical need. Considering the implication of free iron(II) in PD, we report here the design and characterization of a novel hybrid iron chelator, (-).12 (D-607) as a multitarget.directed ligand against PD. Binding and functional assays at dopamine D-2/D-3 receptors indicate potent agonist activity of (-).12. The molecule displayed an efficient preferential iron(II) chelation properties along with poient in vivo activity in a reserpinized PD animal model. The compound also rescued PC12 cells from toxicity induced by iron delivered intracellularly in a dose-dependent manner. However, Fe3+ selective dopamine agonist 1 and a well-known antiparkinsonian drug pramipexole produced little to no neuroprotection effect under the same experimental condition. These observations strongly suggest that (-).12 should be a promising multifunctional lead molecule for a viable symptomatic and disease modifying therapy of PD.

  DOI：

  10.1021/acschemneuro.6b00356

文献信息

• A Novel Iron(II) Preferring Dopamine Agonist Chelator as Potential Symptomatic and Neuroprotective Therapeutic Agent for Parkinson’s Disease
  作者：Banibrata Das、Ashoka Kandegedara、Liping Xu、Tamara Antonio、Timothy Stemmler、Maarten E. A. Reith、Aloke K. Dutta

  DOI：10.1021/acschemneuro.6b00356

  日期：2017.4.19

  parkinson's disease (PD) is a progressive neurodegenerative disorder, and development of disease-modifying treatment is still an 'unmet medical need. Considering the implication of free iron(II) in PD, we report here the design and characterization of a novel hybrid iron chelator, (-).12 (D-607) as a multitarget.directed ligand against PD. Binding and functional assays at dopamine D-2/D-3 receptors indicate potent agonist activity of (-).12. The molecule displayed an efficient preferential iron(II) chelation properties along with poient in vivo activity in a reserpinized PD animal model. The compound also rescued PC12 cells from toxicity induced by iron delivered intracellularly in a dose-dependent manner. However, Fe3+ selective dopamine agonist 1 and a well-known antiparkinsonian drug pramipexole produced little to no neuroprotection effect under the same experimental condition. These observations strongly suggest that (-).12 should be a promising multifunctional lead molecule for a viable symptomatic and disease modifying therapy of PD.