D-264 | 1026084-40-1

• 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-264
• 英文别名: (-)-N⁶-(2-(4-(biphenyl-4-yl)piperazin-1-yl)ethyl)-N⁶-propyl-4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamine；(S)-N6-(2-(4-(biphenyl-4-yl)piperazin-1-yl)ethyl)-N6-propyl-4,5,6,7-tetrahydrobenzo[d]thiazole-2,6-diamine；(6S)-6-N-[2-[4-(4-phenylphenyl)piperazin-1-yl]ethyl]-6-N-propyl-4,5,6,7-tetrahydro-1,3-benzothiazole-2,6-diamine
• CAS: 1026084-40-1
• 化学式: C₂₈H₃₇N₅S
• 分子量: 475.701
• InChiKey: YDLWLYDTYNHXBM-VWLOTQADSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  76.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (4S)-2-oxo-1,3-thiazolidine-4-carbonyl chloride 、 D-264 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  Synthesis and characterization of brain penetrant prodrug of neuroprotective D-264: Potential therapeutic application in the treatment of Parkinson’s disease

  摘要：

  Parkinson's disease (PD) is one of the major debilitating neurodegenerative disorders affecting millions of people worldwide. Progressive loss of dopamine neurons resulting in development of motor dysfunction and other related non-motor symptoms is the hallmark of PD. Previously, we have reported on the neuroprotective property of a potent D3 preferring agonist D-264. In our goal to increase the bioavailability of D-264 in the brain, we have synthesized a modified cysteine based prodrug of D-264 and evaluated its potential in crossing the blood-brain barrier. Herein, we report the synthesis of a novel modified cysteine conjugated prodrug of potent neuroprotective D3 preferring agonist D-264 and systematic evaluation of the hydrolysis pattern of the prodrug to yield D-264 at different time intervals in rat plasma and brain homogenates using HPLC analysis. Furthermore, we have also performed in vivo experiments with the prodrug to evaluate its enhanced brain penetration ability. (C) 2016 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.ejpb.2016.03.017
• 作为产物：
  描述：

  1-(4-联苯基)-哌嗪 在 四丁基氟化铵 、 三氧化硫吡啶 、 三乙酰氧基硼氢化钠 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 二甲基亚砜 、 乙腈 为溶剂， 反应 3.0h， 生成 D-264
  参考文献：
  名称：

  Synthesis and characterization of brain penetrant prodrug of neuroprotective D-264: Potential therapeutic application in the treatment of Parkinson’s disease

  摘要：

  Parkinson's disease (PD) is one of the major debilitating neurodegenerative disorders affecting millions of people worldwide. Progressive loss of dopamine neurons resulting in development of motor dysfunction and other related non-motor symptoms is the hallmark of PD. Previously, we have reported on the neuroprotective property of a potent D3 preferring agonist D-264. In our goal to increase the bioavailability of D-264 in the brain, we have synthesized a modified cysteine based prodrug of D-264 and evaluated its potential in crossing the blood-brain barrier. Herein, we report the synthesis of a novel modified cysteine conjugated prodrug of potent neuroprotective D3 preferring agonist D-264 and systematic evaluation of the hydrolysis pattern of the prodrug to yield D-264 at different time intervals in rat plasma and brain homogenates using HPLC analysis. Furthermore, we have also performed in vivo experiments with the prodrug to evaluate its enhanced brain penetration ability. (C) 2016 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.ejpb.2016.03.017

文献信息

• BIFUNCTIONAL/POLYFUNCTIONAL DOPAMINE D2/D3 AGONIST AS NEUROPROTECTIVE AGENTS FOR TREATMENT OF NEURODEGENERATIVE DISEASES
  申请人：Dutta Aloke K.

  公开号：US20120108815A1

  公开（公告）日：2012-05-03

  A precursor for the deposition of a thin film by atomic layer deposition is provided. The compound has the formula M x L y where M is a metal and L is an amidrazone-derived ligand or an amidate-derived ligand. A process of forming a thin film using the precursors is also provided.

  提供了一种用于原子层沉积薄膜的前体。该化合物具有MxLy的公式，其中M是金属，L是来自酰胺肼衍生的配体或酰胺酸衍生的配体。还提供了使用前体形成薄膜的过程。
• Bioisosteric Heterocyclic Versions of 7-{[2-(4-Phenyl-piperazin-1-yl)ethyl]propylamino}-5,6,7,8-tetrahydronaphthalen-2-ol: Identification of Highly Potent and Selective Agonists for Dopamine D3 Receptor with Potent in Vivo Activity
  作者：Swati Biswas、Stuart Hazeldine、Balaram Ghosh、Ingrid Parrington、Eldo Kuzhikandathil、Maarten E. A. Reith、Aloke K. Dutta

  DOI：10.1021/jm701524h

  日期：2008.5.1

  In the current report, we extend the SAR study on our hybrid structure 7-[2-(4-phenyl-piperazin-1-yl)ethyl]propylamino}-5,6,7,8-tetrahydronaphthalen-2-ol further to include heterocyclic bioisosteric analogues. Binding assays were carried out with HEK-293 cells expressing either D2 or D3 receptors with tritiated spiperone to evaluate inhibition constants (K). Functional activity of selected compounds in stimulating GTP gamma S binding was assessed with CHO cells expressing human D2 receptors and AtT-20 cells expressing human D3 receptors. The highest binding affinity and selectivity for D3 receptors were exhibited by (-)-34 (K-i = 0.92 nM and D2/D3 = 253). In the functional GTP gamma S binding assay, (-)-34 exhibited full agonist activity with picomolar affinity for D3 receptor with high selectivity (EC50 = 0.08 nM and D2/D3 = 248). In the in vivo rotational study, (-)-34 exhibited potent rotational activity in 6-OH-DA unilaterally lesioned rats with long duration of action, which indicates its potential application in neuroprotective treatment of Parkinson's disease.
• US9034877B2
  申请人：——

  公开号：US9034877B2

  公开（公告）日：2015-05-19