NS 8593 | 875755-39-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: NS 8593
• 英文别名: 1H-Benzimidazol-2-amine, N-((1R)-1,2,3,4-tetrahydro-1-naphthalenyl)-；N-[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]-1H-benzimidazol-2-amine
• CAS: 875755-39-8
• 化学式: C₁₇H₁₇N₃
• 分子量: 263.342
• InChiKey: XZIZUQSOFMLIIR-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  40.7
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  2-氯苯并咪唑 、 (R)-(-)-1,2,3,4-四氢-1-萘胺 以 乙腈 为溶剂， 生成 NS 8593
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationship Studies of 2-(N-Substituted)-aminobenzimidazoles as Potent Negative Gating Modulators of Small Conductance Ca²⁺-Activated K⁺ Channels

  摘要：

  Small conductance Ca2+-activated K+ channels (SK channels) participate in the control of neuronal excitability, in the shaping of action potential firing patterns, and in the regulation of synaptic transmission. SK channel inhibitors have the potential of becoming new drugs for treatment of various psychiatric and neurological diseases such as depression, cognition impairment, and Parkinson's disease. In the present study we describe the structure-activity relationship (SAR) of a class of 2-(N-substituted)-2-aminobenzimidazoles that constitute a novel class of selective SK channel inhibitors that, in contrast to classical SK inhibitors, do not block the pore of the channel. The pore blocker apamin is not displaced by these compounds in binding studies, and they still inhibit SK channels in which the apamin binding site has been abolished by point mutations. These novel SK inhibitors shift the concentration-response curve for Ca2+ toward higher values and represent the first example of negative gating modulation as a mode-of-action for inhibition of SK channels. The first described compound in this class is NS8593 (14), and the most potent analogue identified in this study is the racemic compound 39 (NS11757), which reversibly inhibits SK3-rnediated currents with a K-d value of 9 nM.

  DOI：

  10.1021/jm800809f
• 作为试剂：
  描述：

  2-氯苯并咪唑 、 (R)-(-)-1,2,3,4-四氢-1-萘胺 在 NS 8593 、 乙腈 作用下， 反应 0.67h， 以to give the title compound as a HCl salt (white solid, mp 264-265° C.)的产率得到NS 8593
  参考文献：
  名称：

  Novel 2-amino benzimidazole derivatives and their use as modulators of small-conductance calcium-activated potassium channels

  摘要：

  本发明涉及一种新颖的2-氨基苯并咪唑衍生物，可用作小电导钙激活钾通道（SK通道）的调节剂。在其他方面，本发明涉及这些化合物在治疗方法中的使用，以及包含本发明化合物的制药组合物。

  公开号：

  US20070197618A1

文献信息

• 2-AMINO BENZIMIDAZOLE DERIVATIVES AND THEIR USE AS MODULATORS OF SMALL-CONDUCTANCE CALCIUM-ACTIVATED POTASSIUM CHANNELS
  申请人：Sørensen Ulrik Svane

  公开号：US20100035951A1

  公开（公告）日：2010-02-11

  This invention relates to 2-amino benzimidazole derivatives of Formula 1a or 1b: which are useful as modulators of small-conductance calcium-activated potassium channels (SK channels). In other aspects the invention relates to the use of these compounds in a method for therapy and to pharmaceutical compositions comprising the compounds of the invention.

  本发明涉及公式1a或1b的2-氨基苯并咪唑衍生物，其可用作小导电钙激活钾通道（SK通道）的调节剂。在其他方面，本发明涉及使用这些化合物的方法进行治疗，并涉及包含本发明化合物的制药组合物。
• 2-amino benzimidazole derivatives and their use as modulators of small-conductance calcium-activated potassium channels
  申请人：Neurosearch A/S

  公开号：US07737167B2

  公开（公告）日：2010-06-15

  This invention relates to novel 2-amino benzimidazole derivatives useful as modulators of small-conductance calcium-activated potassium channels (SK channels). In other aspects the invention relates to the use of these compounds in a method for therapy and to pharmaceutical compositions comprising the compounds of the invention.

  本发明涉及一种新型的2-氨基苯并咪唑衍生物，可用作小电导钙激活钾通道（SK通道）的调节剂。在其他方面，本发明涉及这些化合物在治疗方法中的使用，以及包含本发明化合物的制药组合物。
• Treatment of learning disabilities and other neurological disorders with SK channel inhibitor(s)
  申请人：Children's National Medical Center

  公开号：US10555989B2

  公开（公告）日：2020-02-11

  Methods for treating learning disabilities associated with fetal alcohol syndrome and other neurological disorders by administering SK channel blockers, antagonists, inhibitors or modifiers like tamapin.

  通过施用 SK 通道阻滞剂、拮抗剂、抑制剂或他马平等调节剂来治疗与胎儿酒精综合征和其他神经系统疾病相关的学习障碍的方法。
• Potassium channel inhibitors
  申请人：ACESION PHARMA ApS

  公开号：US11168074B2

  公开（公告）日：2021-11-09

  A compound of the general formula (I). The compounds of formula I are useful for treatment of a cardiac disease, disorder or condition in a mammal.

  通式 (I) 的化合物。式 I 的化合物可用于治疗哺乳动物的心脏疾病、失调或状况。
• Supramolecular hydrogel applications to the carotid bodies to treat hypertension and sleep apnea in obesity
  申请人：THE JOHNS HOPKINS UNIVERSITY

  公开号：US11229614B2

  公开（公告）日：2022-01-25

  The present invention provides compositions and methods for treating hypertension and obstructive sleep apnea utilizing hydrogel compositions comprising drug amphiphiles with TRPM 7 antagonists for use in a subject, including use on the carotid body of a subject.

  本发明提供了用于治疗高血压和阻塞性睡眠呼吸暂停的组合物和方法，这些组合物包括用于受试者（包括用于受试者的颈动脉体）的具有 TRPM 7 拮抗剂的药物两性化合物水凝胶组合物。