3-肟-6,7-二氯-1H-吲哚-2,3-二酮 | 18711-16-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 3-肟-6,7-二氯-1H-吲哚-2,3-二酮
• 中文别名: 6,7-二氯-1H-吲哚-2,3-二酮-3-肟
• 英文名称: 3-oxime-6,7-dichloro-1H-indole-2,3-dione
• 英文别名: 6,7-dichloro-1H-indole-2,3-dione 3-oxime；6,7-dichloro-1H-indole-2,3-dione-3-oxime；NS309；NS 309；6,7-dichloroisatin 3-oxime；6,7-dichloro-3-(hydroxyamino)indol-2-one
• CAS: 18711-16-5
• 化学式: C₈H₄Cl₂N₂O₂
• 分子量: 231.038
• InChiKey: CVOUSAVHMDXCKG-UHFFFAOYSA-N

物化性质

• 熔点：
  190-192℃
• 溶解度：
  二甲基亚砜：~22 mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  2.12
• 重原子数：
  14.0
• 可旋转键数：
  0.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  61.69
• 氢给体数：
  2.0
• 氢受体数：
  3.0

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S26
• 危险类别码：
  R36/37/38
• 海关编码：
  2933790090
• 危险标志：
  GHS07
• 危险性描述：
  H315,H319,H335
• 危险性防范说明：
  P261,P305 + P351 + P338
• 储存条件：
  2-8℃

制备方法与用途

生物活性

NS309 是一种有效且选择性的钙依赖性钾离子通道 SK/IK (Ca2+-activated SK/IK potassium channels) 的激活剂，但在 BK 通道上没有活性。

靶点

• EC50: SK2：0.62 μM，SK3：0.3 μM，KCa3.1/SK4：约20 nM，KCa2/SK通道：约600 nM，hIK：10 nM

体外研究

• NS309 (40 nM) 激活 hSK3 和 hIK 通道，对 hIK 通道的效果尤为显著（电流增加8.5倍，而 hSK3 通道的电流增加仅为1.9倍）。
• 在浓度为 10 μM 的 NS309 作用下，全细胞 SK 现象明显增强，并使逼尿肌平滑肌 (DSM) 细胞静息膜电位去极化。
• NS309 在不同浓度下抑制了孤立 DSM 条片自发的突发收缩幅度、力量、频率、持续时间和张力。

体内研究

NS309 (2 mg/kg，腹腔注射) 能显著改善兔脊髓损伤/再灌注（SCI/R）模型动物的神经功能预后。具体结果如下：

• 动物模型：成年新西兰白兔（体重2.5-3.0 kg）
• 剂量：2 mg/kg
• 给药方式：腹腔注射
• 结果：显著改善了 SCI/R 挑战兔子的神经功能预后

文献信息

• BENZOTHIOPHENE COMPOUND
  申请人：ASTELLAS PHARMA INC.

  公开号：US20140364421A1

  公开（公告）日：2014-12-11

  [Problem] A compound which is useful as an IK1 channel activator is provided. [Means for Solution] As a result of studies on the IK1 channel activator, the present inventors have found that a benzothiophene compound shows effectiveness on visceral pain, inflammatory pain, osteoarthritis pain, neuropathic pain, or fibromyalgia, thereby completing the invention. A compound of the invention has an IK1 channel activation effect, and can also be used as an agent for preventing and/or treating visceral pain, inflammatory pain, osteoarthritis pain, neuropathic pain, or fibromyalgia. In addition, the IK1 channel activator can be used as an agent for preventing and/or treating inflammatory pain, osteoarthritis pain, neuropathic pain, and fibromyalgia.

  [问题] 提供了一种作为IK1通道激活剂有用的化合物。 [解决方案] 通过对IK1通道激活剂的研究，本发明的发明人发现一种苯并噻吩化合物对内脏疼痛、炎症性疼痛、骨关节炎疼痛、神经性疼痛或纤维肌痛显示出有效性，从而完成了本发明。本发明的化合物具有IK1通道激活效果，并且还可以用作预防和/或治疗内脏疼痛、炎症性疼痛、骨关节炎疼痛、神经性疼痛或纤维肌痛的药物。另外，IK1通道激活剂可以用作预防和/或治疗炎症性疼痛、骨关节炎疼痛、神经性疼痛和纤维肌痛的药物。
• Use of isatin derivatives as ion channel activating agents
  申请人：——

  公开号：US20020016354A1

  公开（公告）日：2002-02-07

  The present invention relates to ion channel activating agents. More particularly, the present invention relates to a particular class of chemical compounds that has proven useful as openers of SK Ca and IK Ca channels. In further aspects, the present invention relates to the use of these SK/IK channel activating agents for the manufacture of medicaments and pharmaceutical compositions comprising the SK/IK channel activating agents. The SK/IK channel activating agents of the invention are useful for the treatment or alleviation of diseases and conditions associated with the SK/IK channels, in particular respiratory diseases such as asthma, cystic fibrosis, chronic obstructive pulmonary disease and rhinorrhea, convulsions, vascular spasms, coronary artery spasms, renal disorders, polycystic kidney disease, bladder spasms, urinary incontinence, bladder outflow obstruction, irritable bowel syndrome, gastrointestinal dysfunction, secretory diarrhea, ischaemia, cerebral ischaemia, ischaemic heart disease, angina pectoris, coronary heart disease, traumatic brain injury, psychosis, anxiety, depression, dementia, memory and attention deficits, Alzheimer's disease, dysmenorrhea, narcolepsy, Reynaud's disease, intermittent claudication, Sjorgren's syndrome, migraine, arrhythmia, hypertension, absence seizures, myotonic muscle dystrophia, xerostomi, diabetes type II, hyperinsulinemia, premature labor, baldness, cancer, and immune suppression.

  本发明涉及离子通道激活剂。更具体地说，本发明涉及一类特定的化合物，已被证明对SKCa和IKCa通道的开放具有用处。在进一步方面，本发明涉及利用这些SK/IK通道激活剂制造药物和包含SK/IK通道激活剂的药物组合物。本发明的SK/IK通道激活剂对于治疗或缓解与SK/IK通道相关的疾病和症状非常有用，特别是呼吸道疾病，如哮喘、囊性纤维化、慢性阻塞性肺疾病和鼻涕，痉挛、血管痉挛、冠状动脉痉挛、肾脏疾病、多囊肾病、膀胱痉挛、尿失禁、膀胱排空阻塞、肠易激综合征、胃肠功能障碍、分泌性腹泻、缺血、脑缺血、缺血性心脏病、心绞痛、冠心病、创伤性脑损伤、精神病、焦虑、抑郁、痴呆、记忆和注意力缺陷、阿尔茨海默病、痛经、嗜睡症、雷诺氏病、间歇性跛行、斯约格伦综合征、偏头痛、心律失常、高血压、缺席性癫痫发作、肌肉肌无力、干燥综合征、2型糖尿病、胰岛素过多症、早产、秃头、癌症和免疫抑制。
• [EN] USE OF ISATIN DERIVATIVES AS ION CHANNEL ACTIVATING AGENTS<br/>[FR] UTILISATION DE DERIVES D'ISATINE EN TANT QU'AGENTS D'ACTIVATION DE CANAUX IONIQUES
  申请人：NEUROSEARCH AS

  公开号：WO2000033834A1

  公开（公告）日：2000-06-15

  The present invention relates to ion channel activating agents. More particularly, the present invention relates to a particular class of chemical compounds that has proven useful as openers of SKCa and IKCa channels. In further aspects, the present invention relates to the use of these SK/IK channel activating agents for the manufacture of medicaments, and pharmaceutical compositions comprising the SK/IK channel activating agents. The SK/IK channel activating agents of the invention are useful for the treatment or alleviation of diseases and conditions associated with the SK/IK channels, in particular respiratory diseases such as asthma, cystic fibrosis, chronic obstructive pulmonary disease and rhinorrhea, convulsions, vascular spasms, coronary artery spasms, renal disorders, polycystic kidney disease, bladder spasms, urinary incontinence, bladder outflow obstruction, irritable bowel syndrome, gastrointestinal dysfunction, secretory diarrhoea, ischaemia, cerebral ischaemia, ischaemic hearth disease, angina pectoris, coronary hearth disease, traumatic brain injury, psychosis, anxiety, depression, dementia, memory and attention deficits, Alzheimer's disease, dysmenorrhea, narcolepsy, Reynaud's disease, intermittent claudication, Sjorgren's syndrome, migraine, arrhythmia, hypertension, absence seizures, myotonic muscle dystrophia, xerostomi, diabetes type II, hyperinsulinemia, premature labour, baldness, cancer, and immune suppression.

  本发明涉及离子通道激活剂。更具体地，本发明涉及一类已被证明对SKCa和IKCa通道具有开放作用的化学化合物。在进一步方面，本发明涉及使用这些SK/IK通道激活剂制造药物，以及包括SK/IK通道激活剂的药物组合物。本发明的SK/IK通道激活剂对于治疗或缓解与SK/IK通道相关的疾病和症状非常有用，特别是呼吸系统疾病，如哮喘、囊性纤维化、慢性阻塞性肺疾病和流涕、惊厥、血管痉挛、冠状动脉痉挛、肾功能障碍、多囊肾病、膀胱痉挛、尿失禁、膀胱出口梗阻、肠易激综合征、胃肠功能障碍、分泌性腹泻、缺血、脑缺血、缺血性心脏病、心绞痛、冠心病、创伤性脑损伤、精神病、焦虑、抑郁症、痴呆、记忆和注意力缺陷、阿尔茨海默病、痛经、嗜睡症、雷诺氏病、间歇性跛行、Sjogren综合征、偏头痛、心律失常、高血压、失神发作、肌肉萎缩症、口干症、2型糖尿病、高胰岛素血症、早产、秃发、癌症和免疫抑制等。
• Use of intermediate -conductance potassium channels and modulators for diagnosing and treating diseases having disturbed keratinocyte activity
  申请人：——

  公开号：US20040248099A1

  公开（公告）日：2004-12-09

  The invention relates to the use of intermediate-conductance, calcium-activated potassium channels and/or the nucleic acids coding for the same, from humans or mice, for the diagnosis, prevention and/or treatment of illnesses associated with disturbed keratinocyte activity. The invention also relates to the use of the same for identifying pharmacologically active substances. The invention further relates to the use of modulators of intermediate-conductance, calcium-activated potassium channels for the diagnosis, prevention and/or treatment of illnesses associated with disturbed keratinocyte activity.

  本发明涉及使用来自人类或小鼠的中间导电、钙激活钾通道和/或编码其的核酸，用于诊断、预防和/或治疗与干扰角质形成细胞活动相关的疾病。本发明还涉及使用相同的物质来鉴定药理活性物质。本发明进一步涉及使用中间导电、钙激活钾通道的调节剂，用于诊断、预防和/或治疗与干扰角质形成细胞活动相关的疾病。
• MATERIAL FOR SCREENING COMPOUNDS ACTING ON ION CHANNELS AND USE OF SAID MATERIAL
  申请人：Public University Corporation Nagoya City University

  公开号：EP3536783A1

  公开（公告）日：2019-09-11

  The screening system disclosed in the present specification is provided with a potential-dependent Na ion channel that extends the duration of the action potential associated with depolarization, and a K ion channel that deepens the resting membrane potential in the negative direction, said screening system furthermore including cells provided with ion channels that contribute to deepening the resting membrane potential in the negative direction and/or shortening the duration of the action potential as target ion channels. By such cells, the action of a test compound on the target ion channel can be easily evaluated by providing an inhibitor for the K ion channel to control the probability of cell death.

  本说明书中公开的筛选系统具有电位依赖性 Na 离子通道和 K 离子通道，前者可延长与去极化相关的动作电位持续时间，后者可在负方向上加深静息膜电位，所述筛选系统还包括具有有助于在负方向上加深静息膜电位和/或缩短动作电位持续时间的离子通道作为靶离子通道的细胞。通过这种细胞，可以很容易地评估测试化合物对目标离子通道的作用，方法是提供 K 离子通道的抑制剂，以控制细胞死亡的概率。