5-氟-2-甲氧基-1H-吲哚-3-羧酸 [1-[2-[(甲基磺酰基)氨基]乙基]-4-哌啶基]甲基酯 | 144625-67-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: 5-氟-2-甲氧基-1H-吲哚-3-羧酸 [1-[2-[(甲基磺酰基)氨基]乙基]-4-哌啶基]甲基酯
• 中文别名: 5-氟-2-甲氧基-1H-吲哚-3-羧酸[1-[2-[(甲基磺酰基)氨基]乙基]-4-哌啶基]甲基酯；5-氟2-甲氧基-1H-吲哚3-羧基酸-[1-[2-[(甲磺酰基)氨基]乙基]-4-哌啶基]甲酯；5 - 氟2 - 甲氧基- 1H -吲哚3 - 羧基酸-[1 - [2 - [(甲磺酰基)氨基]乙基] -4 - 哌啶基]甲酯
• 英文名称: GR 125487
• 英文别名: 5-fluoro-2-methoxy-1H-indole-3-carboxylic acid 1-(2-methanesulfonylamino-ethyl)-piperidin-4-ylmethyl ester；5-fluoro-2-methoxy-[1-[2-[(methylsulfonyl)amino]ethyl]-4-piperidinyl]-1H-indole-3-methylcarboxylate；[1-[2-[(methylsulfonyl)amino]ethyl]-4-piperidinyl]methyl-5-fluoro-2-methoxy-1H-indole-3-carboxylate；GR-125487；GR125487；U50488H；(1-(2-(methylsulfonamido)ethyl)piperidin-4-yl)methyl 5-fluoro-2-methoxy-1H-indole-3-carboxylate；[1-[2-(methanesulfonamido)ethyl]piperidin-4-yl]methyl 5-fluoro-2-methoxy-1H-indole-3-carboxylate
• CAS: 144625-67-2
• 化学式: C₁₉H₂₆FN₃O₅S
• 分子量: 427.497
• InChiKey: SSPCCAYAIDNNJX-UHFFFAOYSA-N

物化性质

• 熔点：
  118-120℃
• 沸点：
  613.4±65.0 °C(Predicted)
• 密度：
  1.313±0.06 g/cm3(Predicted)
• 溶解度：
  H2O:~14 mg/mLat 60 °C,可溶

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  109
• 氢给体数：
  2
• 氢受体数：
  8

安全信息

• WGK Germany：
  3
• 海关编码：
  2935009090

反应信息

• 作为反应物：
  描述：

  氨基磺酸 、 5-氟-2-甲氧基-1H-吲哚-3-羧酸 [1-[2-[(甲基磺酰基)氨基]乙基]-4-哌啶基]甲基酯 以 异丙醇 为溶剂， 反应 0.5h， 以58 mg的产率得到sulfamate salt of GR 125487
  参考文献：
  名称：

  Synthesis of GR 125487, a selective 5-HT₄ receptor antagonist

  摘要：

  The 5-HT4 receptor (5-HT4R) agonists are important in treating gastrointestinal motility disorders. Their role is currently being evaluated for the treatment of cognitive and mood disorders. A selective 5-HT4R antagonist GR 125487 is used in many biological assays to cross confirm the 5-HT4R agonist's activity. A practical synthesis of GR 125487 is developed so as to have it in desired quantities. The synthesis consists of seven steps starting from commercially available methyl 5-fluoroindole 3-carboxylate. The GR 125487 thus synthesized was used in blocking the activity of 5-HT4R agonist compound in animal models of cognition.

  DOI：

  10.1080/00397911.2016.1178297
• 作为产物：
  描述：

  5-氟-1H-吲哚-3-羧酸甲酯 在 N-氯代丁二酰亚胺 、 正丁基锂 、 palladium 10% on activated carbon 、 氢气 、 sodium hydroxide 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 、 四氯化碳 、 水 、 乙腈 为溶剂， 反应 93.0h， 生成 5-氟-2-甲氧基-1H-吲哚-3-羧酸 [1-[2-[(甲基磺酰基)氨基]乙基]-4-哌啶基]甲基酯
  参考文献：
  名称：

  Synthesis of GR 125487, a selective 5-HT₄ receptor antagonist

  摘要：

  The 5-HT4 receptor (5-HT4R) agonists are important in treating gastrointestinal motility disorders. Their role is currently being evaluated for the treatment of cognitive and mood disorders. A selective 5-HT4R antagonist GR 125487 is used in many biological assays to cross confirm the 5-HT4R agonist's activity. A practical synthesis of GR 125487 is developed so as to have it in desired quantities. The synthesis consists of seven steps starting from commercially available methyl 5-fluoroindole 3-carboxylate. The GR 125487 thus synthesized was used in blocking the activity of 5-HT4R agonist compound in animal models of cognition.

  DOI：

  10.1080/00397911.2016.1178297

文献信息

• INDOLE AND AZAINDOLE DERIVATIVE HAVING AMPK-ACTIVATING ACTIVITY
  申请人：SHIONOGI & CO., LTD

  公开号：US20150203450A1

  公开（公告）日：2015-07-23

  Disclosed is a compound which is useful as an AMPK activator. A compound represented by formula: or its pharmaceutically acceptable salt, wherein Y is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, or substituted or unsubstituted heterocyclyl; T is —CR 7 ═ or —N═; U is —CR 8 ═ or —N═; R 2 is hydrogen, halogen, cyano, nitro, carboxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted acyl, substituted or unsubstituted carbamoyl, substituted or unsubstituted alkylthio, substituted or unsubstituted alkylsulfinyl, substituted or unsubstituted alkylsulfonyl, or substituted or unsubstituted alkyloxycarbonyl; R 3 is halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted heterocyclyl, or the like; and R 4 , R 7 and R 8 are each independently hydrogen, halogen, hydroxy, cyano, nitro, carboxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted heterocyclyl, or the like.

  本申请公开了一种作为AMPK激活剂有用的化合物。一种由以下结构表示的化合物或其药学上可接受的盐，其中Y被取代或未取代的烷基，取代或未取代的烯基，取代或未取代的炔基，取代或未取代的芳基，取代或未取代的杂环芳基，取代或未取代的环烷基，取代或未取代的环烯基，或取代或未取代的杂环烷基；T为—CR7═或—N═；U为—CR8═或—N═；R2为氢，卤素，氰基，硝基，羧基，取代或未取代的烷基，取代或未取代的烯基，取代或未取代的酰基，取代或未取代的氨基甲酰基，取代或未取代的烷基硫基，取代或未取代的烷基亚砜基，取代或未取代的烷基砜基，或取代或未取代的烷氧羰基；R3为卤素，取代或未取代的烷基，取代或未取代的烯基，取代或未取代的炔基，取代或未取代的芳基，取代或未取代的杂环芳基，取代或未取代的环烷基，取代或未取代的环烯基，取代或未取代的杂环烷基，或类似物；且R4、R7和R8分别独立地为氢，卤素，羟基，氰基，硝基，羧基，取代或未取代的烷基，取代或未取代的烯基，取代或未取代的炔基，取代或未取代的芳基，取代或未取代的杂环芳基，取代或未取代的环烷基，取代或未取代的环烯基，取代或未取代的杂环烷基，或类似物。
• Multi-layered compositions containing histamine or serotonin antagonists
  申请人：GLAXO GROUP LIMITED

  公开号：EP0546593A1

  公开（公告）日：1993-06-16

  This invention relates to a controlled release pharmaceutical composition comprising: (a) an outer layer comprising a pH independent hydrophilic polymer together with one or more fillers; and (b) one or more inner layers each comprising an active ingredient; wherein the outer layer is gradually removed by a combination of dissolution and erosion following administration and the inner layer or layers is gradually removed by a combination of dissolution and erosion or disintegrates rapidly once exposed; and processes for the preparation thereof. In particular the invention relates to pharmaceutical compositions for the controlled release of H2-antagonists or serotonin agonists or antagonists.

  本发明涉及一种控释药物组合物，其中包括 (a) 外层包括与 pH 值无关的亲水性聚合物和一种或多种填料；以及 (b) 一个或多个内层，各包含一种活性成分； 其中外层在给药后通过溶解和侵蚀相结合的方式逐渐去除，内层通过溶解和侵蚀相结合的方式逐渐去除或在暴露后迅速崩解；及其制备工艺。本发明尤其涉及控制释放 H2-拮抗剂或血清素激动剂或拮抗剂的药物组合物。
• INDOLE AND AZAINDOLE DERIVATIVES EACH HAVING AMPK-ACTIVATING ACTIVITY
  申请人：Shionogi & Co., Ltd.

  公开号：EP2963013A1

  公开（公告）日：2016-01-06

  Disclosed is a compound which is useful as an AMPK activator. A compound represented by formula: or its pharmaceutically acceptable salt, wherein Y is substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, or substituted or unsubstituted heterocyclyl; T is -CR7= or -N=; U is -CR8= or -N=; R2 is hydrogen, halogen, cyano, nitro, carboxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted acyl, substituted or unsubstituted carbamoyl, substituted or unsubstituted alkylthio, substituted or unsubstituted alkylsulfinyl, substituted or unsubstituted alkylsulfonyl, or substituted or unsubstituted alkyloxycarbonyl; R3 is halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted heterocyclyl, or the like; and R4, R7 and R8 are each independently hydrogen, halogen, hydroxy, cyano, nitro, carboxy, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted cycloalkenyl, substituted or unsubstituted heterocyclyl, or the like.

  本发明公开了一种可用作 AMPK 激活剂的化合物。一种由式表示的化合物： 或其药学上可接受的盐、 其中 Y 是取代或未取代的烷基、取代或未取代的烯基、取代或未取代的炔基、取代或未取代的芳基、取代或未取代的杂芳基、取代或未取代的环烷基、取代或未取代的环烯基、取代或未取代的杂环基； T 是-CR7= 或-N=； U 是-CR8= 或-N=； R2 是氢、卤素、氰基、硝基、羧基、取代或未取代的烷基、取代或未取代的烯基、取代或未取代的酰基、取代或未取代的氨基甲酰基、取代或未取代的烷硫基、取代或未取代的烷硫基、取代或未取代的烷磺酰基、取代或未取代的烷氧羰基； R3 是卤素、取代或未取代的烷基、取代或未取代的烯基、取代或未取代的炔基、取代或未取代的芳基、取代或未取代的杂芳基、取代或未取代的环烷基、取代或未取代的环烯基、取代或未取代的杂环基，或类似物；和 R4、R7 和 R8 各自独立地为氢、卤素、羟基、氰基、硝基、羧基、取代或未取代的烷基、取代或未取代的烯基、取代或未取代的炔基、取代或未取代的芳基、取代或未取代的杂芳基、取代或未取代的环烷基、取代或未取代的环烯基、取代或未取代的杂环基或类似物。
• Systems pharmacology for treating ocular disorders
  申请人：Case Western Reserve Univeristy

  公开号：US10426773B2

  公开（公告）日：2019-10-01

  A method of treating an ocular disorder in a subject includes administering to the subject subtherapeutic amounts of two or more agents that inhibit and/or blocks the activation of Gs- or Gq-protein coupled receptors or Gs- or Gq-signaling cascade in ocular cells of the subject, and/or activates Gi-protein coupled receptors, which is induced or triggered by light induced all-trans-retinal generation.

  一种治疗受试者眼部疾病的方法包括向受试者施用亚治疗量的两种或两种以上抑制和/或阻断受试者眼部细胞中 Gs 或 Gq 蛋白偶联受体或 Gs 或 Gq 信号级联激活的制剂，和/或激活 Gi- 蛋白偶联受体，这是由光诱导全反式视网膜生成诱导或触发的。
• Compounds and methods of treating ocular disorders
  申请人：Case Western Reserve University

  公开号：US10568851B2

  公开（公告）日：2020-02-25

  A method of treating an ocular disorder in a subject includes administering to the subject a therapeutically effective amount of an agent that modulates at least one target in a signaling cascade associated with light induced retinal degeneration, aberrant all-trans-retinal accumulation, and/or generation of reactive oxygen species (ROS).

  一种治疗受试者眼部疾病的方法包括向受试者施用治疗有效量的制剂，该制剂可调节与光诱导视网膜变性、全反式视网膜异常积聚和/或活性氧（ROS）生成相关的信号级联中的至少一个靶点。