4-(5-methoxy-1H-indol-3-yl)-5,6-dihydropyridine-1(2H)-carboxylic acid tert-butyl ester | 951174-07-5

• 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
• 英文名称: 4-(5-methoxy-1H-indol-3-yl)-5,6-dihydropyridine-1(2H)-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl 4-(5-methoxy-1H-indol-3-yl)-5,6-dihydropyridine-1(2H)-carboxylate；tert-butyl 4-(5-methoxy-1H-indol-3-yl)-3,6-dihydro-1(2H)-pyridinecarboxylate；tert-butyl 4-(5-methoxy-1H-indol-3-yl)-3,6-dihydro-2H-pyridine-1-carboxylate
• CAS: 951174-07-5
• 化学式: C₁₉H₂₄N₂O₃
• 分子量: 328.411
• InChiKey: MVACCESFUXURLC-UHFFFAOYSA-N

物化性质

• 沸点：
  496.2±45.0 °C(Predicted)
• 密度：
  1.187±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  54.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(5-methoxy-1H-indol-3-yl)-5,6-dihydropyridine-1(2H)-carboxylic acid tert-butyl ester 在 盐酸 、 potassium carbonate 、 (叔丁基亚氨基)三(吡咯烷)膦 、 potassium iodide 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 、 丙酮 为溶剂， 反应 48.0h， 生成 7-[5-methoxy-3-(1-propyl-3,6-dihydro-2H-pyridin-4-yl)indol-1-yl]sulfonylquinoline
  参考文献：
  名称：

  N1-Azinylsulfonyl-1H-indoles: 5-HT6 Receptor Antagonists with Procognitive and Antidepressant-Like Properties

  摘要：

  A series of N1-azinylsulfonyl-3-(1,2,3,6,tetrahyrdopyridin-4-yl)-1H-indole derivatives was designed to obtain highly potent 5-HT6 receptor ligands. The study allowed for the identification of 25 (4-{[5-methoxy-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indol-1-yl]sulfonyl}isoquinoline), a potent and selective 5-HT6 receptor antagonist. The selected compound, was evaluated in vivo in a novel object recognition (NOR) and forced swim (FST) tests in rats, demonstrating distinct pro-cognitive and antidepressant-like properties (MED = 1 mg/kg and 0.1 mg/kg, i.p., respectively). Compound SB-742457, used as comparator, reversed memory deficits in NOR task in similar doses, while in FST it was active in 10-30-fold higher dose (3 mg/kg). In contrast to SB-742457, which was active in Vogel test (MED = 3 mg/kg), compound 25 displayed no anxiolytic activity.

  DOI：

  10.1021/acsmedchemlett.6b00056
• 作为产物：
  描述：

  5-甲氧基吲哚 、 1-Boc-2-哌啶酮 在 potassium tert-butylate 作用下， 以 叔丁醇 为溶剂， 生成 4-(5-methoxy-1H-indol-3-yl)-5,6-dihydropyridine-1(2H)-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Pharmaceutical compounds

  摘要：

  这项发明涉及到式(I)的化合物，其中R1至R12，—W—V—，—X—Y—，m和n的值如权利要求1中定义的，它们的制备和用作药物。

  公开号：

  US20040122001A1

文献信息

• N1-arylsulfonyl-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole derivatives are potent and selective 5-HT6 receptor antagonists
  作者：Derek C. Cole、John W. Ellingboe、William J. Lennox、Hossein Mazandarani、Deborah L. Smith、Joseph R. Stock、Guoming Zhang、Ping Zhou、Lee E. Schechter

  DOI：10.1016/j.bmcl.2004.10.064

  日期：2005.1

  A series of Ni-arylsulfonyl-3-(1,2,3,6-tetrahydropyridin-4-yl)indole derivatives was designed and synthesized. These compounds were shown to have high affinity for the 5-HT6 receptor. Two analogs, 4-[3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole-1-sulfonyl]-phenylamine 15g and 4-[3-(1,2,3,6-tetrahydropyridin-4-yl)-5-methoxy-1H-indole-1-sulfonyl]-phenylamine 15y, had 0.4 and 3.0nM affinity, respectively, and antagonized the production of adenylate cyclase at sub-nanomolar concentrations. (C) 2004 Elsevier Ltd. All rights reserved.
• Pyrazole-based cathepsin S inhibitors with improved cellular potency
  作者：Jianmei Wei、Barbara A. Pio、Hui Cai、Steven P. Meduna、Siquan Sun、Yin Gu、Wen Jiang、Robin L. Thurmond、Lars Karlsson、James P. Edwards

  DOI：10.1016/j.bmcl.2007.08.038

  日期：2007.10

  High potency pyrazole-based noncovalent inhibitors of human cathepsin S (CatS) were developed by modification of the benzo-fused 5-membered ring heterocycles found in earlier series of Cats inhibitors. Although substitutions on this heterocyclic framework had a moderate impact on enzymatic potency, dramatic effects on cellular activity were observed. Optimization afforded indole- and benzothiophene-derived analogues that were high affinity Cats inhibitors (IC50 = 20-40 nM) with good cellular potency (IC50 = 30-340 nM). (c) 2007 Elsevier Ltd. All rights reserved.
• Pharmaceutical compounds
  申请人：——

  公开号：US20040122001A1

  公开（公告）日：2004-06-24

  This invention relates to compounds of formula (I) where R 1 to R 12 , —W—V—, —X—Y—, m and n have the values defined in claim 1, their preparation and use as pharmaceuticals. 1

  这项发明涉及到式(I)的化合物，其中R1至R12，—W—V—，—X—Y—，m和n的值如权利要求1中定义的，它们的制备和用作药物。
• <i>N</i>1-Azinylsulfonyl-1<i>H</i>-indoles: 5-HT6 Receptor Antagonists with Procognitive and Antidepressant-Like Properties
  作者：Paweł Zajdel、Krzysztof Marciniec、Grzegorz Satała、Vittorio Canale、Tomasz Kos、Anna Partyka、Magdalena Jastrzębska-Więsek、Anna Wesołowska、Agnieszka Basińska-Ziobroń、Jacek Wójcikowski、Władysława A. Daniel、Andrzej J. Bojarski、Piotr Popik

  DOI：10.1021/acsmedchemlett.6b00056

  日期：2016.6.9

  A series of N1-azinylsulfonyl-3-(1,2,3,6,tetrahyrdopyridin-4-yl)-1H-indole derivatives was designed to obtain highly potent 5-HT6 receptor ligands. The study allowed for the identification of 25 (4-[5-methoxy-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indol-1-yl]sulfonyl}isoquinoline), a potent and selective 5-HT6 receptor antagonist. The selected compound, was evaluated in vivo in a novel object recognition (NOR) and forced swim (FST) tests in rats, demonstrating distinct pro-cognitive and antidepressant-like properties (MED = 1 mg/kg and 0.1 mg/kg, i.p., respectively). Compound SB-742457, used as comparator, reversed memory deficits in NOR task in similar doses, while in FST it was active in 10-30-fold higher dose (3 mg/kg). In contrast to SB-742457, which was active in Vogel test (MED = 3 mg/kg), compound 25 displayed no anxiolytic activity.