6-(6H-2,3-Dihydrothiopyran-4-yl)1-(2-(N,N-dimethylamino)ethyl)-1H-indole | 281202-83-3

• 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: 6-(6H-2,3-Dihydrothiopyran-4-yl)1-(2-(N,N-dimethylamino)ethyl)-1H-indole
• 英文别名: {2-[6-(3,6-Dihydro-2H-thiopyran-4-yl)-indol-1-yl]-ethyl}-dimethyl-amine；2-[6-(3,6-dihydro-2H-thiopyran-4-yl)indol-1-yl]-N,N-dimethylethanamine
• CAS: 281202-83-3
• 化学式: C₁₇H₂₂N₂S
• 分子量: 286.441
• InChiKey: DMVIFNBSEKFYMW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  33.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-(6H-2,3-Dihydrothiopyran-4-yl)1-(2-(N,N-dimethylamino)ethyl)-1H-indole 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 生成 1-(2-(N,N-Dimethylamino)ethyl)-6-(tetrahydrothiopyran-4-yl)-1H-indole
  参考文献：
  名称：

  Design, synthesis and biological activity of novel dimethyl-{2-[6-substituted-indol-1-yl]-ethyl}-amine as potent, selective, and orally-Bioavailable 5-HT 1D agonists

  摘要：

  A novel series of highly potent human 5-HT1D agonists, dimethyl-{2-[6-substituted-indol-1-yl]-ethyl}-amine, was synthesized. Structure-activity relationship (SAR) investigation revealed 4-[1-(2-dimethylamino-ethyl)-1H-indol-6-yl]-tetrahydro-thiopyran-4-ol, 11b (ALX-2732), as a potent (K-i = 2.4 nM) agonist at the human 5-HT1D receptor with good selectivity over the other serotonin receptor subtypes. This compound demonstrated favorable in vitro metabolic stability in human and rat liver microsomes and was found to be orally bioavailable in rats (F-po = 51%) (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.09.025
• 作为产物：
  描述：

  6-溴吲哚 在 叔丁基锂 、 potassium hydride 、 sodium hydride 、 二异丁基氢化铝 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 6-(6H-2,3-Dihydrothiopyran-4-yl)1-(2-(N,N-dimethylamino)ethyl)-1H-indole
  参考文献：
  名称：

  Design, synthesis and biological activity of novel dimethyl-{2-[6-substituted-indol-1-yl]-ethyl}-amine as potent, selective, and orally-Bioavailable 5-HT 1D agonists

  摘要：

  A novel series of highly potent human 5-HT1D agonists, dimethyl-{2-[6-substituted-indol-1-yl]-ethyl}-amine, was synthesized. Structure-activity relationship (SAR) investigation revealed 4-[1-(2-dimethylamino-ethyl)-1H-indol-6-yl]-tetrahydro-thiopyran-4-ol, 11b (ALX-2732), as a potent (K-i = 2.4 nM) agonist at the human 5-HT1D receptor with good selectivity over the other serotonin receptor subtypes. This compound demonstrated favorable in vitro metabolic stability in human and rat liver microsomes and was found to be orally bioavailable in rats (F-po = 51%) (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.09.025

文献信息

• Use of N-alkylamino-heterocylic compounds for the treatment of migraine
  申请人：NPS Allexlix Corp.

  公开号：US20020169322A1

  公开（公告）日：2002-11-14

  Described are compounds having formula I or II: 1 wherein: X is N, CH or C-lower alkyl; R 1 represents a 5 to 7-membered monocyclic or benzo-fused heterocyclic ring, Ak represents a C 1-3 alkylene chain; R 3 and R 4 are H, lower alkyl, lower alkenyl or optionally-substituted benzyl; or one pair of R 2 , R 3 or R 3 , R 4 together may form an alkylene or alkenylene bridge which, with the nitrogen atom, form a 3- to 7-membered ring; R 5 is H, lower alkyl or a 4- to 7-membered carbocyclic or heterocyclic group; R 6 represents a 5 to 7-membered monocyclic or benzo-fused heterocyclic ring; R 8 and R 9 are H, lower alkyl, lower alkenyl or optionally-substituted benzyl; R 10 is H, lower alkyl or a 4- to 7-membered carbocyclic or heterocyclic group; and a salt, solvate or prodrug thereof.

  描述了具有公式I或II的化合物：1其中：X为N、CH或C-较低烷基；R1表示5至7成员的单环或苯并嵌杂环；Ak表示C1-3烷基链；R3和R4为H、较低烷基、较低烯基或可选取代苄基；或者R2、R3或R3、R4中的一对可以共同形成与氮原子一起形成3至7成员环的烷基或烯基桥；R5为H、较低烷基或4至7成员的碳环或杂环基团；R6表示5至7成员的单环或苯并嵌杂环；R8和R9为H、较低烷基、较低烯基或可选取代苄基；R10为H、较低烷基或4至7成员的碳环或杂环基团；以及其盐、溶剂化物或前药。
• US6380242B1
  申请人：——

  公开号：US6380242B1

  公开（公告）日：2002-04-30
• US6635639B2
  申请人：——

  公开号：US6635639B2

  公开（公告）日：2003-10-21
• Design, synthesis and biological activity of novel dimethyl-{2-[6-substituted-indol-1-yl]-ethyl}-amine as potent, selective, and orally-Bioavailable 5-HT 1D agonists
  作者：Methvin Isaac、Malik Slassi、Tao Xin、Jalaj Arora、Anne O'Brien、Louise Edwards、Neil MacLean、Julie Wilson、Lidia Demschyshyn、Phillipe Labrie、Angela Naismith、Shawn Maddaford、Damon Papac、Shuree Harrison、Hua Wang、Stan Draper、Ashok Tehim

  DOI：10.1016/j.bmcl.2003.09.025

  日期：2003.12

  A novel series of highly potent human 5-HT1D agonists, dimethyl-2-[6-substituted-indol-1-yl]-ethyl}-amine, was synthesized. Structure-activity relationship (SAR) investigation revealed 4-[1-(2-dimethylamino-ethyl)-1H-indol-6-yl]-tetrahydro-thiopyran-4-ol, 11b (ALX-2732), as a potent (K-i = 2.4 nM) agonist at the human 5-HT1D receptor with good selectivity over the other serotonin receptor subtypes. This compound demonstrated favorable in vitro metabolic stability in human and rat liver microsomes and was found to be orally bioavailable in rats (F-po = 51%) (C) 2003 Elsevier Ltd. All rights reserved.