1-[2-[4-(6-氟-1H-3-吲哚基)-3,6-二氢-1(2H)-吡啶基]乙基]-3,4-二氢-3-(1-甲基乙基)-6-(甲磺酰基)-1H-2,1,3-苯并噻二嗪2,2-二氧化物 | 271780-64-4

• 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: 1-[2-[4-(6-氟-1H-3-吲哚基)-3,6-二氢-1(2H)-吡啶基]乙基]-3,4-二氢-3-(1-甲基乙基)-6-(甲磺酰基)-1H-2,1,3-苯并噻二嗪2,2-二氧化物
• 英文名称: LY 393558
• 英文别名: 1-[2-[4-(6-fluoro-1H-indol-3-yl)-3,6-dihydro-1(2H)-pyridinyl]ethyl]-3,4-dihydro-3-(1-methylethyl)-6-methylsulfonyl-1H-2,1,3-benzothiadiazine-2,2-dioxide；1-[2-[4-(6-Fluoro-1H-indol-3-yl)-3,6-dihydro-2H-pyridin-1-yl]ethyl]-6-methylsulfonyl-3-propan-2-yl-4H-2lambda6,1,3-benzothiadiazine 2,2-dioxide；1-[2-[4-(6-fluoro-1H-indol-3-yl)-3,6-dihydro-2H-pyridin-1-yl]ethyl]-6-methylsulfonyl-3-propan-2-yl-4H-2λ6,1,3-benzothiadiazine 2,2-dioxide
• CAS: 271780-64-4
• 化学式: C₂₆H₃₁FN₄O₄S₂
• 分子量: 546.687
• InChiKey: QUSLYAPLTMMCFE-UHFFFAOYSA-N

物化性质

• 沸点：
  785.7±60.0 °C(Predicted)
• 密度：
  1.359±0.06 g/cm3(Predicted)
• 溶解度：
  在 DMSO 中溶解度为 100 mM

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  37
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  111
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1-[2-[4-(6-氟-1H-3-吲哚基)-3,6-二氢-1(2H)-吡啶基]乙基]-3,4-二氢-3-(1-甲基乙基)-6-(甲磺酰基)-1H-2,1,3-苯并噻二嗪2,2-二氧化物 在 盐酸 、 sodium tetrahydroborate 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 生成 1-[2-[4-(6-fluoro-1H-indol-3-yl)-1-piperidinyl]ethyl]-3,4-dihydro-3-(1-methylethyl)-6-methylsulfonyl-1H-2,1,3-benzothiadiazine-2,2-dioxide
  参考文献：
  名称：

  Novel chemoselective reduction of the tetrahydro-4-pyridyl versus indole moiety governed by electron donation: first X-ray evidence for indolopiperidyl–borane complexation

  摘要：

  A series of amino-borane complexes of structure type 2 are the key intermediates in the preparation of 3-(piperidyl) indole derivatives. The selective reduction of the tetrahydro-4-pyridyl double bond via 2 under strongly acidic conditions is feasible only when the pyridyl double bond is conjugated with electron rich substituents, such as indoles. This reduction methodology allows the presence of reducible and hydrogenolizable functional groups. An improved process to prepare 2 by treatment of the 3-(tetrahydro-4-pyridyl) indole derivatives with NaBH4 in THF under acidic conditions (AcOH or CF3COOH) is also described. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(02)01927-5
• 作为产物：
  描述：

  3,4-dihydro-3-(1-methylethyl)-6-(methylsulfonyl)-1H-2,1,3-benzothiadiazine-2,2-dioxide 、 2-(4-(6-fluoro-1H-indol-3-yl)-3,6-dihydro-1(2H)-pyridinyl)ethanol 在 三苯基膦 作用下， 以 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 生成 1-[2-[4-(6-氟-1H-3-吲哚基)-3,6-二氢-1(2H)-吡啶基]乙基]-3,4-二氢-3-(1-甲基乙基)-6-(甲磺酰基)-1H-2,1,3-苯并噻二嗪2,2-二氧化物
  参考文献：
  名称：

  Pharmaceutical compounds

  摘要：

  该药物化合物的化学式如下：其中R1和R2分别为氢、卤素、氰基或甲基，虚线代表可选的双键，其中R4和R5分别为氢、C1-6烷基、环丙基或环丙基-C1-6烷基，n为0或1，而R3为—SR6、—SOR6、—SO2R6、—COR6、—CH2OH或—CONHR7，其中R6为C1-6烷基，R7为氢或C1-6烷基；但当R1和R2中有一个为氢，另一个为氟时，R4和R5分别为氢或C1-6烷基，n为0时，R3不为—COR6或—CONHR7；以及其盐。

  公开号：

  US06329366B1

文献信息

• INDOLE DERIVATIVES AND THEIR USE AS SEROTONIN RECEPTOR LIGANDS
  申请人：ELI LILLY AND COMPANY LIMITED

  公开号：EP1131321B1

  公开（公告）日：2003-09-10
• COMPOUNDS ACTING ON THE SEROTONIN TRANSPORTER
  申请人：Wiborg Ove Kjaer

  公开号：US20100048713A1

  公开（公告）日：2010-02-25

  The invention relates to new chemical compounds acting on the serotonin transporter (SERT), and associated pharmaceutical compositions, methods for use as therapeutic agents, and methods of preparation thereof. In particular the new chemical compounds are useful for the treatment of a variety of central nervous system (CNS) disorders—for example anxiety, depression, epilepsy, obsessive-compulsive disorders, migraine, cognitive disorders, sleep disorders, feeding disorders, panic attacks, disorders related to withdrawl from drug abuse, schizophrenia, or the like, or in the treatment of gastrointestinal disorders such as irritable bowel syndrome.
• US6329366B1
  申请人：——

  公开号：US6329366B1

  公开（公告）日：2001-12-11
• Pharmaceutical compounds
  申请人：Eli Lilly and Company Limited

  公开号：US06329366B1

  公开（公告）日：2001-12-11

  A pharmaceutical compound of the formula in which R1 and R2 are each hydrogen, halo, cyano or methyl, the dotted line represents an optional double bond, where R4 and R5 are each hydrogen, C1-6 alkyl, cyclopropyl or cyclopropyl-C1-6 alkyl, n is 0 or 1, and R3 is —SR6, —SOR6, —SO2R6, —COR6, —CH2OH or —CONHR7, where R6 is C1-6 alkyl and R7 is hydrogen or C1-6 alkyl; provided that when one of R1 and R2 is hydrogen and the other is fluoro, R4 and R5 are each hydrogen or C1-6 alkyl, and n is 0, then R3 is not —COR6 or —CONHR7; and salts thereof.

  该药物化合物的化学式如下：其中R1和R2分别为氢、卤素、氰基或甲基，虚线代表可选的双键，其中R4和R5分别为氢、C1-6烷基、环丙基或环丙基-C1-6烷基，n为0或1，而R3为—SR6、—SOR6、—SO2R6、—COR6、—CH2OH或—CONHR7，其中R6为C1-6烷基，R7为氢或C1-6烷基；但当R1和R2中有一个为氢，另一个为氟时，R4和R5分别为氢或C1-6烷基，n为0时，R3不为—COR6或—CONHR7；以及其盐。
• Novel chemoselective reduction of the tetrahydro-4-pyridyl versus indole moiety governed by electron donation: first X-ray evidence for indolopiperidyl–borane complexation
  作者：Alfio Borghese、Luc Antoine、Gregory Stephenson

  DOI：10.1016/s0040-4039(02)01927-5

  日期：2002.11

  A series of amino-borane complexes of structure type 2 are the key intermediates in the preparation of 3-(piperidyl) indole derivatives. The selective reduction of the tetrahydro-4-pyridyl double bond via 2 under strongly acidic conditions is feasible only when the pyridyl double bond is conjugated with electron rich substituents, such as indoles. This reduction methodology allows the presence of reducible and hydrogenolizable functional groups. An improved process to prepare 2 by treatment of the 3-(tetrahydro-4-pyridyl) indole derivatives with NaBH4 in THF under acidic conditions (AcOH or CF3COOH) is also described. (C) 2002 Elsevier Science Ltd. All rights reserved.