6-羟基-1,2,3,4-四氢异喹啉-1-羧酸乙酯盐酸盐 | 128073-50-7

• 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: 6-羟基-1,2,3,4-四氢异喹啉-1-羧酸乙酯盐酸盐
• 英文名称: ethyl (1SR)-6-hydroxy-1,2,3,4-tetrahydroisoquinoline-1-carboxylate hydrochloride
• 英文别名: ethyl 6-hydroxy-1,2,3,4-tetrahydroisoquinoline-1-carboxylate hydrochloride；ethyl 6-hydroxy-1,2,3,4-tetrahydro-1-isoquinoline carboxylate hydrochloride；ethyl 6-hydroxy-1,2,3,4-tetrahydroisoquinoline-1-carboxylate;hydrochloride
• CAS: 128073-50-7
• 化学式: C₁₂H₁₅NO₃*ClH
• 分子量: 257.717
• InChiKey: PMQLEMKSBRHVJY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.56
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  58.6
• 氢给体数：
  3
• 氢受体数：
  4

安全信息

• 海关编码：
  2933499090
• 危险性防范说明：
  P261,P304+P340,P405,P280,P305+P351+P338
• 危险性描述：
  H319,H315,H302,H335

反应信息

• 作为反应物：
  描述：

  6-羟基-1,2,3,4-四氢异喹啉-1-羧酸乙酯盐酸盐 在 palladium on activated charcoal 、 Rh on carbon 4 A molecular sieve 、 氢气 、 sodium hexamethyldisilazane 、 N,N-二异丙基乙胺 、 pyridinium chlorochromate 作用下， 以 乙醇 、 二氯甲烷 、 溶剂黄146 为溶剂， 25.0~60.0 ℃ 、413.69 kPa 条件下， 反应 54.5h， 生成 ethyl decahydro-6-(diethylphosphonomethyl)-2-t-butoxycarbonyl-1-isoquinoline carboxylate
  参考文献：
  名称：

  6-Substituted decahydroisoquinoline-3-carboxylic acids as potent and selective conformationally constrained NMDA receptor antagonists

  摘要：

  We have prepared a series of 6-substituted decahydroisoquinoline-3-carboxylic acids, and structurally similar analogs, as potential N-methyl-D-aspartate receptor antagonists. There is a large body of evidence to support the use of such compounds as cerebroprotective agents in a variety of acute and chronic neurodegenerative disorders, where some component of glutamate-mediated excitotoxicity may exist. The compounds prepared were evaluated in vitro in both receptor binding assays ([H-3]CGS19755, [H-3]AMPA, and [H-3]kainic acid) and in a cortical wedge preparation (versus NMDA, AMPA, and kainic acid) to determine affinity, potency, and selectivity. The new amino acids were also evaluated in vivo for their ability to block NMDA-induced lethality in mice. We synthesized many of the possible diastereomers of the decahydroisoquinoline nucleus in order to examine the spatial and steric requirements for affinity at the NMDA receptor and activity as NMDA antagonists. From our structure-activity relationship we identified two potent and selective NMDA receptor antagonists, the phosphonate- and tetrazole-substituted amino acids 31a and 32a, respectively, that show good activity in animals following systemic administration. For example, 31a and 32a selectively displaced [H-3]CGS19755 binding with IC50s of 55 +/- 14 and 856 +/- 136 nM, respectively, and selectively antagonized responses due to NMDA in a cortical wedge preparation with IC50s of 0.15 +/- 0.01 and 1.39 +/- 0.29-mu-M, respectively. And compounds 31a and 32a blocked NMDA-induced lethality in mice with minimum effective doses of 1.25 and 2.5 mg/kg (intraperitoneal), respectively. These novel amino acids are among some of the most potent NMDA antagonists described thus far, and are excellent candidates for development as neuroprotective agents for a number of CNS disorders.

  DOI：

  10.1021/jm00097a012
• 作为产物：
  描述：

  乙醛酸乙酯 、 3-羟基苯乙胺盐酸盐 以 乙醇 、 甲苯 为溶剂， 反应 18.0h， 以90%的产率得到6-羟基-1,2,3,4-四氢异喹啉-1-羧酸乙酯盐酸盐
  参考文献：
  名称：

  TW2016/2105

  摘要：

  公开号：

文献信息

• Excitatory amino acid receptor antagonists
  申请人：Eli Lilly and Company

  公开号：US04902695A1

  公开（公告）日：1990-02-20

  The present invention provides novel bicyclic derivatives useful as excitatory amino acid receptor antagonists and in treating a variety of associated nervous system disorders.

  本发明提供了一种新颖的双环衍生物，可用作兴奋性氨基酸受体拮抗剂，并用于治疗各种相关的神经系统疾病。
• Heterocyclic compound
  申请人：Takeda Pharmaceutical Company Limited

  公开号：US09365520B2

  公开（公告）日：2016-06-14

  The present invention provides a heterocyclic compound having a RORγt inhibitory action. The present invention relates to a compound represented by the formula (I): wherein each symbol is as defined in the specification. or a salt thereof.

  本发明提供了一种具有RORγt抑制作用的杂环化合物。本发明涉及一种由公式（I）表示的化合物：其中每个符号如规范中所定义，或其盐。
• HETEROCYCLIC COMPOUND
  申请人：Takeda Pharmaceutical Company Limited

  公开号：US20160176872A1

  公开（公告）日：2016-06-23

  The present invention provides a heterocyclic compound having a RORγt inhibitory action. The present invention relates to a compound represented by the formula (I): wherein each symbol is as defined in the specification. or a salt thereof.

  本发明提供了一种具有RORγt抑制作用的杂环化合物。本发明涉及一种由式(I)表示的化合物：其中每个符号如规范中所定义，或其盐。
• Heterocyclic compounds and their use as retinoid-related orphan receptor (ROR) gamma-T inhibitors
  申请人：Takeda Pharmaceutical Company Limited

  公开号：US10093629B2

  公开（公告）日：2018-10-09

  Provided are heterocyclic compounds having a RORγt inhibitory action represented by the formula (I): wherein each symbol is as defined in the specification, or a salt thereof.

  所提供的是具有 RORγt 抑制作用的杂环化合物，由式（I）表示：其中各符号如说明书中所定义，或其盐。
• Decahydro isoquinoline derivatives, process for their preparation and use as medicines
  申请人：ELI LILLY AND COMPANY

  公开号：EP0383504B1

  公开（公告）日：1995-07-19