6-羟基-1,2,3,4-四氢-异喹啉-1-羧酸乙酯 | 780004-18-4

• 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
• 中文别名: 6-羟基-四氢异喹啉-1-羧酸乙酯
• 英文名称: ethyl (1SR)-6-hydroxy-1,2,3,4-tetrahydroisoquinoline-1-carboxylate
• 英文别名: Ethyl 6-hydroxy-1,2,3,4-tetrahydroisoquinoline-1-carboxylate
• CAS: 780004-18-4
• 化学式: C₁₂H₁₅NO₃
• 分子量: 221.256
• InChiKey: UYKVSJYMKQPONE-UHFFFAOYSA-N

物化性质

• 沸点：
  380.4±42.0 °C(Predicted)
• 密度：
  1.196±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  16
• 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：
  2
• 氢受体数：
  4

安全信息

• 海关编码：
  2933499090

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 在 Candida antarctica lipase B 、 水 、 二正丙胺 作用下， 以 异丙醇 、 乙腈 为溶剂， 反应 48.0h， 以87%的产率得到(R)-6-hydroxy-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid
  参考文献：
  名称：

  Efficient dynamic kinetic resolution method for the synthesis of enantiopure 6-hydroxy- and 6-methoxy-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid

  摘要：

  Enantiomeric 6-hydroxy-1,2,3,4-tetrahydroisoquinoline-1-carboxylic acid (ee >99%), useful in the synthesis of modulators of nuclear receptors, including liver X receptor and its analogue 6-methoxy-1,2,3,4-tetrahydroisoquinoline-l-carboxylic acid (ee >99%), a source of the above enantiomer was synthesized through Candida antarctica lipase B-catalysed dynamic kinetic hydrolysis of the corresponding 1,2,3,4-tetrahydroisoquinoline-1-carboxylic esters (+/-)-4 center dot HCl and (+/-)-5. (R)-Selective hydrolysis in both organic solvents and an aqueous NH4OAc buffer at pH 8.5 was observed and the amino acids were obtained in good chemical yields (>87%). (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2016.10.011
• 作为产物：
  描述：

  m-酪胺氢溴酸盐 在 盐酸 作用下， 以 水 为溶剂， 反应 6.5h， 生成 6-羟基-1,2,3,4-四氢-异喹啉-1-羧酸乙酯
  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

文献信息

• [EN] HETEROCYCLIC COMPOUNDS AND THEIR USE AS RETINOID-RELATED ORPHAN RECEPTOR (ROR) GAMMA-T INHIBITORS<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES ET LEUR UTILISATION EN TANT QU'INHIBITEURS GAMMA-T DU RÉCEPTEUR ORPHELIN APPARENTÉ AUX RÉCEPTEURS DES RÉTINOÏDES (ROR) )
  申请人：TAKEDA PHARMACEUTICAL

  公开号：WO2016002968A1

  公开（公告）日：2016-01-07

  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.

  提供的是具有RORγt抑制作用的杂环化合物，其由公式(I)表示：其中每个符号如说明书中定义，或其盐。
• SUBSTITUTED TETRAHYDROISOCHINOLINES AS MMP INHIBITORS, RELATED PRODUCTION METHOD AND USE AS MEDICINE
  申请人：HOFMEISTER Armin

  公开号：US20080090821A1

  公开（公告）日：2008-04-17

  The present invention is directed to a compound of formula (1), wherein R 1 , R 2 , R 3 , R 4 , A, L and n are as defined herein, its pharmaceutical composition, preparation and uses as a MMP inhibitor.

  本发明涉及化合物式（1），其中R1、R2、R3、R4、A、L和n如本文所定义，以及其制备的药物组合物和用途作为MMP抑制剂。
• 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。
• [EN] BIARYL COMPOUND CAPABLE OF SERVING AS RORγ MODULATOR<br/>[FR] COMPOSÉ BIARYLE CAPABLE DE SERVIR DE MODULATEUR DE RORγ<br/>[ZH] 可用作RORγ调节剂的联芳基类化合物
  申请人：SHANGHAI LITEDD CO LTD

  公开号：WO2021228216A1

  公开（公告）日：2021-11-18

  本发明涉及式(I)化合物、其立体异构体、互变异构体、稳定的同位素变体、药学上可接受的盐或溶剂合物、包含其的药物组合物、使用其治疗或预防与RORγt有关的疾病的方法，以及其在制备用于治疗或预防RORγt有关的疾病的药物中的用途。
• SUBSTITUIERTE TETRAHYDROISOCHINOLINE ALS MMP-INHIBITOREN, VERFAHREN ZU IHRER HERSTELLUNG UND IHRE VERWENDUNG ALS MEDIKAMENT
  申请人：Sanofi-Aventis

  公开号：EP1869001B1

  公开（公告）日：2011-01-12