Ethyl (3S,4aR,6S,8aR)-6-(hydroxymethyl)-2-(methoxycarbonyl)-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylate | 157006-69-4

• 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
• 英文名称: Ethyl (3S,4aR,6S,8aR)-6-(hydroxymethyl)-2-(methoxycarbonyl)-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylate
• 英文别名: ethyl (3S,4aR,6S,8aR)-6-(hydroxymethyl)-2-(methoxycarbonyl)-1,2,3,4,4a,5,6,7,8,82-decahydroisoquinoline-3-carboxylate；ethyl (3S,4aR,6S,8aR)-6-hydroxymethyl-2-methoxycarbonyl-decahydroisoquinoline-3-carboxylate；3-O-ethyl 2-O-methyl (3S,4aR,6S,8aR)-6-(hydroxymethyl)-3,4,4a,5,6,7,8,8a-octahydro-1H-isoquinoline-2,3-dicarboxylate
• CAS: 157006-69-4
• 化学式: C₁₅H₂₅NO₅
• 分子量: 299.367
• InChiKey: NOFGNXFKVUJDOY-RVMXOQNASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.87
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  Ethyl (3S,4aR,6S,8aR)-6-(hydroxymethyl)-2-(methoxycarbonyl)-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylate 在 盐酸 、 甲醇 、 草酰氯 、 sodium hydride 、 magnesium 、 二甲基亚砜 、 三乙胺 、 三正丁基叠氮化锡 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 替占帕奈
  参考文献：
  名称：

  （3SR，4aRS，6RS，8aRS）-6- [2-（1H-四唑-5-基）乙基]十氢异喹啉-3-羧酸：一种结构新颖的，具有系统活性的竞争性AMPA受体拮抗剂。

  摘要：

  DOI：

  10.1021/jm00066a016
• 作为产物：
  描述：

  Ethyl (3SR,4aRS,6RS,8aRS)-6-formyl-2-(methoxycarbonyl)-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylate 在 咪唑 、 sodium hydroxide 、 sodium tetrahydroborate 、 dimethyl sulfide borane 、 双氧水 、 碘 、 三苯基膦 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 10.25h， 生成 Ethyl (3S,4aR,6S,8aR)-6-(hydroxymethyl)-2-(methoxycarbonyl)-1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinoline-3-carboxylate
  参考文献：
  名称：

  Stereoselective Synthesis of 6-Substituted Decahydroisoquinoline-3-carboxylates: Intermediates for the Preparation of Conformationally Constrained Acidic Amino Acids

  摘要：

  In this article we describe the stereoselective preparation of two 6-(hydroxymethyl) substituted decahydroisoquinoline-3-carboxylates, which are useful in the synthesis of a number of excitatory amino acid antagonists, e.g., (-)-1a (LY235959), (-)-2a (LY202157) and (-)-3a(LY293558). For example, the known ketone 4 was converted to either the (3SR,4aRS,6SR,8aRS)-alcohol 18 or the (3SR,4aRS,6RS,8aRS)-alcohol 21, the former via a stereoselective hydroboration reaction, the latter via a stereoselective enol ether hydrolysis followed by reduction. These C-6 epimeric alcohols were easily converted to a number of useful intermediates, e.g., aldehydes, bromides and iodides. If we used resolved ketone 4, then these intermediates could be obtained in optically active form. In either racemic or non-racemic form, these intermediates provided access to a number of diastereomerically pure amino acids that were difficult to obtain by earlier routes.

  DOI：

  10.1021/jo00104a051

文献信息

• [EN] ISOQUINOLINE-3-CARBOXYLIC ACID DERIVATIVES AS EXCITATORY AMINO ACID RECEPTOR ANTAGONISTS<br/>[FR] DERIVES D'ACIDE ISOQUINOLINE-3-CARBOXYLIQUE EN TANT QU'ANTAGONISTES DU RECEPTEUR D'ACIDE AMINE EXCITATEUR
  申请人：LILLY CO ELI

  公开号：WO2003082856A1

  公开（公告）日：2003-10-09

  The present invention provides a compound of Formula I, or a pharmaceutically acceptable salt thereof, pharmaceutical compositions comprising an effective amount of a compound of Formula I in combination with a suitable carrier, diluent, or excipient, and methods for treating neurological disorders and neurodegenerative diseases comprising administering to a patient in need thereof an effective amount of a compound of Formula I.

  本发明提供了一种化合物I的化合物，或其药用可接受的盐，包含化合物I的有效量与适当载体、稀释剂或赋形剂结合的药物组合物，以及治疗神经系统疾病和神经退行性疾病的方法，包括向需要的患者施用化合物I的有效量。
• [EN] EXCITATORY AMINO ACID RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DU RECEPTEUR D'ACIDE AMINE EXCITATEUR
  申请人：LILLY CO ELI

  公开号：WO2002053561A1

  公开（公告）日：2002-07-11

  The present invention provides novel pharmaceutically acceptable salts of the compounds of Formula (I) and Formula (Ia), as well as methods for using the pharmaceutically acceptable salts, and also provides processes for making compounds of Formula (I) and Formula (Ia), or the pharmaceutically acceptable salts thereof. Compounds of formula (I) and formula (Ia) are useful for the treatment of neurological disorders, especially migraine.

  本发明提供了化合物(I)和化合物(Ia)的新型药用可接受盐，以及使用药用可接受盐的方法，并提供制备化合物(I)和化合物(Ia)或其药用可接受盐的方法。化合物(I)和化合物(Ia)的用途为治疗神经系统疾病，特别是偏头痛。
• Selective iglur5 receptor antagonists
  申请人：——

  公开号：US20030055081A1

  公开（公告）日：2003-03-20

  The present invention provides compounds of formula (I): wherein W represents hydrogen, C 1 -C 4 alkyl, —CH 2 CO 2 H, or CO 2 H; and X represents hydrogen, C 1 -C 4 alkyl, —CH 2 CO 2 H, or CO 2 H; with the proviso that at least one of W or X must be other than hydrogen; or a prodrug or a pharmaceutically acceptable salt thereof; which are useful for treating migraine.

  本发明提供式（I）的化合物：其中W代表氢，C1-C4烷基，—CH2CO2H或CO2H；X代表氢，C1-C4烷基，—CH2CO2H或CO2H；但须满足W或X中至少有一个不是氢；或其前药或药学上可接受的盐；用于治疗偏头痛。
• Excitatory amino acid receptor antagonists
  申请人：——

  公开号：US20040082606A1

  公开（公告）日：2004-04-29

  The present invention provides novel pharmaceutically acceptable salts of the compounds of Formula (I) and Formula (Ia), as well as methods for using the pharmaceutically acceptable salts, and also provides processes for making compounds of Formula (I) and Formula (Ia), or the pharmaceutically acceptable salts thereof. Compounds of formula (I) and formula (Ia) are useful for the treatment of neurological disorders, especially migraine.

  本发明提供了式(I)和式(Ia)化合物的新型药学上可接受的盐，以及使用药学上可接受的盐的方法，还提供了式(I)和式(Ia)化合物或其药学上可接受的盐的制造工艺。式（I）和式（Ia）化合物可用于治疗神经系统疾病，尤其是偏头痛。
• [Tetrazoyl-11C]LY202157 synthesis forin vivo studies of the NMDA receptor channel complex
  作者：M. Ponchant、H. Galéa、M. Bottlaender、C. Coulon、C. Fuseau、M. Ottaviani、C. Crouzel

  DOI：10.1002/1099-1344(200011)43:13<1311::aid-jlcr422>3.0.co;2-b

  日期：2000.11

  [Tetrazoyl-C-11]LY202157 8 was prepared via a three step synthesis from ethyl (3S,4aR,6S,8aR)-6-bromomethyl-2-methoxycarbonyl 1,2,3,4,4a,5,6,7,8,8a-decahydroisoquinol This bromo precursor was reacted with [C-11]hydrogen cyanide affording the corresponding [C-11]nitrile. Conversion to the tetrazole was achieved by treatment with azidotributyltin followed by hydrolysis with 6N hydrochloric acid at 200 degreesC. After HPLC purification and analytical HPLC control, more than 370 MBq (10 mCi) of [tetrazoyl-C-11] LY202157 were obtained after an overall 60 minute synthesis time with 38% yield (EOB) and specific activity of 25.9 GBq/mu mol (700 mCi/mu mol). Ex vivo biological studies showed that the [tetrazoyl-C-11] LY202157 did not cross the brain blood barrier.