LY544344*HCl

• 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: LY544344*HCl
• 英文别名: (1S,2S,5R,6S)-2-[(2'S)-(2'-amino)propionyl]aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid hydrochloride；Talaglumetad hydrochloride；[(2S)-1-[[(1S,2S,5R,6S)-2,6-dicarboxy-2-bicyclo[3.1.0]hexanyl]amino]-1-oxopropan-2-yl]azanium;chloride
• 化学式: C₁₁H₁₆N₂O₅*ClH
• 分子量: 292.719
• InChiKey: TWZDLCLCMKMJPE-OAOSNHGPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.56
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  130
• 氢给体数：
  5
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (1S,2S,5R,6S)-2-氨基二环[3.1.0]己烷-2,6-二羧酸 在 盐酸 、 硫酸氢铵 作用下， 以 二氯甲烷 为溶剂， 反应 4.75h， 生成 LY544344*HCl
  参考文献：
  名称：

  Use of Silyl Ester and Enamine Protection for an Efficient Alternate Synthesis of (1S,2S,5R,6S)-2-[(2′S)-(2′-Amino)propionyl]aminobicyclo[3.1.0]hexane-2,6-dicarboxylic Acid Hydrochloride (LY544344·HCl)

  摘要：

  使用 N-(2-甲氧基羰基-1-甲基乙烯基)-1-丙氨酸钠盐 (6) 和 2-氨基双环[3.1.0]己烷-2,6-二甲酸 (1) 替代合成标题化合物 (5)已顺利完成。甲硅烷基酯保护的结合和烯胺保护基的使用可以省去几个加工步骤。

  DOI：

  10.1055/s-2006-942487

文献信息

• Prodrugs of excitatory amino acids
  申请人：Eli Lilly & Company

  公开号：EP1310480A1

  公开（公告）日：2003-05-14

  This invention relates to synthetic excitatory amino acid prodrugs according to formula (I) and processes for their preparation. The invention further relates to methods of using, and pharmaceutical compositions comprising, the coumpounds for the treatment of neurological disorders and psychiatric disorders.

  本发明涉及根据公式（I）的合成兴奋性氨基酸前药及其制备方法。本发明还涉及使用该化合物治疗神经系统障碍和精神障碍的方法和制药组合物。
• [EN] PRODRUGS OF EXCITATORY AMINO ACIDS<br/>[FR] PROMEDICAMENTS D'ACIDES AMINES EXCITATEURS
  申请人：LILLY CO ELI

  公开号：WO2002055485A1

  公开（公告）日：2002-07-18

  This invention relates to synthetic excitatory amino acid prodrugs of formula (I), wherein R11 is CO¿2?R?14 and R12¿ is hydrogen or fluoro; or R11 is hydrogen or fluoro and R12 is CO¿2?R?14; R13 and R14¿ are, independently, hydrogen, (1-10C) alkyl, (2-4C) alkenyl, aryl or arylalkyl; A is (Q)p; p is an integer from 1-10; and Q is independently selected, each time taken, from the group amino acyl; provided that the compound is not one in which R11 is CO¿2?R?14; R12, R13 and R14¿ are hydrogen; p is any integer from 1-10; and Q is independently selected, each time taken, from the group amino acyl; provided that the compound is not one in which R11 is CO¿2?R?14; R12, R13 and R14¿ are hydrogen; p is 1; and Q is L-alanyl; or a pharmaceutically acceptable salt thereof and processes for their preparation. The invention further relates to methods of using, and pharmaceutical compositions comprising, the compounds for the treatment of neurological disorders and psychiatric disorders.

  本发明涉及式(I)的合成兴奋性氨基酸前药，其中R11为CO2R14，R12为氢或氟；或R11为氢或氟，R12为CO2R14；R13和R14独立地为氢，(1-10C)烷基，(2-4C)烯基，芳基或芳基烷基；A为(Q)p；p为1-10的整数；Q每次均从氨基酰基组中独立选择；但化合物不是其中R11为CO2R14，R12，R13和R14为氢，p为1-10的任何整数，Q每次从氨基酰基组中独立选择；但化合物不是其中R11为CO2R14，R12，R13和R14为氢，p为1，Q为L-丙氨酰基；或其药学上可接受的盐及其制备方法。本发明还涉及使用该化合物和制药组合物治疗神经系统和精神系统疾病的方法。
• Therapy for psychoses combining an atypical antipsychotic and an mglu2/3 receptor agonist
  申请人：Johnson Glenn Bryan

  公开号：US20050192273A1

  公开（公告）日：2005-09-01

  The present invention provides for a pharmaceutical composition and methods for treating psychosis comprising the combination or a first component which is an atypical antipsychotic with a second component which is a mGlu2/3 receptor agonist. The present invention also provides for a pharmaceutical composition and method of treating a psychiatric disorder comprising the combination of a first component which is an atypical antipsychotic with a second component which is a compound which allosterically enhances receptor activity for mGlu2 and/or mGlu3.

  本发明提供了一种治疗精神病的药物组合物和方法，包括第一种成分（非典型抗精神病药）与第二种成分（mGlu2/3受体激动剂）的组合。本发明还提供了一种治疗精神病的药物组合物和方法，包括第一种成分（非典型抗精神病药）与第二种成分（异位增强 mGlu2 和/或 mGlu3 受体活性的化合物）的组合。
• An efficient synthesis of LY544344·HCl: a prodrug of mGluR2 agonist LY354740
  作者：D. Scott Coffey、Mai Khanh Hawk、Steven W. Pedersen、Radhe K. Vaid

  DOI：10.1016/j.tetlet.2005.08.144

  日期：2005.10

  LY544344-HCl was efficiently prepared in two steps from LY354740. The key step highlighted the in situ masking of the carboxylic acid groups as trimethylsilyl esters to facilitate an effective acylation reaction. (c) 2005 Elsevier Ltd. All rights reserved.
• Large Scale Deprotection of a <i>tert</i>-Butoxycarbonyl (Boc) Group Using Aqueous HCl and Acetone
  作者：D. Scott Coffey、Mai Khanh N. Hawk、Steven W. Pedersen,、Steven J. Ghera、Paul G. Marler、Paul N. Dodson、Michelle L. Lytle

  DOI：10.1021/op049842z

  日期：2004.11.1

  A procedure for tert-butoxycarbonyl (Boc) group removal using concentrated HCl and acetone was developed and utilized on multi-kilogram scale in the synthesis of LY544344(.)HCl (1). The details surrounding this procedure and the advantages offered by it are described herein.