diethyl (1S,2S,5R,6S)-2-acetamidospiro[bicyclo[3.1.0]hexane-4,1'-cyclopropane]-2,6-dicarboxylate | 1448707-60-5

• 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: diethyl (1S,2S,5R,6S)-2-acetamidospiro[bicyclo[3.1.0]hexane-4,1'-cyclopropane]-2,6-dicarboxylate
• 英文别名: diethyl (1S,2S,5R,6S)-2-acetamidospiro[bicyclo[3.1.0]-hexane-4,1′-cyclopropane]-2,6-dicarboxylate
• CAS: 1448707-60-5
• 化学式: C₁₆H₂₃NO₅
• 分子量: 309.362
• InChiKey: JRGYKBDBEUBGSE-OVZMXSCWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  81.7
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  diethyl (1S,2S,5R,6S)-2-acetamidospiro[bicyclo[3.1.0]hexane-4,1'-cyclopropane]-2,6-dicarboxylate 在 sodium hydroxide 作用下， 反应 141.0h， 以795 mg的产率得到LY-2934747
  参考文献：
  名称：

  MGLU 2/3 AGONISTS

  摘要：

  本发明提供了一种在治疗神经系统或精神疾病中有用的新型mGlu2/3激动剂。

  公开号：

  US20130197079A1
• 作为产物：
  描述：

  di-tert-butyl (1S,2S,5R,6R)-2-(tert-butoxycarbonylamino)-4-oxo-bicyclo[3.1.0]hexane-2,6-dicarboxylate 在 氯化亚砜 、 diethylzinc 、 sodium hexamethyldisilazane 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 正庚烷 、 二氯甲烷 为溶剂， 反应 49.5h， 生成 diethyl (1S,2S,5R,6S)-2-acetamidospiro[bicyclo[3.1.0]hexane-4,1'-cyclopropane]-2,6-dicarboxylate
  参考文献：
  名称：

  MGLU 2/3 AGONISTS

  摘要：

  本发明提供了一种在治疗神经系统或精神疾病中有用的新型mGlu2/3激动剂。

  公开号：

  US20130197079A1

文献信息

• MGlu 2/3 agonists
  申请人：Eli Lilly and Company

  公开号：US08575214B2

  公开（公告）日：2013-11-05

  The present invention provides novel mGlu2/3 agonists of the formula wherein R1, R2, and R3 are as defined herein, for use in the treatment of neurological or psychiatric disorders.

  本发明提供了一种新型的mGlu2/3激动剂，其化学式为其中R1、R2和R3的定义如本文所述，用于治疗神经系统或精神障碍。
• Synthesis and Pharmacological Characterization of C4-Disubstituted Analogs of 1<i>S</i>,2<i>S</i>,5<i>R</i>,6<i>S</i>-2-Aminobicyclo[3.1.0]hexane-2,6-dicarboxylate: Identification of a Potent, Selective Metabotropic Glutamate Receptor Agonist and Determination of Agonist-Bound Human mGlu2 and mGlu3 Amino Terminal Domain Structures
  作者：James A. Monn、Lourdes Prieto、Lorena Taboada、Concepcion Pedregal、Junliang Hao、Matt R. Reinhard、Steven S. Henry、Paul J. Goldsmith、Christopher D. Beadle、Lesley Walton、Teresa Man、Helene Rudyk、Barry Clark、David Tupper、S. Richard Baker、Carlos Lamas、Carlos Montero、Alicia Marcos、Jaime Blanco、Mark Bures、David K. Clawson、Shane Atwell、Frances Lu、Jing Wang、Marijane Russell、Beverly A. Heinz、Xushan Wang、Joan H. Carter、Chuanxi Xiang、John T. Catlow、Steven Swanson、Helen Sanger、Lisa M. Broad、Michael P. Johnson、Kelly L. Knopp、Rosa M. A. Simmons、Bryan G. Johnson、David B. Shaw、David L. McKinzie

  DOI：10.1021/jm501612y

  日期：2015.2.26

  As part of our ongoing research to identify novel agents acting at metabotropic glutamate 2 (mGlu2) and 3 (mGlu3) receptors, we have previously reported the identification of the C4(alpha)-methyl analog of mGlu2/3 receptor agonist 1 (LY354740). This molecule, 1S,2S,4R,5R,6S-2-amino-4-methylbicyclo[3.1.0]hexane-2,6-dicarboxylate 2 (LY541850), exhibited an unexpected mGlu2 agonist/mGlu3 antagonist pharmacological profile, whereas the C4 beta-methyl diastereomer (3) possessed dual mGlu2/3 receptor agonist activity. We have now further explored this structure-activity relationship through the preparation of cyclic and acyclic C4-disubstituted analogs of 1, leading to the identification of C4-spirocyclopropane 5 (LY2934747), a novel, potent, and systemically bioavailable mGlu2/3 receptor agonist which exhibits both antipsychotic and analgesic properties in vivo. In addition, through the combined use of proteinligand X-ray crystallography employing recombinant human mGlu2/3 receptor amino terminal domains, molecular modeling, and site-directed mutagenesis, a molecular basis for the observed pharmacological profile of compound 2 is proposed.
• US8575214B2
  申请人：——

  公开号：US8575214B2

  公开（公告）日：2013-11-05
• [EN] MGLU 2/3 AGONISTS<br/>[FR] AGONISTES MGLU 2/3
  申请人：LILLY CO ELI

  公开号：WO2013116174A1

  公开（公告）日：2013-08-08

  The present invention provides novel mGlu2/3 agonists of formula (I) useful in the treatment of neurological or psychiatric disorders.
• MGLU 2/3 AGONISTS
  申请人：Eli Lily and Company

  公开号：US20130197079A1

  公开（公告）日：2013-08-01

  The present invention provides novel mGlu2/3 agonists useful in the treatment of neurological or psychiatric disorders.

  本发明提供了一种在治疗神经系统或精神疾病中有用的新型mGlu2/3激动剂。