(3aR,7aR)-2-(4-amino-2-chlorophenyl)-3a,4,5,6,7,7a-hexahydroisoindole-1,3-dione

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (3aR,7aR)-2-(4-amino-2-chlorophenyl)-3a,4,5,6,7,7a-hexahydroisoindole-1,3-dione
• 化学式: C₁₄H₁₅ClN₂O₂
• 分子量: 278.738
• InChiKey: CLQZERAISIDQOF-NXEZZACHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  19.0
• 可旋转键数：
  1.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  63.4
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  3-甲基-2-糠酸 、 (3aR,7aR)-2-(4-amino-2-chlorophenyl)-3a,4,5,6,7,7a-hexahydroisoindole-1,3-dione 在 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 为溶剂， 生成 N-[4-[(3aR,7aR)-1,3-dioxo-3a,4,5,6,7,7a-hexahydroisoindol-2-yl]-3-chlorophenyl]-3-methylfuran-2-carboxamide
  参考文献：
  名称：

  Lead optimization of the VU0486321 series of mGlu1 PAMs. Part 3. Engineering plasma stability by discovery and optimization of isoindolinone analogs

  摘要：

  This Letter describes the further lead optimization of the VU0486321 series of mGlu(1) positive allosteric modulators (PAMs), focused on addressing the recurrent issue of plasma instability of the phthalimide moiety. Here, we evaluated a number of phthalimide bioisosteres, and ultimately identified isoindolinones as the ideal replacement that effectively address plasma instability, while maintaining acceptable mGlu(1) PAM potency, DMPK profile, CNS penetration and mGluR selectivity. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.03.031
• 作为产物：
  描述：

  3-氯-4-氟硝基苯 在 palladium on activated charcoal 、 氢气 、 potassium carbonate 作用下， 以 乙醇 、 乙腈 为溶剂， 生成 (3aR,7aR)-2-(4-amino-2-chlorophenyl)-3a,4,5,6,7,7a-hexahydroisoindole-1,3-dione
  参考文献：
  名称：

  Lead optimization of the VU0486321 series of mGlu1 PAMs. Part 3. Engineering plasma stability by discovery and optimization of isoindolinone analogs

  摘要：

  This Letter describes the further lead optimization of the VU0486321 series of mGlu(1) positive allosteric modulators (PAMs), focused on addressing the recurrent issue of plasma instability of the phthalimide moiety. Here, we evaluated a number of phthalimide bioisosteres, and ultimately identified isoindolinones as the ideal replacement that effectively address plasma instability, while maintaining acceptable mGlu(1) PAM potency, DMPK profile, CNS penetration and mGluR selectivity. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2016.03.031

文献信息

• Lead optimization of the VU0486321 series of mGlu1 PAMs. Part 3. Engineering plasma stability by discovery and optimization of isoindolinone analogs
  作者：Pedro M. Garcia-Barrantes、Hyekyung P. Cho、Anna L. Blobaum、Colleen M. Niswender、P. Jeffrey Conn、Craig W. Lindsley

  DOI：10.1016/j.bmcl.2016.03.031

  日期：2016.4

  This Letter describes the further lead optimization of the VU0486321 series of mGlu(1) positive allosteric modulators (PAMs), focused on addressing the recurrent issue of plasma instability of the phthalimide moiety. Here, we evaluated a number of phthalimide bioisosteres, and ultimately identified isoindolinones as the ideal replacement that effectively address plasma instability, while maintaining acceptable mGlu(1) PAM potency, DMPK profile, CNS penetration and mGluR selectivity. (C) 2016 Elsevier Ltd. All rights reserved.