2,3-dihydro-5-(4-morpholinyl)-1H-isoindole | 850876-30-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 2,3-dihydro-5-(4-morpholinyl)-1H-isoindole
• 英文别名: 4-(2,3-dihydro-1H-isoindol-5-yl)morpholine
• CAS: 850876-30-1
• 化学式: C₁₂H₁₆N₂O
• 分子量: 204.272
• InChiKey: YDQNBBMAXWCRFN-UHFFFAOYSA-N

物化性质

• 沸点：
  387.2±42.0 °C(Predicted)
• 密度：
  1.148±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  24.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (S)-2-(1-甲基-2,2,2-三氟乙氧基)-5-甲基磺酰基苯甲酸 、 2,3-dihydro-5-(4-morpholinyl)-1H-isoindole 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 [5-methanesulfonyl-2-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-phenyl]-(5-morpholin-4-yl-1,3-dihydro-isoindol-2-yl)-methanone
  参考文献：
  名称：

  Discovery of benzoylisoindolines as a novel class of potent, selective and orally active GlyT1 inhibitors

  摘要：

  Benzoylisoindolines were discovered as a novel structural class of GlyT1 inhibitors. SAR studies and subsequent lead optimization efforts focused primarily on addressing hERG liability and on improving in vivo efficacy resulted in the identification of potent GlyT1 inhibitors displaying excellent selectivity and in vivo PD and PK profiles. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.09.124
• 作为产物：
  描述：

  1,1-dimethylethyl 1,3-dihydro-5 -(4-morpholinyl)-2H-isoindole-2-carboxylate 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 生成 2,3-dihydro-5-(4-morpholinyl)-1H-isoindole
  参考文献：
  名称：

  Discovery of benzoylisoindolines as a novel class of potent, selective and orally active GlyT1 inhibitors

  摘要：

  Benzoylisoindolines were discovered as a novel structural class of GlyT1 inhibitors. SAR studies and subsequent lead optimization efforts focused primarily on addressing hERG liability and on improving in vivo efficacy resulted in the identification of potent GlyT1 inhibitors displaying excellent selectivity and in vivo PD and PK profiles. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.09.124

文献信息

• Macrocyclic compounds as inhibitors of viral replication
  申请人：Blatt M. Lawrence

  公开号：US20050267018A1

  公开（公告）日：2005-12-01

  The embodiments provide compounds of the general formulas I-XIX, as well as compositions, including pharmaceutical compositions, comprising a subject compound. The embodiments further provide treatment methods, including methods of treating flaviviral infection, including hepatitis C virus infection and methods of treating liver fibrosis, the methods generally involving administering to an individual in need thereof an effective amount of a subject compound or composition.

  该实施例提供了一般式I-XIX的化合物，以及包括药物组合在内的组合物，其中包括一种主体化合物。该实施例还提供了治疗方法，包括治疗黄病毒感染的方法，包括丙型肝炎病毒感染的方法和治疗肝纤维化的方法，这些方法通常涉及向需要的个体施用一种主体化合物或组合物的有效量。
• Investigating isoindoline, tetrahydroisoquinoline, and tetrahydrobenzazepine scaffolds for their sigma receptor binding properties
  作者：Kathryn Linkens、Hayden R. Schmidt、James J. Sahn、Andrew C. Kruse、Stephen F. Martin

  DOI：10.1016/j.ejmech.2018.02.024

  日期：2018.5

  Substituted norbenzomorphans are known to display high affinity and selectivity for the two sigma receptor (σR) subtypes. In order to study the effects of simplifying the structures of these compounds, a scaffold hopping strategy was used to design several novel sets of substituted isoindolines, tetrahydroisoquinolines and tetrahydro-2-benzazepines. The binding affinities of these new compounds for

  已知被取代的去甲苯并吗啡烷对两种sigma受体（σR）亚型表现出高亲和力和选择性。为了研究简化这些化合物的结构的效果，使用支架跳跃策略设计了几组新颖的取代异吲哚啉，四氢异喹啉和四氢-2-苯并ze庚因。确定了这些新化合物对sigma 1（σ1R）和sigma 2（σ2R）受体的结合亲和力，并鉴定了一些具有高亲和力的类似物（K i ≤25 nM）和对σ1R或σ2R的显着选择性（> 10倍）。通过建模研究预测了所选化合物与σ1R的优选结合方式，芳香环上的取代基和双环骨架氮原子的取代基的性质似乎影响了σ1R-优先配体的优选结合方向。
• Design and Synthesis of Highly Potent and Specific ABHD6 Inhibitors
  作者：Michael S. Malamas、Manjunath Lamani、Shrouq I. Farah、Khadijah A. Mohammad、Christina Yume Miyabe、Girija Rajarshi、Simiao Wu、Nikolai Zvonok、Honrao Chandrashekhar、JodiAnne Wood、Alexandros Makriyannis

  DOI：10.1002/cmdc.202100406

  日期：——

  isoindoline “signature templates” for ABHD6 with single-digit nanomolar inhibitory and specificity for the target, and >1000-fold selectivity against serine hydrolase MGL and FAAH. One ABHD6 inhibitor attenuated AMPA-induced glia activation and produced retinal neuroprotection in rats. These new ABHD6 inhibitors provide early leads to develop therapeutics for neuroprotection and the treatment of inflammation

  ABHD6 特征模板：我们报道了 ABHD6 的四氢异喹啉和异吲哚啉“特征模板”，对靶标具有个位数的纳摩尔抑制和特异性，以及对丝氨酸水解酶 MGL 和 FAAH 的 >1000 倍选择性。一种 ABHD6 抑制剂减弱了 AMPA 诱导的神经胶质细胞活化，并在大鼠中产生了视网膜神经保护作用。这些新的 ABHD6 抑制剂为开发神经保护以及炎症和糖尿病治疗疗法提供了早期线索。
• MACROCYCLIC COMPOUNDS AS INHIBITORS OF VIRAL REPLICATION
  申请人：BLATT LAWRENCE M.

  公开号：US20090286843A1

  公开（公告）日：2009-11-19

  The embodiments provide compounds of the general formulas I-XIX, as well as compositions, including pharmaceutical compositions, comprising a subject compound. The embodiments further provide treatment methods, including methods of treating flaviviral infection, including hepatitis C virus infection and methods of treating liver fibrosis, the methods generally involving administering to an individual in need thereof an effective amount of a subject compound or composition.

  该实施例提供了一般式I-XIX的化合物，以及包括药物组合物在内的组合物。该实施例还提供了治疗方法，包括治疗黄热病毒感染的方法，包括丙型肝炎病毒感染的方法和治疗肝纤维化的方法，通常涉及向需要治疗的个体施用所述化合物或组合物的有效量。
• Organic Compounds and their uses
  申请人：Britt Shawn D.

  公开号：US20100240638A1

  公开（公告）日：2010-09-23

  The present application describes macrocyclic compounds of formula (I) with NS3 protease inhibitory activity for treating hepatitis C virus infection.

  本申请描述了公式（I）的大环化合物，具有NS3蛋白酶抑制活性，用于治疗丙型肝炎病毒感染。