(+)-(R)-2-(3-hydroxy-2-methylpropyl)-1H-isoindole-1,3(2H)-dione | 267402-35-7

• 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: (+)-(R)-2-(3-hydroxy-2-methylpropyl)-1H-isoindole-1,3(2H)-dione
• 英文别名: (R)-2-(3-hydroxy-2-methylpropyl)-1H-isoindole-1,3(2H)-dione；(R)-3-phthaloylamino-2-methylpropan-1-ol；2-[(2R)-3-hydroxy-2-methylpropyl]isoindole-1,3-dione
• CAS: 267402-35-7
• 化学式: C₁₂H₁₃NO₃
• 分子量: 219.24
• InChiKey: DVEGUJIAVRCLNH-MRVPVSSYSA-N

物化性质

• 沸点：
  378.6±25.0 °C(Predicted)
• 密度：
  1.281±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  57.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (+)-(R)-2-(3-hydroxy-2-methylpropyl)-1H-isoindole-1,3(2H)-dione 在 氢溴酸 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 8.0h， 生成 (-)-(R)-2-[3-(2,6-dimethylphenoxy)-2-methylpropyl]-1H-isoindole-1,3(2H)-dione
  参考文献：
  名称：

  Homologation of mexiletine alkyl chain and stereoselective blockade of skeletal muscle sodium channels

  摘要：

  The optical isomers (-)-(S)- and (+)-(R)-3-(2,6-dimethylphenoxy)-2-methyl-1-propanamine (Me2), homologues of the antiarrhythmic and antimyotonic drug mexiletine (Mex), were synthesized and assayed as new potential antimyotonic agents. As observed with Mex, Me2 exhibits an enantioselective behaviour. Tests carried out on sodium currents of single muscle fibres of Rana esculenta demonstrated that (-)-(S)- and (+)-(R)-Me2 were less potent than Mex in producing tonic block, but showed a higher use-dependent block. (-)-(S)-Me2 and (-)-(R)-Mex were also used to study the excitability of muscle fibres of myotonic ADR mice, a phenotype of a recessive form of low C-Cl myotonia. (-)-(S)-Me2 reduced spontaneous discharges and after discharges better than (-)-(R)-Mex in agreement with the use-dependent block of sodium currents. (C) 2000 Editions scientifiques et medicales Elsevier SAS.

  DOI：

  10.1016/s0223-5234(00)00115-x
• 作为产物：
  描述：

  2-((R)-2-methyl-3-(tetrahydro-2H-pyran-2-yloxy)propyl)isoindoline-1,3-dione 在 4-甲基苯磺酸吡啶 作用下， 以 乙醇 为溶剂， 反应 3.0h， 生成 (+)-(R)-2-(3-hydroxy-2-methylpropyl)-1H-isoindole-1,3(2H)-dione
  参考文献：
  名称：

  The First Potent Inhibitors for Human Glutaminyl Cyclase:  Synthesis and Structure−Activity Relationship

  摘要：

  The first effective inhibitors for human glutaminyl cyclase (QC) are described. The structures are developed by applying a ligand-based optimization approach starting from imidazole. Screening of derivatives of that heterocycle led to compounds of the imidazol-1-yl-alkyl thiourea type as a lead scaffold. A library of thiourea derivatives was synthesized, resulting in an inhibitory improvement by 2 orders of magnitude, leading to 1-(3-(1H-imidazol-1-yl)propyl)-3-(3,4-dimethoxyphenyl)thiourea as a potent inhibitor. Systematic exploitation of the scaffold revealed a strong impact on the inhibitory efficacy and resulted in the development of imidazole-propyl-thioamides as another new class of potent inhibitors. A flexible alignment of the most potent compounds of the thioamide and thiourea class and a QC substrate revealed a good match of characteristic features of the molecules, which suggests a similar binding mode of both inhibitors and the substrate to the active site of QC.

  DOI：

  10.1021/jm050756e

文献信息

• Tunable <i>P</i>-Chiral Bisdihydrobenzooxaphosphole Ligands for Enantioselective Hydroformylation
  作者：Renchang Tan、Xin Zheng、Bo Qu、C. Avery Sader、Keith R. Fandrick、Chris H. Senanayake、Xumu Zhang

  DOI：10.1021/acs.orglett.6b01452

  日期：2016.7.15

  Air-stable and tunable chiral bisdihydrobenzooxaphosphole ligands (BIBOPs) were employed in rhodium-catalyzed asymmetric hydroformylation of various terminal olefins with excellent conversions (>99%), moderate-to-excellent enantioselectivities (up to 95:5 er), and branched to linear ratios (b:l) of up to 400.

  空气稳定且可调的手性双二氢苯并恶唑磷配体（BIBOP）用于铑催化的各种末端烯烃的不对称加氢甲酰化反应，具有出色的转化率（> 99％），中等至优异的对映选择性（高达95：5 er），并分支为线性比（b：l）高达400。
• Synthesis of (R)- and (S)-isomers of 2-methylspermidine
  作者：Maxim A. Khomutov、Alexander O. Chizhov、Sergey N. Kochetkov、Alex R. Khomutov

  DOI：10.1016/j.mencom.2019.11.025

  日期：2019.11

  The title compounds, (R)- and (S)-isomers of 1,8-diamino-2-methyl-4-azaoctane, were prepared from commercially available enantiomers of 3-bromo-2-methylpropan-1-ol, each in six steps and good overall yields.
• The First Potent Inhibitors for Human Glutaminyl Cyclase:  Synthesis and Structure−Activity Relationship
  作者：Mirko Buchholz、Ulrich Heiser、Stephan Schilling、André J. Niestroj、Katrin Zunkel、Hans-Ulrich Demuth

  DOI：10.1021/jm050756e

  日期：2006.1.1

  The first effective inhibitors for human glutaminyl cyclase (QC) are described. The structures are developed by applying a ligand-based optimization approach starting from imidazole. Screening of derivatives of that heterocycle led to compounds of the imidazol-1-yl-alkyl thiourea type as a lead scaffold. A library of thiourea derivatives was synthesized, resulting in an inhibitory improvement by 2 orders of magnitude, leading to 1-(3-(1H-imidazol-1-yl)propyl)-3-(3,4-dimethoxyphenyl)thiourea as a potent inhibitor. Systematic exploitation of the scaffold revealed a strong impact on the inhibitory efficacy and resulted in the development of imidazole-propyl-thioamides as another new class of potent inhibitors. A flexible alignment of the most potent compounds of the thioamide and thiourea class and a QC substrate revealed a good match of characteristic features of the molecules, which suggests a similar binding mode of both inhibitors and the substrate to the active site of QC.
• Homologation of mexiletine alkyl chain and stereoselective blockade of skeletal muscle sodium channels
  作者：A Duranti

  DOI：10.1016/s0223-5234(00)00115-x

  日期：2000.1

  The optical isomers (-)-(S)- and (+)-(R)-3-(2,6-dimethylphenoxy)-2-methyl-1-propanamine (Me2), homologues of the antiarrhythmic and antimyotonic drug mexiletine (Mex), were synthesized and assayed as new potential antimyotonic agents. As observed with Mex, Me2 exhibits an enantioselective behaviour. Tests carried out on sodium currents of single muscle fibres of Rana esculenta demonstrated that (-)-(S)- and (+)-(R)-Me2 were less potent than Mex in producing tonic block, but showed a higher use-dependent block. (-)-(S)-Me2 and (-)-(R)-Mex were also used to study the excitability of muscle fibres of myotonic ADR mice, a phenotype of a recessive form of low C-Cl myotonia. (-)-(S)-Me2 reduced spontaneous discharges and after discharges better than (-)-(R)-Mex in agreement with the use-dependent block of sodium currents. (C) 2000 Editions scientifiques et medicales Elsevier SAS.