(-)-(R)-2-(3-bromo-2-methylpropyl)-1H-isoindole-1,3(2H)-dione | 267402-37-9

• 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-bromo-2-methylpropyl)-1H-isoindole-1,3(2H)-dione
• 英文别名: (R)-2-(3-bromo-2-methylpropyl)isoindoline-1,3-dione；2-[(2R)-3-bromo-2-methylpropyl]isoindole-1,3-dione
• CAS: 267402-37-9
• 化学式: C₁₂H₁₂BrNO₂
• 分子量: 282.137
• InChiKey: NAWIPGKAGCJNBR-QMMMGPOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 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：
  37.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2,6-二甲基苯酚 、 (-)-(R)-2-(3-bromo-2-methylpropyl)-1H-isoindole-1,3(2H)-dione 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 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：

  (+)-(R)-2-(3-hydroxy-2-methylpropyl)-1H-isoindole-1,3(2H)-dione 在 氢溴酸 作用下， 以 甲苯 为溶剂， 反应 5.0h， 生成 (-)-(R)-2-(3-bromo-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

文献信息

• [EN] MACROCYCLIC COMPOUNDS AS TRK KINASE INHIBITORS<br/>[FR] COMPOSÉS MACROCYCLIQUES EN TANT QU'INHIBITEURS DE KINASE TRK
  申请人：ARRAY BIOPHARMA INC

  公开号：WO2011146336A1

  公开（公告）日：2011-11-24

  Compounds of Formula I: and pharmaceutically acceptable salts thereof, wherein ring A, ring B, W, m, D, R2, R2a, R3, R3a, and Z are as defined herein, are inhibitors of Trk kinases and are useful in the treatment of pain, cancer, inflammation, neurodegenerative diseases and certain infectious diseases.

  式I的化合物及其药用可接受盐，其中环A、环B、W、m、D、R2、R2a、R3、R3a和Z按照定义，是Trk激酶的抑制剂，可用于治疗疼痛、癌症、炎症、神经退行性疾病和某些传染病。
• MACROCYCLIC COMPOUNDS AS TRK KINASE INHIBITORS
  申请人：Andrews Steven Wade

  公开号：US20130203776A1

  公开（公告）日：2013-08-08

  Compounds of Formula I: and pharmaceutically acceptable salts thereof, wherein ring A, ring B, W, m, D, R 2 , R 2a , R 3 , R 3a , and Z are as defined herein, are inhibitors of Trk kinases and are useful in the treatment of pain, cancer, inflammation, neurodegenerative diseases and certain infectious diseases.

  公式I的化合物和药物可接受的盐，其中环A、环B、W、m、D、R2、R2a、R3、R3a和Z的定义如此处所述，是Trk激酶的抑制剂，并且在治疗疼痛、癌症、炎症、神经退行性疾病和某些传染病方面很有用。
• Macrocyclic compounds as Trk kinase inhibitors
  申请人：Andrews Steven Wade

  公开号：US08933084B2

  公开（公告）日：2015-01-13

  Compounds of Formula I: and pharmaceutically acceptable salts thereof, wherein ring A, ring B, W, m, D, R2, R2a, R3, R3a, and Z are as defined herein, are inhibitors of Trk kinases and are useful in the treatment of pain, cancer, inflammation, neurodegenerative diseases and certain infectious diseases.

  化合物I的公式及其药物可接受的盐，其中环A、环B、W、m、D、R2、R2a、R3、R3a和Z的定义如本文所述，是Trk激酶的抑制剂，并可用于治疗疼痛、癌症、炎症、神经退行性疾病和某些传染病。
• Macrocyclic compounds as TRK kinase inhibitors
  申请人：Array Biopharma, Inc.

  公开号：EP2918588A1

  公开（公告）日：2015-09-16

  Compounds of Formula I: and pharmaceutically acceptable salts thereof, wherein ring A, ring B, W, m, D, R2, R2a, R3, R3a, and Z are as defined herein, are inhibitors of Trk kinases and are useful in the treatment of pain, cancer, inflammation, neurodegenerative diseases and certain infectious diseases.

  式 I 的化合物： 及其药学上可接受的盐类，其中环 A、环 B、W、m、D、R2、R2a、R3、R3a 和 Z 如本文所定义，是 Trk 激酶的抑制剂，可用于治疗疼痛、癌症、炎症、神经退行性疾病和某些传染性疾病。
• EP3205654A1
  申请人：——

  公开号：EP3205654A1

  公开（公告）日：2017-08-16