5-hydroxy-2-isobutylisoindoline-1,3-dione | 3975-52-8

• 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: 5-hydroxy-2-isobutylisoindoline-1,3-dione
• 英文别名: 4-hydroxy-N-isobutylphthalimide；5-hydroxy-2-(2-methylpropyl)isoindole-1,3-dione
• CAS: 3975-52-8
• 化学式: C₁₂H₁₃NO₃
• 分子量: 219.24
• InChiKey: KUSVONSTRXHWDH-UHFFFAOYSA-N

物化性质

• 熔点：
  144-146 °C
• 沸点：
  378.4±25.0 °C(Predicted)
• 密度：
  1.274±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  16
• 可旋转键数：
  2
• 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：

  5-hydroxy-2-isobutylisoindoline-1,3-dione 在 水 、 potassium carbonate 、 溶剂黄146 、 lithium hydroxide 、 锌 作用下， 以 四氢呋喃 、 丙酮 为溶剂， 反应 0.08h， 生成 4-chloro-3'-((2-isobutyl-1-oxoisoindolin-5-yloxy)methyl)biphenyl-3-carboxylic acid
  参考文献：
  名称：

  Design and Synthesis of an Orally Active Metabotropic Glutamate Receptor Subtype-2 (mGluR2) Positive Allosteric Modulator (PAM) That Decreases Cocaine Self-Administration in Rats

  摘要：

  The modification of 3'((2-cyclopentyl-6,7-dimethyl-1-oxo-2,3-dihydro-1 H-inden-5-yloxy)methyl)biphenyl 4-carboxylic acid (BINA, 1) by incorporating heteroatoms into the structure and replacing the cyclopentyl moiety led to the development of new mGluR2 positive allosteric modulators (PAMs) with optimized potency and superior druglike properties These analogues are more potent than 1 in vitro and are highly selective for mGluR2 vs other mGluR subtypes They have significantly improved pharmacokinetic (PK) properties, with excellent oral bioavailability and brain penetration The benzisothiazol-3-one derivative 14 decreased cocaine self-administration in rats, providing proof-of-concept for the use of mGluR2 PAMs for the treatment of cocaine dependence

  DOI：

  10.1021/jm1012165
• 作为产物：
  描述：

  4-羟基邻苯二甲酸 以 甲苯 为溶剂， 反应 12.0h， 生成 5-hydroxy-2-isobutylisoindoline-1,3-dione
  参考文献：
  名称：

  Design and Synthesis of an Orally Active Metabotropic Glutamate Receptor Subtype-2 (mGluR2) Positive Allosteric Modulator (PAM) That Decreases Cocaine Self-Administration in Rats

  摘要：

  The modification of 3'((2-cyclopentyl-6,7-dimethyl-1-oxo-2,3-dihydro-1 H-inden-5-yloxy)methyl)biphenyl 4-carboxylic acid (BINA, 1) by incorporating heteroatoms into the structure and replacing the cyclopentyl moiety led to the development of new mGluR2 positive allosteric modulators (PAMs) with optimized potency and superior druglike properties These analogues are more potent than 1 in vitro and are highly selective for mGluR2 vs other mGluR subtypes They have significantly improved pharmacokinetic (PK) properties, with excellent oral bioavailability and brain penetration The benzisothiazol-3-one derivative 14 decreased cocaine self-administration in rats, providing proof-of-concept for the use of mGluR2 PAMs for the treatment of cocaine dependence

  DOI：

  10.1021/jm1012165
• 作为试剂：
  描述：

  4-乙酰氧基邻苯二甲酸酐 、 异丁胺 、 对甲苯磺酸 在 5-hydroxy-2-isobutylisoindoline-1,3-dione 、 乙酸乙酯 、 Brine 、 magnesium sulfate 、 环己烷 作用下， 以 甲苯 为溶剂， 20.0~140.0 ℃ 、266.64 kPa 条件下， 反应 5.5h， 以4.0 g of 4-hydroxy-N-isobutylphthalimide are thus obtained in the form of a white solid的产率得到5-hydroxy-2-isobutylisoindoline-1,3-dione
  参考文献：
  名称：

  Isoindolone derivatives, preparation process and intermediates of this process, their use as medicaments, and pharmaceutical compositions comprising them

  摘要：

  本发明涉及公式I中R1至R6具有权利要求中所述含义的新型异吲哚酮衍生物。这些创新化合物适用于抗心律失常药物，具有心脏保护成分，可用于预防心肌梗死和治疗心肌梗死以及治疗心绞痛。它们还能以预防性方式抑制与缺血性损伤发展相关的病理生理过程，特别是在缺血性心脏心律失常和心力衰竭的触发方面。

  公开号：

  US20060148880A1

文献信息

• [EN] N- ((3-OXO2, 3-DIHYDRO-1H-ISOINDOL-1-YL) ACETYL) GUANIDINE DERIVATIVES AS NHE-1 INHIBITORS FOR THE TREATMENT OF INFARCTION AND ANGINA PECTORIS<br/>[FR] DERIVES DE GUANIDINE N- ((3-OXO-2, 3-DIHYDRO-1H-ISOINDOLE-1-YLE) ACETYLE) COMME INHIBITEURS DE NHE-1 POUR TRAITER L'INFARCTUS ET L'ANGINE PECTORALE
  申请人：AVENTIS PHARMA GMBH

  公开号：WO2003101450A1

  公开（公告）日：2003-12-11

  Isoindolone derivatives, preparation process and intermediates of this process, their use as medicaments, and pharmaceutical compositions comprising them. The present invention relates to the novel isoindolone derivatives of the Formula (I), in which R1 to R6 have the meanings stated in the claims. The inventive compounds are suitable as antiarrhythmic medicaments with a cardioprotective component for infarction prophylaxis and infarction treatment and for the treatment of angina pectoris. They also inhibit in a preventive manner the pathophysiological processes associated with the development of ischemia-induced damage, in particular in the triggering of ischemia-induced cardiac arrhythmias and of heart failure.

  异吲哚酮衍生物、制备方法及该过程的中间体，它们作为药物的用途，以及包括它们的药物组合物。本发明涉及新型异吲哚酮衍生物的公式(I)，其中R1至R6具有权利要求中所述的含义。这些创新化合物适用于作为具有心脏保护成分的抗心律失常药物，用于心梗预防和心梗治疗以及心绞痛的治疗。它们还以预防方式抑制与缺血性损伤发展相关的病理生理过程，特别是在诱发缺血性心脏心律失常和心力衰竭方面。
• N-((3-OXO-2,3-DIHYDRO-1H-ISOINDOL-1-YL)ACETYL)GUANIDINE DERIVATIVES AS NHE1-INHIBITORS FOR THE TREATMENT OF INFARCTION AND ANGINA PECTORIS
  申请人：Aventis Pharma Deutschland GmbH

  公开号：EP1528923A1

  公开（公告）日：2005-05-11
• US7078428B2
  申请人：——

  公开号：US7078428B2

  公开（公告）日：2006-07-18
• US7589117B2
  申请人：——

  公开号：US7589117B2

  公开（公告）日：2009-09-15
• Isoindolone derivatives, preparation process and intermediates of this process, their use as medicaments, and pharmaceutical compositions comprising them
  申请人：Aventis Pharma Deuschland GmbH

  公开号：US20040048916A1

  公开（公告）日：2004-03-11

  The present invention relates to the novel isoindolone derivatives of the formula I 1 in which R1 to R6 have the meanings stated in the claims. The inventive compounds are suitable as antiarrhythmic medicaments with a cardioprotective component for infarction prophylaxis and infarction treatment and for the treatment of angina pectoris. They also inhibit in a preventive manner the pathophysiological processes associated with the development of ischemia-induced damage, in particular in the triggering of ischemia-induced cardiac arrhythmias and of heart failure.

  本发明涉及具有以下式I1的新异吲哚酮衍生物，其中R1至R6具有权利要求中所述的含义。这些创新化合物适用于作为抗心律失常药物，具有心脏保护成分，用于梗死预防和梗死治疗以及心绞痛的治疗。它们还以一种预防性方式抑制与缺血性损伤发展相关的病理生理过程，特别是在诱发缺血性心律失常和心力衰竭的发生中。