5-hydroxy-2-isopropylisoindolin-1-one

• 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-isopropylisoindolin-1-one
• 英文别名: 5-hydroxy-2-propan-2-yl-3H-isoindol-1-one
• 化学式: C₁₁H₁₃NO₂
• 分子量: 191.23
• InChiKey: YRNRMYFHXRSFKD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-hydroxy-2-isopropylisoindolin-1-one 、 methyl 3′-(bromomethyl)-4-chlorobiphenyl-3-carboxylate 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 生成 methyl 2-chloro-5-[3-[(1-oxo-2-propan-2-yl-3H-isoindol-5-yl)oxymethyl]phenyl]benzoate
  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 在 溶剂黄146 、 锌 作用下， 以 甲苯 为溶剂， 反应 12.08h， 生成 5-hydroxy-2-isopropylisoindolin-1-one
  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

文献信息

• A Short and Efficient Synthesis of Isoindolin-1-ones
  作者：Takayuki Tsuritani、Satoshi Kii、Atsushi Akao、Kimihiko Sato、Nobuaki Nonoyama、Toshiaki Mase、Nobuyoshi Yasuda

  DOI：10.1055/s-2006-933114

  日期：——

  Here, we report a short and efficient synthesis of isoindolin-1-ones. Base-induced cyclization of o-hydroxymethyl-benzamides, which was easily prepared from the corresponding phthalides and amines, led predominantly to N-alkylation in good yield. The reaction proceeded under mild conditions and bromine and nitrile substituents were tolerated. The selectivity is explained by HASB theory.

  在这里，我们报告了 isoindolin-1-ones 的简短而有效的合成。邻羟甲基苯甲酰胺的碱诱导环化很容易由相应的邻苯二甲醚和胺制备，主要导致 N-烷基化，收率良好。反应在温和的条件下进行，并且可以耐受溴和腈取代基。HASB 理论解释了选择性。