5-hydroxy-2-(1-propyl)isoindole-1,3-dione | 3913-46-0

• 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-(1-propyl)isoindole-1,3-dione
• 英文别名: 5-hydroxy-2-propylisoindoline-1,3-dione；N-Propyl-5-hydroxy-phthalimid；5-Hydroxy-2-propylisoindole-1,3-dione
• CAS: 3913-46-0
• 化学式: C₁₁H₁₁NO₃
• 分子量: 205.213
• InChiKey: RHUYJPRDQPJFPB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 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-(1-propyl)isoindole-1,3-dione 在 溶剂黄146 、 锌 作用下， 以 甲苯 为溶剂， 反应 0.08h， 以22%的产率得到5-hydroxy-2-propylisoindolin-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
• 作为产物：
  描述：

  4-羟基邻苯二甲酸 以 甲苯 为溶剂， 200.0 ℃ 、79.99 Pa 条件下， 生成 5-hydroxy-2-(1-propyl)isoindole-1,3-dione
  参考文献：
  名称：

  [（N-烷基-1,3-二氧代-1H，3H-异吲哚-5-基）氧基]链烷酸，[（N-烷基-1-氧代-1H，3H-异吲哚-5-基]氧基的作用]丁酸和相关衍生物对原代星形胶质细胞培养物中氯的流入。

  摘要：

  业已表明，抑制氯离子流入并因此降低脑灰质星形细胞中主要细胞类型的细胞内氯水平的试剂在体外和体内均抑制星形胶质细胞的肿胀。在我们的实验室中，已经合成了4-[（（N-烷基-1,3-二氧杂-1H，3H-异吲哚基-5-基）氧基]链烷酸和相关衍生物，并测试了降低细胞内星形细胞氯化物水平的能力。建立了体外培养的大鼠星形胶质细胞模型。通常，具有氮取代基（例如相对小的烷基）的衍生物在0.1 mM和/或0.5 mM的水平上具有活性，而较大的取代基（例如环戊基和环己基）的活性较低。芳环上的卤素取代没有增强活性。

  DOI：

  10.1021/jm00393a020

文献信息

• Effects of [(N-alkyl-1,3-dioxo-1H,3H-isoindolin-5-yl)oxy]alkanoic acids, [(N-alkyl-1-oxo-1H,3H-isoindolin-5-yl)oxy]butanoic acids, and related derivatives on chloride influx in primary astroglial cultures
  作者：Steven D. Wyrick、Forrest T. Smith、W. Evans Kemp、Anne A. Grippo

  DOI：10.1021/jm00393a020

  日期：1987.10

  agents that inhibit chloride influx and therefore lower intracellular chloride levels in a major cell type in cerebral gray matter, the astrocyte, inhibit astrocytic swelling in vitro and in vivo. In our laboratories, 4-[(N-alkyl-1,3-dioxo-1H,3H-isoindolin-5-yl)oxy]alkanoic acids and related derivatives have been synthesized and tested for ability to lower intracellular astrocytic chloride levels in an established

  业已表明，抑制氯离子流入并因此降低脑灰质星形细胞中主要细胞类型的细胞内氯水平的试剂在体外和体内均抑制星形胶质细胞的肿胀。在我们的实验室中，已经合成了4-[（（N-烷基-1,3-二氧杂-1H，3H-异吲哚基-5-基）氧基]链烷酸和相关衍生物，并测试了降低细胞内星形细胞氯化物水平的能力。建立了体外培养的大鼠星形胶质细胞模型。通常，具有氮取代基（例如相对小的烷基）的衍生物在0.1 mM和/或0.5 mM的水平上具有活性，而较大的取代基（例如环戊基和环己基）的活性较低。芳环上的卤素取代没有增强活性。
• Development of tryptase inhibitors derived from thalidomide
  作者：Masashi Tetsuhashi、Minoru Ishikawa、Mariko Hashimoto、Yuichi Hashimoto、Hiroshi Aoyama

  DOI：10.1016/j.bmc.2010.05.037

  日期：2010.7

  A novel series of tryptase inhibitors with a N-phenylphthalimide skeleton structurally derived from thalidomide (1) has been developed. Structure-activity relationship studies led to a potent and selective tryptase inhibitor, 2-(4-cyanophenyl) isoindole-1,3-dione-5-yl 3-(2-aminopyridin-5-yl) propanoate (7), with the IC50 value of 78 nM. (C) 2010 Elsevier Ltd. All rights reserved.
• HAKAMYPA, TADASI;NAKAMURA, KOITI;YANAGI, XIDEHKI;YAMADZAKI, XARUMASA
  作者：HAKAMYPA, TADASI、NAKAMURA, KOITI、YANAGI, XIDEHKI、YAMADZAKI, XARUMASA

  DOI：——

  日期：——
• WYRICK, STEVEN D.;SMITH, FORREST T.;KEMP, W. EVANS;GRIPPO, ANNE A., J. MED. CHEM., 30,(1987) N 10, 1798-1806
  作者：WYRICK, STEVEN D.、SMITH, FORREST T.、KEMP, W. EVANS、GRIPPO, ANNE A.

  DOI：——

  日期：——
• Design and Synthesis of an Orally Active Metabotropic Glutamate Receptor Subtype-2 (mGluR2) Positive Allosteric Modulator (PAM) That Decreases Cocaine Self-Administration in Rats
  作者：Raveendra-Panickar Dhanya、Shyama Sidique、Douglas J. Sheffler、Hilary Highfield Nickols、Ananda Herath、Li Yang、Russell Dahl、Robert Ardecky、Svetlana Semenova、Athina Markou、P. Jeffrey Conn、Nicholas D. P. Cosford

  DOI：10.1021/jm1012165

  日期：2011.1.13

  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