3-oxo-2-phenethyl-2,3-dihydro-1H-isoindole-5-carboxylic acid | 943251-45-4

• 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: 3-oxo-2-phenethyl-2,3-dihydro-1H-isoindole-5-carboxylic acid
• 英文别名: 3-Oxo-2-phenethyl-2,3-dihydro-1H-isoindole-4-carboxylic acid；3-oxo-2-(2-phenylethyl)-1H-isoindole-4-carboxylic acid
• CAS: 943251-45-4
• 化学式: C₁₇H₁₅NO₃
• mdl: MFCD08457204
• 分子量: 281.311
• InChiKey: HBUKVBROECOTSV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 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：

  3-oxo-2-phenethyl-2,3-dihydro-1H-isoindole-5-carboxylic acid 在 lithium aluminium tetrahydride 、 cesium fluoride 作用下， 以 乙醚 、 乙腈 为溶剂， 生成 N-(1,3-dihydro-2-benzofuran-4-ylmethyl)-N-(2-phenylethyl)aniline
  参考文献：
  名称：

  The interaction of 4-hydroxymethyl isoindolines with dehydrobenzene. Synthesis of 3-phenylaminomethyldihydrobenzo[c]furanes

  摘要：

  2-Alkyl or 2-aryl-substituted 4-hydroxymethylisoindolines smoothly undergo intramolecular recyclization through reaction with arynes to give isobenzofurans with good yields. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2015.01.022
• 作为产物：
  描述：

  4-oxo-3-phenethyl-10-oxa-3-azatricyclo[5.2.1.0^1,5]dec-8-ene-6-carboxylic acid 在 对甲苯磺酸 作用下， 以 甲苯 为溶剂， 以48%的产率得到3-oxo-2-phenethyl-2,3-dihydro-1H-isoindole-5-carboxylic acid
  参考文献：
  名称：

  列诺沙明类似物高级中间体的合成

  摘要：

  本文介绍了一种简单易行的方法，用于合成高级异吲哚酮中间体伦诺沙明及其类似物。呋喃的分子内 Diels-Alder 反应是该合成的关键步骤。

  DOI：

  10.1055/s-2007-965950

文献信息

• Discovery of 2-[1-(4,4-Difluorocyclohexyl)piperidin-4-yl]-6-fluoro-3-oxo-2,3-dihydro-1<i>H</i>-isoindole-4-carboxamide (NMS-P118): A Potent, Orally Available, and Highly Selective PARP-1 Inhibitor for Cancer Therapy
  作者：Gianluca Papeo、Helena Posteri、Daniela Borghi、Alina A. Busel、Francesco Caprera、Elena Casale、Marina Ciomei、Alessandra Cirla、Emiliana Corti、Matteo D’Anello、Marina Fasolini、Barbara Forte、Arturo Galvani、Antonella Isacchi、Alexander Khvat、Mikhail Y. Krasavin、Rosita Lupi、Paolo Orsini、Rita Perego、Enrico Pesenti、Daniele Pezzetta、Sonia Rainoldi、Federico Riccardi-Sirtori、Alessandra Scolaro、Francesco Sola、Fabio Zuccotto、Eduard R. Felder、Daniele Donati、Alessia Montagnoli

  DOI：10.1021/acs.jmedchem.5b00680

  日期：2015.9.10

  The nuclear protein poly(ADP-ribose) polymerase-1 (PARP-1) has a well-established role in the signaling and repair of DNA and is a prominent target in oncology, as testified by the number of candidates in clinical testing that unselectively target both PARP-1 and its closest isoform PARP-2. The goal of our program was to find a PARP-1 selective inhibitor that would potentially mitigate toxicities arising from cross-inhibition of PARP-2. Thus, an HTS campaign on the proprietary Nerviano Medical Sciences (NMS) chemical collection, followed by SAR optimization, allowed us to discover 2-[1-4,4-difluorocyclohexyl)piperidin-4-yl] -6-fluoro-3-oxo-2,3-dihydro-1H-isoindole-4-carboxamide (NMS-P118, 20by). NMS-P118 proved to be a potent, orally available, and highly selective PARP-1 inhibitor endowed with excellent ADME and pharmacokinetic profiles and high efficacy in vivo both as a single agent and in combination with Temozolomide in MDA-MB-436 and Capan-1 xenograft models, respectively. Cocrystal structures of 20by with both PARP-1 and PARP-2 catalytic domain proteins allowed rationalization of the observed selectivity.
• Synthesis of Advanced Intermediates of Lennoxamine Analogues
  作者：Girish Trivedi、Manikrao Salunkhe、Prajakta Sarang、Arun Yadav、Prashant Patil、Urlam Krishna

  DOI：10.1055/s-2007-965950

  日期：2007.4

  A simple and convenient method for synthesis of advanced isoindolone intermediates of lennoxamine and analogues is described in this paper. The intramolecular Diels-Alder reaction of furan is used as a key step in this synthesis.

  本文介绍了一种简单易行的方法，用于合成高级异吲哚酮中间体伦诺沙明及其类似物。呋喃的分子内 Diels-Alder 反应是该合成的关键步骤。
• The interaction of 4-hydroxymethyl isoindolines with dehydrobenzene. Synthesis of 3-phenylaminomethyldihydrobenzo[c]furanes
  作者：Alexey V. Varlamov、Natalia I. Guranova、Tatiana N. Borisova、Flavien A.A. Toze、Maxim V. Ovcharov、Sindi Kristancho、Leonid G. Voskressensky

  DOI：10.1016/j.tet.2015.01.022

  日期：2015.2

  2-Alkyl or 2-aryl-substituted 4-hydroxymethylisoindolines smoothly undergo intramolecular recyclization through reaction with arynes to give isobenzofurans with good yields. (C) 2015 Elsevier Ltd. All rights reserved.