N-(3-chloropropyl)isoindoline

• 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: N-(3-chloropropyl)isoindoline
• 英文别名: 2-(3-chloropropyl)-1,3-dihydroisoindole
• 化学式: C₁₁H₁₄ClN
• 分子量: 195.692
• InChiKey: BIFCBZFFXPSYKI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  3.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  N-(3-chloropropyl)isoindoline 、 吩噻嗪 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 以56%的产率得到10-[3-(isoindolin-2-yl)propyl]phenothiazine
  参考文献：
  名称：

  Carboline- and phenothiazine-derivated heterocycles as potent SIGMA-1 protein ligands

  摘要：

  Sigma 1 receptors are associated with neurodegenerative and psychiatric disorders. These receptors, via their chaperoning functions that counteract endoplasmic reticulum stress and block neurodegeneration, may serve as a target for a new generation of antidepressants or neuroprotective agents. The involvement of these receptors has also been observed in neuropathic pain and cancer. Only a few ligands, such as Igmesine and Anavex 2-73, have been involved in clinical trials. Thus the development of sigma 1 ligands is of interest to a new generation of drugs. Previous work in our lab underlined the potency of benzannulated bicyclic compounds as interesting ligands. Herein the work was extended to a series of novel tricyclic compounds. Carboline- and phenothiazine-derivated compounds were designed and synthesized. In vitro competition binding assays for sigma 1 and 2 receptors showed that most of them have high affinity for sigma 1 receptor (K-i = 2.5-18 nM), and selectivity toward sigma 2 receptor, without cytotoxic effects on SY5Y cells. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.10.053
• 作为产物：
  描述：

  N-(3-氯苯基)邻苯二甲酰亚胺 在 diborane(6) 作用下， 以 四氢呋喃 为溶剂， 反应 72.0h， 以90%的产率得到N-(3-chloropropyl)isoindoline
  参考文献：
  名称：

  乙硼烷将邻苯二甲酰亚胺转化为异吲哚啉

  摘要：

  本文描述了通过乙硼烷将 N- 烷基取代的邻苯二甲酰亚胺还原 成相应的异吲哚啉。

  DOI：

  10.1007/s00706-006-0554-5

文献信息

• Discovery of a Potent, Selective, and Cell-Active SPIN1 Inhibitor
  作者：Yan Xiong、Holger Greschik、Catrine Johansson、Ludwig Seifert、Vicki Gamble、Kwang-su Park、Vincent Fagan、Fengling Li、Irene Chau、Masoud Vedadi、Cheryl H. Arrowsmith、Paul Brennan、Oleg Fedorov、Manfred Jung、Gillian Farnie、Jing Liu、Udo Oppermann、Roland Schüle、Jian Jin

  DOI：10.1021/acs.jmedchem.4c00121

  日期：2024.4.11

  Very few cellularly active SPIN1 inhibitors have been developed. We previously reported that our G9a/GLP inhibitor UNC0638 weakly inhibited SPIN1. Here, we present our comprehensive structure–activity relationship study that led to the discovery of compound 11, a dual SPIN1 and G9a/GLP inhibitor, and compound 18 (MS8535), a SPIN1 selective inhibitor. We solved the cocrystal structure of SPIN1 in complex

  甲基赖氨酸阅读蛋白SPIN1在多种人类疾病中发挥着重要作用。然而，针对甲基赖氨酸读取蛋白一直具有挑战性。目前已开发出的细胞活性 SPIN1 抑制剂非常少。我们之前报道过我们的 G9a/GLP 抑制剂 UNC0638 弱抑制 SPIN1。在这里，我们介绍了我们全面的构效关系研究，该研究导致了化合物11 （一种 SPIN1 和 G9a/GLP 双重抑制剂）和化合物18 (MS8535)（一种 SPIN1 选择性抑制剂）的发现。我们解析了 SPIN1 与11复合物的共晶结构，证实11占据了三个 Tudor 结构域之一。重要的是，与包括 G9a/GLP 在内的 38 个表观遗传靶标相比， 18 个对 SPIN1 显示出高选择性，并且浓度依赖性地破坏细胞中 SPIN1 和 H3 的相互作用。此外， 18在小鼠体内具有生物利用度。我们还开发了19 (MS8535N)，它对 SPIN1 没有活性，作为1
• Indolylpiperidine derivatives as potent and selective α1B adrenoceptor antagonists
  作者：Ryoji Hayashi、Eiji Ohmori、Mitsuhiro Moriwaki、Hiroki Kumagai、Masafumi Isogaya

  DOI：10.1016/j.bmcl.2015.07.046

  日期：2015.9

  series of novel indolylpiperidine derivatives were synthesized, and their pharmacological profiles were assessed at rat alpha(1A) and alpha(1B) adrenoceptors through in vitro binding studies. Compound 12 (2-(3-(4-(6-fluoro-1H-indol-3-yl)piperidin-1-yl)propyl)-1,2,3,4-tetrahydroisoquinoline) was a potent alpha(1B) adrenoceptor antagonist (K-i = 0.61 nM) and was about 40-fold more selective for the alpha(1B) adrenoceptor than for the alpha(1A) adrenoceptor. In addition, useful structure-activity relationship information was acquired for further improving selectivity for the alpha(1B) adrenoceptor. (C) 2015 Elsevier Ltd. All rights reserved.
• Synthesis and pharmacological evaluation of benzannulated derivatives as potent and selective sigma-1 protein ligands
  作者：Marion Donnier-Maréchal、Pascal Carato、Delphine Le Broc、Christophe Furman、Patricia Melnyk

  DOI：10.1016/j.ejmech.2014.01.013

  日期：2015.3

  The sigma(1) proteins are considered to be a new class of target structures for several central nervous system disorders, including depression, anxiety, psychosis, and Parkinson's and Alzheimer's diseases. Recently, the involvement of these receptors in neuropathic pain and cancer has also been observed. So far, only a few ligands are in clinical trials. In a continuation of our previous studies on the development of sigma(1) ligands, a new series of benzannulated heterocycles was designed and synthesised. In vitro competition binding assays showed that many of them possessed high cri receptor affinity (K-i = 0.6-10.3 nM), and good sigma(2)/sigma(1) subtype selectivity, without cytotoxic effects on SY5Y cells (human neuroblastoma cell line). (C) 2014 Elsevier Masson SAS. All rights reserved.