5'-甲氧基-6'-[3-(1-吡咯烷基)丙氧基]螺[环丁烷-1,3'-[3H]吲哚]-2'-胺 | 1527503-11-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: 5'-甲氧基-6'-[3-(1-吡咯烷基)丙氧基]螺[环丁烷-1,3'-[3H]吲哚]-2'-胺
• 英文名称: A-366
• 英文别名: 5'-methoxy-6'-(3-(pyrrolidin-1-yl)propoxy)spiro[cyclobutane-1,3'-indol]-2'-amine；5'-methoxy-6'-(3-pyrrolidin-1-ylpropoxy)spiro[cyclobutane-1,3'-indole]-2'-amine
• CAS: 1527503-11-2
• 化学式: C₁₉H₂₇N₃O₂
• 分子量: 329.442
• InChiKey: BKCDJTRMYWSXMC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.63
• 拓扑面积：
  60.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-苯甲氧基-3-甲氧基苯基乙腈 在 palladium 10% on activated carbon 、 四丁基溴化铵 、 氢气 、 硝酸 、 乙酸酐 、 potassium carbonate 、 溶剂黄146 、 sodium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 83.33h， 生成 5'-甲氧基-6'-[3-(1-吡咯烷基)丙氧基]螺[环丁烷-1,3'-[3H]吲哚]-2'-胺
  参考文献：
  名称：

  INHIBITORS OF HISTONE METHYLTRANSFERASE G9a

  摘要：

  本文介绍了一种用于治疗癌症、炎症或自身免疫疾病，或用于抑制组蛋白甲基转移酶G9a的化合物、药物组合物和方法。

  公开号：

  US20150274660A1

文献信息

• Inhibitors of histone methyltransferase G9a
  申请人：AbbVie Inc.

  公开号：US09284272B2

  公开（公告）日：2016-03-15

  Described herein are compounds, pharmaceutical compositions and methods for treating cancer, inflammation, or autoimmune disease in a subject, or for inhibiting histone methyltransferase G9a.

  本文描述了一种化合物、药物组合物和治疗癌症、炎症或自身免疫性疾病的方法，或抑制组蛋白甲基转移酶G9a的方法。
• SPIRO-CONDENSED INDOLE COMPOUNDS AS EHMT2 INHIBITORS
  申请人：Epizyme Inc

  公开号：EP4105203A1

  公开（公告）日：2022-12-21

  The present disclosure relates to substituted fused bi- or tri- heterocyclic compounds of formula (Va) to (Vf). The present disclosure also relates to pharmaceutical compositions containing these compounds. Said compounds are for use in methods of treating a disorder (e.g., sickle cell anemia) via inhibition of a methyltransferase enzyme selected from EHMT1 and EHMT2.

  本公开涉及式（Va）至（Vf）的取代融合二或三杂环化合物。本公开还涉及含有这些化合物的药物组合物。所述化合物用于通过抑制选自 EHMT1 和 EHMT2 的甲基转移酶来治疗疾病（例如镰状细胞贫血）的方法。
• Methods and compositions to increase somatic cell nuclear transfer (SCNT) efficiency by removing histone H3-lysine trimethylation
  申请人：CHILDREN'S MEDICAL CENTER CORPORATION

  公开号：US10266848B2

  公开（公告）日：2019-04-23

  The present invention provides methods and compostions to improve the efficiency of somatic cell nuclear transfer (SCNT) and the consequent production of nuclear transfer ESC (ntESC) and transgenic cells and/or non-human animals. More specifically, the present invention relates to the discovery that trimethylation of Histone H3-Lysine 9 (H3K9me3) in reprogramming resistant regions (RRRs) in the nuclear genetic material of donor somatic cells prevents efficient somatic cell nuclear reprogramming or SCNT. The present invention provide methods and compositions to decrease H3K9me3 in methods to improve efficacy of SCNT by exogenous or overexpression of the demethylase Kdm4 family and/or inhibiting methylation of H3K9me3 by inhibiting the histone methyltransferases Suv39h1 and/or Suv39h2.

  本发明提供了提高体细胞核移植（SCNT）效率以及由此产生核移植 ESC（NTESC）和转基因细胞和/或非人动物的方法和合成方法。更具体地说，本发明涉及发现供体体细胞核遗传物质中的重编程抗性区域（RRRs）中组蛋白 H3-赖氨酸 9（H3K9me3）的三甲基化会阻碍高效的体细胞核重编程或 SCNT。本发明提供了通过外源或过量表达去甲基化酶 Kdm4 家族和/或通过抑制组蛋白甲基转移酶 Suv39h1 和/或 Suv39h2 来抑制 H3K9me3 的甲基化，从而降低 H3K9me3 以提高 SCNT 效力的方法和组合物。
• Methods for production of functional beta cells
  申请人：Janssen Biotech, Inc.

  公开号：US10633635B2

  公开（公告）日：2020-04-28

  The invention provides for methods of differentiating pancreatic endocrine cells into pancreatic beta cells expressing PDX1, NKX6.1, MAFA, UCN3 and SLC2A. These pancreatic beta cells may be obtained by step-wise differentiation of pluripotent stem cells. The pancreatic beta cells exhibit glucose-dependent mitochondrial respiration and glucose-stimulated insulin secretion similar to islet cells.

  本发明提供了将胰腺内分泌细胞分化成表达PDX1、NKX6.1、MAFA、UCN3和SLC2A的胰腺β细胞的方法。这些胰腺β细胞可通过多能干细胞的逐步分化获得。胰岛β细胞表现出与胰岛细胞相似的葡萄糖依赖性线粒体呼吸和葡萄糖刺激的胰岛素分泌。
• Discovery and Development of Potent and Selective Inhibitors of Histone Methyltransferase G9a
  作者：Ramzi F. Sweis、Marina Pliushchev、Peter J. Brown、Jun Guo、Fengling Li、David Maag、Andrew M. Petros、Nirupama B. Soni、Chris Tse、Masoud Vedadi、Michael R. Michaelides、Gary G. Chiang、William N. Pappano

  DOI：10.1021/ml400496h

  日期：2014.2.13

  G9a is a histone lysine methyltransferase responsible for the methylation of histone H3 lysine 9. The discovery of A-366 arose from a unique diversity screening hit, which was optimized by incorporation of a propyl-pyrrolidine subunit to occupy the enzyme lysine channel. A-366 is a potent inhibitor of G9a (IC50: 3.3 nM) with greater than 1000-fold selectivity over 21 other methyltransferases.