4-[5-[[(3-碘苯基)甲基]硫基]-1,3,4-恶二唑-2-基]吡啶 | 478482-75-6

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 中文名称: 4-[5-[[(3-碘苯基)甲基]硫基]-1,3,4-恶二唑-2-基]吡啶
• 中文别名: GSK-3抑制剂II
• 英文名称: GSK-3b Inhibitor II
• 英文别名: 2-[(3-iodophenyl)methylsulfanyl]-5-pyridin-4-yl-1,3,4-oxadiazole；2-(3-iodobenzylthio)-5-(pyridin-4-yl)-1,3,4-oxadiazole；361541 GSK-3β inhibitor II；2-thio(3-iodobenzyl)-5-(1-pyridyl)-[1,3,4]-oxadiazole；2-thio(3-iodobenzyl)-5-(1-pyridyl)-[1,3,4]oxadiazole；GSK-3 Inhibitor II
• CAS: 478482-75-6
• 化学式: C₁₄H₁₀IN₃OS
• 分子量: 395.223
• InChiKey: ZRHRPGSSSVYBRG-UHFFFAOYSA-N

物化性质

• 沸点：
  532.6±60.0 °C(Predicted)
• 密度：
  1.79±0.1 g/cm3(Predicted)
• 溶解度：
  DMSO 中≤3mg/ml；二甲基甲酰胺中10mg/ml

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  77.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  异烟酸甲酯 在 一水合肼 、 三乙胺 、 sodium hydroxide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 4-[5-[[(3-碘苯基)甲基]硫基]-1,3,4-恶二唑-2-基]吡啶
  参考文献：
  名称：

  Identification of Glycogen Synthase Kinase-3 Inhibitors with a Selective Sting for Glycogen Synthase Kinase-3α

  摘要：

  The glycogen synthase kinase-3 (GSK-3) has been linked to the pathogenesis of colorectal cancer, diabetes, cardiovascular disease, acute myeloid leukemia (AML), and Alzheimer's disease (AD). The debate on the respective contributions of GSK-3 alpha and GSK-3 beta to AD pathology and AML is ongoing. Thus, the identification of potent GSK-3 alpha-selective inhibitors, endowed with favorable pharmacokinetic properties, may elucidate the effect of GSK-3 alpha inhibition in AD and AML models. The analysis of all available crystallized GSK-3 structures provided a simplified scheme of the relevant hot spots responsible for ligand binding and potency. This resulted in the identification of novel scorpion shaped GSK-3 inhibitors. It is noteworthy, compounds 14d and 15b showed the highest GSK-3 alpha selectivity reported so far. In addition, compound 14d did not display significant inhibition of 48 out of 50 kinases in the test panel. The GSK-3 inhibitors were further profiled for efficacy and toxicity in the wild-type (wt) zebrafish embryo assay.

  DOI：

  10.1021/jm300309a

文献信息

• Compositions And Methods For Inhibiting Expression Of GSK-3 Genes
  申请人：Alnylam Pharmaceuticals, Inc.

  公开号：US20160024497A1

  公开（公告）日：2016-01-28

  The invention relates to a double-stranded ribonucleic acid (dsRNA) targeting Glycogen Synthase Kinase-3 (GSK-3), and methods of using the dsRNA to inhibit expression of GSK-3.

  这项发明涉及一种靶向糖原合成酶激酶-3（GSK-3）的双链核糖核酸（dsRNA），以及使用该dsRNA抑制GSK-3表达的方法。
• SMALL MOLECULE INHIBITORS OF SUPEROXIDE DISMUTASE EXPRESSION
  申请人：Northwestern University

  公开号：US20150210679A1

  公开（公告）日：2015-07-30

  Disclosed are new small molecules and the uses thereof for inhibiting superoxide dismutase (SOD) expression. Also disclosed are pharmaceutical compositions comprising the small molecule inhibitors which may be administered in methods of treating diseases or disorders associated with elevated SOD expression or activity, including neurological diseases and disorders such as amyotrophic lateral sclerosis (ALS).

  本发明涉及新的小分子化合物及其用途，用于抑制超氧化物歧化酶（SOD）表达。还公开了包含这些小分子抑制剂的药物组合物，可以在治疗与升高的SOD表达或活性相关的疾病或疾病的方法中使用，包括神经疾病和疾病，如肌萎缩侧索硬化症（ALS）。
• Compositions and methods for epithelial stem cell expansion and culture
  申请人：The Brigham and Women's Hospital, Inc.

  公开号：US10041046B2

  公开（公告）日：2018-08-07

  Described are cell culture solutions and systems for epithelial stem cell and organoid cultures, formation of epithelial constructs and uses of the same in transplantation. A single layer of epithelial cells that actively self-renews and is organized into crypts and villi clothes the intestine. It has been recently shown that the renewal of intestinal epithelium is driven by Lgr5+ intestinal stem cells (ISC) that reside at the base of these crypts (Barker et al., 2007). Lgr5+ stem cells can be isolated and cultured in vitro to form organoids containing crypt-vcllus structures that recapitulates the native intestinal epithelium (Sato et al., 2009).

  描述了用于上皮干细胞和类器官培养的细胞培养液和系统、上皮构建体的形成及其在移植中的应用。上皮细胞是一种单层上皮细胞，能主动自我更新，并被组织成隐窝和绒毛，为肠道穿衣。最近的研究表明，肠上皮细胞的更新是由位于这些隐窝底部的Lgr5+肠干细胞（ISC）驱动的（Barker等人，2007年）。Lgr5+干细胞可被分离出来并在体外培养，形成含有隐窝-绒毛结构的器官组织，从而再现原生肠上皮（Sato等人，2009年）。
• Generation of pancreatic endoderm from pluripotent stem cells using small molecules
  申请人：Novo Nordisk A/S

  公开号：US10221392B2

  公开（公告）日：2019-03-05

  A method of producing pancreatic cells or pancreatic cell precursors expressing at least 5% PDX1/NKX6.1 double positive, comprising exposing definitive endoderm cells to an effective amount of one or more small molecules, to differentiate the human definitive endoderm cells into the pancreatic cells or pancreatic cell precursors. The present invention also relates to pancreatic endoderm cells produced by said methods and uses of said pancreatic endoderm cells.

  一种生产表达至少5% PDX1/NKX6.1双阳性的胰腺细胞或胰腺细胞前体的方法，包括将确定性内胚层细胞暴露于有效量的一种或多种小分子，使人类确定性内胚层细胞分化为胰腺细胞或胰腺细胞前体。本发明还涉及通过上述方法产生的胰腺内胚层细胞以及上述胰腺内胚层细胞的用途。
• Producing astrocytes using small molecules
  申请人：CITY OF HOPE

  公开号：US11413286B2

  公开（公告）日：2022-08-16

  Disclosed herein are methods of reprograming autologous tissues or cells into astrocytes or astroglial progenitor cells using one or more small molecule compounds only without any transgenes. Also disclosed are methods of preventing or treating neurodegenerative diseases or neurological disorders associated with dysfunction of astrocytes, such as Alzheimer's Disease, by transplanting the astrocytes or astroglial progenitor cells produced by the methods disclosed herein into the brain of a subject suffering from the neurodegenerative disease or neurological disorder.

  本文公开了仅使用一种或多种小分子化合物而不使用任何转基因将自体组织或细胞重编程为星形胶质细胞或星形胶质祖细胞的方法。还公开了预防或治疗与星形胶质细胞功能障碍有关的神经退行性疾病或神经系统疾病（如阿尔茨海默病）的方法，方法是将通过本文公开的方法产生的星形胶质细胞或星形胶质祖细胞移植到患有神经退行性疾病或神经系统疾病的患者的大脑中。