3-pyridin-3-yl-N-[1-[[6-[4-[(3-pyridin-3-ylbenzoyl)amino]piperidin-1-yl]pyridin-3-yl]methyl]piperidin-4-yl]benzamide | 1404361-93-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 3-pyridin-3-yl-N-[1-[[6-[4-[(3-pyridin-3-ylbenzoyl)amino]piperidin-1-yl]pyridin-3-yl]methyl]piperidin-4-yl]benzamide
• CAS: 1404361-93-8
• 化学式: C₄₀H₄₁N₇O₂
• 分子量: 651.811
• InChiKey: CHEGQSMAFNABCA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  49
• 可旋转键数：
  9
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  103
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3-吡啶-3-基苯甲酸 在 三乙酰氧基硼氢化钠 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 3.0h， 生成 3-pyridin-3-yl-N-[1-[[6-[4-[(3-pyridin-3-ylbenzoyl)amino]piperidin-1-yl]pyridin-3-yl]methyl]piperidin-4-yl]benzamide
  参考文献：
  名称：

  Identification of a novel Smoothened antagonist that potently suppresses Hedgehog signaling

  摘要：

  The Hedgehog signaling pathway plays an essential role in embryo development and adult tissue homeostasis, in regulating stem cells and is abnormally activated in many cancers. Given the importance of this signaling pathway, we developed a novel and versatile high-throughput, cell-based screening platform using confocal imaging, based on the role of beta-arrestin in Hedgehog signal transduction, that can identify agonists or antagonist of the pathway by a simple change to the screening protocol. Here we report the use of this assay in the antagonist mode to identify novel antagonists of Smoothened, including a compound (A8) with low nanomolar activity against wild-type Smo also capable of binding the Smo point mutant D473H associated with clinical resistance in medulloblastoma. Our data validate this novel screening approach in the further development of A8 and related congeners to treat hedgehog related diseases, including the treatment of basal cell carcinoma and medulloblastoma. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.09.030

文献信息

• SMOOTHENED MODULATORS AND METHODS OF USE THEREOF
  申请人：Duke University

  公开号：US20150166509A1

  公开（公告）日：2015-06-18

  Compounds of general Formulas (I), (IA), (IB) are described, along with compositions containing the same and methods of use thereof, inhibiting the hedgehog pathway in a cell or inhibiting unwanted proliferation of a cell.

  描述了一般式(I)、(IA)、(IB)的化合物，以及含有这些化合物的组合物及其使用方法，用于抑制细胞中的刺猬通路或抑制细胞的不良增殖。
• [EN] SMOOTHENED MODULATORS AND METHODS OF USE THEREOF<br/>[FR] MODULATEURS DE SMOOTHENED ET LEURS PROCÉDÉS D'UTILISATION
  申请人：UNIV DUKE

  公开号：WO2014043608A3

  公开（公告）日：2015-07-16
• US9512106B2
  申请人：——

  公开号：US9512106B2

  公开（公告）日：2016-12-06
• Identification of a novel Smoothened antagonist that potently suppresses Hedgehog signaling
  作者：Jiangbo Wang、Robert A. Mook、Jiuyi Lu、David M. Gooden、Anthony Ribeiro、Anchen Guo、Larry S. Barak、H. Kim Lyerly、Wei Chen

  DOI：10.1016/j.bmc.2012.09.030

  日期：2012.11

  The Hedgehog signaling pathway plays an essential role in embryo development and adult tissue homeostasis, in regulating stem cells and is abnormally activated in many cancers. Given the importance of this signaling pathway, we developed a novel and versatile high-throughput, cell-based screening platform using confocal imaging, based on the role of beta-arrestin in Hedgehog signal transduction, that can identify agonists or antagonist of the pathway by a simple change to the screening protocol. Here we report the use of this assay in the antagonist mode to identify novel antagonists of Smoothened, including a compound (A8) with low nanomolar activity against wild-type Smo also capable of binding the Smo point mutant D473H associated with clinical resistance in medulloblastoma. Our data validate this novel screening approach in the further development of A8 and related congeners to treat hedgehog related diseases, including the treatment of basal cell carcinoma and medulloblastoma. (C) 2012 Elsevier Ltd. All rights reserved.