N-ethyl-N-methyl-2-chloronicotinic acid amide | 720693-05-0

• 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: N-ethyl-N-methyl-2-chloronicotinic acid amide
• 英文别名: N-ethyl-N-methyl-6-chloronicotinamide；6-chloro-N-ethyl-N-methylpyridine-3-carboxamide
• CAS: 720693-05-0
• 化学式: C₉H₁₁ClN₂O
• 分子量: 198.652
• InChiKey: KRBIGUVPPLFHHE-UHFFFAOYSA-N

物化性质

• 沸点：
  342.1±27.0 °C(Predicted)
• 密度：
  1.193±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  33.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-ethyl-N-methyl-2-chloronicotinic acid amide 在 盐酸 、 硼烷 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 水 为溶剂， 反应 22.5h， 生成 1-[5-[[Ethyl(methyl)amino]methyl]pyridin-2-yl]piperidin-4-amine
  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
• 作为产物：
  描述：

  6-氯烟酸 、 N-乙基甲基胺 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以75%的产率得到N-ethyl-N-methyl-2-chloronicotinic acid amide
  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。
• Novel benzazepine derivatives
  申请人：Glaxo Group Limited

  公开号：EP2133340A1

  公开（公告）日：2009-12-16

  The present invention relates to novel benzazepine derivatives having pharmacological activity, processes for their preparation, to compositions containing them and to their use in the treatment of neurological and psychiatric disorders. More specifically, the invention relates to a compound of formula (I) or a pharmaceutically acceptable salt thereof: wherein formula (I) is as defined herein.

  本发明涉及具有药理活性的新型苯并氮杂卓衍生物、其制备工艺、含有它们的组合物以及它们在治疗神经和精神疾病中的用途。 更具体地说，本发明涉及式（I）化合物或其药学上可接受的盐： 其中式 (I) 如本文所定义。
• Novel benzazepine derivative
  申请人：Glaxo Group Limited

  公开号：EP2186516A1

  公开（公告）日：2010-05-19

  The present invention relates to a compound which is 6-(3-cyclobutyl-2,3,4,5-tetrahydro-1H-benzo[d]azepin-7-yloxy)-N-methyl-nicotinamide or a pharmaceutically acceptable salt thereof. This compound and its pharmaceutically acceptable salts have affinity for and are antagonists and/or inverse agonists of the histamine H3 receptor. The present invention also relates to processes for the preparation of this benzazepine derivative, to compositions containing it, and to the use of the benzazepine derivative in the treatment of neurological and psychiatric disorders.

  本发明涉及一种化合物，它是 6-(3-环丁基-2,3,4,5-四氢-1H-苯并[d]氮杂卓-7-氧基)-N-甲基烟酰胺 或其药学上可接受的盐。 该化合物及其药学上可接受的盐对组胺 H3 受体具有亲和力，是组胺 H3 受体的拮抗剂和/或反向激动剂。 本发明还涉及该苯并氮杂卓衍生物的制备工艺、含有该衍生物的组合物以及该苯并氮杂卓衍生物在治疗神经和精神疾病中的用途。
• [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
• BENZO[D]AZEPINE DERIVATIVES FOR THE TREATMENT OF NEUROLOGICAL DISORDERS
  申请人：GLAXO GROUP LIMITED

  公开号：EP1572215B1

  公开（公告）日：2009-09-02