Cinnoline-3-carbonyl chloride | 1398583-92-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: Cinnoline-3-carbonyl chloride
• CAS: 1398583-92-0
• 化学式: C₉H₅ClN₂O
• 分子量: 192.605
• InChiKey: XVFZSWDTGVRBCN-UHFFFAOYSA-N

物化性质

• 沸点：
  348.0±34.0 °C(predicted)
• 密度：
  1.411±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  42.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  Cinnoline-3-carbonyl chloride 、 methyl-3-({[(1R)-1-(4-fluorophenyl)ethyl]amino}methyl)benzoate 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  Discovery of a Selective TRPM8 Antagonist with Clinical Efficacy in Cold-Related Pain

  摘要：

  The transient receptor potential (TRP) family of ion channels comprises nonselective cation channels that respond to a wide range of chemical and thermal stimuli. TRPM8, a member of the melastatin subfamily, is activated by cold temperatures (<28 degrees C), and antagonists of this channel have the potential to treat cold induced allodynia and hyperalgesia. However, TRPM8 has also been implicated in mammalian thermoregulation and antagonists have the potential to induce hypothermia in patients. We report herein the identification and optimization of a series of TRPM8 antagonists that ultimately led to the discovery of PF-05105679. The clinical finding with this compound will be discussed, including both efficacy and its ability to affect thermoregulation processes in humans.

  DOI：

  10.1021/ml500479v
• 作为产物：
  描述：

  3-噌啉甲醛 在 sodium chlorite 、 氯化亚砜 、 2-甲基-2-丁烯 作用下， 以 水 、 叔丁醇 为溶剂， 反应 2.5h， 生成 Cinnoline-3-carbonyl chloride
  参考文献：
  名称：

  Discovery of a Selective TRPM8 Antagonist with Clinical Efficacy in Cold-Related Pain

  摘要：

  The transient receptor potential (TRP) family of ion channels comprises nonselective cation channels that respond to a wide range of chemical and thermal stimuli. TRPM8, a member of the melastatin subfamily, is activated by cold temperatures (<28 degrees C), and antagonists of this channel have the potential to treat cold induced allodynia and hyperalgesia. However, TRPM8 has also been implicated in mammalian thermoregulation and antagonists have the potential to induce hypothermia in patients. We report herein the identification and optimization of a series of TRPM8 antagonists that ultimately led to the discovery of PF-05105679. The clinical finding with this compound will be discussed, including both efficacy and its ability to affect thermoregulation processes in humans.

  DOI：

  10.1021/ml500479v

文献信息

• [EN] ARYL SUBSTITUTED CARBOXAMIDE DERIVATIVES AS TRPM8 MODULATORS<br/>[FR] DÉRIVÉS DE CARBOXAMIDE SUBSTITUÉS PAR ARYLE EN TANT QUE MODULATEURS DE TRPM8
  申请人：PFIZER LTD

  公开号：WO2012120398A1

  公开（公告）日：2012-09-13

  The invention provides a compound of the formula (I): wherein A, R1, R2 and R3 are as defined herein, or a pharmaceutically acceptable salt thereof. Such compounds are small molecule TRPM8 blockers and therefore useful in the propylaxis or treatment of a wide range of diseases, conditions or syndromes, including cold allodynia and Raynaulds syndrome.

  本发明提供了一种化合物，其化学式为（I）：其中A、R1、R2和R3如本文所定义，或其药学上可接受的盐。这些化合物是小分子TRPM8阻断剂，因此在预防或治疗包括寒冷痛觉异常和雷诺综合征在内的各种疾病、症状或综合征中有用。
• Process for production of N,N-disubstituted carboxylic acid amides
  申请人：TOKUYAMA SODA KABUSHIKI KAISHA

  公开号：EP0189774A1

  公开（公告）日：1986-08-06

  A novel process for producing N,N-disubstituted carboxylic acid amides represented by the following formula wherein R, R1, R2 and R3 are as defined in claim 1, which comprises contacting a Schiff base represented by the following formula (III) wherein R, R1 and R2 are as defined above, with a carboxylic acid derivative represented by the following formula (III) wherein R3 is as defined above, and M represents a halogen atom or the moiety in the presence of a silane compound represented by the following formula (IV) wherein X, Y and Z, independently from each other, represent a hydrogen atom or a halogen atom, in the presence or absence of an inert organic solvent.

  1.一种生产下式所代表的N，N-二取代羧酸酰胺的新工艺，其中R、R1、R2和R3如权利要求1所定义，该工艺包括在有或无惰性有机溶剂存在的情况下，将下式(III)所代表的希夫碱(其中R、R1和R2如上所定义)与下式(III)所代表的羧酸衍生物(其中R3如上所定义)和M代表卤素原子或分子在下式(IV)所代表的硅烷化合物(其中X、Y和Z各自代表氢原子或卤素原子)存在的情况下接触。