3-Ethyl-Cinchophen | 224633-08-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 3-Ethyl-Cinchophen
• 英文别名: 3-ethyl-2-phenyl-quinoline-4-carboxylic acid；3-Aethyl-2-phenyl-chinolin-4-carbonsaeure；3-Ethyl-2-phenylquinoline-4-carboxylic acid
• CAS: 224633-08-3
• 化学式: C₁₈H₁₅NO₂
• mdl: MFCD04035071
• 分子量: 277.323
• InChiKey: TWIGHWNCHZAVQI-UHFFFAOYSA-N

物化性质

• 熔点：
  286 °C
• 沸点：
  462.2±45.0 °C(Predicted)
• 密度：
  1.219±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  50.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-Ethyl-Cinchophen 在 草酰氯 作用下， 以 二氯甲烷 为溶剂， 生成 3-Ethyl-2-phenylquinoline-4-carbonyl chloride
  参考文献：
  名称：

  Discovery of a Novel Class of Selective Non-Peptide Antagonists for the Human Neurokinin-3 Receptor. 2. Identification of (S)-N-(1-Phenylpropyl)-3-hydroxy-2- phenylquinoline-4-carboxamide (SB 223412)

  摘要：

  Optimization of the previously reported 2-phenyl-4-quinolinecarboxamide NK-3 receptor antagonist 14, with regard to potential metabolic instability of the ester moiety and affinity and selectivity for the human neurokinin-3 (hNK-3) receptor, is described. The ester functionality could be successfully replaced by the ketone (31) or by lower alkyl groups (Et, 21, or n-Pr, 24). Investigation of the substitution pattern of the quinoline ring resulted in the identification of position 3 as a key position to enhance hNK-3 binding affinity and selectivity for the hNK-3 versus the hNK-2 receptor. All of the chemical groups introduced at this position, with the exception of halogens, increased the hNK-3 binding affinity, and compounds 53 (3-OH, SE 223412, hNK-3-CHO binding K-i = 1.4 nM) and 55 (3-NHz, hNK-3-CHO binding K-i = 1.2 nM) were the most potent compounds of this series. Selectivity studies versus the other neurokinin receptors (hNK-8-CHO and hNK-1-CHO) revealed that 53 is about 100-fold selective for the hNK-3 versus hNK-2 receptor, with no affinity for the hNK-1 at concentrations up to 100 mu M. In vitro studies demonstrated that 53 is a potent functional antagonist of the hNK-3 receptor (reversal of senktide-induced contractions in rabbit isolated iris sphincter muscles and reversal of NKB-induced Ca2+ mobilization in CHO cells stably expressing the hNK-3 receptor), while in vivo this compound showed oral and intravenous activity in NK-3 receptor-driven models (senktide-induced behavioral responses in mice and senktide-induced miosis in rabbits). Overall, the biological data indicate that (S)-N-(1-phenylpropyl)-3-hydroxy-2-phenylquinoline-4-carboxamide (53, SE 223412) may serve as a pharmacological tool in animal models of disease to assess the functional and pathophysiological role of the NK-3 receptor and to establish therapeutic indications for non-peptide NK-3 receptor antagonists.

  DOI：

  10.1021/jm980633c
• 作为产物：
  描述：

  靛红 、 苯丁酮 在 氢氧化钾 作用下， 生成 3-Ethyl-Cinchophen
  参考文献：
  名称：

  Utilization of Alkoxy Ketones in the Synthesis of Quinolines by the Pfitzinger Reaction. II¹

  摘要：

  DOI：

  10.1021/ja01260a041

文献信息

• Quinoline 4-carboxamide derivatives and their use as neurokinin 3 (nk-3) receptor antagonists
  申请人：Chan Ngor Wai

  公开号：US20070142431A1

  公开（公告）日：2007-06-21

  The invention relates to novel quinoline derivatives, processes for their preparation, pharmaceutical compositions containing them and their use as medicaments particularly in treating disorders of the central nervous system (CNS).

  本发明涉及新的喹啉衍生物、其制备方法、含有它们的制药组合物以及它们作为药物的用途，特别是用于治疗中枢神经系统（CNS）疾病。
• Discovery of a Novel Class of Selective Non-Peptide Antagonists for the Human Neurokinin-3 Receptor. 2. Identification of (<i>S</i>)-<i>N</i>-(1-Phenylpropyl)-3-hydroxy-2- phenylquinoline-4-carboxamide (SB 223412)
  作者：Giuseppe A. M. Giardina、Luca F. Raveglia、Mario Grugni、Henry M. Sarau、Carlo Farina、Andrew D. Medhurst、Davide Graziani、Dulcie B. Schmidt、Roberto Rigolio、Mark Luttmann、Stefano Cavagnera、James J. Foley、Vittorio Vecchietti、Douglas W. P. Hay

  DOI：10.1021/jm980633c

  日期：1999.3.1

  Optimization of the previously reported 2-phenyl-4-quinolinecarboxamide NK-3 receptor antagonist 14, with regard to potential metabolic instability of the ester moiety and affinity and selectivity for the human neurokinin-3 (hNK-3) receptor, is described. The ester functionality could be successfully replaced by the ketone (31) or by lower alkyl groups (Et, 21, or n-Pr, 24). Investigation of the substitution pattern of the quinoline ring resulted in the identification of position 3 as a key position to enhance hNK-3 binding affinity and selectivity for the hNK-3 versus the hNK-2 receptor. All of the chemical groups introduced at this position, with the exception of halogens, increased the hNK-3 binding affinity, and compounds 53 (3-OH, SE 223412, hNK-3-CHO binding K-i = 1.4 nM) and 55 (3-NHz, hNK-3-CHO binding K-i = 1.2 nM) were the most potent compounds of this series. Selectivity studies versus the other neurokinin receptors (hNK-8-CHO and hNK-1-CHO) revealed that 53 is about 100-fold selective for the hNK-3 versus hNK-2 receptor, with no affinity for the hNK-1 at concentrations up to 100 mu M. In vitro studies demonstrated that 53 is a potent functional antagonist of the hNK-3 receptor (reversal of senktide-induced contractions in rabbit isolated iris sphincter muscles and reversal of NKB-induced Ca2+ mobilization in CHO cells stably expressing the hNK-3 receptor), while in vivo this compound showed oral and intravenous activity in NK-3 receptor-driven models (senktide-induced behavioral responses in mice and senktide-induced miosis in rabbits). Overall, the biological data indicate that (S)-N-(1-phenylpropyl)-3-hydroxy-2-phenylquinoline-4-carboxamide (53, SE 223412) may serve as a pharmacological tool in animal models of disease to assess the functional and pathophysiological role of the NK-3 receptor and to establish therapeutic indications for non-peptide NK-3 receptor antagonists.
• Utilization of Alkoxy Ketones in the Synthesis of Quinolines by the Pfitzinger Reaction. II¹
  作者：Sherman D. Lesesne、Henry R. Henze

  DOI：10.1021/ja01260a041

  日期：1942.8