3-(dimethylaminomethyl)-2-phenylquinoline-4-carboxylic cid | 224633-12-9

• 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-(dimethylaminomethyl)-2-phenylquinoline-4-carboxylic cid
• 英文别名: 3-[(Dimethylamino)methyl]-2-phenylquinoline-4-carboxylic acid
• CAS: 224633-12-9
• 化学式: C₁₉H₁₈N₂O₂
• 分子量: 306.364
• InChiKey: WAMLEVYZXBZLRH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  53.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(dimethylaminomethyl)-2-phenylquinoline-4-carboxylic cid 在 草酰氯 、 potassium carbonate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 (+)-(S)-N-(α-Ethylbenzyl)-3-dimethylaminomethyl-2-phenylquinoline-4-carboxamide hydrochloride
  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：

  3-溴甲基-2-苯基喹啉-4-羧酸甲酯 在 盐酸 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 生成 3-(dimethylaminomethyl)-2-phenylquinoline-4-carboxylic cid
  参考文献：
  名称：

  逐步调节喹啉速激肽受体拮抗剂中神经激肽3和神经激肽2受体的亲和力和选择性。

  摘要：

  描述了使用相同的2-苯基喹啉模板从人神经激肽3受体（hNK-3R）选择拮抗剂逐步转化为有效和组合的hNK-3R和hNK-2R拮抗剂的逐步化学修饰方法。用hNK-3和hNK-2受体的3-D模型对接研究来驱动化学设计并加快对两种受体的有效和联合拮抗作用的鉴定。（S）-（+）-N-（1-环己基乙基）-3-[（4-吗啉-4-基）哌啶-1-基]甲基-2-苯基喹啉-4-羧酰胺（化合物25，SB-400238 ：hNK-3R结合亲和力，K（i）= 0.8 nM； hNK-2R结合亲和力，K（i）= 0.8 nM）成为这种方法的最佳例子。进一步的研究导致鉴定（S）-（+）-N-（1,2,2-三甲基丙基）-3-[（4-哌啶-1-基）哌啶-1-基]甲基-2-苯基喹啉-4-羧酰胺（化合物28，SB-414240：hNK-3R结合亲和力，K（i）= 193 nM；hNK-2R结合亲和力，K（i）= 1.0 nM）

  DOI：

  10.1021/jm000501v

文献信息

• Quinoline-4-carboxamide derivatives as NK-3 and NK-2 receptor antagonists
  申请人：Farina Carlo

  公开号：US20050176762A1

  公开（公告）日：2005-08-11

  A compound of formula (I) as detailed in the specification or a pharmaceutically acceptable salt or solvate thereof, a process for preparing such compounds, a pharmaceutical composition comprising such compounds and the use of such compounds in medicine.

  公式（I）的化合物，其详细说明或其药学上可接受的盐或溶剂，制备这种化合物的过程，包含这种化合物的药物组合物以及这种化合物在医学上的用途。
• N-Oxo-Heterocycle and N-Oxo-Alkyl Quinoline-4-Carboxamides as Nk-3 Receptor Ligands
  申请人：Campbell James B.

  公开号：US20080234269A1

  公开（公告）日：2008-09-25

  Compounds of Formula I wherein R 1 , A, R 2 , R 3 , R 4 , R 5 , n, m and q are as described in the specification, pharmaceutically-acceptable salts, methods of making, pharmaceutical compositions containing and methods for using the same.

  公式I的化合物，其中R1，A，R2，R3，R4，R5，n，m和q如规范所述，可以形成药物可接受的盐，制备方法，含有这些化合物的制药组合物以及使用这些化合物的方法。
• QUINOLINE-4-CARBOXAMIDE DERIVATIVES AS NK-3 and NK-2 RECEPTOR ANTAGONISTS
  申请人：Farina Carlo

  公开号：US20070161647A1

  公开（公告）日：2007-07-12

  A compound of formula (I) as detailed in the specification or a pharmaceutically acceptable salt or solvate thereof, a process for preparing such compounds, a pharmaceutical composition comprising such compounds and the use of such compounds in medicine.

  式(I)的化合物，如规范中所述，或其药学上可接受的盐或溶剂合物，制备此类化合物的方法，包含此类化合物的制药组合物以及在医学中使用此类化合物。
• QUINOLINE-4-CARBOXAMIDE DERIVATIVES AS NK-3 AND NK-2 RECEPTOR ANTAGONISTS
  申请人：GlaxoSmithKline S.p.A.

  公开号：EP1377567A1

  公开（公告）日：2004-01-07
• N-OXO-HETEROCYCLE AND N-OXO-ALKYL QUINOLINE-4-CARBOXAMIDES AS NK-3 RECEPTOR LIGANDS
  申请人：AstraZeneca AB

  公开号：EP1940795A1

  公开（公告）日：2008-07-09