(S)-N-(α-ethylbenzyl)-3-(carboxymethoxy)-2-phenylquinoline-4-carboxamide hydrochloride

• 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: (S)-N-(α-ethylbenzyl)-3-(carboxymethoxy)-2-phenylquinoline-4-carboxamide hydrochloride
• 英文别名: (S)-N-(alpha-ethylbenzyl)-3-(carboxymethoxy)-2-phenylquinoline-4-carboxamide hydrochloride；2-[2-phenyl-4-[[(1S)-1-phenylpropyl]carbamoyl]quinolin-3-yl]oxyacetic acid;hydrochloride
• 化学式: C₂₇H₂₄N₂O₄*ClH
• 分子量: 476.959
• InChiKey: RSBTWFTXHWRIOQ-BOXHHOBZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.67
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  88.5
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (-)-(S)-N-(alpha-乙基苄基)-3-羟基-2-苯基喹啉-4-羧酰胺 在 盐酸 、 potassium carbonate 、 potassium iodide 作用下， 以 四氢呋喃 为溶剂， 反应 0.33h， 生成 (S)-N-(α-ethylbenzyl)-3-(carboxymethoxy)-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

文献信息

• Quinoline derivatives
  申请人：SmithKline Beecham S.p.A.

  公开号：US06277862B1

  公开（公告）日：2001-08-21

  A compound, or a solvate or a salt thereof, of formula (I), wherein, Ar is an optionally substituted aryl or a C5-7 cycloalkdienyl group, or an optionally substituted single or fused ring aromatic heterocyclic group; R, R1, R2 and R3 are as defined in the description; a process for the preparation of such a compound, a pharmaceutical composition containing such a compound or composition in medicine.

  一种化合物，或其溶剂合物或盐，其化学式为（I），其中Ar是可选择取代的芳基或C5-7环烯基基团，或可选择取代的单环或融合环芳香杂环基团；R，R1，R2和R3如描述中定义；一种制备这种化合物的方法，包含这种化合物或组合物的药物组合物在医学上的应用。
• QUINOLINE DERIVATIVES
  申请人：Smithkline Beecham S.p.A.

  公开号：EP0876347A1

  公开（公告）日：1998-11-11
• US6277862B1
  申请人：——

  公开号：US6277862B1

  公开（公告）日：2001-08-21
• [EN] QUINOLINE DERIVATIVES<br/>[FR] DERIVES DE QUINOLINE
  申请人：——

  公开号：WO1997021680A1

  公开（公告）日：1997-06-19

  [EN] A compound, or a solvate or a salt thereof, of formula (I), wherein, Ar is an optionally substituted aryl or a C5-7 cycloalkdienyl group, or an optionally substituted single or fused ring aromatic heterocyclic group; R, R1, R2 and R3 are as defined in the description; a process for the preparation of such a compound, a pharmaceutical composition containing such a compound or composition in medicine.
  [FR] On décrit un composé, ou un solvate ou sel de celui-ci, répondant à la formule (I) dans laquelle Ar représente aryle éventuellement substitué ou un groupe cycloalkdiényle C5-7, ou un groupe hétérocyclique aromatique à noyau simple ou condensé, éventuellement substitué; R, R1, R2 et R3 sont tels que définis dans la description. On décrit également un procédé de préparation d'un tel composé, une composition pharmaceutique contenant celui-ci, ainsi que l'utilisation de ce composé ou de cette composition en médecine.
• [EN] NOVEL USE<br/>[FR] NOUVELLE UTILISATION
  申请人：SMITHKLINE BEECHAM CORP

  公开号：WO2002040023A1

  公开（公告）日：2002-05-23

  A method for the treatment or prophylaxis of the common cold, or respiratory viral infection caused by human rhinovirus infection (HRV), other enteroviruses, coronavirus, influenza virus, parainfluenza virus, respiratory syncytial virus, or adenovirus infection in a human in need thereof, which method comprises administering to said human an effective amount of an NK3 antagonist.