1-(7-chloroquinolin-4-yl)-5-(2-methoxyphenyl)-1H-pyrazole-3-carboxylic acid | 1146757-94-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(7-chloroquinolin-4-yl)-5-(2-methoxyphenyl)-1H-pyrazole-3-carboxylic acid
• 英文别名: 1-(7-Chloroquinolin-4-yl)-5-(2-methoxyphenyl)pyrazole-3-carboxylic acid
• CAS: 1146757-94-9
• 化学式: C₂₀H₁₄ClN₃O₃
• 分子量: 379.802
• InChiKey: YDWDKMSUUVVCDU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  77.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(7-chloroquinolin-4-yl)-5-(2-methoxyphenyl)-1H-pyrazole-3-carboxylic acid 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 32.0h， 生成 (2S)-({[1-(7-chloroquinolin-4-yl)-5-(2-methoxyphenyl)-1H-pyrazol-3-yl]carbonyl}amino)(cyclohexyl)ethanoic acid
  参考文献：
  名称：

  Identification of 1-({[1-(4-Fluorophenyl)-5-(2-methoxyphenyl)-1H-pyrazol-3-yl]carbonyl}amino)cyclohexane Carboxylic Acid as a Selective Nonpeptide Neurotensin Receptor Type 2 Compound

  摘要：

  Compounds active at neurotensin receptors (NTS1 and NTS2) exert analgesic effects on different types of nociceptive modalities, including thermal, mechanical, and chemical stimuli. The NTS2 preferring peptide JMV-431 (2) and the NTS2 selective nonpeptide compound levocabastine (6) have been shown to be effective in relieving the pain associated with peripheral neuropathies. With the aim of identifying novel nonpeptide compounds selective for NTS2, we examined analogues of SR48692 (5a) using a FLIPR calcium assay in CHO cells stably expressing rat NTS2. This led to the discovery of the NTS2 selective nonpeptide compound 1-({[1-(4-fluorophenyl)-5-(2-methoxyphenyl)-1H-pyrazol-3-yl]carbonyl}amino)cyclohexane carboxylic acid (NTRC-739, 7b) starting from the nonselective compound 5a.

  DOI：

  10.1021/jm5003843
• 作为产物：
  描述：

  sodium methyl 4-(2-methoxyphenyl)-2,4-dioxo-butanoate 在 盐酸 、 溶剂黄146 、 lithium hydroxide 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 16.0h， 生成 1-(7-chloroquinolin-4-yl)-5-(2-methoxyphenyl)-1H-pyrazole-3-carboxylic acid
  参考文献：
  名称：

  Identification of 1-({[1-(4-Fluorophenyl)-5-(2-methoxyphenyl)-1H-pyrazol-3-yl]carbonyl}amino)cyclohexane Carboxylic Acid as a Selective Nonpeptide Neurotensin Receptor Type 2 Compound

  摘要：

  Compounds active at neurotensin receptors (NTS1 and NTS2) exert analgesic effects on different types of nociceptive modalities, including thermal, mechanical, and chemical stimuli. The NTS2 preferring peptide JMV-431 (2) and the NTS2 selective nonpeptide compound levocabastine (6) have been shown to be effective in relieving the pain associated with peripheral neuropathies. With the aim of identifying novel nonpeptide compounds selective for NTS2, we examined analogues of SR48692 (5a) using a FLIPR calcium assay in CHO cells stably expressing rat NTS2. This led to the discovery of the NTS2 selective nonpeptide compound 1-({[1-(4-fluorophenyl)-5-(2-methoxyphenyl)-1H-pyrazol-3-yl]carbonyl}amino)cyclohexane carboxylic acid (NTRC-739, 7b) starting from the nonselective compound 5a.

  DOI：

  10.1021/jm5003843

文献信息

• [EN] PYRAZOLE COMPOUNDS SELECTIVE FOR NEUROTENSIN 2 RECEPTOR<br/>[FR] COMPOSÉS DE PYRAZOLE SÉLECTIFS VIS-À-VIS DU RÉCEPTEUR DE LA NEUROTENSINE DE SOUS-TYPE 2
  申请人：RES TRIANGLE INST

  公开号：WO2015148465A1

  公开（公告）日：2015-10-01

  This invention relates generally to the discovery of pyrazole compounds selective for the neurotensin receptor 2 (NTR2) and uses thereof.

  这项发明通常涉及发现对神经肽受体2（NTR2）具有选择性的吡唑化合物以及其用途。
• The identification of nonpeptide neurotensin receptor partial agonists from the potent antagonist SR48692 using a calcium mobilization assay
  作者：James B. Thomas、Hernán Navarro、Keith R. Warner、Brian Gilmour

  DOI：10.1016/j.bmcl.2009.01.024

  日期：2009.3

  In a search for nonpeptide agonists for the neurotensin receptor (NTR1), we replaced the adamantyl amino acid moiety found in the antagonist SR48692 (1a) with leucine and related alpha-alkylamino acids found in peptide agonists. When tested in a calcium mobilization assay, we found that both D- and L-leucine confer partial agonist activity to the pyrazole scaffold with the L-enantiomer (3a) providing a significantly greater response. A brief SAR survey demonstrated that the observed agonist activity was resilient to changes made to the dimethoxyaryl ring in 3a. The resulting compounds were less potent relative to 3a but showed greater agonist responses. The partial agonist activity was extinguished when the chloroquinoline ring was replaced with naphthalene. Thus, while L-leucine appears to possess a powerful agonist directing affect for the NTR1 receptor, its presence alone in the molecular architecture is not sufficient to insure agonist behavior. (C) 2009 Elsevier Ltd. All rights reserved.
• PYRAZOLE COMPOUNDS SELECTIVE FOR NEUROTENSIN 2 RECEPTOR
  申请人：RESEARCH TRIANGLE INSTITUTE

  公开号：US20170174633A1

  公开（公告）日：2017-06-22

  This invention relates generally to the discovery of pyrazole compounds selective for the neurotensin receptor 2 (NTR2) and uses thereof.
• Identification of 1-({[1-(4-Fluorophenyl)-5-(2-methoxyphenyl)-1<i>H</i>-pyrazol-3-yl]carbonyl}amino)cyclohexane Carboxylic Acid as a Selective Nonpeptide Neurotensin Receptor Type 2 Compound
  作者：James B. Thomas、Angela M. Giddings、Robert W. Wiethe、Srinivas Olepu、Keith R. Warner、Philippe Sarret、Louis Gendron、Jean-Michel Longpre、Yanan Zhang、Scott P. Runyon、Brian P. Gilmour

  DOI：10.1021/jm5003843

  日期：2014.6.26

  Compounds active at neurotensin receptors (NTS1 and NTS2) exert analgesic effects on different types of nociceptive modalities, including thermal, mechanical, and chemical stimuli. The NTS2 preferring peptide JMV-431 (2) and the NTS2 selective nonpeptide compound levocabastine (6) have been shown to be effective in relieving the pain associated with peripheral neuropathies. With the aim of identifying novel nonpeptide compounds selective for NTS2, we examined analogues of SR48692 (5a) using a FLIPR calcium assay in CHO cells stably expressing rat NTS2. This led to the discovery of the NTS2 selective nonpeptide compound 1-([1-(4-fluorophenyl)-5-(2-methoxyphenyl)-1H-pyrazol-3-yl]carbonyl}amino)cyclohexane carboxylic acid (NTRC-739, 7b) starting from the nonselective compound 5a.