1-(7-氯喹啉-4-基)-5-(2,6-二甲氧基苯基)-1H-吡唑-3-羧酸 | 1146757-92-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 1-(7-氯喹啉-4-基)-5-(2,6-二甲氧基苯基)-1H-吡唑-3-羧酸
• 英文名称: 1-(7-chloroquinolin-4-yl)-5-(2,6-dimethoxyphenyl)-1H-pyrazole-3-carboxylic acid
• 英文别名: 1-(7-chloroquinolin-4-yl)-5-(2,6-dimethoxyphenyl)pyrazole-3-carboxylic acid
• CAS: 1146757-92-7
• 化学式: C₂₁H₁₆ClN₃O₄
• 分子量: 409.829
• InChiKey: YIYYOCQXJQNBKM-UHFFFAOYSA-N

物化性质

• 沸点：
  608.4±55.0 °C(Predicted)
• 密度：
  1.40±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  86.5
• 氢给体数：
  1
• 氢受体数：
  6

安全信息

• 储存条件：
  2-8°C

反应信息

• 作为反应物：
  描述：

  1-(7-氯喹啉-4-基)-5-(2,6-二甲氧基苯基)-1H-吡唑-3-羧酸 在 氯化亚砜 、 N,N-二异丙基乙胺 、 bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.5h， 生成 2-[[[1-(7-氯-4-喹啉)-5-(2,6-二甲氧基苯基)-1H-吡唑-3-基]羰基]氨基]-三环[3.3.1.13,7]癸烷-2-羧酸
  参考文献：
  名称：

  The synthesis of neurotensin antagonist SR 48692 for prostate cancer research

  摘要：

  An improved synthesis of the molecule SR 48692 is presented and its use as a neurotensin antagonist biological probe for use in cancer research is described. The preparation includes an number of enhanced chemical conversions and strategies to overcome some of the limiting synthetic transformations in the original chemical route. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.04.075
• 作为产物：
  描述：

  methyl 4-(2,6-dimethoxyphenyl)-2,4-dioxobutanoate sodium salt 在 盐酸 、 水 、 溶剂黄146 、 lithium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 5.0h， 生成 1-(7-氯喹啉-4-基)-5-(2,6-二甲氧基苯基)-1H-吡唑-3-羧酸
  参考文献：
  名称：

  [EN] PYRAZOLE COMPOUNDS SELECTIVE FOR NEUROTENSIN 2 RECEPTOR
  [FR] COMPOSÉS DE PYRAZOLE SÉLECTIFS VIS-À-VIS DU RÉCEPTEUR DE LA NEUROTENSINE DE SOUS-TYPE 2

  摘要：

  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。

  公开号：

  WO2015148465A1

文献信息

• A Machine-Assisted Flow Synthesis of SR48692: A Probe for the Investigation of Neurotensin Receptor-1
  作者：Claudio Battilocchio、Benjamin J. Deadman、Nikzad Nikbin、Matthew O. Kitching、Ian R. Baxendale、Steven V. Ley

  DOI：10.1002/chem.201300696

  日期：2013.6.10

  Here we report the direct comparison of a conventional batch mode synthesis of Meclinertant (SR48692, 1), a neurotensin receptor‐1 antagonist, with its machine‐assisted flow chemistry alternative. By using these enabling tools, combined with solid‐supported reagents and scavengers, many process advantages were observed. Care, however, must be taken not to convert these techniques into expensive solutions

  这里，我们报告Meclinertant（SR48692，的常规分批方式合成的直接比较1），神经降压素受体-1拮抗剂，以其机器辅助流动化学替代。通过使用这些辅助工具，再加上固体支持的试剂和清除剂，可以观察到许多工艺优势。但是，必须注意不要将这些技术转换为不存在的问题的昂贵解决方案。
• 3-amidopyrazole derivatives and pharmaceutical compositions containing
  申请人：Sanofi

  公开号：US05744493A1

  公开（公告）日：1998-04-28

  The present invention relates to new pyrazole derivatives possessing an amide group substituted with an amino acid or one of its derivatives at position 3 and variously substituted in positions 1, 2, 4 or 5 of the pyrazole ring, to a process for preparing these and to pharmaceutical compositions containing the said pyrazole derivatives as an active ingredient.

  本发明涉及一种新的吡唑衍生物，其在3位上具有取代氨基酸或其衍生物的酰胺基团，并在吡唑环的1、2、4或5位上具有不同的取代基。还涉及制备这些衍生物的方法以及含有所述吡唑衍生物作为活性成分的制药组合物。
• 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.
• 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.
• Drugs Fut. 1993, 18, 1137
  作者：

  DOI：——

  日期：——