2-cyclopentyl-6,7-dimethoxy-4-(4-(2-methoxyphenyl)piperazin-1-yl)quinazoline | 1448676-61-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 2-cyclopentyl-6,7-dimethoxy-4-(4-(2-methoxyphenyl)piperazin-1-yl)quinazoline
• 英文别名: 1-[4-(2-Cyclopentyl-6,7-dimethoxyquinazolin-4-yl)piperazinyl]-2-methoxybenzene；2-cyclopentyl-6,7-dimethoxy-4-[4-(2-methoxyphenyl)piperazin-1-yl]quinazoline
• CAS: 1448676-61-6
• 化学式: C₂₆H₃₂N₄O₃
• 分子量: 448.565
• InChiKey: VEWIAFHMDFXVFL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  60
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-氨基-4,5-二甲氧基苯甲酸甲酯 在 盐酸 、 potassium carbonate 、 三氯氧磷 作用下， 以 1,4-二氧六环 为溶剂， 反应 31.5h， 生成 2-cyclopentyl-6,7-dimethoxy-4-(4-(2-methoxyphenyl)piperazin-1-yl)quinazoline
  参考文献：
  名称：

  Discovery of ML314, a Brain Penetrant Nonpeptidic β-Arrestin Biased Agonist of the Neurotensin NTR1 Receptor

  摘要：

  The neurotensin 1 receptor (NTR1) is an important therapeutic target for a range of disease states including addiction. A high-throughput screening campaign, followed by medicinal chemistry optimization, led to the discovery of a nonpeptidic beta-arrestin biased agonist for NTR1. The lead compound, 2-cyclopropyl-6,7-dimethoxy-4-(4-(2-methoxyphenyl)-piperazin-1-yl)quinazoline, 32 (ML314), exhibits full agonist behavior against NTR1 (EC50 = 2.0 mu M) in the primary assay and selectivity against NTR2. The effect of 32 is blocked by the NTR1 antagonist SR142948A in a dose-dependent manner. Unlike peptide-based NTR1 agonists, compound 32 has no significant response in a Ca2+ mobilization assay and is thus a biased agonist that activates the beta-arrestin pathway rather than the traditional G(q) coupled pathway. This bias has distinct biochemical and functional consequences that may lead to physiological advantages. Compound 32 displays good brain penetration in rodents, and studies examining its in vivo properties are underway.

  DOI：

  10.1021/ml400176n

文献信息

• [EN] SMALL MOLECULE AGONISTS OF NEUROTENSIN RECEPTOR 1<br/>[FR] AGONISTES À PETITES MOLÉCULES DE RÉCEPTEUR DE NEUROTENSINE 1
  申请人：SANFORD BURNHAM MED RES INST

  公开号：WO2014100501A1

  公开（公告）日：2014-06-26

  Provided herein are small molecule neurotensin receptor agonists, compositions comprising the compounds, and methods of using the compounds and compositions comprising the compounds.

  提供的是小分子神经降压素受体激动剂，包含这些化合物的组合物，以及使用这些化合物和包含这些化合物的组合物的方法。
• SMALL MOLECULE AGONISTS OF NEUROTENSIN RECEPTOR 1
  申请人：SANFORD-BURNHAM MEDICAL RESEARCH INSTITUTE

  公开号：US20150329497A1

  公开（公告）日：2015-11-19

  Provided herein are small molecule neurotensin receptor agonists, compositions comprising the compounds, and methods of using the compounds and compositions comprising the compounds.

  本文提供了小分子神经肽T受体激动剂，包括这些化合物的组合物和使用这些化合物和组合物的方法。
• US9868707B2
  申请人：——

  公开号：US9868707B2

  公开（公告）日：2018-01-16
• Discovery of ML314, a Brain Penetrant Nonpeptidic β-Arrestin Biased Agonist of the Neurotensin NTR1 Receptor
  作者：Satyamaheshwar Peddibhotla、Michael P. Hedrick、Paul Hershberger、Patrick R. Maloney、Yujie Li、Monika Milewski、Palak Gosalia、Wilson Gray、Alka Mehta、Eliot Sugarman、Becky Hood、Eigo Suyama、Kevin Nguyen、Susanne Heynen-Genel、Stefan Vasile、Sumeet Salaniwal、Derek Stonich、Ying Su、Arianna Mangravita-Novo、Michael Vicchiarelli、Gregory P. Roth、Layton H. Smith、Thomas D. Y. Chung、Glen R. Hanson、James B. Thomas、Marc G. Caron、Lawrence S. Barak、Anthony B. Pinkerton

  DOI：10.1021/ml400176n

  日期：2013.9.12

  The neurotensin 1 receptor (NTR1) is an important therapeutic target for a range of disease states including addiction. A high-throughput screening campaign, followed by medicinal chemistry optimization, led to the discovery of a nonpeptidic beta-arrestin biased agonist for NTR1. The lead compound, 2-cyclopropyl-6,7-dimethoxy-4-(4-(2-methoxyphenyl)-piperazin-1-yl)quinazoline, 32 (ML314), exhibits full agonist behavior against NTR1 (EC50 = 2.0 mu M) in the primary assay and selectivity against NTR2. The effect of 32 is blocked by the NTR1 antagonist SR142948A in a dose-dependent manner. Unlike peptide-based NTR1 agonists, compound 32 has no significant response in a Ca2+ mobilization assay and is thus a biased agonist that activates the beta-arrestin pathway rather than the traditional G(q) coupled pathway. This bias has distinct biochemical and functional consequences that may lead to physiological advantages. Compound 32 displays good brain penetration in rodents, and studies examining its in vivo properties are underway.