4-chloro-2-cyclopropyl-6,7-dimethoxyquinazoline | 1448676-37-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 4-chloro-2-cyclopropyl-6,7-dimethoxyquinazoline
• CAS: 1448676-37-6
• 化学式: C₁₃H₁₃ClN₂O₂
• 分子量: 264.711
• InChiKey: OEJOIELCVIWDSE-UHFFFAOYSA-N

物化性质

• 沸点：
  328.1±42.0 °C(Predicted)
• 密度：
  1.337±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  44.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-chloro-2-cyclopropyl-6,7-dimethoxyquinazoline 在 铁粉 、 sodium cyanoborohydride 、 potassium carbonate 、 氯化铵 、 溶剂黄146 作用下， 以 甲醇 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 21.0h， 生成 (2-chloro-ethyl)-{2-[4-(2-cyclopropyl-6,7-dimethoxy-quinazolin-4-yl)-piperazin-1-yl]-phenyl}-amine
  参考文献：
  名称：

  [EN] SMALL MOLECULE AGONISTS OF NEUROTENSIN RECEPTOR 1
  [FR] AGONISTES À PETITES MOLÉCULES DE RÉCEPTEUR DE NEUROTENSINE 1

  摘要：

  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。

  公开号：

  WO2014100501A1
• 作为产物：
  描述：

  2-氨基-4,5-二甲氧基苯甲酸甲酯 在 盐酸 、 三氯氧磷 作用下， 以 1,4-二氧六环 为溶剂， 生成 4-chloro-2-cyclopropyl-6,7-dimethoxyquinazoline
  参考文献：
  名称：

  [EN] SMALL MOLECULE AGONISTS OF NEUROTENSIN RECEPTOR 1
  [FR] AGONISTES À PETITES MOLÉCULES DE RÉCEPTEUR DE NEUROTENSINE 1

  摘要：

  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。

  公开号：

  WO2014100501A1

文献信息

• Discovery of β-Arrestin Biased, Orally Bioavailable, and CNS Penetrant Neurotensin Receptor 1 (NTR1) Allosteric Modulators
  作者：Anthony B. Pinkerton、Satyamaheshwar Peddibhotla、Fusayo Yamamoto、Lauren M. Slosky、Yushi Bai、Patrick Maloney、Paul Hershberger、Michael P. Hedrick、Bekhi Falter、Robert J. Ardecky、Layton H. Smith、Thomas D. Y. Chung、Michael R. Jackson、Marc G. Caron、Lawrence S. Barak

  DOI：10.1021/acs.jmedchem.9b00340

  日期：2019.9.12

  Neurotensin receptor 1 (NTR1) is a G protein coupled receptor that is widely expressed throughout the central nervous system where it acts as a neuromodulator. Neurotensin receptors have been implicated in a wide variety of CNS disorders, but despite extensive efforts to develop small molecule ligands there are few reports of such compounds. Herein we describe the optimization of a quinazoline based

  神经降压素受体1（NTR1）是一种G蛋白偶联受体，在整个中枢神经系统中广泛表达，在其中它充当神经调节剂。神经降压素受体与多种中枢神经系统疾病有关，但是尽管为开发小分子配体付出了巨大的努力，但很少有此类化合物的报道。在这里，我们描述了基于喹唑啉的铅的优化，以得到18（SBI-553），这是一种有效的脑渗透NTR1变构调节剂。
• [EN] ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE-1 (ENPP1) INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS D'ECTONUCLÉOTIDE PYROPHOSPHATASE-PHOSPHODIESTÉRASE 1 (ENPP1) ET LEURS UTILISATIONS
  申请人：INTEGRAL BIOSCIENCES PRIVATE LTD

  公开号：WO2022091048A1

  公开（公告）日：2022-05-05

  The present invention discloses compounds useful in treatment of conditions associated with dysfunction of ectonucleotide pyrophosphatase / phosphodiesterase-1 (ENPP1) enzyme. Specifically, the present invention discloses compound of formula (J) which exhibit inhibitory activity against ENPP1. Method of treating conditions associated with over-expression of ENPP1 gene with such compound is disclosed. Uses thereof, pharmaceutical composition, and kits are also disclosed.

  本发明揭示了在治疗与外核苷酸焦磷酸酶/磷酸二酯酶-1 (ENPP1)酶功能障碍相关的疾病中有用的化合物。具体而言，本发明揭示了公式（J）的化合物，这些化合物表现出对ENPP1的抑制活性。揭示了使用这种化合物治疗与ENPP1基因过度表达相关的疾病的方法。还揭示了其用途、制药组合物和试剂盒。
• 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。
• 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.
• ECTONUCLEOTIDE PYROPHOSPHATASE-PHOSPHODIESTERASE-1 (ENPP1) INHIBITORS AND USES THEREOF
  申请人：INTEGRAL BIOSCIENCES PRIVATE LIMITED

  公开号：US20220135598A1

  公开（公告）日：2022-05-05

  The present invention discloses compounds useful in treatment of conditions associated with dysfunction of ectonucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1) enzyme. Specifically, the present invention discloses compound of formula (J) which exhibit inhibitory activity against ENPP1. Method of treating conditions associated with over-expression of ENPP1 gene with such compound is disclosed. Uses thereof, pharmaceutical composition, and kits are also disclosed.