4-chloro-6,7-dimethoxy-2-propylquinazoline | 162364-65-0

• 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-6,7-dimethoxy-2-propylquinazoline
• CAS: 162364-65-0
• 化学式: C₁₃H₁₅ClN₂O₂
• 分子量: 266.727
• InChiKey: VGBCOWRHPAPCEK-UHFFFAOYSA-N

物化性质

• 沸点：
  320.2±42.0 °C(Predicted)
• 密度：
  1.216±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.384
• 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-6,7-dimethoxy-2-propylquinazoline 、 1-(2-methoxyphenyl)piperazine hydrochloride 在 potassium carbonate 作用下， 以 1,4-二氧六环 为溶剂， 反应 1.5h， 以244.6 mg的产率得到6,7-dimethoxy-4-(4-(2-methoxyphenyl)piperazin-1-yl)-2-propylquinazoline
  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
• 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， 反应 30.0h， 生成 4-chloro-6,7-dimethoxy-2-propylquinazoline
  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。
• Benzotriazines having adenosine uptake inhibitor activity
  申请人：Kyowa Hakko Kogyo Co., Ltd.

  公开号：US05605900A1

  公开（公告）日：1997-02-25

  The present invention relates to an adenosine uptake inhibitor and an agent for the myocardium protection or the prevention or treatment of inflammatory edema, comprising a 1,2,3,4-tetrahydro-2,4-dioxoquinazoline derivative represented by formula (I): ##STR1## wherein R.sup.1 represents hydrogen, substituted or unsubstituted lower alkyl, alkenyl, or substituted or unsubstituted aralkyl; R.sup.2, R.sup.3, R.sup.4, and R.sup.5 independently represent hydrogen, halogen, amino, mono- or di(lower alkyl)amino, lower alkanoylamino, nitro, cyano, substituted or unsubstituted lower alkyl, hydroxy, lower alkoxy, lower alkylthio, carboxy, lower alkoxycarbonyl, lower alkanoyl, aralkyloxy, or lower alkanoyloxy; R.sup.6, R.sup.7, R.sup.8, and R.sup.9 independently represent hydrogen, hydroxy, substituted or unsubstituted lower alkoxy, or aralkyloxy, or any adjoining two of them are combined to form methylenedioxy; R.sup.10 represents hydrogen or lower alkyl; and Y and Z independently represent N or C-R.sup.11 (wherein R.sup.11 represents hydrogen, substituted or unsubstituted lower alkyl, or halogen), or a pharmaceutically acceptable salt thereof as an active ingredient.

  本发明涉及一种腺苷摄取抑制剂和用于心肌保护或预防或治疗炎性水肿的药剂，包括由式（I）表示的1,2,3,4-四氢-2,4-二氧喹唑啉衍生物：其中R.sup.1表示氢，取代或未取代的较低烷基，烯基或取代或未取代的芳基烷基；R.sup.2，R.sup.3，R.sup.4和R.sup.5独立地表示氢，卤素，氨基，单或二（较低烷基）氨基，较低烷酰胺基，硝基，氰基，取代或未取代的较低烷基，羟基，较低烷氧基，较低烷基硫基，羧基，较低烷氧羰基，较低烷酰基，芳基烷氧基或较低烷氧基酰氧基；R.sup.6，R.sup.7，R.sup.8和R.sup.9独立地表示氢，羟基，取代或未取代的较低烷氧基或芳基烷氧基，或其中任意相邻的两个被结合形成亚甲二氧基；R.sup.10表示氢或较低烷基；Y和Z独立地表示N或C-R.sup.11（其中R.sup.11表示氢，取代或未取代的较低烷基或卤素），或其药学上可接受的盐作为活性成分。
• Piperidinyl-dioxoquinazolines as adenosine reuptake inhibitors
  申请人：Kyowa Hakko Kogyo Co., Ltd.

  公开号：US05624926A1

  公开（公告）日：1997-04-29

  The present invention relates to an adenosine uptake inhibitor and an agent for the myocardium protection or the prevention or treatment of inflammatory edema, comprising a 1,2,3,4-tetrahydro-2,4-dioxoquinazoline derivative represented by formula (I): ##STR1## wherein R.sup.1 represents hydrogen, substituted or unsubstituted lower alkyl, alkenyl, or substituted or unsubstituted aralkyl; R.sup.2, R.sup.3, R.sup.4, and R.sup.5 independently represent hydrogen, halogen, amino, mono- or di(lower alkyl)amino, lower alkanoylamino, nitro, cyano, substituted or unsubstituted lower alkyl, hydroxy, lower alkoxy, lower alkylthio, carboxy, lower alkoxycarbonyl, lower alkanoyl, aralkyloxy, or lower alkanoyloxy; R.sup.6, R.sup.7, R.sup.8, and R.sup.9 independently represent hydrogen, hydroxy, substituted or unsubstituted lower alkoxy, or aralkyloxy, or any adjoining two of them are combined to form methylenedioxy; R.sup.10 represents hydrogen or lower alkyl; and Y and Z independently represent N or C--R.sup.11 (wherein R.sup.11 represents hydrogen, substituted or unsubstituted lower alkyl, or halogen), or a pharmaceutically acceptable salt thereof as an active ingredient.

  本发明涉及一种腺苷摄取抑制剂和用于心肌保护、预防或治疗炎性水肿的药剂，包括由式(I)表示的1,2,3,4-四氢-2,4-二氧喹唑啉衍生物：##STR1## 其中R.sup.1表示氢、取代或未取代的低级烷基、烯基或取代或未取代的芳基烷基；R.sup.2、R.sup.3、R.sup.4和R.sup.5独立地表示氢、卤素、氨基、单-或双(低级烷基)氨基、低级烷酰胺基、硝基、氰基、取代或未取代的低级烷基、羟基、低级烷氧基、低级烷硫基、羧基、低级烷氧羰基、低级烷酰基、芳基烷氧基或低级烷氧羰氧基；R.sup.6、R.sup.7、R.sup.8和R.sup.9独立地表示氢、羟基、取代或未取代的低级烷氧基或芳基烷氧基，或其中任意相邻的两个结合形成亚甲二氧基；R.sup.10表示氢或低级烷基；Y和Z独立地表示N或C-R.sup.11（其中R.sup.11表示氢、取代或未取代的低级烷基或卤素），或其药学上可接受的盐作为活性成分。
• Isoquinolines having adenosine uptake inhibitor activity
  申请人：Kyowa Hakko Kogyo Co., Ltd.

  公开号：US05658917A1

  公开（公告）日：1997-08-19

  The present invention relates to an adenosine uptake inhibitor and an agent for the myocardium protection or the prevention or treatment of inflammatory edema, comprising a 1,2,3,4-tetrahydro-2,4-dioxoquinazoline derivative represented by formula (I): ##STR1## wherein R.sup.1 represents hydrogen, substituted or unsubstituted lower alkyl, alkenyl, or substituted or unsubstituted aralkyl; R.sup.2, R.sup.3, R.sup.4, and R.sup.5 independently represent hydrogen, halogen, amino, mono- or di(lower alkyl)amino, lower alkanoylamino, nitro, cyano, substituted or unsubstituted lower alkyl, hydroxy, lower alkoxy, lower alkylthio, carboxy, lower alkoxycarbonyl, lower alkanoyl, aralkyloxy, or lower alkanoyloxy; R.sup.6, R.sup.7, R.sup.8, and R.sup.9 independently represent hydrogen, hydroxy, substituted or unsubstituted lower alkoxy, or aralkyloxy, or any adjoining two of them are combined to form methylenedioxy; R.sup.10 represents hydrogen or lower alkyl; and Y and Z independently represent N or C--R.sup.11 (wherein R.sup.11 represents hydrogen, substituted or unsubstituted lower alkyl, or halogen), or a pharmaceutically acceptable salt thereof as an active ingredient.

  本发明涉及一种腺苷摄取抑制剂和用于心肌保护或预防或治疗炎性水肿的药剂，包括由式（I）表示的1,2,3,4-四氢-2,4-二氧喹唑啉衍生物：##STR1## 其中R.sup.1表示氢，取代或未取代的低碳基，烯基或取代或未取代的芳基甲基；R.sup.2、R.sup.3、R.sup.4和R.sup.5分别表示氢，卤素，氨基，单-或二（低碳基）氨基，低烷酰胺基，硝基，氰基，取代或未取代的低碳基，羟基，低烷氧基，低烷硫基，羧基，低烷氧羰基，低烷酰基，芳基甲氧基或低烷氧基酰氧基；R.sup.6、R.sup.7、R.sup.8和R.sup.9独立地表示氢，羟基，取代或未取代的低烷氧基或芳基甲氧基，或其中任意相邻两个结合形成亚甲二氧基；R.sup.10表示氢或低碳基；Y和Z独立地表示N或C--R.sup.11（其中R.sup.11表示氢，取代或未取代的低碳基或卤素），或其药学上可接受的盐作为活性成分。
• 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。