8-溴-2,3,4,5-四氢-1H-苯并[D]氮杂 | 223915-77-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 中文名称: 8-溴-2,3,4,5-四氢-1H-苯并[D]氮杂
• 英文名称: 8-bromo-2,3,4,5-tetrahydro-1H-2-benzazepine
• 英文别名: 8-Bromo-2,3,4,5-tetrahydro-1H-benzo[c]azepine
• CAS: 223915-77-3
• 化学式: C₁₀H₁₂BrN
• 分子量: 226.116
• InChiKey: QDGYYHVMHIRDNT-UHFFFAOYSA-N

物化性质

• 沸点：
  296.7±35.0 °C(Predicted)
• 密度：
  1.360±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  12
• 氢给体数：
  1
• 氢受体数：
  1

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  8-溴-2,3,4,5-四氢-1H-苯并[D]氮杂 在 4-二甲氨基吡啶 、 正丁基锂 、 三乙胺 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 为溶剂， 反应 30.0h， 生成 8-methylsulfanyl-2,3,4,5-tetrahydro-1H-2-benzazepine
  参考文献：
  名称：

  Effects of a 3-Alkyl-, 4-Hydroxy- and/or 8-Aromatic-substituent on the Phenylethanolamine N-Methyltransferase Inhibitor Potency and α2-Adrenoceptor Affinity of 2,3,4,5-Tetrahydro-1H-2-benzazepines

  摘要：

  2,3,4,5-Tetrahydro-1H-2-benzazepine (THBA; 1) is nearly 100-fold more selective an inhibitor of phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28) versus the alpha (2)-adrenoceptor than is 1,2,3,4-tetrahydroisoquinoline (THIQ; 2) (1: PNMT K-i = 3.3 muM, alpha (2)-adrenoceptor K-i = 11 muM, selectivity [alpha (2) K-i/PNMT K-i = 3.3; 2: PNMT K-i = 9.7 muM, alpha (2) K-i = 0.35 muM, selectivity 0.036;). Since the PNMT inhibitory activity and selectivity of THIQ were enhanced by the introduction of a hydrophilic electron-withdrawing 7-substituent and a 3-alkyl-substituent, a similar study was conducted on THBA. 8-Nitro-THBA (3) was found to be as potent an inhibitor of PNMT as its THIQ analogue (21) and to be more selective due to its reduced alpha (2)-adrenoceptor affinity (3: PNMT K-i = 0.39 muM, alpha (2) K-i = 66 muM, selectivity = 170; 21: PNMT K-i = 0.41 muM, (alpha (2) K-i = 4.3 muM, selectivity = 10). Introduction of a 3-alkyl substituent on the THBA nucleus decreased both the alpha (2)-adrenoceptor affinity and the PNMT inhibitory activity, suggesting an area of steric bulk intolerance at both sites. 4-Hydroxy-THBA (15), which can be considered a conformationally-restricted analogue of 3-hydroxymethyl-THIQ (30), exhibited poorer PNMT inhibitory activity and less selectivity than 30 (15: PNMT K-i = 58 muM, alpha (2) K-i = 100 muM, selectivity = 1.7; 30 PNMT K-i = 1.1 muM, alpha (2) K-i = 6.6 muM, selectivity = 6.0). While the addition of an 8-nitro group to 15 increased the selectivity of 16 as compared to its THIQ analogue (31), it was not as potent at PNMT nor as selective as 8-nitro-THBA (3) (16, PNMT K-i = 5.3 muM, alpha (2) K-i = 680 muM, selectivity = 130; 31: PNMT K-i = 0.29 muM, alpha (2) K-i = 19 muM, selectivity = 66). Compound 3 is the most selective (PNMT/alpha (2) and one of the more potent at PNMT compounds yet reported in the benzazepine series, and should have sufficient lipophilicity to penetrate the blood-brain barrier (CLogP = 1.8). (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00112-2
• 作为产物：
  描述：

  8-硝基-2,3,4,5-四氢-1H-苯并[c]氮杂卓 在 platinum(IV) oxide 氢溴酸 、 氢气 、 亚硝酸 作用下， 以 乙醇 、 水 为溶剂， 80.0 ℃ 、344.74 kPa 条件下， 反应 4.5h， 生成 8-溴-2,3,4,5-四氢-1H-苯并[D]氮杂
  参考文献：
  名称：

  Effects of a 3-Alkyl-, 4-Hydroxy- and/or 8-Aromatic-substituent on the Phenylethanolamine N-Methyltransferase Inhibitor Potency and α2-Adrenoceptor Affinity of 2,3,4,5-Tetrahydro-1H-2-benzazepines

  摘要：

  2,3,4,5-Tetrahydro-1H-2-benzazepine (THBA; 1) is nearly 100-fold more selective an inhibitor of phenylethanolamine N-methyltransferase (PNMT, EC 2.1.1.28) versus the alpha (2)-adrenoceptor than is 1,2,3,4-tetrahydroisoquinoline (THIQ; 2) (1: PNMT K-i = 3.3 muM, alpha (2)-adrenoceptor K-i = 11 muM, selectivity [alpha (2) K-i/PNMT K-i = 3.3; 2: PNMT K-i = 9.7 muM, alpha (2) K-i = 0.35 muM, selectivity 0.036;). Since the PNMT inhibitory activity and selectivity of THIQ were enhanced by the introduction of a hydrophilic electron-withdrawing 7-substituent and a 3-alkyl-substituent, a similar study was conducted on THBA. 8-Nitro-THBA (3) was found to be as potent an inhibitor of PNMT as its THIQ analogue (21) and to be more selective due to its reduced alpha (2)-adrenoceptor affinity (3: PNMT K-i = 0.39 muM, alpha (2) K-i = 66 muM, selectivity = 170; 21: PNMT K-i = 0.41 muM, (alpha (2) K-i = 4.3 muM, selectivity = 10). Introduction of a 3-alkyl substituent on the THBA nucleus decreased both the alpha (2)-adrenoceptor affinity and the PNMT inhibitory activity, suggesting an area of steric bulk intolerance at both sites. 4-Hydroxy-THBA (15), which can be considered a conformationally-restricted analogue of 3-hydroxymethyl-THIQ (30), exhibited poorer PNMT inhibitory activity and less selectivity than 30 (15: PNMT K-i = 58 muM, alpha (2) K-i = 100 muM, selectivity = 1.7; 30 PNMT K-i = 1.1 muM, alpha (2) K-i = 6.6 muM, selectivity = 6.0). While the addition of an 8-nitro group to 15 increased the selectivity of 16 as compared to its THIQ analogue (31), it was not as potent at PNMT nor as selective as 8-nitro-THBA (3) (16, PNMT K-i = 5.3 muM, alpha (2) K-i = 680 muM, selectivity = 130; 31: PNMT K-i = 0.29 muM, alpha (2) K-i = 19 muM, selectivity = 66). Compound 3 is the most selective (PNMT/alpha (2) and one of the more potent at PNMT compounds yet reported in the benzazepine series, and should have sufficient lipophilicity to penetrate the blood-brain barrier (CLogP = 1.8). (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(01)00112-2

文献信息

• [EN] NRF2 ACTIVATOR<br/>[FR] ACTIVATEUR DE NRF2
  申请人：BIOGEN MA INC

  公开号：WO2018140876A1

  公开（公告）日：2018-08-02

  Provided are tetrahydroisoquinoline derivatives as Nrf2 activators.

  提供了四氢异喹啉衍生物作为Nrf2激活剂。
• N-Myristoyl Transferase Inhibitors
  申请人：Brand Stephen

  公开号：US20110312921A1

  公开（公告）日：2011-12-22

  The present invention relates to N-heterocyclic sulphonamide compounds, in particular pyrazole sulphonamide compounds, and their use as N-myristoyl transferase inhibitors.

  本发明涉及N-杂环磺胺化合物，特别是吡唑磺胺化合物，以及它们作为N-肉豆蔻酰转移酶抑制剂的用途。
• N-myristoyl transferase inhibitors
  申请人：Brand Stephen

  公开号：US09156811B2

  公开（公告）日：2015-10-13

  The present invention relates to N-heterocyclic sulphonamide compounds, in particular pyrazole sulphonamide compounds, and their use as N-myristoyl transferase inhibitors.

  本发明涉及N-杂环磺胺化合物，特别是吡唑磺胺化合物，以及它们作为N-肟酰基转移酶抑制剂的用途。
• [EN] COMPOUNDS AS GLP-1R AGONISTS<br/>[FR] COMPOSÉS EN TANT QU'AGONISTES DE GLP-1R
  申请人：TERNS PHARMACEUTICALS INC

  公开号：WO2022040600A1

  公开（公告）日：2022-02-24

  The present application provides compounds that may be used as a glucagon-like peptide-1 receptors (GLP-1R) agonist, or stereoisomers, tautomers, or pharmaceutically acceptable salts of any of the foregoing. Also provided are pharmaceutical compositions containing such compounds, or stereoisomers, tautomers, or pharmaceutically acceptable salts of any of the foregoing. Methods of prepare these compounds and compositions and method of using them to treat or present a disease or a condition mediated by GLP-1R.

  本申请提供了可用作胰高血糖素样肽-1受体（GLP-1R）激动剂的化合物，或者是这些化合物的立体异构体、互变异构体，或者是任何这些化合物的药用可接受盐。还提供了含有这些化合物、或者这些化合物的立体异构体、互变异构体，或者这些化合物的药用可接受盐的药物组合物。制备这些化合物和组合物的方法，以及使用它们来治疗或预防由GLP-1R介导的疾病或状况的方法。
• N-MYRISTOYL TRANSFERASE INHIBITORS
  申请人：Brand Stephen

  公开号：US20160060224A1

  公开（公告）日：2016-03-03

  The present invention relates to N-heterocyclic sulphonamide compounds, in particular pyrazole sulphonamide compounds, and their use as N-myristoyl transferase inhibitors.

  本发明涉及N-杂环磺酰胺化合物，特别是吡唑磺酰胺化合物，及其作为N-肉豆蔻酰转移酶抑制剂的用途。