8-aMino-2,3,4,5-tetrahydro-1H-benzo[c]azepine | 72232-25-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: 8-aMino-2,3,4,5-tetrahydro-1H-benzo[c]azepine
• 英文别名: 2,3,4,5-tetrahydro-1H-2-benzazepin-8-amine
• CAS: 72232-25-8
• 化学式: C₁₀H₁₄N₂
• 分子量: 162.235
• InChiKey: DAEJBLXGXUDKSD-UHFFFAOYSA-N

物化性质

• 沸点：
  325.7±37.0 °C(Predicted)
• 密度：
  1.065±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 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：
  38
• 氢给体数：
  2
• 氢受体数：
  2

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  8-aMino-2,3,4,5-tetrahydro-1H-benzo[c]azepine 在 4-二甲氨基吡啶 、 正丁基锂 、 氢溴酸 、 亚硝酸 、 三乙胺 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 水 为溶剂， 反应 31.5h， 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 氢气 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以95%的产率得到8-aMino-2,3,4,5-tetrahydro-1H-benzo[c]azepine
  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] HETEROARYL COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS HÉTÉROARYLE ET LEURS UTILISATIONS
  申请人：CELGENE AVILOMICS RES INC

  公开号：WO2016090079A1

  公开（公告）日：2016-06-09

  The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same. It has now been found that compounds of this invention, and pharmaceutically acceptable compositions thereof, are effective as inhibitors of one or more protein kinases. Such compounds have general formula I or a pharmaceutically acceptable salt thereof, wherein Ring A, Ring B, W, Ry, R3 and R4 are as defined herein.

  本发明提供了化合物、其药学上可接受的组合物，以及使用它们的方法。现在已经发现，本发明的化合物及其药学上可接受的组合物作为一种或多种蛋白激酶的抑制剂是有效的。这些化合物具有通式I或其药学上可接受的盐，其中环A、环B、W、Ry、R3和R4如本文所定义。
• 2-Benzazepine compounds, processes for their preparation and pharmaceutical compositions containing them
  申请人：SMITHKLINE BECKMAN CORPORATION

  公开号：EP0002624A1

  公开（公告）日：1979-06-27

  This invention concerns a process for preparing 2- benzazepine compounds which inhibit the enzyme phenylethanolamine N-methyltransferase and show activity in reducing anxiety. The compounds produced have substituents in the 8- and/or 9-positions, and optionally substituents in the 1- and 2-positions. The compounds are prepared by debenzylating an appropriately substituted N-benzyl 2-benzazepine with optional acylation and reduction, or with optional ozidation and alkylation of the debenzylated product to introduce 2- and 1-position substituents, respectively. Acid addition salts of the compounds are also prepared.

  本发明涉及一种制备 2-苯并氮杂卓化合物的工艺，该化合物可抑制苯乙醇胺 N-甲基转移酶，并具有减轻焦虑的活性。所制备的化合物在 8 位和/或 9 位上有取代基，在 1 位和 2 位上也有取代基。这些化合物的制备方法是将适当取代的 N-苄基 2-苯并氮杂卓进行去苄基化，然后进行任选的酰化和还原，或对去苄基化产物进行任选的羰基化和烷基化，以分别引入 2 位和 1 位取代基。还可制备这些化合物的酸加成盐。
• IMIDAZOPYRIDINE DERIVATIVES AS KINASE INHIBITORS
  申请人：GLAXO GROUP LIMITED

  公开号：EP1490367B1

  公开（公告）日：2008-07-23
• 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
  作者：Gary L. Grunewald、Vilas H. Dahanukar、Kevin R. Criscione

  DOI：10.1016/s0968-0896(01)00112-2

  日期：2001.8

  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.