8-aminosulfonyl-2,3,4,5-tetrahydro-1H-2-benzazepin-1-one | 373384-99-7

• 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-aminosulfonyl-2,3,4,5-tetrahydro-1H-2-benzazepin-1-one
• 英文别名: 1-oxo-2,3,4,5-tetrahydro-1H-2-benzazepine-8-sulfonamide；1-oxo-2,3,4,5-tetrahydro-2-benzazepine-8-sulfonamide
• CAS: 373384-99-7
• 化学式: C₁₀H₁₂N₂O₃S
• 分子量: 240.283
• InChiKey: SDGXZLWHCXDFHJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  97.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  8-aminosulfonyl-2,3,4,5-tetrahydro-1H-2-benzazepin-1-one 在 硼烷四氢呋喃络合物 、 盐酸 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 27.0h， 以73%的产率得到8-aminosulfonyl-2,3,4,5-tetrahydro-1H-2-benzazepine hydrochloride
  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：

  在 ammonium hydroxide 作用下， 以 乙腈 为溶剂， 反应 2.0h， 以0.35 g的产率得到8-aminosulfonyl-2,3,4,5-tetrahydro-1H-2-benzazepin-1-one
  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