(Z)-2-{1-[2-chloro-4-(3-methyl-1H-pyrazol-1-yl)benzoyl]-4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepin-5-ylidene}-N-(thiazol-2-ylmethyl)acetamide | 530090-23-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: (Z)-2-{1-[2-chloro-4-(3-methyl-1H-pyrazol-1-yl)benzoyl]-4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepin-5-ylidene}-N-(thiazol-2-ylmethyl)acetamide
• 英文别名: 5H-1-benzazepin-5-ylidene acetamide, 1m；(2Z)-2-[1-[2-chloro-4-(3-methylpyrazol-1-yl)benzoyl]-4,4-difluoro-2,3-dihydro-1-benzazepin-5-ylidene]-N-(1,3-thiazol-2-ylmethyl)acetamide
• CAS: 530090-23-4
• 化学式: C₂₇H₂₂ClF₂N₅O₂S
• 分子量: 554.02
• InChiKey: KVUXXTSFKCYQJS-QNGOZBTKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  38
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  108
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-氨基甲基噻唑 、 (2Z)-{1-[2-chloro-4-(3-methyl-1H-pyrazol-1-yl)benzoyl]-4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepin-5-ylidene}acetic acid 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以74%的产率得到(Z)-2-{1-[2-chloro-4-(3-methyl-1H-pyrazol-1-yl)benzoyl]-4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepin-5-ylidene}-N-(thiazol-2-ylmethyl)acetamide
  参考文献：
  名称：

  Synthesis and structure–activity relationships of amide derivatives of (4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepin-5-ylidene)acetic acid as selective arginine vasopressin V2 receptor agonists

  摘要：

  A series of (4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepin-5-ylidene)acetamide derivatives was synthesized, and their structure-activity relationships were examined in order to identify potent and selective arginine vasopressin V-2 receptor agonists. Attempts to substitute other chemical groups in place of the 2-pyridilmethyl moiety of 1a led to the discovery that potent V-2 binding affinity could be obtained with a wide range of functional groups. This structural tolerance allowed for the manipulation of other attributes, such as selectivity against V-1a receptor affinity or avoidance of the undesirable inhibition of cytochrome P450 (CYP), without losing potent affinity for the V-2 receptor. Some representative compounds obtained in this study were also found to decrease urine volume in awake rats. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.03.001

文献信息

• Synthesis and structure–activity relationships of amide derivatives of (4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepin-5-ylidene)acetic acid as selective arginine vasopressin V2 receptor agonists
  作者：Issei Tsukamoto、Hiroyuki Koshio、Takahiro Kuramochi、Chikashi Saitoh、Hiroko Yanai-Inamura、Chika Kitada-Nozawa、Eisaku Yamamoto、Takeyuki Yatsu、Yoshiaki Shimada、Shuichi Sakamoto、Shin-ichi Tsukamoto

  DOI：10.1016/j.bmc.2009.03.001

  日期：2009.4

  A series of (4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepin-5-ylidene)acetamide derivatives was synthesized, and their structure-activity relationships were examined in order to identify potent and selective arginine vasopressin V-2 receptor agonists. Attempts to substitute other chemical groups in place of the 2-pyridilmethyl moiety of 1a led to the discovery that potent V-2 binding affinity could be obtained with a wide range of functional groups. This structural tolerance allowed for the manipulation of other attributes, such as selectivity against V-1a receptor affinity or avoidance of the undesirable inhibition of cytochrome P450 (CYP), without losing potent affinity for the V-2 receptor. Some representative compounds obtained in this study were also found to decrease urine volume in awake rats. (C) 2009 Elsevier Ltd. All rights reserved.