methyl (2Z)-(4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepin-5-ylidene)acetate | 183171-54-2

• 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: methyl (2Z)-(4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepin-5-ylidene)acetate
• 英文别名: methyl (Z)-(4,4-difluoro-2,3,4,5-tetrahydro-1H-1-benzazepin-5-ylidene)acetate；methyl (Z)-[4,4-difluoro-2,3,4,5-tetrahydro-1H-1-benzoazepin-5-ylidene]acetate；(Z)-methyl (4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepin-5-ylidene)acetate；[(Z)-4,4-Difluoro-2,3,4,5-tetrahydro-1H-1-benzazepine-5-ylidene]acetic acid methyl ester；methyl (2Z)-2-(4,4-difluoro-2,3-dihydro-1H-1-benzazepin-5-ylidene)acetate
• CAS: 183171-54-2
• 化学式: C₁₃H₁₃F₂NO₂
• 分子量: 253.249
• InChiKey: HNTTUOZVNTUYCD-NTMALXAHSA-N

物化性质

• 沸点：
  356.3±42.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl (2Z)-(4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepin-5-ylidene)acetate 在 吡啶 、 sodium hydroxide 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 tin(ll) chloride 作用下， 以 甲醇 、 二氯甲烷 、 乙酸乙酯 、 乙腈 为溶剂， 反应 33.0h， 生成 YM218
  参考文献：
  名称：

  Synthesis and biological activity of novel 4,4-difluorobenzazepine derivatives as non-peptide antagonists of the arginine vasopressin V1A receptor

  摘要：

  To find potent and selective antagonists of the arginine vasopressin (AVP) V-1A receptor, optimization studies of compounds structurally related to (Z)-N-{4'-[(4,4-difluoro-5-carbamoylmethylidene-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl)carbon-yl]phenyl}carboxamide were performed. The synthesis and phamacological properties of these compounds are described. We first investigated the effect of the carboxamide moiety, and found that a 2-methylfuran-3-carbonyl group at this position increased V-1A binding affinity and selectivity for the V-1A receptor versus the V-2 receptor. The amino group of the 5-carbamoylmethylidene moiety was also examined, and a 4-piperidinopiperidino group was found to be optimal at this position. The hemifumarate of compound 121 (YM218) was shown to exhibit potent binding affinity, V-1A receptor selectivity, and in vivo antagonist activity. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.10.035
• 作为产物：
  描述：

  (E/Z)-(4,4-difluoro-1-tosyl-1,2,3,4-tetrahydro-5H-1-benzazepin-5-ylidene)acetic acid 在 硫酸 作用下， 反应 21.5h， 生成 methyl (2Z)-(4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepin-5-ylidene)acetate
  参考文献：
  名称：

  使用二价阴离子霍纳-沃兹沃斯-埃蒙斯试剂立体选择性合成（Z）-（4,4-二氟-2,3,4,5-四氢-1H-1-苯并ze庚因-5-亚甲基）乙酸甲酯。

  摘要：

  描述了（Z）-（4,4-二氟-2,3,4,5-四氢-1H-1-苯并ze庚因-5-亚烷基）乙酸酯（1a）的立体选择性合成。基于对将亚甲基引入苯并ze庚因的5-位上的反应条件的研究，获得了霍纳-沃兹沃思-埃蒙斯（HWE）反应的Z-选择性。

  DOI：

  10.1248/cpb.53.589

文献信息

• 4,4-difluoro-2,3,4,5-tetrahydro-1H-1-benzoazepine derivatives and drug compositions containing them
  申请人：Yamanouchi Pharmaceutical Co., Ltd.

  公开号：US06340678B1

  公开（公告）日：2002-01-22

  4,4-difluoro-2,3,4,5-tetrahydro-1H-1-benzoazepine compounds or salts thereof and pharmaceutical compositions containing 4,4-difluoro-2,3,4,5-tetrahydro-1H-1-benzoazepine compounds, or salts thereof, and a pharmaceutically acceptable carrier. The chemical structure of these compounds is characterized by a difluoro group on a ring carbon atom adjacent to an azepine ring carbon atom substituted with a methylidene group. Pharmaceutical compositions containing these compounds are particularly useful as oxytocin antagonists and are effective in inhibiting threatened premature birth or abortion and precesarean birth, and are effective as a remedy for dysmenorrhea and other such conditions.

  4,4-二氟-2,3,4,5-四氢-1H-1-苯并氮杂环化合物或其盐，以及含有4,4-二氟-2,3,4,5-四氢-1H-1-苯并氮杂环化合物或其盐和药用辅料的药物组合物。这些化合物的化学结构特点是在与氮杂环碳原子相邻的环碳原子上有一个二氟基团，该氮杂环碳原子被甲基亚基团取代。含有这些化合物的药物组合物特别用作催产素拮抗剂，在抑制早产或流产、以及前置胎盘分娩方面有效，并且作为治疗痛经和其他此类病症的药物有效。
• Preparation of (4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepin-5-ylidene)acetamide derivatives as novel arginine vasopressin V2 receptor agonists
  作者：Issei Tsukamoto、Hiroyuki Koshio、Seijiro Akamatsu、Takahiro Kuramochi、Chikashi Saitoh、Takeyuki Yatsu、Hiroko Yanai-Inamura、Chika Kitada、Eisaku Yamamoto、Shuichi Sakamoto、Shin-ichi Tsukamoto

  DOI：10.1016/j.bmc.2008.09.039

  日期：2008.11

  The present work describes the discovery of novel series of (4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepine-5-ylidene)acetamide derivatives as arginine vasopressin (AVP) V(2) receptor agonists. By replacing the amide juncture in YM-35278 with a direct ring connection gave compound 10a, which acts as a V(2) receptor agonist. These studies provided the potent, orally active non-peptidic V(2) receptor

  本工作描述了作为精氨酸加压素（AVP）V（2）受体的新系列（4,4-二氟-1,2,3,4-四氢-5H-1-苯并ze庚因-5-亚基）乙酰胺衍生物的发现。激动剂。通过用直接环连接取代YM-35278中的酰胺键，得到化合物10a，它起V（2）受体激动剂的作用。这些研究提供了有效的，口服活性的非肽V（2）受体激动剂10a和10j。
• Optimization of (4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepine-5-ylidene)acetamide derivatives as arginine vasopressin V2 receptor agonists and discussion of their binding modes
  作者：Issei Tsukamoto、Hiroyuki Koshio、Masaya Orita、Chikashi Saitoh、Hiroko Yanai-Inamura、Chika Kitada-Nozawa、Eisaku Yamamoto、Takeyuki Yatsu、Shuichi Sakamoto、Shin-ichi Tsukamoto

  DOI：10.1016/j.bmc.2009.10.038

  日期：2009.12.15

  A series of (4,4-difluoro-1,2,3,4-tetrahydro-5H-1-benzazepine-5-ylidene)acetamide derivatives were optimized to achieve potent agonistic activity, both in vitro and in vivo, for the arginine vasopressin V-2 receptor, resulting in the eventual discovery of compound 1g. Molecular modeling of compound 1g with V-2 receptor was also examined to evaluate the binding mode of this series of compounds. (C) 2009 Elsevier Ltd. All rights reserved.
• 4,4-DIFLUORO-1,2,3,4-TETRAHYDRO-5H-1-BENZAZEPINE DERIVATIVE OR SALT THEREOF
  申请人：Astellas Pharma Inc.

  公开号：EP1619185B1

  公开（公告）日：2011-06-15
• 4,4-DIFLUORO-1, 2, 3, 4-TETRAHYDRO-5H-1-BENZAZEPINE DERIVATIVES OR SALTS THEREOF
  申请人：Astellas Pharma Inc.

  公开号：EP1445253B1

  公开（公告）日：2009-08-05