(Z)-{4,4-difluoro-1-[4-(3-methylthiophene-2-carbonylamino)benzoyl]-2,3,4,5-tetrahydro-1H-1-benzazepin-5-ylidene}acetic acid | 168163-17-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (Z)-{4,4-difluoro-1-[4-(3-methylthiophene-2-carbonylamino)benzoyl]-2,3,4,5-tetrahydro-1H-1-benzazepin-5-ylidene}acetic acid
• 英文别名: (Z)-[4,4-difluoro-1-[4-(3-methyl-2-thienyl)carbonylamino]benzoyl-2,3,4,5-tetrahydro-1H-1-benzazepin-5-ylidene]acetic acid；(2Z)-2-[4,4-difluoro-1-[4-[(3-methylthiophene-2-carbonyl)amino]benzoyl]-2,3-dihydro-1-benzazepin-5-ylidene]acetic acid
• CAS: 168163-17-5
• 化学式: C₂₅H₂₀F₂N₂O₄S
• 分子量: 482.508
• InChiKey: MRDRBXNCQGMLPH-RGEXLXHISA-N

物化性质

• 沸点：
  607.4±55.0 °C(Predicted)
• 密度：
  1.45±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  34
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (Z)-{4,4-difluoro-1-[4-(3-methylthiophene-2-carbonylamino)benzoyl]-2,3,4,5-tetrahydro-1H-1-benzazepin-5-ylidene}acetic acid 、 4-二甲氨基哌啶 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 二氯甲烷 、 乙腈 为溶剂， 反应 1.0h， 生成 (Z)-N-{4'-[(4,4-difluoro-5-{2-[4-(dimethylamino)piperidino]-2-oxoethylidene}-2,3,4,5-tetrahydro-1H-1-benzazepin-1-yl)carbonyl]phenyl}-3-methylthiophene-2-carboxamide
  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：

  3-甲基噻吩-2-羰基氯 在 吡啶 、 sodium hydroxide 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 15.0h， 生成 (Z)-{4,4-difluoro-1-[4-(3-methylthiophene-2-carbonylamino)benzoyl]-2,3,4,5-tetrahydro-1H-1-benzazepin-5-ylidene}acetic acid
  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

文献信息

• Benzazepine derivative, pharmaceutical composition thereof, and
  申请人：Yamanouchi Pharmaceutical Co., Ltd.

  公开号：US05710150A1

  公开（公告）日：1998-01-20

  Benzazepine derivatives represented by the following general formula (I) useful as arginine vasopressin antagonists or pharmaceutically acceptable salts thereof, pharmaceutical compositions thereof, and difluorobenzazepinone derivatives represented by the following general formulae (II) and (III) which are useful as production intermediates of the compound (I). ##STR1##

  以下是通用公式（I）表示的苯并哌啶衍生物，可用作精氨酸加压素拮抗剂或其药用盐，以及其药物组合物，以及以下通用公式（II）和（III）表示的二氟苯并哌啶酮衍生物，可用作化合物（I）的生产中间体。 请注意，这是一种化学描述，内容较为专业。
• BENZAZEPINE DERIVATIVE, PHARMACEUTICAL COMPOSITION CONTAINING THE SAME, AND INTERMEDIATE FOR THE SAME
  申请人：YAMANOUCHI PHARMACEUTICAL CO. LTD.

  公开号：EP0716083A1

  公开（公告）日：1996-06-12

  A benzazepine derivative, represented by general formula (I), useful as an arginine vasopressing antagonist; a pharmaceutically acceptable salt thereof; a pharmaceutical composition containing the same; and difluorobenzazepinone derivatives, represented by general formulae (II) and (III), useful as intermediates for producing the compound (I).

  由通式(I)表示的苯并氮杂卓衍生物，可用作精氨酸血管加压拮抗剂；其药学上可接受的盐；含有该衍生物的药物组合物；以及由通式(II)和(III)表示的二氟苯并氮杂卓酮衍生物，可用作生产化合物(I)的中间体。