YM218 | 387816-81-1

• 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: YM218
• 英文别名: N-[4-[(5Z)-4,4-difluoro-5-[2-oxo-2-(4-piperidin-1-ylpiperidin-1-yl)ethylidene]2,3-dihydro-1-benzazepine-1-carbonyl]phenyl]-2-methylfuran-3-carboxamide；N-[4-[(5Z)-4,4-difluoro-5-[2-oxo-2-(4-piperidin-1-ylpiperidin-1-yl)ethylidene]-2,3-dihydro-1-benzazepine-1-carbonyl]phenyl]-2-methylfuran-3-carboxamide
• CAS: 387816-81-1
• 化学式: C₃₅H₃₈F₂N₄O₄
• 分子量: 616.708
• InChiKey: VDUUABBYYOPFAW-WMMMYUQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  45
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  86.1
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  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

文献信息

• [EN] PHARMACEUTICAL COMPOSITIONS FOR TREATMENT OF DIABETIC NEPHROPATHY<br/>[FR] COMPOSITIONS PHARMACEUTIQUES DESTINEES AU TRAITEMENT DE LA NEPHROPATHIE DIABETIQUE
  申请人：YAMANOUCHI PHARMA CO LTD

  公开号：WO2002002553A1

  公开（公告）日：2002-01-10

  Pharmaceutical compositions for the treatment of overt and/or early diabetic nephropathy, containing as the active ingredient (Z)-4'-4,4-difluoro-5-[2-oxo-2-(4-piperidino- piperidino)ethylidene]-2,3,4,5-tetrahydro-1H-1-benzazepine-1-carbonyl}-2-methyl-3-furanilide or pharmaceutically acceptable salts thereof.
• Synthesis and biological activity of novel 4,4-difluorobenzazepine derivatives as non-peptide antagonists of the arginine vasopressin V1A receptor
  作者：Yoshiaki Shimada、Nobuaki Taniguchi、Akira Matsuhisa、Hiroaki Akane、Noriyuki Kawano、Takeshi Suzuki、Takahiko Tobe、Akio Kakefuda、Takeyuki Yatsu、Atsuo Tahara、Yuichi Tomura、Toshiyuki Kusayama、Koh-ichi Wada、Junko Tsukada、Masaya Orita、Takashi Tsunoda、Akihiro Tanaka

  DOI：10.1016/j.bmc.2005.10.035

  日期：2006.3

  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.