ethyl 4-[2-[[[1,1'-biphenyl]-2-carbonyl]amino]-5-[(5,6,7,8-tetrahydro-4H-thieno[3,2-b]azepin-4-yl)carbonyl]phenoxy]butyrate | 190276-52-9

• 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: ethyl 4-[2-[[[1,1'-biphenyl]-2-carbonyl]amino]-5-[(5,6,7,8-tetrahydro-4H-thieno[3,2-b]azepin-4-yl)carbonyl]phenoxy]butyrate
• 英文别名: Ethyl 4-[2-[(2-phenylbenzoyl)amino]-5-(5,6,7,8-tetrahydrothieno[3,2-b]azepine-4-carbonyl)phenoxy]butanoate
• CAS: 190276-52-9
• 化学式: C₃₄H₃₄N₂O₅S
• 分子量: 582.72
• InChiKey: QRBQKWHMBYYVHX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  42
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  113
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 4-[2-[[[1,1'-biphenyl]-2-carbonyl]amino]-5-[(5,6,7,8-tetrahydro-4H-thieno[3,2-b]azepin-4-yl)carbonyl]phenoxy]butyrate 在 氢氧化钾 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以78.6%的产率得到4-[2-[[[1,1'-biphenyl]-2-carbonyl]amino]-5-[(5,6,7,8-tetrahydro-4H-thieno[3,2-b]azepin-4-yl)carbonyl]phenoxy]butyric acid
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of 5,6,7,8-Tetrahydro-4H-thieno[3,2-b]azepine Derivatives:  Novel Arginine Vasopressin Antagonists

  摘要：

  A variety of novel heterocyclic compounds having thienoazepine, pyrroloazepine, furoazepine, and thienodiazepine skeletons were synthesized, most of which exhibited potent antagonism of [H-3]-AVP specific binding in assays using rat liver (V1), rat kidney (V2), human platelet plasma membranes, and recombinant human CHO cells (V2), as well as antagonizing AVP-induced hypertension in rats (V1, intravenous) and showing a diuretic effect in rats (V2, oral). By detailed studies of the structure-activity relationships of these compounds, the thienoazepine derivative 1 was found to be a very potent combined V1 and V2 antagonist. After further pharmacological and toxicological evaluation as well as physical properties, the hydrochloride 2 (JTV-605) of compound 1 was selected for clinical studies as a potent AVP antagonist with a long duration of action.

  DOI：

  10.1021/jm030287l
• 作为产物：
  描述：

  二氢-3-(异十二碳烯基)呋喃-2,5-二酮 在 氯化亚砜 、 三溴化硼 、 potassium carbonate 、 三乙胺 、 potassium iodide 作用下， 以 氯仿 、 丙酮 为溶剂， 反应 16.0h， 生成 ethyl 4-[2-[[[1,1'-biphenyl]-2-carbonyl]amino]-5-[(5,6,7,8-tetrahydro-4H-thieno[3,2-b]azepin-4-yl)carbonyl]phenoxy]butyrate
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of 5,6,7,8-Tetrahydro-4H-thieno[3,2-b]azepine Derivatives:  Novel Arginine Vasopressin Antagonists

  摘要：

  A variety of novel heterocyclic compounds having thienoazepine, pyrroloazepine, furoazepine, and thienodiazepine skeletons were synthesized, most of which exhibited potent antagonism of [H-3]-AVP specific binding in assays using rat liver (V1), rat kidney (V2), human platelet plasma membranes, and recombinant human CHO cells (V2), as well as antagonizing AVP-induced hypertension in rats (V1, intravenous) and showing a diuretic effect in rats (V2, oral). By detailed studies of the structure-activity relationships of these compounds, the thienoazepine derivative 1 was found to be a very potent combined V1 and V2 antagonist. After further pharmacological and toxicological evaluation as well as physical properties, the hydrochloride 2 (JTV-605) of compound 1 was selected for clinical studies as a potent AVP antagonist with a long duration of action.

  DOI：

  10.1021/jm030287l