[2-[(Biphenyl-2-carbonyl)-amino]-5-(5,6,7,8-tetrahydro-thieno[3,2-b]azepine-4-carbonyl)-phenoxy]-acetic acid | 190276-17-6

• 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: [2-[(Biphenyl-2-carbonyl)-amino]-5-(5,6,7,8-tetrahydro-thieno[3,2-b]azepine-4-carbonyl)-phenoxy]-acetic acid
• 英文别名: 2-[2-[(2-Phenylbenzoyl)amino]-5-(5,6,7,8-tetrahydrothieno[3,2-b]azepine-4-carbonyl)phenoxy]acetic acid
• CAS: 190276-17-6
• 化学式: C₃₀H₂₆N₂O₅S
• 分子量: 526.613
• InChiKey: JQRLKMSSBQRDOH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  38
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  124
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-二甲氨基哌啶 、 [2-[(Biphenyl-2-carbonyl)-amino]-5-(5,6,7,8-tetrahydro-thieno[3,2-b]azepine-4-carbonyl)-phenoxy]-acetic acid 在 双(2-氧代-3-恶唑烷基)次磷酰氯 、 三乙胺 作用下， 以 氯仿 为溶剂， 反应 12.0h， 以280 mg的产率得到N-[2-[2-(4-dimethylaminopiperidino)-2-oxoethoxy]-4-[(5,6,7,8-tetrahydro-4H-thieno[3,2-b]azepin-4-yl)carbonyl]phenyl]-(1,1'-biphenyl)-2-carboxamide
  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 氢氧化钾 、 氯化亚砜 、 三溴化硼 、 potassium carbonate 、 三乙胺 、 potassium iodide 作用下， 以 甲醇 、 氯仿 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 11.0h， 生成 [2-[(Biphenyl-2-carbonyl)-amino]-5-(5,6,7,8-tetrahydro-thieno[3,2-b]azepine-4-carbonyl)-phenoxy]-acetic 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