N-[2-[3-(4-methylperhydro-1,4-diazepin-1-yl)propoxy]-4-[(5,6,7,8-tetrahydro-4H-thieno[3,2-b]azepin-4-yl)carbonyl]phenyl]-(1,1'-biphenyl)-2-carboxamide

• 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: N-[2-[3-(4-methylperhydro-1,4-diazepin-1-yl)propoxy]-4-[(5,6,7,8-tetrahydro-4H-thieno[3,2-b]azepin-4-yl)carbonyl]phenyl]-(1,1'-biphenyl)-2-carboxamide
• 英文别名: N-[2-[3-(4-methyl-1,4-diazepan-1-yl)propoxy]-4-(5,6,7,8-tetrahydrothieno[3,2-b]azepine-4-carbonyl)phenyl]-2-phenylbenzamide
• 化学式: C₃₇H₄₂N₄O₃S
• 分子量: 622.831
• InChiKey: MGFWTVPFIGCNLG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  45
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  93.4
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 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 、 N,N-二甲基甲酰胺 、 丙酮 、 乙腈 为溶剂， 反应 23.0h， 生成 N-[2-[3-(4-methylperhydro-1,4-diazepin-1-yl)propoxy]-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

文献信息

• [EN] PHARMACEUTICAL COMPOSITIONS CONTAINING IN COMBINATION AN ARGININE-VASOPRESSIN V1a ANTAGONIST AND AN ANGIOTENSIN II AT1 RECEPTOR ANTAGONIST<br/>[FR] COMPOSITIONS PHARMACEUTIQUES CONTENANT EN ASSOCIATION UN ANTAGONISTE V1a DE L'ARGININE-VASOPRESSINE ET UN ANTAGONISTE DES RECEPTEURS AT1 DE L'ANGIOTENSINE II
  申请人：SANOFI-SYNTHELABO

  公开号：WO1999055340A1

  公开（公告）日：1999-11-04

  (EN) The invention concerns pharmaceutical compositions containing in combination a of arginine-vasopressin V1a antagonist and an angiotensin II AT1 receptor antagonist. The use of said combination is useful for treating cardiac deficiency, high blood pressure and nephropathy.(FR) L'invention a pour objet des compositions pharmaceutiques contenant en association un antagoniste V1a de l'arginine-vasopressine et un antagoniste des récepteurs AT1 de l'angiotensine II. L'utilisation de l'association selon l'invention est utile dans le traitement de la défaillance cardiaque, de l'hypertension et de la néphropathie.