4-(4-nitrobenzoyl)-8-(pyridin-3-ylmethyl)-5,6,7,8-tetrahydro-4H-thieno<2,3-b><1,4>thiazepine | 186808-52-6

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: 4-(4-nitrobenzoyl)-8-(pyridin-3-ylmethyl)-5,6,7,8-tetrahydro-4H-thieno<2,3-b><1,4>thiazepine
• 英文别名: (4-nitrophenyl)-[8-(pyridin-3-ylmethyl)-6,7-dihydro-5H-thieno[2,3-b][1,4]diazepin-4-yl]methanone
• CAS: 186808-52-6
• 化学式: C₂₀H₁₈N₄O₃S
• 分子量: 394.454
• InChiKey: PCRYEMJZHGEMQS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  111
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-(4-nitrobenzoyl)-8-(pyridin-3-ylmethyl)-5,6,7,8-tetrahydro-4H-thieno<2,3-b><1,4>thiazepine 在 platinum(IV) oxide 氢气 、 三乙胺 作用下， 生成 N-<4-(8-(pyridin-3-ylmethyl)-5,6,7,8-tetrahydro-4H-thieno<2,3-b><1,4>diazepin-4-yl)carbonyl>phenyl-2-phenylbenzamide
  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：

  5,6,7,8-tetrahydro-4H-thieno<2,3-b><1,4>diazepine 在 potassium carbonate 、 三乙胺 、 potassium iodide 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 23.0h， 生成 4-(4-nitrobenzoyl)-8-(pyridin-3-ylmethyl)-5,6,7,8-tetrahydro-4H-thieno<2,3-b><1,4>thiazepine
  参考文献：
  名称：

  Synthesis of Novel 5,6,7,8-Tetrahydro-4H-thieno[2,3-b][1,4]diazepine Derivatives

  摘要：

  Unsubstituted 5,6,7, 8-tetrahydro-4H-thieno[2, 3-b][1,4]diazepine (1) and 4H-thieno[2,3-b][1,4]diazepine-5,7(6H,8H)-dione (2) were newly synthesized. Benzoylation of 1 regioselectively afforded thienodiazepine (13) substituted with a benzoyl group nl position 4. Alternatively, novel synthetic procedures were devised to yield thienodiazepine (22) substituted with an alkyl group or compound (14) with an aralkyl group at position 8. Thus, the ingenious introduction of functional groups at the N-4 or 8 position of a thienodiazepine skeleton was achieved and then a variety of 5,6,7,8-tetrahydro-4H-thieno[2,3-b][1,4]diazepines (5)-(9), and (27), some of which exhibited potent arginine vasopressin antagonistic activity, were obtained using the key intermediates and (1), (13), (14) and (22).

  DOI：

  10.3987/com-98-8179