1-Methyl-1,4,5,6,7,8-hexahydro-pyrrolo[3,2-b]azepin

• 分子结构分类: 有机化合物 - 有机杂环化合物 - Pyrroloazepines
• 英文名称: 1-Methyl-1,4,5,6,7,8-hexahydro-pyrrolo[3,2-b]azepin
• 英文别名: 1-methyl-1,4,5,6,7,8-hexahydropyrrolo[3,2-b]azepine；1-methyl-5,6,7,8-tetrahydro-4H-pyrrolo[3,2-b]azepine
• 化学式: C₉H₁₄N₂
• 分子量: 150.224
• InChiKey: SNFDJRZOXDAJNF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  17
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  1-Methyl-1,4,5,6,7,8-hexahydro-pyrrolo[3,2-b]azepin 在 palladium on activated charcoal 氢气 、 三乙胺 作用下， 以 氯仿 为溶剂， 生成
  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：

  1-methyl-6,7-dihydro-1H-indol-4(5H)-one oxime 在 二异丁基氢化铝 作用下， 生成 1-Methyl-1,4,5,6,7,8-hexahydro-pyrrolo[3,2-b]azepin
  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

• Regioselective Synthesis of Several Heterocyclic Fused Azepines Using Diisobutylaluminum Hydride
  作者：Hidetsura Cho、Kengo Murakami、Hiroyuki Nakanishi、Hirotaka Isoshima、Kazuhide Hayakawa、Itsuo Uchida

  DOI：10.3987/com-98-8104

  日期：——

  5,6,7,8-Tetrahydrothieno[3,2-b]azepine,5,6,7,8-tetrahydro-1H-furo[3,- 2b]azepine, and 1,4,5,6,7,8-hexahydropyrrolo [3,2-b]azepine were synthesized by the ring expansion reaction of heterocyclic fused cyclohexanone oximes with diisobutylaluminum hydride (DIBAH). The mechanism of the reaction was different from that of Beckmann rearrangement.
• Synthesis and Structure−Activity Relationships of 5,6,7,8-Tetrahydro-4<i>H</i>-thieno[3,2-<i>b</i>]azepine Derivatives:  Novel Arginine Vasopressin Antagonists
  作者：Hidetsura Cho、Kengo Murakami、Hiroyuki Nakanishi、Akitaka Fujisawa、Hirotaka Isoshima、Misako Niwa、Kazuhide Hayakawa、Yasunori Hase、Itsuo Uchida、Hidenori Watanabe、Korekiyo Wakitani、Kazuo Aisaka

  DOI：10.1021/jm030287l

  日期：2004.1.1

  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.