(1-Methyl-5,6,7,8-tetrahydropyrrolo[3,2-b]azepin-4-yl)-(4-nitrophenyl)methanone | 186808-30-0

• 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-5,6,7,8-tetrahydropyrrolo[3,2-b]azepin-4-yl)-(4-nitrophenyl)methanone
• 英文别名: (1-methyl-5,6,7,8-tetrahydropyrrolo[3,2-b]azepin-4-yl)-(4-nitrophenyl)methanone
• CAS: 186808-30-0
• 化学式: C₁₆H₁₇N₃O₃
• 分子量: 299.329
• InChiKey: LTAHPKLUJTVPBB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  71.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1-Methyl-5,6,7,8-tetrahydropyrrolo[3,2-b]azepin-4-yl)-(4-nitrophenyl)methanone 在 palladium on activated charcoal 氢气 、 三乙胺 作用下， 生成 Biphenyl-2-carboxylic acid [4-(1-methyl-5,6,7,8-tetrahydro-1H-pyrrolo[3,2-b]azepine-4-carbonyl)-phenyl]-amide
  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：

  1,5,6,7-四氢-4H-吲哚-4-酮 在 吡啶 、 盐酸羟胺 、 sodium hydride 、 二异丁基氢化铝 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 (1-Methyl-5,6,7,8-tetrahydropyrrolo[3,2-b]azepin-4-yl)-(4-nitrophenyl)methanone
  参考文献：
  名称：

  Regioselective Synthesis of Several Heterocyclic Fused Azepines Using Diisobutylaluminum Hydride

  摘要：

  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.

  DOI：

  10.3987/com-98-8104

文献信息

• 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.
• 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.