N-(1-ethyl-1H-hexahydroazepin-3-yl)-6-methoxy-1H-benzotriazole-5-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并三唑类
• 英文名称: N-(1-ethyl-1H-hexahydroazepin-3-yl)-6-methoxy-1H-benzotriazole-5-carboxamide
• 英文别名: N-(1-ethylazepan-3-yl)-6-methoxy-3H-benzotriazole-5-carboxamide
• 化学式: C₁₆H₂₃N₅O₂
• 分子量: 317.391
• InChiKey: BGULOBIRXSRYQJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  83.1
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-乙酰胺基-2-甲氧基-5-硝基苯甲酸甲酯 在 palladium on activated charcoal 盐酸 、 sodium hydroxide 、 氢气 、 N,N'-羰基二咪唑 、 sodium nitrite 作用下， 生成 N-(1-ethyl-1H-hexahydroazepin-3-yl)-6-methoxy-1H-benzotriazole-5-carboxamide
  参考文献：
  名称：

  A novel series of 6-methoxy-1H-benzotriazole-5-carboxamide derivatives with dual antiemetic and gastroprokinetic activities

  摘要：

  A novel series of 6-methoxy-1H-benzotriazole-5-carboxamide derivatives with a medium perhydroazacycle ring in the amine moiety were prepared, and their antiemetic and gastroprokinetic activities were evaluated. Among them, N-(1-ethylhexahydroazepin-3-yl)-, N-(1-ethyloctahydroazocin-3-yl)- and N-(1-ethyloctahydroazonin-3-yl)-6-methoxy-1H-benzotriazole-5-carboxamides (24, 36, 37) showed a potent antiemetic activity (inhibition of apomorphine-induced emesis in dogs) along with gastroprokinetic activity (gastric emptying in rats). (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(98)00341-2

文献信息

• 6-METHOXY-1H-BENZOTRIAZOLE-5-CARBOXAMIDE DERIVATIVES, PROCESS FOR PRODUCING THE SAME, AND MEDICINAL COMPOSITION CONTAINING THE SAME
  申请人：DAINIPPON PHARMACEUTICAL CO., LTD.

  公开号：EP0794184A1

  公开（公告）日：1997-09-10

  6-Methoxy-1H-benzotriazole-5-carboxamide derivatives which are represented by the formula (I) below: [in which R1 stands for ethyl or cyclopropylmethyl group, R2 stands for hydrogen atom, methyl or ethyl group, n is 1, 2 or 3, and the wavy line () signifies that configuration of the substituents on the carbon atom bound to the N-atom in the amide moiety is racemic (RS) or optically active (R or S)] or their pharmaceutically acceptable acid addition salts; processes for their preparation; pharmaceutical compositions containing a compound of formula (I) or its pharmaceutically acceptable acid addition salt; and novel intermediates. The compounds of the present invention possess concurrently excellent antiemetic activity and gastrointestinal motility enhancing activity. They furthermore exhibit less central nervous system (CNS) depressant activity and, therefore, are used for treatments and prophylaxis of functional disorders of gastrointestinal tract associated with various diseases and therapeutical treatments, as gastrointestinal motility enhancing agent.

  6-甲氧基-1H-苯并三唑-5-甲酰胺衍生物，由下式（I）表示： [其中 R1 代表乙基或环丙基甲基、 R2 代表氢原子、甲基或乙基、 n 为 1、2 或 3，以及 波浪线（）表示与酰胺分子中 N 原子结合的碳原子上的取代基的构型为外消旋（RS）或光学活性（R 或 S）]。 或其药学上可接受的酸加成盐；其制备工艺；含有式（I）化合物或其药学上可接受的酸加成盐的药物组合物；以及新型中间体。 本发明的化合物同时具有优异的止吐活性和胃肠道蠕动增强活性。此外，它们还表现出较低的中枢神经系统（CNS）抑制活性，因此可作为胃肠道蠕动增强剂，用于治疗和预防与各种疾病和治疗相关的胃肠道功能紊乱。
• [EN] (R)-N-(1-ETHYL-1H-HEXAHYDROAZEPIN-3-YL)-6-METHOXY-1H-BENZOTRIAZOLE-5-CARBOXAMIDE MONOFUMARATE MONOHYDRATE AND PROCESS FOR PRODUCING THE SAME<br/>[FR] (R)-N-(1-ETHYL-1H-HEXAHYDROAZEPINE-3-YL)-6-METHOXY-1H-BENZOTRIAZOLE-5-CARBOOXAMIDE MONOFUMARATE MONOHYDRATE ET SON PROCEDE DE PRODUCTION
  申请人：DAINIPPON PHARMACEUTICAL CO., LTD.

  公开号：WO1999002522A1

  公开（公告）日：1999-01-21

  (EN) (R)-N-(1-Ethyl-1H-hexahydroazepin-3-yl)-6-methoxy-1H-benzotriazole-5-carboxamide monofumarate monohydrate represented by formula (I) which is useful as an agent for improving digestive functions; and a process for producing (R)-N-(1-ethyl-1H-hexahydroazepin-3-yl)-6-methoxy-1H-benzotriazole-5-carboxamide monofumarate from an alcoholic solvate thereof. The compound of formula (I) can be obtained in the form of physically stable crystals and can be steadily supplied industrially as medicinal bulk powders.(FR) L'invention porte sur (R)-N-(1-éthyl-1H-hexahydroazépine-3-yl)-6-méthoxy-1H-benzotriazole-5-carboxamide monofumarate représentée par la formule générale (I), ce composé étant utilisé comme agent pour améliorer les fonctions digestives. L'invention porte également sur un procédé de production de (R)-N-(1-éthyl-1H-hexahydroazépine-3-yl)-6-méthoxy-1H-benzotriazole-5-carboxamide monofumarate à partir d'un solvate alcoolique de celui-ci. Le composé de la formule (I) peut être obtenu sous forme de cristaux physiquement stables et peut être produit industriellement sous forme de poudres médicinales en vrac.

  这项发明涉及化学式(I)表示的(R)-N-(1-乙基-1H-六氢甲氧嗪-3-yl)-6-甲氧基-1H-苯并三azole-5-羧酰胺单水物，该化合物可作为改善消化功能的药物使用。此外，该发明还涉及从以该溶剂为原料的酒精溶剂中生产(R)-N-(1-乙基-1H-六氢甲氧嗪-3-yl)-6-甲氧基-1H-苯并三azole-5-羧酰胺单水物的方法。化学式(I)形式的这种化合物可以通过稳定的物理晶体形式获得，并可稳定地工业上以医药粉末形式提供。
• JPH08208643A
  申请人：——

  公开号：JPH08208643A

  公开（公告）日：1996-08-13
• US5932568A
  申请人：——

  公开号：US5932568A

  公开（公告）日：1999-08-03
• A novel series of 6-methoxy-1H-benzotriazole-5-carboxamide derivatives with dual antiemetic and gastroprokinetic activities
  作者：Yoshimi Hirokawa、Hiroshi Yamazaki、Naoyuki Yoshida、Shiro Kato

  DOI：10.1016/s0960-894x(98)00341-2

  日期：1998.8

  A novel series of 6-methoxy-1H-benzotriazole-5-carboxamide derivatives with a medium perhydroazacycle ring in the amine moiety were prepared, and their antiemetic and gastroprokinetic activities were evaluated. Among them, N-(1-ethylhexahydroazepin-3-yl)-, N-(1-ethyloctahydroazocin-3-yl)- and N-(1-ethyloctahydroazonin-3-yl)-6-methoxy-1H-benzotriazole-5-carboxamides (24, 36, 37) showed a potent antiemetic activity (inhibition of apomorphine-induced emesis in dogs) along with gastroprokinetic activity (gastric emptying in rats). (C) 1998 Elsevier Science Ltd. All rights reserved.