(R)-5-bromo-N-(1-ethyl-4-methylhexahydro-1H-1,4-diazepin-6-yl)-2-methoxy-6-methylamino-3-pyridinecarboxamide | 187480-02-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: (R)-5-bromo-N-(1-ethyl-4-methylhexahydro-1H-1,4-diazepin-6-yl)-2-methoxy-6-methylamino-3-pyridinecarboxamide
• 英文别名: 5-Bromo-N-((R)-1-ethyl-4-methyl-[1,4]diazepan-6-yl)-2-methoxy-6-methylamino-nicotinamide；5-bromo-N-[(6R)-1-ethyl-4-methyl-1,4-diazepan-6-yl]-2-methoxy-6-(methylamino)pyridine-3-carboxamide
• CAS: 187480-02-0
• 化学式: C₁₆H₂₆BrN₅O₂
• 分子量: 400.319
• InChiKey: FKDXBULKZKICQO-LLVKDONJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  69.7
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  5-溴-2-甲氧基-6-(甲氨基)吡啶-3-羧酸甲酯 在 sodium hydroxide 、 N,N'-羰基二咪唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (R)-5-bromo-N-(1-ethyl-4-methylhexahydro-1H-1,4-diazepin-6-yl)-2-methoxy-6-methylamino-3-pyridinecarboxamide
  参考文献：
  名称：

  Synthesis of N-(1-ethyl-4-methylhexahydro-1,4-diazepin-6-yl)nicotinamides and their affinities for 5-HT3 and dopamine D2 receptors

  摘要：

  A series of N-(1-ethyl-4-methylhexahydro-1,4-diazepin-6-yl) derivatives were prepared and evaluated for their binding to 5-HT3 and dopamine D-2 receptors. Among them, the 5-bromo-2-methoxy-6-methylaminonicotinamide 16 and its (R)-isomer were found to have potent affinities for both receptors. The affinities of(R)-16 for 5-HT3 and dopamine D-2 receptors are approximately 3-fold higher than those of the corresponding benzamide (R)-1 (IC50:1.1 and 12 nM vs. 2.9 and 35 nM, respectively). (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(98)00258-3

文献信息

• (R)-5-bromo-N-(1-ethyl-4-methylhexahydr
  申请人：Dainippon Pharmaceutical Co., Ltd.

  公开号：US05945415A1

  公开（公告）日：1999-08-31

  This invention discloses a compound which is expressed by formula (I) below: ##STR1## or physiologically acceptable acid addition salts thereof. The claimed compound exhibits excellent antiemetic effect based on its potent serotonin S.sub.3 and dopamine D.sub.2 receptor antagonistic activities, and is useful for treatment or prophylaxis of various gastrointestinal symptoms which are associated with various diseases and drug administration.

  本发明揭示了一种由以下公式（I）表示的化合物：##STR1##或其生理上可接受的酸盐。所述化合物具有出色的抗恶心作用，基于其强效的5-羟色胺S.sub.3受体和多巴胺D.sub.2受体拮抗活性，并且可用于治疗或预防与各种疾病和药物使用相关的各种胃肠症状。
• Synthesis and Structure−Affinity Relationships of Novel <i>N</i>-(1-Ethyl-4-methylhexahydro-1,4-diazepin-6-yl)pyridine-3-carboxamides with Potent Serotonin 5-HT₃ and Dopamine D₂ Receptor Antagonistic Activity
  作者：Yoshimi Hirokawa、Iwao Fujiwara、Kenji Suzuki、Hiroshi Harada、Takashi Yoshikawa、Naoyuki Yoshida、Shiro Kato

  DOI：10.1021/jm020270n

  日期：2003.2.1

  dopamine D(2) receptor while keeping a potent serotonin 5-HT(3) receptor binding affinity. As a result of structure-affinity relationships, the 5-bromo-2-methoxy-6-methylaminopyridine-3-carboxamide 53 was selected as the most promising product showing a high binding affinity for both receptors. Compound 53 affinity for the dopamine D(2) and serotonin 5-HT(3) receptors was much more potent than that of

  制备了由相应的苯甲酰胺5衍生的N-（1-乙基-4-甲基六氢-1,4-二氮杂-6-6-基）吡啶-3-甲酰胺的结构原始系列，并评估了其对多巴胺D（ 2）和分别使用大鼠纹状体和大鼠皮质膜的血清素5-HT（3）受体。许多合成的吡啶-3-羧酰胺对5-羟色胺5-HT（3）受体具有纳摩尔结合亲和力，对多巴胺D（2）受体具有中等至高结合亲和力。在吡啶环的5-位和6-位上分别引入更具亲脂性的溴原子和甲基氨基，增强了对多巴胺D（2）受体的亲和力，同时保持了强大的5-羟色胺5-HT（3）受体结合亲和力。由于结构相似性关系，选择5-溴-2-甲氧基-6-甲基氨基吡啶-3-羧酰胺53作为最有前途的产品，该产品对两种受体都具有高结合亲和力。化合物53对多巴胺D（2）和5-羟色胺5-HT（3）受体的亲和力比甲氧氯普胺（多巴胺D（2）受体； 23.3 nM对444 nM，5-羟色胺5-HT（3）受体的亲和力强得多。 0.97
• [EN] (R)-5-BROMO-N-(1-ETHYL-4-METHYLHEXAHYDRO-1H-1,4-DIAZEPIN-6-YL)-2-METHOXY-6-METHYLAMINO-3-PYRIDINE-CARBOXAMIDE, PROCESS FOR PRODUCING THE SAME AND MEDICINAL COMPOSITION CONTAINING THE SAME<br/>[FR] (R)-5-BROMO-N-(1-ETHYL-4-METHYLHEXAHYDRO-1H-1,4-DIAZEPIN-6-YL)-2-METHOXY-6-METHYLAMINO-3-PYRIDINE-CARBOXAMIDE, SON PROCEDE D'OBTENTION ET MEDICAMENT LE CONTENANT
  申请人：DAINIPPON PHARMACEUTICAL CO., LTD.

  公开号：WO1997005129A1

  公开（公告）日：1997-02-13

  (EN) The compound represented by formula (I) and physiologically acceptable acid-addition salts thereof. The compounds have an excellent antiemetic effect based on potent antagonism against serotonin S3 and dopamine D2 receptors and, therefore, are usable as an antiemetic agent in the treatment or prevention of various diseases and many digestive symptoms accompanying the administration of drugs, etc.(FR) L'invention porte sur un composé de formule (1) et sur des sels d'addition d'acides pharmacocompatibles qui se caractérisent par leur excellent pouvoir antiémétique résultant de leur puissant antagonisme vis à vis des récepteurs de la sérotonine S3 et de la dopamine D2. On peut les utiliser comme antiémétiques pour le traitement ou la prévention de différentes maladies et troubles digestifs liés à l'administration de médicaments.

  化合物式(I)及其生理上可接受的酸加成盐。这些化合物具有出色的抗恶心作用，基于对5-羟色胺S3和多巴胺D2受体的强大拮抗作用，因此可用作治疗或预防各种疾病以及伴随药物治疗等引起的许多消化症状的抗恶心剂。
• HETEROCYCLIC CARBOXAMIDE COMPOUNDS
  申请人：Terasawa Takeshi

  公开号：US20110166161A1

  公开（公告）日：2011-07-07

  This invention relates to novel heterocyclic carboxamide derivatives and salts thereof. More particularly, it relates to novel heterocyclic carboxamide derivatives and salts thereof which act as a ROCK inhibitor, to a pharmaceutical composition comprising the same and to a method of using the same therapeutically in the treatment and/or prevention of ROCK-related disease.

  本发明涉及新颖的杂环羧酰胺衍生物及其盐。更具体地，涉及一种作为ROCK抑制剂的新颖杂环羧酰胺衍生物及其盐，以及包含其的制药组合物和在治疗和/或预防ROCK相关疾病方面的治疗方法。
• (R)-5-BROMO-N-(1-ETHYL-4-METHYLHEXAHYDRO-1H-1,4-DIAZEPIN-6-YL)-2-METHOXY-6-METHYLAMINO-3-PYRIDINE-CARBOXAMIDE, PROCESS FOR PRODUCING THE SAME AND MEDICINAL COMPOSITION CONTAINING THE SAME
  申请人：DAINIPPON PHARMACEUTICAL CO., LTD.

  公开号：EP0855397A1

  公开（公告）日：1998-07-29

  This invention discloses a compound which is expressed by formula (I) below: or physiologically acceptable acid addition salts thereof. The claimed compound exhibits excellent antiemetic effect based on its potent serotonin S3 and dopamine D2 receptor antagonistic activities, and is useful for treatment or prophylaxis of various gastrointestinal symptoms which are associated with various diseases and drug administration.

  本发明公开了一种由下式（I）表示的化合物： 或其生理上可接受的酸加成盐。 该化合物具有强效的血清素 S3 和多巴胺 D2 受体拮抗活性，因此具有良好的止吐效果，可用于治疗或预防与各种疾病和用药相关的各种胃肠道症状。