阿贝卡尔 | 111841-85-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: 阿贝卡尔
• 中文别名: 艾白卡利
• 英文名称: abecarnil
• 英文别名: 6-benzyloxy-4-methoxymethyl-9H-pyrido[3,4-b]indole-3-carboxylic acid-1-methylethyl-ester；isopropyl 6-benzyloxy-4-methoxymethyl-9H-pyrido[3,4-b]indole-3-carboxylate；isopropyl 6-benzyloxy-4-methoxymethyl-β-carboline-3-carboxylate；6-benzyloxy-4-methoxymethyl-β-carboline-3-carboxylic acid isopropyl ester；propan-2-yl 4-(methoxymethyl)-6-phenylmethoxy-9H-pyrido[3,4-b]indole-3-carboxylate
• CAS: 111841-85-1
• 化学式: C₂₄H₂₄N₂O₄
• 分子量: 404.466
• InChiKey: RLFKILXOLJVUNF-UHFFFAOYSA-N

物化性质

• 熔点：
  150-151°
• 沸点：
  620.2±55.0 °C(Predicted)
• 密度：
  1.246±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  73.4
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 储存条件：
  -20°C

制备方法与用途

阿贝卡尼(ZK 112119)是苯二氮卓(BZ)受体的配体或部分激动剂，具有抗焦虑和抗惊厥的效果。它还能作为GABAA受体的正变构调节剂。研究显示，阿贝卡尼能抑制BZ[3H]氯美西泮与大鼠大脑皮层膜的结合，IC50值为0.82 nM。因此，阿贝卡尼常用于癫痫的研究中。

反应信息

• 作为反应物：
  描述：

  阿贝卡尔 在 氢氧化钾 、 sodium hydroxide 、 三甲基氯硅烷 、 盐酸羟胺 、 三乙胺 作用下， 以 (2S)-N-methyl-1-phenylpropan-2-amine hydrate 、 乙醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 生成 6-benzyloxy-4-methoxymethyl-β-carboline-3-carbaldehyde oxime
  参考文献：
  名称：

  Isoxazole-.beta.-carboline derivatives

  摘要：

  通式I中的.beta.-Carbolines，其中Y表示残基##STR2##和R.sup.a和R.sup.b，分别表示氢，C.sub.1-6-烷氧基，苯基，C.sub.3-7-环烷基，可选地取代的C.sub.1-6-烷基或C.sub.1-6-烷氧羰基，而R.sup.c和R.sup.d分别表示氢或C.sub.1-6-烷基或联合连接，R.sup.4表示氢，C.sub.1-6-烷基或C.sub.1-6-烷氧基-C.sub.1-6-烷基，R.sup.5表示氢，卤素，OR.sup.6，NR.sup.7R.sup.8或CH R.sup.9R.sup.10，其中R.sup.6表示C.sub.1-6-烷基，C.sub.3-7-环烷基或可选取代的芳基，芳基或杂环基残基，R.sup.7和R.sup.8分别表示氢，C.sub.1-6-烷基，C.sub.3-6-烯基，或与氮原子一起形成饱和的杂环五元或六元环，该环可选择包含进一步的杂原子，R.sup.9表示氢或C.sub.1-6-烷基，R.sup.10表示氢，C.sub.1-6-烷基，OR.sup.11或NR.sup.12R.sup.13，其中R.sup.11表示C.sub.1-6-烷基，R.sup.12和R.sup.13相同或不同，表示氢，C.sub.1-6-烷基或与氮原子一起形成饱和的杂环五元或六元环，该环可选择包含进一步的杂原子，可用于治疗癫痫或焦虑症。

  公开号：

  US04933345A1
• 作为产物：
  描述：

  5-benzyloxy-3-iodo-1-(methoxymethyl)indole-2-methylene-tertbutylamine 在 盐酸 、 palladium diacetate 、 三正丁胺 、 三苯基膦 作用下， 以 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 24.0h， 生成 阿贝卡尔
  参考文献：
  名称：

  Synthesis of β- and γ-Carbolines by the Palladium-Catalyzed Iminoannulation of Alkynes

  摘要：

  A variety of substituted beta- and gamma-carbolines have been prepared in moderate to excellent yields by the palladium-catalyzed annulation of internal and terminal acetylenes by the tert-butylimines of N-substituted 3-iodoindole-2-carboxaldehydes and 2-haloindole-3-carboxaldehydes, respectively. This annulation chemistry is effective for a wide range of alkynes, including aryl-, alkyl-, hydroxymethyl-, ethoxycarbonyl-, and trimethylsilyl-substituted alkynes. When an unsymmetrical internal alkyne is employed, this method generally gives two regioisomers. When a terminal alkyne is employed, only one regioisomer has been isolated. This palladium-catalyzed annulation chemistry has also been successfully applied to the synthesis of two biologically interesting beta-carboline alkaloids, ZK93423 and abecarnil (ZK112119).

  DOI：

  10.1021/jo026317u

文献信息

• Hydroxylated nebivolol metabolites
  申请人：O'Donnell P. John

  公开号：US20070014733A1

  公开（公告）日：2007-01-18

  Hydroxylated nebivolol metabolites increase NO release from human endothelial cell preparations in a concentration dependent fashion following acute administration. In addition, hydroxylated nebivolol metabolites, including but not limited to 4-hydroxy-6,6′difluoro-, 4-hydroxy-5-phenol-6,6′difluoro-, and 4-hydroxy-8-pheno-6,6′difluoro-, have the ability to increase the capacity for NO release in human endothelial cells following chronic administration. This invention provides hydroxylated nebivolol metabolites and compositions comprising nebivolol and/or at least one hydroxylated metabolite of nebivolol and/or at least one additional compound used to treat cardiovascular diseases or a pharmaceutically acceptable salt thereof. In addition, this invention provides methods of treating and/or preventing vascular diseases by administering at least one hydroxylated metabolite of nebivolol that is capable of releasing a therapeutically effective amount of nitric oxide to a targeted site affected by the vascular disease. Also, this invention is directed to the treatment and/or prevention of migraine headaches administering at least one hydroxylated metabolite of nebivolol. This invention may also be used in conjunction with or as a single treatment of metabolic syndrome disorders.

  羟基化奈必洛尔代谢物在急性给药后以浓度依赖性方式增加人内皮细胞制剂的一氧化氮释放。此外，羟基化奈必洛尔代谢物，包括但不限于4-羟基-6,6'-二氟代-、4-羟基-5-苯酚-6,6'-二氟代-和4-羟基-8-苯并-6,6'-二氟代-，在慢性给药后能够增加人内皮细胞的一氧化氮释放能力。本发明提供了羟基化奈必洛尔代谢物和包含奈必洛尔和/或至少一种羟基化奈必洛尔代谢物和/或至少一种用于治疗心血管疾病的附加化合物的组合物，以及可药用的盐。此外，本发明还提供了通过给药至少一种能够释放治疗有效量的一氧化氮到受血管疾病影响的靶向部位的羟基化奈必洛尔代谢物来治疗和/或预防血管疾病的方法。本发明还涉及通过给药至少一种羟基化奈必洛尔代谢物来治疗和/或预防偏头痛。本发明还可以与治疗代谢综合征障碍的其他治疗联合使用，或作为单一治疗。
• Nitric Oxide Releasing Prodrugs of Therapeutic Agents
  申请人：SATYAM Apparao

  公开号：US20110263526A1

  公开（公告）日：2011-10-27

  The present invention relates to nitric oxide releasing prodrugs of known drugs or therapeutic agents which are represented herein as compounds of formula (I) wherein the drugs or therapeutic agents contain one or more functional groups independently selected from a carboxylic acid, an amino, a hydroxyl and a sulfhydryl group. The invention also relates to processes for the preparation of the nitric oxide releasing prodrugs (the compounds of formula (I)), to pharmaceutical compositions containing them and to methods of using the prodrugs.

  本发明涉及已知药物或治疗剂的一氧化氮释放前药，其在此处表示为式(I)的化合物，其中药物或治疗剂包含一个或多个功能基团，独立地选自羧酸、氨基、羟基和巯基。该发明还涉及制备一氧化氮释放前药（式(I)的化合物）的方法，含有它们的药物组合物以及使用这些前药的方法。
• [EN] PRODRUG COMPOSITIONS AND METHODS OF TREATMENT<br/>[FR] COMPOSITIONS DE PROMÉDICAMENT ET PROCÉDÉS DE TRAITEMENT
  申请人：AQUESTIVE THERAPEUTICS INC

  公开号：WO2021087359A1

  公开（公告）日：2021-05-06

  Pharmaceutical compositions include a prodrug of epinephrine are described.

  药物组合物包括表述的肾上腺素前药。
• Multi-functional ionic liquid compositions for overcoming polymorphism and imparting improved properties for active pharmaceutical, biological, nutritional, and energetic ingredients
  申请人：Rogers D. Robin

  公开号：US20070093462A1

  公开（公告）日：2007-04-26

  Disclosed are ionic liquids and methods of preparing ionic liquid compositions of active pharmaceutical, biological, nutritional, and energetic ingredients. Also disclosed are methods of using the compositions described herein to overcome polymorphism, overcome solubility and delivery problems, to control release rates, add functionality, enhance efficacy (synergy), and improve ease of use and manufacture.

  揭示了离子液体及制备活性药物、生物、营养和能量成分的离子液体组合物的方法。还揭示了利用本文描述的组合物的方法，以克服多型性、克服溶解度和输送问题、控制释放速率、增加功能性、增强功效（协同作用）以及改善易用性和制造工艺。
• [EN] RADIOLABELED COMPOUNDS AND METHODS THEREOF<br/>[FR] COMPOSÉS RADIOMARQUÉS ET LEURS PROCÉDÉS
  申请人：GE HEALTHCARE LTD

  公开号：WO2011150183A1

  公开（公告）日：2011-12-01

  The present invention relates to radiodiagnostic compounds, methods of making those compounds, and methods of use thereof as imaging agents for preferably a HA serotonin 5-HT1A receptor for use in PET or SPECT, preferably PET. Compositions comprising an imaging-effective amount of radiolabeled compounds are also disclosed. The present invention also relates to non-radiolabeled compounds, methods of making those compounds, and methods of use thereof to treat various neurological and/or psychiatric disorders.

  本发明涉及放射诊断化合物，制备这些化合物的方法，以及将其用作HA血清素5-HT1A受体的成像剂，用于PET或SPECT，更好地使用PET的方法。还披露了包含放射标记化合物的成像有效量的组合物。本发明还涉及非放射标记化合物，制备这些化合物的方法，以及将其用于治疗各种神经学和/或精神疾病的方法。