3-乙基中氮茚-1-羧酸 | 120221-65-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 中文名称: 3-乙基中氮茚-1-羧酸
• 英文名称: 3-Ethylindolizine-l-carboxylic acid
• 英文别名: 3-ethylindolizine-1-carboxylic acid；3-ethylindolizin-1-carboxylic acid
• CAS: 120221-65-0
• 化学式: C₁₁H₁₁NO₂
• 分子量: 189.214
• InChiKey: QBZMDEDJWGGNAZ-UHFFFAOYSA-N

物化性质

• 密度：
  1.20±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  41.7
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-乙基中氮茚-1-羧酸 在 草酰氯 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 氯仿 为溶剂， 反应 20.0h， 生成 3-Ethyl-indolizine-1-carboxylic acid [(1S,7aS)-1-(hexahydro-pyrrolizin-1-yl)methyl]-amide
  参考文献：
  名称：

  吡咯嗪核苷酯和酰胺作为5-HT4受体激动剂和拮抗剂。

  摘要：

  制备了一系列吡咯嗪核苷酯，酰胺和脲，并在大鼠上皮肌膜（TMM）分析中测试了5-HT（4）和5-HT（3）受体结合，5-HT（4）受体激动作用，在Bezold-Jarisch反射测定中对5-HT（3）受体介导的功能拮抗作用。鉴定出几种对5-HT（4）受体具有高亲和力的吡咯烷嗪衍生物，包括苯甲酰胺12a（SC-53116），这是一种有效且选择性的5-HT（4）部分激动剂，在促进窦性收缩方面具有功效，并在促进中具有活性。犬模型中的胃排空。还发现了5-HT（4）受体拮抗剂，包括咪唑并吡啶酰胺12h（SC-53606），这是一种有效且选择性的5-HT（4）受体拮抗剂，在大鼠TMM分析中的pA（2）值为8.13。 。N-甲基吲哚酯13d被确定为有效的5-HT（4）拮抗剂，pA（2）值为8.93。与其他单胺受体，包括5-HT（1），5-HT（2），D（1），D（2），α（1），α（2）和β相比，这些吡咯烷啶衍生物具有很高的选择性受体。

  DOI：

  10.1021/jm0509501
• 作为产物：
  描述：

  2-吡啶乙酸甲酯 在 2,6-二甲基吡啶 、 sodium hydroxide 作用下， 以 乙醇 、 xylene 为溶剂， 反应 21.0h， 生成 3-乙基中氮茚-1-羧酸
  参考文献：
  名称：

  5-羟色胺（5-HT3）受体拮抗剂。1.吲唑和吲哚嗪-3-羧酸衍生物。

  摘要：

  甲氧氯普胺（1）是一种胃动力刺激剂，是一种弱的多巴胺和5-HT3受体拮抗剂。构象限制了氮杂双环托烷形式的1的（二乙基氨基）乙基侧链产生了3，一种非常有效的胃动力刺激剂和5-HT3受体拮抗剂，但没有明显的多巴胺受体拮抗剂特性。芳香核的随后改变导致吲唑6a-h，1-吲哚并3-吲哚并酮7b-d和8以及咪唑并[1,5-α]吡啶9和10被鉴定为有效的5-HT3受体拮抗剂。缺乏多巴胺拮抗剂或胃动力刺激特性。侧链的进一步构象限制确定奎核苷11和异喹核苷12为有效的5-HT3受体拮抗剂，它们模拟了托烷的扭曲椅构象，在11的情况下，N-甲基为轴向。从这些系列中，发现6g（BRL 43694）具有强效和选择性，并已被证明是一种非常有效的止吐药，可对抗雪貂和人体内由细胞毒性药物引起的呕吐。

  DOI：

  10.1021/jm00169a016

文献信息

• Certain heterocyclic N-substituted carboxamides
  申请人：Beecham Group p.l.c.

  公开号：US04882327A1

  公开（公告）日：1989-11-21

  Compounds of formula (I), or a pharmaceutically acceptable salt thereof: Y-CO-L-Z (I) wherein L is NH or O; Y is a group of formula (a), (b) or (c): ##STR1## wherein R.sub.1 and R.sub.2, R.sub.5 and R.sub.6, R.sub.9 and R.sub.10, are independently selected from hydrogen or halogen; X is N or CR.sub.3 wherein R.sub.3 is hydrogen or C.sub.1-6 alkoxy; R.sub.4 is hydrogen, halogen, CH.sub.3, C.sub.1-6 alkyl, C.sub.1-6 alkoxy, C.sub.1-6 alkylthio, C.sub.1-6 alkylsulphonyl, C.sub.1-6 alkylsulphinyl, C.sub.1-7 acyl, cyano, C.sub.1-6 alkoxycarbonyl, C.sub.1-7 acylamino, hydroxy, nitro or amino, aminocarbonyl, or aminosulphonyl, optionally N-substituted by one or two groups selected from C.sub.1-6 alkyl, C.sub.3-8 cycloalkyl, and C.sub.3-8 cycloalkyl C.sub.1-4 alkyl or disubstituted by C.sub.4 or C.sub.5 polymethylene; phenyl or phenyl C.sub.1-4 alkyl group optionally substituted in the phenyl ring by one or two of halogen, C.sub.1-6 alkoxy or C.sub.1-6 alkyl groups; one of R.sub.7 and R.sub.8 is C.sub.1-6 alkyl and the other is C.sub.1-6 alkyl, phenyl or phenyl C.sub.1-4 alkyl optionally substituted in either phenyl ring by one or two of C.sub.1-6 alkoxy or halogen; or R.sub.7 and R.sub.8 together are C.sub.2-6 polymethylene or C.sub.2-5 polymethylene interrupted by an -O- linkage; R.sub.11 is hydrogen or C.sub.1-6 alkoxy; R.sub.12 is hydrogen, halogen, CF.sub.3, C.sub.1-6 alkyl, C.sub.1-6 alkoxy, C.sub.1-6 alkylthio, C.sub.1-6 alkylsulphonyl, C.sub.1-6 alkylsulphinyl, C.sub.1-7 acyl, cyano, C.sub.1-6 alkoxycarbonyl, C.sub.1-7 acylamino, hydroxy, nitro or amino, aminocarbonyl, or aminosulphonyl, optionally N-substituted by one or two groups selected from C.sub.1-6 alkyl, C.sub.3-8 cycloalkyl, and C.sub.3-8 cycloalkyl C.sub.1-4 alkyl or disubstituted by C.sub.4 or C.sub.5 polymethylene; phenyl or phenyl C.sub.1-4 alkyl optionally substituted in either phenyl ring by one or two of halogen, C.sub.1-6 alkoxy or C.sub.1-6 alkyl groups; Z is a group of formula (d), (e) or (f): ##STR2## wherein n is 2 or 3; p is 1 or 2; q is 1 to 3; r is 1 to 3; and R.sub.13 and R.sub.14 is C.sub.1-4 alkyl; having 5-HT.sub.3 receptor antagonist activity, a process for their preparation and their use as pharmaceuticals.

  式(I)的化合物或其药学上可接受的盐：Y-CO-L-Z (I)，其中L为NH或O；Y为式(a)、(b)或(c)的基团：##STR1## 其中R.sub.1和R.sub.2、R.sub.5和R.sub.6、R.sub.9和R.sub.10独立选择自氢或卤素；X为N或CR.sub.3，其中R.sub.3为氢或C.sub.1-6烷氧基；R.sub.4为氢、卤素、CH.sub.3、C.sub.1-6烷基、C.sub.1-6烷氧基、C.sub.1-6烷基硫基、C.sub.1-6烷基磺酰基、C.sub.1-6烷基亚磺酰基、C.sub.1-7酰基、氰基、C.sub.1-6烷氧羰基、C.sub.1-7酰胺基、羟基、硝基或氨基、氨基羰基或氨基磺酰基，可选地被一或两个选择自C.sub.1-6烷基、C.sub.3-8环烷基和C.sub.3-8环烷基C.sub.1-4烷基的基团N取代，或被C.sub.4或C.sub.5聚亚甲基二取代；苯基或苯基C.sub.1-4烷基基团，可选地在苯环上被一个或两个卤素、C.sub.1-6烷氧基或C.sub.1-6烷基基团取代；R.sub.7和R.sub.8中的一个为C.sub.1-6烷基，另一个为C.sub.1-6烷基、苯基或苯基C.sub.1-4烷基，可选地在任一苯环上被一个或两个C.sub.1-6烷氧基或卤素取代；或R.sub.7和R.sub.8在一起为C.sub.2-6聚亚甲基或C.sub.2-5聚亚甲基，中断处为-O-连接；R.sub.11为氢或C.sub.1-6烷氧基；R.sub.12为氢、卤素、CF.sub.3、C.sub.1-6烷基、C.sub.1-6烷氧基、C.sub.1-6烷基硫基、C.sub.1-6烷基磺酰基、C.sub.1-6烷基亚磺酰基、C.sub.1-7酰基、氰基、C.sub.1-6烷氧羰基、C.sub.1-7酰胺基、羟基、硝基或氨基、氨基羰基或氨基磺酰基，可选地被一或两个选择自C.sub.1-6烷基、C.sub.3-8环烷基和C.sub.3-8环烷基C.sub.1-4烷基的基团N取代，或被C.sub.4或C.sub.5聚亚甲基二取代；苯基或苯基C.sub.1-4烷基，可选地在任一苯环上被一个或两个卤素、C.sub.1-6烷氧基或C.sub.1-6烷基基团取代；Z为式(d)、(e)或(f)的基团：##STR2## 其中n为2或3；p为1或2；q为1至3；r为1至3；R.sub.13和R.sub.14为C.sub.1-4烷基；具有5-HT.sub.3受体拮抗剂活性，其制备方法以及作为药物的用途。
• Amino-aza-adamantane derivatives and methods of use
  申请人：Schrimpf R. Michael

  公开号：US20070072892A1

  公开（公告）日：2007-03-29

  The invention relates to amine-substituted aza-adamantane derivatives, compositions comprising such compounds, and methods of treating conditions and disorders using such compounds and compositions. Radiolabelled compounds useful for evaluating the binding affinity to α7 nicotinic acetylcholine receptors also are described.

  本发明涉及胺基取代的氮杂亚金刚烷衍生物，包含这些化合物的组合物，以及使用这些化合物和组合物治疗疾病和疾病的方法。还描述了用于评估与α7尼古丁酸乙酰胆碱受体结合亲和力的放射性标记化合物。
• Meso-azacyclic amides of imidazopyridine carboxylic acids and analogs
  申请人：G. D. Searle & Co.

  公开号：US05196547A1

  公开（公告）日：1993-03-23

  The imidazopyridines containing meso-azacycle side chains as described herein find utility as antagonists of the serotonin 5-HT.sub.3 receptor. As such they are useful for the treatment of humans and animals wherein antagonism of 5-HT.sub.3 receptors is beneficial. Therapy is indicated for, but not limited to, the treatment of anxiety, psychoses, depression (especially depression accompanied by anxiety), cognitive disorders, substance abuse dependence and/or withdrawal, gastrointestinal motility disturbancies (including esophageal reflux, dyspepsia, irritable bowel syndrome), emesis caused by chemotherapeutic agents, and visceral pain. Additionally, the compounds of the present invention may find utility as enhancers of nasal absorption of bioactive compounds.

  本文所述的含有meso-azacycle侧链的咪唑吡啶类化合物可作为5-HT.sub.3受体拮抗剂。因此，它们对于治疗需要5-HT.sub.3受体拮抗剂的人类和动物是有用的。治疗适用于但不限于焦虑症、精神病、抑郁症（尤其是伴随焦虑的抑郁症）、认知障碍、物质滥用依赖和/或戒断、胃肠动力障碍（包括食管反流、消化不良、肠易激综合征）、化疗药物引起的呕吐和内脏疼痛。此外，本发明的化合物还可以作为生物活性化合物鼻吸收增强剂。
• Pharmaceutically useful meso-azacyclic amides of imidazopyridine
  申请人：G. D. Searle & Co.

  公开号：US05219850A1

  公开（公告）日：1993-06-15

  The imidazopyridines containing meso-azacycle side chains as described herein find utility as antagonists of the serotonin 5-HT.sub.3 receptor. As such they are useful for the treatment of humans and animals wherein antagonism of 5-HT.sub.3 receptors is beneficial. Therapy is indicated for, but not limited to, the treatment of anxiety, psychoses, depression (especially depression accompanied by anxiety), cognitive disorders, substance abuse dependence and/or withdrawal, gastrointestinal motility disturbancies (including esophageal reflux, dyspepsia, irritable bowel syndrome), emesis caused by chemotherapeutic agents, and visceral pain. Additionally, the compounds of the present invention may find utility as enhancers of nasal absorption of bioactive compounds.

  本文所描述的含有中环側鏈的咪唑吡啶类化合物可用作血清素5-HT3受体的拮抗剂。因此，它们可用于治疗对5-HT3受体拮抗有益的人类和动物。治疗适用于但不限于焦虑症，精神病，抑郁症（特别是伴随焦虑的抑郁症），认知障碍，物质滥用依赖和/或戒断，胃肠动力障碍（包括食管反流，消化不良，肠易激综合征），化疗药物引起的呕吐和内脏疼痛。此外，本发明的化合物可能作为生物活性化合物鼻吸收的增强剂。
• Meso-azacyclic amides of certain bicyclic carboxylic acids
  申请人：G. D. Searle & Co.

  公开号：US05227377A1

  公开（公告）日：1993-07-13

  The imidazopyridines containing meso-azacycle side chains as described herein find utility as antagonists of the serotonin 5-HT.sub.3 receptor. As such they are useful for the treatment of humans and animals wherein antagonism of 5-HT.sub.3 receptors is beneficial. Therapy is indicated for, but not limited to, the treatment of anxiety, psychoses, depression (especially depression accompanied by anxiety), cognitive disorders, substance abuse dependence and/or withdrawal, gastrointestinal motility disturbancies (including esophageal reflux, dyspepsia, irritable bowel syndrome), emesis caused by chemotherapeutic agents, and visceral pain. Additionally, the compounds of the present invention may find utility as enhancers of nasal absorption of bioactive compounds.

  本文所述的含有中间咪唑吡啶的meso-氮杂环侧链可作为5-HT.sub.3受体拮抗剂。因此，它们可用于治疗对5-HT.sub.3受体拮抗有益的人类和动物。治疗适用于但不限于焦虑症、精神病、抑郁症（尤其是伴有焦虑的抑郁症）、认知障碍、物质滥用依赖和/或戒断、胃肠运动障碍（包括食道反流、消化不良、肠易激综合征）、化疗药物引起的呕吐和内脏疼痛。此外，本发明的化合物可作为生物活性化合物鼻吸收增强剂。