3-氮杂双环[2.2.2]辛烷-3-羧酸乙酯 | 39926-11-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 3-氮杂双环[2.2.2]辛烷-3-羧酸乙酯
• 中文别名: 1-氮-二环[2.2.2]辛烷-2-甲酸乙酯
• 英文名称: (+/-)-ethyl quinuclidine-2-carboxylate
• 英文别名: ethyl quinuclidine-2-carboxylate；2-carboethoxy-2-quinuclidine；1-aza-bicyclo[2.2.2]octane-2-carboxylic acid ethyl ester；quinuclidine-2-carboxylic acid ethyl ester；Chinuclidin-2-carbonsaeure-aethylester；rac-Chinulcidin-carbonsaeure-(2)-ethylester；ethyl 1-azabicyclo[2.2.2]octane-2-carboxylate
• CAS: 39926-11-9
• 化学式: C₁₀H₁₇NO₂
• mdl: MFCD01684892
• 分子量: 183.25
• InChiKey: KCCLFMFYEDPKEL-UHFFFAOYSA-N

物化性质

• 沸点：
  122-123 °C(Press: 14 Torr)
• 密度：
  1.09±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  3-氮杂双环[2.2.2]辛烷-3-羧酸乙酯 在 吡啶 、 三光气 、 氨 作用下， 以 甲醇 为溶剂， 生成 2-氰基奎宁环
  参考文献：
  名称：

  了解锇催化的不对称二羟基化 (AD) 中的高对映选择性。1. 动力学

  摘要：

  了解锇催化的不对称二羟基化 (AD) 中的高对映选择性。1. 动力学

  DOI：

  10.1021/ja00083a014
• 作为产物：
  描述：

  2-carboethoxy-2-dehydroquinuclidine 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 反应 1.0h， 生成 3-氮杂双环[2.2.2]辛烷-3-羧酸乙酯
  参考文献：
  名称：

  Ricciardi, Fiore J.; Doukas, Peter H., Heterocycles, 1986, vol. 24, # 4, p. 971 - 977

  摘要：

  DOI：

文献信息

• Mono- and diaryl-2-quinuclidinylcarbinols with local anesthetic and antiarrhythmic activity
  作者：P. H. Nelson、A. M. Strosberg、K. G. Untch

  DOI：10.1021/jm00176a014

  日期：1980.2

  The reaction between 2-carboethoxyquinuclidine and various aryl- and heteroarylithium reagents gave mixtures of aryl 2-quinuclidinyl ketones and diaryl-2-quinuclidinylcarbinols. Diborane reduction of the ketones gave the erythro-carbinols, stereochemically analogous to quinidine. Several of the mono- and diarylcarbinols exhibited potent local anesthetic and antiarrhythmic activity, in some cases greater

  2-羰基乙氧基奎宁环烷与各种芳基和杂芳基锂试剂之间的反应得到了芳基2-奎宁环烷基酮和二芳基-2-奎宁环烷基羰基的混合物。乙酮的乙硼烷还原生成立体异构类似于奎尼丁的赤藓醇。几种单和二芳基甲醇会表现出有效的局部麻醉和抗心律不齐活性，在某些情况下，其活性高于奎尼丁。二苯基-2-奎宁环戊基甲醇和（溴甲氧基苯基）（甲氧基苯基）-2-奎宁环基甲醇在犬哇巴因性心律失常的恢复中特别活跃，显示出等效于或大于普萘洛尔的作用力和作用时间。
• Analogs ofCinchona Alkaloids Incorporating a 9,9?-Spirobifluorene Moiety
  作者：Barbara Winter-Werner、Fran�ois Diederich、Volker Gramlich

  DOI：10.1002/hlca.19960790509

  日期：1996.8.7

  that (−)-5 and (+)-5 differ significantly in their conformational preference from their natural counterparts quinine (1) and quinidine (2). Whereas the natural alkaloids prefer the ‘open’ conformation, with the quinuclidine N-atom pointing away from the quinoline ring, analog (±)-5 adopts preferentially (by ca. 4 kcal mol−1) a ‘closed’ conformation, in which the quinuclidine N-atom points into the cleft

  的金鸡纳生物碱类似物（+） -和（ - ） - 5用9,9'-螺二芴部分的附接至C（2）奎宁环-2-甲醇的残余物中通过使锂化的2-溴制备为外消旋混合物将9,9'-螺双芴7与（2-乙氧羰基）喹核苷（±）-6结合，得到酮（±）-8，然后用二异丁基氢化铝（DIBAL-H）进行非对映选择性还原。5的两个对映异构体中C（9）和C（8）的绝对构型，即在甲醇桥和相邻的奎宁环C原子上的绝对构型与（-）-奎宁（1）和（+）-奎尼丁（2）， 分别。为了获得（±）-5的光学分辨率，通过将奎宁经硫醇间隔基共价键合至硅胶表面，制备了用于HPLC的手性固定相。对映体分离在α值为1.61时完成，最后洗脱（±）-5，这与CDCl 3中的1 H-NMR研究表明，（+）- 5与奎宁的宿主-客体缔合更为稳定比（-）- 5。1 H 1 H}核受体的过度劳累效应（NOE）差异光谱分析与CDCl 3中奎宁的结合结合计算机模型检查，可以将绝对配置指定为（+）-（8
• [EN] FIVE-MEMBERED HETEROAROMATIC OLEFINIC AZACYCLIC COMPOUNDS, PHARMACEUTICAL COMPOSITIONS CONTAINING THEM AND THEIR USE AS INHIBITORS OF NCOTINIC CHOLINERGIC RECEPTORS<br/>[FR] COMPOSES HETEROAROMATIQUES OLEFINIQUES AZACYCLIQUES A CINQ ELEMENTS, COMPOSITIONS PHARMACEUTIQUES CONTENANT LESDITS COMPOSES ET LEUR UTILISATION COMME INHIBITEURS DES RECEPTEURS NICOTINIQUES CHOLINERGIQUES
  申请人：TARGACEPT INC

  公开号：WO2004009599A1

  公开（公告）日：2004-01-29

  The present invention relates to five-membered heteroaromatic olefinic azacyclic compounds and five-membered heteroaromatic acetylenic azacylic compounds, having formula (I) wherein the ring including X, XI, XII, XIII and X IV is heteroaromatic, B is a two-carbon bridging species and Q, E, EI, EII, EIII, m and n are as defined herein and pharmaceutical compositions containing them that are capable of affecting nicotic cholinergic receptors.

  本发明涉及五元杂芳烯基氮杂环化合物和五元杂芳乙炔基氮环化合物，其化学式为（I），其中包括X、XI、XII、XIII和XIV的环是杂芳环，B是一个含有两个碳的桥联物种，Q、E、EI、EII、EIII、m和n的定义如本文所述，并含有这些化合物的药物组合物，能够影响烟碱型胆碱受体。
• N-aryl diazaspiracyclic compounds and methods of preparation and use thereof
  申请人：Targacept, Inc.

  公开号：US20040067930A1

  公开（公告）日：2004-04-08

  Compounds, pharmaceutical compositions including the compounds, and methods of preparation and use thereof are disclosed. The compounds are N-aryl diazaspirocyclic compounds, bridged analogs of N-heteroaryl diazaspirocyclic compounds, or prodrugs or metabolites of these compounds. The aryl group can be a five- or six-membered heterocyclic ring (heteroaryl). The compounds and compositions can be used to treat and/or prevent a wide variety of conditions or disorders, particularly those disorders characterized by dysfunction of nicotinic cholinergic neurotransmission, including disorders involving neuromodulation of neurotransmitter release, such as dopamine release. CNS disorders, which are characterized by an alteration in normal neurotransmitter release, are another example of disorders that can be treated and/or prevented. The compounds and compositions can also be used to alleviate pain. The compounds can: (i) alter the number of nicotinic cholinergic receptors of the brain of the patient, (ii) exhibit neuroprotective effects and (iii) when employed in effective amounts, not result in appreciable adverse side effects (e.g., side effects such as significant increases in blood pressure and heart rate, significant negative effects upon the gastro-intestinal tract, and significant effects upon skeletal muscle).

  本文公开了N-芳基二氮杂螺环化合物、N-杂芳基二氮杂螺环化合物的桥接类似物、以及这些化合物的前药或代谢物的制备和使用方法。芳基可以是五元或六元杂环（杂芳基）。这些化合物和组合物可用于治疗和/或预防各种疾病或障碍，特别是那些以尼古丁胆碱能神经递质功能障碍为特征的障碍，包括涉及神经递质释放的神经调节障碍，例如多巴胺释放。中枢神经系统障碍是另一个可以治疗和/或预防的例子，其特征是正常神经递质释放的改变。这些化合物和组合物也可用于缓解疼痛。这些化合物可以：（i）改变患者的大脑中尼古丁胆碱能受体的数量，（ii）表现出神经保护作用，以及（iii）在有效剂量下，不会导致明显的不良副作用（例如，明显增加血压和心率、对胃肠道的明显负面影响以及对骨骼肌的明显影响等副作用）。
• Use of N-aryl diazaspiracyclic compounds in the treatment of addiction
  申请人：Bhatti S. Balwinder

  公开号：US20060058328A1

  公开（公告）日：2006-03-16

  Compounds, compositions and methods for treating drug addiction, nicotine addiction, and/or obesity are disclosed. The compounds are N-aryl diazaspirocyclic compounds, bridged analogs of N-heteroaryl diazaspirocyclic compounds, or prodrugs or metabolites of these compounds. The aryl group can be a five- or six-membered heterocyclic ring (heteroaryl). The compounds are effective at inhibiting dopamine production and/or secretion, and accordingly are effective at inhibiting the physiological “reward” process that is associated with ingestion of nicotine and/or illicit drugs. The compounds and compositions can be administered in effective amounts to inhibit dopamine release, without resulting in appreciable adverse side effects (e.g., side effects such as significant increases in blood pressure and heart rate, significant negative effects upon the gastro-intestinal tract, and significant effects upon skeletal muscle).

  本发明涉及用于治疗药物成瘾、尼古丁成瘾和/或肥胖症的化合物、组合物和方法。这些化合物是N-芳基二氮杂螺环化合物、N-杂芳基二氮杂螺环化合物的桥接类似物或这些化合物的前药或代谢物。芳基可以是五元或六元杂环环（杂芳基）。这些化合物能够有效地抑制多巴胺的产生和/或分泌，从而有效地抑制与尼古丁和/或非法药物摄入相关的生理“奖励”过程。这些化合物和组合物可以以有效剂量给予，以抑制多巴胺的释放，而不会导致明显的不良副作用（例如，显著增加血压和心率、对胃肠道产生显著负面影响以及对骨骼肌产生显著影响等副作用）。