3-(2-氯乙基)-3-氮杂双环[2.2.2]辛烷 | 59882-35-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 中文名称: 3-(2-氯乙基)-3-氮杂双环[2.2.2]辛烷
• 英文名称: 2-(2-Chloroethyl)-2-azabicyclo<2.2.2>octane
• 英文别名: 2-(2-chloroethyl)-2-azabicyclo[2. 2. 2]octane；2-(2-Chloroethyl)-2-azabicyclo[2.2.2]octane
• CAS: 59882-35-8
• 化学式: C₉H₁₆ClN
• 分子量: 173.686
• InChiKey: KZIFBXDJECGAOW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  3.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  3-(2-氯乙基)-3-氮杂双环[2.2.2]辛烷 在 硫酸 、 sodium amide 作用下， 反应 2.92h， 生成 2-[2-(diisopropylamino)ethyl]-2-phenyl-4-(2-azabicyclo[2.2.2]oct-2-yl)butyramide
  参考文献：
  名称：

  α，α-双[（二烷基氨基）烷基]苯基乙酰胺的合成和抗心律失常活性。

  摘要：

  介绍了一系列α，α-双[（二烷基氨基）烷基]苯基乙酰胺的合成和生物学评估。这些化合物在结构上与抗心律失常药双吡amide胺（1）有关，在许多情况下，它们在与冠状动脉结扎的犬中具有更大的抗心律失常活性。在这一系列化合物中，通常还可以从母体化合物7中观察到抗心律失常特性与不必要的心脏抑制药副作用之间的分离。讨论了该系列中的构效关系。这项工作最终确定了化合物35（disobutamide）作为人类抗心律不齐药物的临床评价候选药物。

  DOI：

  10.1021/jm00184a008
• 作为产物：
  描述：

  2-(2-aza-bicyclo[2.2.2]oct-2-yl)-ethanol 、 氯化亚砜 生成 3-(2-氯乙基)-3-氮杂双环[2.2.2]辛烷
  参考文献：
  名称：

  YONAN P. K.; NOVOTNEY R. L.; WOO C. M.; PRODAN K. A.; HERSHENSON F. M., J. MED. CHEM., 1980, 23, NO 10, 1102-1108

  摘要：

  DOI：

文献信息

• 3-[2-(Azabicyclo)
  申请人：Warner-Lambert Company

  公开号：US04404138A1

  公开（公告）日：1983-09-13

  Anticholinergic 3-[2-(azabicyclo)ethyl]-1,2,3,4-tetrahydro-5H-[1]benzopyrano[3,4-c]pyridin -5-ones useful for treating bronchospastic diseases in mammals are disclosed. Also disclosed are methods for preparing said compounds, pharmaceutical compositions containing them and methods for using said pharmaceutical compositions.

  抗胆碱药物3-[2-(氮杂双环)乙基]-1,2,3,4-四氢-5H-[1]苯并吡喃[3,4-c]吡啶-5-酮，用于治疗哺乳动物的支气管痉挛性疾病。还公开了制备这些化合物的方法，含有它们的药物组合物以及使用这些药物组合物的方法。
• 3-(Aminoalkyl)-1,2,3,4-tetrahydro-5H-[1]benzopyrano[3,4-c]pyridin-5-ones as potential anticholinergic bronchodilators
  作者：David T. Connor、Paul C. Unangst、Charles F. Schwender、Roderick J. Sorenson、Mary E. Carethers、Chester Puchalski、Richard E. Brown、Martin P. Finkel

  DOI：10.1021/jm00123a032

  日期：1989.3

  A series of 3-(aminoalkyl)benzopyrano[3,4-c]pyridin-5-ones was prepared and tested as potential orally active anticholinergic bronchodilators. Inhibition of methacholine-induced collapse in guinea pigs and inhibition of pilocarpine-induced bronchoconstriction in dogs served as in vivo models. Simultaneous measurement of salivary inhibition in the dog model allowed determination of a pulmonary selectivity

  制备了一系列3-（氨基烷基）苯并吡喃并[3,4-c]吡啶基-5-酮，并测试了它们作为潜在的口服抗胆碱能支气管扩张剂。在豚鼠中甲乙酰胆碱诱导的塌陷的抑制和狗毛果芸香碱诱导的支气管收缩的抑制被用作体内模型。在狗模型中唾液抑制的同时测量允许确定肺的选择性比。通过苯酚与哌啶β-酮酯的Pechman缩合制备苯并吡喃并[3,4-c]吡啶-5-酮母环系统。用氨基烷基卤化物或用1-氯-2-丙酮烷基化，然后进行还原胺化，得到3-取代的目标化合物。支气管扩张药的效力与围绕侧链末端胺功能的空间拥挤程度有关。将碳α上的甲基取代基加到末端胺上通常会提高效力或肺部选择性。在进行二次药理学评估后，选择了命名为CI-923的化合物7a作为支气管扩张药进行临床试验。
• Anti-diarrheal oxadiazoles
  申请人：G. D. Searle & Co.

  公开号：US04003904A1

  公开（公告）日：1977-01-18

  The present invention encompasses a compound of the formula ##STR1## and the pharmaceutically acceptable acid addition salts thereof wherein Y is alkylene having 1-4 carbon atoms; R.sub.1 and R.sub. 2 together with N is a heterocyclic ring system consisting of an azamonocyclic ring of the formula ##STR2## wherein Z is oxygen, methylene, phenylhydroxymethylene, phenylcarboxymethylene or, phenylloweralkoxymethylene, or an azabicycloalkane structure having 6-9 carbon atoms and having at least 5 atoms in each ring of the azabicycloalkane structure; X is hydrogen, halogen, loweralkyl having 1-7 carbon atoms, or loweralkoxy having 1-7 carbon atoms; and Ar is phenyl, pyridyl, or monosubstituted phenyl wherein the substituent is halogen, loweralkyl having 1-7 carbon atoms, or loweralkoxy having 1-7 carbon atoms when R.sub.3 is hydrogen or Ar is 3 or 4 pyridyl when R.sub.3 is lower alkyl having 1-7 carbon atoms. The compounds of the present invention are prepared by converting the corresponding nitriles to 1H-tetrazoles and in turn reacting the 1H-tetrazole with ethyl chloroglyoxylate, hydrolyzing the resulting ester to the acid and decarboxylation to provide compounds wherein R.sub.3 is hydrogen. Compounds of the present invention are anti diarrheal agents.

  本发明涵盖了以下公式的化合物及其药学上可接受的酸加合盐：其中Y是具有1-4个碳原子的烷基；R.sub.1和R.sub.2与N一起形成一个由以下公式的氮杂单环环组成的杂环环系统：其中Z是氧、亚甲基、苯基羟甲基、苯基羧甲基或苯基低碳基氧甲基，或者是具有6-9个碳原子且在每个环中至少有5个原子的氮杂双环戊烷结构；X是氢、卤素、具有1-7个碳原子的低烷基或具有1-7个碳原子的低烷氧基；Ar是苯基、吡啶基或单取代苯基，其中取代基是卤素、具有1-7个碳原子的低烷基或具有1-7个碳原子的低烷氧基，当R.sub.3为氢或Ar为3或4吡啶基时，取代基为具有1-7个碳原子的低烷基。本发明的化合物是通过将相应的腈转化为1H-四唑，然后将1H-四唑与氯乙酰乙酸乙酯反应，水解得到酯，脱羧得到R.sub.3为氢的化合物。本发明的化合物是抗腹泻剂。
• Anti-diarrheal compounds
  申请人：G. D. Searle & Co.

  公开号：US03998832A1

  公开（公告）日：1976-12-21

  The present invention comprehends a method for treating diarrhea comprising administering to an animal in need of anti-diarrheal treatment an effective antidiarrheal amount of a compound of the formula ##STR1## AND ACID ADDITION SALTS THEREOF WHEREIN Y is alkylene containing 1-4 carbon atoms; R.sub.2 and R.sub.3 together with N is a heterocyclic ring system comprising azamonocyclic ring of the formula ##STR2## wherein Z is phenylhydroxymethylmethylene, phenylhydroxymethylene, phenylcarboxymethylene, phenylcarbalkoxymethylene or azabicycloalkyl or phenyl or hydroxyl substituted azabicycloalkyl containing 6-9 carbon atoms and containing at least 5 atoms in each ring of the azabicycloalkyl or 4-azatricyclo[4.3.1.1.sup.3,8 ]undec-4-yl; Ar.sub.1 and Ar.sub.2 are phenyl, halo-substituted phenyl, (lower alkyl) substituted phenyl, pyridyl, thienyl or furyl, and Ar.sub.3 is phenyl, halo-substituted phenyl, (lower alkyl) substituted phenyl, pyridyl, thienyl, furyl, pyrrolyl, imidazoyl, oxazolinyl, oxazolinyl, thiazolinyl, thiazolyl, 1,2,4-oxodiazolyl, and isoxazolinyl. The present invention also comprehends novel compounds included in the above formula.

  本发明涉及一种治疗腹泻的方法，包括向需要抗腹泻治疗的动物施加有效的抗腹泻剂量的化合物，该化合物的化学式为##STR1##和其酸加成盐，其中Y是含有1-4个碳原子的烷基；R.sub.2和R.sub.3与N一起是一个杂环环系，包括公式##STR2##的氮杂单环环，其中Z是苯基羟甲基亚甲基、苯基羟甲基、苯基羧甲亚甲基、苯基羧基烷氧甲基或含有6-9个碳原子并且每个环中至少有5个原子的苯基或含有4-azatricyclo[4.3.1.1.sup.3,8]undec-4-yl的氮杂环烷基；Ar.sub.1和Ar.sub.2是苯基、卤代苯基、(低烷基)取代苯基、吡啶基、噻吩基或呋喃基，而Ar.sub.3是苯基、卤代苯基、(低烷基)取代苯基、吡啶基、噻吩基、呋喃基、吡咯基、咪唑基、噁唑啉基、噁唑啉基、噻唑啉基、噻唑基、1,2,4-氧二唑基和异噁唑啉基。本发明还包括上述化合物中包含的新化合物。
• 1,1-Diaryl-1H-tetrazole amines
  申请人：G. D. Searle & Co.

  公开号：US04017491A1

  公开（公告）日：1977-04-12

  The present invention relates to compounds of the following formula ##STR1## wherein Y is straight or branched chain alkylene containing 1-4 carbon atoms; X is hydrogen, halo such as fluoro, chloro, bromo or iodo, or lower alkyl containing 1-7 carbon atoms; Ar is phenyl, pyridyl, mono-substituted phenyl, wherein the substituent is halo such as fluoro, chloro, or bromo, or lower alkyl having 1-7 carbon atoms; and R.sub.2 and R.sub.3 are lower alkyl having 1-7 carbon atoms, or R.sub.2 and R.sub.3 together with N is an azamonocyclic ring selected from the group comprising 1-pyrrolidinyl, piperidino, 4-phenyl-4-hydroxypiperidino, 4-phenyl-4-hydroxymethylene, 4-phenyl-4-carboxypiperidino, 4-phenyl-4-carbloweralkoxypiperidino, or 4-phenyl-4-acetoxypiperidino substituted piperidino and morpholino, or an azabicycloalkanyl containing 6 to 9 carbon atoms and having at least 5 atoms in each ring of the azabicycloalkane. These compounds are useful intermediates for preparing potent antidiarrheal compounds.

  本发明涉及以下式的化合物：##STR1## 其中，Y是含有1-4个碳原子的直链或支链烷基；X是氢、卤素，如氟、氯、溴或碘，或含有1-7个碳原子的低级烷基；Ar是苯基、吡啶基、单取代苯基，其中取代基是卤素，如氟、氯或溴，或含有1-7个碳原子的低级烷基；而R.sub.2和R.sub.3是含有1-7个碳原子的低级烷基，或者R.sub.2和R.sub.3与N一起是从1-吡咯啉基、哌啶基、4-苯基-4-羟基哌啶基、4-苯基-4-羟基甲基、4-苯基-4-羧基哌啶基、4-苯基-4-羧低级烷氧基哌啶基、或取代哌啶基和吗啡啉中选择的一种氮杂单环环，或者是含有6-9个碳原子，并且在每个环中至少有5个原子的氮杂双环烷基。这些化合物是制备有效的抗腹泻化合物的有用中间体。