(5S)-1-methyl-5-pyridin-3-ylpyrrolidin-2-ol | 1009088-33-8

• 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: (5S)-1-methyl-5-pyridin-3-ylpyrrolidin-2-ol
• CAS: 1009088-33-8
• 化学式: C₁₀H₁₄N₂O
• 分子量: 178.234
• InChiKey: OTHOSUVCRYJGFQ-RGURZIINSA-N

物化性质

• 沸点：
  300.6±42.0 °C(Predicted)
• 密度：
  1.156±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  36.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (5S)-1-methyl-5-pyridin-3-ylpyrrolidin-2-ol 在 高氯酸 、 溶剂黄146 作用下， 以 乙醚 、 乙醇 、 水 为溶剂， 生成 (S)-nicotine Δ-^1',5'-iminium bisperchlorate
  参考文献：
  名称：

  Stereochemical studies on the cytochrome P-450 catalyzed oxidation of (S)-nicotine to the (S)-nicotine .DELTA.1'(5')-iminium species

  摘要：

  Mammals metabolize the tobacco alkaloid (S)-nicotine primarily to the lactam (S)-cotinine by a pathway involving an initial cytochrome P-450 catalyzed two-electron oxidation at the prochiral 5'-carbon atom. The stereochemical course of this oxidation was examined with human microsomal preparations and the E and Z diastereomers of (S)-nicotine-5'd1. The metabolically generated delta 1'(5')-iminium ion intermediate was trapped and analyzed as the corresponding diastereomeric 5'-cyano derivatives by a capillary column GC-EIMS selected ion monitoring assay. The results of these studies established that this biotransformation proceeds with the stereoselective abstraction of the 5'-pro-E proton, that is, the C-5' proton trans to the bulky pyridyl group. The observed stereoselectivity was independent of proton vs. deuteron abstraction. Additionally, the extent of (S)-cotinine formation was minor and did not influence the stereochemical composition of the metabolically derived alpha-cyano amines. Studies with male Dutch rabbit liver microsomal preparations gave similar results. These findings suggest that the structure of the complex formed between (S)-nicotine and the active site of cytochrome P-450 is highly ordered and dictates the stereochemical course of the reaction pathway.

  DOI：

  10.1021/jm00385a004
• 作为产物：
  描述：

  吡啶吡咯酮 在 红铝 作用下， 以 乙醚 为溶剂， 反应 3.0h， 生成 (5S)-1-methyl-5-pyridin-3-ylpyrrolidin-2-ol
  参考文献：
  名称：

  Stereochemical studies on the cytochrome P-450 catalyzed oxidation of (S)-nicotine to the (S)-nicotine .DELTA.1'(5')-iminium species

  摘要：

  Mammals metabolize the tobacco alkaloid (S)-nicotine primarily to the lactam (S)-cotinine by a pathway involving an initial cytochrome P-450 catalyzed two-electron oxidation at the prochiral 5'-carbon atom. The stereochemical course of this oxidation was examined with human microsomal preparations and the E and Z diastereomers of (S)-nicotine-5'd1. The metabolically generated delta 1'(5')-iminium ion intermediate was trapped and analyzed as the corresponding diastereomeric 5'-cyano derivatives by a capillary column GC-EIMS selected ion monitoring assay. The results of these studies established that this biotransformation proceeds with the stereoselective abstraction of the 5'-pro-E proton, that is, the C-5' proton trans to the bulky pyridyl group. The observed stereoselectivity was independent of proton vs. deuteron abstraction. Additionally, the extent of (S)-cotinine formation was minor and did not influence the stereochemical composition of the metabolically derived alpha-cyano amines. Studies with male Dutch rabbit liver microsomal preparations gave similar results. These findings suggest that the structure of the complex formed between (S)-nicotine and the active site of cytochrome P-450 is highly ordered and dictates the stereochemical course of the reaction pathway.

  DOI：

  10.1021/jm00385a004

文献信息

• SUBSTITUTED BENZYLAMINES AS CYP2A INHIBITORS AND USES THEREOF TO TREAT NICOTINE DEPENDENCE
  申请人：Ghosheh Omar

  公开号：US20090137653A1

  公开（公告）日：2009-05-28

  This invention is directed to substituted benzylamines which are useful as inhibitors of the CYP2A6 enzyme. Pharmaceutical compositions comprising the compounds and methods of using the compounds to treat nicotine dependence are also disclosed.

  本发明涉及替代苯甲胺类化合物，其可用作CYP2A6酶的抑制剂。还公开了包含该化合物的制药组合物以及使用该化合物治疗尼古丁依赖的方法。
• THERAPEUTIC COTININE COMPOSITIONS
  申请人：Scott David Albert

  公开号：US20100143270A1

  公开（公告）日：2010-06-10

  The present invention provides methods and compositions for treating acute and/or chronic inflammation with cotinine or a pharmaceutically acceptable salt thereof.
• [EN] SUBSTITUTED BENZYLAMINES AS CYP2A INHIBITORS AND USES THEREOF TO TREAT NICOTINE DEPENDENCE<br/>[FR] BENZYLAMINES SUBSTITUEES SERVANT D'INHIBITEURS DE CYP2A ET UTILISATIONS DE CELLES-CI POUR TRAITER UNE DEPENDANCE A LA NICOTINE
  申请人：INFLAZYME PHARM LTD

  公开号：WO2006108149A2

  公开（公告）日：2006-10-12

  [EN] This invention is directed to substitued benzylamines which are useful as inhibitors of the CYP2A6 enzyme. Pharmaceutical compositions comprising the compounds and methods of using the compounds to treat nicotine dependence are also disclosed.
  [FR] La présente invention concerne des benzylamines substituées qui sont utilisées comme inhibiteurs de l'enzyme CYP2A6, des compositions pharmaceutiques comprenant ces composés et des procédés pour utiliser ces composés afin de traiter une dépendance à la nicotine.
• [EN] THERAPEUTIC COTININE COMPOSITIONS<br/>[FR] COMPOSITIONS THÉRAPEUTIQUES À BASE DE COTININE
  申请人：UNIV LOUISVILLE RES FOUND

  公开号：WO2008103818A1

  公开（公告）日：2008-08-28

  [EN] The present invention provides methods and compositions for treating acute and/or chronic inflammation with cotinine or a pharmaceutically acceptable salt thereof.
  [FR] La présente invention a pour objet des procédés et des compositions destinés au traitement d'une inflammation aiguë et/ou chronique avec de la cotinine ou l'un de ses sels acceptables sur le plan pharmaceutique.