2,2,2-trichlorocarboxynortropinone | 53912-86-0

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 托烷生物碱
• 英文名称: 2,2,2-trichlorocarboxynortropinone
• 英文别名: N-2,2,2-Trichlorcarbethoxynortropinon；2,2,2-Trichloroethyl 3-oxo-8-azabicyclo[3.2.1]octane-8-carboxylate
• CAS: 53912-86-0
• 化学式: C₁₀H₁₂Cl₃NO₃
• 分子量: 300.569
• InChiKey: DOYNMBXSIVXMMB-UHFFFAOYSA-N

物化性质

• 沸点：
  376.9±42.0 °C(Predicted)
• 密度：
  1.511±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,2,2-trichlorocarboxynortropinone 在 溶剂黄146 、 锌 作用下， 生成 去甲托品酮
  参考文献：
  名称：

  Synthesis and in vitro evaluation of 5,6,7,8,9,10-hexahydro-7,10-iminocyclohept[b]indoles: high-affinity ligands for the N,N'-di-o-tolylguanidine-labeled .sigma. binding site

  摘要：

  A series of 5,6,7,8,9,10-hexahydro-7,10-iminocyclo[b]indoles substituted at the 5 and/or 11 positions was synthesized from tropinone. Affinity for sigma binding sites was determined using [H-3]-N,N'-di-o-tolylguanidine ([H-3]DTG) and [H-3]-(+)-3-(3-hydroxyphenyl)-N-1-propylpiperidine ([H-3]-(+)-3-PPP) and for the dopamine D2 receptor labeled with [H-3]sulpiride. Nearly all compounds studied in this series possessed a higher affinity for [H-3]DTG than [H-3]-(+)-PPP-labeled sigma sites, suggesting that [H-3]DTG and [H-3]-(+)-3-PPP radioligands label pharmacologically distinct sigma binding sites, as reported previously. Substitution at the 11 position with side chains containing a four-carbon tether resulted in compounds having the highest affinity for the [H-3]DTG-labeled a site. The most potent and selective member of this series was 11-[4-(2-furanyl)butyl]-5,6,7,8,9, 10-hexahydro-7,10-iminocyclohept[b]indole(40). Enantioselectivity was investigated by preparing the (+)- and (-)-isomers of 40. These studies revealed that (+)-40 was more potent at the [H-3]-DTG-labeled sigma site whereas (-)-40 had a higher affinity at sigma sites labeled with [H-3]-(+)-PPP. Racemic 40 was observed to possess a higher affinity than either of its respective enantiomers at both the [H-3]DTG- and [H-3]-(+)-3-PPP-labeled sites, suggesting an allosteric interaction.

  DOI：

  10.1021/jm00055a005
• 作为产物：
  描述：

  托品酮 、 氯甲酸-2,2,2-三氯乙酯 在 potassium carbonate 作用下， 生成 2,2,2-trichlorocarboxynortropinone
  参考文献：
  名称：

  Synthesis and in vitro evaluation of 5,6,7,8,9,10-hexahydro-7,10-iminocyclohept[b]indoles: high-affinity ligands for the N,N'-di-o-tolylguanidine-labeled .sigma. binding site

  摘要：

  A series of 5,6,7,8,9,10-hexahydro-7,10-iminocyclo[b]indoles substituted at the 5 and/or 11 positions was synthesized from tropinone. Affinity for sigma binding sites was determined using [H-3]-N,N'-di-o-tolylguanidine ([H-3]DTG) and [H-3]-(+)-3-(3-hydroxyphenyl)-N-1-propylpiperidine ([H-3]-(+)-3-PPP) and for the dopamine D2 receptor labeled with [H-3]sulpiride. Nearly all compounds studied in this series possessed a higher affinity for [H-3]DTG than [H-3]-(+)-PPP-labeled sigma sites, suggesting that [H-3]DTG and [H-3]-(+)-3-PPP radioligands label pharmacologically distinct sigma binding sites, as reported previously. Substitution at the 11 position with side chains containing a four-carbon tether resulted in compounds having the highest affinity for the [H-3]DTG-labeled a site. The most potent and selective member of this series was 11-[4-(2-furanyl)butyl]-5,6,7,8,9, 10-hexahydro-7,10-iminocyclohept[b]indole(40). Enantioselectivity was investigated by preparing the (+)- and (-)-isomers of 40. These studies revealed that (+)-40 was more potent at the [H-3]-DTG-labeled sigma site whereas (-)-40 had a higher affinity at sigma sites labeled with [H-3]-(+)-PPP. Racemic 40 was observed to possess a higher affinity than either of its respective enantiomers at both the [H-3]DTG- and [H-3]-(+)-3-PPP-labeled sites, suggesting an allosteric interaction.

  DOI：

  10.1021/jm00055a005

文献信息

• [EN] NEUROPROTECTIVE INDOLONE AND RELATED DERIVATIVES
  申请人：PFIZER INC

  公开号：WO1991017156A1

  公开（公告）日：1991-11-14

  (EN) 5-(1-Hydroxy-2-piperidinopropyl)-2(1H,3H)-indolone derivatives and analogs; pharmaceutical compositions thereof; methods of treating CNS disorders therewith; and intermediates useful in the preparation of said compounds.(FR) Dérivés de 5-(1-hydroxy-2-piperidinopropyle)-2(1H,3H)-indolone et analogues; compositions pharmaceutiques les contenant; procédés servant à traiter des troubles du système nerveux central avec ces compositions; et intermédiaires utiles dans la préparation des composés de la présente invention.

  5-（1-羟基-2-吡啶乙基）-2（1H,3H）-ione衍生物及其类同物、含其成分的药用合成、用于治疗中枢神经系统紊乱的方法以及制备此类化合物的中间体。
• Ring Cleavage Reaction of Heterocyclic Ketones Based on Crossed Aldol Condensation
  作者：Hiroshi Suemune、Jun Uchida、Kiyoshi Sakai

  DOI：10.3987/com-95-7339

  日期：——

  Ring cleavage reaction based on crossed aldol condensation using heterocyclic ketones such as 4-piperidone and nortropinone derivatives with benzaldehyde under acetalization conditions (BF3 . Et(2)O/ethylene glycol) has been achieved.
• NEUROPROTECTIVE INDOLONE AND RELATED DERIVATIVES
  申请人：PFIZER INC.

  公开号：EP0554247B1

  公开（公告）日：2000-04-26
• US5306723A
  申请人：——

  公开号：US5306723A

  公开（公告）日：1994-04-26
• US5498610A
  申请人：——

  公开号：US5498610A

  公开（公告）日：1996-03-12