5-Chloro-2-(3-oxocyclohexen-1-yl)amino-benzonitrile | 121445-16-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 5-Chloro-2-(3-oxocyclohexen-1-yl)amino-benzonitrile
• 英文别名: 5-chloro-2-[(3-oxocyclohexen-1-yl)amino]benzonitrile
• CAS: 121445-16-7
• 化学式: C₁₃H₁₁ClN₂O
• 分子量: 246.696
• InChiKey: FVGJEEZGZNUJMX-UHFFFAOYSA-N

物化性质

• 沸点：
  406.9±45.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  52.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-Chloro-2-(3-oxocyclohexen-1-yl)amino-benzonitrile 在 copper(l) chloride potassium carbonate 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 以4%的产率得到9-amino-7-chloro-3,4-dihydroacridin-1(2H)-one
  参考文献：
  名称：

  9-Amino-1,2,3,4-tetrahydroacridin-1-ols. Synthesis and evaluation as potential Alzheimer's disease therapeutics

  摘要：

  The synthesis of a series of 9-amino-1,2,3,4-tetrahydroacridin-1-ols is reported. These compounds are related to 1,2,3,4-tetrahydro-9-acridinamine (THA, tacrine). They inhibit acetylcholinesterase in vitro and are active in a model that may be predictive of activity in Alzheimer's disease--the scopolamine-induced impairment of 24-h memory of a passive dark-avoidance paradigm in mice. Two compounds, (+/-)-9-amino-1,2,3,4-tetrahydroacridin-1-ol maleate (1a, HP-029) and (+/-)-9-(benzylamino)-1,2,3,4-tetrahydroacridin-1-ol maleate (1p, HP-128), were also active in reversing the deficit in 72-h retention of a one-trial dark-avoidance task in rats, induced by ibotenic acid lesions in the nucleus basalis magnocellularis. In addition, compound 1 p showed potent in vitro inhibition of the uptake of radiolabeled noradrenaline and dopamine (IC50 = 0.070 and 0.30 microM, respectively). Compounds 1a and 1p, which showed less acute toxicity in both rats and mice than THA, are in phase II and phase I clinical trials, respectively, for Alzheimer's disease.

  DOI：

  10.1021/jm00128a024
• 作为产物：
  描述：

  2-氨基-5-氯苯腈 、 1,3-环己二酮 在 对甲苯磺酸 作用下， 以 甲苯 为溶剂， 反应 2.0h， 生成 5-Chloro-2-(3-oxocyclohexen-1-yl)amino-benzonitrile
  参考文献：
  名称：

  9-Amino-1,2,3,4-tetrahydroacridin-1-ols. Synthesis and evaluation as potential Alzheimer's disease therapeutics

  摘要：

  The synthesis of a series of 9-amino-1,2,3,4-tetrahydroacridin-1-ols is reported. These compounds are related to 1,2,3,4-tetrahydro-9-acridinamine (THA, tacrine). They inhibit acetylcholinesterase in vitro and are active in a model that may be predictive of activity in Alzheimer's disease--the scopolamine-induced impairment of 24-h memory of a passive dark-avoidance paradigm in mice. Two compounds, (+/-)-9-amino-1,2,3,4-tetrahydroacridin-1-ol maleate (1a, HP-029) and (+/-)-9-(benzylamino)-1,2,3,4-tetrahydroacridin-1-ol maleate (1p, HP-128), were also active in reversing the deficit in 72-h retention of a one-trial dark-avoidance task in rats, induced by ibotenic acid lesions in the nucleus basalis magnocellularis. In addition, compound 1 p showed potent in vitro inhibition of the uptake of radiolabeled noradrenaline and dopamine (IC50 = 0.070 and 0.30 microM, respectively). Compounds 1a and 1p, which showed less acute toxicity in both rats and mice than THA, are in phase II and phase I clinical trials, respectively, for Alzheimer's disease.

  DOI：

  10.1021/jm00128a024

文献信息

• Method of preparing 9-amino-1,2,3,4,-tetrahydroacridin-1-ones and
  申请人：Hoechst-Roussel Pharmaceuticals, Inc.

  公开号：US04835275A1

  公开（公告）日：1989-05-30

  There are disclosed compounds having the formula ##STR1## wherein n is 1, 2 or 3; X is hydrogen, loweralkyl, loweralkoxy, halogen, hydroxy, nitro, trifluoromethyl, NHCOR.sub.2 where R.sub.2 is loweralkyl, or NR.sub.3 R.sub.4 where R.sub.3 and R.sub.4 are independently hydrogen or loweralkyl; R is hydrogen or loweralkyl; R.sub.1 is hydrogen, loweralkyl, diloweralkylaminoloweralkyl, arylloweralkyl, diarylloweralkyl, furylloweralkyl, thienylloweralkyl, oxygen-bridged arylloweralkyl, oxygen-bridged diarylloweralkyl, oxygen-bridged furylloweralkyl or oxygen-bridged thienylloweralkyl; Y is C.dbd.O or CR.sub.5 OH where R.sub.5 is hydrogen or loweralkyl; Z is CH.sub.2 or C.dbd.CR.sub.6 R.sub.7 where R.sub.6 and R.sub.7 are independently hydrogen or loweralkyl; or Y and Z taken together is CR.sub.5 .dbd.CH where CR.sub.5 and CH correspond to Y and Z respectively; an optical antipode thereof, or a pharmaceutically acceptable acid addition salt thereof, which are useful for enhancing memory, methods for synthesizing them, and pharmaceutical compositions comprising an effective memory enhancing amount of such a compound.

  公开了具有以下结构式的化合物##STR1##其中n为1、2或3；X为氢、低烷基、低烷氧基、卤素、羟基、硝基、三氟甲基、NHCOR.sub.2，其中R.sub.2为低烷基，或NR.sub.3R.sub.4，其中R.sub.3和R.sub.4独立地为氢或低烷基；R为氢或低烷基；R.sub.1为氢、低烷基、二低烷氨基低烷基、芳基低烷基、二芳基低烷基、呋喃基低烷基、噻吩基低烷基、氧桥芳基低烷基、氧桥二芳基低烷基、氧桥呋喃基低烷基或氧桥噻吩基低烷基；Y为C.dbd.O或CR.sub.5OH，其中R.sub.5为氢或低烷基；Z为CH.sub.2或C.dbd.CR.sub.6R.sub.7，其中R.sub.6和R.sub.7独立地为氢或低烷基；或Y和Z一起为CR.sub.5.dbd.CH，其中CR.sub.5和CH分别对应于Y和Z；其光学对映体或其药学上可接受的酸加盐，它们对增强记忆有用，方法用于合成它们，以及包含有效的增强记忆量的这种化合物的制药组合物。
• SHUTSKE, GREGORY M.;PIERRAT, FRANK A.
  作者：SHUTSKE, GREGORY M.、PIERRAT, FRANK A.

  DOI：——

  日期：——
• SHUTSKA, GREGORY M.;PIERRAT, FRANK A.
  作者：SHUTSKA, GREGORY M.、PIERRAT, FRANK A.

  DOI：——

  日期：——
• SHUTSKE, GREGORY M.;PIERRAT, FRANK A.;KAPPLES, KEVIN J.;CORNFELDT, MICHAE+, J. MED. CHEM., 32,(1989) N, C. 1805-1813
  作者：SHUTSKE, GREGORY M.、PIERRAT, FRANK A.、KAPPLES, KEVIN J.、CORNFELDT, MICHAE+

  DOI：——

  日期：——
• US4754050A
  申请人：——

  公开号：US4754050A

  公开（公告）日：1988-06-28