(+/-)-trans-9-methoxy-1-methyl-1,2,3,4,4a,5,10,10a-octahydrobenzoquinoline | 138312-49-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: (+/-)-trans-9-methoxy-1-methyl-1,2,3,4,4a,5,10,10a-octahydrobenzoquinoline
• 英文别名: (4aS,10aS)-9-methoxy-1-methyl-3,4,4a,5,10,10a-hexahydro-2H-benzo[g]quinoline
• CAS: 138312-49-9
• 化学式: C₁₅H₂₁NO
• 分子量: 231.338
• InChiKey: XEMRQYDVQBEBPK-JSGCOSHPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  12.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (+/-)-trans-9-methoxy-1-methyl-1,2,3,4,4a,5,10,10a-octahydrobenzoquinoline 在 mercury(II) diacetate 、 碘 作用下， 以 溶剂黄146 为溶剂， 生成 (4aR,10aS)-6-Iodo-9-methoxy-1-methyl-1,2,3,4,4a,5,10,10a-octahydro-benzo[g]quinoline
  参考文献：
  名称：

  Centrally acting .alpha.1-adrenoceptor agonists based on hexahydronaphth[2,3-b]-1,4-oxazines and octahydrobenzo[g]quinolines

  摘要：

  Centrally acting alpha(1)-agonists may be of therapeutic value in dementias and other CNS disorders characterized by symptoms of noradrenergic insufficiency. Therefore, on the basis of known peripherally acting alpha(1)-agonists two new groups of centrally acting alpha(1)-agonists with improved lipophilicity, the hexahydronaphth[2,3-b]-1,4-oxazines type A and the octahydrobenzo[g]quinolines type B were designed. The N-methylated derivatives 14 and 33 demonstrate potent, direct agonistic activity at postjunctional alpha(1)-receptors. Ring substituent alterations in compounds of type A and B change the potency of compounds on the rabbit ear artery by over 3 orders of magnitude (pD2 = 5.35-8.40). The efficacy of these compounds varies from 42 to 110%. These alpha(1)-agonists which were selective in the pithed rat increase vigilance in rats. Compound 14 was found to be a centrally acting alpha(1)-agonist with good tolerability in different animal species and in healthy volunteers. Furthermore, 14 selectively stimulates the breakdown of phosphatidylinositol in rat cerebral cortex slices. In vivo, the compound reverses behavioral deficits in animals which received noradrenergic lesions following DDC or DSP4 treatment. Oxazine 14 and its close derivatives are by far more lipophilic than commonly known alpha(1)-agonists. This is demonstrated in a ClogP-PROBIS plot.

  DOI：

  10.1021/jm00081a008
• 作为产物：
  描述：

  2,4-dihydro-5-methoxy-3-oxo-1H-naphthalene-2-carboxylic acid 在 甲酸 、 sodium hydride 、 三乙胺 、 lithium chloride 作用下， 以 甲醇 、 六甲基磷酰三胺 、 乙醇 、 二氯甲烷 、 氯仿 、 甲苯 为溶剂， 5.0~75.0 ℃ 、275.79 kPa 条件下， 反应 73.5h， 生成 (+/-)-trans-9-methoxy-1-methyl-1,2,3,4,4a,5,10,10a-octahydrobenzoquinoline
  参考文献：
  名称：

  Centrally acting .alpha.1-adrenoceptor agonists based on hexahydronaphth[2,3-b]-1,4-oxazines and octahydrobenzo[g]quinolines

  摘要：

  Centrally acting alpha(1)-agonists may be of therapeutic value in dementias and other CNS disorders characterized by symptoms of noradrenergic insufficiency. Therefore, on the basis of known peripherally acting alpha(1)-agonists two new groups of centrally acting alpha(1)-agonists with improved lipophilicity, the hexahydronaphth[2,3-b]-1,4-oxazines type A and the octahydrobenzo[g]quinolines type B were designed. The N-methylated derivatives 14 and 33 demonstrate potent, direct agonistic activity at postjunctional alpha(1)-receptors. Ring substituent alterations in compounds of type A and B change the potency of compounds on the rabbit ear artery by over 3 orders of magnitude (pD2 = 5.35-8.40). The efficacy of these compounds varies from 42 to 110%. These alpha(1)-agonists which were selective in the pithed rat increase vigilance in rats. Compound 14 was found to be a centrally acting alpha(1)-agonist with good tolerability in different animal species and in healthy volunteers. Furthermore, 14 selectively stimulates the breakdown of phosphatidylinositol in rat cerebral cortex slices. In vivo, the compound reverses behavioral deficits in animals which received noradrenergic lesions following DDC or DSP4 treatment. Oxazine 14 and its close derivatives are by far more lipophilic than commonly known alpha(1)-agonists. This is demonstrated in a ClogP-PROBIS plot.

  DOI：

  10.1021/jm00081a008

文献信息

• A New Practical Route for the Manufacture of (4aR,10aR)-9-Methoxy-1-methyl-6-trimethylsilanyl- 1,2,3,4,4a,5,10,10a-octahydrobenzo[<i>g</i>]quinoline
  作者：Markus Bänziger、Ernst Küsters、Luigi La Vecchia、Wolfgang Marterer、J. Nozulak

  DOI：10.1021/op034112x

  日期：2003.11.1

  Different synthetic routes to the enantiomerically pure octahydrobenzo[g]quinoline derivative JNZ092 were evaluated for their suitability to rapidly prepare a first clinical batch on a kilogram scale. On the basis of the experience of previous octahydrobenzo[g]quinoline projects a new linear synthesis of JNZ092 was established and scaled up successfully. The overall yield was increased by a factor

  评估了对映异构纯八氢苯并[g]喹啉衍生物 JNZ092 的不同合成路线，以评估它们是否适合快速制备第一批公斤级临床批次。在以往八氢苯并[g]喹啉项目经验的基础上，建立了新的JNZ092线性合成方法并成功放大。与药物化学路线相比，总收率提高了 10 倍，制备时间显着缩短。作为关键策略，八氢苯并[g]喹啉骨架的所有原子都是通过 6-锂化 1,7-二甲氧基萘与 2-氰基-3-乙氧基丙烯酸乙酯的反应早期引入的。
• [EN] SILYLATED HETEROCYCLIC COMPOUNDS<br/>[FR] COMPOSES HETEROCYCLIQUES SILYLES
  申请人：NOVARTIS AG

  公开号：WO2001036428A1

  公开（公告）日：2001-05-25

  The invention provides a compound of formula (I), wherein X and R1 to R5 are as defined in the description, and the preparation thereof. The compounds of formula (I) are useful as pharmaceuticals.
• Centrally acting .alpha.1-adrenoceptor agonists based on hexahydronaphth[2,3-b]-1,4-oxazines and octahydrobenzo[g]quinolines
  作者：Joachim Nozulak、Jean M. Vigouret、Anne L. Jaton、Alfred Hofmann、Anant R. Dravid、Hans P. Weber、Hans O. Kalkman、Malcolm D. Walkinshaw

  DOI：10.1021/jm00081a008

  日期：1992.2

  Centrally acting alpha(1)-agonists may be of therapeutic value in dementias and other CNS disorders characterized by symptoms of noradrenergic insufficiency. Therefore, on the basis of known peripherally acting alpha(1)-agonists two new groups of centrally acting alpha(1)-agonists with improved lipophilicity, the hexahydronaphth[2,3-b]-1,4-oxazines type A and the octahydrobenzo[g]quinolines type B were designed. The N-methylated derivatives 14 and 33 demonstrate potent, direct agonistic activity at postjunctional alpha(1)-receptors. Ring substituent alterations in compounds of type A and B change the potency of compounds on the rabbit ear artery by over 3 orders of magnitude (pD2 = 5.35-8.40). The efficacy of these compounds varies from 42 to 110%. These alpha(1)-agonists which were selective in the pithed rat increase vigilance in rats. Compound 14 was found to be a centrally acting alpha(1)-agonist with good tolerability in different animal species and in healthy volunteers. Furthermore, 14 selectively stimulates the breakdown of phosphatidylinositol in rat cerebral cortex slices. In vivo, the compound reverses behavioral deficits in animals which received noradrenergic lesions following DDC or DSP4 treatment. Oxazine 14 and its close derivatives are by far more lipophilic than commonly known alpha(1)-agonists. This is demonstrated in a ClogP-PROBIS plot.