(4aR,10aR)-4-ethyl-9-iodo-6-methoxy-2-methyl-2,3,4a,5,10,10a-hexahydrobenzo[g][1,4]benzoxazine | 103009-31-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (4aR,10aR)-4-ethyl-9-iodo-6-methoxy-2-methyl-2,3,4a,5,10,10a-hexahydrobenzo[g][1,4]benzoxazine
• CAS: 103009-31-0
• 化学式: C₁₆H₂₂INO₂
• 分子量: 387.261
• InChiKey: XFMKROARVIIEBN-ITCOCZBTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.88
• 重原子数：
  20.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  21.7
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  lithium methanethiolate 、 (4aR,10aR)-4-ethyl-9-iodo-6-methoxy-2-methyl-2,3,4a,5,10,10a-hexahydrobenzo[g][1,4]benzoxazine 在 copper(I) oxide 作用下， 以 二甲基亚砜 为溶剂， 反应 5.0h， 生成 4-ethyl-6-methoxy-2-methyl-9-(methylthio)-3,4,4a,5,10,10a-hexahydro-2H-naphtho[2,3-b][1,4]oxazine
  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：

  3,4,4a,5,10,10a-hexahydro-6-methoxy-2-methyl-2H-naphth<2,3-b>-1,4-oxazine 在 lithium aluminium tetrahydride 、 mercury(II) diacetate 、 碘 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 溶剂黄146 为溶剂， 反应 16.5h， 生成 (4aR,10aR)-4-ethyl-9-iodo-6-methoxy-2-methyl-2,3,4a,5,10,10a-hexahydrobenzo[g][1,4]benzoxazine
  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