(+)-(4aS,10aS)-3,4,4a,5,10,10a-hexahydro-6-methoxy-4-methyl-9-(methylthio)-2H-naphth<2,3-b>-1,4-oxazine hydrochloride | 103009-41-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: (+)-(4aS,10aS)-3,4,4a,5,10,10a-hexahydro-6-methoxy-4-methyl-9-(methylthio)-2H-naphth<2,3-b>-1,4-oxazine hydrochloride
• 英文别名: (4aS,10aS)-6-methoxy-4-methyl-9-methylsulfanyl-2,3,4a,5,10,10a-hexahydrobenzo[g][1,4]benzoxazine;hydrochloride
• CAS: 103009-41-2
• 化学式: C₁₅H₂₁NO₂S*ClH
• 分子量: 315.864
• InChiKey: CWXFACKMNNJZSY-KYSPHBLOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.64
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  47
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (+/-)-trans-2-chloro-N-(1,2,3,4-tetrahydro-2-hydroxy-5-methoxy-3-naphthyl)acetamide 在 palladium on activated charcoal copper(I) oxide 、 lithium aluminium tetrahydride 、 mercury(II) diacetate 、 氢气 、 碘 、 四丁基碘化铵 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 、 溶剂黄146 、 二甲基亚砜 为溶剂， 20.0~80.0 ℃ 、89.63 kPa 条件下， 反应 31.25h， 生成 (+)-(4aS,10aS)-3,4,4a,5,10,10a-hexahydro-6-methoxy-4-methyl-9-(methylthio)-2H-naphth<2,3-b>-1,4-oxazine hydrochloride
  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

• US4656167A
  申请人：——

  公开号：US4656167A

  公开（公告）日：1987-04-07
• 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.