3-methoxy-1a,2,7,7a-tetrahydronaphtho[2,3-b]oxirene | 103009-62-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: 3-methoxy-1a,2,7,7a-tetrahydronaphtho[2,3-b]oxirene
• 英文别名: 1a,2,7,7a-tetrahydro-3-methoxy-naphth[2,3-b]oxirane
• CAS: 103009-62-7
• 化学式: C₁₁H₁₂O₂
• 分子量: 176.215
• InChiKey: RZXVQSZMNQFCMM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  13
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  21.8
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-methoxy-1a,2,7,7a-tetrahydronaphtho[2,3-b]oxirene 在 lithium aluminium tetrahydride 、 sodium azide 、 硫酸 、 palladium 10% on activated carbon 、 氢气 、 L-Selectride 、 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二甲基亚砜 、 二乙胺 、 mineral oil 为溶剂， 20.0~100.0 ℃ 、250.0 kPa 条件下， 反应 107.0h， 生成 (4aR,10aR)-9-hydroxy-2,3,4a,5,10,10a-hexahydro-naphtho[2,3-b][1,4]oxazine-4-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Synthesis and SAR study of a novel series of dopamine receptor agonists

  摘要：

  The synthesis of a novel series of dopamine receptor agonists are described as well as their in vitro potency and efficacy on dopamine D-1 and D-2 receptors. This series was designed from pergolide and (4aR,10aR)-1-propyl-1,2,3,4,4a,5,10,10a-octahydro-benzo[g] quinolin-6-ol (PHBQ) and resulted in the synthesis of (2R,4aR,10aR)-2-methylsulfanylmethyl-4-propyl-3,4,4a,5,10,10a-hexahydro-2H-naphtho[2,3-b][1,4]oxazin-9-ol (compound 27), which has a D-1 and D-2 receptor profile similar to that of the most recently approved drug for Parkinson's disease, rotigotine. (C)2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.11.012
• 作为产物：
  描述：

  5,8-二氢-1-萘酚 在 potassium carbonate 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 7.5h， 生成 3-methoxy-1a,2,7,7a-tetrahydronaphtho[2,3-b]oxirene
  参考文献：
  名称：

  Synthesis and SAR study of a novel series of dopamine receptor agonists

  摘要：

  The synthesis of a novel series of dopamine receptor agonists are described as well as their in vitro potency and efficacy on dopamine D-1 and D-2 receptors. This series was designed from pergolide and (4aR,10aR)-1-propyl-1,2,3,4,4a,5,10,10a-octahydro-benzo[g] quinolin-6-ol (PHBQ) and resulted in the synthesis of (2R,4aR,10aR)-2-methylsulfanylmethyl-4-propyl-3,4,4a,5,10,10a-hexahydro-2H-naphtho[2,3-b][1,4]oxazin-9-ol (compound 27), which has a D-1 and D-2 receptor profile similar to that of the most recently approved drug for Parkinson's disease, rotigotine. (C)2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.11.012

文献信息

• Naphthoxazines and their use as psychostimulating and antidepressant
  申请人：Sandoz Ltd.

  公开号：US04656167A1

  公开（公告）日：1987-04-07

  3,4,4a,5,10,10a-hexahydro-2H-naphth[2,3-b]-1,4-oxazines are useful as psychostimulating and antidepressant agents.

  3,4,4a,5,10,10a-六氢-2H-萘[2,3-b]-1,4-噁嗪类化合物可用作心理刺激和抗抑郁药物。
• 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.
• US4656167A
  申请人：——

  公开号：US4656167A

  公开（公告）日：1987-04-07
• US5610174A
  申请人：——

  公开号：US5610174A

  公开（公告）日：1997-03-11
• Synthesis and SAR study of a novel series of dopamine receptor agonists
  作者：Rune Risgaard、Martin Jensen、Morten Jørgensen、Benny Bang-Andersen、Claus T. Christoffersen、Klaus G. Jensen、Jesper L. Kristensen、Ask Püschl

  DOI：10.1016/j.bmc.2013.11.012

  日期：2014.1

  The synthesis of a novel series of dopamine receptor agonists are described as well as their in vitro potency and efficacy on dopamine D-1 and D-2 receptors. This series was designed from pergolide and (4aR,10aR)-1-propyl-1,2,3,4,4a,5,10,10a-octahydro-benzo[g] quinolin-6-ol (PHBQ) and resulted in the synthesis of (2R,4aR,10aR)-2-methylsulfanylmethyl-4-propyl-3,4,4a,5,10,10a-hexahydro-2H-naphtho[2,3-b][1,4]oxazin-9-ol (compound 27), which has a D-1 and D-2 receptor profile similar to that of the most recently approved drug for Parkinson's disease, rotigotine. (C)2013 Elsevier Ltd. All rights reserved.