8-(4-methoxyphenyl)-4H-[1,2,4]oxadiazolo[3,4-c][1,4]benzoxazin-1-one | 1219717-30-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 8-(4-methoxyphenyl)-4H-[1,2,4]oxadiazolo[3,4-c][1,4]benzoxazin-1-one
• CAS: 1219717-30-2
• 化学式: C₁₆H₁₂N₂O₄
• 分子量: 296.282
• InChiKey: VWONZIROMQVTID-UHFFFAOYSA-N

物化性质

• 熔点：
  209 °C
• 沸点：
  458.4±55.0 °C(Predicted)
• 密度：
  1.42±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  60.4
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  8-(4-methoxyphenyl)-4H-[1,2,4]oxadiazolo[3,4-c][1,4]benzoxazin-1-one 在 tetraphosphorus decasulfide 、 铜 作用下， 以 5,5-dimethyl-1,3-cyclohexadiene 、 甲苯 为溶剂， 反应 61.0h， 生成 8-(4-methoxyphenyl)-4H-[1,2,4]thiadiazolo[3,4-c][1,4]benzoxazine-1-thione
  参考文献：
  名称：

  Synthesis of sulfur containing analogues of the soluble guanylate cyclase inhibitor 8-bromo-4H-[1,2,4]oxadiazolo[3,4-c][1,4]benzoxazin-1-one NS2028

  摘要：

  Sulfur analogues of the soluble guanylate cyclase (sGC) inhibitor NS2028 la are synthesized. Treating 8-bromo-2H-benzo[b][1,4]oxazin-3(4H)-one oxime (6) with 1,1'-thiocarbonyldiimidazole (1.1 equiv) gave the carbamothioate 8-bromo-4H-[1,2,4]oxadiazolo[3,4-c][1,4]benzoxazine-1-thione (3a) in 83% yield. Alternatively reacting NS2028 1a with P2S5 (0.5 equiv) affords the carbamothioate 3a in 80% yield. Similar treatment of 8-aryl substituted NS2028 analogues 1b-d with P2S5 gave the carbamothioates 3b-d in 64-91% yields. Although quite stable, the carbamothioates 3a-d could be thermally isomerized in the presence of Cu (10 mol X) to afford the thiocarbamates 4a-d in high yields. Interestingly, in the case of carbamothioate 3a Pd and In metals also facilitated the isomerization. Furthermore, treatment of the thiocarbamates 4a-d with P2S5 (0.5 equiv) affords the carbamodithioates 5a-d in 72-89% yields. All new compounds are fully characterized including single crystal X-ray data for carbamothioate 3a and thiocarbamate 4a. Finally, a mechanism is proposed for the carbamothioate to thiocarbamate isomerization. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2011.05.071
• 作为产物：
  描述：

  6-(4-methoxyphenyl)-2H-1,4-benzoxazin-3(4H)-one oxime 、 N,N'-羰基二咪唑 以 四氢呋喃 为溶剂， 反应 24.0h， 以57%的产率得到8-(4-methoxyphenyl)-4H-[1,2,4]oxadiazolo[3,4-c][1,4]benzoxazin-1-one
  参考文献：
  名称：

  Synthesis and biological evaluation of oxadiazole derivatives as inhibitors of soluble guanylyl cyclase

  摘要：

  Soluble guanylyl cyclase (sGC) is an ubiquitously expressed enzyme that generates the second messenger cGMP and hence, leads to a number of physiological responses including vasodilation, inhibition of platelet aggregation and neurotransmission. Whilst many activating and stimulating modulators of sGC were identified and studied in recent years, only two selective inhibitors are known: ODQ and NS 2028. Furthermore, a synthetic approach to these inhibitors has not been reported yet. Herein, we describe a novel and efficient synthesis of these inhibitors, as well as the preparation of three different classes of NS 2028 analogues. Biological evaluation of this library using rat aortic smooth muscle cells revealed four new compounds with good to moderate sGC inhibitory activity. Our experiments underline the major importance of the oxadiazole ring in ODQ and NS 2028 for the efficiency of this class of inhibitors. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.12.027

文献信息

• Suzuki–Miyaura reactions of the soluble guanylate cyclase inhibitor NS2028: a non-product specific route to C-8 substituted analogues
  作者：Andrey A. Berezin、Panayiotis A. Koutentis

  DOI：10.1016/j.tet.2011.04.003

  日期：2011.6

  Both soluble guanylate cyclase (sGC) inhibitors ODQ 1 and NS2028 2 are synthesized via improved protocols. In the former case treating 3,4-dihydroquinoxalin-2(1H)-one oxime 8, which can be prepared in two steps from 1,2-benzenediamine, with 1,1'-carbonyldiimidazole (CDI) gives the dihydro-ODQ 10 that in the presence of KMnO4 oxidises to give ODQ 1 in an overall yield of 46% starting from 1,2-benzenediamine. In the latter case, the synthesis affords NS2028 2 from 2-amino-4-bromophenol 3 in three steps with an overall yield of 85% and avoids the need for chromatography. Furthermore, Suzuki-Miyaura reaction conditions are described that enable the preparation of 8-aryl and 8-heteroaryl derivatives of NS2028 directly from NS2028 2. Finally, demethylation of the 8-(methoxyphenyl) substituted analogues afforded the 8-(hydroxyphenyl) derivatives 40-42. All new products are fully characterised. (C) 2011 Elsevier Ltd. All rights reserved.
• Synthesis and biological evaluation of oxadiazole derivatives as inhibitors of soluble guanylyl cyclase
  作者：Margarete von Wantoch Rekowski、Anastasia Pyriochou、Nektarios Papapetropoulos、Anne Stößel、Andreas Papapetropoulos、Athanassios Giannis

  DOI：10.1016/j.bmc.2009.12.027

  日期：2010.2

  Soluble guanylyl cyclase (sGC) is an ubiquitously expressed enzyme that generates the second messenger cGMP and hence, leads to a number of physiological responses including vasodilation, inhibition of platelet aggregation and neurotransmission. Whilst many activating and stimulating modulators of sGC were identified and studied in recent years, only two selective inhibitors are known: ODQ and NS 2028. Furthermore, a synthetic approach to these inhibitors has not been reported yet. Herein, we describe a novel and efficient synthesis of these inhibitors, as well as the preparation of three different classes of NS 2028 analogues. Biological evaluation of this library using rat aortic smooth muscle cells revealed four new compounds with good to moderate sGC inhibitory activity. Our experiments underline the major importance of the oxadiazole ring in ODQ and NS 2028 for the efficiency of this class of inhibitors. (C) 2009 Elsevier Ltd. All rights reserved.
• Synthesis of sulfur containing analogues of the soluble guanylate cyclase inhibitor 8-bromo-4H-[1,2,4]oxadiazolo[3,4-c][1,4]benzoxazin-1-one NS2028
  作者：Andrey A. Berezin、Panayiotis A. Koutentis、Manolis J. Manos

  DOI：10.1016/j.tet.2011.05.071

  日期：2011.7

  Sulfur analogues of the soluble guanylate cyclase (sGC) inhibitor NS2028 la are synthesized. Treating 8-bromo-2H-benzo[b][1,4]oxazin-3(4H)-one oxime (6) with 1,1'-thiocarbonyldiimidazole (1.1 equiv) gave the carbamothioate 8-bromo-4H-[1,2,4]oxadiazolo[3,4-c][1,4]benzoxazine-1-thione (3a) in 83% yield. Alternatively reacting NS2028 1a with P2S5 (0.5 equiv) affords the carbamothioate 3a in 80% yield. Similar treatment of 8-aryl substituted NS2028 analogues 1b-d with P2S5 gave the carbamothioates 3b-d in 64-91% yields. Although quite stable, the carbamothioates 3a-d could be thermally isomerized in the presence of Cu (10 mol X) to afford the thiocarbamates 4a-d in high yields. Interestingly, in the case of carbamothioate 3a Pd and In metals also facilitated the isomerization. Furthermore, treatment of the thiocarbamates 4a-d with P2S5 (0.5 equiv) affords the carbamodithioates 5a-d in 72-89% yields. All new compounds are fully characterized including single crystal X-ray data for carbamothioate 3a and thiocarbamate 4a. Finally, a mechanism is proposed for the carbamothioate to thiocarbamate isomerization. (C) 2011 Elsevier Ltd. All rights reserved.