4,7-dimethyl-[1,2,5]oxadiazolo[3,4-d]pyridazine 1,5,6-trioxide | 116303-47-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 4,7-dimethyl-[1,2,5]oxadiazolo[3,4-d]pyridazine 1,5,6-trioxide
• 英文别名: 4,7-dimethyl-1,2,5-oxadiazolo[3,4-d]pyridazine 1,5,6-trioxide；4,7-dimethyl-1,2,5-oxadiazolo[3,4-d]pyridazine-1,5,6-trioxide；4,7-dimethyl[1,2,5]oxadiazolo[3,4-d]pyridazine 1,5,6-trioxide；Cambridge id 5314731；4,7-dimethyl-1,5-dioxido-[1,2,5]oxadiazolo[3,4-d]pyridazine-5,6-diium 6-oxide
• CAS: 116303-47-0
• 化学式: C₆H₆N₄O₄
• mdl: MFCD00224152
• 分子量: 198.138
• InChiKey: SNUFURQFLHHQQS-UHFFFAOYSA-N

物化性质

• 熔点：
  184-185 °C(Solv: ethanol (64-17-5))
• 沸点：
  468.4±55.0 °C(Predicted)
• 密度：
  1.87±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.333
• 拓扑面积：
  96.7
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4,7-dimethyl-[1,2,5]oxadiazolo[3,4-d]pyridazine 1,5,6-trioxide 在 硝酸 作用下， 以28%的产率得到1-[4-(1,1-dinitro-ethyl)-2-oxy-furazan-3-yl]-ethanone
  参考文献：
  名称：

  Tselinskii; Mel'nikova; Pirogov, Russian Journal of Organic Chemistry, 1996, vol. 32, # 6, p. 925 - 926

  摘要：

  DOI：
• 作为产物：
  描述：

  3,4-diacetylfuroxan dioxime 在 硝酸 、 三氟乙酸 作用下， 反应 0.17h， 以71%的产率得到4,7-dimethyl-[1,2,5]oxadiazolo[3,4-d]pyridazine 1,5,6-trioxide
  参考文献：
  名称：

  [1,2,5] Oxadiazolo [3,4- d ]哒嗪1,5,6-三氧化物：通过3,4-双（羟基亚氨基）甲基）-1,2,5-恶二唑2-的反应有效合成硝酸与浓硝酸和三氟乙酸混合的氧化物及其结构表征

  摘要：

  由3,4-双（羟基亚氨基）甲基）-1,2,5-恶二唑2有效合成[1,2,5]恶二唑并[3,4- d ]哒嗪1,5,6-三氧化物（1）已经开发出使用浓硝酸和三氟乙酸的混合物的氧化物。确定了非常规反应的范围。4,7-二硝基[1,2,5]恶二唑并[3,4- d ]哒嗪1,5,6-三氧化物1f代表了一种新的高能化合物，但其热稳定性很低。通过单晶X射线衍射分析研究了母体[1,2,5]恶二唑[3,4- d ]哒嗪1,5,6-三氧化物1c，揭示了具有异常长的环内N N键的平面分子1.668（5）Å和意外的exo氮氧基氮原子上的-环键角。在晶体中，1c分子通过强大的π-π堆积和C H⋯O氢键相互作用相互结合成三维框架，从而导致1.833 gcm -3的高晶体密度。

  DOI：

  10.1016/j.tetlet.2018.07.015

文献信息

• Vasorelaxant and antiplatelet activity of 4,7-dimethyl-1,2,5-oxadiazolo[3,4-<i>d</i>]pyridazine 1,5,6-trioxide: role of soluble guanylate cyclase, nitric oxide and thiols
  作者：Alexander Ya Kots、Mikhail A Grafov、Yuri V Khropov、Vasily L Betin、Natalya N Belushkina、Olga G Busygina、Marina Yu Yazykova、Igor V Ovchinnikov、Alexander S Kulikov、Nina N Makhova、Natalya A Medvedeva、Tamara V Bulargina、Irina S Severina

  DOI：10.1038/sj.bjp.0703156

  日期：2000.3

  Certain heterocyclic N‐oxides are vasodilators and inhibitors of platelet aggregation. The pharmacological activity of the furoxan derivative condensed with pyridazine di‐N‐oxide 4,7‐dimethyl‐1,2,5‐oxadiazolo[3,4‐d]pyridazine 1,5,6‐trioxide (FPTO) and the corresponding furazan (FPDO) was studied. FPTO reacted with thiols generating nitrite (NO), S‐nitrosoglutathione and hydroxylamine (nitroxyl) and converted oxyHb to metHb. FPDO did not generate detectable amounts of NO‐like species but reacted with thiols and oxyHb. FPTO and FPDO haem‐dependently stimulated the activity of soluble guanylate cyclase (sGC) and this stimulation was inhibited by 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ) and by 0.1 mM dithiothreitol. FPTO relaxed noradrenaline‐precontracted aortic rings and its concentration‐response curve was biphasic (pIC50=9.03±0.13 and 5.85±0.06). FPDO was significantly less potent vasodilator (pIC50=5.19±0.14). The vasorelaxant activity of FPTO and FPDO was inhibited by ODQ. oxyHb significantly inhibited only FPTO‐dependent relaxation. FPTO and FPDO were equipotent inhibitors of ADP‐induced platelet aggregation (IC50=0.63±0.15 and 0.49±0.05 μM, respectively). The antiplatelet activity of FPTO (but not FPDO) was partially suppressed by oxyHb. The antiaggregatory effects of FPTO and FPDO were only partially blocked by sGC inhibitors. FPTO and FPDO (10–20 μM) significantly increased cyclic GMP levels in aortic rings and platelets and this increase was blocked by ODQ. Thus, FPTO can generate NO and, like FPDO, reacts with thiols and haem. The vasorelaxant activity of FPTO and FPDO is sGC‐dependent and a predominant role is played by NO at FPTO concentrations below 1 μM. On the contrary, inhibition of platelet aggregation is only partially related to sGC activation. British Journal of Pharmacology (2000) 129, 1163–1177; doi:10.1038/sj.bjp.0703156

  某些异杂环氮氧化物是血管扩张剂和血小板聚集抑制剂。研究了呋草烷衍生物与吡啶二氮氧化物缩合的4,7-二甲基-1,2,5-氧杂二唑-[3,4-d]吡啶-1,5,6-三氧化物（FPTO）及其相应的呋喃基化合物（FPDO）的药理活性。 FPTO与硫醇反应，产生亚硝酸盐（NO）、S-硝基谷胱甘肽和羟胺（亚硝酸盐），并且将氧合血红蛋白（oxyHb）转化为高铁血红蛋白（metHb）。FPDO未产生可检测的NO样物质，但与硫醇和oxyHb反应。 FPTO和FPDO依赖血红素刺激可溶性鸟苷酸环化酶（sGC）的活性，这种刺激作用被1H-[1,2,4]氧杂二唑-[4,3-a]喹喔啉-1-酮（ODQ）和0.1 mM二硫苏糖醇抑制。 FPTO松弛了肾上腺素引起的主动脉环收缩，其浓度-反应曲线呈双相（pIC₅₀=9.03±0.13 和 5.85±0.06）。FPDO作为血管扩张剂的效力显著较低（pIC₅₀=5.19±0.14）。FPTO和FPDO的血管舒张活性被ODQ抑制。oxyHb显著抑制仅依赖FPTO的松弛作用。 FPTO和FPDO对ADP诱导的血小板聚集具有相同的抑制效力（IC₅₀=0.63±0.15 和 0.49±0.05 μM）。FPTO（而非FPDO）的抗血小板活性被oxyHb部分抑制。FPTO和FPDO的抗聚集作用仅部分被sGC抑制剂阻断。 FPTO和FPDO（10–20 μM）显著增加了主动脉环和血小板中的环GMP水平，这种增加被ODQ阻断。 因此，FPTO可以产生NO，并且与FPDO一样与硫醇和血红素反应。FPTO和FPDO的血管舒张作用依赖于sGC，而NO在FPTO浓度低于1 μM时起主要作用。相反，血小板聚集的抑制仅部分与sGC活化相关。 British Journal of Pharmacology (2000) 129, 1163–1177; doi:10.1038/sj.bjp.0703156
• Synthesis and structural investigation of 4,4′-dimethyl-[3,3′-bi(1,2,5-oxadiazole)] 5,5′-dioxide
  作者：N. V. Obruchnikova、R. A. Novikov、S. G. Zlotin、P. V. Dorovatovskii、V. N. Khrustalev、O. A. Rakitin

  DOI：10.1007/s11172-018-2326-x

  日期：2018.11

  closure was found to occur involving either two central or two terminal oxime groups to form 4,7-dimethyl[1,2,5]oxadiazolo[3,4-d]pyridazine 1,5,6-trioxide and the previously unknown 4,4′-dimethyl-[3,3′-bi(1,2,5-oxadiazole)] 5,5′-dioxide. The structure of the latter compound was established by X-ray diffraction.

  在不同溶剂中研究了四氧化二氮对己烷-2,3,4,5-四酮四肟的氧化反应。发现主要的呋喃环闭合涉及两个中心或两个末端肟基团，以形成 4,7-二甲基[1,2,5]恶二唑并[3,4-d]哒嗪 1,5,6-三氧化物和以前未知的 4,4'-二甲基-[3,3'-bi(1,2,5-恶二唑)] 5,5'-二氧化物。后一种化合物的结构是通过 X 射线衍射确定的。
• FRUTTERO, ROBERTA;FERRAROTTI, BRUNO;GASCO, ALBERTO;CALESTANI, GIANLUCA;RI+, LIEBIGS ANN. CHEM.,(1988) N 11, C. 1017-1023
  作者：FRUTTERO, ROBERTA、FERRAROTTI, BRUNO、GASCO, ALBERTO、CALESTANI, GIANLUCA、RI+

  DOI：——

  日期：——
• Castration-Resistant Prostate Cancer
  申请人：NUtech Ventures

  公开号：US20160310528A1

  公开（公告）日：2016-10-27

  This invention relates to inhibitors of UDP-glucose dehydrogenase, and more particularly to UDP-glucose dehydrogenase inhibitors that are useful in the treatment of prostate cancer. Methods of inhibiting UDP-glucose dehydrogenase and improving the efficacy of additional prostate cancer therapies are also provided.
• [EN] COMPOSITIONS AND METHODS FOR TREATING ENTEROBACTERIACEAE<br/>[FR] COMPOSITIONS ET MÉTHODES DE TRAITEMENT DES ENTEROBACTERIACEAE
  申请人：UNIV INDIANA RES & TECH CORP

  公开号：WO2013006854A2

  公开（公告）日：2013-01-10

  Methods and compounds for treating bacterial infections are provided. Embodiments of the methods and compounds activate CpxRA to treat bacterial infection.