4-甲基-5-氧基呋咱-3-羧酸 | 37132-21-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 4-甲基-5-氧基呋咱-3-羧酸
• 英文名称: 3-methyl-4-furoxancarboxylic acid
• 英文别名: 4-carboxy-3-methylfuroxan；4-methyl-5-oxy-furazan-3-carboxylic acid；4-Methyl-1,2,5-oxadiazole 5-oxide-3-carboxylic Acid；4-methyl-1,2,5-oxadiazole-5-oxido-3-carboxylic acid；5-methyl-4-furoxancarboxylic acid；4-methyl-5-oxido-1,2,5-oxadiazol-5-ium-3-carboxylic acid
• CAS: 37132-21-1
• 化学式: C₄H₄N₂O₄
• mdl: MFCD00463953
• 分子量: 144.087
• InChiKey: PURTYCIHNLXAAE-UHFFFAOYSA-N

物化性质

• 沸点：
  354.8±34.0 °C(Predicted)
• 密度：
  1.77±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  88.8
• 氢给体数：
  1
• 氢受体数：
  5

安全信息

• 危险等级：
  IRRITANT
• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  4-甲基-5-氧基呋咱-3-羧酸 在 氯化亚砜 作用下， 生成 4-甲基-1,2,5-恶二唑-3-甲酰氯5-氧化物
  参考文献：
  名称：

  研究一些呋喃烷衍生物作为潜在的NO供体的合成和心血管活性。

  摘要：

  设计了一系列结合了呋喃喃和尼可地尔部分的杂合分子，作为具有心血管和脑血管活性的潜在NO供体。通过常规方法成功合成了36个目标分子，并通过红外光谱，1H-NMR光谱和高分辨率质谱进行了表征。测试了这些化合物对KCl诱导的内皮剥落的兔胸主动脉收缩的作用。发现有8种化合物在10 microM时可减少KCl诱导的收缩超过30％。这些化合物之一以外的所有化合物的特征在于，在苯环中存在通过酰胺或酯键与呋喃喃部分连接的吸电子基团。末端羰基键（酯或酰胺）的性质以及桥接两个羰基官能团的烷基链的长度或类型对活性几乎没有影响。测试了一种活性化合物N-（4-甲氧基-苯甲酰基）-N'-[3-甲基呋喃基-4-羰基）哌嗪（17i）在1.5 mg / kg时对麻醉大鼠的降压作用，并发现逐渐和持续的降压作用。结果表明，呋喃根-尼可地尔衍生物是设计用于高血压的NO供体化合物的有用线索。

  DOI：

  10.1248/cpb.48.808
• 作为产物：
  描述：

  4-formyl-3-methylfuroxan 在 potassium permanganate 、 硫酸 作用下， 以 丙酮 为溶剂， 以42.1 %的产率得到4-甲基-5-氧基呋咱-3-羧酸
  参考文献：
  名称：

  基于噻吩并 [2,3-d] 嘧啶的嵌合 BRD4 抑制剂/一氧化氮供体的设计、合成和抗卵巢癌活性

  摘要：

  溴结构域蛋白 4 (BRD4) 是一个有吸引力的表观遗传靶点，可调节多种细胞过程，发现包括 BRD4 在内的双靶点抑制剂是癌症治疗中提高效力和降低耐药性的有效方法。基于多功能药物开发策略，设计并合成了一系列新的硝基氧基（ONO 2）或呋喃（1,2,5-恶二唑2-氧化物）衍生物与BRD4抑制剂能够抑制BRD4并同时释放NO。当在生理条件下用 Griess 试剂测量 NO 浓度时，所有化合物都以微摩尔水平释放 NO，达到有效的抗肿瘤浓度。生物学研究表明，最有效的 BRD4/NO 杂种11a表现出良好的 BRD4 抑制活性和选择性。进一步的机制研究表明，11a显着降低 BRD4 和 c-Myc 的表达，并在体外和体内诱导细胞凋亡和自噬细胞死亡。总之，我们在前期研究的基础上优化了嵌合BRD4-抑制剂/NO-供体，它应该是未来卵巢癌靶向治疗的先导化合物。这种有趣的策略可以扩大 BRDi 在人类恶性肿瘤和内源性胃递质中的应用。

  DOI：

  10.1016/j.ejmech.2022.114970

文献信息

• New addition salts of angiotensin-converting enzyme inhibitors with no donor acids, a process for their preparation and pharmaceutical compositions containing them
  申请人：De Nanteuil Guillaume

  公开号：US20090082393A1

  公开（公告）日：2009-03-26

  Compounds of formula (I): (A) m ·(B) n (I) wherein A represents an angiotensin-converting enzyme inhibitor compound containing at least one salt-forming basic function, B represents a compound containing at least one salt-forming acid function and at least one NO donor group, m represents the number of acid functions of B that have been converted to a salt and n represents the number of basic functions of A that have been converted to a salt, the bond or bonds between A and B being of the ionic type. Medicinal products containing the same which are useful in treating cardiovascular pathologies.

  式(I)的化合物：(A)m·(B)n(I)，其中A代表至少含有一个盐形成碱性功能的抑制血管紧张素转化酶的化合物，B代表至少含有一个盐形成酸性功能和至少一个NO供体基团的化合物，m代表已转化为盐的B的酸性功能的数量，n代表已转化为盐的A的碱性功能的数量，A和B之间的键或键为离子型。含有这些化合物的药品对治疗心血管病理有用。
• 2-Phenyl-substituierte Imidazotriazinone als Phoshodiesterase Inhibitoren
  申请人：Bayer Pharma Aktiengesellschaft

  公开号：EP1174431B1

  公开（公告）日：2012-05-30
• Synthesis, characterization, and biological evaluation of furoxan coupled ibuprofen derivatives as anti-inflammatory agents
  作者：Mohd Amir、Mohd Wasim Akhter、Ozair Alam

  DOI：10.1007/s00706-015-1557-x

  日期：2016.3

  A series of furoxan-based nitric oxide releasing ibuprofen derivatives were synthesized and tested for their anti-inflammatory, analgesic, ulcerogenic, lipid peroxidation, and hepatotoxic properties. The compounds exhibited more protection than ibuprofen with regard to gastric toxicity. Among the tested compounds 4-[2-[2-(4-isobutylphenyl)propanamido] ethoxycarbonyl]-3-methylfuroxan and 4-[2-[2-(4-isobutylphenyl)propanoyl]hydrazinecarbonyl]-3-phenylfuroxan emerged as most active anti-inflammatory agents with reduced gastrotoxicity. The results showed that incorporation of NO donating group caused a moderate increase in anti-inflammatory activity with a marked decrease in gastric ulcerations compared to their parent drug ibuprofen. A molecular docking study of all the compounds was also performed to provide the binding modes of COX-1 enzyme. Among all the titledcompounds, 4-[2-[2-(4isobutylphenyl)propanamido]ethoxycarbonyl]-3-methylfuroxan was found to be most potent and have high docking score showing favorable orientation within the COX-1 binding site.
• Calvino; Di Stilo; Fruttero, Il Farmaco, 1993, vol. 48, # 2, p. 321 - 334
  作者：Calvino、Di Stilo、Fruttero、Gasco、Sorba、Gasco

  DOI：——

  日期：——
• New 1,4-Dihydropyridines Conjugated to Furoxanyl Moieties, Endowed with Both Nitric Oxide-like and Calcium Channel Antagonist Vasodilator Activities
  作者：Antonella Di Stilo、Sonja Visentin、Clara Cena、Andrea Marcello Gasco、Giuseppe Ermondi、Alberto Gasco

  DOI：10.1021/jm9803267

  日期：1998.12.1

  A series of 4-phenyl-1,4-dihydropyridines substituted at the ortho and meta positions of the phenyl ring with NO-donating furoxan moieties and their non-NO-releasing furazan analogues were synthesized and pharmacologically characterized. The vasodilator activities of these compounds were evaluated on rat aorta and expressed as EC50 values or as EC50iGC values when obtained in the presence of inhibitors of guanylate cyclase methylene blue (MB) and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-(ODQ). Affinities to 1,4-DHP receptors on Ca2+ channels, expressed as IC50 values, were determined through displacement experiments of [H-3]-nitrendipine on rat cortex homogenates. A linear correlation between IC50 and EC50 values was found for compounds unable to release NO. EC50calcd values for derivatives containing NO-donor moieties, expression of the Ca2+-blocking component of their vasodilator activity, were interpolated on this linear regression. They showed a good correspondence with EC50iGC values determined in the presence of soluble guanylate cyclase inhibitors. Analysis of (EC50EC50)-E-iGC/ ratios provided a useful tool to distinguish well-balanced hybrids from derivatives biased toward Ca2+-blocking or NO-dependent vasodilator activity. A detrimental effect on affinity to the 1,4-DHP receptor, due to substitution at the ortho and meta positions of the 4-phenyl ring, was observed. SAR to explain this effect is proposed.