1,2,5-噁二唑-3-羧酰胺 4-(羟基甲基)- 2-氧化物 (9ci) | 158590-73-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 中文名称: 1,2,5-噁二唑-3-羧酰胺 4-(羟基甲基)- 2-氧化物 (9ci)
• 中文别名: 1,2,5-噁二唑-3-羧酰胺4-(羟基甲基)-2-氧化物(9ci)；1,2,5-恶二唑-3-甲酰胺,4-(羟甲基)-2,2-氧化物
• 英文名称: CAS 1609
• 英文别名: 4-hydroxymethylfuroxan-3-carboxamide；imexon；1,2,5-Oxadiazole-3-carboxamide, 4-(hydroxymethyl)-, 2-oxide (9CI)；4-(hydroxymethyl)-2-oxido-1,2,5-oxadiazol-2-ium-3-carboxamide
• CAS: 158590-73-9
• 化学式: C₄H₅N₃O₄
• 分子量: 159.101
• InChiKey: IPHRXVUYWVWSTP-UHFFFAOYSA-N

物化性质

• 沸点：
  463.7±55.0 °C(Predicted)
• 密度：
  2.01±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1,2,5-噁二唑-3-羧酰胺 4-(羟基甲基)- 2-氧化物 (9ci) 在 二溴亚砜 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 1,2,5-恶二唑-3-甲酰胺,4-(溴甲基)--2,2-氧化物
  参考文献：
  名称：

  具有体内杀菌抗结核活性的含氮氧化物杂环的设计，合成和表征

  摘要：

  由结核分枝杆菌（Mtb）引起的结核病是导致全世界死亡人数最多的传染病。本文中，合成了22种新的含N-氧化物的化合物，然后在体外和体内评估了它们对Mtb的抗结核潜力。发现化合物8是最有前途的化合物，相对于活性Mtb和非复制Mtb的MIC 90值分别为1.10和6.62μM 。此外，我们进行了体内实验以确认化合物8的安全性和有效性; 该化合物被发现具有口服生物利用度并且非常有效，从而导致Mtb降低至小鼠感染模型中无法检测到的水平。基于微阵列的作用机理初步研究表明化合物8阻止翻译。总而言之，这些结果表明苯并呋喃聚糖衍生物8是用于开发新型化学类抗结核药物的有前途的先导化合物。

  DOI：

  10.1021/acs.jmedchem.7b01332

文献信息

• Design, synthesis and biological evaluation of N-oxide derivatives with potent in vivo antileishmanial activity
  作者：Leandro da Costa Clementino、Guilherme Felipe Santos Fernandes、Igor Muccilo Prokopczyk、Wilquer Castro Laurindo、Danyelle Toyama、Bruno Pereira Motta、Amanda Martins Baviera、Flávio Henrique-Silva、Jean Leandro dos Santos、Marcia A. S. Graminha

  DOI：10.1371/journal.pone.0259008

  日期：——

  Leishmaniasis is a neglected disease that affects 12 million people living mainly in developing countries. Herein, 24 new N-oxide-containing compounds were synthesized followed by in vitro and in vivo evaluation of their antileishmanial activity. Compound 4f, a furoxan derivative, was particularly remarkable in this regard, with EC₅₀ value of 3.6 μM against L. infantum amastigote forms and CC₅₀ value superior to 500 μM against murine peritoneal macrophages. In vitro studies suggested that 4f may act by a dual effect, by releasing nitric oxide after biotransformation and by inhibiting cysteine protease CPB (IC₅₀: 4.5 μM). In vivo studies using an acute model of infection showed that compound 4f at 7.7 mg/Kg reduced ~90% of parasite burden in the liver and spleen of L. infantum-infected BALB/c mice. Altogether, these outcomes highlight furoxan 4f as a promising compound for further evaluation as an antileishmanial agent.

  利什曼病是一种影响主要发展中国家居民的1200万人的被忽视的疾病。在这项研究中，合成了24种新的含氧化物的化合物，随后评估了它们的抗利什曼病活性。其中，一种呋喃氧化物衍生物4f在这方面表现尤为出色，对婴儿利什曼体形式的EC50值为3.6μM，对小鼠腹膜巨噬细胞的CC50值超过500μM。体外研究表明，4f可能通过双重作用发挥作用，经生物转化后释放一氧化氮，并抑制半胱氨酸蛋白酶CPB（IC50：4.5μM）。使用急性感染模型的体内研究表明，7.7毫克/千克的4f化合物可使感染婴儿利什曼体的BALB/c小鼠肝脏和脾脏中的寄生虫负担减少约90%。总的来说，这些结果突出了呋喃氧化物4f作为一种有前途的化合物，值得进一步评估其作为抗利什曼病药物的潜力。
• Novel antioxidant agents deriving from molecular combination of Vitamin C and NO-donor moieties
  作者：Clara Cena、Konstantin Chegaev、Silvia Balbo、Loretta Lazzarato、Barbara Rolando、Marta Giorgis、Elisabetta Marini、Roberta Fruttero、Alberto Gasco

  DOI：10.1016/j.bmc.2008.03.014

  日期：2008.5

  In this paper, we describe a new class of products in which NO-donor moieties are linked to either the 3-OH (4a-f) or 2-OH group (7a-c) of ascorbic acid (ASA). Log Ps and pK(a)s of these products were experimentally evaluated. All the compounds were tested for their antioxidant activity on lipidic peroxidation induced by Fe(3+)-ADP/NADPH in lipids of microsomal membranes of rat hepatocytes. Only 3-O

  在本文中，我们描述了一类新的产品，其中NO供体部分与抗坏血酸（ASA）的3-OH（4a-f）或2-OH基团（7a-c）连接。实验评估了这些产物的Log Ps和pK（a）。测试了所有化合物对大鼠肝细胞微粒体膜脂质中Fe（3 +）-ADP / NADPH诱导的脂质过氧化的抗氧化活性。仅3-O系列显示抗氧化剂活性，并且似乎主要取决于亲脂性。这两个系列均触发了体外NO依赖的血管扩张药特性。
• Nitric Oxide Donor β₂-Agonists:  Furoxan Derivatives Containing the Fenoterol Moiety and Related Furazans
  作者：M. Federica Buonsanti、Massimo Bertinaria、Antonella Di Stilo、Clara Cena、Roberta Fruttero、Alberto Gasco

  DOI：10.1021/jm0704595

  日期：2007.10.1

  has been joined with furoxan NO-donor moieties to give new NO-donor beta2-agonists. The furazan analogues, devoid of the property to release NO, were also synthesized for comparison. All the compounds retained beta2-agonistic activity at micromolar or submicromolar concentration when tested on guinea pig tracheal rings precontracted with carbachol. Among the furoxan derivatives, the NO contribution

  非诺特罗（一种用于治疗的β2肾上腺素受体激动剂）的结构已与呋喃喃的NO供体基团结合在一起，得到了新的NO供体β2受体激动剂。还合成了不具有释放NO的性质的呋喃赞类似物以进行比较。当在与卡巴胆碱预收缩的豚鼠气管环上进行测试时，所有化合物在微摩尔或亚微摩尔浓度下均保持β2激动活性。在呋喃喃衍生物中，在微摩尔浓度的产物15b中，NO对气管舒张的作用是明显的。所有这些新的NO供体杂种都能够扩张与去氧肾上腺素预收缩的大鼠主动脉条。呋喃喃和呋喃山衍生物均显示出比非诺特罗更大的抗氧化活性。
• ——
  作者：Clara Cena、Sonja Visentin、Antonella Di Stilo、Donatella Boschi、Roberta Fruttero、Alberto Gasco

  DOI：10.1023/a:1011072116210

  日期：——

  NO-donor properties, a series of "hybrid" 1,4-dihydropyridines (1,4-DHPs), bearing NO-donating furoxan moieties on the 3-positioned lateral ester chain were synthesized and pharmacologically characterized. Furazan analogues were also prepared and investigated for control purposes, because they are unable to release NO. METHODS Synthesis of the models was achieved by a modified Hantzsch approach. All of the

  用途为了获得具有混合的Ca2 +通道拮抗和NO供体特性的新型心血管药物，一系列“混合”的1,4-二氢吡啶（1,4-DHP）在3位侧酯上带有NO供体的呋喃烷部分合成链并进行药理学表征。还制备并研究了呋喃山类似物用于控制目的，因为它们无法释放NO。方法通过改进的Hantzsch方法实现了模型的综合。通过Griess反应，在存在大量过量的半胱氨酸的情况下，评估了所有最终的呋喃喃1,4-DHPs产生亚硝酸盐的能力。评估大鼠主动脉上的血管舒张活性，并表示为EC50和EC50MB值，分别在不存在和存在亚甲基蓝（MB）的情况下获得，众所周知的鸟苷酸环化酶抑制剂。通过[3H]-硝苯地平对大鼠皮质匀浆的置换实验，确定了对Ca2 +通道上1,4-DHP受体的亲和力，以IC50值表示。结果某些杂化化合物（衍生物15a，15b，16a和16b）显示出血管舒张活性，主要取决于它们的Ca2 +通道阻滞剂特性。相比之下
• Novel R-roscovitine NO-donor hybrid compounds as potential pro-resolution of inflammation agents
  作者：Gabriele Montanaro、Massimo Bertinaria、Barbara Rolando、Roberta Fruttero、Christopher D. Lucas、David A. Dorward、Adriano G. Rossi、Ian L. Megson、Alberto Gasco

  DOI：10.1016/j.bmc.2013.01.009

  日期：2013.4

  Neutrophils play a pivotal role in the pathophysiology of multiple human inflammatory diseases. Novel pharmacological strategies which drive neutrophils to undergo programmed cell death (apoptosis) have been shown to facilitate the resolution of inflammation. Both the cyclin-dependent kinase inhibitor (CDKi) R-roscovitine and nitric oxide (NO) have been shown to enhance apoptosis of neutrophils and possess pro-resolution of inflammation properties. In order to search for new multi-target pro-resolution derivatives, here we describe the design, synthesis and investigation of the biological potential of a small series of hybrid compounds obtained by conjugating R-roscovitine with two different NO-donor moieties (compounds 2, 9a, 9c). The synthesized compounds were tested as potential pro-resolution agents, with their ability to promote human neutrophil apoptosis evaluated. Both compound 9a and 9c showed an increased pro-apoptotic activity when compared with either R-roscovitine or structurally related compounds devoid of the ability to release NO (des-NO analogues). Inhibition of either NO-synthase or soluble guanylate cyclase did not affect the induction of apoptosis by the R-roscovitine derivatives, similar to that reported for other classes of NO-donors. In contrast the NO scavenger PTIO prevented the enhanced apoptosis seen with compound 9a over R-roscovitine. These data show that novel compounds such as CDKi-NO-donor hybrids may have additive pro-resolution of inflammation effects. (C) 2013 Elsevier Ltd. All rights reserved.