4-(bromomethyl)-1,2,5-oxadiazole-3-carboxamide | 676539-82-5

• 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
• 英文名称: 4-(bromomethyl)-1,2,5-oxadiazole-3-carboxamide
• 英文别名: 4-bromomethylfurazan-3-carboxamide
• CAS: 676539-82-5
• 化学式: C₄H₄BrN₃O₂
• 分子量: 205.999
• InChiKey: NUJUBTUUAJJCDC-UHFFFAOYSA-N

物化性质

• 熔点：
  82.8-83.3 °C(Solv: chloroform (67-66-3); ligroine (8032-32-4))
• 沸点：
  355.8±52.0 °C(Predicted)
• 密度：
  1.927±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  10
• 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：
  82
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-methyl-4-amino-1-hydroxybutylidene-1,1-bisphosphonic acid 、 4-(bromomethyl)-1,2,5-oxadiazole-3-carboxamide 在 sodium hydroxide 、 盐酸 作用下， 以 水 、 乙腈 为溶剂， 以34%的产率得到4-(N-methyl-N-[(4-carbamoylfurazan-3-yl)methyl]amino)-1-hydroxybutylidene bis(phosphonic acid)
  参考文献：
  名称：

  Synthesis and preliminary pharmacological characterisation of a new class of nitrogen-containing bisphosphonates (N-BPs)

  摘要：

  A new series of bisphosphonates bearing either the nitrogen-containing NO-donor furoxan (1,2,5-oxadiazole 2-oxide) system or the related furazan (1,2,5-oxadiazole) in lateral chain has been developed. pK(a) values and affinity for hydroxyapatite were determined for all the compounds. The products were able to inhibit osteoclastogenesis on RAW 246.7 cells at 10 mu M concentration. The most active compounds were further assayed on human PBMC cells and on rat microsomes. Unlike most nitrogen-containing bisphosphonates which target farnesyl pyrophosphate synthase, experimental and theoretical investigations suggest that the activity of our derivatives may be related to different mechanisms. The furoxan derivatives were also tested for their ability to relax rat aorta strips in view of their potential NO-dependent vasodilator properties. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.02.058

文献信息

• New praziquantel derivatives containing NO-donor furoxans and related furazans as active agents against Schistosoma mansoni
  作者：Stefano Guglielmo、Daniela Cortese、Francesca Vottero、Barbara Rolando、Valerie P. Kommer、David L. Williams、Roberta Fruttero、Alberto Gasco

  DOI：10.1016/j.ejmech.2014.07.007

  日期：2014.9

  praziquantel hybrid compounds was obtained by combining praziquantel (PZQ) and furoxan moieties in a single entity. NO-donor properties of the furoxan derivatives were evaluated by detecting nitrite after incubation of the products in 7.4 pH buffered solution in the presence of l-cysteine. Structurally-related furazans, devoid of NO release capacity, were also synthesized for control purposes. All

  通过将吡喹酮 (PZQ) 和呋喃酮部分组合在一个实体中，获得了一系列 NO 供体吡喹酮杂化化合物。通过在存在L-半胱氨酸的情况下将产物在 7.4 pH 缓冲溶液中温育后检测亚硝酸盐来评估呋喃酮衍生物的 NO 供体性质。为了控制目的，还合成了结构相关的呋喃嗪，缺乏 NO 释放能力。研究了所有产品抑制重组曼氏血吸虫硫氧还蛋白谷胱甘肽还原酶（TGR）的能力。与 PZQ 相比，评估了在产品存在下培养的成年曼氏血吸虫蠕虫的活动性和死亡。结果分析表明，一些产品同时具有PZQ和NO依赖性抗寄生虫特性。化合物6、7、18和24成为最有趣的平衡杂种，值得对 PZQ 抗性寄生虫进行进一步研究。
• 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.
• Furazan and furoxan sulfonamides are strong α-carbonic anhydrase inhibitors and potential antiglaucoma agents
  作者：Konstantin Chegaev、Loretta Lazzarato、Yasinalli Tamboli、Donatella Boschi、Marco Blangetti、Andrea Scozzafava、Fabrizio Carta、Emanuela Masini、Roberta Fruttero、Claudiu T. Supuran、Alberto Gasco

  DOI：10.1016/j.bmc.2014.06.016

  日期：2014.8

  A series of furazan and furoxan sulfonamides were prepared and studied for their ability to inhibit human carbonic anhydrase (CA, EC 4.2.1.1) isoforms hCA I, hCA II, hCA IX, and hCA XII. The simple methyl substituted products 3-5 were potent inhibitors. Differing structural modifications of these leads had differing effects on potency and selectivity. In particular, products in which the sulfonamide group is separated from the hetero ring by a phenylene bridge retained high potency only on the hCA XII isoform. The sulfonamides 3-5 exerted intraocular pressure (IOP) lowering effects in vivo in hypertensive rabbits more efficiently than dorzolamide. Some other products (39-42), although less effective in vitro hCA II/XII inhibitors, also effectively lowered IOP in two different animal models of glaucoma. (C) 2014 Elsevier Ltd. All rights reserved.