2-<(3-carbamoylfuroxan-4-yl)methoxy>benzaldehyde | 220271-09-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2-<(3-carbamoylfuroxan-4-yl)methoxy>benzaldehyde
• 英文别名: 4-[(2-Formylphenoxy)methyl]-2-oxido-1,2,5-oxadiazol-2-ium-3-carboxamide
• CAS: 220271-09-0
• 化学式: C₁₁H₉N₃O₅
• 分子量: 263.21
• InChiKey: APHLGNXLQSOHAP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  121
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-<(3-carbamoylfuroxan-4-yl)methoxy>benzaldehyde 在 三氟乙酸 、 三氟乙酸酐 作用下， 以 吡啶 、 乙醇 为溶剂， 反应 5.5h， 生成 4-[2-(4-Cyano-5-oxy-furazan-3-ylmethoxy)-phenyl]-2,6-dimethyl-1,4-dihydro-pyridine-3,5-dicarboxylic acid dimethyl ester
  参考文献：
  名称：

  New 1,4-Dihydropyridines Conjugated to Furoxanyl Moieties, Endowed with Both Nitric Oxide-like and Calcium Channel Antagonist Vasodilator Activities

  摘要：

  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.

  DOI：

  10.1021/jm9803267
• 作为产物：
  描述：

  水杨醛 、 1,2,5-恶二唑-3-甲酰胺,4-(溴甲基)--2,2-氧化物 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 2-<(3-carbamoylfuroxan-4-yl)methoxy>benzaldehyde
  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

• New 1,4-Dihydropyridines Endowed with NO-Donor and Calcium Channel Agonist Properties
  作者：Sonja Visentin、Barbara Rolando、Antonella Di Stilo、Roberta Fruttero、Monica Novara、Emilio Carbone、Christian Roussel、Nicolas Vanthuyne、Alberto Gasco

  DOI：10.1021/jm031109v

  日期：2004.5.1

  A new series of calcium channel agonists structurally related to Bay K8644, containing NO donor furoxans and the related furazans unable to release NO, is described. The racemic mixtures were studied for their action on L-type Ca2+ channels expressed in cultured rat insulinoma RINm5F cells. All the products proved to be potent calcium channel agonists. All the racemic mixtures, with the only exception of the carbamoyl derivatives 9, 12 endowed with scanty solubility, were separated by chiral chromatography into the corresponding enantiomers; the (+) enantiomers were found to be potent agonists while the (-) ones were feeble antagonists. The racemic mixtures were also assessed for their positive inotropic activity on electrically stimulated rat papillary muscle and for their ability to increase Ca2+ entry into the vascular smooth muscle of rat aorta strips. The cyanofuroxan 8 proved to be an interesting product with dual Ca2+-dependent positive inotropic and NO-dependent vasodilating activity.
• 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.
• Design, Synthesis, and Characterization of N-Oxide-Containing Heterocycles with in Vivo Sterilizing Antitubercular Activity
  作者：Guilherme Felipe dos Santos Fernandes、Paula Carolina de Souza、Elsa Moreno-Viguri、Mery Santivañez-Veliz、Rocio Paucar、Silvia Pérez-Silanes、Konstantin Chegaev、Stefano Guglielmo、Loretta Lazzarato、Roberta Fruttero、Chung Man Chin、Patricia Bento da Silva、Marlus Chorilli、Mariana Cristina Solcia、Camila Maríngolo Ribeiro、Caio Sander Paiva Silva、Leonardo Biancolino Marino、Priscila Longhin Bosquesi、Debbie M. Hunt、Luiz Pedro S. de Carvalho、Carlos Alberto de Souza Costa、Sang Hyun Cho、Yuehong Wang、Scott Gary Franzblau、Fernando Rogério Pavan、Jean Leandro dos Santos

  DOI：10.1021/acs.jmedchem.7b01332

  日期：2017.10.26

  Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), is the infectious disease responsible for the highest number of deaths worldwide. Herein, 22 new N-oxide-containing compounds were synthesized followed by in vitro and in vivo evaluation of their antitubercular potential against Mtb. Compound 8 was found to be the most promising compound, with MIC90 values of 1.10 and 6.62 μM against active

  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。