1,2-di-O-nitro-3-(o-methoxyphenoxy)propylene glycol

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1,2-di-O-nitro-3-(o-methoxyphenoxy)propylene glycol
• 英文别名: 1-(2,3-bisnitrooxypropoxy)-2-methoxy-benzene；myonovin；1,2-di-O-nitro-3-(o-methoxyphenoxy)propanediol；3-(2-Methoxyphenoxy)propane-1,2-diyl dinitrate；[1-(2-methoxyphenoxy)-3-nitrooxypropan-2-yl] nitrate
• 化学式: C₁₀H₁₂N₂O₈
• 分子量: 288.214
• InChiKey: QXNRRRMQEQGRQH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  129
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  愈创甘油醚 在 氯化亚砜 、 silver nitrate 作用下， 以 四氢呋喃 为溶剂， 反应 14.0h， 生成 1,2-di-O-nitro-3-(o-methoxyphenoxy)propylene glycol
  参考文献：
  名称：

  多元醇硝酸酯及其对心脑血管病的康复治疗用途

  摘要：

  多元醇硝酸酯及其对心脑血管病的康复治疗用途。本发明公开了式(I)化合物或其立体异构体，其中：R1选自ONO2、CH2ONO2、CnH2n+1OH、CH2CH2CH3或H；R2选自ONO2、CH2ONO2、Cn’H2n’+1OH、CH2CH2CH3或H；R3选自ONO2、CH2ONO2、Cn”H2n”+1OH、CH2CH2CH3或H。本发明的有益效果：提供特殊有机一氧化氮前体类化合物，其可用于传递一氧化氮(NO)到体内。根据本发明的化合物和组合物已经显示出可以扩张血管，增加血液循环和供氧，降低血压，提高机体运动功能，恢复体力；根据本发明的化合物和组合物可用于心脑血管病的康复；根据本发明的组合物和化合物已经显示出改善骨质密度和骨头愈合。

  公开号：

  CN110590560A

文献信息

• Pharmaceutical Characterization of MyoNovin, a Novel Skeletal Muscle Regenerator: in silico, in vitro and in vivo Studies
  作者：Samaa Alrushaid、Neal M. Davies、Judy E. Anderson、Tyson Le、Jaime A. Yáñez、Zaid H. Maayah、Ayman O.S. El-Kadi、Ousama Rachid、Casey L. Sayre、Raimar Löbenberg、Frank J. Burczynski

  DOI：10.18433/j3ms8h

  日期：——

  PURPOSE: MyoNovin is a novel skeletal muscle-regenerating compound developed through synthesis of two nitro groups onto a guaifenesin backbone to deliver nitric oxide to skeletal muscle with a potential to treat muscle atrophy. The purpose of this study was to utilize in silico, in vitro, and in vivo approaches to characterize MyoNovin and examine its safety, biodistribution, and feasibility for drug delivery. METHODS: In silico software packages were used to predict the physicochemical and biopharmaceutical properties of MyoNovin. In vitro cardiotoxicity was assessed using human cardiomyocytes (RL-14) while effects on CYP3A4 metabolic enzyme and antioxidant activity were examined using commercial kits. A novel HPLC assay was developed to measure MyoNovin concentration in serum, and delineate initial pharmacokinetic and acute toxicity after intravenous administration (20 mg/kg) to male Sprague-Dawley rats. RESULTS: MyoNovin showed relatively high lipophilicity with a LogP value of 3.49, a 20-fold higher skin permeability (19.89 cm/s*107) compared to guaifenesin (0.66 cm/s*107), and ~10-fold higher effective jejunal permeability (2.24 cm/s*104) compared to guaifenesin (0.26 cm/s*104). In vitro, MyoNovinwas not cytotoxic to cardiomyocytes at concentrations below 8 μM and did not inhibit CYP3A4 or show antioxidant activity. In vivo, MyoNovin had a short half-life (t1/2) of 0.16 h, and a volume of distribution Vss of 0.62 L/kg. Biomarkers of MyoNovincardiac and renal toxicity did not differ significantly from baseline control levels.CONCLUSIONS: The predicted high lipophilicity and skin permeability of MyoNovin render it a potential candidate for transdermal administration while its favourable intestinal permeation suggests it may be suitable for oral administration. Pharmacokinetics following IV administration of MyoNovin were delineated for the first time in a rat model. Preliminary single 20 mg/kg dose assessment of MyoNovin suggest no influenceon cardiac troponin or β-N-Acetylglucosaminidase. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

  目的：MyoNovin 是一种新型骨骼肌再生化合物，它通过在愈创木酚骨架上合成两个硝基来向骨骼肌输送一氧化氮，具有治疗肌肉萎缩的潜力。本研究的目的是利用硅学、体外和体内方法描述 MyoNovin 的特性，并检查其安全性、生物分布和药物输送的可行性。方法：使用硅学软件包预测 MyoNovin 的物理化学和生物制药特性。使用人类心肌细胞（RL-14）评估体外心脏毒性，同时使用商业试剂盒检测对 CYP3A4 代谢酶和抗氧化活性的影响。开发了一种新型高效液相色谱法，用于测量血清中 MyoNovin 的浓度，并确定雄性 Sprague-Dawley 大鼠静脉注射（20 毫克/千克）后的初始药代动力学和急性毒性。结果：MyoNovin 的亲脂性相对较高，LogP 值为 3.49，皮肤渗透性（19.89 cm/s*107）比愈创木酚（0.66 cm/s*107）高 20 倍，有效空肠渗透性（2.24 cm/s*104）比愈创木酚（0.26 cm/s*104）高约 10 倍。在体外，浓度低于 8 μM 时，MyoNovin 不会对心肌细胞产生细胞毒性，也不会抑制 CYP3A4 或显示抗氧化活性。在体内，MyoNovin 的半衰期（t1/2）很短，为 0.16 h，分布容积 Vss 为 0.62 L/kg。MyoNovincardiac和肾毒性的生物标志物与基线对照水平相比没有显著差异：结论：MyoNovin的高亲脂性和皮肤渗透性使其成为透皮给药的潜在候选药物，而其良好的肠道渗透性表明它可能适合口服给药。首次在大鼠模型中阐明了静脉注射 MyoNovin 后的药代动力学。对MyoNovin单次20毫克/千克剂量的初步评估表明，它对心肌肌钙蛋白或β-N-乙酰氨基葡萄糖酶没有影响。本文供发表后审阅。注册读者（见 "致读者"）可点击本期内容页面上的 ABSTRACT 发表评论。
• WO2006/130982
  申请人：——

  公开号：——

  公开（公告）日：——
• COMPOSITIONS AND METHODS FOR TREATING OR PREVENTING METABOLIC SYNDROME DISORDERS
  申请人：Charles R Drew University of Medicine and Science

  公开号：EP2875359A2

  公开（公告）日：2015-05-27
• Compositions and Methods For Enhancing Nitric Oxide Delivery
  申请人：Wang Gu-Qi

  公开号：US20080207713A1

  公开（公告）日：2008-08-28

  The present invention is directed to compounds, combinations, compositions and methods for enhancing nitric oxide (NO) delivery to target sites, and in particular to muscle, both normal and dystrophic. Enhanced NO delivery according to the present invention may be achieved by using a combination of a muscle relaxant and an NO donor compound, or by using a compound of the invention: formula (I) wherein R 1 is H, halo, C 1-6 alkoxy or C 1-6 alkyl; R 2 is H, NO 2 or C(O)NH 2 ; R 3 is H, NO 2 or C(O)NH 2 ; and at least one of R 2 and R 3 is NO 2 ; or a pharmaceutically acceptable salt of the compound.
• US8106080B2
  申请人：——

  公开号：US8106080B2

  公开（公告）日：2012-01-31