4-(hydroxymethyl)benzyl nitrate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-(hydroxymethyl)benzyl nitrate
• 英文别名: (4-((Nitrooxy)methyl)phenyl)methan-1-ol；[4-(hydroxymethyl)phenyl]methyl nitrate
• 化学式: C₈H₉NO₄
• 分子量: 183.164
• InChiKey: GXDKJPXFGSTUTB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  75.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(hydroxymethyl)benzyl nitrate 在 盐酸 、 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 、 乙酸乙酯 为溶剂， 生成 (2S)-2-amino-4-[({4-[(nitrooxy)methyl]phenyl}methyl)oxycarbonyl]butanoic acid hydrochloride
  参考文献：
  名称：

  [EN] NITROSATED GLUTAMIC ACID COMPOUNDS, COMPOSITIONS AND METHODS OF USE
  [FR] COMPOSES D'ACIDE GLUTAMIQUE NITROSES, LEURS COMPOSITIONS ET PROCEDES D'UTILISATION

  摘要：

  公开号：

  WO2005030135A3
• 作为产物：
  描述：

  对苯二甲醇 在 盐酸 、 silver nitrate 作用下， 以 甲苯 、 乙腈 为溶剂， 反应 14.0h， 生成 4-(hydroxymethyl)benzyl nitrate
  参考文献：
  名称：

  New NO-Releasing Pharmacodynamic Hybrids of Losartan and Its Active Metabolite:  Design, Synthesis, and Biopharmacological Properties

  摘要：

  in a preliminary work, we reported two NO-sartans, possessing the characteristics of an AT, antagonist and a "slow NO donor", obtained by adding NO-donor side chains to losartan 1. The NO release from an NO-sartan should be modulated in order to strengthen the antihypertensive activity of the native drug and to ensure additional effects, such as the antiplatelet and anti-ischemic ones. To obtain a collection of prototypical NO-sartans, showing different rates of NO release, new NO-donor moieties have been linked to 1 or its active metabolite 2 (EXP 3174). Almost all the synthesized compounds exhibited both AT(1)-antagonist and NO-mediated vasorelaxing properties, with a wide range of NO-releasing rates. Further pharmacological investigation on compound 4a showed that it possessed anti hypertensive and cardiac antihypertrophic effects similar to those of the reference AT(1)-blocking or ACE-inhibiting drugs. Furthermore, the additional anti-ischemic cardio-protective properties and antiplatelet effects of 4a have been preliminarily investigated.

  DOI：

  10.1021/jm0600186

文献信息

• Evaluation of the NO-releasing properties of NO-donor linkers
  作者：Vincenzo Calderone、Maria Digiacomo、Alma Martelli、Filippo Minutolo、Simona Rapposelli、Lara Testai、Aldo Balsamo

  DOI：10.1211/jpp.60.2.0007

  日期：2010.2.18

  This work describes the synthesis of some benzoic (1–4) and alcoholic (5–7) nitrooxy derivatives, which are nitric oxide (NO) donors in themselves, and can also be seen as useful linkers that can be used in multi-target drugs capable of releasing NO. The NO-mediated vasorelaxing effects of the compounds were tested on endothelium-denuded isolated rat aortic rings pre-contracted with KCl. The pharmacological study of these compounds demonstrated that slight structural modification, such as the insertion of (a) methyl group(s) into the nitrooxymethyl chain or into the aromatic ring, and a change in the position of this nitrooxymethyl chain, could exert a marked (and potentially useful) influence on the NO releasing properties.

  这项工作描述了一些苯甲酸（1-4）和醇类（5-7）亚硝基衍生物的合成，它们本身是一氧化氮（NO）供体，也可以被视为可用于释放NO的多靶药物中的有用连接物。这些化合物的NO介导的血管舒张作用在用KCl预收缩的去内皮离体大鼠主动脉环上进行了测试。对这些化合物的药理学研究表明，轻微的结构修饰，如将（一）甲基基团插入亚硝基甲基链或芳香环中，以及改变这个亚硝基甲基链的位置，可能会对NO释放性能产生显著（且潜在有用）的影响。
• Synthesis and evaluation of multi-functional NO-donor/insulin-secretagogue derivatives for the treatment of type II diabetes and its cardiovascular complications
  作者：Maria Digiacomo、Alma Martelli、Lara Testai、Annalina Lapucci、Maria C. Breschi、Vincenzo Calderone、Simona Rapposelli

  DOI：10.1016/j.bmc.2014.12.043

  日期：2015.2

  aspects of diabetes and the endothelial dysfunction associated with this disease, no hypoglycemic drug has been proven to defeat the cardiovascular complications associated with type II diabetes. The aim of this research was to design new compounds exhibiting a double profile of hypoglycemic agents/NO-donors. The synthesis of molecules obtained by the conjunction of NO-donor moieties with two oral insulin-secretagogue

  尽管在发现有效的疗法以对比糖尿病的病理内分泌和代谢方面以及与该疾病相关的内皮功能障碍方面进行了大量的努力，但是没有降糖药被证明能克服与II型糖尿病相关的心血管并发症。这项研究的目的是设计具有降血糖药/ NO供体双重特征的新化合物。报道了通过NO供体部分与两种口服胰岛素-促分泌药物（瑞格列奈和那格列奈）结合而获得的分子的合成。通过功能测试评估离体内皮剥脱的大鼠主动脉环的NO介导的合成化合物的血管舒张作用。最有效的分子（4进行了测试，以评估其降血糖和抗缺血性心脏保护活性。这项研究表明4应该代表一种具有增强的心血管活性的新的胰岛素-分泌-前体/ NO供体前体药物，这可能与糖尿病的病理学方面和心脏保护活性有关。
• Nitrosated glutamic acid compounds, compositions and methods of use
  申请人：Garvey S. David

  公开号：US20070037821A1

  公开（公告）日：2007-02-15

  The invention describes novel nitrosated glutamic acid compounds and pharmaceutically acceptable salts thereof, and novel compositions comprising at least one nitrosated glutamic acid compound, and, optionally, at least one nitric oxide donor and/or at least one therapeutic agent. The invention also provides novel kits comprising at least one nitrosated glutamic acid compound, and, and, optionally, at least one nitric oxide donor compound and/or at least one therapeutic agent. The invention also provides methods for (a) treating cardiovascular diseases; (b) treating renovascular diseases; (c) treating diabetes; (d) treating diseases resulting from oxidative stress; (e) treating endothelial dysfunctions; (f) treating diseases caused by endothelial dysfunctions; (g) treating cirrhosis; (h) treating pre-eclampsia; (j) treating osteoporosis; (k) treating nephropathy; (l) treating diseases resulting from elevated levels of gamma-glutamyl transpeptidase and (m) the targeted delivery of compounds and nitric oxide to organs, cells or tissues containing the enzyme gamma-glutamyl transpeptidase.

  该发明描述了新型的硝化谷氨酸化合物及其药学上可接受的盐，以及包含至少一种硝化谷氨酸化合物，和/或至少一种一氧化氮供体和/或至少一种治疗剂的新型组合物。该发明还提供了包含至少一种硝化谷氨酸化合物，和/或至少一种一氧化氮供体化合物和/或至少一种治疗剂的新型试剂盒。该发明还提供了治疗心血管疾病、肾血管疾病、糖尿病、氧化应激引起的疾病、内皮功能障碍、内皮功能障碍引起的疾病、肝硬化、先兆子痫、骨质疏松症、肾病、γ-谷氨酰转移酶水平升高引起的疾病以及将化合物和一氧化氮有针对性地输送到含有γ-谷氨酰转移酶的器官、细胞或组织的方法。
• Novel Nitric Oxide Donor–Azole Conjugation Strategy for Efficient Treatment of <i>Cryptococcus neoformans</i> Infections
  作者：Fangfang Wang、Jianbing Wu、Mingke Yuan、Zhengsheng Yan、Xin Liu、Wang Li、Yihua Zhang、Chunquan Sheng、Na Liu、Zhangjian Huang

  DOI：10.1021/acs.jmedchem.3c01308

  日期：2023.10.26
• EP1673384A4
  申请人：——

  公开号：EP1673384A4

  公开（公告）日：2007-02-07