2,6-dimethyl-3-[(nitrooxy)methyl]benzoic acid | 886853-06-1

• 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: 2,6-dimethyl-3-[(nitrooxy)methyl]benzoic acid
• 英文别名: 2,6-Dimethyl-3-(nitrooxymethyl)benzoic acid
• CAS: 886853-06-1
• 化学式: C₁₀H₁₁NO₅
• 分子量: 225.201
• InChiKey: YIWRJEQJOSUWKV-UHFFFAOYSA-N

物化性质

• 熔点：
  123-125 °C
• 沸点：
  395.8±42.0 °C(Predicted)
• 密度：
  1.324±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  92.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  洛沙坦 、 2,6-dimethyl-3-[(nitrooxy)methyl]benzoic acid 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 反应 12.0h， 以34%的产率得到[2-butyl-5-chloro-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methyl 2,6-dimethyl-3-(nitrooxymethyl)benzoate
  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
• 作为产物：
  描述：

  3-(氯甲基)-2,6-二甲基苯甲酸 在 silver nitrate 作用下， 以 乙腈 为溶剂， 反应 4.0h， 以90%的产率得到2,6-dimethyl-3-[(nitrooxy)methyl]benzoic acid
  参考文献：
  名称：

  Evaluation of the NO-releasing properties of NO-donor linkers

  摘要：

  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。

  DOI：

  10.1211/jpp.60.2.0007

文献信息

• New NO-Releasing Pharmacodynamic Hybrids of Losartan and Its Active Metabolite:  Design, Synthesis, and Biopharmacological Properties
  作者：Maria C. Breschi、Vincenzo Calderone、Maria Digiacomo、Marco Macchia、Alma Martelli、Enrica Martinotti、Filippo Minutolo、Simona Rapposelli、Armando Rossello、Lara Testai、Aldo Balsamo

  DOI：10.1021/jm0600186

  日期：2006.4.1

  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.
• 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。