NO-Losartan A

• 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: NO-Losartan A
• 英文别名: [2-butyl-5-chloro-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methyl 3-(nitrooxymethyl)benzoate
• 化学式: C₃₀H₂₈ClN₇O₅
• 分子量: 602.049
• InChiKey: MWJCPZGVGOVWQZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  43
• 可旋转键数：
  13
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  154
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  3-(氯甲基)苯甲酸 在 4-二甲氨基吡啶 、 silver nitrate 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 生成 NO-Losartan A
  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

• NO-Sartans:  A New Class of Pharmacodynamic Hybrids as Cardiovascular Drugs
  作者：Maria C. Breschi、Vincenzo Calderone、Maria Digiacomo、Alma Martelli、Enrica Martinotti、Filippo Minutolo、Simona Rapposelli、Aldo Balsamo

  DOI：10.1021/jm049681p

  日期：2004.11.1

  The aim of this work was to develop lead pharmacodynamic hybrids, NO-sartans, possessing the characteristics of a typical AT-antagonist and of a "slow NO donor", by adding NO-donor side chains to losartan. These new compounds, 2a and 2b, displayed vasorelaxing effects, due to the release of NO, and antagonized the vasocontractile effects of angiotensin II, with potency values similar to that of losartan. In vivo, the antihypertensive effects of 2a were similar to those of losartan and captopril.
• 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.