2-butyl-4-chloro-1-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-5-[(4-(nitrooxymethyl)phenyl)carbonyloxy]methyl-1H-imidazole | 838876-28-1

• 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-butyl-4-chloro-1-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-5-[(4-(nitrooxymethyl)phenyl)carbonyloxy]methyl-1H-imidazole
• 英文别名: Losartan 4-[(nitrooxy)methyl]benzoate；[2-butyl-5-chloro-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methyl 4-(nitrooxymethyl)benzoate
• CAS: 838876-28-1
• 化学式: C₃₀H₂₈ClN₇O₅
• 分子量: 602.049
• InChiKey: WDKMHDPATXJWEF-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：

  对氯甲基苯甲酸 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， 反应 14.0h， 生成 2-butyl-4-chloro-1-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-5-[(4-(nitrooxymethyl)phenyl)carbonyloxy]methyl-1H-imidazole
  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

• [EN] PROCESS FOR PREPARING NITROOXY ESTERS, NITROOXY THIOESTERS, NITROOXY CARBONATES AND NITROOXY THIOCARBONATES, INTERMEDIATES USEFUL IN SAID PROCESS AND PREPARATION THEREOF<br/>[FR] PROCEDE DESTINE A LA PREPARATION D'ESTERS NITRO-OXY, DE THIOESTERS NITRO-OXY, DE CARBONATES NITRO-OXY ET DE THIOCARBONATES NITRO-OXY, PRODUITS INTERMEDIAIRES UTILES DANS CE PROCEDE ET LEUR PREPARATION
  申请人：NICOX SA

  公开号：WO2006008196A1

  公开（公告）日：2006-01-26

  The present invention relates to a process for preparing nitrooxy esters, nitrooxy thioesters, nitrooxy carbonates and nitrooxy thiocarbonates of compounds having at least a hydroxyl or thiol functional group, according to the following reaction scheme, (I), (II), (III). The invention also relates to intermediates useful in said process and to their preparation.

  本发明涉及一种制备具有至少一个羟基或硫醇官能团的化合物的硝基酯、硝基硫酯、硝基碳酸酯和硝基硫代碳酸酯的过程，根据以下反应方案(I)、(II)、(III)。该发明还涉及在该过程中有用的中间体及其制备方法。
• Process for Preparing Nitrooxy Esters, Nitrooxy Thioesters Nitrooxy Carbonates and Nitrooxy Thiocarbinates, Intermediates Useful in Said Process and Preparation Thereof
  申请人：Almirante Nicoletta

  公开号：US20070238882A1

  公开（公告）日：2007-10-11

  The present invention relates to a process for preparing nitrooxy esters, nitrooxy thioesters, nitrooxy carbonates and nitrooxy thiocarbonates of compounds having at least an hydroxyl or thiol functional group, according to the following reaction scheme The invention also relates to intermediates useful in said process and to their preparation.

  本发明涉及一种制备至少具有羟基或硫醇官能团的化合物的硝氧酯、硝氧硫酯、硝氧碳酸酯和硝氧硫代碳酸酯的过程，如下反应方案所示。本发明还涉及该过程中有用的中间体及其制备方法。
• Nitoroxy derivatives of losartan, valsatan, candesartan, telmisartan, eprosartan and olmesartan as angiotensin-II receptor blockers for the treatment of cardiovascular diseases
  申请人：Almirante Nicoletta

  公开号：US20060276523A1

  公开（公告）日：2006-12-07

  Angiotensin II receptor blocker nitroderivatives of formula (I): R—(Y—ONO 2 ) s (I) having wider pharmacological activity and enhanced tolerability. They can be employed for treating cardiovascular, renal and chronic liver diseases and inflammatory processes.

  公式（I）的血管紧张素II受体阻滞剂硝基衍生物：R—（Y—ONO2）s（I），具有更广泛的药理活性和增强的耐受性。它们可用于治疗心血管、肾脏和慢性肝脏疾病以及炎症过程。
• WO2006/79610
  申请人：——

  公开号：——

  公开（公告）日：——
• NITROOXY DERIVATIVES OF LOSARTAN, VALSATAN, CANDESARTAN, TELMISARTAN, EPROSARTAN AND OLMESARTAN AS ANGIOTENSIN-II RECEPTOR BLOCKERS FOR THE TREATMENT OF CARDIOVASCULAR DISEASES
  申请人：NICOX S.A.

  公开号：EP1653950A2

  公开（公告）日：2006-05-10