2-butyl-4-chloro-1-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-5-[(4-nitrooxybutyl)carbonyloxy]methyl-1H-imidazole

• 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-nitrooxybutyl)carbonyloxy]methyl-1H-imidazole
• 英文别名: Losartan 5-(nitrooxy)pentanoate；[2-butyl-5-chloro-3-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methyl 5-nitrooxypentanoate
• 化学式: C₂₇H₃₀ClN₇O₅
• 分子量: 568.032
• InChiKey: CCALZSTUWJROFY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  40
• 可旋转键数：
  15
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 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：

  5-氯戊酸 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 2-butyl-4-chloro-1-[[2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl]methyl]-5-[(4-nitrooxybutyl)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

• [DE] VERFAHREN ZUR HERSTELLUNG VON 3-PHENYL(THIO)URACILEN UND 3-PHENYLDITHIOURACILEN<br/>[EN] METHOD FOR PRODUCING 3-PHENYL(THIO)URACILS AND 3-PHENYLDITHIOURACILS<br/>[FR] PROCÉDÉ DE PRODUCTION DE 3-PHÉNYL(THIO)URACILES ET DE 3-PHÉNYLDITHIOURACILES
  申请人：BASF AG

  公开号：WO2005054208A1

  公开（公告）日：2005-06-16

  Beschrieben wird ein Verfahren zur Herstellung von 3-Phenyl(thio)uracilen oder 3-Phenyldithiouracilen der Formel I, bei dem ein Phenyliso(thio)cyanat der Formel II mit einem Enamin der Formel III umgesetzt und gegebenenfalls in einem weiteren Schritt das erhaltene 3-Phenyl(thio)uracil oder 3-Phenyldithiouracil der Formel I mit R1=R1a, wenn R1 für Wasserstoff steht, mit einem Aminierungsmittel der Formel IV zu 3-Phenyl(thio)uracilen oder 3-Phenyldithiouracilen der Formel I mit R1=Amino umgesetzt wird: worin die Variablen R1, R1a, R2, R3, R4, X1, X2, X3, Ar, A und L1 die in Anspruch 1 genannten Bedeutungen aufweisen.

  该方法描述了一种制备式I的3-苯基（硫）尿嘧啶或3-苯基二硫尿嘧啶的方法，其中式II的苯基异（硫）氰酸酯与式III的恩酰亚胺反应，必要时在进一步的步骤中，将得到的式I的3-苯基（硫）尿嘧啶或3-苯基二硫尿嘧啶（当R1代表氢时，R1 = R1a）与式IV的氨化剂反应，以制备式I的3-苯基（硫）尿嘧啶或3-苯基二硫尿嘧啶（当R1 = 氨基时）。其中变量R1，R1a，R2，R3，R4，X1，X2，X3，Ar，A和L1具有权利要求1中所述的含义。
• 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。
• Mehtod for producing 3-phenyl(thio)uracils and 3-phenyldithiouracils
  申请人：Hamprecht Gerhard

  公开号：US20060293520A1

  公开（公告）日：2006-12-28

  A process is described for preparing 3-phenyl(thio)uracils or 3-phenyldithiouracils of the formula I, by reacting a phenyl iso(thio)cyanate of the formula II with an enamine of the formula III and, if appropriate, in a further step, the resulting 3-phenyl(thio)uracil or 3-phenyldithiouracil of the formula I where R 1 =R 1a , when R 1 =hydrogen, is reacted with an aminating agent of the formula IV to give 3-phenyl(thio)uracils or 3-phenyldithiouracils of the formula I where R 1 =amino where the variables R 1 , R 1a , R 2 , R 3 , R 4 , X 1 , X 2 , X 3 , Ar, A and L1 are each as defined in claim 1.

  本发明涉及一种制备式I的3-苯基（硫）尿嘧啶或3-苯基二硫尿嘧啶的方法，该方法通过将式II的苯基异（硫）氰酸酯与式III的烯胺反应，如果适用，在进一步步骤中，将生成的式I的3-苯基（硫）尿嘧啶或3-苯基二硫尿嘧啶（其中R1=氢时R1a=R1）与式IV的氨化剂反应，以得到式I的3-苯基（硫）尿嘧啶或3-苯基二硫尿嘧啶（其中R1=氨基），其中变量R1、R1a、R2、R3、R4、X1、X2、X3、Ar、A和L1均如权利要求1所定义。
• Process for preparing nitrooxy esters, nitrooxy thioesters nitrooxy carbonates and nitrooxy thiocarbinates, intermediates useful in said process and preparation thereof
  申请人：Nicox S.A.

  公开号：US07723529B2

  公开（公告）日：2010-05-25

  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基氧酯、硝基氧代硫酯、硝基氧代碳酸酯和硝基氧代硫代碳酸酯的过程，如下所示的反应方案。本发明还涉及该过程中有用的中间体及其制备方法。
• 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.