N-[(2'-氰基联苯-4-基)甲基]-L-缬氨酸苄酯 | 137864-23-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: N-[(2'-氰基联苯-4-基)甲基]-L-缬氨酸苄酯
• 英文名称: (S)-N-[(2'-Cyano-biphenyl-4-yl)methyl]valine benzyl ester
• 英文别名: (S)-N-[(2'-cyanobiphenyl-4-yl)methyl]-(L)-valine benzyl ester；N-[(2'-cyanobiphenyl-4-yl)methyl]-(L)-valine benzyl ester；(2S)-2-(2'-Cyano-4-biphenylylmethylamino)-3-methylbutyric acid benzyl ester；benzyl (2S)-2-[[4-(2-cyanophenyl)phenyl]methylamino]-3-methylbutanoate
• CAS: 137864-23-4
• 化学式: C₂₆H₂₆N₂O₂
• 分子量: 398.505
• InChiKey: HBOXXGYMTVDAJN-VWLOTQADSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  62.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-[(2'-氰基联苯-4-基)甲基]-L-缬氨酸苄酯 在 N,N-二异丙基乙胺 、 三正丁基叠氮化锡 作用下， 以 二氯甲烷 、 xylene 为溶剂， 生成 4-氧-缬纱坦苄酯
  参考文献：
  名称：

  Pharmacokinetics, disposition and biotransformation of [14C]-radiolabelled valsartan in healthy male volunteers after a single oral dose

  摘要：

  1. The disposition of valsartan, a potent angiotensin II receptor antagonist, was investigated in six healthy male volunteers. They each received a single oral dose of 80 mg of a C-14-labelled preparation as a neutral buffered solution.2. Peak concentrations of radioactivity and valsartan in plasma measured Ih after dosing showed rapid onset of absorption. The results of this study combined with other available data indicate that at least 51% of the dose was absorbed.3. Valsartan was the predominant radioactive compound in plasma. Elimination of valsartan and radioactivity was fast and multiexponential. beta-Half-lives of 6 +/- 1 h were observed. In a terminal elimination phase, low radioactivity levels decreased with a half-life of 81 +/- 33 h. A minor, pharmacologically inactive metabolite (valeryl-4-hydroxy-valsartan; M1) was detected in the plasma at rime points later than 2 h after dosing, representing approximately 11% of the AUC((24 h)) of plasma radioactivity.4. The bulk of the dose was excreted within 4 days. The total excretion within 7 days amounted to 99 +/- 1% of dose. Faecal excretion was predominant (86 +/- 5% of dose). Valsartan was largely excreted unchanged (81 +/- 5% of the dose in the excreta). The predominant clearance mechanism appeared to be direct elimination via bile. 5. An inactive metabolite, M1, was formed by oxidative biotransformation and accounted for 9 +/- 3% of the dose in the excreta.

  DOI：

  10.1080/004982597240767
• 作为产物：
  描述：

  (S)-2-[(2'-cyanobiphenyl-4-ylmethyl)amino]-3-methylbutyric acid benzyl ester hydrochloride 在 碳酸氢钠 作用下， 以 水 、 甲苯 为溶剂， 反应 1.0h， 生成 N-[(2'-氰基联苯-4-基)甲基]-L-缬氨酸苄酯
  参考文献：
  名称：

  Process for the Preparation of Valsartan and its Intermediates

  摘要：

  本发明涉及一种制备化合物I的缬沙坦的方法：包括通过结晶从包含亲水溶剂、非极性质子溶剂和水的三元混合物中提纯较低纯度的苄基缬沙坦的中间体苄基缬沙坦的公式IV；从该三元混合物中回收苄基缬沙坦，然后通过从包含非极性脱质子溶剂或极性脱质子溶剂或它们的混合物的第二溶剂中结晶苄基缬沙坦；回收基本无有机锡杂质的苄基缬沙坦；并将所述的苄基缬沙坦转化为缬沙坦。

  公开号：

  EP1714963A1

文献信息

• Acyl compounds
  申请人：Ciba-Geigy Corp

  公开号：US05399578A1

  公开（公告）日：1995-03-21

  Compounds of the formula ##STR1## in which R.sub.1 is an aliphatic hydrocarbon radical which is unsubstituted or substituted by halogen or hydroxyl, or a cycloaliphatic or araliphatic hydrocarbon radical; X.sub.1 is CO, SO.sub.2, or --O--C(.dbd.O)-- with the carbon atom of the carbonyl group being attached to the nitrogen atom shown in formula I; X.sub.2 is a divalent aliphatic hydrocarbon radical which is unsubstituted or substituted by hydroxyl, carboxyl, amino, guanidino or a cycloaliphatic or aromatic radical, or is a divalent cycloaliphatic hydrocarbon radical, it being possible for a carbon atom of the aliphatic hydrocarbon radical to be additionally bridged by a divalent aliphatic hydrocarbon radical; R.sub.2 is carboxyl which, if desired, is esterified or amidated, substituted or unsubstituted amino, formyl which, if desired, is acetalized, 1H-tetrazol-5-yl, pyridyl, hydroxyl which, if desired, is etherified, S(O).sub.m --R where m is 0, 1 or 2 and R is hydrogen or an aliphatic hydrocarbon radical, alkanoyl, unsubstituted or N-substituted sulfamoyl or PO.sub.n H.sub.2 where n is 2 or 3; X.sub.3 is a divalent aliphatic hydrocarbon; R.sub.3 is carboxyl, 5-tetrazolyl, SO.sub.3 H, PO.sub.2 H.sub.2, PO.sub.3 H.sub.2 or haloalkylsulfamoyl; and the rings A and B independently of one another are substituted or unsubstituted; in free form or in salt form, can be prepared in a manner known per se and can be used, for example, as medicament active ingredients.

  式为##STR1##的化合物，其中R.sub.1是未取代或取代为卤素或羟基的脂肪烃基，或者是环脂烃或芳基脂肪烃基；X.sub.1是CO、SO.sub.2或--O--C(.dbd.O)--，其中羰基的碳原子连接到式I中显示的氮原子；X.sub.2是未取代或取代为羟基、羧基、氨基、胍基或环脂烃或芳香基的二价脂肪烃基，或者是二价环脂烃脂肪烃基，脂肪烃基的碳原子还可以通过另一个二价脂肪烃基进行桥接；R.sub.2是羧基，如果需要，可以酯化或酰胺化，取代或未取代的氨基，甲酰基，如果需要，可以缩醛化，1H-四唑-5-基，吡啶基，羟基，如果需要，可以醚化，S(O).sub.m --R，其中m为0、1或2，R为氢或脂肪烃基，烷酰基，未取代或N-取代的磺酰胺基或PO.sub.n H.sub.2，其中n为2或3；X.sub.3是二价脂肪烃基；R.sub.3是羧基，5-四唑基，SO.sub.3 H，PO.sub.2 H.sub.2，PO.sub.3 H.sub.2或卤代烷基磺酰胺基；环A和B彼此独立地被取代或未取代；以自由形式或盐形式，可以按已知方法制备，并可用作药物活性成分。
• PROCESSES FOR THE PREPARATION OF INTERMEDIATES OF VALSARTAN
  申请人：Saxena Ira

  公开号：US20090203921A1

  公开（公告）日：2009-08-13

  The present invention relates to processes for the preparation of intermediates of valsartan.

  本发明涉及用于制备缬沙坦中间体的方法。
• Process for the preparation of valsartan and its intermediates
  申请人：Kumar Ashok

  公开号：US20060281801A1

  公开（公告）日：2006-12-14

  The present invention relates to an improved process for the preparation of valsartan and its intermediates in substantially pure enantiomeric form. In particular, the present invention provides a process for preparing benzyl valsartan intermediate substantially free of organotin impurities. The valsartan produced from such benzyl valsartan intermediate requires significantly lower catalyst loading and has superior purity.

  本发明涉及一种改进的过程，用于以基本纯的对映体形式制备缬沙坦及其中间体。具体而言，本发明提供了一种用于制备苯甲基缬沙坦中间体的过程，该中间体基本上不含有有机锡杂质。从这种苯甲基缬沙坦中间体生产的缬沙坦需要显着较低的催化剂负载量，并具有更高的纯度。
• [EN] PROCESS FOR ISOLATION OF VALSARTAN<br/>[FR] PROCEDE D'ISOLEMENT DE VALSARTAN
  申请人：RANBAXY LAB LTD

  公开号：WO2005049588A1

  公开（公告）日：2005-06-02

  A process for isolation of valsartan is provided. The process forms solid valsartan having a purity of at least 99 %.

  提供了一种瓦力普坦的分离工艺。该工艺形成纯度至少为 99% 的固体瓦力普坦。
• USE OF VALSARTAN OR ITS METABOLITE TO IN HIBIT PLATELET AGGREGATION
  申请人：Malinin Alex

  公开号：US20100048654A1

  公开（公告）日：2010-02-25

  The invention relates to a method of inhibiting platelet aggregation comprising administering a therapeutically effective amount of an ARB or its metabolite, especially Valsartan or its metabolite valeryl 4-hydroxy valsartan. Conditions to be treated by inhibition of platelet aggregation include acute myocardial infarction, ischemic stroke, angina pectoris, acute coronary syndromes, TIA (transient ischemic attacks, or acute cerebrovascular syndromes), heart failure, chest pain of ischemic etiology, syndrome X, thromboembolism, pulmonary hypertension, diabetes mellitus, peripheral vascular disease, deep vein thrombosis, arterial thrombosis of any vessel, catheter thrombotic occlusion or reocclusion.

  本发明涉及一种抑制血小板聚集的方法，包括给予治疗有效量的ARB或其代谢物，特别是Valsartan或其代谢物Valeryl 4-羟基Valsartan。通过抑制血小板聚集来治疗的疾病包括急性心肌梗死、缺血性卒中、心绞痛、急性冠状动脉综合征、TIA（短暂性缺血性发作，或急性脑血管综合征）、心力衰竭、缺血性胸痛、X综合征、血栓栓塞、肺动脉高压、糖尿病、外周血管疾病、深静脉血栓形成、任何血管的动脉血栓形成、导管血栓性闭塞或再闭塞。