LCZ696杂质C | 149709-63-7

• 物质功能分类: 分析化学 - 对照品
• 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: LCZ696杂质C
• 英文名称: α-ethyl (αS,γS)-γ-<(3-carboxy-1-oxopropyl)amino>-α-methyl<1,1'-biphenyl>-4-pentanoate
• 英文别名: sacubitril；(2S,4S)-Sacubitril；4-[[(2S,4S)-5-ethoxy-4-methyl-5-oxo-1-(4-phenylphenyl)pentan-2-yl]amino]-4-oxobutanoic acid
• CAS: 149709-63-7
• 化学式: C₂₄H₂₉NO₅
• 分子量: 411.498
• InChiKey: PYNXFZCZUAOOQC-UWJYYQICSA-N

物化性质

• 沸点：
  656.9±55.0 °C(Predicted)
• 密度：
  1.151±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  30
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  92.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (2S,4S)-5-biphenyl-4-yl-(4-tert-butoxycarbonylamino)-2-methylpentanoic acid cyclohexylamine salt 在 氯化亚砜 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 生成 LCZ696杂质C
  参考文献：
  名称：

  cu屈特立的立体异构体的合成，分离与分析

  摘要：

  已经开发了一种高效的杀虫灵工业合成方法。已合成，分离并鉴定了衍生自沙比特利及其关键中间体的立体异构体，以进行质量控制。这些立体异构体通过光谱数据（MS和NMR）表征，并用作开发HPLC方法的参考标准。

  DOI：

  10.1021/acs.oprd.8b00350

文献信息

• [EN] SOLID FORMS OF (2R,4S)-5-(BIPHENYL-4-YL)-4-[(3-CARBOXYPROPIONYL)AMINO]-2- -METHYLPENTANOIC ACID ETHYL ESTER, ITS SALTS AND A PREPARATION METHOD<br/>[FR] FORMES SOLIDES D'ESTER ÉTHYLIQUE D'ACIDE (2R,4S)-5-(BIPHÉNYL-4-YL)-4-[(3-CARBOXYPROPIONYL)AMINO]-2-MÉTHYLPENTANOÏQUE, SES SELS ET SON PROCÉDÉ DE PRÉPARATION
  申请人：ZENTIVA KS

  公开号：WO2017097275A1

  公开（公告）日：2017-06-15

  The invention relates to solid forms of the free acid of sacubitril of formula 1, especially a crystalline form, incl. a method of removing chemical impurities from the crude free acid of sacubitril that is characterized in the use of well crystallizing salts of sacubitril with the amines of formula 9, where R1, R2, R3 independently stand for hydrogen or a C1-C7 alkyl, preferably the salt with cyclohexylamine, tert-butylamine or iso-propylamine. The invention further relates to a novel solid, crystalline form of sacubitril (8) - hemisolvate of the potassium salt of sacubitril, incl. a direct and highly efficient and industrially usable preparation methods of a solid form of sacubitril free acid and its pharmaceutically applicable salts, especially the crystalline sodium salt of formula 5, calcium salt of sacubitril of formula 6 and hemisolvate of the potassium salt of sacubitril of formula 8.

  该发明涉及公式1的沙库比替尔游离酸的固体形式，特别是结晶形式，包括一种从粗沙库比替尔游离酸中去除化学杂质的方法，其特征在于使用沙库比替尔与公式9的胺的良好结晶盐，其中R1、R2、R3独立代表氢或C1-C7烷基，优选与环己胺、叔丁胺或异丙胺的盐。该发明还涉及沙库比替尔的新型固体结晶形式（8）-沙库比替尔钾盐的半溶剂包含物，包括沙库比替尔游离酸及其药用适用盐的固体形式的直接、高效和工业可用制备方法，特别是公式5的结晶钠盐、公式6的钙盐和公式8的沙库比替尔钾盐的半溶剂。
• [EN] NOVEL PROCESS FOR THE PREPARATION OF SACUBITRIL AND ITS INTERMEDIATES<br/>[FR] NOUVEAU PROCÉDÉ POUR LA PRÉPARATION DE SACUBITRIL ET DE SES INTERMÉDIAIRES
  申请人：MYLAN LABORATORIES LTD

  公开号：WO2016135751A1

  公开（公告）日：2016-09-01

  A process for the preparation of sacubitril and its intermediates is disclosed. By practicing the methods disclosed herein, a solid form of sacubitril may be generated. A crystalline form of sacubitril is also disclosed.

  揭示了一种制备沙库比特利及其中间体的方法。通过实施此处披露的方法，可以生成沙库比特利的固体形式。还披露了沙库比特利的结晶形式。
• 不对称催化氢化制备沙库巴曲化合物的方法
  申请人：瑞博（苏州）制药有限公司

  公开号：CN115974634A

  公开（公告）日：2023-04-18

  本发明公开了不对称催化氢化制备沙库巴曲化合物的方法，是一条具备工业化的生产路线。本发明通过不对称催化氢化反应合成沙库巴曲化合物的路线为：
• Dicarboxylic Acid Dipeptide Neutral Endopeptidase Inhibitors
  作者：Gary M. Ksander、Raj D. Ghai、Reynalda deJesus、Clive Diefenbacher、Andrew Yuan、Carol Berry、Yumi Sakane、Angelo Trapani

  DOI：10.1021/jm00010a014

  日期：1995.5

  The synthesis of three series of dicarboxylic acid dipeptide neutral endopeptidase 24.11 (NEP) inhibitors is described. In particular, the amino butyramide 21a exhibited potent NEP inhibitory activity (IC50 = 5.0 nM) in vitro and in vivo. Blood levels of 21a were determined using an ex vivo method by measuring plasma inhibitory activity in conscious rats, mongrel dogs, and cynomolgus monkeys. Free drug concentrations were 10-1500 times greater than the inhibitory constant for NEP over the course of a 6 h experiment. A good correlation of free drug concentrations was obtained when comparing values determined by the ex vivo analysis to those calculated from direct HPLC measurements. Plasma atrial natriuretic factor (exogenous) levels were elevated in rats and dogs after oral administration of 19a. Urinary volume and urinary sodium excretion were also potentiated in anesthetized dogs treated with 21a.
• COMPOUNDS CONTAINING S-N-VALERYL-N-{[2'-(1H-TETRAZOLE-5-YL)-BIPHENYL-4-YL]-METHYL}-VALINE AND (2R,4S)-5-BIPHENYL-4-YL-4-(3-CARBOXY-PROPIONYLAMINO)-2-METHYL-PENTANOIC ACID ETHYL ESTER MOIETIES AND CATIONS
  申请人：Novartis Pharmaceuticals Corporation

  公开号：US20210361610A1

  公开（公告）日：2021-11-25

  A compound comprising of the angiotensin receptor antagonist (ARB) valsartan, the neutral endopeptidase inhibitor (NEPi) (2R,4S)-5-biphenyl-4-yl-4-(3-carboxy-propionylamino)-2-methylpentanoic acid ethyl ester and one or more monovalent cations such as Na + useful for the treatment of hypertension and/or heart failure.