(S)-5-biphenyl-4-yl-4-tert-butoxycarbonylaminopentanoic acid ethyl ester | 153037-44-6

• 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: (S)-5-biphenyl-4-yl-4-tert-butoxycarbonylaminopentanoic acid ethyl ester
• 英文别名: (S)-ethyl 5-(biphenyl-4-yl)-4-(tert-butoxycarbonylamino)pentanoate；(S)-4-(t-butoxycarbonylamino)-5-(biphenyl-4-yl)-pentanoic acid ethyl ester；ethyl (4S)-4-[(2-methylpropan-2-yl)oxycarbonylamino]-5-(4-phenylphenyl)pentanoate
• CAS: 153037-44-6
• 化学式: C₂₄H₃₁NO₄
• 分子量: 397.514
• InChiKey: GBLCNFRIIVXAGH-NRFANRHFSA-N

物化性质

• 沸点：
  543.1±50.0 °C(Predicted)
• 密度：
  1.077±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  29
• 可旋转键数：
  11
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-5-biphenyl-4-yl-4-tert-butoxycarbonylaminopentanoic acid ethyl ester 在 氯化亚砜 、 乙醇 作用下， 反应 2.25h， 生成 (S)-4-amino-5-biphenyl-4-ylpentanoic acid ethyl ester hydrochloride
  参考文献：
  名称：

  WO2008/83967

  摘要：

  公开号：
• 作为产物：
  描述：

  methyl N-(tert-butoxycarbonyl)-O-[(trifluoromethyl)sulfonyl]-D-tyrosinate 在 palladium on activated charcoal 、 四(三苯基膦)钯 sodium hydroxide 、 lithium aluminium tetrahydride 、 氢气 、 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 乙醇 、 二氯甲烷 、 甲苯 为溶剂， 80.0 ℃ 、344.73 kPa 条件下， 反应 40.33h， 生成 (S)-5-biphenyl-4-yl-4-tert-butoxycarbonylaminopentanoic acid ethyl ester
  参考文献：
  名称：

  Dicarboxylic Acid Dipeptide Neutral Endopeptidase Inhibitors

  摘要：

  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.

  DOI：

  10.1021/jm00010a014

文献信息

• Phosphono/biaryl substituted amino acid derivatives
  申请人：Ciba-Geigy Corporation

  公开号：US05250522A1

  公开（公告）日：1993-10-05

  The present invention relates to the N-phosphonomethyl-biaryl substituted amino acid derivatives of formula I ##STR1## wherein X represents a direct bond, C.sub.1-4 -alkylene or C.sub.2 -C.sub.4 -alkenylene; R and R' represent independently hydrogen, carbocyclic aryl, 6-tetrahydronaphthyl, 5-indanyl, .alpha.-(trichloromethyl, carboxyl, esterified carboxyl or amidated carboxyl)substituted-(lower alkyl or aryl-lower alkyl), acyloxymethyl optionally monosubstituted on methyl carbon by C.sub.1-20 -alkyl, by C.sub.5 -C.sub.7 -cycloalkyl, by aryl or by aryl-lower alkyl; R.sub.1 represents monocyclic carbocyclic or monocyclic heterocyclic aryl; COR.sub.3 represents carboxyl or carboxyl derivatized in form of a pharmaceutically acceptable ester; R.sub.2 and R.sub.4 represent hydrogen, lower alkyl, trifluoromethyl, lower alkoxy or halogen; and pharmaceutically acceptable salts thereof; pharmaceutical compositions comprising said compounds; methods for preparation of said compounds and for the preparation of intermediates; and methods of treating disorders in mammals which are responsive to the inhibition of neutral endopeptidases by administration of said compounds to mammals in need of such treatment.

  本发明涉及公式I的N-磷酸甲基-联苯取代氨基酸衍生物，其中X代表直接键，C.sub.1-4-烷基或C.sub.2-C.sub.4-烯基；R和R'独立地代表氢、碳环芳基、6-四氢萘基、5-茚基、α-(三氯甲基、羧基、酯化羧基或酰胺化羧基)取代-(较低烷基或芳基-较低烷基)、酰氧甲基，可选地在甲基碳上单取代为C.sub.1-20-烷基、C.sub.5-C.sub.7-环烷基、芳基或芳基-较低烷基；R.sub.1代表单环碳环芳基或单环杂环芳基；COR.sub.3代表羧基或以药学上可接受的酯形式衍生的羧基；R.sub.2和R.sub.4代表氢、较低烷基、三氟甲基、较低烷氧基或卤素；以及其药学上可接受的盐；包括所述化合物的药物组合物；制备所述化合物和中间体的方法；以及通过将所述化合物用于需要此类治疗的哺乳动物来抑制中性内肽酶以治疗哺乳动物的疾病的方法。
• Phosphono substituted tetrazole derivatives as ECE inhibitors
  申请人：Ciba-Geigy Corporation

  公开号：US05550119A1

  公开（公告）日：1996-08-27

  The present invention relates to the N-phosphonomethyl substituted compounds of formula ##STR1##

  本发明涉及公式##STR1##的N-磷酸甲基取代化合物。
• [EN] BIPHENYL-SUBSTITUED 4-AMINO-BUTYRIC ACID DERIVATIVES AND THEIR USE IN THE SYNTHESIS OF NEP INHIBITORS<br/>[FR] DÉRIVÉS D'ACIDE 4-AMINÉ-BUTYRIQUE SUBSTITUÉS PAR LE BIPHÉNYLE, ET LEUR UTILISATION DANS LA SYNTHÈSE D'INHIBITEURS DE NEP
  申请人：NOVARTIS AG

  公开号：WO2017033128A1

  公开（公告）日：2017-03-02

  The invention relates to a novel process, novel process steps and novel intermediates useful in the synthesis of pharmaceutically active compounds, in particular neutral endopeptidase (NEP) inhibitors and prodrugs thereof.

  该发明涉及一种新颖的过程、新颖的过程步骤和新颖的中间体，用于合成药用活性化合物，特别是中性内源性肽酶（NEP）抑制剂及其前药。
• Process for preparing biaryl substituted 4-amino-butyric acid or derivatives thereof and their use in the production of NEP inhibitors
  申请人：Novartis AG

  公开号：EP1903027A1

  公开（公告）日：2008-03-26

  The invention relates to a process for producing a compound according to formula (i) wherein R1 and R1' are independently hydrogen or an amine protecting group and R2 is a carboxylic group or derivative thereof, comprising reacting a compound according to formula (ii) wherein R1, R1' and R2 are defined as above, with hydrogen in the presence of a transition metal catalyst and optionally a chiral ligand, wherein the transition metal is selected from group 7, 8 or 9 of the periodic table. Furthermore, the invention relates to products obtainable by said process and to their use in the production of NEP inhibitors. Moreover, the invention relates to the use of transition metal catalyst in the preparation of NEP inhibitors or prodrugs thereof.

  本发明涉及一种制备公式(i)化合物的方法，其中R1和R1'独立地为氢或胺保护基，R2为羧基或其衍生物，包括在过渡金属催化剂和可选手性配体的存在下，将公式(ii)化合物与氢反应，其中R1、R1'和R2如上所定义，所述过渡金属选自周期表中的第7、8或9族。此外，本发明还涉及所述方法获得的产品及其在制备NEP抑制剂中的用途。此外，本发明还涉及在制备NEP抑制剂或其前药中使用过渡金属催化剂的用途。
• PROCESS FOR PREPARING BIARYL SUBSTITUTED 4-AMINO-BUTYRIC ACID OR DERIVATIVES THEREOF AND THEIR USE IN THE PRODUCTION OF NEP INHIBITORS
  申请人：Hook David

  公开号：US20090326066A1

  公开（公告）日：2009-12-31

  The invention relates to a process for producing a compound according to formula (i) or salt thereof, wherein R1 and R1′ are independently hydrogen or an amine protecting group and R2 is a carboxyl group or an ester group, comprising reacting a compound according to formula (ii) or salt thereof, wherein R1, R1′ and R2 are defined as above, with hydrogen in the presence of a transition metal catalyst and a chiral ligand, wherein the transition metal is selected from group 7, 8 or 9 of the periodic table. Furthermore, the invention relates to products obtainable by said process and to their use in the production of NEP inhibitors. Moreover, the invention relates to the use of transition metal catalyst in the preparation of NEP inhibitors or prodrugs thereof.

  本发明涉及一种制备公式（i）化合物或其盐的过程，其中R1和R1'独立地是氢或氨基保护基，R2是羧基或酯基，包括在过渡金属催化剂和手性配体的存在下，将公式（ii）化合物或其盐，其中R1、R1'和R2如上所定义，与氢反应。其中，所述过渡金属选自周期表的7、8或9组。此外，本发明还涉及通过该过程获得的产品及其在制备NEP抑制剂中的应用。此外，本发明还涉及在制备NEP抑制剂或其前药中使用过渡金属催化剂的用途。