Carbamic acid, N-[(1S)-2-[1,1'-biphenyl]-4-yl-1-formylethyl]-, 1,1-dimethylethyl ester | 182192-86-5

• 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: Carbamic acid, N-[(1S)-2-[1,1'-biphenyl]-4-yl-1-formylethyl]-, 1,1-dimethylethyl ester
• 英文别名: tert-butyl N-[(2S)-1-oxo-3-(4-phenylphenyl)propan-2-yl]carbamate
• CAS: 182192-86-5
• 化学式: C₂₀H₂₃NO₃
• 分子量: 325.408
• InChiKey: OWIZSBUSCSIZSA-SFHVURJKSA-N

物化性质

• 沸点：
  475.1±45.0 °C(Predicted)
• 密度：
  1.097±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  Carbamic acid, N-[(1S)-2-[1,1'-biphenyl]-4-yl-1-formylethyl]-, 1,1-dimethylethyl ester 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 25.0 ℃ 、344.73 kPa 条件下， 反应 22.0h， 生成 ethyl (4R)-2-methyl-4-[(2-methylpropan-2-yl)oxycarbonylamino]-5-(4-phenylphenyl)pentanoate
  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
• 作为产物：
  描述：

  N-叔丁氧羰基-3-(4-联苯基)-L-丙氨酸 在 lithium aluminium tetrahydride 、 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 乙醚 、 二氯甲烷 为溶剂， 反应 16.33h， 生成 Carbamic acid, N-[(1S)-2-[1,1'-biphenyl]-4-yl-1-formylethyl]-, 1,1-dimethylethyl 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

• Tubulysine derivatives
  申请人：R & D Biopharmaceuticals Gmbh

  公开号：EP2532673A2

  公开（公告）日：2012-12-12

  The present invention relates to tubulysine derivatives and their use for the treatment of cancer and other diseases.

  本发明涉及管花苷衍生物及其治疗癌症和其他疾病的用途。
• TUBULYSINE DERIVATIVES
  申请人：R & D Biopharmaceuticals Gmbh

  公开号：EP2148886B1

  公开（公告）日：2014-02-19
• US8980833B2
  申请人：——

  公开号：US8980833B2

  公开（公告）日：2015-03-17
• [EN] TUBULYSINE DERIVATIVES<br/>[FR] DÉRIVÉS DE TUBULYSINE
  申请人：R & D BIOPHARMACEUTICALS GMBH

  公开号：WO2008138561A1

  公开（公告）日：2008-11-20

  [EN] The present invention relates to novel cytotoxic molecules and their use for the treatment of cancer and other diseases.
  [FR] La présente invention porte sur de nouvelles molécules cytotoxiques et sur leur utilisation pour le traitement du cancer et d'autres maladies.
• 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.