4-<(diethylphosphono)difluoromethyl>-L-phenylalanine | 160751-42-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 4-<(diethylphosphono)difluoromethyl>-L-phenylalanine
• 英文别名: L-Phenylalanine, 4-[(diethoxyphosphinyl)difluoromethyl]-；(2S)-2-amino-3-[4-[diethoxyphosphoryl(difluoro)methyl]phenyl]propanoic acid
• CAS: 160751-42-8
• 化学式: C₁₄H₂₀F₂NO₅P
• 分子量: 351.287
• InChiKey: SNSFIWGJZZYFDH-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  23
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  98.8
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-<(diethylphosphono)difluoromethyl>-L-phenylalanine 在 bis(trimethylsilyl)trifluoroacetamide 、 碘代三甲硅烷 、 碳酸氢钠 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 为溶剂， 反应 3.0h， 生成 N-Α-FMOC-4-(膦酰基二氟甲基)-L-苯基丙氨酸
  参考文献：
  名称：

  An Efficient Synthesis of N-α-Fmoc-4-(Phosphonodifluoromethyl)-l- phenylalanine

  摘要：

  DOI：

  10.1021/jo9517508
• 作为产物：
  描述：

  对溴甲基苯甲酰溴 在 palladium dichloride 六甲基磷酰三胺 、 (diethylamido)sulfur trifluoride 、 氢气 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 甲苯 为溶剂， -78.0~25.0 ℃ 、344.73 kPa 条件下， 反应 21.42h， 生成 4-<(diethylphosphono)difluoromethyl>-L-phenylalanine
  参考文献：
  名称：

  An Efficient Synthesis of N-α-Fmoc-4-(Phosphonodifluoromethyl)-l- phenylalanine

  摘要：

  DOI：

  10.1021/jo9517508

文献信息

• [EN] METHODS AND SYSTEMS FOR PREPARING IRREVERSIBLE INHIBITORS OF PROTEIN TYROSINE PHOSPHATASES<br/>[FR] PROCÉDÉS ET SYSTÈMES POUR PRÉPARER DES INHIBITEURS IRRÉVERSIBLES DE PROTÉINES TYROSINES PHOSPHATASES
  申请人：UNIV ALBERTA

  公开号：WO2011106898A1

  公开（公告）日：2011-09-09

  Described herein are the preparation and use of novel bromo- phosphonomethylphenylalanine amino acid derivatives (BrPmp) and BrPmp-containing peptides as specific, irreversible protein tyrosine phosphatase inhibitors, which are suitable for application in peptide synthesis. These derivatives are particularly advantageous since their synthesis is both easy and scalable, and they are suitable for peptide synthesis. The BrPmp derivatives described herein can be appropriately protected to allow for solid phase peptide synthesis (SPPS) and incorporation into peptides for preparation of protein tyrosine phosphatase inhibitors and inhibitor libraries. The peptides and peptide libraries can be used to identify new protein tyrosine phosphatase specific sequences and profile protein tyrosine phosphatase activity in cell lysates, diagnostic samples and biopsy samples.

  在本发明中，描述了新颖的溴代磷酰甲基苯丙氨酸氨基酸衍生物（BrPmp）及其含BrPmp肽段的制备和应用，这些衍生物是特异性的、不可逆的蛋白酪氨酸磷酸酶抑制剂，适用于肽合成中的应用。这些衍生物的合成既简单又可放大，适合于肽合成。所述的BrPmp衍生物可以适当地进行保护，以便进行固相肽合成（SPPS）并并入肽中，用于制备蛋白酪氨酸磷酸酶抑制剂和抑制剂库。所得到的肽和肽库可用于识别新的蛋白酪氨酸磷酸酶特异序列，并在细胞裂解液、诊断样本和活检样本中分析蛋白酪氨酸磷酸酶的活性。
• Methods and Systems for Preparing Irreversible Inhibitors of Protein Tyrosine Phosphatases
  申请人：Cairo Christopher Warren

  公开号：US20130165333A1

  公开（公告）日：2013-06-27

  Described herein are the preparation and use of novel bromo-phosphonomethylphenylalanine amino acid derivatives (BrPmp) and BrPmp-containing peptides as specific, irreversible protein tyrosine phosphatase inhibitors, which are suitable for application in peptide synthesis. These derivatives are particularly advantageous since their synthesis is both easy and scalable, and they are suitable for peptide synthesis. The BrPmp derivatives described herein can be appropriately protected to allow for solid phase peptide synthesis (SPPS) and incorporation into peptides for preparation of protein tyrosine phosphatase inhibitors and inhibitor libraries. The peptides and peptide libraries can be used to identify new protein tyrosine phosphatase specific sequences and profile protein tyrosine phosphatase activity in cell lysates, diagnostic samples and biopsy samples.

  本文描述了一种新型溴代磷酸甲基苯丙氨酸氨基酸衍生物（BrPmp）和含有BrPmp的肽的制备和使用，作为特异性、不可逆的蛋白酪氨酸磷酸酶抑制剂，适用于肽合成。这些衍生物特别优越，因为它们的合成既容易又可扩展，并且它们适用于肽合成。本文所述的BrPmp衍生物可以适当地保护，以允许固相肽合成（SPPS）和将其纳入肽中，以制备蛋白酪氨酸磷酸酶抑制剂和抑制剂库。这些肽和肽库可用于识别新的蛋白酪氨酸磷酸酶特异性序列，并在细胞裂解物、诊断样本和活检样本中分析蛋白酪氨酸磷酸酶活性。
• Cyclic polypeptides for PCSK9 inhibition
  申请人：Merck Sharp & Dohme LLC

  公开号：US11530244B2

  公开（公告）日：2022-12-20

  Provided herein are cyclic polypeptide compounds that can, e.g., bind specifically to human proprotein convertase subtilisin/kexin type 9 (PCSK9) and optionally also inhibit interaction between human PCSK9 and human low density lipoprotein receptor (LDLR), and pharmaceutical compositions comprising one or more of these compounds. Also provided are methods of reducing LDL cholesterol level in a subject in need thereof that include administering to the subject one or more of the cyclic polypeptide compounds or a pharmaceutical composition provided herein.

  本文提供的环状多肽化合物，例如，可与人促蛋白转化酶亚基酶/kexin 9型（PCSK9）特异性结合，还可选择性地抑制人PCSK9与人低密度脂蛋白受体（LDLR）之间的相互作用，以及包含一种或多种这些化合物的药物组合物。还提供了降低有需要的受试者的低密度脂蛋白胆固醇水平的方法，该方法包括向受试者施用一种或多种本文提供的环多肽化合物或药物组合物。
• CYCLIC POLYPEPTIDES FOR PCSK9 INHIBITION
  申请人：Merck Sharp & Dohme corp.

  公开号：US20210284694A1

  公开（公告）日：2021-09-16

  Provided herein are cyclic polypeptide compounds that can, e.g., bind specifically to human proprotein convertase subtilisin/kexin type 9 (PCSK9) and optionally also inhibit interaction between human PCSK9 and human low density lipoprotein receptor (LDLR), and pharmaceutical compositions comprising one or more of these compounds. Also provided are methods of reducing LDL cholesterol level in a subject in need thereof that include administering to the subject one or more of the cyclic polypeptide compounds or a pharmaceutical composition provided herein.
• US9399653B2
  申请人：——

  公开号：US9399653B2

  公开（公告）日：2016-07-26