4-[二氟(膦酰)甲基]-L-苯丙氨酸 | 188642-79-7

• 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
• 中文名称: 4-[二氟(膦酰)甲基]-L-苯丙氨酸
• 英文名称: 4-phosphono(difluoromethyl) phenylalanine
• 英文别名: 4-(Phosphonodifluoromethyl)-L-phenylalanine；(2S)-2-amino-3-[4-[difluoro(phosphono)methyl]phenyl]propanoic acid
• CAS: 188642-79-7
• 化学式: C₁₀H₁₂F₂NO₅P
• 分子量: 295.18
• InChiKey: HRDUMKHDIFUQGB-QMMMGPOBSA-N

物化性质

• 沸点：
  519.5±60.0 °C(Predicted)
• 密度：
  1.598±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -2.7
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  121
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  Fmoc-L-缬氨酸 、 Fmoc-L-脯氨酸 、 4-[二氟(膦酰)甲基]-L-苯丙氨酸 、 N-(9-fluorenylmethoxycarbonyl)-L-methioninamide 生成 {[4-((S)-2-Amino-2-{(S)-1-[(S)-2-((S)-1-carbamoyl-3-methylsulfanyl-propylcarbamoyl)-pyrrolidine-1-carbonyl]-2-methyl-propylcarbamoyl}-ethyl)-phenyl]-difluoro-methyl}-phosphonic acid
  参考文献：
  名称：

  Design of Peptidomimetics That Inhibit the Association of Phosphatidylinositol 3-Kinase with Platelet-Derived Growth Factor-β Receptor and Possess Cellular Activity

  摘要：

  Phosphorylated tyrosine residues of growth factor receptors that associate with intracellular proteins containing src-homology 2 (SH2) domains are integral components in several signal transduction pathways related to proliferative diseases such as cancer, atherosclerosis, and restenosis. In particular, a phosphorylated pentapeptide [pTyr(751)-Val-Pro-Met(754)-Leu (PTyr = phosphotyrosine)] derived from the primary sequence of platelet-derived growth factor-beta (PDGF-beta) receptor blocks the association of the C-terminal SH2 domain of the p85 subunit of phosphatidylinositol 3-kinase (PI 3-kinase) to PDGF-beta receptor with an IC50 of 0.445 +/- 0.047 mu M. Further evaluation of the structure-activity relationships for pTyr(751)-Val-Pro-Met-Leu resulted in the design of smaller peptidomimetics with enhanced affinity including Ac-pTyr-Val-Ala-N(C6H13)(2) (IC50 = 0.076 +/- 0.010 mu M). In addition, the phosphotyrosine residue was replaced with a difluorophosphonate derivative [4-phosphono(difluoromethyl)phenylalanine (CF(2)Pmp)] which has been shown to be stable to cellular phosphatases. The extracellular administration of either CF(2)Pmp-Val-Pro-Met-Leu or Ac-CF(2)Pmp-Val-Pro-Met-NH2 in a whole cell assay resulted in specific inhibition of the PDGF-stimulated association from the C-terminal SH2 domain of the p85 subunit of PI 3-kinase to the PDGF-beta receptor in a dose-dependent manner. These compounds were also effective in inhibiting GLUT4 translocation, c-fos expression, and cell membrane ruffling in single-cell microinjection assay.

  DOI：

  10.1021/jm9802766
• 作为产物：
  描述：

  Fmoc-(4-phosphonodifluoromethyl)-Phe-OMe 在 lithium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 3.0h， 以69%的产率得到4-[二氟(膦酰)甲基]-L-苯丙氨酸
  参考文献：
  名称：

  氨基酸的内在疏水性量表及其在含氟化合物中的应用

  摘要：

  引入了100多种疏水性标度，每种均基于独特的冷凝相方法。但是，比较不同技术获得的疏水性值及其相对等级并不是一件容易的事，因为环境和氨基酸之间的相互作用对于每种方法都是唯一的。在这里，我们通过研究气相洁净室环境中氨基酸的特性来克服这一局限性。在气相中，默认情况下不存在疏水作用产生的熵贡献，只有侧链的极性决定了自组装。这允许推导新的疏水性标度，它仅基于簇内单个氨基酸单元之间的相互作用，因此更准确地反映了侧链的内在本质。该原理可进一步用于对非天然衍生物进行分类，如此处所示的氟化氨基酸变体所示。

  DOI：

  10.1002/anie.201813954

文献信息

• Inhibitors of signal transduction and activator of transcription 3
  申请人：McMurray S. John

  公开号：US20070010428A1

  公开（公告）日：2007-01-11

  Stat3 inhibitor compounds are disclosed, wherein the compounds are structural analogs of Ac-pTyr-Leu-Pro-Gln-Thr-NH 2 and bind to the SH2 domain of Stat3 under physiological conditions to inhibit a cellular signaling activity of Stat3.

  抑制剂化合物Stat3被披露，其中这些化合物是Ac-pTyr-Leu-Pro-Gln-Thr-NH2的结构类似物，并在生理条件下与Stat3的SH2结构域结合，从而抑制Stat3的细胞信号活性。
• Synthesis of L-2,3,5,6-tetrafluoro-4-(phosphonomethyl) phenylalanine, a novel non-hydrolyzable phosphotyrosine mimetic and L-4-(phosphonodifluoromethyl)phenylalanine
  作者：Wang-Qing Liu、Bernard P. Roques、Christiane Garbay

  DOI：10.1016/s0040-4039(97)00027-0

  日期：1997.2

  A new non-hydrolyzable phosphotyrosine analogue, L-F4Pmp and its N-Fmoc protected derivative were prepared by using an enantioselective synthetic pathway with camphor sultam as chiral auxiliary. The side chain pKa2 (6.9) of L-F4Pmp was determined. A new synthesis of L-F2Pmp was also described.

  通过使用樟脑舒马坦作为手性助剂的对映选择性合成途径，制备了一种新的不可水解的磷酸酪氨酸类似物LF 4 Pmp及其受N-Fmoc保护的衍生物。测定了LF 4 Pmp的侧链pKa 2（6.9）。还描述了LF 2 Pmp的新合成。
• [EN] HYBRIDIZED POLY(AMIDOAMINE)-AMINO ACID DENDRIMERS<br/>[FR] DENDRIMÈRES POLY(AMIDOAMINE)-ACIDES AMINÉS HYBRIDÉS
  申请人：UNIV NORTH CAROLINA STATE

  公开号：WO2021046307A1

  公开（公告）日：2021-03-11

  Disclosed herein are hybrid poly(amidoamine)-amino acid dendrimers, their methods of manufacture, and uses thereof. In accordance with the purposes of the disclosed materials and methods, as embodied and broadly described herein, the disclosed subject matter, in one aspect, relates to dendrimer compounds, methods for their manufacture, and uses thereof. More specifically, the subject matter disclosed herein relates to hybridized poly(amidoamine)-amino acid dendrimer compounds of Formula I as described herein, their methods of manufacture, and uses thereof.

  本文揭示了混合聚酰胺胺-氨基酸树状分子、它们的制造方法和用途。根据本文所体现和广泛描述的所揭示材料和方法的目的，本文所揭示的主题在一个方面涉及树状分子化合物、它们的制造方法和用途。更具体地，本文所揭示的主题涉及到公式I所描述的混合聚酰胺胺-氨基酸树状分子化合物、它们的制造方法和用途。
• [EN] INHIBITION OF CYTOKINE-INDUCED SH2 PROTEIN IN NK CELLS<br/>[FR] INHIBITION DE PROTÉINES SH2 INDUITES PAR DES CYTOKINES DANS DES CELLULES NK
  申请人：THE WALTER AND ELIZA HALL INST OF MEDICAL RES

  公开号：WO2017100861A1

  公开（公告）日：2017-06-22

  The present invention relates to therapeutic and prophylactic methods based on inhibition of CIS in NK cells. In particular, the present invention relates to treating or preventing a NK-responsive condition by administering to a subject a CIS inhibitor, or administering CIS-inhibited NK cells. The invention further relates to methods for identifying a CIS inhibitor, and for determining a likelihood of cancer response to treatment with CIS inhibition.

  本发明涉及基于抑制NK细胞中CIS的治疗和预防方法。具体而言，本发明涉及通过向受试者施用CIS抑制剂或施用CIS抑制的NK细胞来治疗或预防NK细胞响应性疾病。本发明还涉及识别CIS抑制剂的方法，以及确定癌症对CIS抑制治疗的反应可能性的方法。
• Cell penetrating peptides and methods of making and using thereof
  申请人：Entrada Therapeutics, Inc.

  公开号：US10626147B2

  公开（公告）日：2020-04-21

  Disclosed herein are compounds having activity as cell penetrating peptides. In some examples, the compounds can comprise a cell penetrating peptide moiety and a cargo moiety. The cargo moiety can comprise one or more detectable moieties, one or more therapeutic moieties, one or more targeting moieties, or any combination thereof. In some examples, the cell penetrating peptide moiety is cyclic. In some examples, the cell penetrating peptide moiety and cargo moiety together are cyclic. In some examples, the cell penetrating peptide moiety is cyclic and the cargo moiety is appended to the cyclic cell penetrating peptide moiety structure. In some examples, the cargo moiety is cyclic and the cell penetrating peptide moiety is cyclic, and together they form a fused bicyclic system.

  本文公开了具有细胞穿透肽活性的化合物。在一些例子中，这些化合物可以包括细胞穿透肽分子和货物分子。货物分子可以包括一个或多个可检测分子、一个或多个治疗分子、一个或多个靶向分子或它们的任意组合。在某些例子中，细胞穿透肽分子是环状的。在某些例子中，细胞穿透肽分子和货物分子是环状的。在某些例子中，细胞渗透肽分子是环状的，而货物分子被附加到环状细胞渗透肽分子结构上。在某些例子中，货物分子是环状的，而细胞穿透肽分子是环状的，它们共同形成一个融合的双环系统。