((R)-1-(((benzyloxy)carbonyl)amino)-2-phenylethyl)phosphinic acid | 118636-74-1

• 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: ((R)-1-(((benzyloxy)carbonyl)amino)-2-phenylethyl)phosphinic acid
• 英文别名: [(1R)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphinic acid
• CAS: 118636-74-1
• 化学式: C₁₆H₁₈NO₄P
• 分子量: 319.297
• InChiKey: JEFFINAXGSNNQU-OAHLLOKOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ((R)-1-(((benzyloxy)carbonyl)amino)-2-phenylethyl)phosphinic acid 在 palladium dihydroxide Dowex-Li⁺ 、 氢气 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 叔丁胺 、 三乙胺 作用下， 以 四氯化碳 、 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 35.5h， 生成
  参考文献：
  名称：

  Transition State Analogy of Phosphonic Acid Peptide Inhibitors of Pepsin

  摘要：

  A series of 11 phosphonate peptide analogs, RO(2)C-Xaa-Yaa-Phe-(PO2--O)-Phe O-(3-(4-pyridyl)propyl ester), were synthesized and evaluated as inhibitors of the aspartic peptidase pepsin. For the inhibitors with Gly or Ala at the P-2 position, the K-i values correlate with the K-m/k(cat) values of the corresponding substrates, demonstrating that these analogs mimic the transition state in the way the P-2-P-4 residues bind. Deviations from the correlation for the other inhibitor/substrate pairs imply a different binding orientation as a result of N-substitution at P-2 (Pro), contamination with the more potent diastereomer (D-Ala), or a change in rate-limiting step for turnover (lie).

  DOI：

  10.1021/jo952074c
• 作为产物：
  描述：

  苯乙醛 在 R(+)-alpha-甲基苄胺 、 氢溴酸 、 次磷酸 、 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 14.67h， 生成 ((R)-1-(((benzyloxy)carbonyl)amino)-2-phenylethyl)phosphinic acid
  参考文献：
  名称：

  Molecular tools that block maturation of the nuclear lamin A and decelerate cancer cell migration

  摘要：

  Lamin A contributes to the structure of nuclei in all mammalian cells and plays an important role in cell division and migration. Mature lamin A is derived from a farnesylated precursor protein, known as prelamin A, which undergoes post-translational cleavage catalyzed by the zinc metalloprotease STE24 (ZPMSTE24). Accumulation of farnesylated prelamin A in the nuclear envelope compromises cell division, impairs mitosis and induces an increased expression of inflammatory gene products. ZMPSTE24 has been proposed as a potential therapeutic target in oncology. A library of peptidomimetic compounds were synthesized and screened for their ability to induce accumulation of prelamin A in cancer cells and block cell migration in pancreatic ductal adenocarcinoma cells. The results of this study suggest that inhibitors of lamin A maturation may interfere with cell migration, the biological process required for cancer metastasis.

  DOI：

  10.1016/j.bmc.2018.10.001

文献信息

• [EN] AURISTATIN DERIVATIVES AND CONJUGATES THEREOF<br/>[FR] DÉRIVÉS D'AURISTATINE ET CONJUGUÉS DE CEUX-CI
  申请人：NOVARTIS AG

  公开号：WO2015189791A1

  公开（公告）日：2015-12-17

  Disclosed herein are novel compounds of formula (I) as described herein, and the use of such peptides in making immunoconjugates (i.e Antibody Drug Conjugates) Also described herein are immunoconjugates (i.e Antibody Drug Conjugates) comprising such novel compound linked to an antigen binding moiety, such as an antibody; where such immunoconjugates are useful for treating cell proliferative disorders. The invention further provides pharmaceutical compositions comprising these immunoconjugates, compositions comprising the immunoconjugates with a therapeutic co-agent, and methods to use these immunoconjugates and compositions for treating cell proliferation disorders.

  本文披露了如下所述的化合物(I)的新颖化合物，以及在制备免疫结合物（即抗体药物结合物）中使用这些肽的用途。本文还描述了包括这种新颖化合物与抗原结合基团（如抗体）连接的免疫结合物（即抗体药物结合物），这些免疫结合物可用于治疗细胞增殖性疾病。该发明还提供了包括这些免疫结合物的药物组合物，包括与治疗性辅助剂一起的免疫结合物的组合物，以及使用这些免疫结合物和组合物治疗细胞增殖性疾病的方法。
• [EN] ANTIBODY DRUG CONJUGATES<br/>[FR] CONJUGUÉS ANTICORPS-MÉDICAMENT
  申请人：NOVARTIS AG

  公开号：WO2016203432A1

  公开（公告）日：2016-12-22

  This application discloses anti-P-cadherin antibodies, antigen binding fragments thereof, and antibody drug conjugates of said antibodies or antigen binding fragments, particularly antibody drug conjugates comprising anti-P-cadherin antibodies conjugated to auristatin analogs. The invention also relates to methods of treating cancer using the antibody drug conjugates. Also disclosed herein are methods of making the antibodies, antigen binding fragments, and antibody drug conjugates, and methods of using the antibodies and antigen binding fragments as diagnostic reagents.

  该应用程序披露了抗P-钙粘蛋白抗体、其抗原结合片段，以及所述抗体或抗原结合片段的抗体药物偶联物，特别是包括与奥利司他汀类似物偶联的抗P-钙粘蛋白抗体的抗体药物偶联物。该发明还涉及使用抗体药物偶联物治疗癌症的方法。本文还披露了制备抗体、抗原结合片段和抗体药物偶联物的方法，以及将抗体和抗原结合片段用作诊断试剂的方法。
• Phosphinic Amino Acid Compounds
  申请人：Dive Vincent

  公开号：US20080153890A1

  公开（公告）日：2008-06-26

  Compounds of formula (I): wherein: R 1 represents hydrogen, alkylcarbonyloxyalkyl or alkylcarbonylthioalkyl, R 2 represents hydrogen, alkylcarbonyloxyalkyl, arylcarbonylthioalkyl or optionally substituted arylalkyl, R 3 represents phenyl, which is optionally substituted, or indolyl, their isomers, and addition salts thereof with a pharmaceutically acceptable acid or base. Medicinal products containing the same which are useful in the treatment of arterial hypertension and complications thereof.

  式(I)的化合物：其中：R1代表氢、烷基羰基氧烷基或烷基羰基硫烷基，R2代表氢、烷基羰基氧烷基、芳基羰基硫烷基或可选择取代的芳基烷基，R3代表苯基（可选择取代）或吲哚基，它们的异构体以及与药学上可接受的酸或碱形成的加合物。含有这些化合物的药物，用于治疗动脉高血压及其并发症。
• Practical Synthesis of Phosphinic Dipeptides by Tandem Esterification of Aminophosphinic and Acrylic Acids under Silylating Conditions
  作者：Paraskevi Kokkala、Kostas Voreakos、Angelos Lelis、Konstantinos Patiniotis、Nikolaos Skoulikas、Laurent Devel、Angeliki Ziotopoulou、Eleni Kaloumenou、Dimitris Georgiadis

  DOI：10.3390/molecules27041242

  日期：——

  acrylic acids and (R)-α-aminophosphinic acids, and high yields were achieved in all cases. In most examples reported herein, the isolation of biologically relevant (R,S)-diastereoisomers became possible by simple crystallization from the crude products, thus enhancing the operational simplicity of the proposed method. Finally, functional groups corresponding to acidic or basic natural amino acids are also

  在本报告中，提出了一种制备 5 型次膦酸二肽的合成方案。这些化合物可作为开发药用相关锌金属蛋白酶和天冬氨酰蛋白酶的高效膦肽抑制剂的重要组成部分。所提出的方法基于 α-氨基次膦酸和丙烯酸在甲硅烷基化条件下的串联酯化，以便随后参与 P-Michael 反应。通过使用多种容易获得的丙烯酸和 (R)-α-氨基次膦酸来研究转化的范围，并且在所有情况下都实现了高产率。在本文报道的大多数例子中，生物学相关的 (R,S)-非对映异构体的分离成为可能通过从粗产物中简单结晶，从而提高了所提出方法的操作简单性。最后，对应于酸性或碱性天然氨基酸的官能团也与反应条件相容。基于以上所述，我们预计所提出协议的实用性将有助于发现药理上有用的生物活性次膦酸肽。
• Diastereoselective Solution and Multipin-Based Combinatorial Array Synthesis of a Novel Class of Potent Phosphinic Metalloprotease Inhibitors
  作者：Anastasios Makaritis、Dimitris Georgiadis、Vincent Dive、Athanasios Yiotakis

  DOI：10.1002/chem.200204456

  日期：2003.5.9

  preparation of a novel class of isoxazole-containing phosphinic peptides (peptides 5 a-i). Solid-phase version of this strategy was efficiently achieved on multipin solid technology, by developing a new protocol for the coupling of P-unprotected dipeptidic blocks with solid supported amino acids in a quantitative and diastereoselective manner. Optimization of dipolar cycloadditions onto pin-embodied

  以高收率和光学纯度（3 ad单元）实现了含有三键的新膦肽肽结构单元的溶液相合成和拆分。通过NMR研究明确地确定了目标化合物的绝对构型。这些嵌段的组装后多样化策略是通过各种原位制备的腈氧化物的1，3-偶极环加成反应开发的。该策略导致快速有效地非对映选择性地制备了新型的含异恶唑的次膦酸肽（肽5 ai）。通过开发一种新的方案，可以定量和非对映选择性地将P-未保护的二肽嵌段与固体负载的氨基酸偶联，从而在多针固体技术上有效地实现了该策略的固相形式。偶极次膦肽上偶极环加成反应的优化使得可以方便地制备这种新型的伪肽。如通过RP-HPLC测定，以高产率和纯度获得粗品次膦肽（9ak）。这些肽中的某些的抑制分析表明，它们在效力方面表现出非常强的MMP抑制剂的性能，与以前报道的次膦酸酯肽相媲美（K（i）在几nM范围内）。