(2S,4R)-1-(((benzyloxy)carbonyl)-L-valyl)-4-hydroxypyrrolidine-2-carboxylic acid | 194033-06-2

• 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: (2S,4R)-1-(((benzyloxy)carbonyl)-L-valyl)-4-hydroxypyrrolidine-2-carboxylic acid
• 英文别名: N-benzyloxycarbonyl-L-valyl-4R-hydroxy-L-proline；Z-Val-Hyp-OH；Cbz-Val-Hyp-OH；(2S,4R)-4-hydroxy-1-[(2S)-3-methyl-2-(phenylmethoxycarbonylamino)butanoyl]pyrrolidine-2-carboxylic acid
• CAS: 194033-06-2
• 化学式: C₁₈H₂₄N₂O₆
• 分子量: 364.398
• InChiKey: ZFDPMERECAAAAR-ILXRZTDVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  116
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2S,4R)-1-(((benzyloxy)carbonyl)-L-valyl)-4-hydroxypyrrolidine-2-carboxylic acid 在 palladium on activated charcoal 氢气 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 20.0 ℃ 、172.37 kPa 条件下， 反应 26.0h， 生成 [1-[2',5'-bis-O-(tert-butyldimethylsilyl)-β-D-ribofuranosyl]-3-N-[3-N'-[valyl-(2S,4R)-4-hydroxyprolylamino]propyl]thymine]-3'-spiro-5''-[4''-amino-1'',2''-oxathiole-2'',2''-dioxide]
  参考文献：
  名称：

  Design and Discovery of a Novel Dipeptidyl-peptidase IV (CD26)-Based Prodrug Approach

  摘要：

  Here we describe a novel type of enzyme-based prodrug approach in which a dipeptide moiety is linked to a nonpeptidic therapeutic drug through an amide bond which is specifically cleaved by the dipeptidyl-peptidase IV ( DPP IV/CD26) enzyme activity present in plasma and on the surface of certain cells. DPP IV has high substrate selectivity for peptides with a proline ( or an alanine) at the penultimate amino acid position at the N-terminus but tolerates a wide range of natural amino acids at the amino terminal end. A variety of dipeptidyl amide prodrugs of anti-HIV TSAO molecules were synthesized and evaluated for their ability to act as substrates for the enzyme. Our data revealed that DPP IV/CD26 can efficiently recognize such prodrugs as substrates, releasing the parent compound. Moreover, it is possible to modify the half-life and the lipophilicity of the prodrugs by changing the nature of the dipeptide. All conjugates have shown marked in vitro antiviral activities irrespective the the nature of the terminal and/or the penultimate amino acid moiety.

  DOI：

  10.1021/jm0606490
• 作为产物：
  描述：

  CBZ-L-缬氨酸 在 sodium hydroxide 、 TEA 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 15.0h， 生成 (2S,4R)-1-(((benzyloxy)carbonyl)-L-valyl)-4-hydroxypyrrolidine-2-carboxylic acid
  参考文献：
  名称：

  Design and Discovery of a Novel Dipeptidyl-peptidase IV (CD26)-Based Prodrug Approach

  摘要：

  Here we describe a novel type of enzyme-based prodrug approach in which a dipeptide moiety is linked to a nonpeptidic therapeutic drug through an amide bond which is specifically cleaved by the dipeptidyl-peptidase IV ( DPP IV/CD26) enzyme activity present in plasma and on the surface of certain cells. DPP IV has high substrate selectivity for peptides with a proline ( or an alanine) at the penultimate amino acid position at the N-terminus but tolerates a wide range of natural amino acids at the amino terminal end. A variety of dipeptidyl amide prodrugs of anti-HIV TSAO molecules were synthesized and evaluated for their ability to act as substrates for the enzyme. Our data revealed that DPP IV/CD26 can efficiently recognize such prodrugs as substrates, releasing the parent compound. Moreover, it is possible to modify the half-life and the lipophilicity of the prodrugs by changing the nature of the dipeptide. All conjugates have shown marked in vitro antiviral activities irrespective the the nature of the terminal and/or the penultimate amino acid moiety.

  DOI：

  10.1021/jm0606490

文献信息

• [EN] MALT1 INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE MALT1 ET LEURS UTILISATIONS
  申请人：UNIV CORNELL

  公开号：WO2017040304A1

  公开（公告）日：2017-03-09

  Provided herein are compounds of Formula (I) and pharmaceutical compositions thereof, which may be useful as MALT1 inhibitors. Also provided are for the treatment of proliferative disorders (e.g., cancer (e.g., non-Hodgkin' s lymphoma, diffuse large B-cell lymphoma, MALT lymphoma), benign neoplasm, a disease associated with angiogenesis,an autoimmune disease, an inflammatory disease, an autoinflammatory disease) by administering a compound of Formula (I).

  本文提供了化合物的化学式(I)及其药物组合物，可用作MALT1抑制剂。还提供了通过给予化合物的化学式(I)来治疗增生性疾病（例如癌症（例如非霍奇金淋巴瘤、弥漫性大B细胞淋巴瘤、MALT淋巴瘤）、良性肿瘤、与血管生成有关的疾病、自身免疫疾病、炎症性疾病、自身炎症性疾病）的方法。
• MALT1 inhibitors and uses thereof
  申请人：Cornell University

  公开号：US10711036B2

  公开（公告）日：2020-07-14

  Provided herein are compounds of Formula (I) and pharmaceutical compositions thereof, which may be useful as MALT1 inhibitors. Also provided are for the treatment of proliferative disorders (e.g., cancer (e.g., non-Hodgkin's lymphoma, diffuse large B-cell lymphoma, MALT lymphoma), benign neoplasm, a disease associated with angiogenesis, an autoimmune disease, an inflammatory disease, an autoinflammatory disease) by administering a compound of Formula (I).

  本文提供的式(I)化合物及其药物组合物可用作 MALT1 抑制剂。还提供了通过施用式（I）化合物治疗增殖性疾病（如癌症（如非霍奇金淋巴瘤、弥漫大 B 细胞淋巴瘤、MALT 淋巴瘤）、良性肿瘤、与血管生成相关的疾病、自身免疫性疾病、炎症性疾病、自身炎症性疾病）。
• Peptide-based covalent inhibitors of MALT1 paracaspase
  作者：John M. Hatcher、Guangyan Du、Lorena Fontán、Ilkay Us、Qi Qiao、Spandan Chennamadhavuni、Jay Shao、Hao Wu、Ari Melnick、Nathanael S. Gray、David A. Scott

  DOI：10.1016/j.bmcl.2019.03.046

  日期：2019.6

  Potent and selective substrate-based covalent inhibitors of MALT1 protease were developed from the tetrapeptide tool compound Z-VRPR-fmk. To improve cell permeability, we replaced one arginine residue. We further optimized a series of tripeptides and identified compounds that were potent in both a GloSensor reporter assay measuring cellular MALT1 protease activity, and an OCI-Ly3 cell proliferation assay. Example compounds showed good overall selectivity towards cysteine proteases, and one compound was selected for further profiling in ABL-DLBCL cells and xenograft efficacy models.
• EP3341007B1
  申请人：——

  公开号：EP3341007B1

  公开（公告）日：2020-12-23
• Domino Process Achieves Site-Selective Peptide Modification with High Optical Purity. Applications to Chain Diversification and Peptide Ligation
  作者：Ivan Romero-Estudillo、Alicia Boto

  DOI：10.1021/acs.joc.5b00932

  日期：2015.10.2

  The development of peptide libraries by site-selective modification of a few parent peptides would save valuable time and materials in discovery processes but still is a difficult synthetic challenge. Herein, we introduce natural hydroxyproline as a convertible unit for the production of a variety of optically pure amino acids, including expensive N-alkyl amino acids, homoserine lactones, and Agl lactams, and to achieve the mild, efficient, and site-selective modification of peptides. A domino process is used to cleave the customizable Hyp unit under mild, metal-free conditions. Both terminal and internal positions can be modified, and similar customizable units can be differentiated. The resulting products possess two reactive chains which can be manipulated independently. The versatility and scope of this process is highlighted by its application to the ligation of two peptide chains, and the generation of peptides with several chains and peptides with conformational restrictions.