Z-Val-Val-MeVal-Pro-OH | 172837-42-2

• 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: Z-Val-Val-MeVal-Pro-OH
• 英文别名: (2S)-1-[(2S)-3-methyl-2-[methyl-[(2S)-3-methyl-2-[[(2S)-3-methyl-2-(phenylmethoxycarbonylamino)butanoyl]amino]butanoyl]amino]butanoyl]pyrrolidine-2-carboxylic acid
• CAS: 172837-42-2
• 化学式: C₂₉H₄₄N₄O₇
• 分子量: 560.691
• InChiKey: VKIXFGCGRNUELQ-ZJZGAYNASA-N

物化性质

• 沸点：
  786.8±60.0 °C(Predicted)
• 密度：
  1.185±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  40
• 可旋转键数：
  13
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  145
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Z-Val-Val-MeVal-Pro-OH 在 氢溴酸 、 溶剂黄146 、 N,N-二异丙基乙胺 、 bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 (2R,3R)-3-Methoxy-2-methyl-N-((S)-2-phenyl-1-thiazol-2-yl-ethyl)-3-[(S)-1-((S)-pyrrolidine-2-carbonyl)-pyrrolidin-2-yl]-propionamide
  参考文献：
  名称：

  Synthesis and Biological Activity of Chimeric Structures Derived from the Cytotoxic Natural Compounds Dolastatin 10 and Dolastatin 15

  摘要：

  The natural cytotoxic compounds dolastatins 10 and 15 exhibit great similarities in structure and in their biological activity profiles. Two compounds (1 and 2) formed by interchanging the dolaisoleuine residue of dolastatin 10 and the MeVal-Pro dipeptide of dolastatin 15 were synthesized in order to evaluate the possible equivalence of these units. These compounds can be considered as chimeras of dolastatins 10 and 15 formed by the N-terminal part of the former and the C-terminal part of the latter and vice versa. Both analogues exhibited a marked decrease in their cytotoxic activity but showed similar differential cytotoxicity with regard to the cell Lines assayed compared with the parent compounds. HT-29 cell line was the least sensitive one. However, this activity was in the nanomolar level and close to that of vincristine. The differences in their effect on tubulin polymerization were less pronounced. We confirmed the already known crucial role of the Dil residue in this assay. The nonequivalence of the Dil unit and the MeVal-Pro dipeptide probably reflects modification in the relative positions of the N-dimethylamino and the phenyl moieties.

  DOI：

  10.1021/jm970800t
• 作为产物：
  描述：

  N-苄氧羰基-N-甲基-L-缬氨酸 在 palladium on activated charcoal 盐酸 、 氢气 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 25.0 ℃ 、101.33 kPa 条件下， 反应 40.0h， 生成 Z-Val-Val-MeVal-Pro-OH
  参考文献：
  名称：

  Synthesis and Biological Activity of Chimeric Structures Derived from the Cytotoxic Natural Compounds Dolastatin 10 and Dolastatin 15

  摘要：

  The natural cytotoxic compounds dolastatins 10 and 15 exhibit great similarities in structure and in their biological activity profiles. Two compounds (1 and 2) formed by interchanging the dolaisoleuine residue of dolastatin 10 and the MeVal-Pro dipeptide of dolastatin 15 were synthesized in order to evaluate the possible equivalence of these units. These compounds can be considered as chimeras of dolastatins 10 and 15 formed by the N-terminal part of the former and the C-terminal part of the latter and vice versa. Both analogues exhibited a marked decrease in their cytotoxic activity but showed similar differential cytotoxicity with regard to the cell Lines assayed compared with the parent compounds. HT-29 cell line was the least sensitive one. However, this activity was in the nanomolar level and close to that of vincristine. The differences in their effect on tubulin polymerization were less pronounced. We confirmed the already known crucial role of the Dil residue in this assay. The nonequivalence of the Dil unit and the MeVal-Pro dipeptide probably reflects modification in the relative positions of the N-dimethylamino and the phenyl moieties.

  DOI：

  10.1021/jm970800t

文献信息

• Dolastatin-15 derivatives in combination with taxanes
  申请人：BASF Aktiengesellschaft

  公开号：US06103698A1

  公开（公告）日：2000-08-15

  The present invention provides compositions and methods for the treatment of cancer in a subject wherein compounds of Formula I as defined herein in combination with paclitaxel, taxotere or modified taxane or taxoid analogs provide enhanced anticancer effects over the effects achieved with the individual compounds.

  本发明提供了一种用于治疗患者癌症的组合物和方法，其中公式I中定义的化合物与紫杉醇、紫杉醇衍生物或类似物结合使用，可以比单独使用这些化合物更有效地产生抗癌效果。
• Antineoplastic peptides
  申请人：BASF Aktiengesellschaft Germany

  公开号：US20010009901A1

  公开（公告）日：2001-07-26

  The present invention provides antineoplastic peptides of formula I, R 1 R 2 N-CHX-CO-A-B-D-E-(G) s -K  I wherein R 1 , R 2 , X, A, B, D, E, G, K and s have the meanings stated in the description. The compounds have antineoplastic activity.

  本发明提供了式I的抗肿瘤肽，其中R1R2N-CHX-CO-A-B-D-E-(G)s-K  I，其中R1、R2、X、A、B、D、E、G、K和s的含义如说明书所述。这些化合物具有抗肿瘤活性。
• Antitumor peptides
  申请人：BASF Aktiengesellschaft

  公开号：US05831002A1

  公开（公告）日：1998-11-03

  Novel compounds of the formula R.sup.1 R.sup.2 N--CHX-CO-A-B-D-(E).sub.s -(F).sub.t -(G).sub.U -KI in which R.sup.1, R.sup.2, A, B, D, E, F, G, K, X, s, t, and u have the meanings stated in the description, and the preparation thereof are described. The novel substances have an antineoplastic effect.

  本发明涉及一种新型化合物，其化学式为R.sup.1 R.sup.2 N--CHX-CO-A-B-D-(E).sub.s -(F).sub.t -(G).sub.U -KI，其中R.sup.1，R.sup.2，A，B，D，E，F，G，K，X，s，t和u的含义如说明书所述，并且还描述了其制备方法。这些新型物质具有抗肿瘤作用。
• Methods and compositions for treating rheumatoid arthritis
  申请人：BASF Aktiengesellschaft

  公开号：US06015790A1

  公开（公告）日：2000-01-18

  The present invention provides compositions and methods for the treatment of rheumatoid arthritis in a subject wherein one or more compounds of Formula I as defined herein alone or in combination with one or more other antiarthritic drugs provide suppression of rheumatoid arthritis.

  本发明提供了用于治疗风湿性关节炎的组合物和方法，其中本发明中所定义的一种或多种I式化合物单独或与一种或多种其他抗关节炎药物联合使用，可提供对风湿性关节炎的抑制。
• Synthesis and Biological Activity of Chimeric Structures Derived from the Cytotoxic Natural Compounds Dolastatin 10 and Dolastatin 15
  作者：Joël Poncet、Magali Busquet、Florence Roux、Alain Pierré、Ghanem Atassi、Patrick Jouin

  DOI：10.1021/jm970800t

  日期：1998.4.1

  The natural cytotoxic compounds dolastatins 10 and 15 exhibit great similarities in structure and in their biological activity profiles. Two compounds (1 and 2) formed by interchanging the dolaisoleuine residue of dolastatin 10 and the MeVal-Pro dipeptide of dolastatin 15 were synthesized in order to evaluate the possible equivalence of these units. These compounds can be considered as chimeras of dolastatins 10 and 15 formed by the N-terminal part of the former and the C-terminal part of the latter and vice versa. Both analogues exhibited a marked decrease in their cytotoxic activity but showed similar differential cytotoxicity with regard to the cell Lines assayed compared with the parent compounds. HT-29 cell line was the least sensitive one. However, this activity was in the nanomolar level and close to that of vincristine. The differences in their effect on tubulin polymerization were less pronounced. We confirmed the already known crucial role of the Dil residue in this assay. The nonequivalence of the Dil unit and the MeVal-Pro dipeptide probably reflects modification in the relative positions of the N-dimethylamino and the phenyl moieties.