D-Ala-Phe-Lys | 99264-74-1

• 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: D-Ala-Phe-Lys
• 英文别名: H-D-Ala-Phe-Lys-OH；(2S)-6-amino-2-[[(2S)-2-[[(2R)-2-aminopropanoyl]amino]-3-phenylpropanoyl]amino]hexanoic acid
• CAS: 99264-74-1
• 化学式: C₁₈H₂₈N₄O₄
• 分子量: 364.445
• InChiKey: WEZNQZHACPSMEF-SNPRPXQTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.6
• 重原子数：
  26
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  148
• 氢给体数：
  5
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  D-Ala-Phe-Lys 在 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 5.0h， 生成 Z-D-Ala-Phe-Lys(Z)-N(Me)-(CH2)2-N(Me)-Boc
  参考文献：
  名称：

  Synthesis and Biological Evaluation of 2‘-Carbamate-Linked and 2‘-Carbonate-Linked Prodrugs of Paclitaxel:  Selective Activation by the Tumor-Associated Protease Plasmin

  摘要：

  The nontoxic paclitaxel-2'-carbamate prodrugs 2-5 and paclitaxel-2'-carbonate prodrug 6 were synthesized and tested for activation by the tumor-associated enzyme plasmin. A generally applicable method for the synthesis of paditaxel-2'-carbamates was developed. In buffer solution, prodrug 2, which contained an unsubstituted ethylenediamine spacer, was not stable, whereas prodrugs 3-6 were highly stable. Prodrugs 3-6 showed on average a decrease in cytotoxicity of more than 8000-fold in comparison with the parent drug in seven human tumor cell lines. Prodrugs 5 and 6 are the most nontoxic prodrugs of paclitaxel that yield the free parent drug upon selective activation currently reported. Enzyme hydrolysis and spacer elimination rates were determined by incubation of prodrugs 5 and 6 in the presence of human plasmin. From these results, prodrug 6 was selected as the promising prodrug for further in vivo studies.

  DOI：

  10.1021/jm0009078
• 作为产物：
  描述：

  Z-D-Ala-Phe-Lys(Z)-OH 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 、 水 为溶剂， 生成 D-Ala-Phe-Lys
  参考文献：
  名称：

  Markowska, Agnieszka; Midura-Nowaczek, Krystyna; Bruzgo, Irena, Acta poloniae pharmaceutica, 2007, vol. 64, # 4, p. 355 - 358

  摘要：

  DOI：

文献信息

• Water-Soluble CC-1065 Analogs and Their Conjugates
  申请人：Beusker Patrick Henry

  公开号：US20090318668A1

  公开（公告）日：2009-12-24

  This invention relates to novel analogs of the DNA-binding alkylating agent CC-1065 and to their conjugates. Furthermore this invention concerns intermediates for the preparation of said agents and their conjugates. The conjugates are designed to release their (multiple) payload after one or more activation steps and/or at a rate and time span controlled by the conjugate in order to selectively deliver and/or controllably release one or more of said DNA alkylating agents. The agents, conjugates, and intermediates can be used to treat an illness that is characterized by undesired (cell) proliferation. As an example, the agents and the conjugates of this invention may be used to treat a tumor.

  这项发明涉及DNA结合烷基化剂CC-1065的新型类似物及其结合物。此外，该发明涉及用于制备上述剂和它们的结合物的中间体。这些结合物设计为在一个或多个激活步骤之后以及/或由结合物控制的速率和时间跨度下释放它们的（多种）荷载，以便选择性地传递和/或可控地释放一个或多个所述的DNA烷基化剂。这些剂、结合物和中间体可用于治疗以不良（细胞）增殖为特征的疾病。例如，这项发明的剂和结合物可用于治疗肿瘤。
• Triazole-Containing Releasable Linkers, Conjugates Thereof, and Methods of Preparation
  申请人：Beusker Patrick Henry

  公开号：US20080311136A1

  公开（公告）日：2008-12-18

  This invention relates to compounds comprising one or more therapeutic and/or diagnostic moieties and one or more functional moieties linked together via one or more triazole-containing linkers and to their intermediates and methods of their preparation. The triazole-containing linker may optionally contain one or more conditionally-cleavable or conditionally-transformable moieties and one or more spacer systems in between said moiety/moieties and the one or more therapeutic and/or diagnostic moieties.

  本发明涉及一种化合物，其中包含一个或多个治疗和/或诊断基团，以及一个或多个功能基团，通过一个或多个三唑含链连接在一起，以及它们的中间体和制备方法。三唑含链连接物可以选择性地包含一个或多个有条件可裂解或有条件可转化的基团，以及一个或多个间隔系统，位于所述基团和一个或多个治疗和/或诊断基团之间。
• [EN] PROCESS FOR THE PREPARATION OF MONO-PROTECTED alpha,omega-DIAMINO ALKANES<br/>[FR] PROCÉDÉ DE PRÉPARATION D'ALPHA, OMÉGA-DIAMINO ALCANES MONO-PROTÉGÉS
  申请人：SYNTHON BIOPHARMACEUTICALS BV

  公开号：WO2018086993A1

  公开（公告）日：2018-05-17

  The present invention relates to a process for the synthesis of mono-protected α,ω-diamino alkanes, the use of said proces in a process for the synthesis of a linker drug comprising an α,ω-diamino alkane moiety and the use of the process of the present invention in a process for preparing an antibody-drug conjugate comprising an α,ω-diamino alkane moiety.

  本发明涉及一种合成单保护的α，ω-双氨基烷的方法，以及该方法在合成含有α，ω-双氨基烷基团的连接药物的过程中的应用，以及本发明方法在制备含有α，ω-双氨基烷基团的抗体药物结合物的过程中的应用。
• [EN] SUBSTITUTED CC-1065 ANALOGS AND THEIR CONJUGATES<br/>[FR] ANALOGUES CC-1065 SUBSTITUÉS ET LEURS CONJUGUÉS
  申请人：SYNTARGA BV

  公开号：WO2009017394A1

  公开（公告）日：2009-02-05

  This invention relates to novel agents that are analogs of the DNA-alkylating agent CC-1065 and to their conjugates. Furthermore this invention concerns intermediates for the preparation of said agents and their conjugates. The conjugates are designed to release their (multiple) payload after one or more activation steps and/or at a rate and time span controlled by the conjugate in order to selectively deliver and/or controllably release one or more of said DNA alkylating agents. The agents, conjugates, and intermediates can be used to treat an illness that is characterized by undesired (cell) proliferation. As an example, the agents and the conjugates of this invention may be used to treat a tumor.

  本发明涉及一种与DNA-烷基化剂CC-1065类似的新型剂，以及它们的共轭物。此外，本发明涉及用于制备所述剂和它们的共轭物的中间体。共轭物被设计为在一个或多个激活步骤后释放它们的（多个）有效载荷和/或由共轭物控制的速率和时间跨度，以有选择地传递和/或可控释放一个或多个所述的DNA烷基化剂。这些剂、共轭物和中间体可用于治疗其特征为不受欢迎的（细胞）增殖的疾病。例如，本发明的剂和共轭物可用于治疗肿瘤。
• [EN] ELONGATED AND MULTIPLE SPACERS IN ACTIVATIBLE PRODRUGS<br/>[FR] ESPACEURS ALLONGES ET MULTIPLES DE PRODROGUES ACTIVABLES
  申请人：DE GROOT FRANCISCUS MARINUS HE

  公开号：WO2002083180A1

  公开（公告）日：2002-10-24

  This invention is directed to prodrugs that can be activated at the preferred site of action in order to selectively deliver the corresponding therapeutic parent drugs to target cells or to the target site. This invention will therefore primarily but not exclusively relate to tumor cells as target cells. More specifically the prodrugs are compounds of the formula V-(W)k-(X)1-A-Z, wherein: V is a specifier; (W)k-(X)1-A is an elongated self-elimination spacer system; W and X are each a 1,(4+2n) electronic cascade spacer, being the same or different; A is either a spacer group of formula (Y)m wherein: Y is a 1,(4+2n) electronic cascade spacer, or a group of formula U being a cyclisation elimination spacer; Z is a therapeutic drug; k, 1 and m are integers from 0 (included) to 5 (included); n is an integer of 0 (included) to 10 (included), with the provisos that: - when A is (Y)m: k+1+m ≥ 1, and if k+1+m = 1; - when A is U: k+1 ≥ 1.

  本发明涉及一种前药，可以在首选作用部位激活，以有选择地将相应的治疗母药物传递到目标细胞或目标部位。因此，本发明主要但不仅限于将肿瘤细胞作为目标细胞。更具体地，前药是化合物V-(W)k-(X)1-A-Z，其中：V是说明符；(W)k-(X)1-A是一个延长的自我消除间隔系统；W和X分别是1，（4+2n）电子级联间隔器，相同或不同；A是公式（Y）m的间隔基团，其中：Y是1，（4+2n）电子级联间隔器，或者是公式U的基团，是环化消除间隔器；Z是治疗药物；k，1和m是从0（包括）到5（包括）的整数；n是0（包括）到10（包括）的整数，但前提是：当A为（Y）m时：k+1+m≥1，如果k+1+m=1；当A为U时：k+1≥1。