cyclo[Ala-D-Phe-Phe-DL-Pro-Pro-Phe-D-Phe-Val-DL-Pro-Pro] | 16898-32-1

• 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: cyclo[Ala-D-Phe-Phe-DL-Pro-Pro-Phe-D-Phe-Val-DL-Pro-Pro]
• 英文别名: (9S,12R,15S,18S,30S,33R,36S,39S)-9,12,33,36-tetrabenzyl-15-methyl-30-propan-2-yl-1,7,10,13,16,22,28,31,34,37-decazapentacyclo[37.3.0.03,7.018,22.024,28]dotetracontane-2,8,11,14,17,23,29,32,35,38-decone
• CAS: 16898-32-1
• 化学式: C₆₄H₇₈N₁₀O₁₀
• 分子量: 1147.4
• InChiKey: WTINJQXJTHUFRF-XMNAFNJFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  84
• 可旋转键数：
  9
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  256
• 氢给体数：
  6
• 氢受体数：
  10

文献信息

• [EN] MACROCYCLIZATION OF PEPTIDOMIMETICS<br/>[FR] MACROCYCLISATION DE PEPTIDOMIMÉTIQUES
  申请人：UNIV WARWICK

  公开号：WO2019186174A1

  公开（公告）日：2019-10-03

  The invention provides an improved method of macrocyclization of peptidomimetics, as measured by isolated yields and product distribution, which comprises substitution of one or more of the backbone amide C=O bonds with a turn-inducing motif. The method is general with enhancements seen across a range of ring sizes (e.g. tri-, tetra-, penta- and hexapeptides). Specifically, the invention provides a peptidomimetic macrocycle comprising a carbonyl bioisosteric turn-inducing element having the structure: (I) wherein X is a heteroatom; and wherein R1 to R6 are each independently selected from alkyl, aryl, heteroaryl and H.

  该发明提供了一种改进的肽类类似物的大环化方法，通过孤立产量和产物分布来衡量，其中包括用诱导转向基团替代一个或多个骨架酰胺C=O键。该方法是通用的，在一系列环大小（例如三肽、四肽、五肽和六肽）中均可见到增强效果。具体而言，该发明提供了一种包含具有结构的羰基生物等同体诱导转向元素的肽类类似物大环：（I）其中X是杂原子；其中R1至R6分别独立地选自烷基、芳基、杂芳基和氢。
• [EN] AMANITIN ANTIBODY CONJUGATES<br/>[FR] CONJUGUÉS D'ANTICORPS À BASE D'AMANITINE
  申请人：HEIDELBERG PHARMA RES GMBH

  公开号：WO2018115466A1

  公开（公告）日：2018-06-28

  The invention relates to a conjugate comprising (a) an amatoxin comprising (i) an amino acid 4 with a 6'-deoxy position; and (ii) an amino acid 8 with an S-deoxy position; (b) a BCMA-binding moiety comprising (i) the variable domains of humanized antibody J22.9-ISY, and (ii) a heavy chain constant region comprising a D265C mutation; and (c) a protease-cleavable linker linking said amatoxin and said target-binding moiety. The invention furthermore relates to a pharmaceutical composition comprising such conjugate, particularly for use in the treatment of multiple myeloma.

  该发明涉及一种共轭物，包括(a) 包含(i) 具有6'-去氧位的氨基酸4；和(ii) 具有S-去氧位的氨基酸8 的毒蕈碱；(b) 包括(i) 人源化抗体J22.9-ISY的可变区域；和(ii) 包括D265C突变的重链常数区域的BCMA结合基团；以及(c) 连接所述毒蕈碱和目标结合基团的蛋白酶可切割连接物。该发明还涉及包括这种共轭物的药物组合物，特别用于治疗多发性骨髓瘤。
• [EN] ANTIBODY DRUG CONJUGATES WITH CLEAVABLE LINKERS<br/>[FR] CONJUGUÉS ANTICORPS-MÉDICAMENT POURVUS DE LIEURS CLIVABLES
  申请人：HEIDELBERG PHARMA RES GMBH

  公开号：WO2020234461A1

  公开（公告）日：2020-11-26

  The present invention relates to prodrugs comprising a linker comprising five- or six-membered cyclic acetals and an adjacent specific cleavage site, and to precursor compounds for the synthesis of said prodrugs. In one aspect the present invention relates to antibody-targeted amatoxin conjugates comprising said linkers, to methods for their synthesis, and to the use of said antibody-targeted amatoxin conjugates. In a further aspect, the invention relates to pharmaceutical compositions comprising said conjugates, and to the use of said conjugates or compositions for therapeutic purposes, in particular for tumor therapy and oncology.

  本发明涉及包含具有五元或六元环缩醛的连接物以及相邻特定裂解位点的前药，以及用于合成所述前药的前体化合物。在一个方面，本发明涉及包含所述连接物的抗体靶向阿毛氧素结合物，以及其合成方法和所述抗体靶向阿毛氧素结合物的应用。在另一个方面，该发明涉及包含所述结合物的药物组合物，以及用于治疗目的，特别是用于肿瘤治疗和肿瘤学的所述结合物或组合物的应用。
• Amatoxin-Armed Therapeutic Cell Surface Binding Components Designed for Tumour Therapy
  申请人：Faulstich Heinz

  公开号：US20120100161A1

  公开（公告）日：2012-04-26

  The invention relates to tumour therapy. In one aspect, the present invention relates to conjugates of a toxin and a target-binding moiety, e.g. an antibody, which are useful in the treatment of cancer. In particular, the toxin is an amatoxin, and the target-binding moiety is preferably directed against tumour-associated antigens. In particular, the amatoxin is conjugated to the antibody by linker moieties. In particular the linker moieties are covalently bound to functional groups located in positions of the amatoxin proved as preferred positions for the attachment of linkers with respect to optimum antitumor activity. In a further aspect the invention relates to pharmaceutical compositions comprising such target-binding moiety toxin conjugates and to the use of such target-binding moiety toxin conjugates for the preparation of such pharmaceutical compositions. The target-binding moiety toxin conjugates and pharmaceutical compositions of the invention are useful for the treatment of cancer.

  本发明涉及肿瘤治疗。在一个方面，本发明涉及毒素和靶向结合基团（例如抗体）的共轭物，其在癌症治疗中有用。特别地，毒素是一种阿马毒素，靶向结合基团首选针对肿瘤相关抗原。特别地，阿马毒素通过连接基团与抗体结合。特别地，连接基团是共价结合到阿马毒素中被证明是最佳抗肿瘤活性的位置上的功能基团。在另一个方面，本发明涉及包括这样的靶向结合基团毒素共轭物的制药组合物，并且涉及使用这样的靶向结合基团毒素共轭物制备这样的制药组合物。本发明的靶向结合基团毒素共轭物和制药组合物对于肿瘤治疗有用。
• Amatoxin-Armed Tartget-Binding Moieties for the Treatment of Cancer
  申请人：Faulstich Heinz

  公开号：US20120213805A1

  公开（公告）日：2012-08-23

  The invention relates to tumour therapy. In one aspect, the present invention relates to conjugates of target-binding moieties and toxins that are useful in the treatment of cancer. In particular, the toxin is an amatoxin, and the target-binding moieties (e.g. antibodies) are directed against tumour-associated antigens, such as epithelial cell adhesion molecule (EpCAM). In a further aspect the invention relates to pharmaceutical compositions comprising such target-binding moiety toxin conjugates and to the use of such target-binding moiety toxin conjugates for the preparation of such pharmaceutical compositions. The target-binding moiety toxin conjugates and pharmaceutical compositions of the invention are useful for the treatment of cancer, in particular adenocarcinoma, such as pancreatic cancer, cholangiocarcinoma, breast cancer, and colorectal cancer.

  本发明涉及肿瘤治疗。在一个方面，本发明涉及靶向结合物和毒素的共轭物，其在癌症治疗中有用。特别地，毒素是阿马毒素，而靶向结合物（例如抗体）针对肿瘤相关抗原，如上皮细胞粘附分子（EpCAM）。在另一个方面，本发明涉及包括这种靶向结合物毒素共轭物的制药组合物以及使用这种靶向结合物毒素共轭物制备这种制药组合物的用途。本发明的靶向结合物毒素共轭物和制药组合物对于癌症治疗有用，特别是腺癌，如胰腺癌、胆管癌、乳腺癌和结肠直肠癌。