Duocarmazine | 1345681-58-4

• 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: Duocarmazine
• 英文别名: [(1S)-1-(chloromethyl)-3-[6-[(4-hydroxybenzoyl)amino]imidazo[1,2-a]pyridine-2-carbonyl]-9-methyl-1,2-dihydrobenzo[e]indol-5-yl] N-[2-[[4-[[(2S)-5-(carbamoylamino)-2-[[(2S)-2-[2-[2-(2,5-dioxopyrrol-1-yl)ethoxy]ethoxycarbonylamino]-3-methylbutanoyl]amino]pentanoyl]amino]phenyl]methoxycarbonyl-methylamino]ethyl]-N-[2-(2-hydroxyethoxy)ethyl]carbamate
• CAS: 1345681-58-4
• 化学式: C₆₅H₇₅ClN₁₂O₁₇
• 分子量: 1331.8
• InChiKey: RFQYSAASDBNNDZ-UCGHAGIGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  95
• 可旋转键数：
  34
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  374
• 氢给体数：
  8
• 氢受体数：
  18

文献信息

• [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] IMPROVED PROCESS FOR THE SYNTHESIS OF LINKER-DRUG VC-SECO-DUBA<br/>[FR] PROCÉDÉ AMÉLIORÉ POUR LA SYNTHÈSE DE MÉDICAMENT-LIEUR DE VC-SECO-DUBA
  申请人：SYNTHON BIOPHARMACEUTICALS BV

  公开号：WO2019101850A1

  公开（公告）日：2019-05-31

  The present invention relates to an improved process for the synthesis of linker-drug vc-seco-DUBA and its intermediates, as well as to the use of said improved process in a process for preparing an antibody-drug conjugate comprising the vc-seco-DUBA linker-drug.

  本发明涉及一种改进的链接剂药物vc-seco-DUBA及其中间体的合成过程，以及在制备含vc-seco-DUBA链接剂药物的抗体-药物结合物的过程中使用所述改进过程的方法。
• Method for purifying Cys-linked antibody-drug conjugates
  申请人：SYNTHON BIOPHARMACEUTICALS B.V.

  公开号：US10266606B2

  公开（公告）日：2019-04-23

  The present invention relates to a method for purifying a mixture of cysteine-linked antibody-drug conjugates, wherein the amount of non-conjugated antibody is in the range of 0-40% by weight, using hydrophobic interaction chromatography (HIC). The mixture is loaded onto a preparative HIC column using a 0.2-1.5 M aqueous salt solution, in which non-conjugated antibody is collected in a flow-through fraction, followed by elution of a purified mixture of cysteine-linked antibody-drug conjugates using a 0-100 mM aqueous salt solution.

  本发明涉及一种利用疏水相互作用色谱法（HIC）纯化半胱氨酸连接抗体-药物共轭物混合物的方法，其中非结合抗体的量按重量计在 0-40% 的范围内。使用 0.2-1.5 M 的水盐溶液将混合物装载到制备型疏水相互作用色谱柱上，在流过部分收集非结合抗体，然后使用 0-100 mM 的水盐溶液洗脱纯化的半胱氨酸连接抗体-药物共轭物混合物。
• B7-H3 binding molecules, antibody drug conjugates thereof and methods of use thereof
  申请人：MacroGenics, Inc.

  公开号：US10961311B2

  公开（公告）日：2021-03-30

  The present invention is directed to novel B7-H3-binding molecules capable of binding to human and non-human B7-H3, and in particular to such molecules that are cross-reactive with B7-H3 of a non-human primate (e.g., a cynomolgus monkey). The invention additionally pertains to B7-H3-binding molecules that comprise Variable Light Chain and/or Variable Heavy Chain (VH) Domains that have been humanized and/or deimmunized so as to exhibit a reduced immunogenicity upon administration to recipient subjects. The invention particularly pertains to bispecific, trispecific or multispecific B7-H3-binding molecules, including bispecific diabodies, BiTEs, bispecific antibodies, trivalent binding molecules, etc. that comprise: (i) such B7-H3-binding Variable Domains and (ii) a domain capable of binding to an epitope of a molecule present on the surface of an effector cell. The invention is also directed to pharmaceutical compositions that contain any of such B7-H3-binding molecules, and to methods involving the use of any of such B7-H3-binding molecules in the treatment of cancer and other diseases and conditions. The invention also particularly pertains to a molecule that comprises the human B7-H3 binding domain of a humanized anti-human B7-H3 antibody conjugated to at least one drug moiety (a “B7-H3-ADC”). The invention is also directed to pharmaceutical compositions that contain such B7-H3-ADCs, and to methods involving the use of any of such B7-H3-ADCs in the treatment of cancer and other diseases and conditions.

  本发明涉及能够与人类和非人类 B7-H3 结合的新型 B7-H3 结合分子，特别是与非人灵长类动物（如猕猴）的 B7-H3 具有交叉反应的分子。此外，本发明还涉及包含可变轻链和/或可变重链（VH）域的 B7-H3 结合分子，这些分子已被人源化和/或去免疫化，以便在给受试者用药时显示出较低的免疫原性。本发明尤其涉及双特异性、三特异性或多特异性 B7-H3 结合分子，包括双特异性二抗体、双特异性抗体、双特异性抗体、三价结合分子等，这些分子包含：(i) 这种 B7-H3 结合可变区；(ii) 能够与效应细胞表面存在的分子表位结合的结构域。本发明还涉及含有任何此类 B7-H3 结合分子的药物组合物，以及涉及使用任何此类 B7-H3 结合分子治疗癌症及其他疾病和病症的方法。本发明还特别涉及一种分子，该分子包括与至少一种药物分子（"B7-H3-ADC"）共轭的人源化抗人 B7-H3 抗体的人 B7-H3 结合域。本发明还涉及含有此类 B7-H3-ADC 的药物组合物，以及涉及使用任何此类 B7-H3-ADC 治疗癌症及其他疾病和病症的方法。
• Conjugates of CC-1065 analogs and bifunctional linkers
  申请人：SYNTARGA BV

  公开号：US11052155B2

  公开（公告）日：2021-07-06

  This invention relates to novel analogs of the DNA-alkylating agent CC-1065 and to their conjugates. Furthermore this invention concerns intermediates for the preparation of said agents and 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 DNA 烷基化剂 CC-1065 的新型类似物及其共轭物。此外，本发明还涉及制备上述制剂和共轭物的中间体。这些共轭物的设计目的是在一个或多个活化步骤之后和/或以共轭物控制的速率和时间跨度释放它们的（多重）有效载荷，以便选择性地递送和/或可控地释放一种或多种所述 DNA 烷化剂。这些制剂、共轭物和中间体可用于治疗以不希望的（细胞）增殖为特征的疾病。例如，本发明的制剂和共轭物可用于治疗肿瘤。