(9H-fluoren-9-yl)methyl (S)-(1-((4-(hydroxymethyl)phenyl)amino)-6-(((4-methoxyphenyl)diphenylmethyl)amino)-1-oxohexan-2-yl)carbamate | 450366-22-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: (9H-fluoren-9-yl)methyl (S)-(1-((4-(hydroxymethyl)phenyl)amino)-6-(((4-methoxyphenyl)diphenylmethyl)amino)-1-oxohexan-2-yl)carbamate
• 英文别名: Fmoc-Lys(Mmt)-aminobenzyl alcohol；9H-fluoren-9-ylmethyl N-[(2S)-1-[4-(hydroxymethyl)anilino]-6-[[(4-methoxyphenyl)-diphenylmethyl]amino]-1-oxohexan-2-yl]carbamate
• CAS: 450366-22-0
• 化学式: C₄₈H₄₇N₃O₅
• 分子量: 745.918
• InChiKey: LVWOSFVCKUKLDV-GWHBCOKCSA-N

物化性质

• 沸点：
  932.0±65.0 °C(Predicted)
• 密度：
  1.223±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  8.4
• 重原子数：
  56
• 可旋转键数：
  17
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  109
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (9H-fluoren-9-yl)methyl (S)-(1-((4-(hydroxymethyl)phenyl)amino)-6-(((4-methoxyphenyl)diphenylmethyl)amino)-1-oxohexan-2-yl)carbamate 在 二乙胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 (S)-2-((S)-2-氨基-3-苯基丙酰胺基)-N-(4-(羟甲基)苯基)-6-(((4-甲氧基苯基)二苯基甲基)氨基)己酰胺
  参考文献：
  名称：

  Synthesis of an immunoconjugate of camptothecin

  摘要：

  The first immunoconjugate of camptothecin has been synthesized wherein the drug is attached to the tumor-recognizing antibody BR96 via a Cathepsin B cleavable linker. Endocytosis of the immunoconjugate upon binding to the tumor cell followed by enzymatic cleavage of the linker inside the endosome ensures tumor-specific release of the drug. In this way, it is hoped that the dose-limiting side effects associated with camptothecin can be eliminated while the antitumor activity is preserved. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(01)00707-7
• 作为产物：
  描述：

  对氨基苯甲醇 在 2-乙氧基-1-乙氧碳酰基-1,2-二氢喹啉 作用下， 生成 (9H-fluoren-9-yl)methyl (S)-(1-((4-(hydroxymethyl)phenyl)amino)-6-(((4-methoxyphenyl)diphenylmethyl)amino)-1-oxohexan-2-yl)carbamate
  参考文献：
  名称：

  CONJUGATE IN WHICH FL118 DRUG IS LINKED TO ACID-SENSITIVE LINKER, AND IMMUNOCONJUGATE USING SAME

  摘要：

  The present invention relates to a conjugate in which FL118 is linked to an acid-sensitive linker, and an immunoconjugate using the same. The present invention is characterized in that at least one FL118 drug of Formula 1 is linked to an antibody or antigen-binding site-containing fragment thereof through an acid-sensitive linker; wherein after being targeted to cancer cells by an antigen-binding site that targets an antigen of cancer cells, the acid-sensitive linker is degraded in acidic atmosphere around cancer (pH≤7) to free at least a part of the FL118 drug of Formula 1 and the free FL118 drug of Formula 1 penetrates a cell membrane and moves into the cells; and wherein FL118 drug of Formula 1 inhibits the action an efflux pump to enrich the intracellular free FL118 drug of Formula 1.

  公开号：

  US20230270867A1

文献信息

• Development of a diketopiperazine-forming dipeptidyl Gly-Pro spacer for preparation of an antibody–drug conjugate
  作者：Shino Manabe、Hikaru Machida、Yoshiyuki Aihara、Masahiro Yasunaga、Yukishige Ito、Yasuhiro Matsumura

  DOI：10.1039/c3md00075c

  日期：——

  We developed a novel diketopiperazine-forming dipeptidyl spacer aimed at application in antibody–drug conjugates. Enzymatic cleavage of a peptide linked to the Gly-Pro spacer resulted in formation of diketopiperazine, which was stable and non-toxic, and release of the parent drug.

  我们开发了一种新型二酮哌嗪二肽间隔物，旨在应用于抗体药物共轭物。通过酶解与 Gly-Pro 中间体相连的肽，形成了稳定无毒的二酮哌嗪，并释放出了母体药物。
• [EN] ANTIBODY-DRUG CONJUGATE AND USE THEREOF<br/>[FR] CONJUGUÉ ANTICORPS-MÉDICAMENT ET SON UTILISATION<br/>[ZH] 抗体-药物偶联物及其应用
  申请人：KUNSHAN XINYUNDA BIOTECH CO LTD

  公开号：WO2022078279A1

  公开（公告）日：2022-04-21

  一种抗体-药物偶联物、其制备方法及应用，所述抗体-药物偶联物是将化合物(T)与抗体(AB)经由下式(III)或(VII)表示的接头连接而成，T表示式(II)所示化合物。所述抗体-药物偶联物具有更快起效时间、更长药物半衰期、更适中的稳定性、良好的生物相容性、低免疫原性和安全性，并且可以防止聚集，具有优异的抗肿瘤效果。 AB-S-Q1-L1-L2-La-T (IV) AB-S-Q2-L3-L4-LP-Lb-T (VIII) -Q1-L1-L2-La- (III) -Q2-L3-L4-LP-Lb- (VII)
• WO2019236954A5
  申请人：——

  公开号：WO2019236954A5

  公开（公告）日：2022-06-15
• WO2024081372A1
  申请人：——

  公开号：——

  公开（公告）日：——
• CEACAM5 ANTIBODY-DRUG CONJUGATES AND METHODS OF USE THEREOF
  申请人：[en]SANOFI

  公开号：WO2024108053A1

  公开（公告）日：2024-05-23

  The present invention relates to antibody-drug conjugates comprising an antibody that binds to CEACAM5 conjugated to a drug, such as a Topoisomerase I inhibitor. Also provided herein are methods of treating cancer comprising administering such ADCs.