(2S,3S,4S,5R,6S)-6-[2-[3-[(2-bromoacetyl)amino]propanoylamino]-4-[[1-(chloromethyl)-3-[(E)-3-(4-methoxyphenyl)prop-2-enoyl]-1,2-dihydrobenzo[e]indol-5-yl]carbamoyloxymethyl]phenoxy]-3,4,5-trihydroxyoxane-2-carboxylic acid | 939808-45-4

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (2S,3S,4S,5R,6S)-6-[2-[3-[(2-bromoacetyl)amino]propanoylamino]-4-[[1-(chloromethyl)-3-[(E)-3-(4-methoxyphenyl)prop-2-enoyl]-1,2-dihydrobenzo[e]indol-5-yl]carbamoyloxymethyl]phenoxy]-3,4,5-trihydroxyoxane-2-carboxylic acid
• CAS: 939808-45-4
• 化学式: C₄₂H₄₂BrClN₄O₁₃
• 分子量: 926.171
• InChiKey: SCQCMKIUJHZCDU-LDLLXPGBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  61
• 可旋转键数：
  16
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  243
• 氢给体数：
  7
• 氢受体数：
  13

反应信息

• 作为产物：
  描述：

  (2S,3S,4S,5R,6S)-6-[2-(3-aminopropanoylamino)-4-[[1-(chloromethyl)-3-[(E)-3-(4-methoxyphenyl)prop-2-enoyl]-1,2-dihydrobenzo[e]indol-5-yl]carbamoyloxymethyl]phenoxy]-3,4,5-trihydroxyoxane-2-carboxylic acid 、 溴乙酸 N-羟基琥珀酰亚胺酯 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (2S,3S,4S,5R,6S)-6-[2-[3-[(2-bromoacetyl)amino]propanoylamino]-4-[[1-(chloromethyl)-3-[(E)-3-(4-methoxyphenyl)prop-2-enoyl]-1,2-dihydrobenzo[e]indol-5-yl]carbamoyloxymethyl]phenoxy]-3,4,5-trihydroxyoxane-2-carboxylic acid
  参考文献：
  名称：

  Minor groove binder antibody conjugates employing a water soluble β-glucuronide linker

  摘要：

  The minor groove binder beta-glucuronide drug-linker 3 was constructed from amino CBI 1 and determined to be a substrate for Escherichia coli beta-glucuronidase (EC 3.2.1,31), resulting in facile drug release. Compound 3 was conjugated to mAbs cAC10 (anti-CD30) and h1F6 (anti-CD70) to give antibody-drug conjugates (ADCs) with potencies comparable to that of free drug 1. The ADCs were largely monomeric at intermediate loading levels (4-5 drug/mAb), in contrast to highly aggregated p-aminobenzylcarbamate dipeptide-based ADCs of I previously reported. Significant levels of immunologic specificity were observed with cAC10-3 by comparing antigen positive versus negative cell lines and binding versus non-binding control ADCs. The water soluble beta-glucuronide linker is stable in plasma and effectively delivers drugs to target cells leading to potent cytotoxic activities. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.01.071

文献信息

• Beta-Glucuronide-Linker Drug Conjugates
  申请人：Jeffrey Scott

  公开号：US20080241128A1

  公开（公告）日：2008-10-02

  Ligand Drug conjugate compounds comprising a β-glucuronide-based linker and methods of using such compounds are provided.

  提供了包含基于β-葡萄糖醛酸的连接剂的配体药物共轭化合物及使用这种化合物的方法。
• BETA-GLUCURONIDE-LINKER DRUG CONJUGATES
  申请人：Jeffrey Scott

  公开号：US20140031535A1

  公开（公告）日：2014-01-30

  Ligand Drug conjugate compounds comprising a β-glucuronide-based linker and methods of using such compounds are provided.

  本发明提供了包括基于β-葡萄糖醛酸的连接物的配体药物结合物化合物以及使用这种化合物的方法。
• US8039273B2
  申请人：——

  公开号：US8039273B2

  公开（公告）日：2011-10-18
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  申请人：——

  公开号：US8568728B2

  公开（公告）日：2013-10-29
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  申请人：——

  公开号：US9731030B2

  公开（公告）日：2017-08-15