MC-Phe-Lys(MMT)-PAB-OH | 159857-65-5

• 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: MC-Phe-Lys(MMT)-PAB-OH
• 英文别名: (S)-2-((S)-2-(6-(2,5-Dioxo-2,5-dihydro-1H-pyrrol-1-yl)hexanamido)-3-phenylpropanamido)-N-(4-(hydroxymethyl)phenyl)-6-(((4-methoxyphenyl)diphenylmethyl)amino)hexanamide；(2S)-2-[[(2S)-2-[6-(2,5-dioxopyrrol-1-yl)hexanoylamino]-3-phenylpropanoyl]amino]-N-[4-(hydroxymethyl)phenyl]-6-[[(4-methoxyphenyl)-diphenylmethyl]amino]hexanamide
• CAS: 159857-65-5
• 化学式: C₅₂H₅₇N₅O₇
• 分子量: 864.054
• InChiKey: JZJLLDINRJFDCM-ZYBCLOSLSA-N

物化性质

• 沸点：
  1087.1±65.0 °C(Predicted)
• 密度：
  1.228±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  64
• 可旋转键数：
  24
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  166
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  MC-Phe-Lys(MMT)-PAB-OH 在 吡啶 、 苯甲醚 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 生成
  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：

  (S)-2-((((9h-芴-9-基)甲氧基)羰基)氨基)-6-(((4-甲氧基苯基)二苯基甲基)氨基)己酸 在 lithium hydroxide 、 2-乙氧基-1-乙氧碳酰基-1,2-二氢喹啉 、 二乙胺 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 42.0h， 生成 MC-Phe-Lys(MMT)-PAB-OH
  参考文献：
  名称：

  Monomethoxytrityl (MMT) as a versatile amino protecting group for complex prodrugs of anticancer compounds sensitive to strong acids, bases and nucleophiles

  摘要：

  Cathepsin B-sensitive maleimidocaproyl-Phe-Lys linker compounds containing acid-sensitive anticancer drugs doxorubicin, mitomycin C and paclitaxel (taxol(R)) attached through a self-immolative p-aminobenzylcarbonyl spacer were prepared using monomethoxytrityl (MMT) as the amino protecting group for Lys. MMT could be removed cleanly and in high yield by dichloroacetic and chloroacetic acids in the presence of anisole with minimal workup. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0040-4039(97)01158-1

文献信息

• Antibody Conjugates of 7-Ethyl-10-hydroxycamptothecin (SN-38) for Targeted Cancer Chemotherapy
  作者：Sung-Ju Moon、Serengulam V. Govindan、Thomas M. Cardillo、Christopher A. D’Souza、Hans J. Hansen、David M. Goldenberg

  DOI：10.1021/jm800719t

  日期：2008.11.13

  CPT-11 is a clinically used cancer drug, and it is a prodrug of the potent topoisomerase I inhibitor, SN-38 (7-ethyl-10-hydroxycamptothecin). To bypass the need for the in vivo conversion of CPT-11 and increase the therapeutic index, bifunctional derivatives of SN-38 were prepared for use in anti body-based targeted therapy of cancer. The general synthetic scheme incorporated an acetylene-azide click cycloaddition step in the design, a short polyethylene glycol spacer for aqueous solubility, and a maleimide group conjugation. Conjugates of a humanized anti-CEACAM5 monoclonal antibody, hMN-14, prepared using, these SN-38 derivatives were evaluated in vitro for stability in buffer and human serum and for antigen-binding and cytotoxicity in a human colon adenocarcinoma cell line. Conjugates of hMN-14 and SN-38 derivatives 16 and 17 were found promising for further development.
• Synthesis of an immunoconjugate of camptothecin
  作者：Michael A Walker、Gene M Dubowchik、Sandra J Hofstead、Pamela A Trail、Raymond A Firestone

  DOI：10.1016/s0960-894x(01)00707-7

  日期：2002.1

  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.
• Monomethoxytrityl (MMT) as a versatile amino protecting group for complex prodrugs of anticancer compounds sensitive to strong acids, bases and nucleophiles
  作者：Gene M. Dubowchik、Shilpa Radia

  DOI：10.1016/s0040-4039(97)01158-1

  日期：1997.7

  Cathepsin B-sensitive maleimidocaproyl-Phe-Lys linker compounds containing acid-sensitive anticancer drugs doxorubicin, mitomycin C and paclitaxel (taxol(R)) attached through a self-immolative p-aminobenzylcarbonyl spacer were prepared using monomethoxytrityl (MMT) as the amino protecting group for Lys. MMT could be removed cleanly and in high yield by dichloroacetic and chloroacetic acids in the presence of anisole with minimal workup. (C) 1997 Elsevier Science Ltd.