2-(3-Hydroxy-propyl)-oxazolidine-3-carboxylic acid 4-[(S)-2-((S)-2-amino-3-methyl-butyrylamino)-propionylamino]-benzyl ester | 873923-27-4

• 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: 2-(3-Hydroxy-propyl)-oxazolidine-3-carboxylic acid 4-[(S)-2-((S)-2-amino-3-methyl-butyrylamino)-propionylamino]-benzyl ester
• CAS: 873923-27-4
• 化学式: C₂₂H₃₄N₄O₆
• 分子量: 450.535
• InChiKey: DKFPWDUKPWFDNF-GZMMRYBBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.18
• 重原子数：
  32.0
• 可旋转键数：
  10.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  143.22
• 氢给体数：
  4.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  2-(3-Hydroxy-propyl)-oxazolidine-3-carboxylic acid 4-[(S)-2-((S)-2-amino-3-methyl-butyrylamino)-propionylamino]-benzyl ester 在 sodium cyanoborohydride 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成
  参考文献：
  名称：

  Dipeptide-based highly potent doxorubicin antibody conjugates

  摘要：

  Highly potent and novel derivatives of doxorubicin were linked to monoclonal antibodies (mAbs) for site-specific drug delivery. Drug linker 5 consisted of a dipeptide linker attached directly to the daunosamine nitrogen of the n-butyldiacetate doxorubicin derivative 2a. Upon hydrolysis of the peptide linker and acetate groups, the free daunosamine nitrogen is able to form the highly potent 2-pyrrolinodoxorubicin (3a). The second approach involved the use of an oxazolidine carbamate (13) to mask an activating aldehyde group until proteolytic hydrolysis releases 3a. Both drug linkers were shown to be substrates for the lysosomal enzyme cathepsin B. Each molecule was conjugated to the mAbs c1F6 (anti-CD70) and cAC10 (anti-CD30) to give potent drug conjugates against renal cell carcinoma and anaplastic large cell lymphoma cell lines, respectively. The activities were immunologically selective, since antigen negative cell lines were much less sensitive to treatment with the drug conjugates. The approaches described here for attaching highly potent doxorubicin derivatives to mAbs are novel and allow for control of drug stability while covalently bound to the delivery agent. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.09.081
• 作为产物：
  描述：

  2-[3-(tert-Butyl-diphenyl-silanyloxy)-propyl]-oxazolidine-3-carboxylic acid 4-{(S)-2-[(S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-methyl-butyrylamino]-propionylamino}-benzyl ester 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 以82%的产率得到2-(3-Hydroxy-propyl)-oxazolidine-3-carboxylic acid 4-[(S)-2-((S)-2-amino-3-methyl-butyrylamino)-propionylamino]-benzyl ester
  参考文献：
  名称：

  Dipeptide-based highly potent doxorubicin antibody conjugates

  摘要：

  Highly potent and novel derivatives of doxorubicin were linked to monoclonal antibodies (mAbs) for site-specific drug delivery. Drug linker 5 consisted of a dipeptide linker attached directly to the daunosamine nitrogen of the n-butyldiacetate doxorubicin derivative 2a. Upon hydrolysis of the peptide linker and acetate groups, the free daunosamine nitrogen is able to form the highly potent 2-pyrrolinodoxorubicin (3a). The second approach involved the use of an oxazolidine carbamate (13) to mask an activating aldehyde group until proteolytic hydrolysis releases 3a. Both drug linkers were shown to be substrates for the lysosomal enzyme cathepsin B. Each molecule was conjugated to the mAbs c1F6 (anti-CD70) and cAC10 (anti-CD30) to give potent drug conjugates against renal cell carcinoma and anaplastic large cell lymphoma cell lines, respectively. The activities were immunologically selective, since antigen negative cell lines were much less sensitive to treatment with the drug conjugates. The approaches described here for attaching highly potent doxorubicin derivatives to mAbs are novel and allow for control of drug stability while covalently bound to the delivery agent. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2005.09.081