1,4-Dioxa-8,11-diazacyclohexadec-13-ene-2,5,9,12-tetrone,10-[(4-chlorophenyl)methyl]-16-[(1R,2E)-1-methyl-3-phenyl-2-propenyl]-3-(2-methylpropyl)-, (3S,10R,13E,16S)- | 654068-71-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: 1,4-Dioxa-8,11-diazacyclohexadec-13-ene-2,5,9,12-tetrone,10-[(4-chlorophenyl)methyl]-16-[(1R,2E)-1-methyl-3-phenyl-2-propenyl]-3-(2-methylpropyl)-, (3S,10R,13E,16S)-
• 英文别名: 10-(4'-chlorobenzyl)demethoxybenzyldesepoxycryptophycin-24
• CAS: 654068-71-0
• 化学式: C₃₃H₃₉ClN₂O₆
• 分子量: 595.135
• InChiKey: MRCPZJSLXRSBAP-BRYREQRZSA-N

物化性质

• 熔点：
  225-227 °C
• 沸点：
  853.6±65.0 °C(Predicted)
• 密度：
  1.145±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.05
• 重原子数：
  42.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  110.8
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  1,4-Dioxa-8,11-diazacyclohexadec-13-ene-2,5,9,12-tetrone,10-[(4-chlorophenyl)methyl]-16-[(1R,2E)-1-methyl-3-phenyl-2-propenyl]-3-(2-methylpropyl)-, (3S,10R,13E,16S)- 在 二甲基二环氧乙烷 作用下， 以 丙酮 为溶剂， 反应 5.0h， 生成 10-(4'-chlorobenzyl)demethoxybenzylcryptophycin-24 、 (E)-(3S,10R,16S)-10-(4-Chloro-benzyl)-3-isobutyl-16-[(S)-1-((2S,3S)-3-phenyl-oxiranyl)-ethyl]-1,4-dioxa-8,11-diaza-cyclohexadec-13-ene-2,5,9,12-tetraone
  参考文献：
  名称：

  Total Synthesis and Antitubulin Activity of C10 Analogues of Cryptophycin-24

  摘要：

  The unsubstituted, 3'-C1, 4'-C1, and 3',4'-diC1 C10 analogues of cryptophycin-24 were prepared via total synthesis and tested in vitro for cytotoxicity against MCF-7 and multi-drug-resistant MCF-7/ADR breast cancer cell lines and in a tubulin assembly assay. The ED50 values ranged from 7.2 to 15.8 muM in the tubulin assay and from 0.05 to 3.4 nM in the cell assays. The presence of a 3'-C1 and/or 4'-C1 substituent on the C10 phenyl ring increased cytotoxicity in the MCF-7 cell line compared to the unsubstituted phenyl ring. The most potent compound in this series possessed a X-Cl substituent on the C10 phenyl ring. The X-Cl analogue had ED50 values of 50 and 580 pM in the MCF-7 and MCF-7/ADR cell lines, respectively. Its activity was very similar to the parent compound cryptophycin-24. Substitution of the 4'-MeO group in cryptophycin-24 with a 4'-C1 moiety did not significantly affect cytotoxicity against MCF-7 and MCF-7/ADR cells compared to the parent compound. These results demonstrated that the 4'-MeO group in cryptophycin-24 is not essential and can be replaced with X-Cl or 4'-C1 substituents.

  DOI：

  10.1021/jm030278c
• 作为产物：
  描述：

  (2S)-2-[3-[(2R)-2-tert-butoxycarbonylamino-3-(4-chlorophenyl)propionylamino]propionyloxy]-4-methylpentanoic acid 在 4-二甲氨基吡啶 、 2,4,6-三氯苯甲酰氯 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 9.0h， 生成 1,4-Dioxa-8,11-diazacyclohexadec-13-ene-2,5,9,12-tetrone,10-[(4-chlorophenyl)methyl]-16-[(1R,2E)-1-methyl-3-phenyl-2-propenyl]-3-(2-methylpropyl)-, (3S,10R,13E,16S)-
  参考文献：
  名称：

  Total Synthesis and Antitubulin Activity of C10 Analogues of Cryptophycin-24

  摘要：

  The unsubstituted, 3'-C1, 4'-C1, and 3',4'-diC1 C10 analogues of cryptophycin-24 were prepared via total synthesis and tested in vitro for cytotoxicity against MCF-7 and multi-drug-resistant MCF-7/ADR breast cancer cell lines and in a tubulin assembly assay. The ED50 values ranged from 7.2 to 15.8 muM in the tubulin assay and from 0.05 to 3.4 nM in the cell assays. The presence of a 3'-C1 and/or 4'-C1 substituent on the C10 phenyl ring increased cytotoxicity in the MCF-7 cell line compared to the unsubstituted phenyl ring. The most potent compound in this series possessed a X-Cl substituent on the C10 phenyl ring. The X-Cl analogue had ED50 values of 50 and 580 pM in the MCF-7 and MCF-7/ADR cell lines, respectively. Its activity was very similar to the parent compound cryptophycin-24. Substitution of the 4'-MeO group in cryptophycin-24 with a 4'-C1 moiety did not significantly affect cytotoxicity against MCF-7 and MCF-7/ADR cells compared to the parent compound. These results demonstrated that the 4'-MeO group in cryptophycin-24 is not essential and can be replaced with X-Cl or 4'-C1 substituents.

  DOI：

  10.1021/jm030278c