3-(1-ethoxyethoxy)-4-cyclohexyl-2-azetidinone | 201856-52-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: 3-(1-ethoxyethoxy)-4-cyclohexyl-2-azetidinone
• 英文别名: (3R,4S)-4-cyclohexyl-3-(1-ethoxyethoxy)azetidin-2-one
• CAS: 201856-52-2
• 化学式: C₁₃H₂₃NO₃
• 分子量: 241.331
• InChiKey: HEXRCFLQWXZCKV-CLGJWYQZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(1-ethoxyethoxy)-4-cyclohexyl-2-azetidinone 在 4-二甲氨基吡啶 、 sodium hexamethyldisilazane 、 溶剂黄146 、 三乙胺 、 锌 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 、 二氯甲烷 为溶剂， 反应 4.5h， 生成 3'-cyclohexyl-3'-dephenyldocetaxel
  参考文献：
  名称：

  Synthesis and Structure-Activity Relationships of New Antitumor Taxoids. Effects of Cyclohexyl Substitution at the C-3' and/or C-2 of Taxotere (Docetaxel)

  摘要：

  Synthesis and cytotoxicity of the new analogs (11-13) of docetaxel possessing cyclohexyl groups instead of phenyl groups at the C-3' and/or C-2 benzoate positions are described. The C-2 cyclohexanecarboxylate analog of paclitaxel(15) is also synthesized for comparison. The potency of these new taxoids were examined for their inhibitory activity for microtubule disassembly and also for their cytotoxicity against murine P388 leukemia cell line as well. as doxorubicin-resistant P388 leukemia cell line (P388/Dox). It is found that 3'-dephenyl-3'-cyclohexyldocetaxel (11) (0.72T) and 2-(hexahydro)docetaxel (12) (0.85T) possess strong inhibitory activity for microtubule disassembly equivalent to docetaxel (0.7T), which is more potent than paclitaxel (1.0T). The results clearly indicate that phenyl or an aromatic group at C-3' or C-2 is not a requisite for strong binding to the microtubules. This finding has opened an avenue for development of new nonaromatic analogs of docetaxel and paclitaxel. 3'-Dephenyl-3'-cyclohexyl-2-(hexahydro)docetaxel (13) (2T) turns out to be a substantially weaker inhibitor. The cytotoxicities of 11-13 against P388 are, however, in the same range that is 8-12 times weaker than docetaxel and 4-6 times weaker than paclitaxel, i.e., 13 shows equivalent cytotoxicity to that of 11 or 12 in spite of much lower microtubule disassembly inhibitory activity. The cytotoxicities of these new taxoids against the P388/Dox cell line are only 2-2.5 times lower than that of docetaxel. The potency of 2-(hexahydro)paclitaxel (15) for these assays is much lower than the docetaxel counterpart 12. The significant loss of activity in vivo against B16 melanoma is observed for 11-13, i.e., 11 is only marginal (T/C = 38% at 20 mg/kg/day), and 12 and 13 are inactive (T/C = 76% and 79%, respectively). This could be ascribed to faster metabolism, faster excretion or other bioavailability problems.

  DOI：

  10.1021/jm00042a013
• 作为产物：
  描述：

  (3R,4S)-3-羟基-4-苯基-2-氮杂环丁酮 在 Rh on carbon 氢气 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 90.0 ℃ 、5.52 MPa 条件下， 反应 122.0h， 生成 3-(1-ethoxyethoxy)-4-cyclohexyl-2-azetidinone
  参考文献：
  名称：

  Synthesis and Structure-Activity Relationships of New Antitumor Taxoids. Effects of Cyclohexyl Substitution at the C-3' and/or C-2 of Taxotere (Docetaxel)

  摘要：

  Synthesis and cytotoxicity of the new analogs (11-13) of docetaxel possessing cyclohexyl groups instead of phenyl groups at the C-3' and/or C-2 benzoate positions are described. The C-2 cyclohexanecarboxylate analog of paclitaxel(15) is also synthesized for comparison. The potency of these new taxoids were examined for their inhibitory activity for microtubule disassembly and also for their cytotoxicity against murine P388 leukemia cell line as well. as doxorubicin-resistant P388 leukemia cell line (P388/Dox). It is found that 3'-dephenyl-3'-cyclohexyldocetaxel (11) (0.72T) and 2-(hexahydro)docetaxel (12) (0.85T) possess strong inhibitory activity for microtubule disassembly equivalent to docetaxel (0.7T), which is more potent than paclitaxel (1.0T). The results clearly indicate that phenyl or an aromatic group at C-3' or C-2 is not a requisite for strong binding to the microtubules. This finding has opened an avenue for development of new nonaromatic analogs of docetaxel and paclitaxel. 3'-Dephenyl-3'-cyclohexyl-2-(hexahydro)docetaxel (13) (2T) turns out to be a substantially weaker inhibitor. The cytotoxicities of 11-13 against P388 are, however, in the same range that is 8-12 times weaker than docetaxel and 4-6 times weaker than paclitaxel, i.e., 13 shows equivalent cytotoxicity to that of 11 or 12 in spite of much lower microtubule disassembly inhibitory activity. The cytotoxicities of these new taxoids against the P388/Dox cell line are only 2-2.5 times lower than that of docetaxel. The potency of 2-(hexahydro)paclitaxel (15) for these assays is much lower than the docetaxel counterpart 12. The significant loss of activity in vivo against B16 melanoma is observed for 11-13, i.e., 11 is only marginal (T/C = 38% at 20 mg/kg/day), and 12 and 13 are inactive (T/C = 76% and 79%, respectively). This could be ascribed to faster metabolism, faster excretion or other bioavailability problems.

  DOI：

  10.1021/jm00042a013

文献信息

• PROCESS FOR PREPARATION OF TAXANE DERIVATIVES AND BETA-LACTAM INTERMEDIATES THEREFOR
  申请人：THE RESEARCH FOUNDATION OF STATE UNIVERSITY OF NEW YORK

  公开号：EP0681568B1

  公开（公告）日：2006-07-26
• ANTI-TUMOR COMPOUNDS, PHARMACEUTICAL COMPOSITIONS, METHODS FOR PREPARATION THEREOF AND FOR TREATMENT
  申请人：THE RESEARCH FOUNDATION OF STATE UNIVERSITY OF NEW YORK

  公开号：EP0690856A1

  公开（公告）日：1996-01-10
• EP0690856A4
  申请人：——

  公开号：EP0690856A4

  公开（公告）日：1996-02-07
• US5475011A
  申请人：——

  公开号：US5475011A

  公开（公告）日：1995-12-12
• US5599820A
  申请人：——

  公开号：US5599820A

  公开（公告）日：1997-02-04