2-carbomethoxy-4-(4'-carbomethoxyphenyl)cyclohexanone | 137464-99-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-carbomethoxy-4-(4'-carbomethoxyphenyl)cyclohexanone
• 英文别名: methyl 4-(3-methoxycarbonyl-4-oxocyclohexyl)benzoate
• CAS: 137464-99-4
• 化学式: C₁₆H₁₈O₅
• 分子量: 290.316
• InChiKey: XKZAQSLNNSAGQI-UHFFFAOYSA-N

物化性质

• 沸点：
  423.8±45.0 °C(Predicted)
• 密度：
  1.196±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  69.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-carbomethoxy-4-(4'-carbomethoxyphenyl)cyclohexanone 在 sodium hydroxide 、 硼烷四氢呋喃络合物 、 三乙胺 、 2,3-二氯-5,6-二氰基-1,4-苯醌 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 二苯醚 、 乙二醇甲醚 、 溶剂黄146 为溶剂， 反应 79.5h， 生成 5,10-ethano-5,10-dideazaaminopterin diethyl ester
  参考文献：
  名称：

  Synthesis and antifolate properties of 5,10-ethano-5,10-dideazaaminopterin

  摘要：

  2-Carbomethoxy-4-(p-carbomethoxyphenyl)cyclohexanone was prepared in a four-step process and thermally condensed with 2,4,6-triaminopyrimidine to afford methyl 2,4-diamino-4-deoxy-7-hydroxy-5,10-ethano-5,10-dideazapteroate. Reduction of the 7-oxo function with borane gave the 7,8-dihydro pterin which was subsequently oxidized to the fully aromatic pteroate ester with dicyanodichlorobenzoquinone. Saponification of the benzoate ester, coupling with diethyl glutamate and final ester hydrolysis afforded the title compound. This novel deazaaminopterin analogue was approximately as potent as methotrexate in vitro in terms of DHFR and L1210 cell growth inhibition. There are indications of diastereomeric differences in the enzyme inhibition measurements. A significant transport advantage over MTX for influx into L1210 cells was observed. The compound was active against the E 0771 murine mammary solid tumor, but further investigation with individual diastereomers is required to define the ED50.

  DOI：

  10.1021/jm00080a017
• 作为产物：
  描述：

  4-(4-氧代环己基)苯甲酸 在 盐酸 、 potassium hydride 、 sodium hydride 作用下， 反应 2.0h， 生成 2-carbomethoxy-4-(4'-carbomethoxyphenyl)cyclohexanone
  参考文献：
  名称：

  Synthesis and antifolate properties of 5,10-ethano-5,10-dideazaaminopterin

  摘要：

  2-Carbomethoxy-4-(p-carbomethoxyphenyl)cyclohexanone was prepared in a four-step process and thermally condensed with 2,4,6-triaminopyrimidine to afford methyl 2,4-diamino-4-deoxy-7-hydroxy-5,10-ethano-5,10-dideazapteroate. Reduction of the 7-oxo function with borane gave the 7,8-dihydro pterin which was subsequently oxidized to the fully aromatic pteroate ester with dicyanodichlorobenzoquinone. Saponification of the benzoate ester, coupling with diethyl glutamate and final ester hydrolysis afforded the title compound. This novel deazaaminopterin analogue was approximately as potent as methotrexate in vitro in terms of DHFR and L1210 cell growth inhibition. There are indications of diastereomeric differences in the enzyme inhibition measurements. A significant transport advantage over MTX for influx into L1210 cells was observed. The compound was active against the E 0771 murine mammary solid tumor, but further investigation with individual diastereomers is required to define the ED50.

  DOI：

  10.1021/jm00080a017

文献信息

• Cyclized 5,10-dideazaaminopterin compounds
  申请人：——

  公开号：US05077404A1

  公开（公告）日：1991-12-31

  5,10-Dialkyl substituted 5,10-dideazaaminopterins and a cyclized derivative thereof are disclosed as potent antineoplastic agents. Also disclosed is an improved process for the preparation of 10-ethyl-10-deazaaminopterin using the intermediate methyl 4-[[2-(2,4-diamino-6-pteridinyl)-1-ethyl]ethenyl]benzoate.

  公开了5,10-二烷基取代的5,10-二脱氨基对氨基甲酸叶酸和其环化衍生物作为有效的抗肿瘤药物。还公开了一种改进的制备10-乙基-10-脱氨基对氨基甲酸叶酸的方法，该方法使用中间体甲基4-[[2-(2,4-二氨基-6-对二氨基嘌呤基)-1-乙基]乙烯基]苯甲酸酯。
• [EN] DEAZAAMINOPTERINS
  申请人：SOUTHERN RESEARCH INSTITUTE

  公开号：WO1993013102A1

  公开（公告）日：1993-07-08

  (EN) 5,10-Diakyl substituted 5,10-dideazaaminopterin and a cyclized derivative thereof are disclosed as potent antineoplastic agents. Also disclosed in an improved process for preparation of 10-ethyl-10-deazaaminopterin using the intermediate methyl 4-[[2-(2,4-diamino-6-pteridinyl)-1-ethyl]ethenyl]benzoate.(FR) On décrit la 5,10-didéazaaminoptérine substituée par 5,10-diakyle ainsi qu'un dérivé cyclisé de celle-ci comme agents antinéoplastiques puissants. On décrit également un procédé perfectionné de préparation de 10-éthyle-10-déazaaminoptérine à l'aide de l'intermédiaire méthyle-4-[[2-(2,4-diamino-6-ptéridinyle)-1-éthyle]éthényle]benzoate.

  5,10-丁基取代的5,10-二羟基异 rigsineopsin及其环化衍生物被披露为强效的抗肿瘤剂。此外，还披露了一种优化了的合成10-乙基-10-二羟基异 rigsineopsin的方法，使用中间体甲苯4-[[2-(2,4-二氨基-6-pteridinyl)-1-乙基]乙烯基]苯zoate。
• US5077404A
  申请人：——

  公开号：US5077404A

  公开（公告）日：1991-12-31
• Synthesis and antifolate properties of 5,10-ethano-5,10-dideazaaminopterin
  作者：Joseph I. DeGraw、Pamela H. Christie、William T. Colwell、Francis M. Sirotnak

  DOI：10.1021/jm00080a017

  日期：1992.1

  2-Carbomethoxy-4-(p-carbomethoxyphenyl)cyclohexanone was prepared in a four-step process and thermally condensed with 2,4,6-triaminopyrimidine to afford methyl 2,4-diamino-4-deoxy-7-hydroxy-5,10-ethano-5,10-dideazapteroate. Reduction of the 7-oxo function with borane gave the 7,8-dihydro pterin which was subsequently oxidized to the fully aromatic pteroate ester with dicyanodichlorobenzoquinone. Saponification of the benzoate ester, coupling with diethyl glutamate and final ester hydrolysis afforded the title compound. This novel deazaaminopterin analogue was approximately as potent as methotrexate in vitro in terms of DHFR and L1210 cell growth inhibition. There are indications of diastereomeric differences in the enzyme inhibition measurements. A significant transport advantage over MTX for influx into L1210 cells was observed. The compound was active against the E 0771 murine mammary solid tumor, but further investigation with individual diastereomers is required to define the ED50.