γ-tert-butyl N-(4-amino-4-deoxy-N10-formylpteroyl)-L-glutamate | 95485-00-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 蝶啶及其衍生物
• 英文名称: γ-tert-butyl N-(4-amino-4-deoxy-N10-formylpteroyl)-L-glutamate
• 英文别名: γ-tert-butyl N-(4-amino-4-deoxy-N¹⁰-formylpteroyl)-L-glutamate
• CAS: 95485-00-0
• 化学式: C₂₄H₂₈N₈O₆
• 分子量: 524.536
• InChiKey: MYBHDISQEPMSHO-INIZCTEOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.05
• 重原子数：
  38.0
• 可旋转键数：
  10.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  216.61
• 氢给体数：
  4.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  γ-tert-butyl N-(4-amino-4-deoxy-N10-formylpteroyl)-L-glutamate 在 sodium hydroxide 作用下， 反应 1.75h， 以52%的产率得到gamma-叔丁基氨基喋呤
  参考文献：
  名称：

  Methotrexate Analogues. 25. Chemical and Biological Studies on the γ-tert-Butyl Esters of Methotrexate and Aminopterin

  摘要：

  gamma-tert-Butylaminopterin (gamma-tBAMT), the first example of an aminopterin (AMT) gamma-monoester, was synthesized, and new routes to the known N10-methyl analogue gamma-tert-butyl methotrexate (gamma-tBMTX) were developed. The inhibitory effects of gamma-tBAMT on the activity of purified dihydrofolate reductase (DHFR) from L1210 murine leukemia cells, the growth of L1210 cells and CEM human leukemic lymphoblasts in suspension culture, and the growth of several lines of human squamous cell carcinoma of the head and neck in monolayer culture were compared with the effects of gamma-tBMTX and the parent acids AMT and methotrexate (MTX). Patterns of cross-resistance to gamma-tBAMT, gamma-tBMTX, and AMT among several MTX-resistant cell lines were examined. In vivo antitumor activities of gamma-tBAMT and gamma-tBMTX were compared in mice with L1210 leukemia. While the activity of gamma-tBAMT was very close to that of gamma-tBMTX in the DHFR inhibition assay, the AMT ester was more potent than the MTX ester against cells in culture and against L1210 leukemia in vivo. Only partial cross-resistance was shown against gamma-tBMTX and gamma-tBAMT in cultured cells that were resistant to MTX by virtue of a transport defect or a combination of defective transport and elevated DHFR activity.

  DOI：

  10.1021/jm50001a021
• 作为产物：
  描述：

  2,4-二氨基-6-羟甲基蝶啶 在 溴 、 乙酸酐 、 三乙胺 、 三苯基膦 、 barium(II) oxide 作用下， 以 N,N-二甲基乙酰胺 、 N,N-二甲基甲酰胺 为溶剂， 反应 135.5h， 生成 γ-tert-butyl N-(4-amino-4-deoxy-N10-formylpteroyl)-L-glutamate
  参考文献：
  名称：

  Methotrexate Analogues. 25. Chemical and Biological Studies on the γ-tert-Butyl Esters of Methotrexate and Aminopterin

  摘要：

  gamma-tert-Butylaminopterin (gamma-tBAMT), the first example of an aminopterin (AMT) gamma-monoester, was synthesized, and new routes to the known N10-methyl analogue gamma-tert-butyl methotrexate (gamma-tBMTX) were developed. The inhibitory effects of gamma-tBAMT on the activity of purified dihydrofolate reductase (DHFR) from L1210 murine leukemia cells, the growth of L1210 cells and CEM human leukemic lymphoblasts in suspension culture, and the growth of several lines of human squamous cell carcinoma of the head and neck in monolayer culture were compared with the effects of gamma-tBMTX and the parent acids AMT and methotrexate (MTX). Patterns of cross-resistance to gamma-tBAMT, gamma-tBMTX, and AMT among several MTX-resistant cell lines were examined. In vivo antitumor activities of gamma-tBAMT and gamma-tBMTX were compared in mice with L1210 leukemia. While the activity of gamma-tBAMT was very close to that of gamma-tBMTX in the DHFR inhibition assay, the AMT ester was more potent than the MTX ester against cells in culture and against L1210 leukemia in vivo. Only partial cross-resistance was shown against gamma-tBMTX and gamma-tBAMT in cultured cells that were resistant to MTX by virtue of a transport defect or a combination of defective transport and elevated DHFR activity.

  DOI：

  10.1021/jm50001a021