N-[4-[[2-(2,4-diamino-5-allyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-6-yl)methyl]amino]-3-bromo-benzoyl]-L-glutamic acid | 1146384-23-7

• 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: N-[4-[[2-(2,4-diamino-5-allyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-6-yl)methyl]amino]-3-bromo-benzoyl]-L-glutamic acid
• 英文别名: (2S)-2-[[3-bromo-4-[(2,4-diamino-5-prop-2-enyl-7,8-dihydro-6H-pyrido[3,2-d]pyrimidin-6-yl)methylamino]benzoyl]amino]pentanedioic acid
• CAS: 1146384-23-7
• 化学式: C₂₃H₂₈BrN₇O₅
• 分子量: 562.423
• InChiKey: WDHACPDURGLUTQ-RUINGEJQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  36
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  197
• 氢给体数：
  6
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  diethyl N-[4-[[2-(2,4-diamino-5-allyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-6-yl)methyl]amino]-3-bromo-benzoyl]-L-glutamate 在 sodium hydroxide 、 水 、 盐酸 作用下， 以 四氢呋喃 为溶剂， 以79%的产率得到N-[4-[[2-(2,4-diamino-5-allyl-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-6-yl)methyl]amino]-3-bromo-benzoyl]-L-glutamic acid
  参考文献：
  名称：

  Novel 8-deaza-5,6,7,8-tetrahydroaminopterin derivatives as dihydrofolate inhibitor: Design, synthesis and antifolate activity

  摘要：

  We report, for the first time, the synthesis and biological activities of 8-deaza-5,6,7,8-tetrahydroaminopterin 9, and the 5-substituted and 5,10-disubstituted analogues 11, 13, 15, and 17. The analogues were obtained from key compound diethyl 8-deaza-5,6,7,8-tetrahydroaminopterin 8 following the catalytic reduction of the pyridine ring of diethyl 8-deaza aminopterin 5. The five novel 8-deaza-5,6,7,8-tetrahydroaminopterin derivatives were assayed in vitro for their cytotoxicity on BGC-823, HL-60, Bel-7402 and Hela tumor cell lines, and inhibition on recombinant human dihydrofolate reductase (DHFR), among which the most potent molecule (compound 9) was about 4- to 10-fold poorer than MTX on the four kinds of tumor cell lines, and its effect on DHFR was about 17-fold poorer than MTX. The docking studies were followed to explain the biological testing results. (c) 2008 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2008.04.017

文献信息

• Novel 8-deaza-5,6,7,8-tetrahydroaminopterin derivatives as dihydrofolate inhibitor: Design, synthesis and antifolate activity
  作者：Zhili Zhang、Jun Wu、Fuxiang Ran、Ying Guo、Ran Tian、Shouxin Zhou、Xiaowei Wang、Zhenming Liu、Liangren Zhang、Jingrong Cui、Junyi Liu

  DOI：10.1016/j.ejmech.2008.04.017

  日期：2009.2

  We report, for the first time, the synthesis and biological activities of 8-deaza-5,6,7,8-tetrahydroaminopterin 9, and the 5-substituted and 5,10-disubstituted analogues 11, 13, 15, and 17. The analogues were obtained from key compound diethyl 8-deaza-5,6,7,8-tetrahydroaminopterin 8 following the catalytic reduction of the pyridine ring of diethyl 8-deaza aminopterin 5. The five novel 8-deaza-5,6,7,8-tetrahydroaminopterin derivatives were assayed in vitro for their cytotoxicity on BGC-823, HL-60, Bel-7402 and Hela tumor cell lines, and inhibition on recombinant human dihydrofolate reductase (DHFR), among which the most potent molecule (compound 9) was about 4- to 10-fold poorer than MTX on the four kinds of tumor cell lines, and its effect on DHFR was about 17-fold poorer than MTX. The docking studies were followed to explain the biological testing results. (c) 2008 Elsevier Masson SAS. All rights reserved.