Diethyl 8-Deazaaminopterin | 76807-59-5

• 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: Diethyl 8-Deazaaminopterin
• 英文别名: diethyl (2S)-2-[[4-[(2,4-diaminopyrido[3,2-d]pyrimidin-6-yl)methylamino]benzoyl]amino]pentanedioate
• CAS: 76807-59-5
• 化学式: C₂₄H₂₉N₇O₅
• 分子量: 495.538
• InChiKey: SJAOKKOZYMNKFV-SFHVURJKSA-N

物化性质

• 密度：
  1.347±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  36
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  184
• 氢给体数：
  4
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  Diethyl 8-Deazaaminopterin 在 platinum(IV) oxide 、 氢气 、 三氟乙酸 作用下， 以 溶剂黄146 为溶剂， 20.0 ℃ 、300.01 kPa 条件下， 反应 74.0h， 生成 diethyl N-[4-[2-(2,4-diamino-5,6,7,8-tetrahydropyrido[3,2-d]pyrimidin-6-yl methyl)acetylamino]benzoyl]-L-glutamate
  参考文献：
  名称：

  N 5取代的四氢叶酸类似物作为钴胺素依赖性蛋氨酸合酶抑制剂和潜在抗癌药的基于机理的设计，合成和生物学研究

  摘要：

  基于蛋氨酸合酶的作用机理，设计合成了许多在N 5上带有亲电基团的8-脱氮氢叶酸，并对其生物学活性进行了研究。化合物（11b，12b和16）对甲硫氨酸合酶表现出最强的活性（IC 50：8.11μM，1.73μM，1.43μM）。此外，还评估了目标化合物对人肿瘤细胞系的细胞毒性和二氢叶酸还原酶（DHFR）的抑制作用。

  DOI：

  10.1016/j.ejmech.2012.09.027
• 作为产物：
  描述：

  6-甲基-1H-吡啶并[2,3-e]嘧啶-2,4-二酮 在 氨 、 三溴化磷 、 三乙胺 、 间氯过氧苯甲酸 、 三氯氧磷 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 N,N-二甲基乙酰胺 、 溶剂黄146 为溶剂， 反应 113.5h， 生成 Diethyl 8-Deazaaminopterin
  参考文献：
  名称：

  Pyridopyrimidines. 12. Synthesis of 8-deaza analogs of aminopterin and folic acid

  摘要：

  DOI：

  10.1021/jo00322a004

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.
• Folate analogs as inhibitors of thymidylate synthase
  作者：Diana I. Brixner、Takamori Ueda、Yung Chi Cheng、John B. Hynes、Arthur D. Broom

  DOI：10.1021/jm00387a016

  日期：1987.4

  Recent demonstrations that deazafolate analogues may act as potent inhibitors of thymidylate synthase (TS) provided a firm rationale for the synthesis of N10-propargyl derivatives of 8-deazafolate and 8-deazaaminopterin (4). A complete assignment of the 1H NMR spectra of these compounds was made possible through application of 2D (COSY) techniques at 200 MHz. Data describing the inhibition of TS derived from human leukemia (K562) cells are presented. IC50 values of 2.25 and 1.26 microM were determined for 8-deaza-10-propargylfolate (3) and 8-deaza-10-propargylaminopterin, respectively. Comparison of the data for various folate analogues reveals a striking dependence of TS inhibitory potency upon the number of nitrogens in the folate pyrazine ring.
• Mechanism-based design, synthesis and biological studies of N5-substituted tetrahydrofolate analogs as inhibitors of cobalamin-dependent methionine synthase and potential anticancer agents
  作者：Zhili Zhang、Chao Tian、Shouxin Zhou、Wei Wang、Ying Guo、Jie Xia、Zhenming Liu、Biao Wang、Xiaowei Wang、Bernard T. Golding、Roger J. Griff、Yansheng Du、Junyi Liu

  DOI：10.1016/j.ejmech.2012.09.027

  日期：2012.12

  8-deazatetrahydrofolates bearing electrophilic groups on N5 were designed and synthesized based on the action mechanism of methionine synthase, and their biological activities were investigated as well. Compounds (11b, 12b and 16) showed the most active against methionine synthase (IC50: 8.11 μM, 1.73 μM, 1.43 μM). In addition, the cytotoxicity to human tumor cell lines and dihydrofolate reductase (DHFR)

  基于蛋氨酸合酶的作用机理，设计合成了许多在N 5上带有亲电基团的8-脱氮氢叶酸，并对其生物学活性进行了研究。化合物（11b，12b和16）对甲硫氨酸合酶表现出最强的活性（IC 50：8.11μM，1.73μM，1.43μM）。此外，还评估了目标化合物对人肿瘤细胞系的细胞毒性和二氢叶酸还原酶（DHFR）的抑制作用。
• Pyridopyrimidines. 12. Synthesis of 8-deaza analogs of aminopterin and folic acid
  作者：Ananthachari Srinivasan、Arthur D. Broom

  DOI：10.1021/jo00322a004

  日期：1981.4