2-desamino-2-methyl-5,8-dideazaisoaminopterin | 159382-32-8

• 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: 2-desamino-2-methyl-5,8-dideazaisoaminopterin
• CAS: 159382-32-8
• 化学式: C₂₂H₂₃N₅O₅
• 分子量: 437.455
• InChiKey: IBFJTQFMFTYXHU-SFHVURJKSA-N

物化性质

• 沸点：
  725.0±60.0 °C(predicted)
• 密度：
  1.435±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.18
• 重原子数：
  32.0
• 可旋转键数：
  9.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  167.53
• 氢给体数：
  5.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  聚合甲醛 、 2-desamino-2-methyl-5,8-dideazaisoaminopterin 在 sodium cyanoborohydride 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 以68%的产率得到2-desamino-2,9-dimethyl-5,8-dideazaisoaminopterin
  参考文献：
  名称：

  Studies on the antitumor effects of analogues of 5,8-dideazaisofolic acid and 5,8-dideazaisoaminopterin

  摘要：

  Six new analogues of 5,8-dideazaisofolic acid and 5,8-dideazaisoaminopterin were synthesized in an effort to obtain enhanced antitumor activity. The modifications included the replacement of the 2-amino group by hydrogen or methyl as well as the inclusion of a methyl substituent at position 9. Based upon activity against L1210 leukemia cells in culture, three of the new analogues together with one compound described previously were evaluated for cytotoxicity in vitro using three human tumor cell lines (Cole 320 DM, Hep G2 and HL-60). The most effective compound was 2-desamino-N-9-methyl-5,8-dideazaisoaminopterin (2c) with the HL-60 cells being the most sensitive to its cytotoxic effects. These analogues were evaluated in vitro as inhibitors of dihydrofolate reductase (DHFR) and thymidylate synthase (TS) from human as well as bacterial (Lactobacillus casei) sources. All four of the 4-amino analogues were most effective toward L. casei DHFR compared with human DHFR, with 2-desamino-2-methyl-5,8-dideazaisoaminopterin (2d) and its 9-methyl derivative (2e) having 818- and 430-fold greater selectivity (L. caseilhuman). Most of the compounds studied were found to be only modest inhibitors of human TS (I-50 values = 1.5 to 20 mu M) and were therefore at least 40-fold less inhibitory than 10-propargyl-5,8-dideazafolic acid. Nevertheless, reversal of cytotoxicity studies with thymidine, hypoxanthine and folinic acid using the HL-60 cell line suggested that TS is the primary target for these analogues.

  DOI：

  10.1016/0006-2952(95)00203-c
• 作为产物：
  描述：

  2-甲基喹唑啉-4,6-二胺 在 Raney 30 氢气 、 溶剂黄146 、 三氟乙酸 作用下， 反应 2.5h， 生成 2-desamino-2-methyl-5,8-dideazaisoaminopterin
  参考文献：
  名称：

  Studies on the antitumor effects of analogues of 5,8-dideazaisofolic acid and 5,8-dideazaisoaminopterin

  摘要：

  Six new analogues of 5,8-dideazaisofolic acid and 5,8-dideazaisoaminopterin were synthesized in an effort to obtain enhanced antitumor activity. The modifications included the replacement of the 2-amino group by hydrogen or methyl as well as the inclusion of a methyl substituent at position 9. Based upon activity against L1210 leukemia cells in culture, three of the new analogues together with one compound described previously were evaluated for cytotoxicity in vitro using three human tumor cell lines (Cole 320 DM, Hep G2 and HL-60). The most effective compound was 2-desamino-N-9-methyl-5,8-dideazaisoaminopterin (2c) with the HL-60 cells being the most sensitive to its cytotoxic effects. These analogues were evaluated in vitro as inhibitors of dihydrofolate reductase (DHFR) and thymidylate synthase (TS) from human as well as bacterial (Lactobacillus casei) sources. All four of the 4-amino analogues were most effective toward L. casei DHFR compared with human DHFR, with 2-desamino-2-methyl-5,8-dideazaisoaminopterin (2d) and its 9-methyl derivative (2e) having 818- and 430-fold greater selectivity (L. caseilhuman). Most of the compounds studied were found to be only modest inhibitors of human TS (I-50 values = 1.5 to 20 mu M) and were therefore at least 40-fold less inhibitory than 10-propargyl-5,8-dideazafolic acid. Nevertheless, reversal of cytotoxicity studies with thymidine, hypoxanthine and folinic acid using the HL-60 cell line suggested that TS is the primary target for these analogues.

  DOI：

  10.1016/0006-2952(95)00203-c