TX-2245 | 1017855-70-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: TX-2245
• 英文别名: 2-[N-(2-nitro-1H-imidazol-1-yl)-N-methylacetylamino]ethyl 2,3,4,6-tetra-O-acetyl-β-D-galactopyranoside；[(2R,3S,4S,5R,6R)-3,4,5-triacetyloxy-6-[2-[methyl-[2-(2-nitroimidazol-1-yl)acetyl]amino]ethoxy]oxan-2-yl]methyl acetate
• CAS: 1017855-70-7
• 化学式: C₂₂H₃₀N₄O₁₃
• 分子量: 558.499
• InChiKey: CVKZLONXWICGAT-OBJCFNGXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  39
• 可旋转键数：
  15
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  208
• 氢给体数：
  0
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  TX-2245 在 甲醇 、 sodium methylate 作用下， 以45%的产率得到TX-2218
  参考文献：
  名称：

  Design, synthesis, and radiosensitizing activities of sugar-hybrid hypoxic cell radiosensitizers

  摘要：

  We have designed sugar-hybrid TX-1877 derivatives conjugated with sugar moieties including beta-glucose (beta-Glc), beta-galactose (beta-Gal), alpha-mannose (alpha-Man) and N-acetyl-beta-galactosamine (beta-GaINAc). Compound 1 (TX-1877) was glycosylated with appropriate peracetylated sugars using BF3-OEt2 to give acetylated sugar-hybrids, 5 (TX-2244), 6 (TX-2245), 7 (TX-2246), and 10 (TX-2243). Removal of the acetyl groups afforded the sugar-hybrids having free hydroxyl groups, 11 (TX-2141), 12 (TX-2218), 13 (TX-2217) and 14 (TX-2068). We evaluated their radiosensitizing activities by an in vitro radiosensitization assay. All free hydroxyl hybrids have lower enhancement ratio (ER) values (ER <= 1.43) and lower n-octanol/water partition coefficient (P-oct) values (P-oct < 1.00 X 10(-2)) than does 1 (TX-1877, ER = 1.75, P-oct: 5.60 x 10(-2)). All acetylated hybrids have similar P-oct values (3.55 x 10(-2)-1.05 x 10(-1)) to 1 (TX-1877) and have improved ER values (ER >= 1.47) compared to the hybrids having free hydroxyl groups. Among these, 5 (TX-2244) is the most active radiosensitizer (ER = 2.30). We found a good correlation (r = 0.866) between the magnitude of P-oct (logP(oct)) and the ER value of 5 (TX-2244), 6 (TX-2245), 7 (TX-2246), 10 (TX-2243) and I (TX-1877), suggesting that increasing the hydrophobicity is reflected in increased in vitro radiosensitizing activity. In the present study, we have Succeeded in producing sugar-hybrid hypoxic cell radiosensitizers that have an increased radiosensitizing activity that does not depend on increased hydrophobicity. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.10.035
• 作为产物：
  描述：

  2,3,4,6-tetra-O-acetyl-β-D-galactopyranose 、 TX-1877 在 三氟化硼乙醚 作用下， 以 硝基甲烷 为溶剂， 反应 72.0h， 以7%的产率得到TX-2245
  参考文献：
  名称：

  Design, synthesis, and radiosensitizing activities of sugar-hybrid hypoxic cell radiosensitizers

  摘要：

  We have designed sugar-hybrid TX-1877 derivatives conjugated with sugar moieties including beta-glucose (beta-Glc), beta-galactose (beta-Gal), alpha-mannose (alpha-Man) and N-acetyl-beta-galactosamine (beta-GaINAc). Compound 1 (TX-1877) was glycosylated with appropriate peracetylated sugars using BF3-OEt2 to give acetylated sugar-hybrids, 5 (TX-2244), 6 (TX-2245), 7 (TX-2246), and 10 (TX-2243). Removal of the acetyl groups afforded the sugar-hybrids having free hydroxyl groups, 11 (TX-2141), 12 (TX-2218), 13 (TX-2217) and 14 (TX-2068). We evaluated their radiosensitizing activities by an in vitro radiosensitization assay. All free hydroxyl hybrids have lower enhancement ratio (ER) values (ER <= 1.43) and lower n-octanol/water partition coefficient (P-oct) values (P-oct < 1.00 X 10(-2)) than does 1 (TX-1877, ER = 1.75, P-oct: 5.60 x 10(-2)). All acetylated hybrids have similar P-oct values (3.55 x 10(-2)-1.05 x 10(-1)) to 1 (TX-1877) and have improved ER values (ER >= 1.47) compared to the hybrids having free hydroxyl groups. Among these, 5 (TX-2244) is the most active radiosensitizer (ER = 2.30). We found a good correlation (r = 0.866) between the magnitude of P-oct (logP(oct)) and the ER value of 5 (TX-2244), 6 (TX-2245), 7 (TX-2246), 10 (TX-2243) and I (TX-1877), suggesting that increasing the hydrophobicity is reflected in increased in vitro radiosensitizing activity. In the present study, we have Succeeded in producing sugar-hybrid hypoxic cell radiosensitizers that have an increased radiosensitizing activity that does not depend on increased hydrophobicity. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2007.10.035

文献信息

• Design, synthesis, and radiosensitizing activities of sugar-hybrid hypoxic cell radiosensitizers
  作者：Takashi Nakae、Yoshihiro Uto、Motoko Tanaka、Haruna Shibata、Eiji Nakata、Masahide Tominaga、Hiroshi Maezawa、Toshihiro Hashimoto、Kenneth L. Kirk、Hideko Nagasawa、Hitoshi Hori

  DOI：10.1016/j.bmc.2007.10.035

  日期：2008.1

  We have designed sugar-hybrid TX-1877 derivatives conjugated with sugar moieties including beta-glucose (beta-Glc), beta-galactose (beta-Gal), alpha-mannose (alpha-Man) and N-acetyl-beta-galactosamine (beta-GaINAc). Compound 1 (TX-1877) was glycosylated with appropriate peracetylated sugars using BF3-OEt2 to give acetylated sugar-hybrids, 5 (TX-2244), 6 (TX-2245), 7 (TX-2246), and 10 (TX-2243). Removal of the acetyl groups afforded the sugar-hybrids having free hydroxyl groups, 11 (TX-2141), 12 (TX-2218), 13 (TX-2217) and 14 (TX-2068). We evaluated their radiosensitizing activities by an in vitro radiosensitization assay. All free hydroxyl hybrids have lower enhancement ratio (ER) values (ER <= 1.43) and lower n-octanol/water partition coefficient (P-oct) values (P-oct < 1.00 X 10(-2)) than does 1 (TX-1877, ER = 1.75, P-oct: 5.60 x 10(-2)). All acetylated hybrids have similar P-oct values (3.55 x 10(-2)-1.05 x 10(-1)) to 1 (TX-1877) and have improved ER values (ER >= 1.47) compared to the hybrids having free hydroxyl groups. Among these, 5 (TX-2244) is the most active radiosensitizer (ER = 2.30). We found a good correlation (r = 0.866) between the magnitude of P-oct (logP(oct)) and the ER value of 5 (TX-2244), 6 (TX-2245), 7 (TX-2246), 10 (TX-2243) and I (TX-1877), suggesting that increasing the hydrophobicity is reflected in increased in vitro radiosensitizing activity. In the present study, we have Succeeded in producing sugar-hybrid hypoxic cell radiosensitizers that have an increased radiosensitizing activity that does not depend on increased hydrophobicity. (c) 2007 Elsevier Ltd. All rights reserved.