2-amino-2-[4-(1,3-butadiynyl)phenethyl]-1,3-propanediol | 1070895-11-2

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2-amino-2-[4-(1,3-butadiynyl)phenethyl]-1,3-propanediol
• 英文别名: TX-2152；2-Amino-2-[2-(4-buta-1,3-diynylphenyl)ethyl]propane-1,3-diol
• CAS: 1070895-11-2
• 化学式: C₁₅H₁₇NO₂
• 分子量: 243.305
• InChiKey: GXLUOIIGQJPRRO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  66.5
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  [2-Acetamido-2-(acetyloxymethyl)-4-[4-(4-trimethylsilylbuta-1,3-diynyl)phenyl]butyl] acetate 在 lithium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 0.67h， 以53%的产率得到2-amino-2-[4-(1,3-butadiynyl)phenethyl]-1,3-propanediol
  参考文献：
  名称：

  TX-2152: A conformationally rigid and electron-rich diyne analogue of FTY720 with in vivo antiangiogenic activity

  摘要：

  We designed FTY720 analogues with conformationally rigid and electron-rich acetylenic chains as anti-angiogenic agents ( the monoyne 1: TX-2148, the diyne 2: TX-2152, the triyne 3: TX-2256). Molecular orbital ( MO) calculations of our designed acetylenic analogues and FTY720 showed that the localization of the lowest unoccupied MO and the highest occupied MO increased from phenyl ring to acetylenic chain compared with that of FTY720. These acetylenic analogues were synthesized from p-hydroxyphenylethanol as a starting material. The construction of the acetylenic chain was carried out by an iterative strategy using a Sonogashira cross-coupling reaction and desilylative bromination in two steps. The corresponding overall yields of the monoyne 1, the diyne 2, and the triyne 3 were 27% ( 11 steps), 13% ( 13 steps), and 10% ( 15 steps). The in vivo antiangiogenic activities of these acetylenic analogues and FTY720 were evaluated by the chick embryo chorioallantoic membrane ( CAM) assay and compared to the activities of the known antiangiogenic agent TNP-470. The diyne 2 showed more potent antiangiogenic activity ( 90% inhibition) than FTY720 ( 77% inhibition) and other acetylenic analogues ( the monoyne 1: 42% inhibition, the triyne 3: 60% inhibition), and TNP-470 ( 82% inhibition) at a dose of 10 mu g/CAM, without showing toxicity. The diyne 2 also had potent inhibitory activity at a dose of 5 and 2.5 mu g/CAM. These results indicate that the flexibility of C8 alkyl chain of FTY720 is not required for its antiangiogenic activity. We suggest that the diyne 2 ( TX-2152) may be a promising candidate as an antiangiogenic agent for antineoplastic drug discovery. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.07.003

文献信息

• TX-2152: A conformationally rigid and electron-rich diyne analogue of FTY720 with in vivo antiangiogenic activity
  作者：Shinichi Nakayama、Yoshihiro Uto、Kanako Tanimoto、Yasuhiro Okuno、Yuki Sasaki、Hideko Nagasawa、Eiji Nakata、Ken Arai、Kaori Momose、Tetsuro Fujita、Toshihiro Hashimoto、Yasuko Okamoto、Yoshinori Asakawa、Satoru Goto、Hitoshi Hori

  DOI：10.1016/j.bmc.2008.07.003

  日期：2008.8

  We designed FTY720 analogues with conformationally rigid and electron-rich acetylenic chains as anti-angiogenic agents ( the monoyne 1: TX-2148, the diyne 2: TX-2152, the triyne 3: TX-2256). Molecular orbital ( MO) calculations of our designed acetylenic analogues and FTY720 showed that the localization of the lowest unoccupied MO and the highest occupied MO increased from phenyl ring to acetylenic chain compared with that of FTY720. These acetylenic analogues were synthesized from p-hydroxyphenylethanol as a starting material. The construction of the acetylenic chain was carried out by an iterative strategy using a Sonogashira cross-coupling reaction and desilylative bromination in two steps. The corresponding overall yields of the monoyne 1, the diyne 2, and the triyne 3 were 27% ( 11 steps), 13% ( 13 steps), and 10% ( 15 steps). The in vivo antiangiogenic activities of these acetylenic analogues and FTY720 were evaluated by the chick embryo chorioallantoic membrane ( CAM) assay and compared to the activities of the known antiangiogenic agent TNP-470. The diyne 2 showed more potent antiangiogenic activity ( 90% inhibition) than FTY720 ( 77% inhibition) and other acetylenic analogues ( the monoyne 1: 42% inhibition, the triyne 3: 60% inhibition), and TNP-470 ( 82% inhibition) at a dose of 10 mu g/CAM, without showing toxicity. The diyne 2 also had potent inhibitory activity at a dose of 5 and 2.5 mu g/CAM. These results indicate that the flexibility of C8 alkyl chain of FTY720 is not required for its antiangiogenic activity. We suggest that the diyne 2 ( TX-2152) may be a promising candidate as an antiangiogenic agent for antineoplastic drug discovery. (C) 2008 Elsevier Ltd. All rights reserved.