N10-(trifluoroacetyl)pyrofolic acid | 197151-66-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N10-(trifluoroacetyl)pyrofolic acid
• 英文别名: Unk-N(Tfa)4Abz-Pyr-OH；(2S)-1-[4-[(2-amino-4-oxo-3H-pteridin-6-yl)methyl-(2,2,2-trifluoroacetyl)amino]benzoyl]-5-oxopyrrolidine-2-carboxylic acid
• CAS: 197151-66-9
• 化学式: C₂₁H₁₆F₃N₇O₆
• 分子量: 519.397
• InChiKey: QPNWGDDPYOIIRR-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  37
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  188
• 氢给体数：
  3
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  N10-(trifluoroacetyl)pyrofolic acid 在 亚硝酸特丁酯 、 potassium thioacyanate 、 三氟乙酸 、 肼 作用下， 以 二甲基亚砜 为溶剂， 反应 12.0h， 生成 pteroyl azide
  参考文献：
  名称：

  Synthesis, characterization, and anticancer activity of folate γ-ferrocenyl conjugates

  摘要：

  通过一个特定的路线合成了新型的叶酸γ-二茂铁共轭物，并且表现出对Frα阳性的恶性细胞的选择性和增强的细胞毒性。

  DOI：

  10.1039/c9nj04954a
• 作为产物：
  描述：

  三氟乙酸酐 、 folate 以 四氢呋喃 为溶剂， 反应 6.5h， 以88%的产率得到N10-(trifluoroacetyl)pyrofolic acid
  参考文献：
  名称：

  Folate-modified cholesterol-bearing pullulan as a drug carrier

  摘要：

  叶酸修饰的胆固醇载体泊洛聚糖（FA-CHP）是通过叶酸γ-2-氨基乙酰胺和4-硝基苯基氯甲酸酯活化的胆固醇载体泊洛聚糖反应合成的，其中叶酸和泊洛聚糖通过一个NH—CH2—CH2—NH基团连接。每约100个葡糖苷单元中连接了大约0.5-1个叶酸。然后，对叶酸修饰的胆固醇载体泊洛聚糖（FA-CHP）、胆固醇载体泊洛聚糖（CHP）和阿霉素（DOX）混合物进行了多种组合的癌症选择性细胞毒性测试。FA-CHP、CHP和DOX的混合物比例为1:4:0.02（重量比）对人表皮癌KB细胞具有高叶酸受体表达水平的细胞造成了明显和选择性的损伤。同样的混合物抑制了HuH7细胞的生长，这是一种人类肝细胞癌，并且未知是否具有叶酸受体。

  公开号：

  US20070042970A1

文献信息

• Design and structure activity relationship of tumor-homing histone deacetylase inhibitors conjugated to folic and pteroic acids
  作者：Quaovi H. Sodji、James R. Kornacki、John F. McDonald、Milan Mrksich、Adegboyega K. Oyelere

  DOI：10.1016/j.ejmech.2015.04.014

  日期：2015.5

  Histone deacetylase (HDAC) inhibition has recently emerged as a novel therapeutic approach for the treatment of various pathological conditions including cancer. Currently, two HDAC inhibitors (HDACi) - Vorinostat and Romidepsin - have been approved for the treatment of cutaneous T-cell lymphoma. However, HDACi remain ineffective against solid tumors and are associated with adverse events including cardiotoxicity. Targeted delivery may enhance the therapeutic indices of HDACi and enable them to be efficacious against solid tumors. We showed herein that morphing of folic and pteroic acids into the surface recognition group of HDACi results in hydroxamate and benzamide HDACi which derived tumor homing by targeting folate receptor (FR), a receptor commonly overexpressed in solid tumors. We observed a correlation between the potency of HDAC1 inhibition and cytotoxicity as only the potent pteroate hydroxamates, 11d and 11e, displayed antiproliferative activity against two representative FR-expression cancer cells. Our observation further supports the previous results which suggest that for a drug to be successfully targeted using the FR, it must be extremely potent against its primary target as the FR has a low delivery efficiency. Published by Elsevier Masson SAS.
• Folic acid conjugates of a bleomycin mimic for selective targeting of folate receptor positive cancer cells
  作者：Arjan Geersing、Reinder H. de Vries、Gerrit Jansen、Marianne G. Rots、Gerard Roelfes

  DOI：10.1016/j.bmcl.2019.05.047

  日期：2019.8

  A major challenge in the application of cytotoxic anti-cancer drugs is their general lack of selectivity, which often leads to systematic toxicity due to their inability to discriminate between malignant and healthy cells. A particularly promising target for selective targeting are the folate receptors (FR) that are often over-expressed on cancer cells. Here, we report on a conjugate of the pentadentate nitrogen ligand N4Py to folic acid, via a cleavable disulphide linker, which shows selective cytotoxicity against folate receptor expressing cancer cells.
• Folate-modified cholesterol-bearing pullulan as a drug carrier
  申请人：Sunamoto Junzo

  公开号：US20070042970A1

  公开（公告）日：2007-02-22

  Folate modified cholesterol-bearing pullulan (FA-CHP) was synthesized by the reaction of folic acid γ-2-aminoethylamide and 4-nitorophenyl chloroformate-activated cholesterol-bearing pullulan, wherein folate and pullulan are connected through a NH—CH 2 —CH 2 —NH group. Approximately 0.5-1 folates are connected per about 100 glycoside units of pullulan. Then, several combinations of FA-CHP, cholesterol-bearing pullulan (CHP) and doxorubicin (DOX) mixture were tested for cancer selective cytotoxicity. A mixture of FA-CHP, CHP and DOX of 1:4:0.02 (weight ratio) gave sharp and selective damage to cells of a human epidermoid cancer KB known as expressing a high level of folate receptor. The same mixture inhibited the growth of HuH7 cells, which is a human hepatocellular carcinoma and is unknown as a folate receptor.

  叶酸修饰的胆固醇载体泊洛聚糖（FA-CHP）是通过叶酸γ-2-氨基乙酰胺和4-硝基苯基氯甲酸酯活化的胆固醇载体泊洛聚糖反应合成的，其中叶酸和泊洛聚糖通过一个NH—CH2—CH2—NH基团连接。每约100个葡糖苷单元中连接了大约0.5-1个叶酸。然后，对叶酸修饰的胆固醇载体泊洛聚糖（FA-CHP）、胆固醇载体泊洛聚糖（CHP）和阿霉素（DOX）混合物进行了多种组合的癌症选择性细胞毒性测试。FA-CHP、CHP和DOX的混合物比例为1:4:0.02（重量比）对人表皮癌KB细胞具有高叶酸受体表达水平的细胞造成了明显和选择性的损伤。同样的混合物抑制了HuH7细胞的生长，这是一种人类肝细胞癌，并且未知是否具有叶酸受体。
• Synthesis, characterization, and anticancer activity of folate γ-ferrocenyl conjugates
  作者：Diego L. Bertuzzi、Gabriel Perli、Carolyne B. Braga、Catia Ornelas

  DOI：10.1039/c9nj04954a

  日期：——

  Novel folate γ-ferrocene conjugates were synthesized through a regiospecific route, and showed selectivity and enhanced cytotoxicity against Frα-positive malignant cells.

  通过一个特定的路线合成了新型的叶酸γ-二茂铁共轭物，并且表现出对Frα阳性的恶性细胞的选择性和增强的细胞毒性。