| 2734746-28-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并嘧啶类
• CAS: 2734746-28-0
• 化学式: C₃₁H₄₉ClN₅O₁₁P
• 分子量: 734.18
• InChiKey: SVJHDTLAGWSRKV-XBGIRIFCSA-N

物化性质

• 密度：
  1.45±0.1 g/cm³ (Predicted,Temp: 20 °C; Press: 760 Torr)
• pKa：
  13.54±0.10 (Predicted,Most Acidic Temp: 25 °C)

反应信息

• 作为反应物：
  描述：

  在 triethylamine radical cation 、 三甲基溴硅烷 、 三氟乙酸 、 水 作用下， 以 乙腈 为溶剂， 以65 %的产率得到6-chloro-N-cyclopentyl-1-{5-O-[(2R)-1-hydroxy-3-methoxy-2-phosphonopropan-2-yl]-beta-D-ribofuranosyl}-1H-pyrazolo[3,4-d]pyrimidin-4-amine
  参考文献：
  名称：

  Orally Bioavailable Small-Molecule CD73 Inhibitor (OP-5244) Reverses Immunosuppression through Blockade of Adenosine Production

  摘要：

  The adenosinergic pathway represents an attractive new therapeutic approach in cancer immunotherapy. In this pathway, ecto-5-nucleotidase CD73 has the unique function of regulating production of immunosuppressive adenosine (ADO) through the hydrolysis of AMP. CD73 is overexpressed in many cancers, resulting in elevated levels of ADO that correspond to poor patient prognosis. Therefore, reducing the level of ADO via inhibition of CD73 is a potential strategy for treating cancers. Based on the binding mode of adenosine 5'-(alpha,beta-methylene)-diphosphate (AOPCP) with human CD73, we designed a series of novel monophosphonate small-molecule CD73 inhibitors. Among them, OP-5244 (35) proved to be a highly potent and orally bioavailable CD73 inhibitor. In preclinical studies, 35 completely inhibited ADO production in both human cancer cells and CD8(+) T cells. Furthermore, 35 lowered the ratio of ADO/AMP significantly and reversed immunosuppression in mouse models, indicating its potential as an in vivo tool compound for further development.

  DOI：

  10.1021/acs.jmedchem.0c01086