methyl 5-((3,5-dichloropyridin-4-yl)thio)-4-nitrothiophene-2-carboxylate | 1247820-24-1

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: methyl 5-((3,5-dichloropyridin-4-yl)thio)-4-nitrothiophene-2-carboxylate
• 英文别名: methyl 5-[(3,5-dichloro-4-pyridyl)sulfanyl]-4-nitrothiophene-2-carboxylate；Methyl 5-[(3,5-dichloro-4-pyridyl)sulfanyl]-4-nitro-thiophene-2-carboxylate；methyl 5-(3,5-dichloropyridin-4-yl)sulfanyl-4-nitrothiophene-2-carboxylate
• CAS: 1247820-24-1
• 化学式: C₁₁H₆Cl₂N₂O₄S₂
• 分子量: 365.218
• InChiKey: DMZVIOUGSPCFAB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  139
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl 5-((3,5-dichloropyridin-4-yl)thio)-4-nitrothiophene-2-carboxylate 在 水 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 、 sodium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 4.0h， 生成 5-[(3,5-dichloropyridin-4-yl)thio]-4-nitro-N-(4-sulfamoylphenyl)thiophene-2-carboxamide
  参考文献：
  名称：

  Selective Dual Inhibitors of the Cancer-Related Deubiquitylating Proteases USP7 and USP47

  摘要：

  Inhibitors of the cancer-related cysteine isopeptidase human ubiquitin-specific proteases 7 (USP7) and 47 (USP47) are considered to have potential as cancer therapeutics, owing to their ability to stabilize the tumor suppressor p53 and to decrease DNA polymerase beta (Pol beta), both of which are potential anticancer effects. A new class of dual small molecule inhibitors of these enzymes has been discovered. Compound 1, a selective inhibitor of USP7 and USP47 with moderate potency, demonstrates inhibition of USP7 in cells and induces elevated p53 and apoptosis in cancer cell lines. Compound 1 has been shown to demonstrate modest activity in human xenograft multiple myeloma and B-cell leukemia in vivo models. This activity may be the result of dual inhibition of USP7 and USP47. To address issues regarding potency and developability, analogues of compound 1 have been synthesized and tested, leading to improvements in potency, solubility, and metabolic reactivity profile. Further optimization is expected to yield preclinical candidates and, ultimately, clinical candidates for the treatment of multiple myeloma, prostate cancer, and other cancers.

  DOI：

  10.1021/ml200276j
• 作为产物：
  描述：

  3,4,5-三氯吡啶 在 sodium hydrogen sulfide 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 异丙醇 为溶剂， 生成 methyl 5-((3,5-dichloropyridin-4-yl)thio)-4-nitrothiophene-2-carboxylate
  参考文献：
  名称：

  Methods of treating cancer through the inhibition of USP7 and immune system modulation

  摘要：

  提供了治疗癌症的方法和化合物，例如通过调节免疫系统活性。

  公开号：

  US09717717B1

文献信息

• [EN] ANTI-NEOPLASTIC COMPOUNDS, COMPOSITIONS AND METHODS<br/>[FR] COMPOSÉS ANTINÉOPLASIQUES, COMPOSITIONS ET PROCÉDÉS
  申请人：PROGENRA INC

  公开号：WO2010114881A1

  公开（公告）日：2010-10-07

  Disclosed are novel compounds which are useful as therapeutics, especially in anti-neoplastic therapy and in other therapeutic regimes where cysteine protease inhibition is implicated.

  公开的是新型化合物，这些化合物在治疗上具有用途，特别是在抗肿瘤治疗和其他涉及半胱氨酸蛋白酶抑制的治疗方案中。
• Methods of treating cancer through the inhibition of USP7 and immune system modulation
  申请人：Progenra, Inc.

  公开号：US09717717B1

  公开（公告）日：2017-08-01

  Methods and compounds for treating cancer by, for example, modulating immune system activity, are provided.

  提供了治疗癌症的方法和化合物，例如通过调节免疫系统活性。
• 噻吩类化合物及其作为USP7抑制剂和抗肿瘤药物的应用
  申请人：中国药科大学

  公开号：CN109096271A

  公开（公告）日：2018-12-28

  本发明公开了如通式I所示的化合物或其氮氧化物、药学上可接受的盐或溶剂化物、其制备方法以及在制药中的用途，尤其是其作为USP7抑制剂和抗肿瘤药物的应用。药效学实验结果表明，本发明的式I化合物对USP7酶具有抑制作用，同时对人结肠癌细胞HCT‑116具有增殖抑制作用。因此本发明化合物可以用于制备预防或治疗肿瘤相关疾病的药物。
• ANTI-NEOPLASTIC COMPOUNDS, COMPOSITIONS AND METHODS
  申请人：Cao Ping

  公开号：US20120114765A1

  公开（公告）日：2012-05-10

  Disclosed are novel compounds which are useful as therapeutics, especially in anti-neoplastic therapy and in other therapeutic regimes where cysteine protease inhibition is implicated.

  本发明涉及一种新型化合物，可用作治疗剂，特别是在抗肿瘤疗法和其他治疗方案中具有半胱氨酸蛋白酶抑制作用的情况下。
• Anti-neoplastic compounds, compositions and methods
  申请人：Cao Ping

  公开号：US08680139B2

  公开（公告）日：2014-03-25

  Disclosed are novel compounds which are useful as therapeutics, especially in anti-neoplastic therapy and in other therapeutic regimes where cysteine protease inhibition is implicated.

  本发明涉及一种新的化合物，其可作为治疗药物，尤其是在抗肿瘤治疗和其他需要半胱氨酸蛋白酶抑制剂的治疗方案中。