4-氰基-5-[(3,5-二氯-4-吡啶基)硫基]-N-[4-(甲基磺酰基)苯基]-2-噻吩甲酰胺 | 1247825-37-1

• 物质功能分类: 生物化工 - 生化试剂 - 激动剂抑制剂
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 4-氰基-5-[(3,5-二氯-4-吡啶基)硫基]-N-[4-(甲基磺酰基)苯基]-2-噻吩甲酰胺
• 英文名称: 4-cyano-5-[(3,5-dichloropyridin-4-yl)thio]-N-[4-(methylsulfonyl)phenyl]thiophene-2-carboxamide
• 英文别名: P50429；USP7/USP47 inhibitor；4-cyano-5-(3,5-dichloropyridin-4-yl)sulfanyl-N-(4-methylsulfonylphenyl)thiophene-2-carboxamide
• CAS: 1247825-37-1
• 化学式: C₁₈H₁₁Cl₂N₃O₃S₃
• 分子量: 484.408
• InChiKey: GUDJFFQZIISQJB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  29
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  162
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  3,4,5-三氯吡啶 在 sodium hydrogen sulfide monohydrate 、 三甲基铝 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 、 异丙醇 、 甲苯 为溶剂， 反应 18.75h， 生成 4-氰基-5-[(3,5-二氯-4-吡啶基)硫基]-N-[4-(甲基磺酰基)苯基]-2-噻吩甲酰胺
  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

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。
• 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。
• Protein degradation inducing tag and usage thereof
  申请人：Tokyo University of Science Foundation

  公开号：US10976306B2

  公开（公告）日：2021-04-13

  Provided are: a protein degradation inducing tag which is a molecule that has affinity with proteases and does not inhibit degradation of a protein by proteases; a protein degradation inducing molecule that is a conjugate of at least one protein degradation inducing tag and at least one protein binding molecule that binds to a protein; and a usage of those.

  提供了：一种蛋白质降解诱导标签，它是一种与蛋白酶具有亲和力的分子，不会抑制蛋白酶对蛋白质的降解；一种蛋白质降解诱导分子，它是至少一种蛋白质降解诱导标签和至少一种与蛋白质结合的蛋白质结合分子的共轭物；以及它们的用法。
• P53 degradation inducing molecule and pharmaceutical composition
  申请人：Tokyo University of Science Foundation

  公开号：US11007269B2

  公开（公告）日：2021-05-18

  A p53 degradation inducing molecule which can induce degradation of p53 proteins or p53 composites, and a pharmaceutical composition containing said p53 degradation inducing molecule are provided. This p53 degradation inducing molecule is a conjugate of a p53 affinity molecule which has affinity for p53 proteins or p53 composites, and a proteolysis induction tag which has affinity for protease and which does not inhibit proteolysis of proteins by protease.

  本发明提供了一种可诱导 p53 蛋白或 p53 复合物降解的 p53 降解诱导分子，以及一种含有所述 p53 降解诱导分子的药物组合物。这种 p53 降解诱导分子是对 p53 蛋白质或 p53 复合物具有亲和力的 p53 亲和分子与对蛋白酶具有亲和力且不抑制蛋白酶对蛋白质的蛋白水解的蛋白水解诱导标签的共轭物。