N-benzyl-5-[(3,5-dichloro-4-pyridyl)sulfanyl]-4-nitro-thiophene-2-carboxamide | 1247820-29-6

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: N-benzyl-5-[(3,5-dichloro-4-pyridyl)sulfanyl]-4-nitro-thiophene-2-carboxamide
• 英文别名: N-benzyl-5-(3,5-dichloropyridin-4-yl)sulfanyl-4-nitrothiophene-2-carboxamide
• CAS: 1247820-29-6
• 化学式: C₁₇H₁₁Cl₂N₃O₃S₂
• 分子量: 440.331
• InChiKey: QRARWSPKIQBIQB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  27
• 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：
  141
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3,4,5-三氯吡啶 在 sodium hydrogen sulfide monohydrate 、 水 、 potassium carbonate 、 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 、 甲醇 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 25.0h， 生成 N-benzyl-5-[(3,5-dichloro-4-pyridyl)sulfanyl]-4-nitro-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

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。
• US8680139B2
  申请人：——

  公开号：US8680139B2

  公开（公告）日：2014-03-25
• Selective Dual Inhibitors of the Cancer-Related Deubiquitylating Proteases USP7 and USP47
  作者：Joseph Weinstock、Jian Wu、Ping Cao、William D. Kingsbury、Jeffrey L. McDermott、Matthew P. Kodrasov、Devin M. McKelvey、K. G. Suresh Kumar、Seth J. Goldenberg、Michael R. Mattern、Benjamin Nicholson

  DOI：10.1021/ml200276j

  日期：2012.10.11

  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.