N-(2-chloro-5-((4-((4-ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)carbamoyl)phenyl)-5-(thiophen-2-yl)nicotinamide

• 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: N-(2-chloro-5-((4-((4-ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)carbamoyl)phenyl)-5-(thiophen-2-yl)nicotinamide
• 英文别名: N-[2-chloro-5-[[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]carbamoyl]phenyl]-5-thiophen-2-ylpyridine-3-carboxamide
• 化学式: C₃₁H₂₉ClF₃N₅O₂S
• 分子量: 628.118
• InChiKey: OIJXWLXNEXPASL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  43
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  106
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  4-氯-3-硝基苯甲酸 在 铁粉 、 氯化铵 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.5h， 生成 N-(2-chloro-5-((4-((4-ethylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)carbamoyl)phenyl)-5-(thiophen-2-yl)nicotinamide
  参考文献：
  名称：

  发现比人类激酶具有选择性的强效抗疟 II 型激酶抑制剂

  摘要：

  尽管根除疟疾的努力取得了进展，但该疾病仍然对全球健康构成重大威胁。非洲正在出现对一线治疗的获得性耐药，这迫切需要开发新型抗疟药物。鉴于已批准或正在进行临床试验的多种激酶靶向药物的可用性，重新利用人类激酶抑制剂提供了一条潜在的快速途径。对 II 型人类激酶抑制剂库的表型筛选将化合物1鉴定为一种主要抗疟药，该药物最初是针对人类肝配蛋白 A 型受体 2 (EphA2) 开发的。在这里，我们报告了化合物1的构效关系研究和先导化合物优化，最终得到了具有改善的抗疟活性和选择性的化合物33 。

  DOI：

  10.1021/acs.jmedchem.3c02046

文献信息

• Methods to treat lymphoplasmacytic lymphoma
  申请人：Dana-Farber Cancer Institute, Inc.

  公开号：US10597387B2

  公开（公告）日：2020-03-24

  The present invention provides compounds of any one of Formulae (I) to (V) (e.g., compounds of any one of Formulae (I-1) to (I-9)), and methods for treating Waldenström's macroglobulinemia (WM) and other B cell neoplams in a subject using the compounds. The methods comprise administering to a subject in need thereof an effective amount of the compounds. Also provided are methods to treat B cell neoplasms using the compounds in combination with inhibitors of Bruton's tyrosine kinase (BTK), interleukin-1 receptor-associated kinase 1 (IRAK1), interleukin-1 receptor-associated kinase 4 (IRAK4), bone marrow on X chromosome kinase (BMX), phosphoinositide 3-kinase (PI3K), transforming growth factor b-activated kinase-1 (TAK1), and/or a Src family kinase.

  本发明提供了式(I)至(V)中任一项的化合物(例如，式(I-1)至(I-9)中任一项的化合物)，以及使用这些化合物治疗受试者的瓦尔登斯特伦巨球蛋白血症(WM)和其他B细胞肿瘤的方法。这些方法包括向有需要的受试者施用有效量的化合物。还提供了使用化合物与布鲁顿酪氨酸激酶（BTK）、白介素-1 受体相关激酶 1（IRAK1）抑制剂联合治疗 B 细胞肿瘤的方法、白细胞介素-1 受体相关激酶 4 (IRAK4)、骨髓 X 染色体激酶 (BMX)、磷酸肌醇 3- 激酶 (PI3K)、转化生长因子 b 激活激酶-1 (TAK1)和/或 Src 家族激酶的抑制剂。
• METHODS TO TREAT LYMPHOPLASMACYTIC LYMPHOMA
  申请人：DANA-FARBER CANCER INSTITUTE, INC.

  公开号：US20160311807A1

  公开（公告）日：2016-10-27

  The present invention provides compounds of any one of Formulae (I) to (V) (e.g., compounds of any one of Formulae (I-1) to (I-9)), and methods for treating Waldenström's macroglobulinemia (WM) and other B cell neoplams in a subject using the compounds. The methods comprise administering to a subject in need thereof an effective amount of the compounds. Also provided are methods to treat B cell neoplasms using the compounds in combination with inhibitors of Bruton's tyrosine kinase (BTK), interleukin-1 receptor-associated kinase 1 (IRAK1), interleukin-1 receptor-associated kinase 4 (IRAK4), bone marrow on X chromosome kinase (BMX), phosphoinositide 3-kinase (PI3K), transforming growth factor b-activated kinase-1 (TAK1), and/or a Src family kinase.
• US9908872B2
  申请人：——

  公开号：US9908872B2

  公开（公告）日：2018-03-06
• [EN] METHODS TO TREAT LYMPHOPLASMACYTIC LYMPHOMA<br/>[FR] PROCÉDÉ POUR TRAITER UN LYMPHOME LYMPHOPLASMOCYTAIRE
  申请人：DANA FARBER CANCER INST INC

  公开号：WO2015089481A2

  公开（公告）日：2015-06-18

  The present invention provides compounds of any one of Formulae (I) to (V) (e.g., compounds of any one of Formulae (I-l) to (1-9)), and methods for treating Waldenstrom' s macroglobulinemia (WM) and other B cell neoplams in a subject using the compounds. The methods comprise administering to a subject in need thereof an effective amount of the compounds. Also provided are methods to treat B cell neoplasms using the compounds in combination with inhibitors of Bruton's tyrosine kinase (BTK), interleukin- 1 receptor- associated kinase 1 (IRAKI), interleukin- 1 receptor-associated kinase 4 (IRAK4), bone marrow on X chromosome kinase (BMX), phosphoinositide 3-kinase (PI3K), transforming growth factor b-activated kinase- 1 (TAK1), and/or a Src family kinase.