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.
• Discovery of Potent Antimalarial Type II Kinase Inhibitors with Selectivity over Human Kinases
  作者：Lushun Wang、Monica J. Bohmer、Jinhua Wang、Flore Nardella、Jaeson Calla、Mariana Laureano De Souza、Kyra A. Schindler、Lukas Montejo、Nimisha Mittal、Frances Rocamora、Mayland Treat、Jordan T. Charlton、Patrick K. Tumwebaze、Philip J. Rosenthal、Roland A. Cooper、Ratna Chakrabarti、Elizabeth A. Winzeler、Debopam Chakrabarti、Nathanael S. Gray

  DOI：10.1021/acs.jmedchem.3c02046

  日期：2024.1.25

  urging a need for the development of novel antimalarial agents. Repurposing human kinase inhibitors provides a potential expedited route given the availability of a diverse array of kinase-targeting drugs that are approved or in clinical trials. Phenotypic screening of a library of type II human kinase inhibitors identified compound 1 as a lead antimalarial, which was initially developed to target human

  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 。