(R)-N-(4-(3-((5-chloro-4-(1H-indol-3-yl)pyrimidin-2-yl)amino)piperidin-1-yl)phenyl)acrylamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (R)-N-(4-(3-((5-chloro-4-(1H-indol-3-yl)pyrimidin-2-yl)amino)piperidin-1-yl)phenyl)acrylamide
• 英文别名: N-[4-[(3R)-3-[[5-chloro-4-(1H-indol-3-yl)pyrimidin-2-yl]amino]piperidin-1-yl]phenyl]prop-2-enamide
• 化学式: C₂₆H₂₅ClN₆O
• 分子量: 472.977
• InChiKey: AVAYAPINYJTPQZ-GOSISDBHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  85.9
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  1-(苯磺酰基)-3-吲哚硼酸 在 N-甲基吡咯烷酮 、 四(三苯基膦)钯 、 sodium carbonate 、 N,N-二异丙基乙胺 、 三氟乙酸 、 tin(ll) chloride 、 sodium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 16.67h， 生成 (R)-N-(4-(3-((5-chloro-4-(1H-indol-3-yl)pyrimidin-2-yl)amino)piperidin-1-yl)phenyl)acrylamide
  参考文献：
  名称：

  Structure-activity relationship study of THZ531 derivatives enables the discovery of BSJ-01-175 as a dual CDK12/13 covalent inhibitor with efficacy in Ewing sarcoma

  摘要：

  DOI：

  10.1016/j.ejmech.2021.113481

文献信息

• [EN] INHIBITORS OF CYCLIN-DEPENDENT KINASE 12 (CDK12) AND USES THEREOF<br/>[FR] INHIBITEURS DE KINASE 12 DÉPENDANTE DES CYCLINES (CDK12) ET LEURS UTILISATIONS
  申请人：DANA FARBER CANCER INST INC

  公开号：WO2018098361A1

  公开（公告）日：2018-05-31

  The present invention provides novel compounds of Formulae (I') and (II), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating and/or preventing proliferative diseases (e.g., cancers (e.g., leukemia, acute lymphoblastic leukemia, lymphoma, Burkitt's lymphoma, melanoma, multiple myeloma, breast cancer, Ewing's sarcoma, osteosarcoma, brain cancer, ovarian cancer, neuroblastoma, lung cancer, colorectal cancer), benign neoplasms, diseases associated with angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of a kinase, such as a cyclin-dependent kinase (CDK) (e.g., CDK12), and therefore, induce cellular apoptosis and/or inhibit transcription in the subject.

  本发明提供了式(I')和(II)的新化合物，以及这些化合物的药学可接受的盐、溶剂合物、水合物、多晶形态、共晶体、互变异构体、立体异构体、同位素标记衍生物、前药和其组合物。还提供了涉及这些新颖化合物或组合物的方法和试剂盒，用于治疗和/或预防增生性疾病（例如，癌症（例如，白血病、急性淋巴细胞白血病、淋巴瘤、伯基特淋巴瘤、黑色素瘤、多发性骨髓瘤、乳腺癌、尤因氏肉瘤、骨肉瘤、脑癌、卵巢癌、神经母细胞瘤、肺癌、结肠直肠癌）、良性肿瘤、与血管生成有关的疾病、炎症性疾病、自身炎症性疾病和自身免疫疾病）的主体。使用本发明的化合物或组合物治疗患有增生性疾病的主体可能抑制激酶（例如，细胞周期依赖性激酶（CDK）（例如，CDK12））的异常活性，从而诱导主体内的细胞凋亡和/或抑制转录。
• Inhibitors of cyclin-dependent kinase 12 (CDK12) and uses thereof
  申请人：Dana-Farber Cancer Institute, Inc.

  公开号：US11306070B2

  公开（公告）日：2022-04-19

  The present invention provides novel compounds of Formulae (I′) and (II), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. Also provided are methods and kits involving the inventive compounds or compositions for treating and/or preventing proliferative diseases (e.g., cancers (e.g., leukemia, acute lymphoblastic leukemia, lymphoma, Burkitt's lymphoma, melanoma, multiple myeloma, breast cancer, Ewing's sarcoma, osteosarcoma, brain cancer, ovarian cancer, neuroblastoma, lung cancer, colorectal cancer), benign neoplasms, diseases associated with angiogenesis, inflammatory diseases, autoinflammatory diseases, and autoimmune diseases) in a subject. Treatment of a subject with a proliferative disease using a compound or composition of the invention may inhibit the aberrant activity of a kinase, such as a cyclin-dependent kinase (CDK) (e.g., CDK12), and therefore, induce cellular apoptosis and/or inhibit transcription in the subject.

  本发明提供了式(I′)和(II)的新型化合物及其药学上可接受的盐、溶液剂、水合物、多晶型、共晶体、同分异构体、立体异构体、同位素标记的衍生物、原药及其组合物。还提供了涉及本发明化合物或组合物的方法和试剂盒，用于治疗和/或预防增殖性疾病（如癌症（如、白血病、急性淋巴细胞白血病、淋巴瘤、伯基特淋巴瘤、黑色素瘤、多发性骨髓瘤、乳腺癌、尤文氏肉瘤、骨肉瘤、脑癌、卵巢癌、神经母细胞瘤、肺癌、结直肠癌）、良性肿瘤、与血管生成相关的疾病、炎症性疾病、自身炎症性疾病和自身免疫性疾病）的方法和试剂盒。使用本发明的化合物或组合物治疗患有增殖性疾病的受试者，可抑制激酶的异常活性，如细胞周期蛋白依赖性激酶（CDK）（如CDK12），从而诱导细胞凋亡和/或抑制受试者的转录。
• INHIBITORS OF CYCLIN-DEPENDENT KINASE 12 (CDK12) AND USES THEREOF
  申请人：Dana-Farber Cancer Institute, Inc.

  公开号：EP3544971A1

  公开（公告）日：2019-10-02
• Structure-activity relationship study of THZ531 derivatives enables the discovery of BSJ-01-175 as a dual CDK12/13 covalent inhibitor with efficacy in Ewing sarcoma
  作者：Baishan Jiang、Jie Jiang、Ines H. Kaltheuner、Amanda Balboni Iniguez、Kanchan Anand、Fleur M. Ferguson、Scott B. Ficarro、Bo Kyung Alex Seong、Ann Katrin Greifenberg、Sofia Dust、Nicholas P. Kwiatkowski、Jarrod A. Marto、Kimberly Stegmaier、Tinghu Zhang、Matthias Geyer、Nathanael S. Gray

  DOI：10.1016/j.ejmech.2021.113481

  日期：2021.10