3-(5-溴-2-氯嘧啶-4-基)-1-(苯基磺酰基)-1H-吲哚 | 1624262-44-7

• 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: 3-(5-溴-2-氯嘧啶-4-基)-1-(苯基磺酰基)-1H-吲哚
• 英文名称: 3-(5-bromo-2-chloropyrimidin-4-yl)-1-(phenylsulfonyl)-1H-indole
• 英文别名: 3-(5-Bromo-2-chloropyrimidin-4-yl)-1-(phenylsulfonyl)-1H-indole；1-(benzenesulfonyl)-3-(5-bromo-2-chloropyrimidin-4-yl)indole
• CAS: 1624262-44-7
• 化学式: C₁₈H₁₁BrClN₃O₂S
• 分子量: 448.727
• InChiKey: ATOBJZOVMPIWCJ-UHFFFAOYSA-N

物化性质

• 沸点：
  668.1±65.0 °C(Predicted)
• 密度：
  1.65±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  26
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  73.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(5-溴-2-氯嘧啶-4-基)-1-(苯基磺酰基)-1H-吲哚 在 吡啶 、 N-甲基吡咯烷酮 、 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 、 乙腈 为溶剂， 反应 9.17h， 生成 (R,E)-N-(4-(3-((5-bromo-4-(1H-indol-3-yl)pyrimidin-2-yl)amino)piperidine-1-carbonyl)phenyl)-4-(dimethylamino)but-2-enamide
  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
• 作为产物：
  描述：

  吲哚 在 aluminum (III) chloride 、 sodium t-butanolate 作用下， 以 四氢呋喃 、 1,2-二氯乙烷 为溶剂， 反应 19.5h， 生成 3-(5-溴-2-氯嘧啶-4-基)-1-(苯基磺酰基)-1H-吲哚
  参考文献：
  名称：

  [EN] INHIBITORS OF CYCLIN-DEPENDENT KINASE 7 (CDK7)
  [FR] INHIBITEURS DE LA KINASE 7 DÉPENDANTE DES CYCLINES (CDK7)

  摘要：

  公开号：

  WO2018013867A8

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。
• Targeting the Gatekeeper MET146 of C-Jun N-Terminal Kinase 3 Induces a Bivalent Halogen/Chalcogen Bond
  作者：Andreas Lange、Marcel Günther、Felix Michael Büttner、Markus O. Zimmermann、Johannes Heidrich、Susanne Hennig、Stefan Zahn、Christoph Schall、Adrian Sievers-Engler、Francesco Ansideri、Pierre Koch、Michael Laemmerhofer、Thilo Stehle、Stefan A. Laufer、Frank M. Boeckler

  DOI：10.1021/jacs.5b07090

  日期：2015.11.25

  We target the gatekeeper MET 146 of c-Jun N-terminal kinase 3 (JNK3) to exemplify the applicability of X...s halogen bonds in molecular design using computational, synthetic, structural and biophysical techniques. In a designed series of aminopyrimidine-based inhibitors, we unexpectedly encounter a plateau of affinity. Compared to their QM-calculated interaction energies, particularly bromine and iodine fail to reach the full potential according to the size of their sigma-hole. Instead, mutation of the gatekeeper residue into leucine, alanine, or thereonine reveals that the heavier halides can significantly influence selectivity in the human kinome. Thus, we demonstrate that, although the choice of halogen may not always increase affinity, it can still be relevant for inducing selectivity. Determining the crystal structure of the iodine derivative in complex with JNK3 (4X21) reveals an unusual bivalent halogen/chalcogen bond donated by the ligand and the back-pocket residue MET115. Incipient repulsion from the too short halogen bond increase the flexibility of C-epsilon of MET146, whereas the rest of the residue fails to adapt being fixed by the chalcogen bond. This effect can be useful to induce selectivity, as the necessary combination of methionine residues only occurs in 9.3% of human kinases, while methioine is the predominant gatekeeper (39%).
• 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
• [EN] INHIBITORS OF CYCLIN-DEPENDENT KINASE 7 (CDK7)<br/>[FR] INHIBITEURS DE LA KINASE 7 DÉPENDANTE DES CYCLINES (CDK7)
  申请人：MARINEAU JASON J

  公开号：WO2018013867A8

  公开（公告）日：2018-11-15
• 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