5-chloro-4-(1H-indol-3-yl)-N-(piperidin-4-yl)pyrimidin-2-amine | 882563-09-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 5-chloro-4-(1H-indol-3-yl)-N-(piperidin-4-yl)pyrimidin-2-amine
• 英文别名: 5-chloro-4-(1H-indol-3-yl)-N-piperidin-4-ylpyrimidin-2-amine
• CAS: 882563-09-9
• 化学式: C₁₇H₁₈ClN₅
• 分子量: 327.816
• InChiKey: RXQNHZPQQVWITM-UHFFFAOYSA-N

物化性质

• 沸点：
  584.9±60.0 °C(Predicted)
• 密度：
  1.345±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  65.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-chloro-4-(1H-indol-3-yl)-N-(piperidin-4-yl)pyrimidin-2-amine 、 N-乙酰甘氨酸 在 1-羟基苯并三唑 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N-甲基吡咯烷酮 、 二氯甲烷 为溶剂， 以45%的产率得到N-(2-{4-[5-chloro-4-(1H-indol-3-yl)pyrimidin-2-ylamino]piperidin-1-yl}-2-oxoethyl)-acetamide
  参考文献：
  名称：

  [EN] AMINOPYRIMIDINE DERIVATIVES AS JNK INHIBITORS
  [FR] DERIVES D'AMINOPYRIMIDINE EN TANT QU'INHIBITEURS DE LA JNK

  摘要：

  式（I）的化合物或其药学上可接受的盐、溶剂或N-氧化物：其中A代表吡咯、吡唑、咪唑或三唑环；B代表苯、吡啶或嘧啶环；M代表氮杂环丙烷、吡咯丙烷或哌啶环的残基；E代表共价键或含有1至4个碳原子的可选取代的直链或支链烷基链；Z代表氢、-CORa、-C02Rb、-CONKcRd、-CONRcORb、-COCO2Rb、-COCONRcRd、-COCH2NRcRd、-COCH2NRcCONKcRd、COCH2NRcCO2Rb、-NRcCORa、-NRcCO2Rb、-NRcCONRcRd、-S02Re、-SO2NRcRd或-SO2NRcC02Rb；或Z代表可选取代的苯基、杂环芳基或C3-7杂环烷基基团；R1和R2独立地代表氢、卤素、氰基、硝基、C1-6烷基、三氟甲基、羟基、C1-6烷氧基、二氟甲氧基、三氟甲氧基、C1-6烷基磺酰基、氨基、C1-6烷基氨基、二(C1-6)烷基氨基、氨基甲酰基或C2-6烷氧羰基；R3代表氢、C1-6烷基、-CH2CONRcRd或-SO2Re；R4代表氢、C1-6烷氧基、氧代、-CO2Rb或-CONKcRd。本发明的化合物是JNK的有效抑制剂。

  公开号：

  WO2006038001A1
• 作为产物：
  描述：

  1-(苯磺酰基)-3-吲哚硼酸 在 四(三苯基膦)钯 盐酸 、 氢氧化钾 、 sodium carbonate 作用下， 以 甲醇 、 乙醚 、 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 8.0h， 生成 5-chloro-4-(1H-indol-3-yl)-N-(piperidin-4-yl)pyrimidin-2-amine
  参考文献：
  名称：

  Synthesis and SAR of aminopyrimidines as novel c-Jun N-terminal kinase (JNK) inhibitors

  摘要：

  The development of a series of novel aminopyrimidines as inhibitors of c-Jun N-terminal kinases is described. The synthesis, in vitro inhibitory values for JNK1, JNK2 and CDK2, and the in vitro inhibitory value for a c-Jun cellular assay are discussed. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.03.078

文献信息

• INHIBITORS OF CYCLIN-DEPENDENT KINASE 7 (CDK7)
  申请人：Syros Pharmaceuticals, Inc.

  公开号：EP3489232A2

  公开（公告）日：2019-05-29

  The present invention provides novel compounds of Formula (I) and Formula (II) and pharmaceutically acceptable salts, solvates, hydrates, tautomers, stereoisomers, isotopically labeled derivatives, and compositions thereof. Also provided are methods and kits involving the compounds or compositions for treating or preventing proliferative diseases (e.g.,cancers (e.g., leukemia, melanoma, multiple myeloma), benign neoplasms, 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 cyclin-dependent kinase 7 (CDK7), and therefore, induce cellular apoptosis and/or inhibit transcription in the subject.

  本发明提供了式(I)和式(II)的新型化合物及其药学上可接受的盐、溶液剂、水合物、同系物、立体异构体、同位素标记的衍生物及其组合物。还提供了涉及这些化合物或组合物的方法和试剂盒，用于治疗或预防受试者的增殖性疾病（如癌症（如白血病、黑色素瘤、多发性骨髓瘤）、良性肿瘤、血管生成、炎症性疾病、自身炎症性疾病和自身免疫性疾病）。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，可抑制细胞周期蛋白依赖性激酶7（CDK7）的异常活性，从而诱导细胞凋亡和/或抑制受试者体内的转录。
• 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%).
• CYCLIN-DEPENDENT KINASE 12 MODULATORS AND THERAPEUTIC USES THEREOF
  申请人：[en]ALLIANTHERA (SUZHOU) BIOPHARMACEUTICAL CO., LTD.

  公开号：WO2024148210A1

  公开（公告）日：2024-07-11

  Provided herein are compounds having a structure of Formula (I) and pharmaceutically acceptable salts thereof which can act as modulators of cyclin-dependent kinase 12 (CDK12). Further disclosed herein are methods for treating cancer and cancer-related diseases and disorders, such as breast cancer, ovarian cancer, prostate cancer, and gastric cancer.