3-chloro-4-(2-cyano-3-(pyridazin-4-yl)phenoxy)-N-(2,2,6,6-tetramethylpiperidin-4-yl)benzamide | 1377997-28-8

• 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: 3-chloro-4-(2-cyano-3-(pyridazin-4-yl)phenoxy)-N-(2,2,6,6-tetramethylpiperidin-4-yl)benzamide
• 英文别名: EZ-CONS；Ezh2-in-3；3-chloro-4-(2-cyano-3-pyridazin-4-ylphenoxy)-N-(2,2,6,6-tetramethylpiperidin-4-yl)benzamide
• CAS: 1377997-28-8
• 化学式: C₂₇H₂₈ClN₅O₂
• 分子量: 490.005
• InChiKey: XLRMULHWFRKNQV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  35
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  99.9
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-氯-4-羟基苯甲酸 在 bis-triphenylphosphine-palladium(II) chloride 、 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 、 lithium chloride 作用下， 以 二氯甲烷 、 二甲基亚砜 、 甲苯 为溶剂， 反应 18.5h， 生成 3-chloro-4-(2-cyano-3-(pyridazin-4-yl)phenoxy)-N-(2,2,6,6-tetramethylpiperidin-4-yl)benzamide
  参考文献：
  名称：

  Discovery and Optimization of Tetramethylpiperidinyl Benzamides as Inhibitors of EZH2

  摘要：

  The identification and development of a novel series of small molecule Enhancer of Zeste Homologue 2 (EZH2) inhibitors is described. A concise and modular synthesis enabled the rapid development of structure activity relationships, which led to the identification of 44 as a potent, SAM-competitive inhibitor of EZH2 that dose-dependently decreased global H3K27me3 in KARPAS-422 lymphoma cells.

  DOI：

  10.1021/ml400494b

文献信息

• [EN] COMPOSITIONS AND METHODS FOR TREATING EZH2-MEDIATED CANCER<br/>[FR] COMPOSITIONS ET PROCÉDÉS POUR LE TRAITEMENT DU CANCER À MÉDIATION PAR L'EZH2
  申请人：ICAHN SCHOOL MED MOUNT SINAI

  公开号：WO2018081530A1

  公开（公告）日：2018-05-03

  Methods for designing bivalent compounds which selectively degrade/disrupt EZH2 and compositions and methods of using such degraders/disruptors to treat EZH2-mediated cancer are provided.

  提供的设计二价化合物的方法，这些化合物可选择性地降解/破坏EZH2，以及使用这种降解剂/破坏剂治疗EZH2介导的癌症的组合物和方法。
• MODULATORS OF METHYL MODIFYING ENZYMES, COMPOSITIONS AND USES THEREOF
  申请人：Albrecht Brian K.

  公开号：US20130310379A1

  公开（公告）日：2013-11-21

  Agents for modulating methyl modifying enzymes, compositions and uses thereof are provided herein.

  本文提供了用于调节甲基修饰酶的代理，以及其组合物和用途。
• INDOLE COMPOUNDS AS EZH2 INHIBITORS AND USES THEREOF
  申请人：Dana-Farber Cancer Institute, Inc.

  公开号：EP3885343A1

  公开（公告）日：2021-09-29

  The present disclosure provides compounds of Formula (II). The compounds described herein are inhibitors of histone methyltransferases (e.g., enhancer of zeste homolog 1 (EZH1) and enhancer of zeste homolog 2 (EZH2)) and are useful in treating and/or preventing a broad range of diseases (e.g., proliferative diseases). Also provided in the present disclosure are pharmaceutical compositions, kits, methods, and uses including or using a compound described herein. Further provided in the present disclosure are methods of identifying EZH1 and/or EZH2 inhibitors.

  本公开提供了式（II）化合物。 本文所述化合物是组蛋白甲基转移酶（如泽斯特同源增强子 1 (EZH1) 和泽斯特同源增强子 2 (EZH2)）的抑制剂，可用于治疗和/或预防多种疾病（如增殖性疾病）。本公开还提供了包括或使用本文所述化合物的药物组合物、试剂盒、方法和用途。本公开还提供了鉴定EZH1和/或EZH2抑制剂的方法。
• EZH2 inhibitors for treating lymphoma
  申请人：Epizyme, Inc.

  公开号：US10166238B2

  公开（公告）日：2019-01-01

  The present invention relates to compositions comprising inhibitors of human histone methyltransferase EZH2 and their use for the treatment of cancer.

  本发明涉及包含人组蛋白甲基转移酶 EZH2 抑制剂的组合物及其用于治疗癌症的用途。
• Method for treating cancer
  申请人：Epizyme, Inc.

  公开号：US10369155B2

  公开（公告）日：2019-08-06

  The present invention provides a method for treating or alleviating a symptom of a disorder, e.g., immune evasion, cancer-cell induced immune dysfunction, reduced immune response, lowered inflammation, decreased expression of a major histocompatibility complex (MHC), or cancer, characterized by aberrant, misregulated, or increased Enhancer of Zeste Homolog 2 (EZH2) activity in a cell or subject in need thereof by contacting the cell or administering to the subject a therapeutically effective amount of an EZH2 inhibitor.

  本发明提供了一种治疗或缓解紊乱症状的方法，例如免疫逃避、癌细胞诱导的免疫功能障碍、免疫反应减弱、炎症反应减弱、主要组织相容性复合体（MHC）表达减弱或癌症，这些紊乱症状的特征是需要治疗的细胞或受试者的泽斯特同源酶2（EZH2）活性异常、失调或增强，其方法是通过与细胞接触或向受试者施用治疗有效量的EZH2抑制剂。