5-bromo-2,6-dichloronicotinonitrile | 1823375-18-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 5-bromo-2,6-dichloronicotinonitrile
• 英文别名: 5-bromo-2,6-dichloropyridine-3-carbonitrile
• CAS: 1823375-18-3
• 化学式: C₆HBrCl₂N₂
• 分子量: 251.897
• InChiKey: FSLHBMXZVCGMSM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  36.7
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-bromo-2,6-dichloronicotinonitrile 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 碳酸氢钠 、 三氟乙酸 、 肼 作用下， 以 1,4-二氧六环 、 乙醇 、 水 为溶剂， 反应 2.0h， 生成 8-[4-[(Dimethylamino)methyl]phenyl]-5-(furan-2-ylmethylamino)-[1,2,4]triazolo[4,3-a]pyridine-6-carbonitrile
  参考文献：
  名称：

  Discovery of First-in-Class, Potent, and Orally Bioavailable Embryonic Ectoderm Development (EED) Inhibitor with Robust Anticancer Efficacy

  摘要：

  Overexpression and somatic heterozygous mutations of EZH2, the catalytic subunit of polycomb repressive complex 2 (PRC2), are associated with several tumor types. EZH2 inhibitor, EPZ-6438 (tazemetostat), demonstrated clinical efficacy in patients with acceptable safety profile as monotherapy. EED, another subunit of PRC2 complex, is essential for its histone methyltransferase activity through direct binding to trimethylated lysine 27 on histone 3 (H3K27Me3). Herein we disclose the discovery of a first-in-class potent, selective, and orally bioavailable EED inhibitor compound 43 (EED226). Guided by X-ray crystallography, compound 43 was discovered by fragmentation and regrowth of compound 7, a PRC2 HTS hit that directly binds EED. The ensuing scaffold hopping followed by multiparameter optimization led to the discovery of 43. Compound 43 induces robust and sustained tumor regression in EZH2(MUT) preclinical DLBCL model. For the first time we demonstrate that specific and direct inhibition of EED can be effective as an anticancer strategy.

  DOI：

  10.1021/acs.jmedchem.6b01576
• 作为产物：
  描述：

  5-bromo-2,6-dihydroxynicotinonitrile 在 三氯氧磷 作用下， 反应 2.0h， 以27%的产率得到5-bromo-2,6-dichloronicotinonitrile
  参考文献：
  名称：

  Discovery of First-in-Class, Potent, and Orally Bioavailable Embryonic Ectoderm Development (EED) Inhibitor with Robust Anticancer Efficacy

  摘要：

  Overexpression and somatic heterozygous mutations of EZH2, the catalytic subunit of polycomb repressive complex 2 (PRC2), are associated with several tumor types. EZH2 inhibitor, EPZ-6438 (tazemetostat), demonstrated clinical efficacy in patients with acceptable safety profile as monotherapy. EED, another subunit of PRC2 complex, is essential for its histone methyltransferase activity through direct binding to trimethylated lysine 27 on histone 3 (H3K27Me3). Herein we disclose the discovery of a first-in-class potent, selective, and orally bioavailable EED inhibitor compound 43 (EED226). Guided by X-ray crystallography, compound 43 was discovered by fragmentation and regrowth of compound 7, a PRC2 HTS hit that directly binds EED. The ensuing scaffold hopping followed by multiparameter optimization led to the discovery of 43. Compound 43 induces robust and sustained tumor regression in EZH2(MUT) preclinical DLBCL model. For the first time we demonstrate that specific and direct inhibition of EED can be effective as an anticancer strategy.

  DOI：

  10.1021/acs.jmedchem.6b01576

文献信息

• PROCESS FOR PRODUCING CYANOPYRIDINE
  申请人：IHARA CHEMICAL INDUSTRY CO., LTD.

  公开号：EP0700903A1

  公开（公告）日：1996-03-13

  A process for producing a cyanopyridine represented by general formula (3) (wherein R represents hydrogen or halogen; X¹ and X² represent each hydrogen or halogen, provided at least one of them represents halogen; and n represents an integer of 1 or 2), characterized by reacting an ammonium halide with a trichloromethylpyridine represented by general formula (1) (wherein R, X¹, X² and n are each as defined above) in the presence of a metal compound represented by the general formula (2): MXm wherein M represents copper or zinc; X represents halogen or oxygen; and m represents an integer of 2 or 1.

  一种生产通式(3)代表的氰基吡啶的工艺(其中R代表氢或卤素；X¹和X²各自代表氢或卤素，但至少其中一个代表卤素；n代表1或2的整数)，其特征在于在通式(2)代表的金属化合物存在下，使卤化铵与通式(1)代表的三氯甲基吡啶反应(其中R、X¹、X²和n各自如上定义)：MXm 其中 M 代表铜或锌；X 代表卤素或氧；m 代表 2 或 1 的整数。
• [EN] USE OF TRIAZOLOPYRIMIDINE, TRIAZOLOPYRIDINE COMPOUNDS AND COMPOSITION THEREOF FOR TREATING PRC2-MEDIATED DISEASES<br/>[FR] UTILISATION DE TRIAZOLOPYRIMIDINE, DE COMPOSÉS DE TRIAZOLOPYRIDINE ET D'UNE COMPOSITION DE CEUX-CI POUR LE TRAITEMENT DE MALADIES MÉDIÉES PAR PRC2<br/>[ZH] 三氮唑并嘧啶、三氮唑并吡啶化合物及其组合物用于治疗PRC2介导的疾病
  申请人：SHANGHAI INST MATERIA MEDICA CAS

  公开号：WO2019062435A1

  公开（公告）日：2019-04-04

  本发明提供了一种由通式I表示的化合物、其可药用的盐、对映异构体、非对映异构体或外消旋体，其制备方法，包含其的药物组合物，以及其在制备用于治疗由EED和/或PRC2介导的疾病或病症的药物中的用途。本发明所述的化合物可用于治疗由PRC2介导的疾病或病症。(I)
• USE OF TRIAZOLOPYRIMIDINE, TRIAZOLOPYRIDINE COMPOUNDS AND COMPOSITION THEREOF FOR TREATING PRC2-MEDIATED DISEASES
  申请人：Shanghai Institute of Materia Medica, Chinese Academy of Sciences

  公开号：EP3689875B1

  公开（公告）日：2021-10-13
• US5675012A
  申请人：——

  公开号：US5675012A

  公开（公告）日：1997-10-07