6-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(1H-pyrazol-5-yl)nicotinamide

• 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: 6-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(1H-pyrazol-5-yl)nicotinamide
• 英文别名: 6-chloro-N-[4-[chloro(difluoro)methoxy]phenyl]-5-(1H-pyrazol-5-yl)pyridine-3-carboxamide
• 化学式: C₁₆H₁₀Cl₂F₂N₄O₂
• 分子量: 399.184
• InChiKey: XHOUHIJGRZFACR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  79.9
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  6-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(1H-pyrazol-5-yl)nicotinamide 、 beta-丙氨酸乙酯盐酸盐 在 N,N-二异丙基乙胺 作用下， 以 异戊醇 为溶剂， 反应 44.0h， 生成
  参考文献：
  名称：

  Disposition of asciminib, a potent BCR-ABL1 tyrosine kinase inhibitor, in healthy male subjects

  摘要：

  Asciminib is a potent, specific BCR-ABL1 inhibitor being developed for the treatment of patients with chronic myelogenous leukemia (CML) and Philadelphia chromosome positive acute lymphoblastic leukemia (Ph + ALL). Here, we present the results of human oral absorption, distribution, metabolism, excretion (ADME) and in vitro studies that together provide an overall understanding of the metabolism, distribution and clearance of asciminib in humans. Asciminib was rapidly absorbed with a maximum plasma concentration at two hours post-dose. Total radioactivity and asciminib showed similar terminal half-lives in plasma. Oral asciminib absorption ranged between a minimum of 33%, and a maximum of 57% based on the metabolite profiles of late time-point feces collections. Asciminib was eliminated mainly through feces via unchanged asciminib excretion and metabolism. Direct glucuronidation and oxidation were major metabolic pathways in human that were catalyzed predominantly by UDP-glucuronosyltransferase (UGT)2B7 and cytochrome P450 (CYP)3A4, respectively. The relative contribution of the glucuronidation pathway to the total clearance of asciminib via metabolism is estimated to range similar to 28-58%, whereas the relative contribution of the oxidative pathway is estimated to range similar to 37-64%, based upon the maximum oral absorption in humans.

  DOI：

  10.1080/00498254.2019.1594449
• 作为产物：
  描述：

  6-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazol-5-yl)nicotinamide 在 磷酸 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 4.0h， 以2.3 g的产率得到6-chloro-N-(4-(chlorodifluoromethoxy)phenyl)-5-(1H-pyrazol-5-yl)nicotinamide
  参考文献：
  名称：

  [EN] NOVEL HETEROCYCLIC COMPOUNDS AS TYROSINE KINASE BCR-ABL INHIBITORS
  [FR] NOUVEAUX COMPOSÉS HÉTÉROCYCLIQUES COMME INHIBITEURS DE LA TYROSINE KINASE BCR-ABL

  摘要：

  揭示了一种式（Ⅰ）的化合物或其药学上可接受的盐，其中所述的变量在此处描述。还揭示了一种制备化合物的方法，其药用组合物包括作为活性成分的相同化合物，使用这些组合物治疗各种疾病的方法，以及利用这些化合物制造药物以抑制ABL1、ABL2和相关嵌合蛋白的酶活性。

  公开号：

  WO2017186148A1

文献信息

• BENZAMIDE DERIVATIVES FOR INHIBITING THE ACTIVITY OF ABL1, ABL2 AND BCR-ABL1
  申请人：Furet Pascal

  公开号：US20150126485A1

  公开（公告）日：2015-05-07

  The present invention relates to compounds of formula (I): in which Y, Y, R, R 2, R 3 and R 4 are defined in the Summary of the Invention; capable of inhibiting the tyrosine kinase enzymatic activity of the Abelson protein (ABL1), the Abelson-related protein (ABL2) and related chimeric proteins, in particular BCR-ABL1. The invention further provides a process for the preparation of compounds of the invention, pharmaceutical preparations comprising such compounds and methods of using such compounds in the treatment of cancers.

  本发明涉及式（I）的化合物：其中Y，Y，R，R2，R3和R4在本发明的摘要中定义；能够抑制Abelson蛋白（ABL1），Abelson相关蛋白（ABL2）和相关嵌合蛋白的酪氨酸激酶酶活性，特别是BCR-ABL1。本发明还提供了制备本发明化合物的方法，包括这种化合物的制药制剂以及使用这种化合物治疗癌症的方法。
• Benzamide derivatives for inhibiting the activity of ABL1, ABL2 and BCR-ABL1
  申请人：Furet Pascal

  公开号：US09340537B2

  公开（公告）日：2016-05-17

  The present invention relates to compounds of formula (I): in which Y, Y, R, R 2, R 3 and R 4 are defined in the Summary of the Invention; capable of inhibiting the tyrosine kinase enzymatic activity of the Abelson protein (ABL1), the Abelson-related protein (ABL2) and related chimeric proteins, in particular BCR-ABL1. The invention further provides a process for the preparation of compounds of the invention, pharmaceutical preparations comprising such compounds and methods of using such compounds in the treatment of cancers.

  本发明涉及式（I）的化合物：其中Y，Y，R，R2，R3和R4在本发明摘要中定义；能够抑制Abelson蛋白（ABL1），Abelson相关蛋白（ABL2）和相关嵌合蛋白的酪氨酸激酶酶活性，特别是BCR-ABL1。本发明还提供了制备本发明化合物的方法，包括这种化合物的制药配制物以及使用这种化合物治疗癌症的方法。
• COMPOUNDS AND COMPOSITIONS FOR INHIBITING THE ACTIVITY OF ABL1, ABL2 AND BCR-ABL1
  申请人：FURET Pascal

  公开号：US20180134695A1

  公开（公告）日：2018-05-17

  The present invention relates to compounds of formula (I): in which Y, Y 1 , R 1 , R 2 , R 3 and R 4 are defined in the Summary of the Invention; capable of inhibiting the tyrosine kinase enzymatic activity of the Abelson protein (ABL1), the Abelson-related protein (ABL2) and related chimeric proteins, in particular BCR-ABL1. The invention further provides a process for the preparation of compounds of the invention, pharmaceutical preparations comprising such compounds and methods of using such compounds in the treatment of cancers.
• US9340537B2
  申请人：——

  公开号：US9340537B2

  公开（公告）日：2016-05-17
• US9896444B2
  申请人：——

  公开号：US9896444B2

  公开（公告）日：2018-02-20