3-(6-oxo-1-{3-[5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)pyrimidin-2-yl]benzyl}-1,6-dihydro-pyridazin-3-yl)benzonitrile | 1103508-21-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 3-(6-oxo-1-{3-[5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)pyrimidin-2-yl]benzyl}-1,6-dihydro-pyridazin-3-yl)benzonitrile
• 英文别名: 3-(6-Oxo-1-(3-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-yl)benzyl)-1,6-dihydropyridazin-3-yl)benzonitrile；3-[6-oxo-1-[[3-[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidin-2-yl]phenyl]methyl]pyridazin-3-yl]benzonitrile
• CAS: 1103508-21-9
• 化学式: C₂₈H₂₆BN₅O₃
• 分子量: 491.357
• InChiKey: IQAPQJQWOSMZIO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.59
• 重原子数：
  37
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  101
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  3-(6-oxo-1-{3-[5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)pyrimidin-2-yl]benzyl}-1,6-dihydro-pyridazin-3-yl)benzonitrile 在 吡啶 、 水 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 为溶剂， 反应 26.0h， 生成 2-{3-[3-(3-cyanophenyl)-6-oxo-6H-pyridazin-1-ylmethyl]-phenyl}pyrimidin-5-yl isopropyl carboxylate
  参考文献：
  名称：

  PYRIDAZINONE DERIVATIVES

  摘要：

  公式(I)中的化合物，其中Y、R1、R2、R3和R3'具有权利要求1中指出的含义，是酪氨酸激酶的抑制剂，特别是Met激酶的抑制剂，并且可以用于治疗肿瘤等。

  公开号：

  US20110257181A1
• 作为产物：
  描述：

  3-羟甲基苯硼酸 在 bis-triphenylphosphine-palladium(II) chloride 、 氯化亚砜 、 potassium acetate 、 sodium carbonate 、 potassium carbonate 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 38.0h， 生成 3-(6-oxo-1-{3-[5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)pyrimidin-2-yl]benzyl}-1,6-dihydro-pyridazin-3-yl)benzonitrile
  参考文献：
  名称：

  作为 c-Met 和 TrxR 双重抑制剂的新型含硒 Tepotinib 衍生物的设计、合成和抗肿瘤活性。

  摘要：

  细胞间充质上皮转化因子 (c-Met) 是一种致癌性跨膜受体酪氨酸激酶 (RTK)，在胚胎发育和肝再生过程中的细胞增殖中起着至关重要的作用。硫氧还蛋白还原酶 (TrxR) 在大多数与癌症复发密切相关的肿瘤中过表达并具有组成型活性。多靶点定向配体 (MTDL) 策略为药物组合提供了一种合乎逻辑的方法，并将充分解决癌症的病理复杂性。在这项工作中，我们通过基于硒的生物等排修饰设计并合成了一系列含硒的tepotinib衍生物，并评估了它们的抗增殖活性。大多数这些含硒杂化物对 c-Met 和 TrxR 表现出有效的双重抑制活性。其中，化合物8b活性最高，对 MHCC97H 细胞的 IC50 值为 10 nM。作用机制研究表明，化合物 8b 在 G1 期触发细胞周期停滞，并通过靶向 TrxR 引起 ROS 积累，这些作用最终导致细胞凋亡。这些发现强烈表明化合物 8b 可作为 c-Met 和 TrxR

  DOI：

  10.3390/molecules28031304

文献信息

• [EN] NOVEL POLYMORPHIC FORMS OF 3-(1-{3-[5-(1-METHYL-PIPERIDIN-4YLMETHOXY)-PYRIMIDIN-2-YL]-BENZYL}-6-OXO-1,6-DIHYDRO-PYRIDAZIN-3-YL)-BENZONITRILE HYDROCHLORIDE SALT AND PROCESSES OF MANUFACTURING THEREOF<br/>[FR] NOUVELLES FORMES POLYMORPHES DE SEL CHLORHYDRATE DE 3-(1-{3-[5-(1-MÉTHYL-PIPÉRIDIN-4YLMÉTHOXY)-PYRIMIDIN-2-YL]-BENZYL}-6-OXO-1,6-DIHYDRO-PYRIDAZIN-3-YL)-BENZONITRILE ET LEURS PROCÉDÉS DE FABRICATION
  申请人：MERCK PATENT GMBH

  公开号：WO2010078897A1

  公开（公告）日：2010-07-15

  The present invention relates to hydrochloride solvates of 3-(1-3-[5-(1-methyl-piperidin-4-ylmethoxy)-pyrimidin-2-yl]-benzyl}-6-oxo-1,6-dihydro-pyridazin-3-yl)-benzonitrile and crystalline modifications thereof. The present invention further relates to processes of manufacturing these crystalline modifications as well as their use in the treatment and/or prophylaxis of physiological and/or pathophysiological conditions, which are caused, mediated and/or propagated by the inhibition, regulation and/or modulation of signal transduction of kinases, in particular by the inhibition of tyrosine kinases, e.g. pathophysiological conditions such as cancer.

  本发明涉及3-(1-3-[5-(1-甲基哌啶-4-基甲氧基)-嘧啶-2-基]-苄基}-6-氧代-1,6-二氢吡啶-3-基)-苯甲腈的盐酸溶剂化合物及其结晶形态。本发明还涉及制备这些结晶形态的方法，以及它们在治疗和/或预防生理和/或病理条件中的用途，这些条件是由激酶信号传导的抑制、调节和/或调控引起、介导和/或传播的，特别是通过酪氨酸激酶的抑制，例如癌症等病理条件。
• Novel Polymorphic Forms of 3-(1--6-oxo-1,6-dihydro-pyridazin-3-yl)-benzonitrile Hydrochloride Salt and Processes of Manufacturing Thereof
  申请人：Becker Axel

  公开号：US20110269767A1

  公开（公告）日：2011-11-03

  The present invention relates to 3-(1-3-[5-(1-methyl-piperidin-4-ylmethoxy)-pyrimidin-2-yl]-benzyl}-6-oxo-1,6-dihydro-pyridazin-3-yl)-benzonitrile hydrochloride solvates and crystalline modifications thereof. The present invention further relates to processes of manufacturing these crystalline modifications as well as their use in the treatment and/or prophylaxis of physiological and/or pathophysiological conditions, which are caused, mediated and/or propagated by the inhibition, regulation and/or modulation of signal transduction of kinases, in particular by the inhibition of tyrosine kinases, e.g. pathophysiological conditions such as cancer.

  本发明涉及3-(1-3-[5-(1-甲基哌啶-4-基甲氧基)嘧啶-2-基]-苯甲基}-6-氧代-1,6-二氢-吡啶并[3,4-d]嘧啶-3-基)-苯甲腈盐酸盐溶剂和其晶体修饰。本发明还涉及制造这些晶体修饰的过程以及它们在治疗和/或预防由激酶信号转导的抑制、调节和/或调控引起、介导和/或传播的生理和/或病理条件中的使用，特别是通过抑制酪氨酸激酶而引起的病理条件，例如癌症。
• Pyridazinone derivatives
  申请人：Dorsch Dieter

  公开号：US08580781B2

  公开（公告）日：2013-11-12

  Compounds of the formula (I), in which R1, R2, R3, R4, R4′ have the meanings indicated in claim 1, are inhibitors of tyrosine kinases, in particular Met kinase, and can be employed, inter alia, for the treatment of tumors.

  公式（I）的化合物，其中R1，R2，R3，R4，R4'具有权利要求1中所示的含义，是酪氨酸激酶的抑制剂，特别是Met激酶，并可用于治疗肿瘤等疾病。
• NOVEL POLYMORPHIC FORMS OF 3-(1--6-OXO-1,6-DIHYDRO-PYRIDAZIN-3-YL)-BENZONITRILE HYDROCHLORIDE SALT AND PROCESSES OF MANUFACTURING THEREOF
  申请人：Merck Patent GmbH

  公开号：US20150148351A1

  公开（公告）日：2015-05-28

  The present invention relates to 3-(1-3-[5-(1-methyl-piperidin-4-ylmethoxy)-pyrimidin-2-yl]-benzyl}-6-oxo-1,6-dihydro-pyridazin-3-yl)-benzonitrile hydrochloride solvates and crystalline modifications thereof. The present invention further relates to processes of manufacturing these crystalline modifications as well as their use in the treatment and/or prophylaxis of physiological and/or pathophysiological conditions, which are caused, mediated and/or propagated by the inhibition, regulation and/or modulation of signal transduction of kinases, in particular by the inhibition of tyrosine kinases, e.g. pathophysiological conditions such as cancer.

  本发明涉及3-(1-3-[5-(1-甲基哌啶-4-基甲氧基)嘧啶-2-基]-苄基}-6-氧代-1,6-二氢吡啶-3-基)-苯甲腈盐酸盐溶剂和其晶体修饰。本发明还涉及制造这些晶体修饰的过程，以及它们在治疗和/或预防生理和/或病理条件方面的使用，这些条件是由于激酶信号转导的抑制、调节和/或调节引起、介导和/或传播的，特别是通过抑制酪氨酸激酶的抑制，例如病理条件如癌症。
• Polymorphic forms of 3-(1-{3-[5-(1-methyl-piperidin-4-ylmethoxy)-pyrimidin-2-yl]-benzyl}-6-oxo-1,6-dihydro-pyridazin-3-yl)-benzonitrile hydrochloride salt and processes of manufacturing thereof
  申请人：Becker Axel

  公开号：US08710058B2

  公开（公告）日：2014-04-29

  Compounds of the present invention concern 3-(1-3-[5-(1-methyl-piperidin-4-ylmethoxy)-pyrimidin-2-yl]-benzyl}-6-oxo-1,6-dihydro-pyridazin-3-yl)-benzonitrile hydrochloride solvates and crystalline modifications thereof. The compound, 3-(1-3-[5-(1-methyl-piperidin-4-ylmethoxy)-pyrimidin-2-yl]-benzyl}-6-oxo-1,6-dihydro-pyridazin-3-yl)-benzonitrile, has the following structural formula: The hydrochloride solvates and crystalline modifications thereof according to the invention are useful for treatment of physiological and/or pathophysiological conditions, such as cancer, that are caused, mediated and/or propagated by the inhibition, regulation and/or modulation of signal transduction of kinases, in particular by the inhibition of tyrosine kinases, especially Met-kinase. The present invention further relates to processes of manufacturing these crystalline modifications.

  本发明的化合物涉及3-(1-3-[5-(1-甲基哌啶-4-基甲氧基)嘧啶-2-基]-苄基}-6-氧代-1,6-二氢-吡啶并[3,4-d]嘧啶-3-基)-苯甲腈盐酸盐溶剂和其晶体修饰。化合物3-(1-3-[5-(1-甲基哌啶-4-基甲氧基)嘧啶-2-基]-苄基}-6-氧代-1,6-二氢-吡啶并[3,4-d]嘧啶-3-基)-苯甲腈的结构式如下：本发明的盐酸盐溶剂和晶体修饰对于治疗生理和/或病理条件，如由激酶信号转导的抑制、调节和/或调节引起、介导和/或传播的癌症等疾病是有用的，特别是通过抑制酪氨酸激酶，尤其是Met-激酶的抑制。本发明还涉及制造这些晶体修饰的过程。