8-(1,3-dimethyl-1H-pyrazol-4-yl)-1-(3-fluoro-5-methoxypyridin-4-yl)-7-methoxy-3-methyl-1,3-dihydroimidazo[4,5-c]quinolin-2-one | 2495096-26-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 8-(1,3-dimethyl-1H-pyrazol-4-yl)-1-(3-fluoro-5-methoxypyridin-4-yl)-7-methoxy-3-methyl-1,3-dihydroimidazo[4,5-c]quinolin-2-one
• 英文别名: 1-(3-fluoro-5-methoxy-4-pyridyl)-7-methoxy-3-methyl-8-(1,3-dimethylpyrazol-4-yl)imidazo[4,5-c]quinolin-2-one；M4076；M-4076；8-(1,3-dimethylpyrazol-4-yl)-1-(3-fluoro-5-methoxypyridin-4-yl)-7-methoxy-3-methylimidazo[4,5-c]quinolin-2-one
• CAS: 2495096-26-7；2020089-41-0
• 化学式: C₂₃H₂₁FN₆O₃
• 分子量: 448.457
• InChiKey: WNEFOSMCGCLLJU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  33
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  85.6
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  8-(1,3-dimethyl-1H-pyrazol-4-yl)-1-(3-fluoro-5-methoxypyridin-4-yl)-7-methoxy-3-methyl-1,3-dihydroimidazo[4,5-c]quinolin-2-one 以 水 、 丙酮 为溶剂， 生成 C₂₃H₂₁FN₆O₃*C₁₈H₁₄O₈
  参考文献：
  名称：

  Atropisomerism – A Neglected Way to Escape Out of Solubility Flatlands

  摘要：

  Low solubility of drugs represents a major challenge during research and development. Ways to overcome this are either focused on formulation development or optimization of the molecular structure of the drug. The latter is not only governed by the constitution of the molecule but also by its stereochemistry. Development of enantiomers in contrast to racemic mixtures has become the state of the art over the last decades as this leads to higher potency and selectivity. Thus, enantiopure drugs require lower doses compared to their racemates. Additionally, selecting one enantiomer also leads to improved solubility of the drug compared to its racemic compound. While this effect is well known for enantiomers and racemic compounds where chirality is introduced via a chiral central atom, here we describe the first case where improved solubility is realized by selecting an axially chiral atropisomer.

  DOI：

  10.1016/j.xphs.2021.10.011
• 作为产物：
  描述：

  6-bromo-N⁴-(3-fluoro-5-methoxy-4-pyridyl)-7-methoxyquinoline-3,4-diamine 在 四(三苯基膦)钯 、 sodium hydride 、 potassium carbonate 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.17h， 生成 8-(1,3-dimethyl-1H-pyrazol-4-yl)-1-(3-fluoro-5-methoxypyridin-4-yl)-7-methoxy-3-methyl-1,3-dihydroimidazo[4,5-c]quinolin-2-one
  参考文献：
  名称：

  [EN] PHARMACEUTICAL PREPARATION
  [FR] PRÉPARATION PHARMACEUTIQUE

  摘要：

  本发明涉及一种8-(1,3-二甲基-1H-吡唑-4-基)-1-(Sa)-(3-氟-5-甲氧基-吡啶-4-基)-7-甲氧基-3-甲基-1,3-二氢咪唑[4,5-c]喹啉-2-酮的固体制剂，以及制备该制剂的方法和其医学用途。

  公开号：

  WO2022058351A1

文献信息

• [EN] IMIDAZOLONYLQUINOLINE COMPOUNDS AND THERAPEUTIC USES THEREOF<br/>[FR] COMPOSÉS D'IMIDAZOLONYLQUINOLINE ET LEURS UTILISATIONS THÉRAPEUTIQUES
  申请人：MERCK PATENT GMBH

  公开号：WO2020193660A1

  公开（公告）日：2020-10-01

  The present invention relates to atropisomers, solid forms, salt forms and deuterated derivatives of the ATM inhibitor 8-(1,3-Dimethyl-1H-pyrazol-4-yl)-1-(3-fluoro-5-methoxy- pyridin-4-yl)-7-methoxy-3-methyl-1,3-dihydroimidazo[4,5-c]quinolin-2-one as well as compositions thereof. The stable atropisomers do not interconvert and are represented by the following formulae: Compound1, Compound2

  本发明涉及ATM抑制剂8-(1,3-二甲基-1H-吡唑-4-基)-1-(3-氟-5-甲氧基吡啶-4-基)-7-甲氧基-3-甲基-1,3-二氢咪唑[4,5-c]喹啉-2-酮的异构体、固态形式、盐形式和氘代衍生物，以及其组合物。稳定的异构体不会相互转化，由以下式表示：化合物1，化合物2。
• IMIDAZOLONYLQUINOLINES AND THE USE THEREOF AS ATM KINASE INHIBITORS
  申请人：Merck Patent GmbH

  公开号：US20180072715A1

  公开（公告）日：2018-03-15

  Compounds of the formula (I), which are ATM kinase inhibitors and can be employed, inter alia, for the treatment of cancer.

  式(I)的化合物是ATM激酶抑制剂，可用于治疗癌症。
• [EN] COMPOUNDS FOR THE TREATMENT OF VIRAL INFECTIONS<br/>[FR] COMPOSÉS POUR LE TRAITEMENT D'INFECTIONS VIRALES
  申请人：MERCK PATENT GMBH

  公开号：WO2021254982A1

  公开（公告）日：2021-12-23

  The present invention encompasses an ATM inhibitor for use in the treatment of coronavirus infections, including COVID-19, alone or in combination with one or more additional therapeutic agents.

  本发明涵盖了一种ATM抑制剂，用于治疗冠状病毒感染，包括COVID-19，单独使用或与一个或多个其他治疗剂联合使用。
• Imidazolonylquinolines and the use thereof as ATM kinase inhibitors
  申请人：Merck Patent GmbH

  公开号：US10457677B2

  公开（公告）日：2019-10-29

  Compounds of the formula (I), which are ATM kinase inhibitors and can be employed, inter alia, for the treatment of cancer.

  式 (I) 化合物是 ATM 激酶抑制剂，可用于治疗癌症等。
• IMIDAZOLONYLCHINOLINE UND DEREN VERWENDUNG ALS ATM KINASE INHIBITOREN
  申请人：Merck Patent GmbH

  公开号：EP3277681B1

  公开（公告）日：2019-05-08