(RS)-6-[1-bromo-2-(4-fluorophenyl)-2-oxoethyl]-2-(2-tolyl)-2,3-dihydropyridazin-3-one | 882974-29-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (RS)-6-[1-bromo-2-(4-fluorophenyl)-2-oxoethyl]-2-(2-tolyl)-2,3-dihydropyridazin-3-one
• 英文别名: 6-[2-(4-fluorophenyl)-2-oxoethyl]-2-(2-methylphenyl)pyridazin-3(2H)-one；6-[1-bromo-2-(4-fluorophenyl)-2-oxoethyl]-2-(2-methylphenyl)-3(2H)-pyridazinone；6-[1-bromo-2-(4-fluorophenyl)-2-oxoethyl]-2-(2-methylphenyl)pyridazin-3-one
• CAS: 882974-29-0
• 化学式: C₁₉H₁₄BrFN₂O₂
• 分子量: 401.235
• InChiKey: PTJWOGMRIAMKAC-UHFFFAOYSA-N

物化性质

• 沸点：
  498.1±55.0 °C(Predicted)
• 密度：
  1.44±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  49.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (RS)-6-[1-bromo-2-(4-fluorophenyl)-2-oxoethyl]-2-(2-tolyl)-2,3-dihydropyridazin-3-one 在 吡啶 、 溶剂黄146 、 甲基磺酰氯 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 77.0h， 生成 (R)-6-{6-[(benzyloxy)methyl]-2-(4-fluorophenyl)-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidin-3-yl}-2-(2-tolyl)-2,3-dihydropyridazin-3-one
  参考文献：
  名称：

  Development of a Practical and Scalable Synthesis of a Potent p38 Mitogen-Activated Protein Kinase Inhibitor

  摘要：

  Process research and development of a practical and scalable synthetic method toward a potent inhibitor of p38 mitogen-activated protein kinase 1 is described. The medicinal chemistry synthetic method had several issues in scale-up synthesis. In contrast, the synthetic method described here does not require purification by column chromatography for all steps, and the formation of impurities is suppressed well. Aminopyrazole ring formation was achieved by reaction between a new chiral amine building block 7 and bromoketone unit 4 as a key reaction. This highly efficient and scalable process was successfully demonstrated in the large-scale synthesis of 1.HBr.

  DOI：

  10.1021/op300237b
• 作为产物：
  描述：

  对氟苯甲酸乙酯 在 吡啶 、 盐酸 、 水 、 溴 、 copper diacetate 、 sodium acetate 、 对甲苯磺酸 、 溶剂黄146 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 67.0h， 生成 (RS)-6-[1-bromo-2-(4-fluorophenyl)-2-oxoethyl]-2-(2-tolyl)-2,3-dihydropyridazin-3-one
  参考文献：
  名称：

  Development of a Practical and Scalable Synthesis of a Potent p38 Mitogen-Activated Protein Kinase Inhibitor

  摘要：

  Process research and development of a practical and scalable synthetic method toward a potent inhibitor of p38 mitogen-activated protein kinase 1 is described. The medicinal chemistry synthetic method had several issues in scale-up synthesis. In contrast, the synthetic method described here does not require purification by column chromatography for all steps, and the formation of impurities is suppressed well. Aminopyrazole ring formation was achieved by reaction between a new chiral amine building block 7 and bromoketone unit 4 as a key reaction. This highly efficient and scalable process was successfully demonstrated in the large-scale synthesis of 1.HBr.

  DOI：

  10.1021/op300237b

文献信息

• [EN] PYRIDAZINONE DERIVATIVES CYTOKINES INHIBITORS<br/>[FR] DÉRIVÉS DE LA PYRIDAZINONE INHIBITEURS DE CYTOKINES
  申请人：ASTELLAS PHARMA INC

  公开号：WO2006038734A1

  公开（公告）日：2006-04-13

  A pyridazinone derivative shown by the following formula (I): wherein; which is useful as a medicament for cytokines mediated diseases.

  以下是公式（I）所示的吡啶并嗪酮衍生物；其中；该衍生物在细胞因子介导的疾病的药物中有用。
• PYRIDAZINONE DERIVATIVES USED FOR THE TREATMENT OF PAIN
  申请人：Yamazaki Hitoshi

  公开号：US20090042856A1

  公开（公告）日：2009-02-12

  A pyridazinone derivative compound shown by the following formula (I): wherein R 1 is selected from hydrogen, etc.; R 2 is selected from substituted or unsubstituted aryl, etc.; R 3 is hydrogen, etc.; p is 0, 1 or 2; R 4 and R 5 , are each hydrogen, etc.; R 6 and R 7 , are taken together to form a group of the formula: wherein R 8 is hydrogen; X is selected from oxygen, etc; R 10 is selected from hydrogen, etc.; R 11 is selected from hydrogen, etc.; R 12 is selected from hydrogen, etc.; R 13 is selected from hydrogen, etc.; R 14 is selected from hydrogen, etc.; m and n are each 0, 1, or 2, or a pharmaceutically acceptable salt thereof, which is useful as a medicament.

  以下为化学式（I）所示的吡啶并咪唑酮衍生物化合物：其中R1选择氢等；R2选择取代或未取代的芳基等；R3选择氢等；p为0、1或2；R4和R5均为氢等；R6和R7相互结合形成下式的基团：其中R8为氢；X选择氧等；R10选择氢等；R11选择氢等；R12选择氢等；R13选择氢等；R14选择氢等；m和n均为0、1或2，或其药学上可接受的盐，用作药物。
• Identification, Synthesis, and Biological Evaluation of 6-[(6<i>R</i>)-2-(4-Fluorophenyl)-6-(hydroxymethyl)-4,5,6,7-tetrahydropyrazolo[1,5-<i>a</i>]pyrimidin-3-yl]-2-(2-methylphenyl)pyridazin-3(2<i>H</i>)-one (AS1940477), a Potent p38 MAP Kinase Inhibitor
  作者：Toru Asano、Hitoshi Yamazaki、Chiyoshi Kasahara、Hirokazu Kubota、Toru Kontani、Yu Harayama、Kazuki Ohno、Hidekazu Mizuhara、Masaharu Yokomoto、Keiji Misumi、Tomohiko Kinoshita、Mitsuaki Ohta、Makoto Takeuchi.

  DOI：10.1021/jm3008008

  日期：2012.9.13

  Several p38 MAPK inhibitors have been shown to effectively block the production of cytokines such as IL-1 beta, TNF alpha, and IL-6. Inhibitors of p38 MAP kinase therefore have significant therapeutic potential for the treatment of autoimmune disease. Compound 2a was identified as a potent TNF alpha production inhibitor in vitro but suffered from poor oral bioavailability. Structural modification of 2a led to the discovery of tetrahydropyrazolopyrimidine derivatives, exemplified by compound 3, with an improved pharmacokinetic profile. We found that blocking metabolism at the methyl group of the amine and constructing the tetrahydropyrimidine core were important to obtaining compounds with good biological profiles and oral bioavailability. Pursuing the structure-activity relationships of this series led to the discovery of AS1940477 (3f), with excellent cellular activity and a favorable pharmacokinetic profile. This compound represents a highly potent inhibitor of p38 MAP kinase with regard to in vivo activity in an adjuvant-induced arthritis model.
• WO2007/26950
  申请人：——

  公开号：——

  公开（公告）日：——
• [EN] PYRIDAZINONE DERIVATIVES USED FOR THE TREATMENT OF PAIN<br/>[FR] NOUVEAUX COMPOSES
  申请人：ASTELLAS PHARMA INC

  公开号：WO2007026950A1

  公开（公告）日：2007-03-08

  [EN] A pyridazinone derivative compound shown by the following formula (I): wherein R₁ is selected from hydrogen, etc.; R₂ is selected from substituted or unsubstituted aryl, etc.; R₃ is hydrogen, etc.;p is 0, 1 or 2; R₄ and R₅ are each hydrogen, etc.; R₆ and R₇ are taken together to form a group of the formula: wherein R₈ is hydrogen; X is selected from oxygen, etc; R₁₀ is selected from hydrogen, etc.; R₁₁ is selected from hydrogen, etc.; R₁₂ is selected from hydrogen, etc.; R₁₃ is selected from hydrogen, etc.; R₁₄ is selected from hydrogen, etc.; m and n are each 0, 1, or 2, or a pharmaceutically acceptable salt thereof, which is useful as a medicament.
  [FR] L'invention concerne un dérivé de pyridazinone représenté par la formule (I), dans laquelle R₁ est sélectionné dans le groupe comprenant hydrogène, etc., R₂ est sélectionné dans le groupe comprenant aryle substitué ou non substitué, etc., R₃ représente hydrogène, etc., p représente 0, 1 ou 2, R₄ et R₅ représentent chacun hydrogène, etc., R₆ et R₇ sont pris ensemble pour former un groupe représenté par la formule dans laquelle R₈ représente hydrogène, X est sélectionné dans le groupe comprenant oxygène, etc., R₁₀ est sélectionné dans le groupe comprenant hydrogène, etc., R₁₁ est sélectionné dans le groupe comprenant hydrogène, etc., R₁₂ est sélectionné dans le groupe comprenant hydrogène etc., R₁₃ est sélectionné dans le groupe comprenant hydrogène, etc., R₁₄ est sélectionné dans le groupe comprenant hydrogène, etc., m et n représentent chacun 0, 1, ou 2, ou un sel pharmaceutiquement acceptable de celui-ci. Ce dérivé est utile en tant que médicament.