6-(3-chlorophenyl)-3-(pyridin-4-yl)imidazo[1,2-b]pyridazine | 1580453-04-8

• 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: 6-(3-chlorophenyl)-3-(pyridin-4-yl)imidazo[1,2-b]pyridazine
• 英文别名: 6-(3-chlorophenyl)-3-(4-pyridyl)imidazo[1,2-b]pyridazine；6-(3-Chlorophenyl)-3-(4-pyridyl)imidazo[1,2-b]pyridazine；6-(3-chlorophenyl)-3-pyridin-4-ylimidazo[1,2-b]pyridazine
• CAS: 1580453-04-8
• 化学式: C₁₇H₁₁ClN₄
• 分子量: 306.754
• InChiKey: JVSBGPZEUAAMDN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  43.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  6-氯-3-碘咪唑并[1,2-B]哒嗪 在 bis-triphenylphosphine-palladium(II) chloride 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 6-(3-chlorophenyl)-3-(pyridin-4-yl)imidazo[1,2-b]pyridazine
  参考文献：
  名称：

  Medicinal Chemistry Optimization of Antiplasmodial Imidazopyridazine Hits from High Throughput Screening of a SoftFocus Kinase Library: Part 1

  摘要：

  A novel class of imidazopyridazines identified from whole cell screening of a SoftFocus kinase library was synthesized and evaluated for antiplasmodial activity against K1 (multidrug resistant strain) and NF54 (sensitive strain). Structure-activity relationship studies led to the identification of highly potent compounds against both strains. Compound 35 was highly active (IC50: K1 = 6.3 nM, NF54 = 7.3 nM) and comparable in potency to artesunate, and 35 exhibited 98% activity in the in vivo P. berghei mouse model (4-day test by Peters) at 4 × 50 mg/kg po. Compound 35 was also assessed against P. falciparum in the in vivo SCID mouse model where the efficacy was found to be more consistent with the in vitro activity. Furthermore, 35 displayed high (78%) rat oral bioavailability with good oral exposure and plasma half-life. Mice exposure at the same dose was 10-fold lower than in rat, suggesting lower oral absorption and/or higher metabolic clearance in mice.

  DOI：

  10.1021/jm500098s

文献信息

• Methods, compositions, and uses of novel Fyn kinase inhibitors
  申请人：Lau Warren C.

  公开号：US10688093B2

  公开（公告）日：2020-06-23

  The present invention provides methods for inhibiting Fyn kinase, using 5-3-pyridin-2-amine, 6-3-imidazo[1,2-a] pyrazine, 6-3-imidazo[1,2-b] pyridazine, N-(5-imidazo [2,1-b][1,3,4] thiadiazol-2-yl)-amine, 4-3-1H-pyrazolo[3,4-b] pyridine, and N-(3-imidazo [1,2-b] pyridazin-6-yl) amine compounds and methods of treatment, prevention, inhibition or amelioration of diseases and conditions associated with Fyn kinase using such compounds.

  本发明提供了使用 5-3-吡啶-2-胺、6-3-咪唑并[1,2-a]吡嗪、6-3-咪唑并[1,2-b]哒嗪、N-(5-咪唑并[2,1-b][1,3,4]噻二唑-2-基)胺、4-3-1H-吡唑并[3、4-b]吡啶和 N-(3-咪唑并[1,2-b]哒嗪-6-基)胺化合物，以及使用此类化合物治疗、预防、抑制或改善与 Fyn 激酶相关的疾病和病症的方法。
• METHODS, COMPOSITIONS, AND USES OF NOVEL FYN KINASE INHIBITORS
  申请人：Lau, Warren C.

  公开号：EP3347462A1

  公开（公告）日：2018-07-18
• Methods, Compositions, and Uses of Novel FYN Kinase Inhibitors
  申请人：LAU Warren C.

  公开号：US20180250297A1

  公开（公告）日：2018-09-06

  The present invention provides methods for inhibiting Fyn kinase, using 5-3-pyridin-2-amine, 6-3-imidazo[1,2-a] pyrazine, 6-3-imidazo[1,2-b] pyridazine, N-(5-imidazo [2,1-b][1,3,4] thiadiazol-2-yl)-amine, 4-3-1H-pyrazolo[3,4-b] pyridine, and N-(3-imidazo [1,2-b] pyridazin-6-yl) amine compounds and methods of treatment, prevention, inhibition or amelioration of diseases and conditions associated with Fyn kinase using such compounds.
• [EN] METHODS, COMPOSITIONS, AND USES OF NOVEL FYN KINASE INHIBITORS<br/>[FR] MÉTHODES, COMPOSITIONS ET UTILISATIONS DE NOUVEAUX INHIBITEURS DE LA KINASE FYN
  申请人：LAU WARREN C

  公开号：WO2017044623A1

  公开（公告）日：2017-03-16

  The present invention provides methods for inhibiting Fyn kinase, using 5-3-pyridin-2-amine, 6-3-imidazo[1,2-a] pyrazine, 6-3-imidazo[1,2-b] pyridazine, N-(5-imidazo [2,1-b][1,3,4] thiadiazol-2-yl)-amine, 4-3-lH-pyrazolo[3,4- b] pyridine, and N-(3-imidazo [1,2-b] pyridazin-6-yl) amine compounds and methods of treatment, prevention, inhibition or amelioration of diseases and conditions associated with Fyn kinase using such compounds.
• Medicinal Chemistry Optimization of Antiplasmodial Imidazopyridazine Hits from High Throughput Screening of a SoftFocus Kinase Library: Part 1
  作者：Claire Le Manach、Diego Gonzàlez Cabrera、Frederic Douelle、Aloysius T. Nchinda、Yassir Younis、Dale Taylor、Lubbe Wiesner、Karen L. White、Eileen Ryan、Corinne March、Sandra Duffy、Vicky M. Avery、David Waterson、Michael J. Witty、Sergio Wittlin、Susan A. Charman、Leslie J. Street、Kelly Chibale

  DOI：10.1021/jm500098s

  日期：2014.3.27

  A novel class of imidazopyridazines identified from whole cell screening of a SoftFocus kinase library was synthesized and evaluated for antiplasmodial activity against K1 (multidrug resistant strain) and NF54 (sensitive strain). Structure-activity relationship studies led to the identification of highly potent compounds against both strains. Compound 35 was highly active (IC50: K1 = 6.3 nM, NF54 = 7.3 nM) and comparable in potency to artesunate, and 35 exhibited 98% activity in the in vivo P. berghei mouse model (4-day test by Peters) at 4 × 50 mg/kg po. Compound 35 was also assessed against P. falciparum in the in vivo SCID mouse model where the efficacy was found to be more consistent with the in vitro activity. Furthermore, 35 displayed high (78%) rat oral bioavailability with good oral exposure and plasma half-life. Mice exposure at the same dose was 10-fold lower than in rat, suggesting lower oral absorption and/or higher metabolic clearance in mice.