二乙酰基甘油激酶抑制剂II | 120166-69-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 中文名称: 二乙酰基甘油激酶抑制剂II
• 中文别名: 二乙酰基甘油激酶抑制剂II
• 英文名称: Diacylglycerol kinase inhibitor II
• 英文别名: 3-[2-[4-[bis(4-fluorophenyl)methylidene]piperidin-1-yl]ethyl]-2-sulfanylidene-1H-quinazolin-4-one
• CAS: 120166-69-0
• 化学式: C₂₈H₂₅F₂N₃OS
• 分子量: 489.6
• InChiKey: ZCNBZFRECRPCKU-UHFFFAOYSA-N

物化性质

• 熔点：
  228-230 °C
• 沸点：
  637.1±65.0 °C(Predicted)
• 密度：
  1.36±0.1 g/cm3(Predicted)
• 溶解度：
  0.1 M HCl：微溶

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  35
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  36.9
• 氢给体数：
  1
• 氢受体数：
  6

安全信息

• 危险品标志：
  Xi
• 危险类别码：
  R36/37/38
• WGK Germany：
  3
• 安全说明：
  S26,S36

制备方法与用途

生物活性

R59949 是一种泛二酰甘油激酶 (DGK) 抑制剂，IC50 为 300 nM。R59949 强烈抑制 Ⅰ 型 DGKα 和 γ 的活性，中度减弱 Ⅱ 型 DGKθ 和 κ 的活性。R59949 通过提高内源性配体二酰甘油水平来激活蛋白激酶C (PKC)。

体外研究

In the presence of R59949, vasopressin- as well as collagen-induced release reaction and aggregation was strongly increased, independently of the formation of arachidonate metabolites.
In THP‐1 monocytes, R59949 attenuates CCL2‐evoked Ca ²⁺ signalling with a half‐maximal concentration of 8.6 μM.
R59949 inhibits inducible nitric oxide production through decreasing transplasmalemmal L-arginine uptake in vascular smooth muscle cells.

文献信息

• PKC activators and combinations thereof
  申请人：Cognitive Research Enterprises, Inc.

  公开号：US10821079B2

  公开（公告）日：2020-11-03

  The present disclosure relates to PKC activators and combinations thereof. The disclosure further relates to compositions, kits, uses, and methods thereof.

  本公开涉及PKC激活剂及其组合物。该公开进一步涉及这些组合物的组成、试剂盒、用途和方法。
• [EN] SUBSTITUTED AMINOQUINOLONES AS DGKALPHA INHIBITORS FOR IMMUNE ACTIVATION<br/>[FR] AMINOQUINOLONES SUBSTITUÉES EN TANT QU'INHIBITEURS DE DGKALPHA POUR ACTIVATION IMMUNITAIRE
  申请人：BAYER AG

  公开号：WO2021105117A1

  公开（公告）日：2021-06-03

  The present invention covers aminoquinolone compounds of general formula (I), in which R1, R2, R3, R4, R5, R6, R7, R8 and n are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment and/or prophylaxis of diseases, in particular of diacylglycerol kinase alpha regulated disorders, as a sole agent or in combination with other active ingredients.

  本发明涵盖了一般式(I)的氨基喹啉酮化合物，其中R1、R2、R3、R4、R5、R6、R7、R8和n如本文所定义，制备所述化合物的方法，用于制备所述化合物的中间化合物，包括所述化合物的药物组合物和组合物，以及利用所述化合物制造用于治疗和/或预防疾病的药物组合物，特别是二酰基甘油激酶α调节性疾病，作为唯一药剂或与其他活性成分组合使用。
• [EN] SUBSTITUTED AMINOQUINOLONES AS DGKALPHA INHIBITORS FOR IMMUNE ACTIVATION<br/>[FR] AMINOQUINOLONES SUBSTITUÉES UTILISÉES EN TANT QU'INHIBITEURS DE DGKALPHA POUR ACTIVATION IMMUNITAIRE
  申请人：BAYER AG

  公开号：WO2021105115A1

  公开（公告）日：2021-06-03

  The present invention covers aminoquinolone compounds of general formula (I) : in which R1, R2, R3, R4, R5, R6, R7, R8, X and n are as defined herein, methods of preparing said compounds, intermediate compounds useful for preparing said compounds, pharmaceutical compositions and combinations comprising said compounds and the use of said compounds for manufacturing pharmaceutical compositions for the treatment and/or prophylaxis of diseases, in particular of diacylglycerol kinase alpha regulated disorders, as a sole agent or in combination with other active ingredients.

  本发明涵盖了一般式(I)的氨基喹啉化合物：其中R1、R2、R3、R4、R5、R6、R7、R8、X和n如此处所定义，制备所述化合物的方法，制备所述化合物有用的中间体化合物，包括所述化合物的药物组合物和组合物，以及利用所述化合物制造用于治疗和/或预防疾病的药物组合物，特别是对二酰基甘油激酶α调节性疾病的治疗，作为单一药剂或与其他活性成分组合使用。
• PKC ACTIVATORS AND COMBINATIONS THEREOF
  申请人：BLANCHETTE ROCKEFELLER NEUROSCIENCES INSTITUTE

  公开号：US20140315990A1

  公开（公告）日：2014-10-23

  The present disclosure relates to PKC activators and combinations thereof. The disclosure further relates to compositions, kits, uses, and methods thereof.

  本公开涉及PKC激活剂及其组合物。本公开进一步涉及其组成物、套件、用途和方法。
• Therapeutic effects of bryostatins, bryologs, and other related substances on ischemia/stroke-induced memory impairment and brain injury
  申请人：Blanchette Rockefeller Neurosciences Institute

  公开号：EP2737904A2

  公开（公告）日：2014-06-04

  The invention provides for the use of protein kinase activators or boosters of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) or other neurotrophic factors to treat stroke. Specifically, the present invention provides methods of treating stroke comprising the steps of identifying a subject having suffered a stroke and administering to said subject an amount of a pharmaceutical composition comprising a protein kinase C (PKC) activator or 4-methylcatechol acetic acid (MCBA) and a pharmaceutically acceptable carrier effective to treat at least one symptom of stroke.

  本发明提供了使用蛋白激酶激活剂或神经生长因子（NGF）、脑源性神经营养因子（BDNF）或其他神经营养因子的促进剂治疗中风的方法。具体而言，本发明提供了治疗中风的方法，包括以下步骤：确定中风患者，并向所述患者施用一定量的药物组合物，该药物组合物包含蛋白激酶 C (PKC) 激活剂或 4-甲基邻苯二酚乙酸 (MCBA) 和药学上可接受的载体，可有效治疗中风的至少一种症状。