6′-bromo-1′H-spiro[cyclopentane-1,2′-thieno[3,2-d]pyrimidin]-4′(3′H)-one | 1244027-60-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• 英文名称: 6′-bromo-1′H-spiro[cyclopentane-1,2′-thieno[3,2-d]pyrimidin]-4′(3′H)-one
• 英文别名: 6'-bromo-1'H-spiro[cyclopentane-1,2'-thieno[3,2-d]pyrimidin]-4'(3'H)-one；6-bromospiro[1,3-dihydrothieno[3,2-d]pyrimidine-2,1'-cyclopentane]-4-one
• CAS: 1244027-60-8
• 化学式: C₁₀H₁₁BrN₂OS
• 分子量: 287.18
• InChiKey: MVVCTEGXRHHGKW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.94
• 重原子数：
  15.0
• 可旋转键数：
  0.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  41.13
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  6′-bromo-1′H-spiro[cyclopentane-1,2′-thieno[3,2-d]pyrimidin]-4′(3′H)-one 、 N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-yl)cyclopropanecarboxamide 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以51 %的产率得到N-(4-(4’-oxo-3’,4’-dihydro-1’H-spiro[cyclopentane-1,2’-thieno[3,2-d]pyrimidin]-6’-yl)pyridin-2-yl)cyclopropanecarboxamide
  参考文献：
  名称：

  Connecting GSK-3β Inhibitory Activity with IKK-β or ROCK-1 Inhibition to Target Tau Aggregation and Neuroinflammation in Alzheimer’s Disease—Discovery, In Vitro and In Cellulo Activity of Thiazole-Based Inhibitors

  摘要：

  GSK-3β, IKK-β, and ROCK-1 kinases are implicated in the pathomechanism of Alzheimer’s disease due to their involvement in the misfolding and accumulation of amyloid β (Aβ) and tau proteins, as well as inflammatory processes. Among these kinases, GSK-3β plays the most crucial role. In this study, we present compound 62, a novel, remarkably potent, competitive GSK-3β inhibitor (IC50 = 8 nM, Ki = 2 nM) that also exhibits additional ROCK-1 inhibitory activity (IC50 = 2.3 µM) and demonstrates anti-inflammatory and neuroprotective properties. Compound 62 effectively suppresses the production of nitric oxide (NO) and pro-inflammatory cytokines in the lipopolysaccharide-induced model of inflammation in the microglial BV-2 cell line. Furthermore, it shows neuroprotective effects in an okadaic-acid-induced tau hyperphosphorylation cell model of neurodegeneration. The compound also demonstrates the potential for further development, characterized by its chemical and metabolic stability in mouse microsomes and fair solubility.

  DOI：

  10.3390/molecules29112616
• 作为产物：
  描述：

  5-溴-3-叔丁氧基羰基氨基-噻吩-2-羧酸甲酯 在 水 、 碳酸氢铵 、 对甲苯磺酸 、 N,N-二异丙基乙胺 、 三氟乙酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 potassium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 7.08h， 生成 6′-bromo-1′H-spiro[cyclopentane-1,2′-thieno[3,2-d]pyrimidin]-4′(3′H)-one
  参考文献：
  名称：

  Connecting GSK-3β Inhibitory Activity with IKK-β or ROCK-1 Inhibition to Target Tau Aggregation and Neuroinflammation in Alzheimer’s Disease—Discovery, In Vitro and In Cellulo Activity of Thiazole-Based Inhibitors

  摘要：

  GSK-3β, IKK-β, and ROCK-1 kinases are implicated in the pathomechanism of Alzheimer’s disease due to their involvement in the misfolding and accumulation of amyloid β (Aβ) and tau proteins, as well as inflammatory processes. Among these kinases, GSK-3β plays the most crucial role. In this study, we present compound 62, a novel, remarkably potent, competitive GSK-3β inhibitor (IC50 = 8 nM, Ki = 2 nM) that also exhibits additional ROCK-1 inhibitory activity (IC50 = 2.3 µM) and demonstrates anti-inflammatory and neuroprotective properties. Compound 62 effectively suppresses the production of nitric oxide (NO) and pro-inflammatory cytokines in the lipopolysaccharide-induced model of inflammation in the microglial BV-2 cell line. Furthermore, it shows neuroprotective effects in an okadaic-acid-induced tau hyperphosphorylation cell model of neurodegeneration. The compound also demonstrates the potential for further development, characterized by its chemical and metabolic stability in mouse microsomes and fair solubility.

  DOI：

  10.3390/molecules29112616

文献信息

• [EN] THIENOPYRIMIDINE AS CDC7 KINASE INHIBITORS<br/>[FR] THIÉNOPYRIMIDINES EN TANT QU'INHIBITEURS DE LA KINASE CDC7
  申请人：TAKEDA PHARMACEUTICAL

  公开号：WO2010101302A1

  公开（公告）日：2010-09-10

  The present invention relates to a compound represented by the formula (I): wherein each symbol is as defined in the specification, or a salt thereof, or a prodrug thereof, which is useful for the prophylaxis or treatment of cancer.

  本发明涉及一种由式(I)表示的化合物，其中每个符号如规范中定义，或其盐，或其前药，用于预防或治疗癌症。
• THIENOPYRIMIDINE AS CDC7 KINASE INHIBITORS
  申请人：Oguro Yuya

  公开号：US20120040981A1

  公开（公告）日：2012-02-16

  The present invention relates to a compound represented by the formula (I): wherein each symbol is as defined in the specification, or a salt thereof, or a prodrug thereof, which is useful for the prophylaxis or treatment of cancer.

  本发明涉及一种由式(I)所表示的化合物：其中每个符号如规范中定义，或其盐，或其前药，用于癌症的预防或治疗。
• Thienopyrimidine as CDC7 kinase inhibitors
  申请人：Oguro Yuya

  公开号：US08691828B2

  公开（公告）日：2014-04-08

  The present invention relates to a compound represented by the formula (I): wherein each symbol is as defined in the specification, or a salt thereof, or a prodrug thereof, which is useful for the prophylaxis or treatment of cancer.

  本发明涉及一种由公式（I）表示的化合物：其中每个符号如规范中所定义，或其盐，或其前药，用于预防或治疗癌症。