N-(4-bromopyridin-2-yl)isobutyramide | 1285530-32-6

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: N-(4-bromopyridin-2-yl)isobutyramide
• 英文别名: N-(4-bromopyridin-2-yl)-2-methylpropanamide
• CAS: 1285530-32-6
• 化学式: C₉H₁₁BrN₂O
• 分子量: 243.103
• InChiKey: QYRRMFXIRVFLFK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  42
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-(4-bromopyridin-2-yl)isobutyramide 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium acetate 、 potassium carbonate 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 生成 5-(2-isobutyramidopyridin-4-yl)-3-ureidothiophene-2-carboxamide
  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：

  异丁酰氯 、 2-氨基-4-溴吡啶 在 吡啶 作用下， 以 二氯甲烷 为溶剂， 以61 %的产率得到N-(4-bromopyridin-2-yl)isobutyramide
  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

• Phenylpyri(mi)dinylazoles
  申请人：Sudau Alexander

  公开号：US20110183978A1

  公开（公告）日：2011-07-28

  Phenylpyri(mi)dinylazoles of the formula [I-a] and [I-b], wherein the symbols have the meanings stated in the description, and agrochemically active salts thereof and the use thereof for the control of undesired microorganisms in the protection of plants and materials and for the reduction of mycotoxins in plants and plant parts and methods for the production of compounds of the formula [I-a] and [I-b].

  式[I-a]和[I-b]的苯基吡啶基氮唑，其中符号的含义如说明中所述，以及其农业化学活性盐和在保护植物和材料中控制不良微生物以及减少植物和植物部分中真菌毒素的用途，以及制备式[I-a]和[I-b]化合物的方法。
• [EN] E3 LIGASE BINDERS AND USES THEREOF<br/>[FR] LIEURS DE LIGASE E3 ET LEURS UTILISATIONS
  申请人：DANA FARBER CANCER INST INC

  公开号：WO2020263832A1

  公开（公告）日：2020-12-30

  Provided herein are compounds of Formulae (I) and (II), and pharmaceutically acceptable salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, prodrugs, and compositions thereof. The compounds described herein bind an E3 ubiquitin ligase (e.g., Cereblon) and induce degradation of a transcription factor (e.g., IKZF1, IKZF3). Also provided are pharmaceutical compositions comprising the compounds, and methods of treating and/or preventing diseases (e.g., proliferative diseases (e.g., cancers (e.g., carcinoma); leukemia, lung cancer, breast cancer, liver cancer, pancreatic cancer, gastric cancer, ovarian cancer, colon cancer, colorectal cancer, multiple myeloma, and acute myeloid leukemia (AML))). Further provided are methods of inducing the degradation of a transcription factor (e.g., IKZF1, IKZF3) by administering a compound or composition described herein to a subject and/or to a biological sample (e.g., cell or tissue).

  本文提供了I和II式化合物及其药学上可接受的盐、溶剂、水合物、多晶形、共晶体、互变异构体、立体异构体、同位素标记衍生物、前药和其组合物。本文所述化合物能够结合E3泛素连接酶（例如Cereblon）并诱导转录因子（例如IKZF1、IKZF3）的降解。还提供了包含该化合物的制药组合物，并提供了治疗和/或预防疾病（例如增生性疾病（例如癌症（例如癌症；白血病、肺癌、乳腺癌、肝癌、胰腺癌、胃癌、卵巢癌、结肠癌、结直肠癌、多发性骨髓瘤和急性髓细胞白血病（AML）））的方法。此外，还提供了通过向受体和/或生物样品（例如细胞或组织）中给予本文所述的化合物或组合物来诱导转录因子（例如IKZF1、IKZF3）降解的方法。
• Phenylpyri(mi)dinylpyrazole und ihre Verwendung als Fungizide
  申请人：Bayer CropScience AG

  公开号：EP2308866A1

  公开（公告）日：2011-04-13

  Phenylpyri(mi)dinylazole der Formel [I-a] und [I-b], in welcher die Symbole die in der Beschreibung angegebenen Bedeutungen haben, sowie agrochemisch wirksame Salze davon und deren Verwendung zur Bekämpfung unerwünschter Mikroorganismen im Pflanzenschutz und Materialschutz sowie zur Reduktion von Mykotoxinen in Pflanzen und Pflanzenteilen sowie Verfahren zur Herstellung von Verbindungen der Formel [I-a] und [I-b].

  式[I-a]和[I-b]的苯基三（mi）二氮杂环戊烯、 其中的符号具有说明中给出的含义，以及它们的农用化学活性盐和它们在植物保护和材料保护中对抗不良微生物以及减少植物和植物部分中霉菌毒素的用途，以及式[I-a]和[I-b]化合物的制备工艺。
• 3-PHENYL-4-PYRI(MI)DINYL-1H-PYRAZOLE UND IHRE VERWENDUNG ALS FUNGIZIDE
  申请人：Bayer CropScience AG

  公开号：EP2784070A1

  公开（公告）日：2014-10-01

  Phenylpyri(mi)dinylazole der Formel [I-a] und [I-b], in welcher die Symbole die in der Beschreibung angegebenen Bedeutungen haben, sowie agrochemisch wirksame Salze davon und deren Verwendung zur Bekämpfung unerwünschter Mikroorganismen im Pflanzenschutz und Materialschutz sowie zur Reduktion von Mykotoxinen in Pflanzen und Pflanzenteilen sowie Verfahren zur Herstellung von Verbindungen der Formel [I-a] und [I-b].

  式[I-a]和[I-b]的苯基三（mi）二氮杂环戊烯、 其中的符号具有说明中给出的含义，以及它们的农用化学活性盐和它们在植物保护和材料保护中对抗不良微生物以及减少植物和植物部分中霉菌毒素的用途，以及式[I-a]和[I-b]化合物的制备工艺。
• [DE] PHENYLPYRI(MI)DINYLAZOLE<br/>[EN] PHENYLPYRI(MI)DINYLAZOLES<br/>[FR] PHENYLPYRI(MI)DINYLAZOLES
  申请人：BAYER CROPSCIENCE AG

  公开号：WO2011042389A2

  公开（公告）日：2011-04-14

  Phenylpyri(mi)dinylazole der Formel [I-a] und [I-b], in welcher die Symbole die in der Beschreibung angegebenen Bedeutungen haben, sowie agrochemisch wirksame Salze davon und deren Verwendung zur Bekämpfung unerwünschter Mikroorganismen im Pflanzenschutz und Materialschutz sowie zur Reduktion von Mykotoxinen in Pflanzen und Pflanzenteilen sowie Verfahren zur Herstellung von Verbindungen der Formel [I-a] und [I-b].