5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole

• 分子结构分类: 有机化合物 - 有机卤素化合物 - 芳基卤化物
• 英文名称: 5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole
• 英文别名: 5-Bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole；2-[(5-bromopyrazol-1-yl)methoxy]ethyl-trimethylsilane
• 化学式: C₉H₁₇BrN₂OSi
• 分子量: 277.236
• InChiKey: QSCDPCSHHFMZGQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.96
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  27
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole 在 咪唑 、 甲醇 、 sodium tetrahydroborate 、 caesium carbonate 、 臭氧 、 三苯基膦 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 37.0h， 生成 5-(4-((tert-butyldimethylsilyl)oxy)butyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole
  参考文献：
  名称：

  Chemical Compounds

  摘要：

  提供了一系列新颖的吡啶或嘧啶衍生物，可以抑制CDK9，并可能对治疗过度增殖性疾病有用。特别是这些化合物在治疗增殖性疾病方面具有用途，如癌症，包括血液恶性肿瘤，如急性髓细胞白血病，多发性骨髓瘤，慢性淋巴细胞白血病，弥漫性大B细胞淋巴瘤，Burkitt淋巴瘤，滤泡性淋巴瘤以及实体肿瘤，如乳腺癌，肺癌，神经母细胞瘤和结肠癌。

  公开号：

  US20160376287A1
• 作为产物：
  描述：

  三甲基-[2-(吡唑-1-基甲氧基)乙基]硅烷 在 2,2,6,6-tetramethylpiperidinylmagnesium chloride lithium chloride complex 、 1,2-二溴四氯乙烷 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 以88%的产率得到5-bromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole
  参考文献：
  名称：

  吸电子基团取代的吡唑的钯催化的膦酰化

  摘要：

  Pd催化的膦酰化反应涉及一系列被吸电子基团（如酯，三氟甲基或氰基）取代的溴吡唑。在相应的膦酰化的吡唑中获得中等至良好的产率。

  DOI：

  10.1016/j.tet.2015.03.099

文献信息

• [EN] PYRIDO OXAZINE DERIVATIVES AS ALK5 INHIBITORS<br/>[FR] DÉRIVÉS DE PYRIDO-OXAZINE EN TANT QU'INHIBITEURS D'ALK5
  申请人：CHIESI FARM SPA

  公开号：WO2022013311A1

  公开（公告）日：2022-01-20

  PYRIDO OXAZINE DERIVATIVES AS ALK5 INHIBITORS The present invention relates to a compound of general formula (I) inhibiting the transforming growth factor-β (TGF-β) type I receptor (ALK5), methods of preparing such compounds, pharmaceutical compositions containing them and therapeutic use thereof. The compounds of the invention may be useful in the treatment of diseases or conditions associated with a dysregulation of ALK5 signaling pathway in a mammal.

  吡啶噁唑衍生物作为ALK5抑制剂。本发明涉及一种通式（I）的化合物，抑制转化生长因子-β（TGF-β）类型I受体（ALK5），制备这种化合物的方法，含有它们的药物组合物以及其治疗用途。本发明的化合物可能在治疗与哺乳动物ALK5信号通路失调相关的疾病或症状中有用。
• Synthesis and structure–activity relationships of aryl fluorosulfate-based inhibitors as novel antitubercular agents
  作者：Baiyuan Yang、Paridhi Sukheja、Bo Qin、Gencheng Li、Grant A.L. Bare、Alessandro Cascioferro、Melissa S. Love、H. Michael Petrassi、K. Barry Sharpless、Case W. McNamara、Arnab K. Chatterjee

  DOI：10.1016/j.bmcl.2023.129596

  日期：2024.1

  To identify new compounds that can effectively inhibit Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), we screened, synthesized, and evaluated a series of novel aryl fluorosulfate derivatives for their in vitro inhibitory activity against Mtb. Compound 21b exhibited an in vitro minimum inhibitory concentration (MIC) of 0.06 µM against Mtb, no cytotoxicity against both HEK293T

  为了鉴定可以有效抑制结核病 （TB） 病原体结核分枝杆菌 （Mtb） 的新化合物，我们筛选、合成和评价了一系列新型芳基氟硫酸盐衍生物对 Mtb 的体外抑制活性。化合物 21b 对 Mtb 的体外最低抑制浓度 （MIC） 为 0.06 μM，对 HEK293T 和 HepG2 哺乳动物细胞系无细胞毒性， 并且在 20 mg/kg 口服剂量下具有良好的体内小鼠血浆暴露和肺浓度，这支持作为结核病治疗新化学实体的晚期开发。
• Discovery of AZD4573, a Potent and Selective Inhibitor of CDK9 That Enables Short Duration of Target Engagement for the Treatment of Hematological Malignancies
  作者：Bernard Barlaam、Robert Casella、Justin Cidado、Calum Cook、Chris De Savi、Allan Dishington、Craig S. Donald、Lisa Drew、Andrew D. Ferguson、Douglas Ferguson、Steve Glossop、Tyler Grebe、Chungang Gu、Sudhir Hande、Janet Hawkins、Alexander W. Hird、Jane Holmes、James Horstick、Yun Jiang、Michelle L. Lamb、Thomas M. McGuire、Jane E. Moore、Nichole O’Connell、Andy Pike、Kurt G. Pike、Theresa Proia、Bryan Roberts、Maryann San Martin、Ujjal Sarkar、Wenlin Shao、Darren Stead、Neil Sumner、Kumar Thakur、Melissa M. Vasbinder、Jeffrey G. Varnes、Jianyan Wang、Lei Wang、Dedong Wu、Liangwei Wu、Bin Yang、Tieguang Yao

  DOI：10.1021/acs.jmedchem.0c01754

  日期：2020.12.24

  A CDK9 inhibitor having short target engagement would enable a reduction of Mcl-1 activity, resulting in apoptosis in cancer cells dependent on Mcl-1 for survival. We report the optimization of a series of amidopyridines (from compound 2), focusing on properties suitable for achieving short target engagement after intravenous administration. By increasing potency and human metabolic clearance, we identified compound 24, a potent and selective CDK9 inhibitor with suitable predicted human pharmacokinetic properties to deliver transient inhibition of CDK9. Furthermore, the solubility of 24 was considered adequate to allow i.v. formulation at the anticipated effective dose. Short-term treatment with compound 24 led to a rapid dose- and time-dependent decrease of pSer2-RNAP2 and Mcl-1, resulting in cell apoptosis in multiple hematological cancer cell lines. Intermittent dosing of compound 24 demonstrated efficacy in xenograft models derived from multiple hematological tumors. Compound 24 is currently in clinical trials for the treatment of hematological malignancies.
• Palladium-Catalyzed Phosphonylation: Synthesis of C3-, C4-, and C5-Phosphonylated Pyrazoles
  作者：Gaël Tran、Domingo Gomez Pardo、Tomoki Tsuchiya、Stefan Hillebrand、Jean-Pierre Vors、Janine Cossy

  DOI：10.1021/ol402717b

  日期：2013.11

  A palladium-catalyzed cross-coupling between 3-, 4-, and 5-halo-pyrazoles and H-phosphonates, H-phosphinates, and secondary phosphine oxides has been developed. This coupling reaction constitutes the first general method allowing the introduction of a great diversity of phosphorus substituents on the different carbons of the pyrazole ring in a one-step process.