2-(4-氟-2-硝基苯基)-4,4,5,5-四甲基-1,3,2-二噁硼烷 | 1288978-82-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 2-(4-氟-2-硝基苯基)-4,4,5,5-四甲基-1,3,2-二噁硼烷
• 中文别名: (4-氟-2-硝基苯基)-硼酸频哪醇酯
• 英文名称: 2-(4-fluoro-2-nitrophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
• 英文别名: 2-(4-Fluoro-2-nitrophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
• CAS: 1288978-82-4
• 化学式: C₁₂H₁₅BFNO₄
• 分子量: 267.065
• InChiKey: UEMDKWBOUAQJJU-UHFFFAOYSA-N

物化性质

• 沸点：
  354.4±32.0 °C(Predicted)
• 密度：
  1.20±0.1 g/cm3 (20 ºC 760 Torr)

计算性质

• 辛醇/水分配系数(LogP)：
  2.03
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  64.3
• 氢给体数：
  0
• 氢受体数：
  5

安全信息

• 海关编码：
  2934999090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  2-(4-氟-2-硝基苯基)-4,4,5,5-四甲基-1,3,2-二噁硼烷 在 sodium carbonate 、 亚磷酸三乙酯 作用下， 以 甲醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.08h， 生成 tert-butyl ((1r,4r)-4-((7-fluoropyrimido[1,6-b]indazol-3-yl)amino)cyclohexyl)carbamate
  参考文献：
  名称：

  [EN] SELECTIVE CYCLIN-DEPENDENT KINASE INHIBITORS AND METHODS OF THERAPEUTIC USE THEREOF
  [FR] INHIBITEURS SÉLECTIFS DE KINASES DÉPENDANTES DES CYCLINES ET LEURS PROCÉDÉS D'UTILISATION THÉRAPEUTIQUE

  摘要：

  本发明涉及选择性抑制细胞周期蛋白依赖性激酶（CDKs）的方法和它们的治疗应用，包括治疗病毒感染。

  公开号：

  WO2022165162A1

文献信息

• Design, synthesis and biological evaluation of indazole derivatives as selective covalent inhibitors of FGFR4 in wild-type and gatekeeper mutants
  作者：Yingyue Yang、Xiaojie He、Zulong Li、Kai Ran、Ningyu Wang、Lifeng Zhao、Zhihao Liu、Jun Zeng、Bo Chang、Qiang Feng、Qiangsheng Zhang、Luoting Yu

  DOI：10.1016/j.ejmech.2023.115628

  日期：2023.10

  mutations induced acquired resistance remains an unmet clinical challenge for HCC treatment. In this study, a series of 1H-indazole derivatives were designed and synthesized as new irreversible inhibitors of wild-type and gatekeeper mutant FGFR4. These new derivatives showed significant FGFR4 inhibitory and antitumor activities, among which compound 27i was demonstrated to be the most potent compound

  成纤维细胞生长因子受体4（FGFR4）已被证明是癌症治疗的有效靶点。FGF19/FGFR4 信号传导异常是人类肝细胞癌 (HCC) 的致癌驱动力。FGFR4 看门人突变引起的获得性耐药仍然是 HCC 治疗中尚未解决的临床挑战。在本研究中，设计并合成了一系列1H-吲唑衍生物作为野生型和守门突变体FGFR4的新型不可逆抑制剂。这些新衍生物表现出显着的FGFR4抑制和抗肿瘤活性，其中化合物27i被证明是最有效的化合物（FGFR4 IC 50  = 2.4 nM）。值得注意的是，化合物27i在 1 μM 浓度下对一组 381 种激酶没有表现出活性。此外，化合物27i对 huh7 (IC 50  = 21 nM) 和两种突变细胞系 BaF3/ETV6-FGFR4-V550L 和 BaF3/ETV6-FGFR4-N535K (IC 50  = 2.5/171 nM)显示纳摩尔 IC 50 s。同时，化
• Discovery of (1<i>S</i>,2<i>R</i>,3<i>R</i>)-2,3-Dimethyl-2-phenyl-1-sulfamidocyclopropanecarboxylates: Novel and Highly Selective Aggrecanase Inhibitors
  作者：Makoto Shiozaki、Katsuya Maeda、Tomoya Miura、Masayuki Kotoku、Takayuki Yamasaki、Isamu Matsuda、Kenta Aoki、Katsutaka Yasue、Hiroto Imai、Minoru Ubukata、Akira Suma、Masahiro Yokota、Takahiro Hotta、Masahiro Tanaka、Yasunori Hase、Julia Haas、Andrew M. Fryer、Ellen R. Laird、Nicole M. Littmann、Steven W. Andrews、John A. Josey、Takayuki Mimura、Yuichi Shinozaki、Hiromi Yoshiuchi、Takashi Inaba

  DOI：10.1021/jm101609j

  日期：2011.4.28

  Aggrecanases, particularly aggrecanase-1 (ADAMTS-4) and aggrecanase-2 (ADAMTS-5), are believed to be key enzymes involved in the articular cartilage breakdown that leads to osteoarthritis. Thus, aggrecanases are considered to be viable drug targets for the treatment of this debilitating disease. A cries of (1S,2R,3R)-2,3-dimethyl-2-phenyl-1-sulfamidocyclopropanecarboxylates was discovered to be potent, highly selective, aid orally bioavailable aggrecanase inhibitors. These compounds have unique P1' groups comprising novel piperidine- or piperazin e-based heterocycles that are connected to a cyclopropane amino acid scaffold via a sulfamido linkage. These P1' groups are quite effective in imparting selectivity over other MMPs, and this selectivity was further increased by incorporation of a methyl substituent in the 2-position of the cyclopropane ring. In contrast to classical hydroxamate-based inhibitors that tend to lack metabolic stability, our aggrecanase inhibitors bear a carboxylate zinc-binding group and have good oral bioavailability. Lead compound 13b, characterized by the novel P1' portion of 1,2,3,4-tetrahydropyrido[3',4':4,5]imidazo [1,2-a]-pyridine ring, is a potent and selective aggrecanse inhibitor with excellent pharmacokinetic profiles.
• [EN] SELECTIVE CYCLIN-DEPENDENT KINASE INHIBITORS AND METHODS OF THERAPEUTIC USE THEREOF<br/>[FR] INHIBITEURS SÉLECTIFS DE KINASES DÉPENDANTES DES CYCLINES ET LEURS PROCÉDÉS D'UTILISATION THÉRAPEUTIQUE
  申请人：VIROKYNE THERAPEUTICS LLC

  公开号：WO2022165162A1

  公开（公告）日：2022-08-04

  Selective inhibitors of cyclin-dependent kinases (CDKs) and methods of their therapeutic use, including treatment of viral infections, are disclosed.

  本发明涉及选择性抑制细胞周期蛋白依赖性激酶（CDKs）的方法和它们的治疗应用，包括治疗病毒感染。