2-bromomethyl-8-tert-butyldiphenylsilyloxy-5-(N,N-dimethyl)sulfonamidoquinoline | 607708-59-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 2-bromomethyl-8-tert-butyldiphenylsilyloxy-5-(N,N-dimethyl)sulfonamidoquinoline
• 英文别名: 2-(Bromomethyl)-8-((tert-butyldiphenylsilyl)oxy)-N,N-dimethylquinoline-5-sulfonamide；2-(bromomethyl)-8-[tert-butyl(diphenyl)silyl]oxy-N,N-dimethylquinoline-5-sulfonamide
• CAS: 607708-59-8
• 化学式: C₂₈H₃₁BrN₂O₃SSi
• 分子量: 583.621
• InChiKey: OEIZRTQULYVKLF-UHFFFAOYSA-N

物化性质

• 沸点：
  611.8±65.0 °C(Predicted)
• 密度：
  1.36±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.32
• 重原子数：
  36
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  67.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-bromomethyl-8-tert-butyldiphenylsilyloxy-5-(N,N-dimethyl)sulfonamidoquinoline 在 盐酸 、 O-烯丙基-N-(9-蒽甲基)溴化金鸡纳碱 、 cesium hydrochloride monohydrate 、 碳酸氢钠 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 71.0h， 生成 (S)-2-amino-N^α-(9-fluorenylmethyloxycarbonyl)-3-(8-hydroxy-5-(N,N-dimethyl)sylfonamidoquinoline-2-yl)propionic acid
  参考文献：
  名称：

  Modular and Tunable Chemosensor Scaffold for Divalent Zinc

  摘要：

  A modular peptide scaffold has been developed for fluorescent sensing of divalent zinc. The signaling component of the chemosensor is the chelation -sensitive fluorophore 8-hydroxy-5-(N,N-dimethylsulfonamido)-2-methylquinoline, which is prepared as the protected amino acid derivative Fmoc-Sox-OH and integrated into peptide sequences. Nineteen synthetic peptides incorporating the signaling element exhibit a range of affinities for Zn2+ through variation of the type and number of Zn2+ ligands, ligand arrangement and the beta-turn sequence that acts as a preorganization element between the ligands. The stoichiometry of the peptide-Zn2+ complexes is evaluated by several criteria. The fluorescence response of these peptides to pH and various important metal ions is reported. Eleven of these sequences form only 1:1 complexes with Zn2+ and their affinities range from 10 nM to nearly 1 muM. When used in concert, these sensors can provide Zn2+ concentration information in a valuable range.

  DOI：

  10.1021/ja0355980
• 作为产物：
  描述：

  8-hydroxy-2-methyl-quinoline-5-sulfonyl chloride 在 咪唑 、 selenium(IV) oxide 、 sodium tetrahydroborate 、 四溴化碳 、 三苯基膦 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.25h， 生成 2-bromomethyl-8-tert-butyldiphenylsilyloxy-5-(N,N-dimethyl)sulfonamidoquinoline
  参考文献：
  名称：

  设计和合成蛋白质磷酸酶的荧光活性探针。

  摘要：

  蛋白质磷酸酶与蛋白质激酶协同作用，以调节和维持磷酸化蛋白质组。然而，直接监测磷酸酶的酶活性的化学工具目录已经落后于它们的激酶对应物。在本章中，我们提供了用于重新利用磷酸化敏感的磺酰氨基-氧肟荧光团（称为Sox）的方案，以提供磷酸酶的直接活性探针。使用经过验证的活性探针，可以使用重组酶进行抑制剂筛选，并且可以在未分级分离的细胞裂解物中研究磷酸酶在细胞信号传导中的作用。

  DOI：

  10.1016/bs.mie.2019.02.002

文献信息

• [EN] 1, 2, 3-TRIAZOLE CONTAINING PROTEIN KINASE SENSORS<br/>[FR] 1, 2, 3-TRIAZOLE CONTENANT DES DÉTECTEURS DE PROTÉINE KINASE
  申请人：MASSACHUSETTS INST TECHNOLOGY

  公开号：WO2011025546A1

  公开（公告）日：2011-03-03

  The present invention generally relates to compositions and methods for determining kinase activity. In some cases, the compositions comprise a triazole heterocycle. In some embodiments, the compositions comprise a quinoline moiety. In one aspect, the present invention is directed to compositions that undergo chelation- enhanced fluorescence (CHEF). In some cases, the compositions may have fluorescence emission spectra with peak maxima greater than 490 nm. The compositions of the present invention can be used, in certain embodiments, to detect phosphorylated substrates and biological processes such as phosphorylation events.

  本发明通常涉及用于确定激酶活性的组合物和方法。在某些情况下，这些组合物包括三唑杂环。在某些实施例中，这些组合物包括喹啉基团。在一个方面，本发明涉及能够经历螯合增强荧光（CHEF）的组合物。在某些情况下，这些组合物可能具有峰值大于490纳米的荧光发射光谱。在某些实施例中，本发明的组合物可用于检测磷酸化底物和生物过程，如磷酸化事件。
• Recognition-Domain Focused Chemosensors: Versatile and Efficient Reporters of Protein Kinase Activity
  作者：Elvedin Luković、Juan A. González-Vera、Barbara Imperiali

  DOI：10.1021/ja8046188

  日期：2008.9.24

  Sox-containing peptide, the chromophore binds Mg (2+) and undergoes chelation-enhanced fluorescence (CHEF). Although the design was applied successfully to the development of several kinase sensors, an intrinsic limitation was that only residues C- or N-terminal to the phosphorylated residue could be used to derive specificity for the target kinase. To address this limitation, a new, recognition-domain

  在激酶的催化下，丝氨酸/苏氨酸和酪氨酸磷酸化是细胞内调节的重要机制。因此，轻松监测激酶活性的分析在学术和制药环境中都至关重要。我们之前开发了基于 sulfonamido-oxine (Sox) 的荧光肽，遵循 β 转聚焦 (BTF) 设计，用于在体外和细胞裂解物中连续测定激酶活性。含 Sox 的肽磷酸化后，发色团与 Mg (2+) 结合并发生螯合增强荧光 (CHEF)。尽管该设计已成功应用于多种激酶传感器的开发，但一个内在限制是只能使用磷酸化残基的 C 端或 N 端残基来推导出对目标激酶的特异性。为了解决这个限制，一个新的，开发的识别域聚焦 (RDF) 策略也依赖于 CHEF。在这种方法中，通过使用基于 Sox 的衍生物对半胱氨酸残基进行烷基化以提供称为 C-Sox 的氨基酸，消除了对受限 β-转角基序的要求。RDF 设计允许包含扩展的结合决定簇，以最大限度地提高同源激酶的识别率，现在允许构建用于各种代表性
• Sox-based kinase sensor
  申请人：Massachusetts Institute of Technology

  公开号：US07964729B2

  公开（公告）日：2011-06-21

  Peptidyl sensors comprise a metal-binding peptide and one or two kinase recognition sequences with a hydroxyamino acid that can be phosphorylated in the presence of a kinase.

  Peptidyl传感器包括一个金属结合肽和一个或两个携带有氢氧基氨基酸的激酶识别序列，当存在激酶时可以被磷酸化。
• 스핑고신 인산화효소의 검출용 화합물, 형광 프로브 및 이의 용도
  申请人：UNIST(ULSAN NATIONAL INSTITUTE OF SCIENCE AND TECHNOLOGY) 울산과학기술원(120150812047) Corp. No ▼ 230171-0011595BRN ▼620-82-06236

  公开号：KR20220128724A

  公开（公告）日：2022-09-22

  본 발명은 하기 화학식 1 로 표시되는 화합물, 이의 제조 방법, 상기 화합물을 함유하는 스핑고신 인산화효소(sphingosine kinase) 검출용 형광 프로브, 상기 형광 프로브를 시료와 접촉시키는 단계를 포함하는 스핑고신 인산화효소의 검출 방법, 및 상기 형광 프로브를 스핑고신 인산화효소의 저해제 후보물질 및 스핑고신 인산화효소와 접촉시키는 단계를 포함하는, 스핑고신 인산화효소 저해제의 스크리닝 방법이 제공된다: [화학식 1] 화학식 1에 있어서, L 은 단일 결합, 또는 탄소수 1 내지 5의 알킬기를 나타내고,R 및 R 는 각각 독립적으로 탄소수 1 내지 5의 알킬기를 나타내고, x는 1 내지 10의 정수이다.

  本发明涉及以下化学式1所表示的化合物、其制备方法、用于检测鞘氨醇激酶(sphingosine kinase)含有该化合物的荧光探针、检测鞘氨醇激酶的方法，包括将荧光探针与样品接触的步骤，以及用于筛选鞘氨醇激酶抑制剂的荧光探针及将其与鞘氨醇激酶接触的步骤，提供了鞘氨醇激酶抑制剂的筛选方法。[化学式1] 在化学式1中，L表示单键或1至5个碳原子的烷基，R和R各自独立地表示1至5个碳原子的烷基，x是1至10的整数。
• Quantification of a Pharmacodynamic ERK End Point in Melanoma Cell Lysates: Toward Personalized Precision Medicine
  作者：Mangalika Warthaka、Charles H. Adelmann、Tamer S. Kaoud、Ramakrishna Edupuganti、Chunli Yan、William H. Johnson、Scarlett Ferguson、Clint D. Tavares、Lindy J. Pence、Eric V. Anslyn、Pengyu Ren、Kenneth Y. Tsai、Kevin N. Dalby

  DOI：10.1021/ml500198b

  日期：2015.1.8

  Protein kinases are mutated or otherwise rendered constitutively active in numerous cancers where they are attractive therapeutic targets with well over a dozen kinase inhibitors now being used in therapy. While fluorescent sensors have capacity to measure changes in kinase activity, surprisingly they have not been utilized for biomarker studies. A first-generation peptide sensor for ERK based on the Sox fluorophore is described. This sensor called ERK-sensor-D1 possesses high activity toward ERK and more than 10-fold discrimination over other MAPKs. The sensor can rapidly quantify ERK activity in cell lysates and monitor ERK pathway engagement by BRAF and MEK inhibitors in cultured melanoma cell lines. The dynamic range of the sensor assay allows ERK activities that have potential for profound clinical consequences to be rapidly distinguished.