4-bromo-2-hydroxynaphthalene-1-diazonium salt | 53846-22-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 4-bromo-2-hydroxynaphthalene-1-diazonium salt
• 英文别名: 4-Bromo-2-hydroxynaphthalene-1-diazonium
• CAS: 53846-22-3
• 化学式: C₁₀H₆BrN₂O
• 分子量: 250.074
• InChiKey: FYBXDVQWYMPNIR-UHFFFAOYSA-O

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  48.4
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-bromo-2-hydroxynaphthalene-1-diazonium salt 在 sodium tetrahydroborate 、 sodium hydride 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 3.0h， 生成 1-溴-3-甲氧基-萘
  参考文献：
  名称：

  Discovery of Novel Naphthylphenylketone and Naphthylphenylamine Derivatives as Cell Division Cycle 25B (CDC25B) Phosphatase Inhibitors: Design, Synthesis, Inhibition Mechanism, and in Vitro Efficacy against Melanoma Cell Lines

  摘要：

  CDC25 phosphatases play a critical role in the regulation of the cell cycle and thus represent attractive cancer therapeutic targets. We previously discovered the 4-(2-carboxybenzoyl)phthalic acid (NSC28620) as a new CDC25 inhibitor endowed with promising anticancer activity in breast, prostate, and leukemia cells. Herein, we report a structure-based optimization of NSC28620, leading to the identification of a series of novel naphthylphenylketone and naphthylphenylamine derivatives as CDC25B inhibitors. Compounds 7j, 7i, 6e, 7f, and 3 showed higher inhibitory activity than the initial lead, with Ki values in the low micromolar range. Kinetic analysis, intrinsic fluorescence studies, and induced fit docking simulations provided a mechanistic understanding of the activity of these derivatives. All compounds were tested in the highly aggressive human melanoma cell lines A2058 and A375. Compound 4a potently inhibited cell proliferation and colony formation, causing an increase of the G2/M phase and a reduction of the G0/G1 phase of the cell cycle in both cell lines.

  DOI：

  10.1021/acs.jmedchem.9b00632
• 作为产物：
  描述：

  硝基萘 在 三乙基硅烷 、 溴 、 溶剂黄146 、 丙酸 、 palladium dichloride 、 sodium nitrite 作用下， 以 乙醇 、 溶剂黄146 为溶剂， 反应 0.59h， 生成 4-bromo-2-hydroxynaphthalene-1-diazonium salt
  参考文献：
  名称：

  Discovery of Novel Naphthylphenylketone and Naphthylphenylamine Derivatives as Cell Division Cycle 25B (CDC25B) Phosphatase Inhibitors: Design, Synthesis, Inhibition Mechanism, and in Vitro Efficacy against Melanoma Cell Lines

  摘要：

  CDC25 phosphatases play a critical role in the regulation of the cell cycle and thus represent attractive cancer therapeutic targets. We previously discovered the 4-(2-carboxybenzoyl)phthalic acid (NSC28620) as a new CDC25 inhibitor endowed with promising anticancer activity in breast, prostate, and leukemia cells. Herein, we report a structure-based optimization of NSC28620, leading to the identification of a series of novel naphthylphenylketone and naphthylphenylamine derivatives as CDC25B inhibitors. Compounds 7j, 7i, 6e, 7f, and 3 showed higher inhibitory activity than the initial lead, with Ki values in the low micromolar range. Kinetic analysis, intrinsic fluorescence studies, and induced fit docking simulations provided a mechanistic understanding of the activity of these derivatives. All compounds were tested in the highly aggressive human melanoma cell lines A2058 and A375. Compound 4a potently inhibited cell proliferation and colony formation, causing an increase of the G2/M phase and a reduction of the G0/G1 phase of the cell cycle in both cell lines.

  DOI：

  10.1021/acs.jmedchem.9b00632

文献信息

• 6-(BIPHENYL-ESTER)-3H-NAPHTHO[2,1-B]PYRANS AS PHOTOCHROMIC DICHROIC DYES AND OPTICAL ARTICLE CONTAINING THEM
  申请人：Aiken Stuart

  公开号：US20100039688A1

  公开（公告）日：2010-02-18

  A naphthopyran compound represented by the formula (I) wherein: n 1 , n 2 , p, m and q represent an integer; R 1 , R 2 and R 4 , represent a group selected from halogen, —R a , —OH, —OR a , —SH, —SR a , —NH 2 , —NR a R a1 , —NR b R c , —CO—R a , —CO 2 R a1 , —OC(O)—R d , —X—(R e )—Y, linear or branched (C 1 -C 18 ) perfluoroalkyl group, wherein R a , R a1 , R b , R c , X, Y, R e , and R d are as defined in the description; Z represents a group selected from CO, CS, SO, SO 2 , CO 2 , C(O)S, CS 2 , C(O)NH, C(O)NR a , C(S)NH, C(S)NR a and C═NR a ; R 3 represents a group selected from halogen, —R a , linear or branched (C 1-18 ) perfluoroalkyl group —OH, —OR a , —SH, —SR a , —NH 2 , and —NR a R a1 ; R 6 represents a group selected from —R a which may be optionally substituted, linear or branched (C 1-18 ) perfluoroalkyl, cycloalkyl, heterocycloalkyl, aryl, and heteroaryl, which may be optionally substituted; R 5 represents a group selected from: halogen, —R a , linear or branched (C 1-18 ) perfluoroalkyl group, —OH, —OR a , —SH, —SR a , —NH 2 , —NR a R a1 , —CO—R a , —O—C(O)—R a and —CO 2 R a1 ; or when q is equal to 2, then two R 5 together represents further a group —O—(CH 2 ) q1 —O— wherein q 1 represents an integer comprised from 1 to 3 inclusive.

  一种萘吡喃化合物，其化学式为（I），其中：n1、n2、p、m和q表示整数；R1、R2和R4表示从卤素、—Ra、—OH、—ORa、—SH、—SRa、—NH2、—NRaRa1、—NRbRc、—CO—Ra、—CO2Ra1、—OC(O)—Rd、—X—(Re)—Y、线性或支链（C1-C18）全氟烷基组中选择的一个基团，其中Ra、Ra1、Rb、Rc、X、Y、Re和Rd如描述中所定义；Z表示从CO、CS、SO、SO2、CO2、C(O)S、CS2、C(O)NH、C(O)NRa、C(S)NH、C(S)NRa和C═NRa中选择的一个基团；R3表示从卤素、—Ra、线性或支链（C1-18）全氟烷基组、—OH、—ORa、—SH、—SRa、—NH2和—NRaRa1中选择的一个基团；R6表示从可选择替代的—Ra、线性或支链（C1-18）全氟烷基、环烷基、杂环烷基、芳基和杂芳基中选择的一个基团；R5表示从卤素、—Ra、线性或支链（C1-18）全氟烷基组、—OH、—ORa、—SH、—SRa、—NH2、—NRaRa1、—CO—Ra、—O—C(O)—Ra和—CO2Ra1中选择的一个基团；或者当q等于2时，那么两个R5一起进一步表示一个基团—O—(CH2)q1—O—，其中q1表示从1到3的整数。
• Modulators of proteolysis and associated methods of use
  申请人：Arvinas Operations, Inc.

  公开号：US11161841B2

  公开（公告）日：2021-11-02

  The present disclosure relates to bifunctional compounds, which find utility as modulators of Kirsten rat sarcoma protein (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand which binds to the respective E3 ubiquitin ligase and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation/inhibition of target protein. Diseases or disorders that result from aggregation, accumulation, and/or overactivation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

  本公开涉及双功能化合物，它们可用作 Kirsten 大鼠肉瘤蛋白（靶蛋白）的调节剂。特别是，本公开涉及双功能化合物，其一端含有与相应 E3 泛素连接酶结合的 Von Hippel-Lindau、cereblon、Apotosis Proteins 抑制剂或小鼠双敏同源物 2 配体，另一端含有与靶蛋白结合的分子，从而使靶蛋白靠近泛素连接酶以实现对靶蛋白的降解（和抑制）。本公开物具有与降解/抑制靶蛋白相关的广泛药理活性。本公开的化合物和组合物可以治疗或预防因目标蛋白的聚集、积累和/或过度激活而导致的疾病或失调。
• MODULATORS OF PROTEOLYSIS AND ASSOCIATED METHODS OF USE
  申请人：Arvinas Operations, Inc.

  公开号：EP3774777A2

  公开（公告）日：2021-02-17
• US8436184B2
  申请人：——

  公开号：US8436184B2

  公开（公告）日：2013-05-07
• Discovery of Novel Naphthylphenylketone and Naphthylphenylamine Derivatives as Cell Division Cycle 25B (CDC25B) Phosphatase Inhibitors: Design, Synthesis, Inhibition Mechanism, and in Vitro Efficacy against Melanoma Cell Lines
  作者：Carmen Cerchia、Rosarita Nasso、Matteo Mori、Stefania Villa、Arianna Gelain、Alessandra Capasso、Federica Aliotta、Martina Simonetti、Rosario Rullo、Mariorosario Masullo、Emmanuele De Vendittis、Maria Rosaria Ruocco、Antonio Lavecchia

  DOI：10.1021/acs.jmedchem.9b00632

  日期：2019.8.8

  CDC25 phosphatases play a critical role in the regulation of the cell cycle and thus represent attractive cancer therapeutic targets. We previously discovered the 4-(2-carboxybenzoyl)phthalic acid (NSC28620) as a new CDC25 inhibitor endowed with promising anticancer activity in breast, prostate, and leukemia cells. Herein, we report a structure-based optimization of NSC28620, leading to the identification of a series of novel naphthylphenylketone and naphthylphenylamine derivatives as CDC25B inhibitors. Compounds 7j, 7i, 6e, 7f, and 3 showed higher inhibitory activity than the initial lead, with Ki values in the low micromolar range. Kinetic analysis, intrinsic fluorescence studies, and induced fit docking simulations provided a mechanistic understanding of the activity of these derivatives. All compounds were tested in the highly aggressive human melanoma cell lines A2058 and A375. Compound 4a potently inhibited cell proliferation and colony formation, causing an increase of the G2/M phase and a reduction of the G0/G1 phase of the cell cycle in both cell lines.