2-(4-(benzyloxy)-3-nitrophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane | 855738-76-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-(4-(benzyloxy)-3-nitrophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
• 英文别名: [2-Nitro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-carbamic Acid tert-butyl Ester；4,4,5,5-tetramethyl-2-(3-nitro-4-phenylmethoxyphenyl)-1,3,2-dioxaborolane
• CAS: 855738-76-0
• 化学式: C₁₉H₂₂BNO₅
• 分子量: 355.198
• InChiKey: FQSLRJQQEQSWIQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.47
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  73.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(4-(benzyloxy)-3-nitrophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane 在 10% palladium on carbon 、 氢气 作用下， 以 乙醇 为溶剂， 以87%的产率得到3-氨基-4-羟基苯硼酸频那醇酯
  参考文献：
  名称：

  Boron-containing phenoxyacetanilide derivatives as hypoxia-inducible factor (HIF)-1α inhibitors

  摘要：

  A series of boron-containing phenoxyacetanilide derivatives 8a-f, 9a-f, 15, and 16 were synthesized as hypoxia-inducible factor (HIF)-1 alpha inhibitors. Among the compounds synthesized, carboranylphenoxy-acetanilide 16 (GN26361) was found to be a potent inhibitor against HIF-1 alpha accumulation under hypoxic conditions and inhibited the hypoxia-induced HIF-1 transcriptional activity in HeLa cells (IC50 = 0.74 mu M). Compound 16 suppressed hypoxia-induced HIF-1 alpha accumulation and vascular endothelial growth factor mRNA expression in a concentration-dependent manner without affecting the expression of HIF-1 alpha mRNA. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.12.037
• 作为产物：
  描述：

  1-苄氧基-4-溴-2-硝基苯 、 联硼酸频那醇酯 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 potassium acetate 作用下， 以 1,4-二氧六环 为溶剂， 以93%的产率得到2-(4-(benzyloxy)-3-nitrophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane
  参考文献：
  名称：

  Boron-containing phenoxyacetanilide derivatives as hypoxia-inducible factor (HIF)-1α inhibitors

  摘要：

  A series of boron-containing phenoxyacetanilide derivatives 8a-f, 9a-f, 15, and 16 were synthesized as hypoxia-inducible factor (HIF)-1 alpha inhibitors. Among the compounds synthesized, carboranylphenoxy-acetanilide 16 (GN26361) was found to be a potent inhibitor against HIF-1 alpha accumulation under hypoxic conditions and inhibited the hypoxia-induced HIF-1 transcriptional activity in HeLa cells (IC50 = 0.74 mu M). Compound 16 suppressed hypoxia-induced HIF-1 alpha accumulation and vascular endothelial growth factor mRNA expression in a concentration-dependent manner without affecting the expression of HIF-1 alpha mRNA. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.12.037

文献信息

• [EN] WDR5-MYC INHIBITORS<br/>[FR] INHIBITEURS DE WDR5-MYC
  申请人：UNIV VANDERBILT

  公开号：WO2021021951A1

  公开（公告）日：2021-02-04

  Substituted N-phenyl sulfonamide compounds inhibit WDR5-MYC interactions, and the compounds and their pharmaceutical compositions are useful for treating disorders and conditions in a subject, such as cancer cell proliferation.

  取代的N-苯基磺酰胺化合物可以抑制WDR5-MYC相互作用，这些化合物及其药物组合物可用于治疗受试者中的疾病和状况，如癌细胞增殖。
• Discovery and Optimization of Salicylic Acid-Derived Sulfonamide Inhibitors of the WD Repeat-Containing Protein 5–MYC Protein–Protein Interaction
  作者：Jonathan D. Macdonald、Selena Chacón Simon、Changho Han、Feng Wang、J. Grace Shaw、Jennifer E. Howes、Jiqing Sai、Joannes P. Yuh、Demarco Camper、Bethany M. Alicie、Joseph Alvarado、Sameer Nikhar、William Payne、Erin R. Aho、Joshua A. Bauer、Bin Zhao、Jason Phan、Lance R. Thomas、Olivia W. Rossanese、William P. Tansey、Alex G. Waterson、Shaun R. Stauffer、Stephen W. Fesik

  DOI：10.1021/acs.jmedchem.9b01411

  日期：2019.12.26

  The treatment of tumors driven by overexpression or amplification of MYC oncogenes remains a significant challenge in drug discovery. Here, we present a new strategy toward the inhibition of MYC via the disruption of the protein-protein interaction between MYC and its chromatin cofactor WD Repeat-Containing Protein 5. Blocking the association of these proteins is hypothesized to disrupt the localization of MYC to chromatin, thus disrupting the ability of MYC to sustain tumorigenesis. Utilizing a high-throughput screening campaign and subsequent structure-guided design, we identify small-molecule inhibitors of this interaction with potent in vitro binding affinity and report structurally related negative controls that can be used to study the effect of this disruption. Our work suggests that disruption of this protein-protein interaction may provide a path toward an effective approach for the treatment of multiple tumors and anticipate that the molecules disclosed can be used as starting points for future efforts toward compounds with improved drug-like properties.
• Development of hypoxia-inducible factor (HIF)-1α inhibitors: Effect of ortho-carborane substituents on HIF transcriptional activity under hypoxia
  作者：Hiroyuki Nakamura、Yuka Yasui、Minako Maruyama、Hidemitsu Minegishi、Hyun Seung Ban、Shinichi Sato

  DOI：10.1016/j.bmcl.2012.11.081

  日期：2013.2

  A series of substituted ortho-carboranylphenoxyacetanilides were synthesized and evaluated for their ability to inhibit hypoxia-induced HIF-1 transcriptional activity using a cell-based reporter assay in HeLa cells expressing the HRE-dependent firefly luciferase reporter construct (HRE-Luc) and constitutively expressing CMV-driven Renilla luciferase reporter, and their ability to inhibit cell growth (GI(50)) using the MTT assay. Among the compounds synthesized, 1g and 1l showed significant inhibition of hypoxia-induced HIF-1 transcriptional activity (IC50: 1.9 +/- 0.4 and 1.4 +/- 0.2 mu M, respectively). Both compounds suppressed HIF-1 alpha accumulation in a concentration-dependent manner. The porcine heart malate dehydrogenase (MDH) refolding assay revealed that compound 1l inhibited human Hsp60 chaperone activity (IC50: 6.80 +/- 0.25 mu M) and this inhibition activity was higher than that of ETB (IC50: 10.9 +/- 0.63 mu M). (c) 2012 Elsevier Ltd. All rights reserved.
• Boron-containing phenoxyacetanilide derivatives as hypoxia-inducible factor (HIF)-1α inhibitors
  作者：Kazuki Shimizu、Minako Maruyama、Yuka Yasui、Hidemitsu Minegishi、Hyun Seung Ban、Hiroyuki Nakamura

  DOI：10.1016/j.bmcl.2009.12.037

  日期：2010.2

  A series of boron-containing phenoxyacetanilide derivatives 8a-f, 9a-f, 15, and 16 were synthesized as hypoxia-inducible factor (HIF)-1 alpha inhibitors. Among the compounds synthesized, carboranylphenoxy-acetanilide 16 (GN26361) was found to be a potent inhibitor against HIF-1 alpha accumulation under hypoxic conditions and inhibited the hypoxia-induced HIF-1 transcriptional activity in HeLa cells (IC50 = 0.74 mu M). Compound 16 suppressed hypoxia-induced HIF-1 alpha accumulation and vascular endothelial growth factor mRNA expression in a concentration-dependent manner without affecting the expression of HIF-1 alpha mRNA. (C) 2009 Elsevier Ltd. All rights reserved.
• Synthesis and biological evaluation of meta-carborane-containing phenoxyacetanilides as inhibitors of hypoxia-inducible factor (HIF)-1 transcriptional activity
  作者：Guangzhe Li、Soyoko Azuma、Hidemitsu Minegishi、Hiroyuki Nakamura

  DOI：10.1016/j.jorganchem.2015.05.029

  日期：2015.12

  meta-Carboranylphenoxyacetanilides were synthesized by copper catalyzed coupling reaction of meta-carborane and phenyl iodides. The synthesized compounds were evaluated for their ability to inhibit hypoxia-induced HIF-1 transcriptional activity using a cell-based reporter gene assay. Among the compounds synthesized, meta-carborane containing phenoxyanilides 2d and 2h, which have an isobutyl group on meta-carborane, exhibited significant inhibition of hypoxia-induced HIF-1 transcriptional activity toward HeLa cell-based reporter gene assay with the IC50 values of 0.73 and 0.55 mu M, respectively. (C) 2015 Elsevier B.V. All rights reserved.