B-(1-甲基-1H-咪唑-4-基)硼酸 | 957720-01-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: B-(1-甲基-1H-咪唑-4-基)硼酸
• 英文名称: (1-methyl-1H-imidazol-4-yl)boronic acid
• 英文别名: (1-methylimidazol-4-yl)boronic acid
• CAS: 957720-01-3
• 化学式: C₄H₇BN₂O₂
• 分子量: 125.923
• InChiKey: OFMUVGASVDGYKV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.9
• 重原子数：
  9
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  58.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(4-bromophenyl)-6,7-dimethoxy-1,4-dihydroindeno[1,2-c]pyrazole 、 B-(1-甲基-1H-咪唑-4-基)硼酸 在 bis-triphenylphosphine-palladium(II) chloride sodium carbonate 作用下， 以 乙二醇二甲醚 、 乙醇 为溶剂， 生成 6,7-dimethoxy-3-[4-(1-methyl-3H-imidazol-4-yl)-phenyl]-2,4-dihydro-indeno[1,2-c]pyrazole
  参考文献：
  名称：

  Discovery of 4′-(1,4-dihydro-indeno[1,2-c]pyrazol-3-yl)-benzonitriles and 4′-(1,4-dihydro-indeno[1,2-c]pyrazol-3-yl)-pyridine-2′-carbonitriles as potent checkpoint kinase 1 (Chk1) inhibitors

  摘要：

  An extensive structure-activity relationship study of the 3-position of a series of tricyclic pyrazole-based Chk1 inhibitors is described. As a result, 4'-,1,4-dihydro-indeno[1,2-c]pyrazol-3-yl)-benzonitriles (4) and 4'-(1,4-dihydro-indeno[1,2-c]pyrazol-3-yl)pyridine-2'-carbonitriles (29) emerged as new lead series. Compared with the original lead compound 2, these new leads fully retain the biological activity in both enzymatic inhibition and cell-based assays. More importantly, the new leads 4 and 29 exhibit favorable physicochemical properties such as lower molecular weight, lower Clog P, and the absence of a hydroxyl group. Furthermore, structure-activity relationship studies were performed at the 6- and 7-positions of 4, which led to the identification of ideal Chk1 inhibitors 49, 50, 51, and 55. These compounds not only potently inhibit Chk1 in an enzymatic assay but also significantly potentiate the cytotoxicity of DNA-damaging agents in cell-based assays while they show little single agent activity. A cell cycle analysis by FACS confirmed that these Chk1 inhibitors efficiently abrogate the G2/M and S checkpoints induced by DNA-damaging agent. The current work paved the way to the identification of several potent Chk1 inhibitors with good pharmacokinetics that are suitable for in vivo study with oral dosing. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.07.102
• 作为产物：
  描述：

  生成 B-(1-甲基-1H-咪唑-4-基)硼酸
  参考文献：
  名称：

  Mediators of hedgehog signaling pathways, compositions and uses related thereto

  摘要：

  本发明提供了一种抑制由于刺猬增强功能而导致的异常生长状态的方法和试剂，通过将细胞与刺猬拮抗剂（例如小分子）接触，以足够的量来抑制异常生长状态，例如激活正常的ptc途径或拮抗刺猬活性。

  公开号：

  US09173869B2

文献信息

• Delayed and Prolonged Histone Hyperacetylation with a Selective HDAC1/HDAC2 Inhibitor
  作者：Joey L. Methot、Dawn Mampreian Hoffman、David J. Witter、Matthew G. Stanton、Paul Harrington、Christopher Hamblett、Phieng Siliphaivanh、Kevin Wilson、Jed Hubbs、Richard Heidebrecht、Astrid M. Kral、Nicole Ozerova、Judith C. Fleming、Hongmei Wang、Alexander A. Szewczak、Richard E. Middleton、Bethany Hughes、Jonathan C. Cruz、Brian B. Haines、Melissa Chenard、Candia M. Kenific、Andreas Harsch、J. Paul Secrist、Thomas A. Miller

  DOI：10.1021/ml4004233

  日期：2014.4.10

  The identification and in vitro and in vivo characterization of a potent SHI-1:2 are described. Kinetic analysis indicated that biaryl inhibitors exhibit slow binding kinetics in isolated HDAC1 and HDAC2 preparations. Delayed histone hyperacetylation and gene expression changes were also observed in cell culture, and histone acetylation was observed in vivo beyond disappearance of drug from plasma. In vivo studies further demonstrated that continuous target inhibition was well tolerated and efficacious in tumor-bearing mice, leading to tumor growth inhibition with either once-daily or intermittent administration.
• Expanding the structural diversity of diarylureas as multi-target tyrosine kinase inhibitors
  作者：Yuanyuan Shan、Chen Wang、Lin Zhang、Jinfeng Wang、Maoyi Wang、Yalin Dong

  DOI：10.1016/j.bmc.2015.12.038

  日期：2016.2

  Recently approved multi-target inhibitors of receptor tyrosine kinases (RTKs) have significantly improved the clinical treatment of cancers. A series of N,N'-diarylureas incorporated with aromatic heterocycle have been designed, synthesized and evaluated as novel multi-target RTK inhibitors. The preliminary biological evaluation indicated that several compounds exhibited comparable potency with Sorafenib. Among them, compound 6f was identified as the most potent multikinase inhibitor of EGFR, KDR and FGFR1 with IC50 values of 14.83 nM, 21.57 nM, and 28.23 nM, respectively. These compounds expanded the structural diversity of diarylureas as RTK inhibitors. The results demonstrated that compound 6f could be served as novel lead compound for further development of multi-target RTK inhibitors. (c) 2015 Elsevier Ltd. All rights reserved.
• CN115093398
  申请人：——

  公开号：——

  公开（公告）日：——
• CN114957252
  申请人：——

  公开号：——

  公开（公告）日：——
• Discovery of 4′-(1,4-dihydro-indeno[1,2-c]pyrazol-3-yl)-benzonitriles and 4′-(1,4-dihydro-indeno[1,2-c]pyrazol-3-yl)-pyridine-2′-carbonitriles as potent checkpoint kinase 1 (Chk1) inhibitors
  作者：Zhi-Fu Tao、Gaoquan Li、Yunsong Tong、Kent D. Stewart、Zehan Chen、Mai-Ha Bui、Philip Merta、Chang Park、Peter Kovar、Haiying Zhang、Hing L. Sham、Saul H. Rosenberg、Thomas J. Sowin、Nan-Horng Lin

  DOI：10.1016/j.bmcl.2007.07.102

  日期：2007.11

  An extensive structure-activity relationship study of the 3-position of a series of tricyclic pyrazole-based Chk1 inhibitors is described. As a result, 4'-,1,4-dihydro-indeno[1,2-c]pyrazol-3-yl)-benzonitriles (4) and 4'-(1,4-dihydro-indeno[1,2-c]pyrazol-3-yl)pyridine-2'-carbonitriles (29) emerged as new lead series. Compared with the original lead compound 2, these new leads fully retain the biological activity in both enzymatic inhibition and cell-based assays. More importantly, the new leads 4 and 29 exhibit favorable physicochemical properties such as lower molecular weight, lower Clog P, and the absence of a hydroxyl group. Furthermore, structure-activity relationship studies were performed at the 6- and 7-positions of 4, which led to the identification of ideal Chk1 inhibitors 49, 50, 51, and 55. These compounds not only potently inhibit Chk1 in an enzymatic assay but also significantly potentiate the cytotoxicity of DNA-damaging agents in cell-based assays while they show little single agent activity. A cell cycle analysis by FACS confirmed that these Chk1 inhibitors efficiently abrogate the G2/M and S checkpoints induced by DNA-damaging agent. The current work paved the way to the identification of several potent Chk1 inhibitors with good pharmacokinetics that are suitable for in vivo study with oral dosing. (c) 2007 Elsevier Ltd. All rights reserved.