1-甲基-1H-咪唑-5-基 | 849062-28-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 1-甲基-1H-咪唑-5-基
• 英文名称: (1-methyl-1H-imidazol-5-yl)boronic acid
• 英文别名: (3-methylimidazol-4-yl)boronic acid
• CAS: 849062-28-8
• 化学式: C₄H₇BN₂O₂
• mdl: MFCD10696628
• 分子量: 125.923
• InChiKey: DLUBTALXEVEGHN-UHFFFAOYSA-N

物化性质

• 沸点：
  413.3±37.0 °C(Predicted)
• 密度：
  1.23±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.47
• 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

安全信息

• 海关编码：
  2933290090

反应信息

• 作为反应物：
  描述：

  1-甲基-1H-咪唑-5-基 、 2-bromo-5-(3-chloro-4-isopropoxyphenyl)-1,3,4-thiadiazole 生成 2-(3-Chloro-4-propan-2-yloxyphenyl)-5-(3-methylimidazol-4-yl)-1,3,4-thiadiazole
  参考文献：
  名称：

  四氢吡唑并吡啶作为鞘氨醇1-磷酸受体3（S1P 3）的低剂量口服S1P 1激动剂的发现

  摘要：

  FTY720是第一个批准用于治疗复发缓解型多发性硬化症患者的口服小分子药物。它是S1P 1受体的有效激动剂，但对S1P 3受体的选择性缺乏与临床中观察到的大多数心血管副作用有关。这些发现引发了为识别第二代S1P 3 -S1P 1而付出的巨大努力。激动剂。我们最近公开了一系列符合这些标准的口服活性四氢异喹啉（THIQ）化合物。在本文中，我们描述了我们如何定义和实施旨在发现选择性结构不同的后续激动剂的策略。这项努力最终鉴定出一系列口服活性四氢吡唑并吡啶。

  DOI：

  10.1021/acs.jmedchem.5b01512

文献信息

• Discovery and optimization of potent and selective imidazopyridine and imidazopyridazine mTOR inhibitors
  作者：Emily A. Peterson、Alessandro A. Boezio、Paul S. Andrews、Christiane M. Boezio、Tammy L. Bush、Alan C. Cheng、Deborah Choquette、James R. Coats、Adria E. Colletti、Katrina W. Copeland、Michelle DuPont、Russell Graceffa、Barbara Grubinska、Joseph L. Kim、Richard T. Lewis、Jingzhou Liu、Erin L. Mullady、Michele H. Potashman、Karina Romero、Paul L. Shaffer、Mary K. Stanton、John C. Stellwagen、Yohannes Teffera、Shuyan Yi、Ti Cai、Daniel S. La

  DOI：10.1016/j.bmcl.2012.06.033

  日期：2012.8

  of our program to discover ATP-competitive mTOR inhibitors that demonstrate improved pharmacokinetic properties and selectivity compared to our previous leads. Through targeted SAR and structure-guided design, new imidazopyridine and imidazopyridazine scaffolds were identified that demonstrated superior inhibition of mTOR in cellular assays, selectivity over the closely related PIKK family and improved

  mTOR是多种生长因子下游细胞信号传导的关键调节剂。mTOR / PI3K / AKT途径在人类癌症中经常发生突变，因此是重要的肿瘤学靶标。在本文中，我们报告了我们开发发现与ATP竞争的mTOR抑制剂的程序的进展，这些抑制剂与我们以前的产品相比具有更高的药代动力学特性和选择性。通过有针对性的SAR和结构导向的设计，鉴定出了新的咪唑并吡啶和咪唑并哒嗪支架，它们在细胞测定中表现出对mTOR的优异抑制作用，在密切相关的PIKK家族中具有选择性，并且比我们以前报道的苯并咪唑系列具有​​更高的体内清除率。
• [EN] INHIBITORS OF CYTOMEGALOVIRUS<br/>[FR] INHIBITEURS DE CYTOMÉGALOVIRUS
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2014070976A1

  公开（公告）日：2014-05-08

  Compounds of Formula (I) wherein R1, R2, R3A, R3B, Y, Z1 and Z2 are defined herein, are useful for the treatment of cytomegalovirus disease and/or infection.

  式（I）中R1、R2、R3A、R3B、Y、Z1和Z2所定义的化合物对巨细胞病毒疾病和/或感染的治疗具有用处。
• SUBSTITUTED AZAINDAZOLE COMPOUNDS
  申请人：Austin Joel F.

  公开号：US20130231354A1

  公开（公告）日：2013-09-05

  Disclosed are azaindazole compounds of Formula (I): or pharmaceutically acceptable salts thereof, wherein: Q is: (i) 5-membered heteroaryl comprising at least one nitrogen heteroatom and substituted with zero to 2 Rg; or (ii) 9- to 10-membered bicyclic heteroaryl selected from Formula (II) and; wherein Ring A is a 5- to 6-membered aryl or heteroaryl fused ring substituted with zero to 2 Rg; and R1, R2, R3, and Rg are defined herein. Also disclosed are methods of using such compounds in the treatment of at least one CYP17 associated condition, such as, for example, cancer, and pharmaceutical compositions comprising such compounds.

  本发明涉及以下式（I）的吡唑吡嗪化合物或其药学上可接受的盐，其中：Q为：（i）包含至少一个氮杂原子的5-成员杂芳基，取代基为零到2个Rg；或（ii）选自式（II）的9-至10-成员双环杂芳基；其中环A为5-至6-成员芳基或杂芳基融合环，取代基为零到2个Rg；R1、R2、R3和Rg如本文所定义。本发明还涉及使用这种化合物治疗至少一种CYP17相关疾病的方法，例如癌症，以及包含这种化合物的制药组合物。
• 10.1021/acs.jmedchem.4c00855
  作者：Brindani, Nicoletta、Vuong, Linh M.、La Serra, Maria Antonietta、Salvador, Noel、Menichetti, Andrea、Acquistapace, Isabella Maria、Ortega, Jose Antonio、Veronesi, Marina、Bertozzi, Sine Mandrup、Summa, Maria、Girotto, Stefania、Bertorelli, Rosalia、Armirotti, Andrea、Ganesan, Anand K.、De Vivo, Marco

  DOI：10.1021/acs.jmedchem.4c00855

  日期：——

  reported, compound 15 (ARN25499) stands out as the best lead compound with an improved pharmacokinetic profile, increased bioavailability, and efficacy in an in vivo PDX tumor mouse model. Our results indicate that these CDC42 inhibitors represent a promising chemical class toward the discovery of anticancer drugs, with ARN25499 as an additional lead candidate for preclinical development.

  我们之前报道了三取代嘧啶先导化合物，即 ARN22089 和 ARN25062，它们阻断 CDC42 与其特定下游效应器（PAK 蛋白）之间的相互作用。这种相互作用对于多种肿瘤类型的进展至关重要。此类抑制剂在体内表现出抗癌功效。在这里，我们描述了具有良好的药物样特性的第二类 CDC42 抑制剂。在本文报道的 25 种化合物中，化合物15 (ARN25499) 脱颖而出，成为最佳先导化合物，在体内 PDX 肿瘤小鼠模型中具有改善的药代动力学特征、增加的生物利用度和功效。我们的结果表明，这些 CDC42 抑制剂代表了一种有前途的化学类别，有助于发现抗癌药物，其中 ARN25499 是临床前开发的另一个主要候选药物。
• 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.