1-异丁基-1H-吡唑-4-基硼酸 | 929094-25-7

• 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-异丁基-1H-吡唑-4-基硼酸
• 英文名称: [1-(2-methylpropyl)-1H-pyrazol-4-yl]boronic acid
• 英文别名: (1-isobutyl-1H-pyrazol-4-yl)boronic acid；[1-(2-methylpropyl)pyrazol-4-yl]boronic acid
• CAS: 929094-25-7
• 化学式: C₇H₁₃BN₂O₂
• mdl: MFCD09951916
• 分子量: 168.003
• InChiKey: ZNPDFJXJVSSPFF-UHFFFAOYSA-N

物化性质

• 沸点：
  330.6±34.0 °C(Predicted)
• 密度：
  1.12±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.13
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.571
• 拓扑面积：
  58.3
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 海关编码：
  2933199090
• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  6-chloro-N-(4-(trifluoromethoxy)phenyl)pyrimidin-4-amine 、 1-异丁基-1H-吡唑-4-基硼酸 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 水 、 乙腈 为溶剂， 反应 8.0h， 生成 [6-(1-isobutyl-1H-pyrazol-4-yl)pyrimidin-4-yl]-(4-trifluoromethoxyphenyl)amine
  参考文献：
  名称：

  扩大变构 Bcr-Abl 抑制剂的多样性

  摘要：

  伊马替尼对 Bcr-Abl 激酶活性的抑制用于治疗慢性粒细胞白血病 (CML)，目前作为用小分子靶向显性癌基因的范例。我们最近报道了 GNF-2 ( 1 ) 和 GNF-5 ( 2 ) 作为靶向肉豆蔻酸结合位点的细胞 Bcr-Abl 激酶活性的选择性非 ATP 竞争性抑制剂的发现。在这里，我们使用基于细胞的结构-活性关系来指导能够与肉豆蔻酸酯结合位点结合的配体的优化和多样化，并使基于 Abl-化合物1的发现合理化共晶。我们阐明了获得针对 Bcr-Abl 转化细胞的强效抗增殖活性所需的结构-活性关系，并报告了新化合物（5g、5h、6a、14d和21j-I）的发现，这些化合物显示出改进的效力或药理特性。这项工作表明，多种结构可以有效地靶向 Bcr-Abl 肉豆蔻酸酯结合位点，并为开发可靶向该结合位点的药物提供了新的线索。

  DOI：

  10.1021/jm100555f

文献信息

• Biology-Oriented Synthesis of a Withanolide-Inspired Compound Collection Reveals Novel Modulators of Hedgehog Signaling
  作者：Jakub Švenda、Michael Sheremet、Lea Kremer、Lukáš Maier、Jonathan O. Bauer、Carsten Strohmann、Slava Ziegler、Kamal Kumar、Herbert Waldmann

  DOI：10.1002/anie.201500112

  日期：2015.5.4

  Biology‐oriented synthesis employs the structural information encoded in complex natural products to guide the synthesis of compound collections enriched in bioactivity. The trans‐hydrindane dehydro‐δ‐lactone motif defines the characteristic scaffold of the steroid‐like withanolides, a plant‐derived natural product class with a diverse pattern of bioactivity. A withanolide‐inspired compound collection was synthesized

  面向生物学的合成利用复杂天然产物中编码的结构信息来指导富含生物活性的化合物集合的合成。所述反式-hydrindane脱氢δ内酯基序限定的特征的支架的类固醇类的睡茄内酯，植物来源的天然产物类生物活性的不同的图案。通过使用三个关键中间体合成了一个受醇化物启发的化合物，这些中间体包含用不同的反应性官能团衍生的该特征框架。在监测生物信号转导过程的基于细胞的测定中对化合物收集物的生物学评估揭示了针对蛋白质平滑化的一类新的刺猬信号抑制剂。
• Combined Proteomic and In Silico Target Identification Reveal a Role for 5-Lipoxygenase in Developmental Signaling Pathways
  作者：Silke Brand、Sayantani Roy、Peter Schröder、Bernd Rathmer、Jessica Roos、Shobhna Kapoor、Sumersing Patil、Claudia Pommerenke、Thorsten Maier、Petra Janning、Sonja Eberth、Dieter Steinhilber、Dennis Schade、Gisbert Schneider、Kamal Kumar、Slava Ziegler、Herbert Waldmann

  DOI：10.1016/j.chembiol.2018.05.016

  日期：2018.9

  of the Wnt pathway inhibitor Lipoxygenin. Lipoxygenin is a non-redox 5-LO inhibitor, modulates the β-catenin-5-LO complex and induces reduction of both β-catenin and 5-LO levels in the nucleus. Lipoxygenin and the structurally unrelated 5-LO inhibitor CJ-13,610 promote cardiac differentiation of human induced pluripotent stem cells and inhibit Hedgehog, TGF-β, BMP, and Activin A signaling, suggesting

  在基于细胞的筛选中鉴定和鉴定具有生物活性的小分子的靶标具有挑战性，并且常常遇到失败，因此需要开发新的方法。我们证明，化学蛋白质组学在使用SPiDER方法进行的计算机靶标预测中的组合可以为目标候选物的选择和实验深度评估的优先级提供有效的指导。我们确定5-脂氧合酶（5-LO）作为Wnt通路抑制剂脂氧合蛋白的目标。脂氧合蛋白是一种非氧化还原的5-LO抑制剂，可调节β-catenin-5-LO复合物并诱导细胞核内β-catenin和5-LO含量降低。脂氧合蛋白和与结构无关的5-LO抑制剂CJ-13,610促进人诱导的多能干细胞的心脏分化，并抑制刺猬，TGF-β，BMP，
• Discovery, Optimization, and Biological Characterization of 2,3,6‐Trisubstituted Pyridine‐Containing M ₄ Positive Allosteric Modulators
  作者：Jeffrey W. Schubert、Scott T. Harrison、James Mulhearn、Robert Gomez、Robert Tynebor、Kristen Jones、Jaime Bunda、Barbara Hanney、Jenny Miu‐Chen Wai、Chris Cox、John A. McCauley、John M. Sanders、Brian Magliaro、Julie O'Brien、Natasa Pajkovic、Sarah L. Huszar Agrapides、Anne Taylor、Anthony Gotter、Sean M. Smith、Jason Uslaner、Susan Browne、Stefania Risso、Melissa Egbertson

  DOI：10.1002/cmdc.201900088

  日期：2019.5.6

  Herein we describe the discovery and optimization of a new series of 2,3-disubstituted and 2,3,6-trisubstituted muscarinic acetylcholine receptor 4 (M4 ) positive allosteric modulators (PAMs). Iterative libraries enabled rapid exploration of one-dimensional structure-activity relationships (SAR) and identification of potency-enhancing heterocycle and N-alkyl pyrazole substituents. Further optimization

  在此，我们描述了一系列新的2,3-二取代和2,3,6-三取代毒蕈碱乙酰胆碱受体4（M4）正变构调节剂（PAMs）的发现和优化。迭代库使您能够快速探索一维结构-活性关系（SAR），并鉴定出增强效价的杂环和N-烷基吡唑取代基。进一步的优化导致鉴定出有效的，受体亚型选择性，脑渗透性工具化合物24（7- [3- [1-[（[1-氟环戊基）甲基]吡唑-4-基] -6-甲基-2 -吡啶基] -3-甲氧基肉桂啉）。它在临床前测定中可有效预测抗精神病作用，可在大鼠和小鼠中产生剂量依赖性的苯丙胺诱导的运动过度，但在M4基因敲除小鼠中则无效。
• Investigations on the 4-Quinolone-3-carboxylic Acid Motif. 3. Synthesis, Structure−Affinity Relationships, and Pharmacological Characterization of 6-Substituted 4-Quinolone-3-carboxamides as Highly Selective Cannabinoid-2 Receptor Ligands
  作者：Serena Pasquini、Alessia Ligresti、Claudia Mugnaini、Teresa Semeraro、Lavinia Cicione、Maria De Rosa、Francesca Guida、Livio Luongo、Maria De Chiaro、Maria Grazia Cascio、Daniele Bolognini、Pietro Marini、Roger Pertwee、Sabatino Maione、Vincenzo Di Marzo、Federico Corelli

  DOI：10.1021/jm100123x

  日期：2010.8.26

  A set of quinolone-3-carboxamides 2 bearing diverse substituents at position 1, 3, and 6 of the bicyclic nucleus was prepared. Except for six compounds exhibiting K(i) > 100 nM, all the quinolone-3-carboxamides 2 proved to be high affinity CB2 ligands, with K(i) values ranging from 73.2 to 0.7 nM and selectivity [SI = K(i)(CB1)/K(i)(CB2)] varying from > 14285 to 1.9, with only 2ah exhibiting a reverse selectivity (SI < 1). In the formalin test of peripheral acute and inflammatory pain in mice, 2ae showed analgesic activity that was antagonized by a selective CB2 antagonist. By contrast, 2e was inactive per se and antagonized the effect of a selective CB2 agonist. Finally, 2g and 2p exhibited CB2 inverse agonist-like behavior in this in vivo test. However, two different functional assays carried out in vitro on 2e and 2g indicated for both compounds an overall inverse agonist activity at CB2 receptors.
• Fragment-based discovery of potent ERK2 pyrrolopyrazine inhibitors
  作者：Daniel J. Burdick、Shumei Wang、Christopher Heise、Borlan Pan、Jake Drummond、JianPing Yin、Lauren Goeser、Steven Magnuson、Jeff Blaney、John Moffat、Weiru Wang、Huifen Chen

  DOI：10.1016/j.bmcl.2015.08.048

  日期：2015.11

  A fragment-based lead discovery approach was used to discover novel ERK2 inhibitors. The crystal structure of N-benzyl-9H-purin-6-amine 1 in complex with ERK2 elucidated its hinge-binding mode. In addition, the simultaneous binding of an imidazole molecule adjacent to 1 suggested a direction for fragment expansion. Structure-based core hopping applied to 1 led to 5H-pyrrolo[3,2-b] pyrazine (3) that afforded direct vectors to probe the pockets of interest while retaining the essential hinge binding elements. Utilizing the new vectors for SAR exploration, the new core 3 was quickly optimized to compound 39 resulting in a greater than 6600-fold improvement in potency. (C) 2015 Elsevier Ltd. All rights reserved.