3-(哌啶-1-基磺酰)苯基硼酸 | 690662-96-5

• 物质功能分类: 原料药 - 人工合成抗感染类药 - 磺胺类药及增效剂
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 3-(哌啶-1-基磺酰)苯基硼酸
• 中文别名: 3-(哌啶-1-基磺酰基)苯硼酸；3-(1-哌啶基砜基)苯硼酸；3-(1-哌啶磺酰基)苯硼酸
• 英文名称: 3-(piperidin-1-ylsulfonyl)phenylboronic acid
• 英文别名: [3-(piperidin-1-ylsulphonyl)phenyl]boronic acid；3-(piperidine-1-sulfonyl)benzeneboronic acid；(3-piperidin-1-ylsulfonylphenyl)boronic acid
• CAS: 690662-96-5
• 化学式: C₁₁H₁₆BNO₄S
• 分子量: 269.129
• InChiKey: HQOWPGGTRBFYFE-UHFFFAOYSA-N

物化性质

• 熔点：
  166-168℃
• 沸点：
  494.5±55.0 °C(Predicted)
• 密度：
  1.37±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.46
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  86.2
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 危险品标志：
  Xi
• 安全说明：
  S26
• 危险类别码：
  R36
• 海关编码：
  2935009090
• 危险性防范说明：
  P210,P261,P264,P271,P280,P302+P352,P304+P340,P305+P351+P338,P312,P332+P313,P337+P313,P362,P370+P378,P403+P233,P403+P235,P405,P501
• 危险性描述：
  H315,H319,H335

反应信息

• 作为反应物：
  描述：

  N-(3-氯-4-((3-氟苄基)氧基)苯基)-6-碘喹唑啉-4-胺盐酸盐 、 3-(哌啶-1-基磺酰)苯基硼酸 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 乙二醇二甲醚 、 乙醇 、 水 为溶剂， 反应 18.0h， 以24.8%的产率得到N-(3-chloro-4-((3-fluorobenzyl)oxy)phenyl)-6-(3-(piperidin-1-ylsulfonyl)phenyl)quinazolin-4-amine
  参考文献：
  名称：

  Kinase Scaffold Repurposing for Neglected Disease Drug Discovery: Discovery of an Efficacious, Lapatanib-Derived Lead Compound for Trypanosomiasis

  摘要：

  Human African trypanosomiasis (HAT) is a neglected tropical disease caused by the protozoan parasite Trypanosoma brucei. Because drugs in use against HAT are toxic and require intravenous dosing, new drugs are needed. Initiating lead discovery campaigns by using chemical scaffolds from drugs approved for other indications can speed up drug discovery for neglected diseases. We demonstrated recently that the 4-anilinoquinazolines lapatinib (GW572016, 1) and canertinib (CI-1033) kill T. brucei with low micromolar EC50 values. We now report promising activity of analogues of 1, which provided an excellent starting point for optimization of the chemotype. Our compound optimization that has led to synthesis of several potent 4-anilinoquinazolines, including NEU617, 23a, a highly potent, orally bioavailable inhibitor of trypanosome replication. At the cellular level, 23a blocks duplication of the kinetoplast and arrests cytokinesis, making it a new chemical tool for studying regulation of the trypanosome cell cycle.

  DOI：

  10.1021/jm400349k
• 作为产物：
  描述：

  3-(6-Methyl-[1,3,6,2]dioxazaborocan-2-yl)-benzenesulfonyl chloride 在 Dowex 50WX₂-400 resin 作用下， 以 二氯甲烷 为溶剂， 生成 3-(哌啶-1-基磺酰)苯基硼酸
  参考文献：
  名称：

  Synthesis of Sulfonyl Chlorides of Phenylboronic Acids

  摘要：

  苯基硼酸酯的磺酰氯可通过选择性锂化溴代N-甲基二乙醇胺苯基硼酸盐，生成锂亚磺酰苯基硼酸盐中间体，再通过与N-氯代琥珀酰亚胺氧化，得到目标磺酰氯。这些新的试剂在制备苯基硼酸的磺酰胺以及其他化合物中非常有用，这些化合物可用于钯(0)催化的交叉偶联反应。此外，它们还具有作为生理pKa条件下碳水化合物结合剂的潜力。

  DOI：

  10.1055/s-2004-817758

文献信息

• [EN] HALO SULFONYL ARYL BORONATES<br/>[FR] HALO SULFONYL ARYL BORONATES
  申请人：NOVO NORDISK AS

  公开号：WO2004041833A1

  公开（公告）日：2004-05-21

  The present invention relates to halo sulfonyl aryl boronates of the general formula (I): wherein Arylene designates a carbocyclic or heterocyclic, aromatic ring system comprising 1-3 rings; R1, R2 and R3 are, independently, hydrogen, C1-6alkyl, C1-6alkoxy, halogen, nitro, cyano or phenyl;X is fluoro, chloro or bromo; and Y is a boroxine moiety attached via a bond from Arylene to one of the boron atoms of a boroxine ring which ring has a group of the formula -Arylene(R1)(R2)(R3)SO2X, wherein Arylene, R1, R2, R3 and X are as defined above, at each of the other two boron atoms of the boroxine ring, or Y is a boronic acid group or a boronic ester group.The invention also relates to the preparation of the compounds of formula (I) and to their use in organic synthesis.

  本发明涉及一般式(I)的卤磺酰基芳基硼酸酯，其中芳烃代表一个包含1-3个环的碳环或杂环芳香环系统；R1、R2和R3分别是氢、C1-6烷基、C1-6烷氧基、卤素、硝基、氰基或苯基；X是氟、氯或溴；Y是通过一种键连接到芳烃上的硼氧杂环部分，该硼氧杂环具有一个式为-Arylene(R1)(R2)(R3)SO2X的基团，其中Arylene、R1、R2、R3和X如上定义，在硼氧杂环的另外两个硼原子上，或Y是硼酸基团或硼酯基团。该发明还涉及一般式(I)化合物的制备以及它们在有机合成中的应用。
• HETEROCYCLIC COMPOUNDS AND USES THEREOF
  申请人：CASTRO Alfredo C.

  公开号：US20130053362A1

  公开（公告）日：2013-02-28

  Compounds and pharmaceutical compositions that modulate kinase activity, including PI3 kinase activity, and compounds, pharmaceutical compositions, and methods of treatment of diseases and conditions associated with kinase activity, including P13 kinase activity, are described herein.

  本文描述了调节激酶活性的化合物和药物组合物，包括PI3激酶活性，以及与激酶活性相关的疾病和病况的治疗方法，包括PI3激酶活性的化合物、药物组合物和治疗方法。
• Design and Evaluation of Novel Biphenyl Sulfonamide Derivatives with Potent Histamine H₃ Receptor Inverse Agonist Activity
  作者：Jonathan A. Covel、Vincent J. Santora、Jeffrey M. Smith、Rena Hayashi、Charlemagne Gallardo、Michael I. Weinhouse、Jason B. Ibarra、Jeffrey A. Schultz、Douglas M. Park、Scott A. Estrada、Brian J. Hofilena、Michelle D. Pulley、Brian M. Smith、Albert Ren、Marissa Suarez、John Frazer、Jeffrey Edwards、Erin K. Hauser、Jodie Lorea、Graeme Semple、Andrew J. Grottick

  DOI：10.1021/jm900857n

  日期：2009.9.24

  Phenethyl-R-2-methylpyrrolidine containing biphenylsulfonamide compounds were shown to be potent and selective antagonists of the H3 receptor. Several of these compounds demonstrated in vivo activity in a rat model of (R)-α-methyl histamine (RAMH) induced dipsogenia, and one compound (4e) provided an increase in wakefulness in rats as measured by polysomnographic methods. However, more detailed analysis of the PK/PD

  组胺-H 3受体的拮抗作用是探索增加清醒性以治疗诸如过度日间嗜睡（EDS）以及其他睡眠或认知障碍之类的疾病的一种策略。含有苯乙基-R -2-甲基吡咯烷的联苯磺酰胺化合物被证明是H 3受体的有效和选择性拮抗剂。这些化合物中的几种在（R）-α-甲基组胺（RAMH）诱导的成瘾症的大鼠模型中具有体内活性，一种化合物（4e）通过多导睡眠监测法测量了大鼠的清醒度。但是，对PK / PD关系的更详细分析表明存在共同的活性代谢物，这可能会使该系列化合物无法进一步开发。
• Synthesis of Sulfonyl Chlorides of Phenylboronic Acids
  作者：Per Vedsø、Thomas Hoeg-Jensen、Preben H. Olesen

  DOI：10.1055/s-2004-817758

  日期：——

  Sulfonyl chlorides of phenylboronic esters have been made available by selective lithiation of bromo N-methyl-di­ethanolamine phenylboronates to give lithium sulfinyl phenylboronates as intermediates. Oxidations with N-chlorosuccinimide give the target sulfonyl chlorides, which may be isolated or used in situ for further reactions. The novel reagents are useful in preparation of among other sulfonamides of phenylboronic acids for use in Pd(0) catalysed cross-couplings. They also hold potential as carbohydrate binders with physiological pKa.

  苯基硼酸酯的磺酰氯可通过选择性锂化溴代N-甲基二乙醇胺苯基硼酸盐，生成锂亚磺酰苯基硼酸盐中间体，再通过与N-氯代琥珀酰亚胺氧化，得到目标磺酰氯。这些新的试剂在制备苯基硼酸的磺酰胺以及其他化合物中非常有用，这些化合物可用于钯(0)催化的交叉偶联反应。此外，它们还具有作为生理pKa条件下碳水化合物结合剂的潜力。
• Kinase Scaffold Repurposing for Neglected Disease Drug Discovery: Discovery of an Efficacious, Lapatanib-Derived Lead Compound for Trypanosomiasis
  作者：Gautam Patel、Caitlin E. Karver、Ranjan Behera、Paul J. Guyett、Catherine Sullenberger、Peter Edwards、Norma E. Roncal、Kojo Mensa-Wilmot、Michael P. Pollastri

  DOI：10.1021/jm400349k

  日期：2013.5.23

  Human African trypanosomiasis (HAT) is a neglected tropical disease caused by the protozoan parasite Trypanosoma brucei. Because drugs in use against HAT are toxic and require intravenous dosing, new drugs are needed. Initiating lead discovery campaigns by using chemical scaffolds from drugs approved for other indications can speed up drug discovery for neglected diseases. We demonstrated recently that the 4-anilinoquinazolines lapatinib (GW572016, 1) and canertinib (CI-1033) kill T. brucei with low micromolar EC50 values. We now report promising activity of analogues of 1, which provided an excellent starting point for optimization of the chemotype. Our compound optimization that has led to synthesis of several potent 4-anilinoquinazolines, including NEU617, 23a, a highly potent, orally bioavailable inhibitor of trypanosome replication. At the cellular level, 23a blocks duplication of the kinetoplast and arrests cytokinesis, making it a new chemical tool for studying regulation of the trypanosome cell cycle.