频哪醇(4-戊基苯基)硼酸酯 | 1359844-02-2

• 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: 频哪醇(4-戊基苯基)硼酸酯
• 英文名称: 4,4,5,5-tetramethyl-2-(4-pentylphenyl)-1,3,2-dioxaborolane
• 英文别名: Pinacol(4-Pentylphenyl)Boronate
• CAS: 1359844-02-2
• 化学式: C₁₇H₂₇BO₂
• 分子量: 274.211
• InChiKey: YYAOSGNPSXDVEF-UHFFFAOYSA-N

物化性质

• 沸点：
  360.7±21.0 °C(Predicted)
• 密度：
  0.95±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.72
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  频哪醇(4-戊基苯基)硼酸酯 在 potassium hydrogen fluoride 、 三甲基氯硅烷 、 水 作用下， 以 甲醇 、 水 、 乙腈 为溶剂， 反应 1.5h， 生成 4-戊基苯硼酸
  参考文献：
  名称：

  Design and synthesis of boronic acid inhibitors of endothelial lipase

  摘要：

  Endothelial lipase (EL) and lipoprotein lipase (LPL) are homologous lipases that act on plasma lipoproteins. EL is predominantly a phospholipase and appears to be a key regulator of plasma HDL-C. LPL is mainly a triglyceride lipase regulating (V)LDL levels. The existing biological data indicate that inhibitors selective for EL over LPL should have anti-atherogenic activity, mainly through increasing plasma HDL-C levels. We report here the synthesis of alkyl, aryl, or acyl-substituted phenylboronic acids that inhibit EL. Many of the inhibitors evaluated proved to be nearly equally potent against both EL and LPL, but several exhibited moderate to good selectivity for EL. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.12.043
• 作为产物：
  描述：

  4-硝基苯酚三氟甲基磺酸酯 在 2-双环己基膦-2',6'-二甲氧基联苯 、 盐酸 、 potassium phosphate monohydrate 、 palladium on activated charcoal 、 氢气 、 palladium diacetate 、 三乙胺 、 sodium nitrite 作用下， 以 1,4-二氧六环 、 乙醇 、 水 、 甲苯 为溶剂， 生成 频哪醇(4-戊基苯基)硼酸酯
  参考文献：
  名称：

  Design and synthesis of boronic acid inhibitors of endothelial lipase

  摘要：

  Endothelial lipase (EL) and lipoprotein lipase (LPL) are homologous lipases that act on plasma lipoproteins. EL is predominantly a phospholipase and appears to be a key regulator of plasma HDL-C. LPL is mainly a triglyceride lipase regulating (V)LDL levels. The existing biological data indicate that inhibitors selective for EL over LPL should have anti-atherogenic activity, mainly through increasing plasma HDL-C levels. We report here the synthesis of alkyl, aryl, or acyl-substituted phenylboronic acids that inhibit EL. Many of the inhibitors evaluated proved to be nearly equally potent against both EL and LPL, but several exhibited moderate to good selectivity for EL. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.12.043

文献信息

• [EN] SUBSTITUTED AMINOALKYLAZOLES AS MALARIAL ASPARTIC PROTEASE INHIBITORS<br/>[FR] AMINOALKYLAZOLES SUBSTITUÉS UTILISÉS COMME INHIBITEURS DE LA PROTÉASE ASPARTIQUE DU PALUDISME
  申请人：LATVIAN INST ORGANIC SYNTHESIS

  公开号：WO2017069601A1

  公开（公告）日：2017-04-27

  The present invention relates to novel aminoalkylazoles acting as inhibitors of malarial protease plasmepsin II. These can be used as medicines or as constituent of medicines for the treatment of malaria infection.

  本发明涉及作为疟疾蛋白酶质体酶II抑制剂的新型氨基烷基唑类化合物。这些化合物可用作治疗疟疾感染的药物或药物成分。
• Azole-based non-peptidomimetic plasmepsin inhibitors
  作者：Linda Kinena、Gundars Leitis、Iveta Kanepe-Lapsa、Raitis Bobrovs、Kristaps Jaudzems、Vita Ozola、Edgars Suna、Aigars Jirgensons

  DOI：10.1002/ardp.201800151

  日期：2018.9

  The spread of drug‐resistant malaria parasites urges the search for new antimalarial drugs. Malarial aspartic proteases – plasmepsins (Plms) – are differentially expressed in multiple stages of the Plasmodium parasite's lifecycle and are considered as attractive drug targets. We report the development of novel azole‐based non‐peptidomimetic plasmepsin inhibitors that have been designed by bioisosteric

  抗药性疟原虫的传播促使人们寻找新的抗疟药。疟疾天冬氨酸蛋白酶——血浆蛋白酶 (Plms)——在疟原虫生命周期的多个阶段有差异表达，被认为是有吸引力的药物靶点。我们报告了新型唑类非肽模拟血浆蛋白酶抑制剂的开发，该抑制剂是通过对 Actelion 氨基哌嗪抑制剂中的酰胺部分进行生物等排取代而设计的。最好的基于三唑的抑制剂对 Plm II 表现出亚微摩尔的效力，这与母体 Actelion 化合物相当。新抑制剂可作为开发无耐药性抗疟药的起点，靶向非消化性 Plm IX 或 X，这对疟原虫生命周期至关重要。
• Iron-Catalyzed Borylation of Aryl Ethers via Cleavage of C–O Bonds
  作者：Xiaoqin Zeng、Yuxuan Zhang、Zhengli Liu、Shasha Geng、Yun He、Zhang Feng

  DOI：10.1021/acs.orglett.0c00679

  日期：2020.4.17

  Herein, we report the iron-catalyzed borylation of aryl ethers and aryl amines via cleavage of C–O and C–N bonds. This protocol does not require the use of Grignard reagents and displays a broad substrate scope, which allows the late-stage borylation. It also provides facile access to multisubstituted arenes through C–H functionalization using 2-pyridyloxy as the directing group.

  在本文中，我们报道了通过C–O和C–N键的裂解，铁催化的芳基醚和芳基胺的硼化反应。该方案不需要使用格氏试剂，并且显示了较宽的底物范围，可以进行后期硼化。它也可以通过使用2-吡啶氧基作为导向基团的C–H官能化轻松访问多取代的芳烃。
• Synthesis of 2-aminopyridopyrimidinones and their plasmepsin I, II, IV inhibition potency
  作者：Dace Rasina、Georgijs Stakanovs、Iveta Kanepe-Lapsa、Raitis Bobrovs、Kristaps Jaudzems、Aigars Jirgensons

  DOI：10.1007/s10593-020-02731-3

  日期：2020.6

  Malarial aspartic protease, plasmepsin (Plm), is perspective antimalarial drug target. Following up our previosly identified 2-aminoquinazolin-4(3H)-one-based inhibitors, 2-aminopyrido[2,3-d]-, -[3,2-d]-, and -[4,3-d]pyrimidin-4(3H)-ones bearing subpocket-specific substituents at position 7 were prepared and tested for their Plm I, II, IV inhibition potency. The position of the nitrogen atom in 2-

  疟疾天冬氨酸蛋白酶，纤溶酶（Plm）是抗疟疾药物的靶标。跟进我们以前确定的基于2-氨基喹唑啉-4（3 H）-one的抑制剂，2-氨基吡啶[2,3- d ]-，-[3,2- d ]-和-[4,3- d制备在位置7带有亚口袋特异性取代基的]嘧啶-4（3 H）-并测试其对Plm I，II，IV的抑制能力。2-氨基吡啶并嘧啶酮中氮原子的位置在对Plms的抑制效力中起重要作用。吡咯并[2,3- d ]嘧啶-4（3 H）-one衍生物显示对Plms I，II，IV的抑制作用较弱，而与位置7处的取代基无关。但是，吡啶并[4,3-d ] pyrimidin-4（3 H）-ones和吡啶并[3,2- d ] pyrimidin-4（3 H）-ones更适合用于Plm抑制剂的开发。特别地，2-氨基-7- [4-（3-苯基丙基）苯基] -3-[（四氢呋喃-2-基）甲基]吡啶基[3,2 - d ]嘧啶-4（3 H）-显示非常好。对Plm
• 2-Aminoquinazolin-4(3H)-one based plasmepsin inhibitors with improved hydrophilicity and selectivity
  作者：Dace Rasina、Georgijs Stakanovs、Oleksandr V. Borysov、Teodors Pantelejevs、Raitis Bobrovs、Iveta Kanepe-Lapsa、Kaspars Tars、Kristaps Jaudzems、Aigars Jirgensons

  DOI：10.1016/j.bmc.2018.04.012

  日期：2018.5

  2-Aminoquinazolin-4(3H)-ones were previously discovered as perspective leads for antimalarial drug development targeting the plasmepsins. Here we report the lead optimization studies with the aim to reduce inhibitor lipophilicity and increase selectivity versus the human aspartic protease Cathepsin D. Exploiting the solvent exposed area of the enzyme provides an option to install polar groups (R-1) the 5-position of 2-aminoquinazolin-4(3H)-one to inhibitors such as carboxylic acid without scarifying enzymatic potency. Moreover, introduction of R-1 substituents increased selectivity factors of compounds in this series up to 100-fold for Plm II, IV vs CatD inhibition. The introduction of flap pocket substituent (R-2) at 7-postion of 2-aminoquinazolin-4(3H)-one allows to remove Ph group from THF ring without notably impairing Plm inhibitory potency. Based on these findings, inhibitors were developed, which show Plm II and IV inhibitory potency in low nanomolar range and remarkable selectivity against Cathepsin D along with decreased lipophilicity and increased solubility. (C) 2018 Elsevier Ltd. All rights reserved.