5-(三氟甲基)噻吩-2-基硼酸 | 958451-91-7

• 物质功能分类: 化学试剂 - 有机试剂 - 硼酸
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 中文名称: 5-(三氟甲基)噻吩-2-基硼酸
• 中文别名: 5-三氟甲基噻吩-2-硼酸
• 英文名称: (5-(trifluoromethyl)thiophen-2-yl)boronic acid
• 英文别名: [5-(trifluoromethyl)-2-thienyl]boronic acid；[5-(trifluoromethyl)thiophen-2-yl]boronic acid
• CAS: 958451-91-7
• 化学式: C₅H₄BF₃O₂S
• mdl: MFCD11042442
• 分子量: 195.958
• InChiKey: NHBZQJOZVBHDAZ-UHFFFAOYSA-N

物化性质

• 沸点：
  281.3±50.0 °C(Predicted)
• 密度：
  1.51±0.1 g/cm3(Predicted)
• pKa：
  7.70±0.53 (Predicted,Most Acidic Temp: 25 °C)

计算性质

• 辛醇/水分配系数(LogP)：
  2.27
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  68.7
• 氢给体数：
  2
• 氢受体数：
  6

安全信息

• 海关编码：
  2934999090
• 危险性防范说明：
  P280,P305+P351+P338
• 危险性描述：
  H302

反应信息

• 作为反应物：
  描述：

  5-(三氟甲基)噻吩-2-基硼酸 在 吡啶 、 bis-triphenylphosphine-palladium(II) chloride 、 四氯化钛 、 sodium carbonate 作用下， 以 四氢呋喃 、 氯仿 、 水 、 甲苯 为溶剂， 反应 53.5h， 生成 (1-{3-cyano-5-[5-(trifluoromethyl)thien-2-yl]phenyl}-2-methylpropylidene)propanedinitrile
  参考文献：
  名称：

  Antimalarial Inhibitors Targeting Serine Hydroxymethyltransferase (SHMT) with in Vivo Efficacy and Analysis of their Binding Mode Based on X-ray Cocrystal Structures

  摘要：

  Target-based approaches toward new antimalarial treatments are highly valuable to prevent resistance development., We report several series of pyrazolopyran-based inhibitors targeting the enzyme serine hydroxymethyltransferase (SHMT), designed to improve microsomal metabolic stability and to identify suitable candidates for in vivo efficacy evaluation. The best ligands inhibited Plasmodium falciparum (Pf) and Arabidopsis thaliana (At) SHMT in target assays and PfNF54 strains in cell-based assays with values in the low nanomolar range (3.2-55 nM). A set of carboxylate derivatives demonstrated markedly improved in vitro metabolic stability (t(1/2) > 2 h). A selected ligand showed significant in vivo efficacy with 73% of parasitemia reduction in a mouse model. Five new cocrystal structures with PvSHMT were solved at 2.3-2.6 angstrom resolution, revealing a unique water-mediated interaction with Tyr63 at the end of the para-aminobenzoate channel. They also displayed the high degree of conformational flexibility of the Cys364-loop lining this channel.

  DOI：

  10.1021/acs.jmedchem.7b00008

文献信息

• 1<i>H</i>-Pyrrolo[3,2-<i>b</i>]pyridine GluN2B-Selective Negative Allosteric Modulators
  作者：Christa C. Chrovian、Akinola Soyode-Johnson、Jessica L. Wall、Jason C. Rech、Jeff Schoellerman、Brian Lord、Kevin J. Coe、Nicholas I. Carruthers、Leslie Nguyen、Xiaohui Jiang、Tatiana Koudriakova、Bartosz Balana、Michael A. Letavic

  DOI：10.1021/acsmedchemlett.8b00542

  日期：2019.3.14

  Herein, we disclose a series of selective GluN2B negative allosteric modulators containing a 1H-pyrrolo[3,2-b]pyridine core. Lead optimization efforts included increasing brain penetration as well as decreasing cytochrome P450 inhibition and hERG channel binding. The series was also optimized to reduce metabolic turnover in human and rat. Compounds 9, 25, 30, and 34 have good in vitro GluN2B potency

  在本文中，我们公开了一系列含有1 H-吡咯并[3,2- b ]吡啶核的选择性GluN2B负变构调节剂。领先的优化工作包括增加脑部穿透力以及减少细胞色素P450抑制作用和hERG通道结合。该系列产品也进行了优化，以减少人和大鼠的新陈代谢。化合物9，25，30，和34具有体外GluN2B效力和良好的预测吸收好，但中等至高投影间隙。他们在体内进行了评估，以确定他们的目标参与。在大鼠中口服剂量为10 mg / kg后，所有四种化合物均达到> 75％的受体占有率。化合物9在剂量反应实验中测量了受体的占有率，发现其ED 50为2.0 mg / kg。
• [EN] SUBSTITUTED 1H-IMIDAZO[4,5-B]PYRIDIN-2(3H)-ONES AND THEIR USE AS GLUN2B RECEPTOR MODULATORS<br/>[FR] 1H-IMIDAZO[4,5-B]PYRIDIN-2(3H)-ONES SUBSTITUÉES ET LEUR UTILISATION EN TANT QUE MODULATEURS DU RÉCEPTEUR GLUN2B
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2018067786A1

  公开（公告）日：2018-04-12

  Substituted 1 H-imidazo[4,5-b]pyridin-2(3H)-ones as NR2B receptor ligands. Such compounds may be used in NR2B receptor modulation and in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by NR2B receptor activity.

  1-取代的1H-咪唑[4,5-b]吡啶-2(3H)-酮作为NR2B受体配体。这类化合物可用于NR2B受体调节以及用于治疗由NR2B受体活性介导的疾病状态、疾病和病况的药物组合物和方法。
• Design, Synthesis, and Preclinical Evaluation of 3-Methyl-6-(5-thiophenyl)-1,3-dihydro-imidazo[4,5-<i>b</i>]pyridin-2-ones as Selective GluN2B Negative Allosteric Modulators for the Treatment of Mood Disorders
  作者：Christa C. Chrovian、Akinola Soyode-Johnson、Brice Stenne、Daniel J. Pippel、Jeffrey Schoellerman、Brian Lord、Alexandra S. Needham、Chungfang Xia、Kevin J. Coe、Kia Sepassi、Freddy Schoetens、Brian Scott、Leslie Nguyen、Xiaohui Jiang、Tatiana Koudriakova、Bartosz Balana、Michael A. Letavic

  DOI：10.1021/acs.jmedchem.9b02113

  日期：2020.9.10

  Selective inhibitors of the GluN2B subunit of N-methyl-d-aspartate receptors in the ionotropic glutamate receptor superfamily have been targeted for the treatment of mood disorders. We sought to identify structurally novel, brain penetrant, GluN2B-selective inhibitors suitable for evaluation in a clinical setting in patients with major depressive disorder. We identified a new class of negative allosteric

  的GluN2B亚基的选择性抑制剂ñ甲基d在离子型谷氨酸受体-天冬氨酸受体超家族已针对心境障碍的治疗。我们试图确定结构新颖的，脑渗透剂，GluN2B选择性抑制剂，该抑制剂可在重度抑郁症患者的临床环境中进行评估。我们确定了一种新型的GluN2B负变构调节剂，其中包含1,3-二氢咪唑并[4,5- b] pyridin-2-one核心。该系列化合物具有较差的溶解性和较差的渗透性，这可通过两种方法解决。首先，进行了一系列的结构修饰，包括取代氢键供体基团。其次，进行了使能的制剂开发，其中确定了铅化合物12的稳定的纳米悬浮液。发现化合物12在大鼠中具有强大的靶标结合，ED 70为1.4 mg / kg。纳米悬浮液在临床前耐受性研究中有足够的优势，可以提名12名患者进入先进的良好实验室实践研究。
• [EN] SUBSTITUTED HETEROAROMATIC PYRAZOLO-PYRIDINES AND THEIR USE AS GLUN2B RECEPTOR MODULATORS<br/>[FR] PYRAZOLO-PYRIDINES HÉTÉROAROMATIQUES SUBSTITUÉES ET LEUR UTILISATION EN TANT QUE MODULATEURS DU RÉCEPTEUR GLUN2B
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2020249785A1

  公开（公告）日：2020-12-17

  Substituted Pyrazolo-pyridines as GluN2B receptor ligands. Such compounds may be used in GluN2B receptor modulation and in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by GluN2B receptor activity.

  替代性吡唑并吡啶作为GluN2B受体配体。此类化合物可用于GluN2B受体调节，以及用于治疗由GluN2B受体活性介导的疾病状态、紊乱和条件的药物组合物和方法。
• [EN] SUBSTITUTED PYRAZOLO-PYRAZINES AND THEIR USE AS GLUN2B RECEPTOR MODULATORS<br/>[FR] PYRAZOLO-PYRAZINES SUBSTITUÉES ET LEUR UTILISATION EN TANT QUE MODULATEURS DU RÉCEPTEUR DE GLUN2B
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：WO2020249802A1

  公开（公告）日：2020-12-17

  Substituted PYRAZOLO-PYRAZINES as GluN2B receptor ligands. Such compounds may be used in GluN2B receptor modulation and in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions mediated by GluN2B receptor activity.

  将PYRAZOLO-PYRAZINES 替代为GluN2B 受体配体。这类化合物可用于GluN2B 受体调节，并用于治疗由GluN2B 受体活性介导的疾病状态、疾病和病况的药物组合物和方法。