2-(3-bromo-2-methylphenyl)pyridine | 1184298-58-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2-(3-bromo-2-methylphenyl)pyridine
• 英文别名: 2-(3-Bromo-2-methyl-phenyl)-pyridine
• CAS: 1184298-58-5
• 化学式: C₁₂H₁₀BrN
• 分子量: 248.122
• InChiKey: SNCSDASMJBPOOB-UHFFFAOYSA-N

物化性质

• 沸点：
  308.0±27.0 °C(Predicted)
• 密度：
  1.375±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  12.9
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2-(3-bromo-2-methylphenyl)pyridine 在 N-甲基吡咯烷酮 、 potassium fluoride 、 tris-(dibenzylideneacetone)dipalladium(0) 、 磺酰氯 、 溶剂黄146 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 11.91h， 生成 2-methyl-3-(pyridin-2-yl)benzenesulfonyl chloride
  参考文献：
  名称：

  5-Chlorothiophene-2-carboxylic Acid [(S)-2-[2-Methyl-3-(2-oxopyrrolidin-1-yl)benzenesulfonylamino]-3-(4-methylpiperazin-1-yl)-3-oxopropyl]amide (SAR107375), a Selective and Potent Orally Active Dual Thrombin and Factor Xa Inhibitor

  摘要：

  Compound 15 (SAR107375), a novel potent dual thrombin and factor Xa inhibitor resulted from a rational optimization process. Starting from compound 14, with low factor Xa and modest anti-thrombin inhibitory activities (IC50's of 3.5 and 0.39 mu M, respectively), both activities were considerably improved, notably through the incorporation of a neutral chlorothiophene PI fragment and tuning of P2 and P3-P4 fragments. Final optimization of metabolic stability with microsomes led to the identification of 15, which displays strong activity in vitro vs factor Xa and thrombin (with K-i's of 1 and 8 nM, respectively). In addition 15 presents good selectivity versus related serine proteases (roughly 300-fold), including trypsin (1000-fold), and is very active (0.39 mu M) in the thrombin generation time (TGT) coagulation assay in human platelet rich plasma (PRP). Potent in vivo activity in a rat model of venous thrombosis following iv and, more importantly, po administration was also observed (ED50 of 0.07 and 2.8 mg/kg, respectively). Bleeding liability was reduced in the rat wire coil model, more relevant to arterial thrombosis, with 15 (blood loss increase of 2-fold relative to the ED80 value) compared to rivaroxaban 2 and dabigatran etexilate 1a.

  DOI：

  10.1021/jm4005835
• 作为产物：
  描述：

  2-(邻甲苯)吡啶 在 N-溴代丁二酰亚胺(NBS) 、 [ruthenium(II)(η⁶-1-methyl-4-isopropyl-benzene)(chloride)(μ-chloride)]₂ 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 24.0h， 以67%的产率得到2-(3-bromo-2-methylphenyl)pyridine
  参考文献：
  名称：

  钌催化剂对芳烃的直接亚选择性溴化

  摘要：

  钌催化的直接Ç  ħ激活/元芳烃轴承吡啶基，嘧啶基和吡唑基定位基团的-bromination已经研制成功。已经合成了一系列溴代芳基吡啶和嘧啶，并且对于许多代表性的官能化芳烃也已经证明了进一步的偶联反应。初步的机理研究表明，当使用NBS作为溴源时，该反应可能通过自由基介导的溴化反应进行。这种类型的变换已经用于开辟了新的方向上的基团的非本位关于未来的C金属的官能 ħ激活开发将允许芳族系统的远程官能化。

  DOI：

  10.1002/anie.201507100

文献信息

• [EN] 1, 4-SUBSTITUTED PIPERIDINE DERIVATIVES<br/>[FR] DÉRIVÉS DE PIPÉRIDINE 1,4-SUBSTITUÉS
  申请人：CEPHALON INC

  公开号：WO2016205633A1

  公开（公告）日：2016-12-22

  Described herein are 1,4-substituted piperidine compounds according to Formula (I) that have demonstrated activity as fatty acid synthase inhibitors. Also described herein are pharmaceutical compositions containing the described 1,4-substituted piperidine compounds, and methods of treating diseases mediated by fatty acid synthase, by administering one or more of the compounds or pharmaceutical formulations described herein. Also described herein are methods of synthesizing the compounds described, including the described 1,4-substituted piperidine compounds and synthetic intermediates useful in those syntheses.

  本文描述了按照式（I）的1,4-取代哌啶化合物，这些化合物已经表现出作为脂肪酸合成酶抑制剂的活性。本文还描述了含有所述1,4-取代哌啶化合物的药物组合物，以及通过给予所述化合物或药物配方中的一个或多个来治疗由脂肪酸合成酶介导的疾病的方法。本文还描述了合成所述化合物的方法，包括所述的1,4-取代哌啶化合物和在这些合成中有用的合成中间体。
• [EN] CHLOROTHIOPHENE-AMIDES AS INHIBITORS OF COAGULATION FACTORS XA AND THROMBIN<br/>[FR] CHLOROTHIOPHÈNE-AMIDES UTILISÉS COMME INHIBITEURS DES FACTEURS DE COAGULATION XA ET DE LA THROMBINE
  申请人：SANOFI AVENTIS

  公开号：WO2009103440A1

  公开（公告）日：2009-08-27

  The present invention relates to compounds of the formula I wherein R1; R2; R3; R4; R5, R13, R16, X and M have the meanings indicated in the claims. The compounds of formula I are valuable pharmacologically active compounds. They exhibit a strong anti-thrombotic effect and are suitable, for example, for the therapy and prophylaxis of cardio-vascular disorders like thromboembolic diseases or restenoses. They are reversible inhibitors of the blood clotting enzymes factor Xa (FXa) and thrombin and can in general be applied in conditions in which an undesired activity of factor Xa and/or thrombin are present or for the cure or prevention of which an inhibition of factor Xa and thrombin are intended. The invention furthermore relates to processes for the preparation of compounds of the formula I, their use, in particular as active ingredients in pharmaceuticals, and pharmaceutical preparations comprising them.

  本发明涉及具有式I的化合物，其中R1; R2; R3; R4; R5, R13, R16, X和M具有权利要求中所指示的含义。式I的化合物是有价值的药理活性化合物。它们表现出强大的抗血栓作用，例如，适用于治疗和预防心血管疾病，如血栓栓塞疾病或再狭窄。它们是血液凝块酶因子Xa（FXa）和凝血酶的可逆抑制剂，通常可应用于存在因子Xa和/或凝血酶不良活性的情况，或者用于治疗或预防需要抑制因子Xa和凝血酶的情况。此外，本发明还涉及制备式I化合物的方法，它们的用途，特别是作为药物中的活性成分，以及包含它们的药物制剂。
• Directed<i>meta</i>-Selective Bromination of Arenes with Ruthenium Catalysts
  作者：Qingzhen Yu、Le'an Hu、Yue Wang、Shasha Zheng、Jianhui Huang

  DOI：10.1002/anie.201507100

  日期：2015.12.7

  Ru‐catalyzed direct CH activation/meta‐bromination of arenes bearing pyridyl, pyrimidyl, and pyrazolyl directing groups has been developed. A series of bromo aryl pyridines and pyrimidines have been synthesized, and further coupling reactions have also been demonstrated for a number of representative functionalized arenes. Preliminary mechanistic studies have revealed that this reaction may proceed through

  钌催化的直接Ç  ħ激活/元芳烃轴承吡啶基，嘧啶基和吡唑基定位基团的-bromination已经研制成功。已经合成了一系列溴代芳基吡啶和嘧啶，并且对于许多代表性的官能化芳烃也已经证明了进一步的偶联反应。初步的机理研究表明，当使用NBS作为溴源时，该反应可能通过自由基介导的溴化反应进行。这种类型的变换已经用于开辟了新的方向上的基团的非本位关于未来的C金属的官能 ħ激活开发将允许芳族系统的远程官能化。
• 2-(3-卤素苯基)吡啶类衍生物的制备方法
  申请人：天津大学

  公开号：CN104356053B

  公开（公告）日：2017-01-18

  本发明公开了2‑(3‑卤素苯基)吡啶类衍生物的制备方法，包括如下步骤：将2‑苯基吡啶或取代2‑苯基吡啶(I),N‑卤代丁二酰亚胺(II)溶于溶剂中，加入钌催化剂于70‑150℃反应24‑48小时，用乙酸乙酯萃取，水洗、干燥后经柱色谱分离纯化，得到2‑(3‑卤素苯基)吡啶类衍生物(III)；其反应式为：本发明具有操作简单，反应原料以及反应试剂易得，产物取代基类型多样，收率较高等优点。
• CHLOROTHIOPHENE-AMIDES AS INHIBITORS OF COAGULATION FACTORS XA AND THROMBIN
  申请人：FOLLMANN Markus

  公开号：US20110112075A1

  公开（公告）日：2011-05-12

  The present invention relates to compounds of the formula I, wherein R1; R2; R3; R4; R5, R13, R16, X and M have the meanings indicated in the claims. The compounds of formula I are valuable pharmacologically active compounds. They exhibit a strong anti-thrombotic effect and are suitable, for example, for the therapy and prophylaxis of cardio-vascular disorders like thromboembolic diseases or restenoses. They are reversible inhibitors of the blood clotting enzymes factor Xa (FXa) and thrombin and can in general be applied in conditions in which an undesired activity of factor Xa and/or thrombin are present or for the cure or prevention of which an inhibition of factor Xa and thrombin are intended. The invention furthermore relates to processes for the preparation of compounds of the formula I, their use, in particular as active ingredients in pharmaceuticals, and pharmaceutical preparations comprising them.

  本发明涉及式I的化合物，其中R1; R2; R3; R4; R5，R13，R16，X和M具有所述权利要求中指示的含义。式I的化合物是有价值的药理活性化合物。它们具有强烈的抗血栓作用，例如，它们适用于治疗和预防心血管疾病，如血栓栓塞性疾病或再狭窄。它们是血凝酶酶因子Xa（FXa）和凝血酶的可逆抑制剂，并且通常可以应用于存在因子Xa和/或凝血酶不良活性或为治愈或预防而意图抑制因子Xa和凝血酶的情况。此外，本发明还涉及式I化合物的制备方法，它们的用途，特别是作为药物中的活性成分，以及包含它们的制剂。