2-(5-甲氧基吡啶-3-基)乙炔基-三甲基硅烷 | 823199-09-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 2-(5-甲氧基吡啶-3-基)乙炔基-三甲基硅烷
• 英文名称: 3-methoxy-5-((trimethylsilyl)ethynyl)pyridine
• 英文别名: 3-Methoxy-5-[(trimethylsilyl)ethynyl]pyridine；2-(5-methoxypyridin-3-yl)ethynyl-trimethylsilane
• CAS: 823199-09-3
• 化学式: C₁₁H₁₅NOSi
• 分子量: 205.332
• InChiKey: XWVFFWKHNNSPEJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.32
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  22.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(5-甲氧基吡啶-3-基)乙炔基-三甲基硅烷 在 potassium carbonate 作用下， 以 甲醇 为溶剂， 生成 3-乙炔基-5-甲氧基-吡啶
  参考文献：
  名称：

  Controlling hydrogen-bond preferences in bipyridines with competing binding sites

  摘要：

  The design and synthesis of a family of supramolecular reagents (SRs) based on ethynyl-spaced substituted bipyridines are described, and their potential use as molecular 'hubs' for the predictable construction of binary and ternary co-crystals is explored. Each SR was synthesized in good yields through consecutive Pd-catalyzed Sonogashira cross-coupling reactions. Crystal structures of three binary co-crystals are presented with each structure clearly illustrating how accurate supramolecular assembly control can be achieved by increasing/decreasing the strength of the participating hydrogen-bond interactions. (c) 2009 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.molstruc.2009.11.033
• 作为产物：
  描述：

  3,5-二溴吡啶 在 双三苯基磷二氯化钯 copper(l) iodide 、 三乙胺 作用下， 以 甲醇 为溶剂， 反应 29.0h， 生成 2-(5-甲氧基吡啶-3-基)乙炔基-三甲基硅烷
  参考文献：
  名称：

  Synthesis and receptor assay of aromatic–ethynyl–aromatic derivatives with potent mGluR5 antagonist activity

  摘要：

  Noncompetitive antagonists of the human metabotropic glutamate receptor subtype 5 (mGluR5) have been implicated as potential therapeutics for the treatment of a variety of nervous system disorders, including pain, anxiety, and drug addiction. To discover novel noncompetitive antagonists to the mGluR5, we initiated an SAR study around the known lead compounds MPEP and M-MPEP. Our results pointed out the critical role of the para position of the two aromatic rings, which leads to inactive products and permitted the discovery of potent mGluR5 antagonists (e.g., 16, 25, 28, 34 IC50 = 13.5, 11.9, 21, 15nM, respectively). (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.09.042

文献信息

• [EN] PYRIDYL DERIVATIVES AND THEIR USE AS MGLU5 RECEPTOR ANTAGONISTS<br/>[FR] DERIVES DE PYRIDYLE ET LEUR UTILISATION EN TANT QU'ANTAGONISTES DU RECEPTEUR DE MGLU5
  申请人：LILLY CO ELI

  公开号：WO2005094822A1

  公开（公告）日：2005-10-13

  The present invention is directed toward pyridyl derivatives of formula (I) as antagonists of the mGlu5 receptor. As such the compounds may be useful for treatment or prevention of disorders remedied by antagonism of the mGlu5 receptor, wherein Ar is phenyl or napthyl each of which may be substituted by one or more C1-C4 alkyl, C1-C4 alkoxy, C1-C5 acyl, halo, amino, nitro, cyano, hydroxy, C1-C5 acylamino, C1-C4 alkylsulfonylamino, mono-, di- or trifluorinated C1-C3 alkyl, substituents which may be the same or different and may bear a CONH2, CONHCH3, CON(CH3)2, CO2H, CO2CH3, OCF3, CH2NHCOCH3, CH2NH2, CH2N(CH3)2, CH2CN, CH2OH, CH2NHSO2CH3, CH2N(CH3)(CH2)2 CN, CH2N(CH3)CH(CH3)2, CH2NHCH(CH3)2, CH2NH(CH2)2CH3, CH2NHCO2R4, CH2NHCH2CH3, CH2NHCH3 NHCOC(CH3)2, or N(S(O)2CH3)2 substituent; R1 is hydrogen, halo, R4, CN, C(NOH)R3, C(NO-R4)R3, (CH)2CO2R4 , (CH2)n OR3 , COR3 , CF3, SR4 , S(O)R4, S(O)2R4, COCH2CO2R3 , NHSO2R4 , NHCOR3, C(NOR3)NH2, CH2OCOR3 , (CH2)n NH2, CON(CH3)2 (CH2)nNHCO2R4 , CO2R3, CONH2, CSNH2, C(NH)NHOR3, (CH2)nN(CH3)2, or CONHNHCOR3; R2 is 1,2-ethenediyl or 1,2-ethynediyl; R3 is hydrogen or C1-C4 alkyl; R4 is C1-C4 alkyl; and n is 0, 1, 2,3 or 4; or a pharmaceutically acceptable salt thereof, or an N-oxide thereof.

  本发明涉及公式（I）的吡啶衍生物作为mGlu5受体拮抗剂。因此，这些化合物可能对通过拮抗mGlu5受体而得到缓解的疾病的治疗或预防有用，其中Ar是苯基或萘基，每种基可能被一个或多个C1-C4烷基，C1-C4烷氧基，C1-C5酰基，卤素，氨基，硝基，氰基，羟基，C1-C5酰胺基，C1-C4烷基磺酰胺基，单-，二-或三氟代的C1-C3烷基，取代基可能相同也可能不同，并且可能带有CONH2，CONHCH3，CON(CH3)2，CO2H，CO2CH3，OCF3，CH2NHCOCH3，CH2NH2，CH2N(CH3)2，CH2CN，CH2OH，CH2NHSO2CH3，CH2N(CH3)(CH2)2CN，CH2N(CH3)CH(CH3)2，CH2NHCH(CH3)2，CH2NH(CH2)2CH3，CH2NHCO2R4，CH2NHCH2CH3，CH2NHCH3 NHCOC(CH3)2或N(S(O)2CH3)2取代基；R1是氢，卤素，R4，CN，C(NOH)R3，C(NO-R4)R3，(CH)2CO2R4，(CH2)nOR3，COR3，CF3，SR4，S(O)R4，S(O)2R4，COCH2CO2R3，NHSO2R4，NHCOR3，C(NOR3)NH2，CH2OCOR3，(CH2)nNH2，CON(CH3)2(CH2)nNHCO2R4，CO2R3，CONH2，CSNH2，C(NH)NHOR3，(CH2)nN(CH3)2或CONHNHCOR3；R2是1,2-乙烯二基或1,2-乙炔二基；R3是氢或C1-C4烷基；R4是C1-C4烷基；n为0,1,2,3或4；或其药学上可接受的盐，或其N-氧化物。
• [EN] NEW TRIAZOLYLPHENYL SULFONAMIDES AS SERINE/THREONINE KINASE INHIBITORS<br/>[FR] NOUVEAUX TRIAZOLYLPHÉNYL SULFONAMIDES EN TANT QU'INHIBITEURS DE LA SÉRINE/THRÉONINE KINASE
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2012085127A1

  公开（公告）日：2012-06-28

  The present invention encompasses compounds of general formula (I) wherein the groups R2 to R4, A,X and m are defined as in claim 1, which are suitable for the treatment of diseases characterised by excessive or abnormal cell proliferation, pharmaceutical preparations which contain compounds of this kind and their use as medicaments.

  本发明涵盖了一般式（I）中R2到R4、A、X和m所定义的基团，适用于治疗以细胞过度增殖或异常增殖为特征的疾病，包括含有此类化合物的药物制剂以及它们作为药物的用途。
• Triazolylphenyl sulfonamides as serine/threonine kinase inhibitors
  申请人：STEURER Steffen

  公开号：US20120322803A1

  公开（公告）日：2012-12-20

  The present invention encompasses compounds of general formula (I) wherein the groups R 2 to R 4 , A, X and m are defined as in claim 1 , which are suitable for the treatment of diseases characterised by excessive or abnormal cell proliferation, pharmaceutical preparations which contain compounds of this kind and their use as medicaments.

  本发明涵盖了一般式（I）的化合物， 其中R2至R4、A、X和m的定义如权利要求书中所述， 这些化合物适用于治疗以细胞过度或异常增殖为特征的疾病，包括含有此类化合物的药物制剂以及它们作为药物的用途。
• One-pot synthesis of dihydropyridine carboxylic acids via functionalization of 3-((trimethylsilyl)ethynyl)pyridines and an unusual hydration of alkynes: Molecular docking and antifungal activity
  作者：Ricardo Ballinas-Indilí、Omar Gómez-García、Eric Treviño-Crespo、Dulce Andrade-Pavón、Lourdes Villa-Tanaca、Ruben A. Toscano、Cecilio Álvarez-Toledano

  DOI：10.1016/j.tet.2021.132086

  日期：2021.4

  Activation of 3-((trimethylsilyl)ethynyl)pyridine with triflic anhydride followed by nucleophilic addition of bis(trimethylsili) ketene acetals and a unusual alkyne hydration allowed to obtain new series of 3-acetylated dihydropyridine acids 3a-h in a single step. Secondly, docking studies were conducted on four of the test compounds (3b, 3e, 17a and 17b) and a reference drug (fluconazole) at the active

  用三氟甲磺酸酐活化3-（（三甲基甲硅烷基）乙炔基）吡啶，然后亲核加成双（三甲基硅）乙烯酮缩醛和不寻常的炔烃水合反应，可在单个步骤中获得一系列新的3-乙酰化二氢吡啶酸3a-h。其次，对接研究在试验化合物（四个进行3B，3E，图17A和17B）和一个参考药物（氟康唑）在羊毛甾醇14α脱甲基酶（CYP51）的从活性位点念珠菌属，在体外抑制测定用相同的化合物和酵母种类进行。化合物3b，3e，17a17b和17b以与氟康唑相似的方式与CYP51酶活性位点的关键氨基酸相互作用。与氟康唑相比，受试化合物对不同的念珠菌具有更好的结合能值（-4.84至-9.1与-1.51至5.68 kcal / mol）和体外抗真菌活性（较低的MIC值）。因此，二氢吡啶衍生物可以被认为是开发新的抗真菌药物的候选药物。
• Discovery of a Novel Series of Potent and Selective Alkynylthiazole-Derived PI3Kγ Inhibitors
  作者：Upul K. Bandarage、Alex M. Aronov、Jingrong Cao、Jon H. Come、Kevin M. Cottrell、Robert J. Davies、Simon Giroux、Marc Jacobs、Sudipta Mahajan、David Messersmith、Cameron S. Moody、Rebecca Swett、Jinwang Xu

  DOI：10.1021/acsmedchemlett.0c00573

  日期：2021.1.14

  family of enzymes that control a wide variety of cellular functions such as cell growth, proliferation, differentiation, motility, survival, and intracellular trafficking. PI3Kγ plays a critical role in mediating leukocyte chemotaxis as well as mast cell degranulation, making it a potentially interesting target for autoimmune and inflammatory diseases. We previously disclosed a novel series of PI3Kγ inhibitors

  磷酸肌醇 3-激酶 (PI3K) 是一个酶家族，可控制多种细胞功能，例如细胞生长、增殖、分化、运动、存活和细胞内运输。PI3Kγ 在介导白细胞趋化性和肥大细胞脱粒中起关键作用，使其成为自身免疫和炎症性疾病的潜在有趣靶标。我们之前披露了一系列源自苯并噻唑核心的新型 PI3Kγ 抑制剂。苯并噻唑核心的截断导致发现了结构多样的炔基噻唑系列，该系列显示出高 PI3Kγ 效力和亚型选择性。炔基噻唑系列的进一步药物化学优化导致化合物如14和32的鉴定、高效、亚型选择性和 CNS 渗透性 PI3Kγ 抑制剂。化合物14在体内显示出对 PI3Kγ 介导的嗜中性粒细胞迁移的强烈抑制。