2-bromo-N-(pyridin-4-yl)acetamide | 349121-06-8

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 2-bromo-N-(pyridin-4-yl)acetamide
• 英文别名: 2-Bromo-N-4-pyridinylacetamide；2-bromo-N-pyridin-4-ylacetamide
• CAS: 349121-06-8
• 化学式: C₇H₇BrN₂O
• 分子量: 215.049
• InChiKey: YXWYFLGLLHXRIM-UHFFFAOYSA-N

物化性质

• 沸点：
  390.5±22.0 °C(Predicted)
• 密度：
  1.668±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  42
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-bromo-N-(pyridin-4-yl)acetamide 在 sodium azide 、 copper(II) sulfate 、 sodium ascorbate 作用下， 以 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 72.0h， 生成 5-{5-Fluoro-2-[1-(pyridin-4-ylcarbamoylmethyl)-1H-[1,2,3]triazol-4-ylmethoxy]-phenyl}-isoxazole-3-carboxylic acid
  参考文献：
  名称：

  快速组装和原位筛选蛋白酪氨酸磷酸酶的双齿抑制剂。

  摘要：

  [反应：参见文本]我们已经成功设计并合成了一个小的蛋白质酪氨酸磷酸酶（PTP）抑制剂文库，其中包含所谓的“点击化学”或Cu（I）催化的1,3-偶极炔烃-叠氮化物偶联进行反应以快速组装66种不同的二齿化合物。随后的原位酶筛查显示潜在的PTP1B抑制剂（IC（50）= 4.7 microM），其效力比其他PTP高10-100倍。

  DOI：

  10.1021/ol052895w
• 作为产物：
  描述：

  4-氨基吡啶 、 溴乙酰氯 在 吡啶 作用下， 以 氯仿 为溶剂， 生成 2-bromo-N-(pyridin-4-yl)acetamide
  参考文献：
  名称：

  快速组装和原位筛选蛋白酪氨酸磷酸酶的双齿抑制剂。

  摘要：

  [反应：参见文本]我们已经成功设计并合成了一个小的蛋白质酪氨酸磷酸酶（PTP）抑制剂文库，其中包含所谓的“点击化学”或Cu（I）催化的1,3-偶极炔烃-叠氮化物偶联进行反应以快速组装66种不同的二齿化合物。随后的原位酶筛查显示潜在的PTP1B抑制剂（IC（50）= 4.7 microM），其效力比其他PTP高10-100倍。

  DOI：

  10.1021/ol052895w

文献信息

• Design, synthesis and biological evaluation of novel acetamide-substituted doravirine and its prodrugs as potent HIV-1 NNRTIs
  作者：Zhao Wang、Zhao Yu、Dongwei Kang、Jian Zhang、Ye Tian、Dirk Daelemans、Erik De Clercq、Christophe Pannecouque、Peng Zhan、Xinyong Liu

  DOI：10.1016/j.bmc.2018.12.039

  日期：2019.2

  A novel series of acetamide-substituted derivatives and two prodrugs of doravirine were designed and synthesized as potent HIV-1 NNRTIs by employing the structure-based drug design strategy. In MT-4 cell-based assays using the MTT method, it was found that most of the new compounds exhibited moderate to excellent inhibitory potency against the wild-type (WT) HIV-1 strain with a minimum EC50 value of

  通过采用基于结构的药物设计策略，设计并合成了一系列新的乙酰胺取代的衍生物和Doravirine的两种前药，作为有效的HIV-1 NNRTI。在使用MTT方法的基于MT-4细胞的测定中，发现大多数新化合物对野生型（WT）HIV-1菌株均表现出中度至优异的抑制力，最小EC50值为54.8 nM。其中，两种最有效的化合物8i（EC50 = 59.5 nM）和8k（EC50 = 54.8 nM）对野生型HIV-1表现出强大的活性，具有两位数纳摩尔EC50值，优于拉米夫定（3TC，EC50 = 12.8μM ）并与doravirine（EC50 = 13 nM）相当。此外，8i和8k对双RT突变株（K103N + Y181C）HIV-1 RES056株显示中等活性。HIV-1 RT抑制测定进一步验证了结合靶标。通过对代表性化合物的分子模拟，可以深入了解其结构-活性关系（SAR），并指导未来的设计工作
• Synthesis of Highly Charged Ruthenium(II)-Quaterpyridinium Complexes: A Bottom-Up Approach to Monodisperse Nanostructures
  作者：Stefan Bossmann、Aibin Shi、Megh Pokhrel

  DOI：10.1055/s-2007-965901

  日期：2007.2

  Tris-homoleptic ruthenium(II)-quaterpyridine and -quaterpyridinium complexes, possessing geometric dimensions in the nanoscale, have been synthesized. The diameters range from 1.82 to 4.55 nm according to molecular modeling. The new complexes are highly charged (either +8 or +14) and luminescent and represent examples for the ‘bottom-up’ approach to monodisperse nanostructures.

  已合成具有纳米尺度几何尺寸的三聚体同配合物铑(II)-四吡啶和四吡啶阳离子复合物。根据分子建模，直径范围从1.82到4.55纳米。这些新复合物带有高电荷（+8或+14），具有发光特性，代表了用于单分散纳米结构的“自下而上”方法的示例。
• Solvent-Dependent Switch of Ligand Donor Ability and Catalytic Activity of Ruthenium(II) Complexes Containing Pyridinylidene Amide (PYA) N-Heterocyclic Carbene Hybrid Ligands
  作者：Vivienne Leigh、Daniel J. Carleton、Juan Olguin、Helge Mueller-Bunz、L. James Wright、Martin Albrecht

  DOI：10.1021/ic501026k

  日期：2014.8.4

  Chelating ligands incorporating both N-[1-alkylpyridin-4(1H)-ylidene]amide (PYA) and N-heterocyclic carbene (NHC) donor sites were prepared and used for the synthesis of ruthenium(II) complexes. Cyclic voltammetry, NMR, and UV–vis spectroscopy of the complexes indicate a solvent-dependent contribution of the limiting resonance structures associated with the ligand in solution. The neutral pyridylidene

  制备结合了N- [1-烷基吡啶-4（1H）-亚烷基]酰胺（PYA）和N-杂环卡宾（NHC）供体位点的螯合配体，并用于合成钌（II）配合物。配合物的循环伏安法，NMR和UV-vis光谱表明与溶液中配体相关的有限共振结构具有溶剂依赖性。中性亚吡啶基亚胺结构在非极性溶剂（CH 2 Cl 2），而中性吡啶鎓酰胺形式则主要在极性溶剂（MeOH，DMSO）中使用。这些杂化的PYA-NHC配体在不同溶剂中的不同电子性质直接影响钌中心的催化活性，例如，在苯甲醇脱氢为苯甲醛时。在不同溶剂中的活性与溶剂介电常数在质量上相关。
• Structure−Activity Relationships in the Binding of Chemically Derivatized CD4 to gp120 from Human Immunodeficiency Virus
  作者：Hui Xie、Danny Ng、Sergey N. Savinov、Barna Dey、Peter D. Kwong、Richard Wyatt、Amos B. Smith、Wayne A. Hendrickson

  DOI：10.1021/jm070564e

  日期：2007.10.1

  The first step in HIV infection is the binding of the envelope glycoprotein gp120 to the host cell receptor CD4. An interfacial "Phe43 cavity" in gp120, adjacent to residue Phe43 of gp120-bound CD4, has been suggested as a potential target for therapeutic intervention. We designed a CD4 mutant (D1D2F43C) for site-specific coupling of compounds for screening against the cavity. Altogether, 81 cysteine-reactive compounds were designed, synthesized, and tested. Eight derivatives exceeded the affinity of native D1D2 for gp 120. Structure-activity relationships (SAR) for derivatized CD4 binding to gp 120 revealed significant plasticity of the Phe43 cavity and a narrow entrance. The primary contacts for compound recognition inside the cavity were found to be van der Waals interactions, whereas hydrophilic interactions were detected in the entrance. This first SAR on ligand binding to an interior cavity of gp 120 may provide a starting point for structure-based assembly of small molecules targeting gp120-CD4 interaction.
• Development of Highly Potent and Selective Diaminothiazole Inhibitors of Cyclin-Dependent Kinases
  作者：Ernst Schonbrunn、Stephane Betzi、Riazul Alam、Mathew P. Martin、Andreas Becker、Huijong Han、Rawle Francis、Ramappa Chakrasali、Sudhakar Jakkaraj、Aslamuzzaman Kazi、Said M. Sebti、Christopher L. Cubitt、Anthony W. Gebhard、Lori A. Hazlehurst、Joseph S. Tash、Gunda I. Georg

  DOI：10.1021/jm301234k

  日期：2013.5.23

  Cyclin-dependent kinases (CDKs) are serine/threonine protein kinases that act as key regulatory elements in cell cycle progression. We describe the development of highly potent diaminothiazole inhibitors of CDK2 (IC50 = 0.0009-0.0015 mu M) from a single hit compound with weak inhibitory activity (IC50 = 15 mu M), discovered by high-throughput screening. Structure-based design was performed using 35 cocrystal structures of CDK2 liganded with distinct analogues of the parent compound. The profiling of compound 51 against a panel of 339 kinases revealed high selectivity for CDKs, with preference for CDK2 and CDK5 over CDK9, CDK1, CDK4, and CDK6. Compound 51 inhibited the proliferation of 13 out of 15 cancer cell lines with IC50 values between 0.27 and 6.9 mu M, which correlated with the complete suppression of retinoblastoma phosphorylation and the onset of apoptosis. Combined, the results demonstrate the potential of this new inhibitors series for further development into CDK-specific chemical probes or therapeutics.