methyl 4-(2-hydroxyethyl)picolinate | 125545-91-7

• 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: methyl 4-(2-hydroxyethyl)picolinate
• 英文别名: methyl 4-(2-hydroxyethyl)pyridine-2-carboxylate
• CAS: 125545-91-7
• 化学式: C₉H₁₁NO₃
• 分子量: 181.191
• InChiKey: QLWMVPTWEPNPPZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  59.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 4-(2-hydroxyethyl)picolinate 在 正丙胺 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 3.83h， 生成 1-(2-Aza-bicyclo[2.2.2]oct-2-yl)-2-[2-(3,5-dimethyl-phenyl)-3-((S)-2-{2-[2-(1-hydroxy-1-methyl-ethyl)-pyridin-4-yl]-ethylamino}-1-methyl-ethyl)-1H-indol-5-yl]-2-methyl-propan-1-one
  参考文献：
  名称：

  Modification of the pyridine moiety of non-peptidyl indole GnRH receptor antagonists

  摘要：

  The synthesis of a number of indole GnRH antagonists is described. Oxidation of the pyridine ring nitrogen, combined with alkylation at the two position, led to a compound with an excellent in vitro activity profile as well as oral bioavailability in both rats and dogs. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00751-5
• 作为产物：
  描述：

  4-(2-羟乙基)吡啶 在 2,6-二甲基吡啶 、 盐酸 、 硫酸 、 双氧水 、 甲基三氧化铼(VII) 、 二甲氨基甲酰氯 作用下， 以 二氯甲烷 为溶剂， 反应 64.17h， 生成 methyl 4-(2-hydroxyethyl)picolinate
  参考文献：
  名称：

  Modification of the pyridine moiety of non-peptidyl indole GnRH receptor antagonists

  摘要：

  The synthesis of a number of indole GnRH antagonists is described. Oxidation of the pyridine ring nitrogen, combined with alkylation at the two position, led to a compound with an excellent in vitro activity profile as well as oral bioavailability in both rats and dogs. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00751-5

文献信息

• Tetrazole excitatory amino acid receptor antagonists
  申请人：Eli Lilly and Company

  公开号：US04968678A1

  公开（公告）日：1990-11-06

  The present invention provides novel tetrazole derivatives useful as excitatory amino acid receptor antagonists and in treating a variety of associated nervous system disorders.

  本发明提供了一种新型四唑衍生物，可用作兴奋性氨基酸受体拮抗剂，并用于治疗各种相关的神经系统疾病。
• Discovery of Narrow Spectrum Kinase Inhibitors: New Therapeutic Agents for the Treatment of COPD and Steroid-Resistant Asthma
  作者：Stuart T. Onions、Kazuhiro Ito、Catherine E. Charron、Richard J. Brown、Marie Colucci、Fritz Frickel、George Hardy、Kevin Joly、John King-Underwood、Yasuo Kizawa、Ian Knowles、P. John Murray、Andrew Novak、Anjna Rani、Garth Rapeport、Alun Smith、Peter Strong、David M. Taddei、Jonathan G. Williams

  DOI：10.1021/acs.jmedchem.5b01029

  日期：2016.3.10

  The discovery of a novel series of therapeutic agents that has been designed and optimized for treating chronic obstructive pulmonary disease is reported. The pharmacological strategy was based on the identification of compounds that inhibit a defined subset of kinase enzymes modulating inflammatory processes that would be effective against steroid refractory disease and exhibit a sustained duration of action after inhaled delivery.
• US4968678A
  申请人：——

  公开号：US4968678A

  公开（公告）日：1990-11-06
• Design, biological evaluation and X-ray crystallography of nanomolar multifunctional ligands targeting simultaneously acetylcholinesterase and glycogen synthase kinase-3
  作者：Killian Oukoloff、Nicolas Coquelle、Manuela Bartolini、Marina Naldi、Rémy Le Guevel、Stéphane Bach、Béatrice Josselin、Sandrine Ruchaud、Marco Catto、Leonardo Pisani、Nunzio Denora、Rosa Maria Iacobazzi、Israel Silman、Joel L. Sussman、Frédéric Buron、Jacques-Philippe Colletier、Ludovic Jean、Sylvain Routier、Pierre-Yves Renard

  DOI：10.1016/j.ejmech.2018.12.063

  日期：2019.4

  Both cholinesterases (AChE and BChE) and kinases, such as GSK-3 alpha/beta, are associated with the pathology of Alzheimer's disease. Two scaffolds, targeting AChE (tacrine) and GSK-3 alpha/beta (valmerin) simultaneously, were assembled, using copper(I)-catalysed azide alkyne cycloaddition (CuAAC), to generate a new series of multifunctional ligands. A series of eight multi-target directed ligands (MTDLs) was synthesized and evaluated in vitro and in cell cultures. Molecular docking studies, together with the crystal structures of three MTDL/TcAChE complexes, with three tacrine-valmerin hybrids allowed designing an appropriate linker containing a 1,2,3-triazole moiety whose incorporation preserved, and even increased, the original inhibitory potencies of the two selected pharmacophores toward the two targets. Most of the new derivatives exhibited nanomolar affinity for both targets, and the most potent compound of the series displayed inhibitory potencies of 9.5 nM for human acetylcholinesterase (hAChE) and 7 nM for GSK-3 alpha/beta. These novel dual MTDLs may serve as suitable leads for further development, since, in the micromolar range, they exhibited low cytotoxicity on a panel of representative human cell lines including the human neuroblastoma cell line SH-SY5Y. Moreover, these tacrine-valmerin hybrids displayed a good ability to penetrate the blood-brain barrier (BBB) without interacting with efflux pumps such as P-gp. (C) 2019 Elsevier Masson SAS. All rights reserved.
• Modification of the pyridine moiety of non-peptidyl indole GnRH receptor antagonists
  作者：Joseph P Simeone、Robert L Bugianesi、Mitree M Ponpipom、Yi Tien Yang、Jane-Ling Lo、Joel B Yudkovitz、Jisong Cui、George R Mount、Rena Ning Ren、Mellissa Creighton、An-Hua Mao、Stella H Vincent、Kang Cheng、Mark T Goulet

  DOI：10.1016/s0960-894x(02)00751-5

  日期：2002.11

  The synthesis of a number of indole GnRH antagonists is described. Oxidation of the pyridine ring nitrogen, combined with alkylation at the two position, led to a compound with an excellent in vitro activity profile as well as oral bioavailability in both rats and dogs. (C) 2002 Elsevier Science Ltd. All rights reserved.