methyl 4-(3-oxopropyl)picolinate | 663614-45-7

• 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-(3-oxopropyl)picolinate
• 英文别名: Methyl 4-(3-oxopropyl)pyridine-2-carboxylate；methyl 4-(3-oxopropyl)pyridine-2-carboxylate
• CAS: 663614-45-7
• 化学式: C₁₀H₁₁NO₃
• 分子量: 193.202
• InChiKey: TUHHDBRLHQHDGI-UHFFFAOYSA-N

物化性质

• 沸点：
  342.0±32.0 °C(Predicted)
• 密度：
  1.155±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  56.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 4-(3-oxopropyl)picolinate 在 盐酸 、 (1-重氮基-2-氧代丙基)膦酸二甲酯 、 potassium carbonate 、 一水合肼 、 sodium nitrite 作用下， 以 甲醇 、 水 为溶剂， 反应 5.75h， 生成 4-(but-3-yn-1-yl)picolinoyl azide
  参考文献：
  名称：

  Design, biological evaluation and X-ray crystallography of nanomolar multifunctional ligands targeting simultaneously acetylcholinesterase and glycogen synthase kinase-3

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2018.12.063
• 作为产物：
  描述：

  4-吡啶丙醇 在 盐酸 、 4-二甲氨基吡啶 、 氯化亚砜 、 乙酸乙酯 、 N,N-二异丙基乙胺 、 间氯过氧苯甲酸 、 二甲氨基甲酰氯 、 2-碘酰基苯甲酸 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 150.0h， 生成 methyl 4-(3-oxopropyl)picolinate
  参考文献：
  名称：

  Design, biological evaluation and X-ray crystallography of nanomolar multifunctional ligands targeting simultaneously acetylcholinesterase and glycogen synthase kinase-3

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2018.12.063

文献信息

• Lincomycin derivatives possessing antibacterial activity
  申请人：VICURON PHARMACEUTICALS INC.

  公开号：US20040230046A1

  公开（公告）日：2004-11-18

  Novel lincomycin derivatives are disclosed. These lincomycin derivatives exhibit antibacterial activity. As the compounds of the subject invention exhibit potent activities against bacteria, including gram positive organisms, they are useful antimicrobial agents. Methods of synthesis and of use of the compounds are also disclosed.

  揭示了新颖的林可霉素衍生物。这些林可霉素衍生物表现出抗菌活性。由于本发明的化合物对细菌，包括革兰氏阳性生物，表现出强大的活性，它们是有用的抗微生物药剂。还公开了这些化合物的合成和使用方法。
• Visible‐Light‐Induced C4‐Selective Functionalization of Pyridinium Salts with Cyclopropanols
  作者：Mari Vellakkaran、Taehwan Kim、Sungwoo Hong

  DOI：10.1002/anie.202113658

  日期：2022.1.3

  Visible-light-induced β-carbonyl alkylation of pyridines was developed by employing various cyclopropanols and N-amidopyridinium salts under mild conditions. This method provides an effective tool for the synthesis of valuable β-pyridyl-functionalized carbonyl frameworks with excellent C4 selectivity and the late-stage functionalization of complex and medicinally relevant molecules.

  通过在温和条件下使用各种环丙醇和N-氨基吡啶鎓盐开发了可见光诱导的吡啶 β-羰基烷基化。该方法为合成有价值的 β-吡啶基官能化羰基骨架提供了一种有效的工具，该骨架具有优异的 C4 选择性以及复杂和药用相关分子的后期官能化。
• [EN] LINCOMYCIN DERIVATIVES POSSESSING ANTIBACTERIAL ACTIVITY<br/>[FR] DERIVES DE LINCOMYCINE PRESENTANT UNE ACTIVITE ANTIBACTERIENNE
  申请人：VICURON PHARM INC

  公开号：WO2004016632A3

  公开（公告）日：2004-06-24
• LINCOMYCIN DERIVATIVES POSSESSING ANTIBACTERIAL ACTIVITY
  申请人：Vicuron Pharmaceuticals, Inc.

  公开号：EP1529052A2

  公开（公告）日：2005-05-11
• US7164011B2
  申请人：——

  公开号：US7164011B2

  公开（公告）日：2007-01-16