methyl 4-(3-hydroxyprop-1-yl)pyridine-2-carboxylate | 129920-09-8

• 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-hydroxyprop-1-yl)pyridine-2-carboxylate
• 英文别名: methyl 4-(3-hydroxypropyl)picolinate；4-(3-hydroxy-propyl)-pyridine-2-carboxylic acid methyl ester；Methyl 4-(3-hydroxypropyl)pyridine-2-carboxylate
• CAS: 129920-09-8
• 化学式: C₁₀H₁₃NO₃
• 分子量: 195.218
• InChiKey: QIWUKLIBCDMJHW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 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-(3-hydroxyprop-1-yl)pyridine-2-carboxylate 在 乙酸乙酯 、 2-碘酰基苯甲酸 作用下， 反应 12.0h， 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
• 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 、 N,N-二异丙基乙胺 、 间氯过氧苯甲酸 、 二甲氨基甲酰氯 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 138.0h， 生成 methyl 4-(3-hydroxyprop-1-yl)pyridine-2-carboxylate
  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

• Novel lincomycin derivatives possessing antimicrobial activity
  申请人：Lewis G. Jason

  公开号：US20050043248A1

  公开（公告）日：2005-02-24

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

  新型的林可霉素衍生物被披露。这些林可霉素衍生物表现出抗菌活性。本发明的化合物可能对细菌，包括革兰氏阳性生物，表现出强效活性，并且可能是有用的抗微生物药剂。该化合物的合成和使用方法也被披露。
• Novel lincomycin derivatives possessing antibacterial activity
  申请人：Lewis G. Jason

  公开号：US20050215488A1

  公开（公告）日：2005-09-29

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

  新型的林可霉素衍生物已被披露。这些林可霉素衍生物表现出抗菌活性。本发明的化合物可能对细菌，包括革兰氏阳性生物，表现出强效活性，并可能是有用的抗微生物药剂。该化合物的合成和使用方法也已被披露。
• Lincomycin derivatives possessing antibacterial activity
  申请人：Vicuron Pharmaceuticals, Inc.

  公开号：US07256177B2

  公开（公告）日：2007-08-14

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

  本发明公开了一种新型的林可霉素衍生物。这些林可霉素衍生物表现出抗菌活性。本发明的化合物可能表现出对包括革兰氏阳性菌在内的细菌具有强效活性，且可能是有用的抗微生物剂。本发明还公开了化合物的合成和使用方法。
• Lincomycin derivatives possessing antimicrobial activity
  申请人：Vicuron Pharmaceuticals, Inc.

  公开号：US07199106B2

  公开（公告）日：2007-04-03

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

  本发明揭示了新型的林可霉素衍生物。这些林可霉素衍生物表现出抗菌活性。本发明的化合物可能对细菌，包括革兰氏阳性菌具有强效的活性，并可用作有用的抗微生物剂。本发明还揭示了化合物的合成和使用方法。
• 4-(Tetrazolylalkyl)piperidine-2-carboxylic acids. Potent and selective N-methyl-D-aspartic acid receptor antagonists with a short duration of action
  作者：Paul L. Ornstein、Darryle D. Schoepp、M. Brian Arnold、J. David Leander、David Lodge、Jonathan W. Paschal、Tom Elzey

  DOI：10.1021/jm00105a016

  日期：1991.1

  We have prepared a series of cis-4-(tetrazolylalkyl)piperidine-2-carboxylic acids as potent and selective N-methyl-D-aspartic acid (NMDA) receptor antagonists. NMDA antagonists may prove to be useful therapeutic agents, for instance, as anticonvulsants, in the treatment of neurodegenerative disorders such as Alzheimer's disease and in the prevention of neuronal damage that occurs during cerebral ischemia. The compounds prepared were evaluated in vitro in both receptor binding assays ([H-3]CGS-19755, [H-3]AMPA, and [H-3]kainic acid) and in a cortical-wedge preparation (versus NMDA, quisqualic acid, and kainic acid) to determine affinity, potency, and selectivity. The new amino acids were also evaluated in vivo for their ability to block NMDA-induced convulsions in neonatal rats and NMDA-induced lethality in mice. The most potent compound of this series, 15 (LY233053), selectively displaced [H-3]CGS-19755 binding with an IC50 of 107 +/- 7 nM and selectively antagonized responses due to NMDA in a cortical-wedge preparation with an IC50 of 4.2 +/- 0.4-mu-M. Compound 15 blocked both NMDA-induced convulsions in neonatal rats (minimum effective dose (MED) = 20 mg/kg ip) and NMDA-induced lethality in mice (MED = 5 mg/kg ip). This is the first example of an NMDA receptor antagonist that incorporates a tetrazole moiety as an omega-acid bioisostere. These amino acid antagonists are also unique from their phosphonic acid counterparts in that they have a shorter duration of action in vivo. For the treatment of acute disorders such as stroke, where an NMDA antagonist would be administered parenterally, the shorter duration of action may be beneficial, e.g., allowing for better dosage control. The combination of potent NMDA receptor antagonism and a short duration of action may make these compounds useful therapeutic agents in the treatment of a variety of neurological disorders.