methyl 2-amino-5-ethynylbenzoate | 119754-24-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: methyl 2-amino-5-ethynylbenzoate
• 英文别名: Methyl 5-(ethynyl)anthranilate
• CAS: 119754-24-4
• 化学式: C₁₀H₉NO₂
• mdl: MFCD11041434
• 分子量: 175.187
• InChiKey: LMCFGGOORMJGOX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  13
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  52.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 2-amino-5-ethynylbenzoate 在 氢氧化钾 、 copper(l) iodide 、 bis(triphenylphosphine)palladium(II)-chloride 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 29.5h， 生成 2,2',2'',2'''-<<4-<(4'-amino-3'-carboxyphenyl)ethynyl>pyridine-2,6-diyl>bis(methylenenitrilo)>tetrakis(acetic acid)
  参考文献：
  名称：

  以4-（芳乙炔基）吡啶为配体的Euro（III）螯合物的发光

  摘要：

  铕的一些光谱性能和发光强度III螯合物与4-（芳基乙炔基）吡啶-2,6-二羧酸1 - 15和2,2'，2“，2”' - {[4-（芳基乙炔）吡啶-2- -1,6-二基]双（亚甲基次）}四（乙酸）16 - 26，测定两者H中2 O和EtOH中的解决方案用于开发合适的标记的目的在时间分辨基于发光的生物亲和测定中使用（表1和2）。Ar基团的取代对所观察到的发光强度，激发波长和配合物的衰减常数具有显着影响，此外，环境的变化导致某些Eu III螯合物的性质发生很大变化。

  DOI：

  10.1002/hlca.19930760211
• 作为产物：
  描述：

  2-氨基-5-碘苯甲酸 在 盐酸 、 copper(l) iodide 、 bis(triphenylphosphine)palladium(II)-chloride 、 potassium carbonate 、 三乙胺 作用下， 以 甲醇 为溶剂， 反应 30.0h， 生成 methyl 2-amino-5-ethynylbenzoate
  参考文献：
  名称：

  Takalo, Harri; Kankare, Jouko; Haenninen, Elina, Acta chemica Scandinavica. Series B: Organic chemistry and biochemistry, 1988, vol. 42, # 7, p. 448 - 454

  摘要：

  DOI：

文献信息

• SELECTIVE ALPHA-7 NICOTINIC RECEPTOR AGONISTS AND METHODS FOR MAKING AND USING THEM
  申请人：THE REGENTS OF THE UNIVERSITY OF CALIFORNIA

  公开号：US20180244653A1

  公开（公告）日：2018-08-30

  In alternative embodiments, provided are selective agonists having a high affinity for the alpha7 nicotinic acetylcholine receptor (α7 nAChR), assays for selectivity of nicotinic receptor subtype and ligand-gated ion channel subtype based on receptor occupation and response, behavioral assessments for reversing cognitive impairment after scopolamine treatment, enhancing memory retention over time, pharmaceutical compositions and formulations and devices comprising them, and methods for making and using them, including characterizing and efficiently assaying them for receptor subtype selectivity. In alternative embodiments, provided are substituted anti 1,2,3-triazoles compounds with high affinity, and selective binding, for the alpha7 nicotine acetylcholine receptor (α7 nAChR), as exemplified by 5-(1-(2-(Piperidin-1-yl)ethyl)-1H-1,2,3-triazol-4-yl)-1H-indole (“IND1”), 5-((quinuclid-3-yl)-1H-1,2,3-triazol-4-yl)-1H-indole (“IND8”) and 3-(4-hydroxyphenyl-1,2,3-triazol-1-yl) quinuclidine (“QND8”). In alternative embodiments, provided are products of manufacture such as pumps, devices, syringes and the like comprising a compound, pharmaceutical composition or formulation as provided herein.

  在另一种实施方式中，提供了对α7尼古丁乙酰胆碱受体（α7 nAChR）具有高亲和力的选择性激动剂，基于受体占据和响应的选择性尼古丁受体亚型和配体门控离子通道亚型的筛选方法，行为评估用于在施用东莨菪碱后逆转认知障碍，随时间增强记忆保留，包括表征和高效筛选受体亚型选择性的制备和使用方法的制药组合物和配方以及包括它们的装置，提供了具有高亲和力和选择性结合的替代抗1,2,3-三唑化合物，例如5-（1-（2-（哌啶-1-基）乙基）-1H-1,2,3-三唑-4-基）-1H-吲哚（“IND1”），5-（（喹啉-3-基）-1H-1,2,3-三唑-4-基）-1H-吲哚（“IND8”）和3-（4-羟基苯基-1,2,3-三唑-1-基）喹啉（“QND8”）。在另一种实施方式中，提供了制造产品，例如泵、装置、注射器等，其中包括本文提供的化合物、制药组合物或配方。
• Selective alpha-7 nicotinic receptor agonists and methods for making and using them
  申请人：The Regents of the University of California

  公开号：US10308638B2

  公开（公告）日：2019-06-04

  In alternative embodiments, provided are selective agonists having a high affinity for the alpha7 nicotinic acetylcholine receptor (α7 nAChR), assays for selectivity of nicotinic receptor subtype and ligand-gated ion channel subtype based on receptor occupation and response, behavioral assessments for reversing cognitive impairment after scopolamine treatment, enhancing memory retention over time, pharmaceutical compositions and formulations and devices comprising them, and methods for making and using them, including characterizing and efficiently assaying them for receptor subtype selectivity. In alternative embodiments, provided are substituted anti 1,2,3-triazoles compounds with high affinity, and selective binding, for the alpha7 nicotine acetylcholine receptor (α7 nAChR), as exemplified by 5-(1-(2-(Piperidin-1-yl)ethyl)-1H-1,2,3-triazol-4-yl)-1H-indole (“IND1”), 5-((quinuclid-3-yl)-1H-1,2,3-triazol-4-yl)-1H-indole (“IND8”) and 3-(4-hydroxyphenyl-1,2,3-triazol-1-yl) quinuclidine (“QND8”). In alternative embodiments, provided are products of manufacture such as pumps, devices, syringes and the like comprising a compound, pharmaceutical composition or formulation as provided herein.

  在另一个实施方案中，提供了对α7烟碱乙酰胆碱受体（α7 nAChR）具有高亲和力的选择性激动剂、基于受体占据和反应的烟碱受体亚型和配体门控离子通道亚型选择性的检测方法、在东莨菪碱治疗后逆转认知障碍的行为评估、随时间增强记忆保持、药物组合物和制剂及包含它们的装置，以及制造和使用它们的方法，包括表征和有效测定它们的受体亚型选择性。在另一种实施方案中，提供了对α7 尼古丁乙酰胆碱受体（α7 nAChR）具有高亲和力和选择性结合的取代抗 1,2,3-三唑化合物、例如 5-(1-(2-(哌啶-1-基)乙基)-1H-1,2,3-三唑-4-基)-1H-吲哚（"IND1"）、5-((奎宁环-3-基)-1H-1,2,3-三唑-4-基)-1H-吲哚（"IND8"）和 3-(4-羟基苯基-1,2,3-三唑-1-基)奎宁环（"QND8"）。在另一种实施方案中，提供了包含本文所提供的化合物、药物组合物或制剂的制造产品，如泵、装置、注射器等。
• Selectivity Optimization of Substituted 1,2,3-Triazoles as α7 Nicotinic Acetylcholine Receptor Agonists
  作者：Kuntarat Arunrungvichian、Valery V. Fokin、Opa Vajragupta、Palmer Taylor

  DOI：10.1021/acschemneuro.5b00058

  日期：2015.8.19

  Three series of substituted anti-1,2,3-triazoles (IND, PPRD, and QND), synthesized by cycloaddition from azide and alkyne building blocks, were designed to enhance selectivity and potency profiles of a lead alpha 7 nicotinic acetylcholine receptor (alpha 7-nAChR) agonist, TTIn-1. Designed compounds were synthesized and screened for affinity by a radioligand binding assay. Their functional characterization as agonists and antagonists was performed by fluorescence resonance energy transfer assay using cell lines expressing transfected cDNAs, alpha 7-nAChRs, alpha 4 beta 2-nAChRs, and 5HT(3A), receptors, and a fluorescence cell reporter. In the END series, a tropane ring of TTIn-1, substituted at Ni, was replaced by mono- and bicyclic amines to vary length and conformational flexibility of a carbon linker between nitrogen atom and Ni of the triazole. Compounds with a two-carbon atom linker optimized binding with K-d's at the submicromolar level. Further modification at the hydrophobic indole of TTIn-1 was made in PPRD and QND series by fixing the amine center with the highest affinity building blocks in the IND series. Compounds from IND and PPRD series are selective as agonists for the alpha 7-nAChRs over alpha 4 beta 2-nAChRs and 5HT(3A) receptors. Lead compounds in the three series have EC50's between 28 and 260 nM. Based on the EC50, affinity, and selectivity determined from the binding and cellular responses, two of the leads have been advanced to behavioral studies described in the companion article (DOI: 10.1021/acschemneuro.5b00059).
• TAKALO, HARRI;KANKARE, JOUKO;HANNINEN, ELINA, ACTA CHEM. SCAND. B, 42,(1988) N 7, C. 448-454
  作者：TAKALO, HARRI、KANKARE, JOUKO、HANNINEN, ELINA

  DOI：——

  日期：——
• [EN] SELECTIVE ALPHA-7 NICOTINIC RECEPTOR AGONISTS AND METHODS FOR MAKING AND USING THEM<br/>[FR] AGONISTES SÉLECTIFS DU RÉCEPTEUR NICOTINIQUE ALPHA-7 ET LEURS PROCÉDÉS DE FABRICATION ET D'UTILISATION
  申请人：UNIV CALIFORNIA

  公开号：WO2016154434A1

  公开（公告）日：2016-09-29

  In alternative embodiments, provided are selective agonists having a high affinity for the alpha7 nicotinic acetylcholine receptor (α7 nAChR), assays for selectivity of nicotinic receptor subtype and ligand-gated ion channel subtype based on receptor occupation and response, behavioral assessments for reversing cognitive impairment after scopolamine treatment, enhancing memory retention over time, pharmaceutical compositions and formulations and devices comprising them, and methods for making and using them, including characterizing and efficiently assaying them for receptor subtype selectivity. In alternative embodiments, provided are substituted anti 1,2,3-triazoles compounds with high affinity, and selective binding, for the alpha7 nicotine acetylcholine receptor (α7 nAChR), as exemplified by 5-(1-(2-(Piperidin-1-yl)ethyl)-1H-1,2,3-triazol-4-yl)-1H-indole ("IND1"), 5-((quinuclid-3-yl)-1H-1,2,3-triazol-4-yl)-1H-indole ("IND8") and 3-(4-hydroxyphenyl-1,2,3-triazol-1-yl) quinuclidine ("QND8"). In alternative embodiments, provided are products of manufacture such as pumps, devices, syringes and the like comprising a compound, pharmaceutical composition or formulation as provided herein.