methyl 2-methyl-3-(3-methyl-1H-pyrazol-1-yl)propionate | 180741-33-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: methyl 2-methyl-3-(3-methyl-1H-pyrazol-1-yl)propionate
• 英文别名: methyl 2-methyl-3-(3-methylpyrazol-1-yl)propionate；methyl 2-methyl-3-(3-methylpyrazol-1-yl)propanoate
• CAS: 180741-33-7
• 化学式: C₉H₁₄N₂O₂
• 分子量: 182.222
• InChiKey: XIRWTZNGBJWPSJ-UHFFFAOYSA-N

物化性质

• 沸点：
  85 °C(Press: 1 Torr)
• 密度：
  1.0640 g/cm3

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 2-methyl-3-(3-methyl-1H-pyrazol-1-yl)propionate 在 lithium hydroxide monohydrate 、 水 作用下， 以 四氢呋喃 为溶剂， 反应 10.0h， 生成 α-methyl-β-(3-methylpyrazol-1-yl)propionic acid
  参考文献：
  名称：

  Structure-based design, synthesis and biological evaluation of novel β-secretase inhibitors containing a pyrazole or thiazole moiety as the P3 ligand

  摘要：

  We describe structure-based design, synthesis, and biological evaluation of a series of novel inhibitors bearing a pyrazole (compounds 3a-h) or a thiazole moiety (compounds 4a-e) as the P3 ligand. We have also explored Boc-beta-amino-L-alanine as a novel P2 ligand. A number of inhibitors have displayed b-secretase inhibitory potency. Inhibitor 4c has shown potent BACE1 inhibitory activity, K-i = 0.25 nM, cellular EC50 of 194 nM, and displayed good selectivity over BACE2. A model of 4c was created based upon the X-ray structure of 2-bound beta-secretase which revealed critical interactions in the active site. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.11.087
• 作为产物：
  描述：

  3-甲基吡唑 、 甲基丙烯酸甲酯 反应 6.0h， 生成 methyl 2-methyl-3-(3-methyl-1H-pyrazol-1-yl)propionate
  参考文献：
  名称：

  Structure-based design, synthesis and biological evaluation of novel β-secretase inhibitors containing a pyrazole or thiazole moiety as the P3 ligand

  摘要：

  We describe structure-based design, synthesis, and biological evaluation of a series of novel inhibitors bearing a pyrazole (compounds 3a-h) or a thiazole moiety (compounds 4a-e) as the P3 ligand. We have also explored Boc-beta-amino-L-alanine as a novel P2 ligand. A number of inhibitors have displayed b-secretase inhibitory potency. Inhibitor 4c has shown potent BACE1 inhibitory activity, K-i = 0.25 nM, cellular EC50 of 194 nM, and displayed good selectivity over BACE2. A model of 4c was created based upon the X-ray structure of 2-bound beta-secretase which revealed critical interactions in the active site. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.11.087

文献信息

• Synthesis of N- and C-azolyl-substituted pyrazolo[1,5-a]pyrimidines by recyclization of pyrimidinium salts
  作者：Gevorg G. Danagulyan、Araksya K. Tumanyan、Oganes S. Attaryan、Rafael A. Tamazyan、Anna G. Danagulyan、Armen G. Ayvazyan

  DOI：10.1007/s10593-015-1724-3

  日期：2015.5

  We studied the reaction of 2-(ethoxycarbonyl)methyl-1,4,6-trimethylpyrimidinium iodide with hydrazides of N-azolyl- and D-pyrazolylsubstituted carboxylic acids, which were synthesized by reacting the respective esters with hydrazine hydrate. This reaction was shown to result in recyclization and formation of ethyl 2-(pyrazolylalkyl)- and 2-(azolylalkyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidine-3-carboxylates. Besides pyrazolopyrimidines, the separation of reaction mixture provided in some cases also another recyclization product, 2-hydroxy-5,7-dimethylpyrazolo[1,5-a]pyrimidine.
• Synthesis of α-methyl-β-(3-methylpyrazol-1-yl)-and α-methyl-β-(5-methylpyrazol-1-yl)propionic acids and their esterification with vinyl acetate
  作者：O. S. Attaryan、A. O. Baltayan、S. G. Matsoyan

  DOI：10.1134/s107036320702017x

  日期：2007.2

  alpha-Methyl-beta-(3-methylpyrazol-1-yl)- and alpha-methyl-beta-(5-methylpyrazol-1-yl)propionic acids were synthesized by reaction of 3(5)-methylpyrazole with methyl methacrylate, followed by separation of the resulting isomeric esters and their hydrolysis. Esterification of the title acids was performed via vinyl exchange reaction with vinyl acetate in the catalytic system mercury acetate-trifluoroacetic acid.
• US5972064A
  申请人：——

  公开号：US5972064A

  公开（公告）日：1999-10-26
• Structure-based design, synthesis and biological evaluation of novel β-secretase inhibitors containing a pyrazole or thiazole moiety as the P3 ligand
  作者：Arun K. Ghosh、Margherita Brindisi、Yu-Chen Yen、Xiaoming Xu、Xiangping Huang、Thippeswamy Devasamudram、Geoffrey Bilcer、Hui Lei、Gerald Koelsch、Andrew D. Mesecar、Jordan Tang

  DOI：10.1016/j.bmcl.2014.11.087

  日期：2015.2

  We describe structure-based design, synthesis, and biological evaluation of a series of novel inhibitors bearing a pyrazole (compounds 3a-h) or a thiazole moiety (compounds 4a-e) as the P3 ligand. We have also explored Boc-beta-amino-L-alanine as a novel P2 ligand. A number of inhibitors have displayed b-secretase inhibitory potency. Inhibitor 4c has shown potent BACE1 inhibitory activity, K-i = 0.25 nM, cellular EC50 of 194 nM, and displayed good selectivity over BACE2. A model of 4c was created based upon the X-ray structure of 2-bound beta-secretase which revealed critical interactions in the active site. (C) 2014 Elsevier Ltd. All rights reserved.