2-Methyl-3-(3,5-dimethylpyrazol-1-yl)propionsaeuremethylester | 91010-97-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-Methyl-3-(3,5-dimethylpyrazol-1-yl)propionsaeuremethylester
• 英文别名: 3-(3,5-dimethyl-pyrazol-1-yl)-2-methyl-propionic acid methyl ester；β-(3,5-dimethyl-pyrazol-1-yl)-isobutyric acid methyl ester；β-(3,5-Dimethyl-pyrazol-1-yl)-isobuttersaeure-methylester；Methyl 3-(3,5-dimethylpyrazol-1-yl)-2-methylpropanoate
• CAS: 91010-97-8
• 化学式: C₁₀H₁₆N₂O₂
• 分子量: 196.249
• InChiKey: DMJIEBNPPBQEMR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 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：

  2-Methyl-3-(3,5-dimethylpyrazol-1-yl)propionsaeuremethylester 在 lithium hydroxide monohydrate 、 水 作用下， 以 四氢呋喃 为溶剂， 反应 10.0h， 生成 3-(3,5-二甲基-1H-吡唑-1-基)-2-甲基丙酸
  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：

  3,5-二甲基吡唑 、 甲基丙烯酸甲酯 生成 2-Methyl-3-(3,5-dimethylpyrazol-1-yl)propionsaeuremethylester
  参考文献：
  名称：

  Grandberg; Kost, Zhurnal Obshchei Khimii, 1959, vol. 29, p. 1099,1102; engl. Ausg. S. 1069, 1071

  摘要：

  DOI：

文献信息

• Compounds which inhibit beta-secretase activity and methods of use thereof
  申请人：Oklahoma Medical Research Foundation

  公开号：US20040121947A1

  公开（公告）日：2004-06-24

  Compounds inhibit memapsin 2 &bgr;-secretase activity and selectively inhibit memapsin 2 &bgr;-secretase activity relative to memapsin 1 &bgr;-secretase activity. The compounds are employed in methods to inhibit memapsin 2 &bgr;-secretase activity, in the treatment of Alzheimer's disease, in the inhibition of hydrolysis of a &bgr;-secretase site of a &bgr;amyloid precursor protein and to decrease &bgr;-amyloid protein in in vitro samples and in mammals. Proteins of memapsin 2 associated with compounds of the invention are crystallized.

  这些化合物抑制memapsin 2 β-分泌酶活性，并相对选择性地抑制memapsin 2 β-分泌酶活性，而相对于memapsin 1 β-分泌酶活性。这些化合物用于抑制memapsin 2 β-分泌酶活性的方法，用于治疗阿尔茨海默病，用于抑制β淀粉样前体蛋白的β-分泌酶位点的水解，并用于减少体外样本和哺乳动物中的β-淀粉样蛋白。与本发明的化合物相关的memapsin 2蛋白被结晶。
• COMPOUNDS WHICH INHIBIT BETA-SECRETASE ACTIVITY AND METHODS OF USE THEREOF
  申请人：GHOSH Arun K.

  公开号：US20100267609A1

  公开（公告）日：2010-10-21

  Compounds inhibit memapsin 2 β-secretase activity and selectively inhibit memapsin 2 β-secretase activity relative to memapsin 1 β-secretase activity. The compounds are employed in methods to inhibit memapsin 2 β-secretase activity, in the treatment of Alzheimer's disease, in the inhibition of hydrolysis of a β-secretase site of a β-amyloid precursor protein and to decrease β-amyloid protein in in vitro samples and in mammals. Proteins of memapsin 2 associated with compounds of the invention are crystallized.
• [EN] BETA-SECRETASE INHIBITORS AND METHODS OF USE<br/>[FR] INHIBITEURS DE LA BETA-SECRETASE ET LEURS PROCEDE D'UTILISATION
  申请人：OKLAHOMA MED RES FOUND

  公开号：WO2003039454A2

  公开（公告）日：2003-05-15

  Compounds inhibit memapsin 2 β-secretase activity and selectively inhibit memapsin 2 β-secretase activity relative to memapsin 1 β-secretase activity. The compounds are employed in methods to inhibit memapsin 2 β-secretase activity, in the treatment of Alzheimer's disease, in the inhibition of hydrolysis of a β-secretase site of a β-amyloid precursor protein and to decrease β-amyloid protein in in vitro samples and in mammals. Proteins of memapsin 2 associated with compounds of the invention are crystallized.