α-methyl-β-(3-methylpyrazol-1-yl)propionic acid | 371212-60-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: α-methyl-β-(3-methylpyrazol-1-yl)propionic acid
• 英文别名: 2-methyl-3-[3-methylpyrazol-1-yl]propionic acid；2-methyl-3-(3-methyl-1H-pyrazol-2-ium-1-yl)propanoate；2-methyl-3-(5-methyl-1H-pyrazol-2-ium-2-yl)propanoate
• CAS: 371212-60-1
• 化学式: C₈H₁₂N₂O₂
• 分子量: 168.195
• InChiKey: ARJKQIWTIXNRAC-UHFFFAOYSA-N

物化性质

• 熔点：
  103-104 °C(Solv: water (7732-18-5))
• 沸点：
  318.7±25.0 °C(Predicted)
• 密度：
  1.19±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  12
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  55.1
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 危险等级：
  IRRITANT

反应信息

• 作为反应物：
  描述：

  α-methyl-β-(3-methylpyrazol-1-yl)propionic acid 在 4-二甲氨基吡啶 、 lithium hydroxide monohydrate 、 四丁基氟化铵 、 水 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 49.0h， 生成 tert-butyl N-[(2S)-3-[[(4S,5S,7R)-5-hydroxy-2,7-dimethyl-8-[[(2S)-3-methyl-1-(2-methylpropylamino)-1-oxobutan-2-yl]amino]-8-oxooctan-4-yl]amino]-2-[[(2S)-2-methyl-3-(3-methylpyrazol-1-yl)propanoyl]amino]-3-oxopropyl]carbamate
  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：

  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

文献信息

• Discovery of Farnesoid X Receptor Antagonists Based on a Library of Oleanolic Acid 3-O-Esters through Diverse Substituent Design and Molecular Docking Methods
  作者：Shao-Rong Wang、Tingting Xu、Kai Deng、Chi-Wai Wong、Jinsong Liu、Wei-Shuo Fang

  DOI：10.3390/molecules22050690

  日期：——

  receptor (FXR) modulatory activity was modified at its C-3 position to find new FXR-interacting agents. A diverse substitution library of OA derivatives was constructed in silico through a 2D fingerprint similarity cluster strategy. With further docking analysis, four top-scored OA 3-O-ester derivatives were selected for synthesis. The bioassay results indicated that all four compounds 3 inhibited chenodeoxycholic

  具有已知法尼醇 X 受体 (FXR) 调节活性的五环三萜齐墩果酸 (OA, 1) 在其 C-3 位置被修改以寻找新的 FXR 相互作用剂。通过二维指纹相似性聚类策略，在计算机上构建了一个多样化的 OA 衍生物替代库。通过进一步的对接分析，选择了四种得分最高的 OA 3-O-酯衍生物进行合成。生物测定结果表明，所有四种化合物 3 均以浓度依赖性模式抑制鹅去氧胆酸 (CDCA) 诱导的 FXR 反式激活。其中3b和3d比母体化合物OA活性更高。进行了分子模拟研究以试图解释构效关系 (SAR) 和拮抗作用。据我们所知，
• Inhibitors of serine proteases
  申请人：VERTEX PHARMACEUTICALS INCORPORATED

  公开号：EP2366704A1

  公开（公告）日：2011-09-21

  The present invention relates to compounds of formula (I): or pharmaceutically acceptable salts or mixture thereof that inhibit serine protease activity, particularly the activity of hepatitis C virus NS3-NS4A protease.

  本发明涉及式（I）化合物：或其药学上可接受的盐或混合物，可抑制丝氨酸蛋白酶活性，特别是丙型肝炎病毒 NS3-NS4A 蛋白酶的活性。
• Spirocyclic inhibitors of serine proteases for the treatment of hcv infections
  申请人：VERTEX PHARMACEUTICALS INCORPORATED

  公开号：EP2631238A1

  公开（公告）日：2013-08-28

  The present invention relates to compounds of formula (I): or a pharmaceutically acceptable salt thereof. These compounds inhibit serine protease, particularly the hepatitis C virus NS3-NS4A protease.

  本发明涉及式（I）化合物或其药学上可接受的盐。这些化合物可抑制丝氨酸蛋白酶，特别是丙型肝炎病毒 NS3-NS4A 蛋白酶。
• 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.
• INHIBITORS OF SERINE PROTEASES
  申请人：VERTEX PHARMACEUTICALS INCORPORATED

  公开号：EP1917269B1

  公开（公告）日：2011-10-26