1-(2-methylbenzyl)-N-[4,5-bis(4-methoxyphenyl)thiazol-2-yl]piperidine-4-carboxamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 1-(2-methylbenzyl)-N-[4,5-bis(4-methoxyphenyl)thiazol-2-yl]piperidine-4-carboxamide
• 英文别名: N-[4,5-bis(4-methoxyphenyl)-1,3-thiazol-2-yl]-1-[(2-methylphenyl)methyl]piperidine-4-carboxamide
• 化学式: C₃₁H₃₃N₃O₃S
• 分子量: 527.687
• InChiKey: CCXYJRSEOJUDQL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  38
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  91.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(2-methylbenzyl)-N-[4,5-bis(4-methoxyphenyl)thiazol-2-yl]piperidine-4-carboxamide 在 dimethyl sulfide borane 作用下， 以 四氢呋喃 为溶剂， 以88%的产率得到N-[(1-(2-methylbenzyl)piperidin-4-yl)methyl]-4,5-bis(4-methoxyphenyl)thiazol-2-ylamine
  参考文献：
  名称：

  Benzylpiperidine-Linked Diarylthiazoles as Potential Anti-Alzheimer’s Agents: Synthesis and Biological Evaluation

  摘要：

  A novel series of hybrid molecules were designed and synthesized by fusing the pharmacophoric features of cholinesterase inhibitor donepezil and diarylthiazole as potential multitarget-directed ligands for the treatment of Alzheimer's disease (AD). The compounds showed significant in vitro anticholinesterase (anti-ChE) activity, the most potent compound (44) among them showing the highest activity (IC50 value of 0.30 +/- 0.01 mu M) for AChE and (1.84 +/- 0.03 mu M) for BuChE. Compound 44 showed mixed inhibition of AChE in the enzyme kinetic studies. Some compounds exhibited moderate to high inhibition of AChE-induced A beta(1-42) aggregation and noticeable in vitro antioxidant and antiapoptotic properties. Compound 44 showed significant in vivo anti-ChE and antioxidant activities. Furthermore, compound 44 demonstrated in vivo neuroprotection by decreasing A beta(1-42)-induced toxicity by attenuating abnormal levels of A beta(1-42), p-Tau, cleaved caspase-3, and cleaved PARP proteins. Compound 44 exhibited good oral absorption and was well tolerated up to 2000 mg/kg, po, dose without showing toxic effects.

  DOI：

  10.1021/acs.jmedchem.6b00426
• 作为产物：
  描述：

  4,5-双-(4-甲氧基苯基)-噻唑-2-胺 在 potassium carbonate 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 3.0h， 生成 1-(2-methylbenzyl)-N-[4,5-bis(4-methoxyphenyl)thiazol-2-yl]piperidine-4-carboxamide
  参考文献：
  名称：

  Benzylpiperidine-Linked Diarylthiazoles as Potential Anti-Alzheimer’s Agents: Synthesis and Biological Evaluation

  摘要：

  A novel series of hybrid molecules were designed and synthesized by fusing the pharmacophoric features of cholinesterase inhibitor donepezil and diarylthiazole as potential multitarget-directed ligands for the treatment of Alzheimer's disease (AD). The compounds showed significant in vitro anticholinesterase (anti-ChE) activity, the most potent compound (44) among them showing the highest activity (IC50 value of 0.30 +/- 0.01 mu M) for AChE and (1.84 +/- 0.03 mu M) for BuChE. Compound 44 showed mixed inhibition of AChE in the enzyme kinetic studies. Some compounds exhibited moderate to high inhibition of AChE-induced A beta(1-42) aggregation and noticeable in vitro antioxidant and antiapoptotic properties. Compound 44 showed significant in vivo anti-ChE and antioxidant activities. Furthermore, compound 44 demonstrated in vivo neuroprotection by decreasing A beta(1-42)-induced toxicity by attenuating abnormal levels of A beta(1-42), p-Tau, cleaved caspase-3, and cleaved PARP proteins. Compound 44 exhibited good oral absorption and was well tolerated up to 2000 mg/kg, po, dose without showing toxic effects.

  DOI：

  10.1021/acs.jmedchem.6b00426

文献信息

• Benzylpiperidine-Linked Diarylthiazoles as Potential Anti-Alzheimer’s Agents: Synthesis and Biological Evaluation
  作者：Mahesh Shidore、Jatin Machhi、Kaushik Shingala、Prashant Murumkar、Mayank Kumar Sharma、Neetesh Agrawal、Ashutosh Tripathi、Zalak Parikh、Prakash Pillai、Mange Ram Yadav

  DOI：10.1021/acs.jmedchem.6b00426

  日期：2016.6.23

  A novel series of hybrid molecules were designed and synthesized by fusing the pharmacophoric features of cholinesterase inhibitor donepezil and diarylthiazole as potential multitarget-directed ligands for the treatment of Alzheimer's disease (AD). The compounds showed significant in vitro anticholinesterase (anti-ChE) activity, the most potent compound (44) among them showing the highest activity (IC50 value of 0.30 +/- 0.01 mu M) for AChE and (1.84 +/- 0.03 mu M) for BuChE. Compound 44 showed mixed inhibition of AChE in the enzyme kinetic studies. Some compounds exhibited moderate to high inhibition of AChE-induced A beta(1-42) aggregation and noticeable in vitro antioxidant and antiapoptotic properties. Compound 44 showed significant in vivo anti-ChE and antioxidant activities. Furthermore, compound 44 demonstrated in vivo neuroprotection by decreasing A beta(1-42)-induced toxicity by attenuating abnormal levels of A beta(1-42), p-Tau, cleaved caspase-3, and cleaved PARP proteins. Compound 44 exhibited good oral absorption and was well tolerated up to 2000 mg/kg, po, dose without showing toxic effects.