(4-amino-2-((4-chlorophenyl)amino)thiazol-5-yl)(3-nitrophenyl)methanone

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (4-amino-2-((4-chlorophenyl)amino)thiazol-5-yl)(3-nitrophenyl)methanone
• 英文别名: [4-amino-2-(4-chloro-phenylamino)-thiazol-5-yl]-(3-nitro-phenyl)-methanone；{4-Amino-2-[(4-Chlorophenyl)amino]-1,3-Thiazol-5-Yl}(3-Nitrophenyl)methanone；[4-amino-2-(4-chloroanilino)-1,3-thiazol-5-yl]-(3-nitrophenyl)methanone
• 化学式: C₁₆H₁₁ClN₄O₃S
• 分子量: 374.807
• InChiKey: YQRVBHMYUSGXHL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  142
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  氰胺 、 4-氯异硫氰酸苯酯 、 2-溴-3'-硝基苯乙酮 在 potassium tert-butylate 作用下， 以 乙腈 、 叔丁醇 为溶剂， 反应 2.0h， 以59%的产率得到(4-amino-2-((4-chlorophenyl)amino)thiazol-5-yl)(3-nitrophenyl)methanone
  参考文献：
  名称：

  Discovery of thienoquinolone derivatives as selective and ATP non-competitive CDK5/p25 inhibitors by structure-based virtual screening

  摘要：

  Calpain mediated cleavage of CDK5 natural precursor p35 causes a stable complex formation of CDK5/p25, which leads to hyperphosphorylation of tau. Thus inhibition of this complex is a viable target for numerous acute and chronic neurodegenerative diseases involving tau protein, including Alzheimer's disease. Since CDK5 has the highest sequence homology with its mitotic counterpart CDK2, our primary goal was to design selective CDK5/p25 inhibitors targeting neurodegeneration. A novel structure-based virtual screening protocol comprised of e-pharmacophore models and virtual screening workflow was used to identify nine compounds from a commercial database containing 2.84 million compounds. An ATP non-competitive and selective thieno[ 3,2-c] quinolin-4(5H)-one inhibitor (10) with ligand efficiency (LE) of 0.3 was identified as the lead molecule. Further SAR optimization led to the discovery of several low micromolar inhibitors with good selectivity. The research represents a new class of potent ATP noncompetitive CDK5/p25 inhibitors with good CDK2/E selectivity. Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmc.2014.09.043

文献信息

• PDE4B INHIBITORS AND USES THEREFOR
  申请人：Ibrahim Prabha N.

  公开号：US20090286793A1

  公开（公告）日：2009-11-19

  Compounds active on phosphodiesterase PDE4B are provided. Also provided herewith are compositions useful for treatment of PDE4B-mediated diseases or conditions, and methods for the use thereof.

  本发明提供了对磷酸二酯酶PDE4B活性作用的化合物。同时还提供了用于治疗PDE4B介导的疾病或病状的组合物以及其使用方法。
• US7585859B2
  申请人：——

  公开号：US7585859B2

  公开（公告）日：2009-09-08
• US8470821B2
  申请人：——

  公开号：US8470821B2

  公开（公告）日：2013-06-25
• Discovery of thienoquinolone derivatives as selective and ATP non-competitive CDK5/p25 inhibitors by structure-based virtual screening
  作者：Arindam Chatterjee、Stephen J. Cutler、Robert J. Doerksen、Ikhlas A. Khan、John S. Williamson

  DOI：10.1016/j.bmc.2014.09.043

  日期：2014.11

  Calpain mediated cleavage of CDK5 natural precursor p35 causes a stable complex formation of CDK5/p25, which leads to hyperphosphorylation of tau. Thus inhibition of this complex is a viable target for numerous acute and chronic neurodegenerative diseases involving tau protein, including Alzheimer's disease. Since CDK5 has the highest sequence homology with its mitotic counterpart CDK2, our primary goal was to design selective CDK5/p25 inhibitors targeting neurodegeneration. A novel structure-based virtual screening protocol comprised of e-pharmacophore models and virtual screening workflow was used to identify nine compounds from a commercial database containing 2.84 million compounds. An ATP non-competitive and selective thieno[ 3,2-c] quinolin-4(5H)-one inhibitor (10) with ligand efficiency (LE) of 0.3 was identified as the lead molecule. Further SAR optimization led to the discovery of several low micromolar inhibitors with good selectivity. The research represents a new class of potent ATP noncompetitive CDK5/p25 inhibitors with good CDK2/E selectivity. Published by Elsevier Ltd.