4-(2-(4-bromophenyl)quinoline-4-carboxamido)-N-(3,4-dimethylisoxazol-5-yl)benzenesulfonamide

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 4-(2-(4-bromophenyl)quinoline-4-carboxamido)-N-(3,4-dimethylisoxazol-5-yl)benzenesulfonamide
• 英文别名: 2-(4-bromophenyl)-N-[4-[(3,4-dimethyl-1,2-oxazol-5-yl)sulfamoyl]phenyl]quinoline-4-carboxamide
• 化学式: C₂₇H₂₁BrN₄O₄S
• 分子量: 577.458
• InChiKey: FIVUAKVXACIGCT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  37
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  123
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-(4-溴-苯基)-喹啉-4-羧酸 在 吡啶 、 氯化亚砜 作用下， 生成 4-(2-(4-bromophenyl)quinoline-4-carboxamido)-N-(3,4-dimethylisoxazol-5-yl)benzenesulfonamide
  参考文献：
  名称：

  Discovering novel chemical inhibitors of human cyclophilin A: Virtual screening, synthesis, and bioassay

  摘要：

  Cyclophilin A (CypA) is a member of cyclophilins, a family of the highly homologous peptidyl prolyl cis-trans isomerases (PPIases), which can bind to cyclosporin A (CsA). CypA plays critical roles in various biological processes, including protein folding, assembly, transportation, regulation of neuron growth, and HIV replication. The discovery of CypA inhibitor is now of a great special interest in the treatment of immunological disorders. In this study, a series of novel small molecular CypA inhibitors have been discovered by using structure-based virtual screening in conjunction with chemical synthesis and bioassay. The SPECS-1 database containing 85,000 small molecular compounds was searched by virtual screening against the crystal structure of human CypA. After SPR-based binding affinity assay, 15 compounds were found to show binding affinities to CypA at submicro-molar or micromolar level (compounds 1-15). Seven compounds were selected as the starting point for the further structure modification in considering binding activity, synthesis difficulty, and structure similarity. We thus synthesized 40 new small molecular compounds (1-6, 15, 16a-q, 17a-d, and 18a-I), and four of which (compounds 16b, 16h 16k,. and 18g) showed high CypA PPIase inhibition activities with IC50S of 2.5-6,2 mu M. Pharmacological assay indicated that these four Compounds demonstrated somewhat inhibition activities against the proliferation of spleen cells. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.11.006

文献信息

• Discovering novel chemical inhibitors of human cyclophilin A: Virtual screening, synthesis, and bioassay
  作者：Jian Li、Jing Chen、Chunshan Gui、Li Zhang、Yu Qin、Qiang Xu、Jian Zhang、Hong Liu、Xu Shen、Hualiang Jiang

  DOI：10.1016/j.bmc.2005.11.006

  日期：2006.4

  Cyclophilin A (CypA) is a member of cyclophilins, a family of the highly homologous peptidyl prolyl cis-trans isomerases (PPIases), which can bind to cyclosporin A (CsA). CypA plays critical roles in various biological processes, including protein folding, assembly, transportation, regulation of neuron growth, and HIV replication. The discovery of CypA inhibitor is now of a great special interest in the treatment of immunological disorders. In this study, a series of novel small molecular CypA inhibitors have been discovered by using structure-based virtual screening in conjunction with chemical synthesis and bioassay. The SPECS-1 database containing 85,000 small molecular compounds was searched by virtual screening against the crystal structure of human CypA. After SPR-based binding affinity assay, 15 compounds were found to show binding affinities to CypA at submicro-molar or micromolar level (compounds 1-15). Seven compounds were selected as the starting point for the further structure modification in considering binding activity, synthesis difficulty, and structure similarity. We thus synthesized 40 new small molecular compounds (1-6, 15, 16a-q, 17a-d, and 18a-I), and four of which (compounds 16b, 16h 16k,. and 18g) showed high CypA PPIase inhibition activities with IC50S of 2.5-6,2 mu M. Pharmacological assay indicated that these four Compounds demonstrated somewhat inhibition activities against the proliferation of spleen cells. (c) 2005 Elsevier Ltd. All rights reserved.