N-(1,3-benzothiazol-2-ylmethyl)-4-(piperidin-1-yl)aniline | 1443155-73-4

• 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: N-(1,3-benzothiazol-2-ylmethyl)-4-(piperidin-1-yl)aniline
• 英文别名: CHT240B；N-(1,3-benzothiazol-2-ylmethyl)-4-piperidin-1-ylaniline
• CAS: 1443155-73-4
• 化学式: C₁₉H₂₁N₃S
• 分子量: 323.462
• InChiKey: FKXGPAOJWLZLQD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  56.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-(4-硝基苯基)哌啶 在 三乙酰氧基硼氢化钠 、 铁粉 、 溶剂黄146 作用下， 以 乙醇 、 水 、 1,2-二氯乙烷 为溶剂， 反应 2.0h， 生成 N-(1,3-benzothiazol-2-ylmethyl)-4-(piperidin-1-yl)aniline
  参考文献：
  名称：

  Identification of M. tuberculosis Thioredoxin Reductase Inhibitors Based on High-Throughput Docking Using Constraints

  摘要：

  A virtual screening campaign is presented that led to small molecule inhibitors of thioredoxin reductase of Mycobacterium tuberculosis (MtTrxR) that target the protein-protein interaction site for the substrate thioredoxin (Trx). MtTrxR is a promising drug target because it dominates the Trx-dependent hydroperoxide metabolism and the reduction of ribonucleotides, thus facilitating survival and proliferation of M. tuberculosis. Moreover, MtTrxR sufficiently differs from its human homologs to suggest the possibility of selective inhibition if the MtTrxR-Trx interaction site is targeted. To this end, high-throughput docking of 6.5 million virtual compounds to the thioredoxin binding site of MtTrxR combined with constraints as filtering steps was applied. A total of 170 high-scoring compounds yielded 18 compounds that inhibited MtTrxR with IC50 values up to the low micromolar range, thus revealing that the protein-protein interaction site of MtTrxR is indeed druggable. Most importantly, selectivity toward MtTrxR in comparison to human TrxR (HsTrxR) is also demonstrated.

  DOI：

  10.1021/jm3015734

文献信息

• Identification of <i>M. tuberculosis</i> Thioredoxin Reductase Inhibitors Based on High-Throughput Docking Using Constraints
  作者：Oliver Koch、Timo Jäger、Kristin Heller、Purushothama Chary Khandavalli、Jette Pretzel、Katja Becker、Leopold Flohé、Paul M. Selzer

  DOI：10.1021/jm3015734

  日期：2013.6.27

  A virtual screening campaign is presented that led to small molecule inhibitors of thioredoxin reductase of Mycobacterium tuberculosis (MtTrxR) that target the protein-protein interaction site for the substrate thioredoxin (Trx). MtTrxR is a promising drug target because it dominates the Trx-dependent hydroperoxide metabolism and the reduction of ribonucleotides, thus facilitating survival and proliferation of M. tuberculosis. Moreover, MtTrxR sufficiently differs from its human homologs to suggest the possibility of selective inhibition if the MtTrxR-Trx interaction site is targeted. To this end, high-throughput docking of 6.5 million virtual compounds to the thioredoxin binding site of MtTrxR combined with constraints as filtering steps was applied. A total of 170 high-scoring compounds yielded 18 compounds that inhibited MtTrxR with IC50 values up to the low micromolar range, thus revealing that the protein-protein interaction site of MtTrxR is indeed druggable. Most importantly, selectivity toward MtTrxR in comparison to human TrxR (HsTrxR) is also demonstrated.