4-[(5,6,7,8-tetrahydroquinolin-8-ylamino)methyl]benzonitrile | 405174-87-0

• 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-[(5,6,7,8-tetrahydroquinolin-8-ylamino)methyl]benzonitrile
• 英文别名: N-(5,6,7,8-tetrahydro-8-quinolinyl)-4-cyanobenzylamine
• CAS: 405174-87-0
• 化学式: C₁₇H₁₇N₃
• 分子量: 263.342
• InChiKey: SMEAEUDAOVZHPF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  48.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-[(5,6,7,8-tetrahydroquinolin-8-ylamino)methyl]benzonitrile 、 2-(氯甲基)-1H-苯并[d]咪唑-1-羧酸叔丁酯 在 N,N-二异丙基乙胺 、 potassium iodide 作用下， 以 乙腈 为溶剂， 以67%的产率得到Tert-butyl 2-[[(4-cyanophenyl)methyl-(5,6,7,8-tetrahydroquinolin-8-yl)amino]methyl]benzimidazole-1-carboxylate
  参考文献：
  名称：

  Discovery of Novel Small Molecule Orally Bioavailable C−X−C Chemokine Receptor 4 Antagonists That Are Potent Inhibitors of T-Tropic (X4) HIV-1 Replication

  摘要：

  The redesign of azamacrocyclic CXCR4 chemokine receptor antagonists resulted in the discovery of novel, small molecule, orally bioavailable compounds that retained T-tropic (CXCR4 using, X4) anti-HIV-1 activity. A structure activity relationship (SA R) was determined on the basis of the inhibition of replication of X4 HIV-1 NL4.3 in MT-4 cells. As a result of lead optimization, we identified (S)-N'-((1H-benzo[d]imidazol-2-Amethyl)-N'-(5,6,7,8-tetrahydroquinolin-8-yl)butane-1,4-diamine (AMD070) 2 as a potent and selective antagonist of CXCR4 with an IC(50) value of 13 nM in a CXCR4 (125)I-SDF inhibition binding assay. Compound 2 inhibited the replication of T-tropic HIV-1 (NL4.3 strain) in MT-4 cells and PBMCs with an IC(50) of 2 and 26 nM, respectively, while remaining noncytotoxic to cells at concentrations exceeding 23 mu M. The pharmacokinetics of 2 was evaluated in rat and dog, and good oral bioavailability was observed in both species. This compound represents the first small molecule orally bioavailable CXCR4 antagonist that was developed for the treatment of HIV-1 infection.

  DOI：

  10.1021/jm100073m
• 作为产物：
  描述：

  5,6,7,8-四氢-8-氨基喹啉 、 4-氰基苯甲醛 在 三乙酰氧基硼氢化钠 、 溶剂黄146 作用下， 以 二氯甲烷 为溶剂， 以72%的产率得到4-[(5,6,7,8-tetrahydroquinolin-8-ylamino)methyl]benzonitrile
  参考文献：
  名称：

  Discovery of Novel Small Molecule Orally Bioavailable C−X−C Chemokine Receptor 4 Antagonists That Are Potent Inhibitors of T-Tropic (X4) HIV-1 Replication

  摘要：

  The redesign of azamacrocyclic CXCR4 chemokine receptor antagonists resulted in the discovery of novel, small molecule, orally bioavailable compounds that retained T-tropic (CXCR4 using, X4) anti-HIV-1 activity. A structure activity relationship (SA R) was determined on the basis of the inhibition of replication of X4 HIV-1 NL4.3 in MT-4 cells. As a result of lead optimization, we identified (S)-N'-((1H-benzo[d]imidazol-2-Amethyl)-N'-(5,6,7,8-tetrahydroquinolin-8-yl)butane-1,4-diamine (AMD070) 2 as a potent and selective antagonist of CXCR4 with an IC(50) value of 13 nM in a CXCR4 (125)I-SDF inhibition binding assay. Compound 2 inhibited the replication of T-tropic HIV-1 (NL4.3 strain) in MT-4 cells and PBMCs with an IC(50) of 2 and 26 nM, respectively, while remaining noncytotoxic to cells at concentrations exceeding 23 mu M. The pharmacokinetics of 2 was evaluated in rat and dog, and good oral bioavailability was observed in both species. This compound represents the first small molecule orally bioavailable CXCR4 antagonist that was developed for the treatment of HIV-1 infection.

  DOI：

  10.1021/jm100073m

文献信息

• Chemokine receptor binding heterocyclic compounds
  申请人：——

  公开号：US20040220207A1

  公开（公告）日：2004-11-04

  Novel compounds that are useful for targeting chemokine receptors are disclosed. These compounds are complex tertiary amines.

  本发明揭示了用于靶向趋化因子受体的新化合物。这些化合物是复杂的三级胺。
• CHEMOKINE RECEPTOR BINDING HETEROCYCLIC COMPOUNDS
  申请人：ANORMED INC.

  公开号：EP1317445B1

  公开（公告）日：2009-03-11
• US6864265B2
  申请人：——

  公开号：US6864265B2

  公开（公告）日：2005-03-08
• US7084155B2
  申请人：——

  公开号：US7084155B2

  公开（公告）日：2006-08-01
• US7396840B2
  申请人：——

  公开号：US7396840B2

  公开（公告）日：2008-07-08