N-[(1H-benzo[d]imidazol-2-yl)methyl]-N-(3-(aminomethyl)benzyl)-5,6,7,8-tetrahydroquinolin-8-amine | 405058-65-3

• 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: N-[(1H-benzo[d]imidazol-2-yl)methyl]-N-(3-(aminomethyl)benzyl)-5,6,7,8-tetrahydroquinolin-8-amine
• 英文别名: (3-aminomethyl-benzyl)-(1H-benzoimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amine；N-[[3-(aminomethyl)phenyl]methyl]-N-(1H-benzimidazol-2-ylmethyl)-5,6,7,8-tetrahydroquinolin-8-amine
• CAS: 405058-65-3
• 化学式: C₂₅H₂₇N₅
• 分子量: 397.523
• InChiKey: IQFJZKSDDHHGJU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  70.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2,4-二甲基吡啶-3-羧酸 、 N-[(1H-benzo[d]imidazol-2-yl)methyl]-N-(3-(aminomethyl)benzyl)-5,6,7,8-tetrahydroquinolin-8-amine 在 4-二甲氨基吡啶 三乙胺 作用下， 以 氯化亚砜 、 二氯甲烷 为溶剂， 生成 N-(3-{[(1H-benzoimidazol-2-ylmethyl)-(5,6,7,8-tetrahydro-quinolin-8-yl)-amino]-methyl}-benzyl)-2,4-dimethyl-nicotinamide (hydrobromide salt)
  参考文献：
  名称：

  Chemokine receptor binding heterocyclic compounds

  摘要：

  含有多种杂环取代基的三级胺可用作化学受体调节剂。

  公开号：

  US20020147192A1
• 作为产物：
  描述：

  tert-butyl 2-[[(3-cyanophenyl)methyl-(5,6,7,8-tetrahydroquinolin-8-yl)amino]methyl]benzimidazole-1-carboxylate 在 氨 、 氢气 作用下， 以 甲醇 为溶剂， 反应 16.0h， 以4.36 g的产率得到N-[(1H-benzo[d]imidazol-2-yl)methyl]-N-(3-(aminomethyl)benzyl)-5,6,7,8-tetrahydroquinolin-8-amine
  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

• Methods to mobilize progenitor/stem cells
  申请人：Bridger Gary

  公开号：US20050043367A1

  公开（公告）日：2005-02-24

  Methods to elevate progenitor and stem cell counts in animal subjects using compounds which bind to the chemokine receptor CXCR4 are disclosed. Preferred embodiments of such compounds are of the formula Z-linker-Z′  (1) or pharmaceutically acceptable salt thereof wherein Z is of the formula wherein A comprises a monocyclic or bicyclic fused ring system containing at least one N and B is H or an organic moiety of 1-20 atoms, Z′ is of the formula —Ar(Y) j ; wherein Ar is an aromatic or heteroaromatic moiety, and each Y is independently a non-interfering substituent and j is 0-3; and “linker” represents a bond, alkylene (1-6C) or may comprise aryl, fused aryl, oxygen atoms contained in an alkylene chain, or may contain keto groups or nitrogen or sulfur atoms.

  本文揭示了利用与趋化因子受体CXCR4结合的化合物来提高动物主体和干细胞计数的方法。这些化合物的优选实施方式为式Z-连接-Z' (1)或其药用盐，其中Z的式为其中A包括至少含有一个N的单环或双环融合环系统，B为H或含有1-20个原子的有机基团，Z'的式为-Ar(Y)j；其中Ar为芳香或杂芳基团，每个Y独立地表示非干扰取代基，j为0-3；“连接物”代表键，烷基（1-6C）或可能包含芳基，融合芳基，含有在烷基链中的氧原子，或可能含有酮基团或氮或硫原子。
• CHEMOKINE RECEPTOR BINDING HETEROCYCLIC COMPOUNDS
  申请人：Bridger Gary

  公开号：US20080090846A1

  公开（公告）日：2008-04-17

  Tertiary amines containing a multiplicity of heteroaromatic substituents are useful as chemokine receptor modulators.

  含有多种杂环芳基取代基的三级胺可用作趋化因子受体调节剂。
• METHODS FOR INCREASING BLOOD FLOW AND/OR PROMOTING TISSUE REGENERATION
  申请人：Genzyme Corporation

  公开号：EP1991221B1

  公开（公告）日：2014-05-21
• CXCR4 ANTAGONISTS FOR KIDNEY INJURY
  申请人：Zuk Anna

  公开号：US20110245265A1

  公开（公告）日：2011-10-06

  Methods to treat or prevent acute kidney injury and chronic kidney injury in subjects using CXCR4 antagonists are disclosed.
• Methods For Increasing Blood Flow And/Or Promoting Tissue Regeneration
  申请人：BRIDGER Gary J.

  公开号：US20130095076A1

  公开（公告）日：2013-04-18

  Methods for increasing blood flow and/or regenerating tissue using compounds which bind to the chemokine receptor CXCR4 are disclosed. Preferred embodiments of such compounds are of the formula Z-linker-Z′  (1).