diisobutyl-[3-(4-{3-[(thiazol-2-ylmethyl)amino]propyl}piperazin-1-yl)propyl]amine

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: diisobutyl-[3-(4-{3-[(thiazol-2-ylmethyl)amino]propyl}piperazin-1-yl)propyl]amine
• 英文别名: N-[3-(4-{3-[diisobutylamino]propyl}piperazino)propyl]-2-thiazolylmethylamine；2-methyl-N-(2-methylpropyl)-N-[3-[4-[3-(1,3-thiazol-2-ylmethylamino)propyl]piperazin-1-yl]propyl]propan-1-amine
• 化学式: C₂₂H₄₃N₅S
• 分子量: 409.683
• InChiKey: AFQFOQTZEWHNHW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  28
• 可旋转键数：
  14
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  62.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  N¹,N¹-diisobutyl-1,4-bis(3-aminopropyl)piperazine 在 sodium tetrahydroborate 作用下， 以 乙醇 为溶剂， 反应 17.25h， 生成 diisobutyl-[3-(4-{3-[(thiazol-2-ylmethyl)amino]propyl}piperazin-1-yl)propyl]amine
  参考文献：
  名称：

  Chloroquine and Chloroquinoline Derivatives as Models for the Design of Modulators of Amyloid Peptide Precursor Metabolism

  摘要：

  The amyloid precursor protein (APP) plays a central role in Alzheimer's disease (AD). Preventing deregulated APP processing by inhibiting amyloidogenic processing of carboxy-terminal fragments (APP-CTFs), and reducing the toxic effect of amyloid beta (A beta) peptides remain an effective therapeutic strategy. We report the design of piperazine-containing compounds derived from chloroquine structure and evaluation of their effects on APP metabolism and ability to modulate the processing of APP-CTF and the production of A beta peptide. Compounds which retained alkaline properties and high affinity for acidic cell compartments were the most effective. The present study demonstrates that (1) the amino side chain of chloroquine can be efficiently substituted by a bis(alkylamino)piperazine chain, (2) the quinoline nucleus can be replaced by a benzyl or a benzimidazole moiety, and (3) pharmacomodulation of the chemical structure allows the redirection of APP metabolism toward a decrease of A beta peptide release, and increased stability of APP-CTFs and amyloid intracellular fragment. Moreover, the benzimidazole compound 29 increases APP-CTFs in vivo and shows promising activity by the oral route. Together, this family of compounds retains a lysosomotropic activity which inhibits lysosome-related A beta production, and is likely to be beneficial for therapeutic applications in AD.

  DOI：

  10.1021/cn5003013

文献信息

• Use of 1,4-bis (3-aminoalkyl) piperazine derivatives in the treatment of neurodegenerative diseases
  申请人：Sergeant Nicolas

  公开号：US20090149464A1

  公开（公告）日：2009-06-11

  Use of 1,4-bis(3-aminoalkyl)piperazine derivatives as defined in formula I or II for the manufacture of a pharmaceutical composition intended for the treatment of neurodegenerative diseases, related neurodegenerative diseases, developmental diseases or cancer. The instant invention is also directed to some specific 1,4-bis(3-aminoalkyl)piperazine derivatives and pharmaceutical composition including them.

  使用公式I或II中定义的1,4-双(3-氨基烷基)哌嗪衍生物制造用于治疗神经退行性疾病、相关神经退行性疾病、发育性疾病或癌症的药物组合物。本发明还涉及一些特定的1,4-双(3-氨基烷基)哌嗪衍生物和包括它们的药物组合物。
• WO2006/51489
  申请人：——

  公开号：——

  公开（公告）日：——
• USE OF 1,4-BIS (3-AMINOALKYL) PIPERAZINE DERIVATIVES IN THE TREATMENT OF NEURODEGENERATIVE DISEASES
  申请人：INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE (INSERM)

  公开号：EP1809288B1

  公开（公告）日：2011-09-14
• US9044478B2
  申请人：——

  公开号：US9044478B2

  公开（公告）日：2015-06-02
• Chloroquine and Chloroquinoline Derivatives as Models for the Design of Modulators of Amyloid Peptide Precursor Metabolism
  作者：Patricia Melnyk、Valérie Vingtdeux、Stéphane Burlet、Sabiha Eddarkaoui、Marie-Eve Grosjean、Paul-Emmanuel Larchanché、Guillaume Hochart、Christian Sergheraert、Cecilia Estrella、Mathieu Barrier、Virginie Poix、Pauline Plancq、Cécile Lannoo、Malika Hamdane、André Delacourte、Philippe Verwaerde、Luc Buée、Nicolas Sergeant

  DOI：10.1021/cn5003013

  日期：2015.4.15

  The amyloid precursor protein (APP) plays a central role in Alzheimer's disease (AD). Preventing deregulated APP processing by inhibiting amyloidogenic processing of carboxy-terminal fragments (APP-CTFs), and reducing the toxic effect of amyloid beta (A beta) peptides remain an effective therapeutic strategy. We report the design of piperazine-containing compounds derived from chloroquine structure and evaluation of their effects on APP metabolism and ability to modulate the processing of APP-CTF and the production of A beta peptide. Compounds which retained alkaline properties and high affinity for acidic cell compartments were the most effective. The present study demonstrates that (1) the amino side chain of chloroquine can be efficiently substituted by a bis(alkylamino)piperazine chain, (2) the quinoline nucleus can be replaced by a benzyl or a benzimidazole moiety, and (3) pharmacomodulation of the chemical structure allows the redirection of APP metabolism toward a decrease of A beta peptide release, and increased stability of APP-CTFs and amyloid intracellular fragment. Moreover, the benzimidazole compound 29 increases APP-CTFs in vivo and shows promising activity by the oral route. Together, this family of compounds retains a lysosomotropic activity which inhibits lysosome-related A beta production, and is likely to be beneficial for therapeutic applications in AD.