1,4-bis(3',4',5'-trimethoxybenzoyl)-2-(tert-butylcarbonylaminomethyl)piperazine

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1,4-bis(3',4',5'-trimethoxybenzoyl)-2-(tert-butylcarbonylaminomethyl)piperazine
• 英文别名: N-[[1,4-bis(3,4,5-trimethoxybenzoyl)piperazin-2-yl]methyl]-2,2-dimethyl-propanamide；N-[[1,4-bis(3,4,5-trimethoxybenzoyl)piperazin-2-yl]methyl]-2,2-dimethylpropanamide
• 化学式: C₃₀H₄₁N₃O₉
• 分子量: 587.67
• InChiKey: VCHGNWYUIYSETO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  42
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  125
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2-aminomethyl-1,4-dibenzylpiperazine 在 palladium on activated charcoal 盐酸 、 氢气 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 8.0h， 生成 1,4-bis(3',4',5'-trimethoxybenzoyl)-2-(tert-butylcarbonylaminomethyl)piperazine
  参考文献：
  名称：

  Structure−Activity Relationships in Platelet-Activating Factor (PAF). 10. From PAF Antagonism to Inhibition of HIV-1 Replication

  摘要：

  Excessive levels of PAF and cells of macrophage lineage appear to play an important role in neuronal cell injury, inflammatory syndrome, and HIV replication in CNS resulting in AIDS dementia complex (ADC). The beneficial effects of PAF receptor antagonists are evident and give rise to expected therapeutic strategies for neurotrauma. Piperazine derivatives bearing a "cache-oreilles" (ear-muff) electronic distribution are able to inhibit in vitro PAF effects and, thus, could be used in pathologies where this mediator is involved. Therefore, their potential anti-HIV activity was investigated, and we find that (i) these PAF antagonists are effectively active in HIV-infected monocyte-derived macrophages (MDM) but there is no correlation between both anti-HIV and anti-PAF activities; (ii) the presence of a carbamate function (compounds 1a-d) is favorable to the antiviral activity; (iii) the lipophilicity of the substituent on the piperazinic cycle seems to be less important for the anti-PAF activity than for the antiviral one. Our leading compound, PMS 601 (compound la), presents a dual activity with IC50 of 8 and 11 mu M for anti-PAF and anti-HIV activity, respectively, without cytotoxic events at 1000 mu M in MDM. Although its mode of action is not clearly defined, these data suggest that PMS 601, which displays no effect on acellular reverse transcriptase or protease tests, deserves further investigation in the treatment of HIV-1-associated dementia.

  DOI：

  10.1021/jm9911276

文献信息

• Piperazine derivatives inhibiting human immunodeficiency virus replication
  申请人：Universite Paris 7 - Denis Diderot

  公开号：US06531476B1

  公开（公告）日：2003-03-11

  The invention concerns the use of a piperazine derivative of formula (I) wherein: A and B=C═O, C═S or CR7R8 with R7=H, methyl, cyano, cyanomethyl, CO2CH3 or (C═O)CH3 and R8=H or phenyl; R1 to R6=H, OH, or C1-C5 alkoxy; X represents: either C═O, O(C═O), O(C═S), O(SO2), NH(C═O), NH(C═S), NH(SO2), S(C═O) or S(C═S), then Y=NR9R10, CR9R10R11 in which R9, R10 and R11=H, C1-C5 alkyl, C2-C5 alkenyl, or C2-C5 alkynyl or Y=nitrogenous heterocycle comprising 5 to 10 atoms; or X represents O, S, O(C═O)O, NH(C═O)O, or S(C═O)O, then Y=CR9R10R11 with R9, R10, R11 as above; or one of its pharmaceutically acceptable salts for preparing a medicine inhibiting HIV. The invention is useful for treating HIV infection.

  这项发明涉及使用式（I）的哌嗪衍生物，其中：A和B=C═O，C═S或CR7R8，其中R7=H，甲基，氰基，氰甲基，CO2CH3或（C═O）CH3，R8=H或苯基；R1至R6=H，OH或C1-C5烷氧基；X代表：C═O，O（C═O），O（C═S），O（SO2），NH（C═O），NH（C═S），NH（SO2），S（C═O）或S（C═S），然后Y=NR9R10，CR9R10R11，其中R9，R10和R11=H，C1-C5烷基，C2-C5烯基或C2-C5炔基或Y=含有5至10个原子的氮杂环；或X代表O，S，O（C═O）O，NH（C═O）O或S（C═O）O，然后Y=CR9R10R11，其中R9，R10，R11如上；或其制备药用可接受的盐之一，用于制备抑制HIV的药物。这项发明对治疗HIV感染很有用。
• DERIVES DE LA PIPERAZINE POUR L'INHIBITION DE LA REPLICATION DU VIRUS DE L'IMMUNODEFICIENCE HUMAINE
  申请人：UNIVERSITE PARIS 7 - Denis DIDEROT

  公开号：EP1095029B1

  公开（公告）日：2002-09-18
• US6531476B1
  申请人：——

  公开号：US6531476B1

  公开（公告）日：2003-03-11
• Structure−Activity Relationships in Platelet-Activating Factor (PAF). 10. From PAF Antagonism to Inhibition of HIV-1 Replication
  作者：Nawal Serradji、Okkacha Bensaid、Marc Martin、Erwan Kan、Nathalie Dereuddre-Bosquet、Catherine Redeuilh、Jack Huet、Françoise Heymans、Aazdine Lamouri、Pascal Clayette、Chang Zhi Dong、Dominique Dormont、Jean-Jacques Godfroid

  DOI：10.1021/jm9911276

  日期：2000.6.1

  Excessive levels of PAF and cells of macrophage lineage appear to play an important role in neuronal cell injury, inflammatory syndrome, and HIV replication in CNS resulting in AIDS dementia complex (ADC). The beneficial effects of PAF receptor antagonists are evident and give rise to expected therapeutic strategies for neurotrauma. Piperazine derivatives bearing a "cache-oreilles" (ear-muff) electronic distribution are able to inhibit in vitro PAF effects and, thus, could be used in pathologies where this mediator is involved. Therefore, their potential anti-HIV activity was investigated, and we find that (i) these PAF antagonists are effectively active in HIV-infected monocyte-derived macrophages (MDM) but there is no correlation between both anti-HIV and anti-PAF activities; (ii) the presence of a carbamate function (compounds 1a-d) is favorable to the antiviral activity; (iii) the lipophilicity of the substituent on the piperazinic cycle seems to be less important for the anti-PAF activity than for the antiviral one. Our leading compound, PMS 601 (compound la), presents a dual activity with IC50 of 8 and 11 mu M for anti-PAF and anti-HIV activity, respectively, without cytotoxic events at 1000 mu M in MDM. Although its mode of action is not clearly defined, these data suggest that PMS 601, which displays no effect on acellular reverse transcriptase or protease tests, deserves further investigation in the treatment of HIV-1-associated dementia.