Diarylmethylenepiperidine (DAMP) 19

• 分子结构分类: 有机化合物 - 苯类化合物 - 二苯并环庚烯
• 英文名称: Diarylmethylenepiperidine (DAMP) 19
• 英文别名: methyl 4-(2-tricyclo[9.4.0.03,8]pentadeca-1(15),3,5,7,9,11,13-heptaenylidene)piperidine-1-carboxylate
• 化学式: C₂₂H₂₁NO₂
• 分子量: 331.414
• InChiKey: YMRCGLNASQTSNZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  25
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  4-氧代哌啶-1-羧酸甲酯 、 5-二苯并环庚烯酮 在 四氢呋喃 、 四氯化钛 、 锌 作用下， 以 四氢呋喃 为溶剂， 反应 14.0h， 以77.9%的产率得到Diarylmethylenepiperidine (DAMP) 19
  参考文献：
  名称：

  Synthesis of substituted diarylmethylenepiperidines (DAMPs), a novel class of anti-HIV agents

  摘要：

  Substituted diarymethylenepiperidines (DAMPs) were synthesized as conformationally restricted analogues of the alkenyldiarylmethane (ADAM) class of non-nucleoside reverse transcriptase inhibitors (NNRTIs). Although, like the ADAMs, the DAMPs were found to inhibit the cytopathic effect of HIV-1(RF) in CEM-SS cells, they were completely inactive as inhibitors of HIV-1 reverse transcriptase. The DAMPs were assessed for inhibition of HIV attachment and fusion. DAMP 14 was active in both assays with IC50 values of 26.5 muM (TI 3.8) and 12.1 muM (TI: > 8), respectively. DAMP 15 also inhibited HIV fusion with all IC50 12.8 muM (TI: > 6), but not virus attachment. However, attempts to verity inhibition of virus attachment and fusion as antiviral targets using time-of-addition experiments failed to confirm these observations, and instead identified all antiviral target Occurring after completion of reverse transcription. DAMPs 11, 12, 14, and 15 were found to inhibit virus replication if added 8 h post virus exposure, and DAMP 11 was equipotent at inhibition of virus replication if added 24 It after Virus addition. DAMPs 11, 12, and 15 did not inhibit virus replication in TNF-alpha induced latently infected U1 cells, a model for post-integrative antiviral targets. When tested in both 3' end-processing and strand-transfer assays in the presence of HIV-1 integrase. none of the DAMPs showed any inhibitory activity, indicating that HIV-1 integrase is not involved in the mechanism of the antiviral action. Thus, the DAMPs are novel conformationally restricted analogues of the previously published ADAM series with all unidentified antiviral target bounded by the completion of reverse transcription and virus integration. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(02)00095-0

文献信息

• Synthesis of substituted diarylmethylenepiperidines (DAMPs), a novel class of anti-HIV agents
  作者：Guozhang Xu、Arunachalam Kannan、Tracy L Hartman、Heather Wargo、Karen Watson、Jim A Turpin、Robert W Buckheit、Allison A Johnson、Yves Pommier、Mark Cushman

  DOI：10.1016/s0968-0896(02)00095-0

  日期：2002.8

  Substituted diarymethylenepiperidines (DAMPs) were synthesized as conformationally restricted analogues of the alkenyldiarylmethane (ADAM) class of non-nucleoside reverse transcriptase inhibitors (NNRTIs). Although, like the ADAMs, the DAMPs were found to inhibit the cytopathic effect of HIV-1(RF) in CEM-SS cells, they were completely inactive as inhibitors of HIV-1 reverse transcriptase. The DAMPs were assessed for inhibition of HIV attachment and fusion. DAMP 14 was active in both assays with IC50 values of 26.5 muM (TI 3.8) and 12.1 muM (TI: > 8), respectively. DAMP 15 also inhibited HIV fusion with all IC50 12.8 muM (TI: > 6), but not virus attachment. However, attempts to verity inhibition of virus attachment and fusion as antiviral targets using time-of-addition experiments failed to confirm these observations, and instead identified all antiviral target Occurring after completion of reverse transcription. DAMPs 11, 12, 14, and 15 were found to inhibit virus replication if added 8 h post virus exposure, and DAMP 11 was equipotent at inhibition of virus replication if added 24 It after Virus addition. DAMPs 11, 12, and 15 did not inhibit virus replication in TNF-alpha induced latently infected U1 cells, a model for post-integrative antiviral targets. When tested in both 3' end-processing and strand-transfer assays in the presence of HIV-1 integrase. none of the DAMPs showed any inhibitory activity, indicating that HIV-1 integrase is not involved in the mechanism of the antiviral action. Thus, the DAMPs are novel conformationally restricted analogues of the previously published ADAM series with all unidentified antiviral target bounded by the completion of reverse transcription and virus integration. (C) 2002 Elsevier Science Ltd. All rights reserved.