methyl 1-(4-fluorobenzyl)-1H-pyrrole-2-carboxylate | 1256291-05-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: methyl 1-(4-fluorobenzyl)-1H-pyrrole-2-carboxylate
• 英文别名: methyl 1-[(4-fluorophenyl)methyl]pyrrole-2-carboxylate
• CAS: 1256291-05-0
• 化学式: C₁₃H₁₂FNO₂
• 分子量: 233.242
• InChiKey: ACUFSHCHBVFGSM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  31.2
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 1-(4-fluorobenzyl)-1H-pyrrole-2-carboxylate 在 sodium hydroxide 、 盐酸 作用下， 以 甲醇 、 水 为溶剂， 反应 3.0h， 以88%的产率得到1-[(4-fluorophenyl)methyl]-1H-pyrrole-2-carboxylic acid
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Novel Hybrid Dicaffeoyltartaric/Diketo Acid and Tetrazole-Substituted l-Chicoric Acid Analogue Inhibitors of Human Immunodeficiency Virus Type 1 Integrase

  摘要：

  Fourteen analogues of the anti-HIV-1 integrase (IN) inhibitor L-chicoric acid (L-CA) were prepared. Their IC50 values for 3'-end processing and strand transfer against recombinant HIV-1 IN were determined in vitro, and their cell toxicities and EC50 against HIV-1 were measured in cells (ex vivo). Compounds 1-6 are catechol/beta-diketoacid hybrids, the majority of which exhibit submicromolar potency against 3'-end processing and strand transfer, though only with modest antiviral activities. Compounds 7-10 are L-CA/p-fluorobenzylpyrroloyl hybrids, several of which were more potent against strand transfer than 3'-end processing, a phenomenon previously attributed to the beta-diketo acid pharmacophore. Compounds 11-14 are tetrazole bioisosteres of L-CA and its analogues, whose in vitro potencies were comparable to L-CA but with enhanced antiviral potency. The trihydroxyphenyl analogue 14 was 30-fold more potent than L-CA at relatively nontoxic concentrations. These data indicate that L-CA analogues are attractive candidates for development into clinically relevant inhibitors of HIV-1 IN.

  DOI：

  10.1021/jm1010594
• 作为产物：
  描述：

  2-吡咯甲酸甲酯 、 4-氟溴苄 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 0.5h， 以94%的产率得到methyl 1-(4-fluorobenzyl)-1H-pyrrole-2-carboxylate
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Novel Hybrid Dicaffeoyltartaric/Diketo Acid and Tetrazole-Substituted l-Chicoric Acid Analogue Inhibitors of Human Immunodeficiency Virus Type 1 Integrase

  摘要：

  Fourteen analogues of the anti-HIV-1 integrase (IN) inhibitor L-chicoric acid (L-CA) were prepared. Their IC50 values for 3'-end processing and strand transfer against recombinant HIV-1 IN were determined in vitro, and their cell toxicities and EC50 against HIV-1 were measured in cells (ex vivo). Compounds 1-6 are catechol/beta-diketoacid hybrids, the majority of which exhibit submicromolar potency against 3'-end processing and strand transfer, though only with modest antiviral activities. Compounds 7-10 are L-CA/p-fluorobenzylpyrroloyl hybrids, several of which were more potent against strand transfer than 3'-end processing, a phenomenon previously attributed to the beta-diketo acid pharmacophore. Compounds 11-14 are tetrazole bioisosteres of L-CA and its analogues, whose in vitro potencies were comparable to L-CA but with enhanced antiviral potency. The trihydroxyphenyl analogue 14 was 30-fold more potent than L-CA at relatively nontoxic concentrations. These data indicate that L-CA analogues are attractive candidates for development into clinically relevant inhibitors of HIV-1 IN.

  DOI：

  10.1021/jm1010594

文献信息

• Design, Synthesis, and Biological Evaluation of Novel Hybrid Dicaffeoyltartaric/Diketo Acid and Tetrazole-Substituted <scp>l</scp>-Chicoric Acid Analogue Inhibitors of Human Immunodeficiency Virus Type 1 Integrase
  作者：David C. Crosby、Xiangyang Lei、Charles G. Gibbs、Brenda R. McDougall、W. Edward Robinson、Manfred G. Reinecke

  DOI：10.1021/jm1010594

  日期：2010.11.25

  Fourteen analogues of the anti-HIV-1 integrase (IN) inhibitor L-chicoric acid (L-CA) were prepared. Their IC50 values for 3'-end processing and strand transfer against recombinant HIV-1 IN were determined in vitro, and their cell toxicities and EC50 against HIV-1 were measured in cells (ex vivo). Compounds 1-6 are catechol/beta-diketoacid hybrids, the majority of which exhibit submicromolar potency against 3'-end processing and strand transfer, though only with modest antiviral activities. Compounds 7-10 are L-CA/p-fluorobenzylpyrroloyl hybrids, several of which were more potent against strand transfer than 3'-end processing, a phenomenon previously attributed to the beta-diketo acid pharmacophore. Compounds 11-14 are tetrazole bioisosteres of L-CA and its analogues, whose in vitro potencies were comparable to L-CA but with enhanced antiviral potency. The trihydroxyphenyl analogue 14 was 30-fold more potent than L-CA at relatively nontoxic concentrations. These data indicate that L-CA analogues are attractive candidates for development into clinically relevant inhibitors of HIV-1 IN.