methyl 1-(4-fluorobenzyl)-3-iodo-1H-pyrrolo[2,3-c]pyridine-5-carboxylate | 1261530-70-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯并吡啶类
• 英文名称: methyl 1-(4-fluorobenzyl)-3-iodo-1H-pyrrolo[2,3-c]pyridine-5-carboxylate
• 英文别名: Methyl 1-[(4-fluorophenyl)methyl]-3-iodopyrrolo[2,3-c]pyridine-5-carboxylate
• CAS: 1261530-70-4
• 化学式: C₁₆H₁₂FIN₂O₂
• 分子量: 410.186
• InChiKey: HJMVPMKUWCLMNQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(2-methoxyethoxy)prop-1-yne 、 methyl 1-(4-fluorobenzyl)-3-iodo-1H-pyrrolo[2,3-c]pyridine-5-carboxylate 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以72%的产率得到methyl 1-(4-fluorobenzyl)-3-(3-(2-methoxyethoxy)prop-1-ynyl)-1H-pyrrolo[2,3-c]pyridine-5-carboxylate
  参考文献：
  名称：

  Azaindole N-methyl hydroxamic acids as HIV-1 integrase inhibitors-II. The impact of physicochemical properties on ADME and PK

  摘要：

  HIV-1 integrase is one of three enzymes encoded by the HIV genome and is essential for viral replication, and HIV-1 IN inhibitors have emerged as a new promising class of therapeutics. Recently, we reported the discovery of azaindole hydroxamic acids that were potent inhibitors of the HIV-1 IN enzyme. N-Methyl hydroxamic acids were stable against oxidative metabolism, however were cleared rapidly through phase 2 glucuronidation pathways. We were able to introduce polar groups at the beta-position of the azaindole core thereby altering physical properties by lowering calculated log D values (c Log D) which resulted in attenuated clearance rates in human hepatocytes. Pharmacokinetic data in dog for representative compounds demonstrated moderate oral bioavailability and reasonable half-lives. These ends were accomplished without a large negative impact on enzymatic and antiviral activity, thus suggesting opportunities to alter clearance parameters in future series. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.10.022
• 作为产物：
  描述：

  methyl 1-(4-fluorobenzyl)-1H-pyrrolo[2,3-c]pyridine-5-carboxylate 在 N-碘代丁二酰亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以85%的产率得到methyl 1-(4-fluorobenzyl)-3-iodo-1H-pyrrolo[2,3-c]pyridine-5-carboxylate
  参考文献：
  名称：

  Azaindole N-methyl hydroxamic acids as HIV-1 integrase inhibitors-II. The impact of physicochemical properties on ADME and PK

  摘要：

  HIV-1 integrase is one of three enzymes encoded by the HIV genome and is essential for viral replication, and HIV-1 IN inhibitors have emerged as a new promising class of therapeutics. Recently, we reported the discovery of azaindole hydroxamic acids that were potent inhibitors of the HIV-1 IN enzyme. N-Methyl hydroxamic acids were stable against oxidative metabolism, however were cleared rapidly through phase 2 glucuronidation pathways. We were able to introduce polar groups at the beta-position of the azaindole core thereby altering physical properties by lowering calculated log D values (c Log D) which resulted in attenuated clearance rates in human hepatocytes. Pharmacokinetic data in dog for representative compounds demonstrated moderate oral bioavailability and reasonable half-lives. These ends were accomplished without a large negative impact on enzymatic and antiviral activity, thus suggesting opportunities to alter clearance parameters in future series. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.10.022