1-(4-fluorobenzyl)-3-(3-(2-methoxyethoxy)propyl)-1H-pyrrolo[2,3-c]pyridine-5-carboxylic acid | 1261531-53-6

• 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: 1-(4-fluorobenzyl)-3-(3-(2-methoxyethoxy)propyl)-1H-pyrrolo[2,3-c]pyridine-5-carboxylic acid
• CAS: 1261531-53-6
• 化学式: C₂₁H₂₃FN₂O₄
• 分子量: 386.423
• InChiKey: SRXOHRVKADOSSH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.52
• 重原子数：
  28.0
• 可旋转键数：
  10.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  73.58
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  1-(4-fluorobenzyl)-3-(3-(2-methoxyethoxy)propyl)-1H-pyrrolo[2,3-c]pyridine-5-carboxylic acid 、 N-甲基羟胺盐酸盐 在 N-甲基吗啉 、 2-氯-4,6-二甲氧基-1,3,5-三嗪 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以47%的产率得到1-(4-fluorobenzyl)-N-hydroxy-3-(3-(2-methoxyethoxy)propyl)-N-methyl-1H-pyrrolo[2,3-c]pyridine-5-carboxamide
  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)-3-(3-(2-methoxyethoxy)propyl)-1H-pyrrolo[2,3-c]pyridine-5-carboxylate 在 lithium hydrochloride monohydrate 、 水 作用下， 以 甲醇 为溶剂， 以94%的产率得到1-(4-fluorobenzyl)-3-(3-(2-methoxyethoxy)propyl)-1H-pyrrolo[2,3-c]pyridine-5-carboxylic acid
  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