3-{[(2R)-2-(aminocarbonyl)pyrrolidin-1-yl]methyl}-1-(4-fluorobenzyl)-N-hydroxy-N-methyl-1H-pyrrolo[2,3-c]pyridine-5-carboxamide | 1261530-88-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 3-{[(2R)-2-(aminocarbonyl)pyrrolidin-1-yl]methyl}-1-(4-fluorobenzyl)-N-hydroxy-N-methyl-1H-pyrrolo[2,3-c]pyridine-5-carboxamide
• 英文别名: 3-[[(2R)-2-carbamoylpyrrolidin-1-yl]methyl]-1-[(4-fluorophenyl)methyl]-N-hydroxy-N-methyl-pyrrolo[2,3-c]pyridine-5-carboxamide；3-[[(2R)-2-carbamoylpyrrolidin-1-yl]methyl]-1-[(4-fluorophenyl)methyl]-N-hydroxy-N-methylpyrrolo[2,3-c]pyridine-5-carboxamide
• CAS: 1261530-88-4
• 化学式: C₂₂H₂₄FN₅O₃
• 分子量: 425.463
• InChiKey: XGYYVDZJWSDWDE-LJQANCHMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  105
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  methyl 3-{[(2R)-2-(aminocarbonyl)pyrrolidin-1-yl]methyl}-1-(4-fluorobenzyl)-1H-pyrrolo [2,3-c]pyridine-5-carboxylate 、 N-甲基羟胺盐酸盐 在 sodium methylate 作用下， 以 甲醇 为溶剂， 以233 mg的产率得到3-{[(2R)-2-(aminocarbonyl)pyrrolidin-1-yl]methyl}-1-(4-fluorobenzyl)-N-hydroxy-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

文献信息

• [EN] INHIBITORS OF THE HIV INTEGRASE ENZYME<br/>[FR] INHIBITEURS DE L'ENZYME INTEGRASE DU VIH
  申请人：PFIZER

  公开号：WO2006027694A1

  公开（公告）日：2006-03-16

  The present invention relates to compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, pharmaceutical compositions comprisingm compounds of formula (I), and their methods of use in treating HIV-infected mammals.

  本发明涉及公式(I)的化合物，或其药物可接受的盐或溶剂化物，包含公式(I)化合物的药物组合物，以及它们在治疗HIV感染哺乳动物中的用途方法。
• Inhibitors of the Hiv Integrase Enzyme
  申请人：Dress Ruprecht Klaus

  公开号：US20070232644A1

  公开（公告）日：2007-10-04

  The present invention relates to compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, pharmaceutical compositions comprising compounds of formula (I), and their methods of use in treating HIV-infected mammals.

  本发明涉及公式(I)的化合物，或其药学上可接受的盐或溶剂，包括公式(I)的化合物的制药组合物，以及它们在治疗感染HIV的哺乳动物中的使用方法。