5-[[[1-[[6-[2-Chloro-4-(methanesulfonamido)phenoxy]-2-methylpyridin-3-yl]methyl]piperidin-4-yl]-(3-fluorophenyl)carbamoyl]amino]pyridine-2-carboxamide | 1344734-53-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-[[[1-[[6-[2-Chloro-4-(methanesulfonamido)phenoxy]-2-methylpyridin-3-yl]methyl]piperidin-4-yl]-(3-fluorophenyl)carbamoyl]amino]pyridine-2-carboxamide
• CAS: 1344734-53-7
• 化学式: C₃₂H₃₃ClFN₇O₅S
• 分子量: 682.175
• InChiKey: WMHUXCUGXVXAJP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  47
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  168
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  6-氯-2-甲基-3-氰基吡啶 在 三乙酰氧基硼氢化钠 、 二异丁基氢化铝 、 caesium carbonate 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 5-[[[1-[[6-[2-Chloro-4-(methanesulfonamido)phenoxy]-2-methylpyridin-3-yl]methyl]piperidin-4-yl]-(3-fluorophenyl)carbamoyl]amino]pyridine-2-carboxamide
  参考文献：
  名称：

  Discovery of novel pyridyl carboxamides as potent CCR5 antagonists and optimization of their pharmacokinetic profile in rats

  摘要：

  A novel series of pyridyl carboxamide-based CCR5 inhibitors was designed, synthesized, and demonstrated to be highly potent against HIV-1 infection in both HOS and PBL assays. Attempts to evaluate this series of compounds in a rat PK model revealed its instability in rat plasma. A hypothesis for this liability was proposed, and strategies to overcome this issue were pursued, leading to discovery of highly potent 40 and 41, which featured dramatically improved rat PK profiles. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.08.080

文献信息

• Discovery of novel pyridyl carboxamides as potent CCR5 antagonists and optimization of their pharmacokinetic profile in rats
  作者：Maosheng Duan、Wieslaw M. Kazmierski、Pek Y. Chong、Felix DeAnda、Mark Edelstein、Rob Ferris、Jennifer Peckham、Pat Wheelan、Zhiping Xiong、Huichang Zhang、Rena Nishizawa、Yoshikazu Takaoka

  DOI：10.1016/j.bmcl.2011.08.080

  日期：2011.11

  A novel series of pyridyl carboxamide-based CCR5 inhibitors was designed, synthesized, and demonstrated to be highly potent against HIV-1 infection in both HOS and PBL assays. Attempts to evaluate this series of compounds in a rat PK model revealed its instability in rat plasma. A hypothesis for this liability was proposed, and strategies to overcome this issue were pursued, leading to discovery of highly potent 40 and 41, which featured dramatically improved rat PK profiles. (C) 2011 Elsevier Ltd. All rights reserved.