甲基2-{甲基[1-({5-[(甲磺酰)氨基]-1H-吲哚-2-基}羰基)哌啶-4-基]氨基}吡啶-3-羧酸酯 | 179557-42-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: 甲基2-{甲基[1-({5-[(甲磺酰)氨基]-1H-吲哚-2-基}羰基)哌啶-4-基]氨基}吡啶-3-羧酸酯
• 英文名称: 3-Pyridinecarboxylic acid, 2-(methyl(1-((5-((methylsulfonyl)amino)-1H-indol-2-yl)carbonyl)-4-piperidinyl)amino)-, methyl ester
• 英文别名: methyl 2-[[1-[5-(methanesulfonamido)-1H-indole-2-carbonyl]piperidin-4-yl]-methylamino]pyridine-3-carboxylate
• CAS: 179557-42-7
• 化学式: C₂₃H₂₇N₅O₅S
• 分子量: 485.564
• InChiKey: VUIHMLIDUYCGNJ-UHFFFAOYSA-N

物化性质

• 沸点：
  721.8±70.0 °C(Predicted)
• 密度：
  1.419±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  34
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  133
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  1-苄基-4-甲氨基哌啶 在 palladium dihydroxide 氢气 、 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 27.0h， 生成 甲基2-{甲基[1-({5-[(甲磺酰)氨基]-1H-吲哚-2-基}羰基)哌啶-4-基]氨基}吡啶-3-羧酸酯
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of the (Alkylamino)piperidine-Containing BHAP Class of Non-Nucleoside Reverse Transcriptase Inhibitors:  Effect of 3-Alkylpyridine Ring Substitution

  摘要：

  Development of resistance to currently approved HIV therapies has continued to fuel research efforts to improve the metabolic stability and spectrum of activity of the (alkyl amino)piperidine containing bis(heteroaryl)piperazine (AAP-BHAP) class of non-nucleoside reverse transcriptase inhibitors (NNRTIs). The synthesis of analogues in which the usual 3-alkylamino substituent on the pyridine ring is replaced by a 3-alkyl substituent led to compounds which retained activity against recombinant P236L and wild-type (WT) reverse transcriptase (RT), while inhibition of the Y181C mutant RT was reduced relative to the activity of the 3-alkylamino-substituted congeners. Testing of representative analogues in an in vitro liver microsome assay indicated that the alkyl substituent would not appreciably improve the metabolic stability of the AAP-BHAP template. In vivo pharmacokinetic evaluation of three compounds confirmed these results in that high systemic clearances were observed. Nevertheless, one compound (13), PNU-103657, possessed oral bioavailability in rats approaching that of the structurally related NNRTI drug delavirdine which is currently on the market for the treatment of HIV infection.

  DOI：

  10.1021/jm990051a

文献信息

• Synthesis and Structure−Activity Relationships of the (Alkylamino)piperidine-Containing BHAP Class of Non-Nucleoside Reverse Transcriptase Inhibitors:  Effect of 3-Alkylpyridine Ring Substitution
  作者：Michael J. Genin、Toni J. Poel、Paul D. May、Laurice A. Kopta、Yoshihiko Yagi、Robert A. Olmsted、Janice M. Friis、Richard L. Voorman、Wade J. Adams、Richard C. Thomas、Donna L. Romero

  DOI：10.1021/jm990051a

  日期：1999.10.1

  Development of resistance to currently approved HIV therapies has continued to fuel research efforts to improve the metabolic stability and spectrum of activity of the (alkyl amino)piperidine containing bis(heteroaryl)piperazine (AAP-BHAP) class of non-nucleoside reverse transcriptase inhibitors (NNRTIs). The synthesis of analogues in which the usual 3-alkylamino substituent on the pyridine ring is replaced by a 3-alkyl substituent led to compounds which retained activity against recombinant P236L and wild-type (WT) reverse transcriptase (RT), while inhibition of the Y181C mutant RT was reduced relative to the activity of the 3-alkylamino-substituted congeners. Testing of representative analogues in an in vitro liver microsome assay indicated that the alkyl substituent would not appreciably improve the metabolic stability of the AAP-BHAP template. In vivo pharmacokinetic evaluation of three compounds confirmed these results in that high systemic clearances were observed. Nevertheless, one compound (13), PNU-103657, possessed oral bioavailability in rats approaching that of the structurally related NNRTI drug delavirdine which is currently on the market for the treatment of HIV infection.