1-butylsulfonylindole-3-carboxylic acid | 1266348-80-4

• 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
• 英文名称: 1-butylsulfonylindole-3-carboxylic acid
• CAS: 1266348-80-4
• 化学式: C₁₃H₁₅NO₄S
• 分子量: 281.332
• InChiKey: VRMBQPFHKGXDFF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.32
• 重原子数：
  19.0
• 可旋转键数：
  5.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  76.37
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为产物：
  描述：

  1-Butylsulfonylindole-3-carbaldehyde 在 sodium chlorite 、 HO₄P^(1-)*Na⁽¹⁺⁾ 、 异丁烯 作用下， 以 四氢呋喃 、 叔丁醇 为溶剂， 反应 24.0h， 生成 1-butylsulfonylindole-3-carboxylic acid
  参考文献：
  名称：

  Synthesis and SAR of indole-and 7-azaindole-1,3-dicarboxamide hydroxyethylamine inhibitors of BACE-1

  摘要：

  Heterocyclic replacement of the isophthalamide phenyl ring in hydroxyethylamine (HEA) BACE-1 inhibitors was explored. A variety of indole-1,3-dicarboxamide HEAs exhibited potent BACE-1 enzyme inhibition, but displayed poor cellular activity. Improvements in cellular activity and aspartic protease selectivity were observed for 7-azaindole-1,3-dicarboxamide HEAs. A methylprolinol-bearing derivative (10n) demonstrated robust reductions in rat plasma A beta levels, but did not lower rat brain A beta due to poor central exposure. The same analog exhibited a high efflux ratio in a bidirectional Caco-2 assay and was likely a substrate of the efflux transporter P-glycoprotein. X-ray crystal structures are reported for two indole HEAs in complex with BACE-1. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.10.079

文献信息

• Synthesis and SAR of indole-and 7-azaindole-1,3-dicarboxamide hydroxyethylamine inhibitors of BACE-1
  作者：Lawrence R. Marcin、Mendi A. Higgins、F. Christopher Zusi、Yunhui Zhang、Michael F. Dee、Michael F. Parker、Jodi K. Muckelbauer、Daniel M. Camac、Paul E. Morin、Vidhyashankar Ramamurthy、Andrew J. Tebben、Kimberley A. Lentz、James E. Grace、Jovita A. Marcinkeviciene、Lisa M. Kopcho、Catherine R. Burton、Donna M. Barten、Jeremy H. Toyn、Jere E. Meredith、Charles F. Albright、Joanne J. Bronson、John E. Macor、Lorin A. Thompson

  DOI：10.1016/j.bmcl.2010.10.079

  日期：2011.1

  Heterocyclic replacement of the isophthalamide phenyl ring in hydroxyethylamine (HEA) BACE-1 inhibitors was explored. A variety of indole-1,3-dicarboxamide HEAs exhibited potent BACE-1 enzyme inhibition, but displayed poor cellular activity. Improvements in cellular activity and aspartic protease selectivity were observed for 7-azaindole-1,3-dicarboxamide HEAs. A methylprolinol-bearing derivative (10n) demonstrated robust reductions in rat plasma A beta levels, but did not lower rat brain A beta due to poor central exposure. The same analog exhibited a high efflux ratio in a bidirectional Caco-2 assay and was likely a substrate of the efflux transporter P-glycoprotein. X-ray crystal structures are reported for two indole HEAs in complex with BACE-1. (C) 2010 Elsevier Ltd. All rights reserved.