5-[[(4S,6R)-2,2-dimethyl-6-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-1,3-dioxan-4-yl]methoxy]-1-(4-fluorophenyl)-4-propan-2-ylpyrazole-3-carboxylic acid | 906645-36-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-[[(4S,6R)-2,2-dimethyl-6-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-1,3-dioxan-4-yl]methoxy]-1-(4-fluorophenyl)-4-propan-2-ylpyrazole-3-carboxylic acid
• CAS: 906645-36-1
• 化学式: C₂₆H₃₅FN₂O₇
• 分子量: 506.572
• InChiKey: PILFMSFMEVOLCH-MOPGFXCFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  36
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  109
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  5-[[(4S,6R)-2,2-dimethyl-6-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-1,3-dioxan-4-yl]methoxy]-1-(4-fluorophenyl)-4-propan-2-ylpyrazole-3-carboxylic acid 、 3-氯苄胺 在 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 生成 tert-butyl 2-((4R,6S)-6-(((3-((3-chlorobenzyl)carbamoyl)-1-(4-fluorophenyl)-4-isopropyl-1H-pyrazol-5-yl)oxy)methyl)-2,2-dimethyl-1,3-dioxan-4-yl)acetate
  参考文献：
  名称：

  Pyrazole inhibitors of HMG-CoA reductase: An attempt to dramatically reduce synthetic complexity through minimal analog re-design

  摘要：

  An extraordinarily potent and hepatoselective class of HMG-CoA reductase inhibitors containing a pyrazole core was recently reported; however, its development was hampered by a long and difficult synthetic route. We attempted to circumvent this obstacle by preparing closely related analogs wherein the key dihydroxyheptanoic acid sidechain was tethered to the pyrazole core via an oxygen linker ('oxypyrazoles'). This minor change reduced the total number of synthetic steps from 14 to 7. Although the resulting analogs maintained much of the in vitro and cell activity of the pyrazoles, inferior in vivo activity precluded further development. Caco-2 cell permeability data suggest that enhanced cellular efflux of the oxypyrazoles relative to the pyrazoles may be responsible for the poor in vivo activity. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.08.004
• 作为产物：
  描述：

  benzyl 5-[[(4S,6R)-2,2-dimethyl-6-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-1,3-dioxan-4-yl]methoxy]-1-(4-fluorophenyl)-4-propan-2-ylpyrazole-3-carboxylate 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 以95%的产率得到5-[[(4S,6R)-2,2-dimethyl-6-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethyl]-1,3-dioxan-4-yl]methoxy]-1-(4-fluorophenyl)-4-propan-2-ylpyrazole-3-carboxylic acid
  参考文献：
  名称：

  Pyrazole inhibitors of HMG-CoA reductase: An attempt to dramatically reduce synthetic complexity through minimal analog re-design

  摘要：

  An extraordinarily potent and hepatoselective class of HMG-CoA reductase inhibitors containing a pyrazole core was recently reported; however, its development was hampered by a long and difficult synthetic route. We attempted to circumvent this obstacle by preparing closely related analogs wherein the key dihydroxyheptanoic acid sidechain was tethered to the pyrazole core via an oxygen linker ('oxypyrazoles'). This minor change reduced the total number of synthetic steps from 14 to 7. Although the resulting analogs maintained much of the in vitro and cell activity of the pyrazoles, inferior in vivo activity precluded further development. Caco-2 cell permeability data suggest that enhanced cellular efflux of the oxypyrazoles relative to the pyrazoles may be responsible for the poor in vivo activity. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.08.004