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    • 6. 发明申请
    • Methodology for preparing combinatorial libraries based upon a bicyclic scaffold
    • 基于双环支架制备组合文库的方法
    • US20050176683A1
    • 2005-08-11
    • US11005098
    • 2004-12-06
    • David HangauerMohamed Al-Zahaby
    • David HangauerMohamed Al-Zahaby
    • A61K31/4188A61K31/675A61K31/69C07D20060101C07D487/04G01N33/53
    • C40B40/04C07D487/04C40B50/14
    • The present invention relates to tetrahydro-pyrrolo[1,2-a]imidazole-2,5-dione derivative compounds, hexahydro-pyrrolo[1,2-a]pyrimidine-2,6-dione derivative compounds, and combinatorial libraries comprising such compounds. The present invention also relates to methods of preparing such compounds. The methods first involve providing a functionalized resin solid support. Next, the functionalized resin solid support is reacted with amino acids under conditions effective to produce a resin bound dipeptide or tripeptide alcohol intermediate compound. Then, the resin bound dipeptide or tripeptide alcohol intermediate compound is oxidized under conditions effective to convert the resin bound dipeptide or tripeptide alcohol intermediate compound to a resin bound dipeptide or tripeptide aldehyde intermediate compound. Finally, the resin bound dipeptide or tripeptide aldehyde intermediate compound is cyclized under conditions effective to produce the tetrahydro-pyrrolo[1,2-a]imidazole-2,5-dione derivative or hexahydro-pyrrolo[1,2-a]pyrimidine-2,6-dione derivative compound. The methods can be performed in solid phase, solid/solution phase, or solution phase.
    • 本发明涉及四氢 - 吡咯并[1,2-a]咪唑-2,5-二酮衍生物化合物,六氢 - 吡咯并[1,2-a]嘧啶-2,6-二酮衍生物化合物,以及包含这些化合物的组合文库 化合物。 本发明还涉及制备这些化合物的方法。 该方法首先涉及提供官能化的树脂固体支持物。 接下来,官能化树脂固体支持物在有效产生树脂结合二肽或三肽醇中间体化合物的条件下与氨基酸反应。 然后,树脂结合的二肽或三肽醇中间体化合物在有效将树脂结合的二肽或三肽醇中间体化合物转化为树脂结合的二肽或三肽醛中间体化合物的条件下被氧化。 最后,将树脂结合的二肽或三肽醛中间体化合物在有效产生四氢 - 吡咯并[1,2-a]咪唑-2,5-二酮衍生物或六氢 - 吡咯并[1,2-a] 2,6-二酮衍生物。 该方法可以在固相,固相/溶液相或溶液相中进行。