Discovery of Dual Target Inhibitors against Cyclooxygenases and Leukotriene A4 Hydrolyase
摘要:
Dual target inhibitors against COX-2. and LTA(4)H were designed by adding functional groups from a marketed COX-2 inhibitor, Nimesulide, to an existing LTA(4)H inhibitor 1-(2-(4-phenoxyphenoxy) ethyl) pyrrolidine. A series of phenoxyphenyl pyrrolidine compounds were synthesized and tested for their inhibition activities using enzyme assays and human whole blood assay. Introduction of small electron withdrawing groups like NO2 and CF3 in the ortho-position of the terminal phenyl ring was found to change the original single target LTA(4)H inhibitor to dual target LTA(4)H and COX-2 inhibitors. Compound 5a and 5m showed dual LTA(4)H and COX-2 inhibition activities in the enzyme assays and the I-EWE assay with IC50 values in the micromolar to submicromolar range. As their activities in HWB assay were comparable to the two starting single target inhibitors, the two compounds are promising for further studies. The strategy used in the current study may be generally applicable to other dual target drug designs.
The present invention relates to a process for the preparation of optionally substituted (N-heterocyclyl) aryl ethers.
本发明涉及一种制备可选取代的(N-杂环基)芳基醚的方法。
HETEROARYL ARYL ETHERS
申请人:Kreis Michael
公开号:US20100174089A1
公开(公告)日:2010-07-08
The present invention relates to a process for the preparation of optionally substituted heteroaryl aryl ethers, in particular of phenoxypyridines.
本发明涉及一种制备可选取代杂环芳基芳醚的方法,特别是苯氧吡啶的制备方法。
Herstellung von (N-Heterozyklyl)-Arylethern
申请人:Saltigo GmbH
公开号:EP2179988A1
公开(公告)日:2010-04-28
Die vorliegende Erfindung betrifft ein Verfahren zur Herstellung von gegebenenfalls substituierten (N-Heterozyklyl)-Arylethem.
本发明涉及一种制备任选取代的(N-杂环基)芳基莱姆的工艺。
Verfahren zur Herstellung von Heteroaryl-Arylethers
申请人:Saltigo GmbH
公开号:EP2179989A2
公开(公告)日:2010-04-28
Die vorliegende Erfindung betrifft ein Verfahren zur Herstellung von gegebenenfalls substituierten Heteroaryl-Arylethern, insbesondere von Phenoxypyridinen.