1160554-10-8Relevant academic research and scientific papers
Synthesis and evaluation of 2-(2-arylmorpholino)ethyl esters of ibuprofen hydrochlorides as COX-2 and serotonin reuptake inhibitors
Dou, Jie,Shi, Lei,Hu, Aixi,Dong, Minyu,Xu, Jiangping,Liu, Ailin,Jiang, Yiping
, p. 89 - 95 (2014/03/21)
Based on the positive effects of COX-2 inhibitors on depressive symptoms and the desirable physicochemical and biological properties of the morpholine group, a series of novel 2-(2-arylmorpholino)ethyl esters of ibuprofen hydrochlorides were designed, synthesized, and tested for their COX-2 inhibitory and serotonin reuptake inhibitory activities in vitro. The structure-activity relationships of the 2-(2-arylmorpholino)ethyl esters of ibuprofen hydrochlorides as dual COX-2 and serotonin reuptake inhibitors were determined and discussed in detail. The biological assays indicated that five of the compounds possess good COX-2 selectivity (selectivity index COX-1/COX-2 42.8-158.1). The compound 2-[2-(4-benzyloxyphenyl)morpholino]ethyl 2-(4-iso-butylphenyl)-propanoate hydrochloride (1k) shows better COX-2 inhibitory activity (IC50 = 0.78 μM) than ibuprofen (IC 50 = 7.6 μM), and it simultaneously possesses favorable serotonin reuptake inhibitory activity. A series of novel 2-(2-arylmorpholino)ethyl esters of ibuprofen were tested for their COX-2 inhibitory and serotonin reuptake inhibitory activities in vitro. Most of the compounds possess good COX-2 selectivity. Compound 1k shows better COX-2 inhibitory activity than ibuprofen and possesses favorable serotonin reuptake inhibitory activity. According to the results of the biological assays, 2-arylmorpholine-substituted ibuprofen could be used as a core structure to design novel dual COX-2 and serotonin reuptake inhibitors.
Design, synthesis and biological evaluation of 2-(2-aryl-morpholino-4-yl) ethyl esters of indomethacin as potential cyclooxygenase-2 (COX-2) inhibitors
Shi, Lei,Hu, Aixi,Xu, Jiangping,Jiang, Yiping
, p. 1339 - 1344 (2012/08/29)
A number of novel 2-(2-arylmorpholino-4-yl)ethyl 1-(4-chlorobenzoyl)-5- methoxy-2-methyl-1H-indol-3-acetate hydrochlorides were synthesized and tested for their cyclooxygenase (COX-1 and COX-2) inhibition properties in vitro. Many of these compounds exhibited moderate to good selective COX-2 inhibition, and subtle structural changes in the substituents on the side chain of the ester moiety altered the inhibitory properties significantly. 2-[2-(4-Butoxyphenyl) morpholino-4-yl]ethyl 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-acetate hydrochloride (1f), showed good selective COX-2 inhibitory activity (Selective index (SI) 182), which is comparative with celecoxib (SI 214), a COX-2 inhibitor of diarylpyrazoles. While 2-[2-(2,4-dichloro-5-fluorophenyl)morpholino-4-yl] ethyl 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-acetate hydrochloride (1g), showed greater selective COX-2 inhibitory activity (SI 358) than celecoxib. Both compounds were identified as compromising derivatives in this class to reduce the side effects generated by nonsteroidal anti-inflammatory drugs (NSAIDs) indomethacin.
