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Synthesis and Evaluation of 2‐(2‐ A rylmorpholino)ethyl Esters of Ibuprofen Hydrochlorides as COX ‐2 and Serotonin Reuptake Inhibitors
Author(s) -
Dou Jie,
Shi Lei,
Hu Aixi,
Dong Minyu,
Xu Jiangping,
Liu Ailin,
Jiang Yiping
Publication year - 2014
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201300279
Subject(s) - ibuprofen , chemistry , serotonin , pharmacology , serotonin reuptake inhibitor , reuptake inhibitor , medicine , biochemistry , receptor
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 (IC 50 = 0.78 µM) than ibuprofen (IC 50 = 7.6 µM), and it simultaneously possesses favorable serotonin reuptake inhibitory activity.