1394012-10-2Relevant academic research and scientific papers
Synthesis and biological evaluation of sorafenib- and regorafenib-like sEH inhibitors
Hwang, Sung Hee,Wecksler, Aaron T.,Zhang, Guodong,Morisseau, Christophe,Nguyen, Long V.,Fu, Samuel H.,Hammock, Bruce D.
supporting information, p. 3732 - 3737 (2013/07/27)
To reduce the pro-angiogenic effects of sEH inhibition, a structure-activity relationship (SAR) study was performed by incorporating structural features of the anti-angiogenic multi-kinase inhibitor sorafenib into soluble epoxide hydrolase (sEH) inhibitors. The structural modifications of this series of molecules enabled the altering of selectivity towards the pro-angiogenic kinases C-RAF and vascular endothelial growth factor receptor-2 (VEGFR-2), while retaining their sEH inhibition. As a result, sEH inhibitors with greater potency against C-RAF and VEGFR-2 were obtained. Compound 4 (t-CUPM) possesses inhibition potency higher than sorafenib towards sEH but similar against C-RAF and VEGFR-2. Compound 7 (t-CUCB) selectively inhibits sEH, while inhibiting HUVEC cell proliferation, a potential anti-angiogenic property, without liver cancer cell cytotoxicity. The data presented suggest a potential rational approach to control the angiogenic responses stemming from sEH inhibition.
SORAFENIB DERIVATIVES AS sEH INHIBITORS
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Page/Page column 58, (2012/09/10)
The present invention provides compounds for the inhibition of soluble epoxide hydrolase and associated disease conditions.
