200058-85-1Relevant academic research and scientific papers
4-[18F]fluorophenyl ureas via carbamate-4-nitrophenyl esters and 4-[18F]fluoroaniline
Olma, Sebastian,Ermert, Johannes,Coenen, Heinz H.
, p. 1037 - 1050 (2007/10/03)
Four different no carrier added (n.c.a.) 4-[18F]fluorophenylurea derivatives are synthesized as model compounds via two alternative routes. In both cases carbamate-4-nitrophenylesters are used as intermediates. Either n.c.a. 4-[18F]fluoroaniline reacts with carbamates of several amines, or the carbamate of n.c.a. 4-[18F]fluoroaniline is formed at first and an amine is added subsequently to yield the urea derivative. The choice of the appropriate way of reaction depends on the possibilities of precursor synthesis. The radiochemical yields reach up to 80% after 50 min of synthesis time while no radiochemical by-products can be determined. These high yields were possible due to an optimized preparation of n.c.a. 4-[18F] fluoroaniline with a radiochemical yield of up to 90%. From the various ways of its radiosynthesis, the substitution with n.c.a. [18F]fluoride on dinitrobenzene is chosen, using phosphorous acid and palladium black for reduction of the second nitro group. Copyright
Structural refinement of inhibitors of urea-based soluble epoxide hydrolases
Morisseau, Christophe,Goodrow, Marvin H.,Newman, John W.,Wheelock, Craig E.,Dowdy, Deanna L.,Hammock, Bruce D.
, p. 1599 - 1608 (2007/10/03)
The soluble epoxide hydrolase (sEH) is involved in the metabolism of arachidonic, linoleic, and other fatty acid epoxides, endogenous chemical mediators that play an important role in blood pressure regulation and inflammation. 1,3-Disubstituted ureas, carbamates, and amides are new potent and stable inhibitors of sEH. However, the poor solubility of the lead compounds limits their use. Inhibitor structure-activity relationships were investigated to better define the structural requirements for inhibition and to identify points in the molecular topography that could accept polar groups without diminishing inhibition potency. Results indicate that lipophilicity is an important factor controlling inhibitor potency. Polar groups could be incorporated into one of the alkyl groups without loss of activity if they were placed at a sufficient distance from the urea function. The resulting compounds had a 2-fold higher water solubility. These findings will facilitate the rational design and optimization of sEH inhibitors with better physical properties.
