N,N′-Disubstituted thiourea and urea derivatives: design, synthesis, docking studies and biological evaluation against nitric oxide synthase Chayah Ghaddab, Meriem Camacho Quesada, Encarnación Carrión Peregrina, María Dora Gallo Mezo, Miguel Ángel Romero Pérez, Miguel Duarte Pérez, Juan Manuel Thiourea Urea Nitric oxide synthase The synthesis and biological evaluation of new types of N,N′-disubstituted thiourea and urea derivatives as inhibitors of both neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) are described. These compounds have been designed by reduction of the carbonyl group in the thiourea and urea kynurenamine derivatives 3 previously synthesized by our research group. The synthetic route performed to this new family also allows us to obtain the molecules 3 with less synthetic steps and higher global yield. Regarding the biological results, in general, the new derivatives 4a–q inhibit the neuronal NOS isoform better than the inducible one. Furthermore, thioureas exhibit higher inhibition than ureas for both isoenzymes. Among all the tested compounds, 4g shows significant nNOS (80.6%) and iNOS (76.6%) inhibition values without inhibiting eNOS. This molecule could be an interesting starting point for the design of new inhibitors with application in neurological disorders where both isoenzymes are implicated such as Parkinson's disease. 2017-07-28T11:30:56Z 2017-07-28T11:30:56Z 2016-01-04 info:eu-repo/semantics/article Chayah, M.; et al. N,N′-Disubstituted thiourea and urea derivatives: design, synthesis, docking studies and biological evaluation against nitric oxide synthase. MedChemComm, 7: 667-678 (2016). [http://hdl.handle.net/10481/47297] 2040-2511 http://hdl.handle.net/10481/47297 10.1039/C5MD00477B eng http://creativecommons.org/licenses/by-nc-nd/3.0/ info:eu-repo/semantics/openAccess Creative Commons Attribution-NonCommercial-NoDerivs 3.0 License Royal Society of Chemistry