N,N′-Disubstituted thiourea and urea derivatives: design, synthesis, docking studies and biological evaluation against nitric oxide synthase

MedChemComm
2016.0

Abstract

The synthesis and biological evaluation of a new type of N,N'-disubstituted thiourea and urea derivatives as inhibitors of both neuronal and inducible nitric oxide synthase (nNOS and 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 better the neuronal NOS isoform 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 disease.

Knowledge Graph

Similar Paper

N,N′-Disubstituted thiourea and urea derivatives: design, synthesis, docking studies and biological evaluation against nitric oxide synthase
MedChemComm 2016.0
Design and synthesis of urea and thiourea derivatives and their inhibitory activities on lipopolysaccharide-induced NO production
Bioorganic & Medicinal Chemistry Letters 2007.0
Design, synthesis, and evaluation of potential inhibitors of nitric oxide synthase
Bioorganic & Medicinal Chemistry 2008.0
Synthesis and in vitro urease inhibitory activity of N,N′-disubstituted thioureas
European Journal of Medicinal Chemistry 2014.0
Disubstituted thiourea derivatives and their activity on CNS: Synthesis and biological evaluation
European Journal of Medicinal Chemistry 2012.0
Synthesis and biological evaluation of 3-benzyl-1-methyl- and 1-methyl-3-phenyl-isothioureas as potential inhibitors of iNOS
Bioorganic & Medicinal Chemistry Letters 2005.0
Synthesis, bioevaluation and docking studies of new imidamide derivatives as nitric oxide synthase inhibitors
Bioorganic & Medicinal Chemistry 2021.0
N-Substituted acetamidines and 2-methylimidazole derivatives as selective inhibitors of neuronal nitric oxide synthase
Bioorganic & Medicinal Chemistry Letters 2010.0
Synthesis and biological evaluation of indazole derivatives
European Journal of Medicinal Chemistry 2011.0
Solution-phase microwave assisted parallel synthesis, biological evaluation and in silico docking studies of N,N′-disubstituted thioureas derived from 3-chlorobenzoic acid
Bioorganic & Medicinal Chemistry 2016.0