Article

1,3,4-Thiadiazole derivatives as selective inhibitors of iNOS versus nNOS: Synthesis and structure-activity dependence.

Departamento de Química Farmacéutica y Orgánica, Facultad de Farmacia, Universidad de Granada, Spain.
European journal of medicinal chemistry (impact factor: 3.27). 02/2012; 50:129-39. DOI:10.1016/j.ejmech.2012.01.047
Source: PubMed

ABSTRACT The synthesis of new compounds with a 1,3,4-thiadiazole structure, and their in vitro biological evaluation as inhibitors of both neuronal and inducible Nitric Oxide Synthase (nNOS and iNOS) is described. These compounds have been designed by an isosteric modification of a series of 4,5-dihydro-1H-pyrazole derivatives, previously described as the nNOS inhibitors. The insertion of the S atom in the heterocyclic ring induces a selective inhibition of the iNOS isoform. Some of these compounds show as iNOS inhibition percentage near of 100% at a concentration of 50 μM, and the IC(50) values measured for the more potent compounds are in a range of 20-40 μM.

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Keywords

1,3,4-thiadiazole structure
 
4,5-dihydro-1H-pyrazole derivatives
 
inducible Nitric Oxide Synthase
 
inhibitors
 
insertion
 
isosteric modification
 
nNOS
 
nNOS inhibitors
 
potent compounds
 
S atom
 
selective inhibition
 
vitro biological evaluation