- Thiadiazoline- And pyrazoline-based carboxamides and carbothioamides: Synthesis and inhibition against nitric oxide synthase
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Two new families of pyrazoline and thiadiazoline heterocycles have been developed. Their inhibitory activities against two different isoforms of nitric oxide synthase (inducible and neuronal NOS) are reported. The novel derivatives were synthesized combining the arylthiadiazoline or arylpyrazoline skeleton and a carboxamide or carbothioamide moiety, used as starting material ethyl 2-nitrobenzoates or substituted nitrobenzaldehydes, respectively. The structure-activity relationships of final molecules are discussed in terms of the R1 radical effects in the aromatic ring, the Y atom in the heterocyclic system, the X heteroatom in the main chain, and the R2 substituent in the carboxamide or carbothioamide rest. In general, thiadiazolines (5a-e) inhibit preferentially the neuronal isoform; among them, 5a is the best nNOS inhibitor (74.11% at 1 mM, IC50 = 420 M). In contrast, pyrazolines (6a-r) behave better as iNOS than nNOS inhibitors, 6m being the best molecule of this series (76.86% at 1 mM of iNOS inhibition, IC50 = 130 M) and the most potent of all tested compounds.
- Arias, Fabio,Encarnación Camacho,Dora Carrión,Chayah, Meriem,Romero, Miguel,Duarte, Juan,Gallo, Miguel A.
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- Synthesis and biological evaluation of 4,5-dihydro-1H-pyrazole derivatives as potential nNOS/iNOS selective inhibitors. Part 2: Influence of diverse substituents in both the phenyl moiety and the acyl group
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In a preliminary article, we reported a series of 4,5-dihydro-1H-pyrazole derivatives as neuronal nitric oxide synthase (nNOS) inhibitors. Here we present the data about the inhibition of inducible nitric oxide synthase (iNOS) of these compounds. In gener
- Carrión, M. Dora,Chayah, Mariem,Entrena, Antonio,López, Ana,Gallo, Miguel A.,Acu?a-Castroviejo, Darío,Camacho, M. Encarnación
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p. 4132 - 4142
(2013/07/25)
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