Thiadiazoline- and Pyrazoline-Based Carboxamides and Carbothioamides: Synthesis and Inhibition against Nitric Oxide Synthase
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AuthorArias Bordajandi, Fabio; Camacho Quesada, Encarnación; Carrión Peregrina, María Dora; Chayah Ghaddab, Meriem; Romero Pérez, Miguel; Duarte Pérez, Juan Manuel; Gallo Mezo, Miguel Ángel
Hindawi Publishing Corporation
Arias Bordajandi, Fabio; et. al. Thiadiazoline- and Pyrazoline-Based Carboxamides and Carbothioamides: Synthesis and Inhibition against Nitric Oxide Synthase. Journal of Chemistry Volume 2018, Article ID 9242616, 15 pages [http://hdl.handle.net/10481/51156]
SponsorshipThis work was partially supported by the Instituto de Salud Carlos III through Grant FI11/00432.
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 μM). 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 μM) and the most potent of all tested compounds.