- 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 of oxadiazoline and quinazolinone derivatives and their biological evaluation as nitric oxide synthase inhibitors
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The synthesis of two new families of compounds with oxadiazoline and quinazolinone structures and their in vitro biological evaluation as inhibitors of both neuronal and inducible nitric oxide synthases (nNOS and iNOS) are described. These derivatives have been obtained from cyclization of substituted benzohydrazides with acid anhydrides followed by reduction, using different synthetic procedures. Their structures were confirmed by high-resolution mass spectroscopy and 1H and 13C nuclear magnetic resonance data. In general, the assayed compounds show better inhibition values of nNOS than of iNOS, being 7d the most active derivative with a quinazolinone scaffold, and 6t the best oxadiazoline one and the best nNOS inhibitor of all tested compounds. The structure–activity relationships are discussed in terms of the effects of the substituents on both 2- and 3-positions of the heterocyclic rings.
- Pineda de las Infantas, M. José,Carrión, M. Dora,Chayah, Mariem,López-Cara, Luisa C.,Gallo, Miguel A.,Acu?a-Castroviejo, Darío,Camacho, M. Encarnación
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p. 1260 - 1273
(2016/07/06)
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- 1,3,4-Thiadiazole derivatives as selective inhibitors of iNOS versus nNOS: Synthesis and structure-activity dependence
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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
- López-Cara, Luisa C.,Carrión, M. Dora,Entrena, Antonio,Gallo, Miguel A.,Espinosa, Antonio,López, Ana,Escames, Germaine,Acu?a-Castroviejo, Darío,Camacho, M. Encarnación
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experimental part
p. 129 - 139
(2012/07/03)
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