Substituded pyrazolylhydrazones: a new class of platelet aggregation inhibitors

Silveira, I. A. F. B; Paulo, L. G; Miranda, A. L. P; Rocha, S. O; Freitas, A. C. C; Barreiro, E. J

Silveira, I. A. F. B; Paulo, L. G; Miranda, A. L. P; Rocha, S. O; Freitas, A. C. C; Barreiro, E. J.

Rev. bras. pesqui. méd. biol ; Braz. j. med. biol. res;24(9): 947-51, Sept. 1991. ilus, tab

Article en En | LILACS | ID: lil-102105

Biblioteca responsable: BR1.1

ABSTRACT

ABSTRACT

A series of 5-pyrazolylhydrazone derivates (I) were designed to be mixed hybrid isosteres of both BW-755C and CBS-1108 which belong to the class of dual cyclooxygenase and 5-lipoxygenase inhibitors. Pharmacological evaluation of some members of this series (Ia, 1-formy 1-3,4-methylenedioxy-6-nitrobenzene-5-(1-phenyl-3-methyl-4-nitropyrazolil)hydrazone; Ib, 2-formylfurane-5-(1-phenyl-3-methyll-4-nitropyrazolyl)hidrazone; Ic, (E)-2-(formylethenylfurane)-5-(1-phenyl-3-methyl-4-nitropyrazolyl)hydrazone showed that they inhibit the in vitro platelet aggregation of citrated platelet-rich rabbit plasma induced by ADP (5µM), collagen (5µg/ml) and arachidonic acid (100 µM). Compounds Ia and Ic at 100 µM concentration showed 49% and 58% inhibition, respectively, of ADP-induced aggregation. In the arachidonic acid-induced aggregation, compounds Ia and Ib at 100 µM concentration fully inhibited platelet aggregation. All compounds significantly inhibited the collagen-induced aggregation. In contrast, indomethacin (10 µM) showed 100% and 85% aggregation inhibition against arachidonic acid and collagen, respectivelym, and was inactive in the ADP- induced aggregation test. These results suggest that the structure-activity relationship in this series of compounds is dependent on the hydrazone moiety at position 5 of the pyrazole ring and on the distance between the aryl ring and the pyrazole ring and that the 2-furyl ring is at the optimal distance for the maximal activity

Asunto(s)

Hidrazonas/química; Técnicas In Vitro; Inhibidores de Agregación Plaquetaria/química; 4,5-dihidro-1-(3-(trifluorometil)fenil)-1H-pirazol-3-amina; Relación Estructura-Actividad

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Colección: 01-internacional Base de datos: LILACS Asunto principal: Técnicas In Vitro / Inhibidores de Agregación Plaquetaria / Hidrazonas Idioma: En Revista: Braz. j. med. biol. res / Rev. bras. pesqui. méd. biol Asunto de la revista: BIOLOGIA / MEDICINA Año: 1991 Tipo del documento: Article / Congress and conference / Project document Pais de publicación: Brasil

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