Some optically active 3-(arylmethylidene)aminoxy- (3a-g, 4a-g) and fluorenylideneaminoxy-2-methylpropionic acids (5, 6), were prepared as analogues of the antiinflammatory arylpropionic acids of type B, in which the aromatic group is substituted by an MAOM moiety. Some of the new compounds. tested in vivo for their antiinflammatory properties by means of the carrageenan-induced paw edema method in rats, exhibited activity indices similar to that shown in the same test by ibuprofen. Compounds 3a.b and 4a,b, for which at least one of the two enantiomers had shown an inhibition value higher than 40% in the in vivo test, were assayed for their in vitro enzymatic inhibitory activity. showing percentage inhibition values between 40 and 50% at a concentration of 10 muM against COX-2: at the same concentration, they appeared to be devoid of any activity towards COX-1. Compounds 3a.b and 4a,b also proved to possess a similar toxicity. The lack of enantioselectivity shown by compounds 3-6 was tentatively explained in terms of a conformational freedom of the enantiomers which allows their quasi-superimposition.

Enantiopure 3-(arylmethylidene)aminoxy-2-methylpropionic acids: synthesis and antiinflammatory properties

LAPUCCI, ANNALINA;NENCETTI, SUSANNA;ORLANDINI, ELISABETTA;RAPPOSELLI, SIMONA;ROSSELLO, ARMANDO;
2001

Abstract

Some optically active 3-(arylmethylidene)aminoxy- (3a-g, 4a-g) and fluorenylideneaminoxy-2-methylpropionic acids (5, 6), were prepared as analogues of the antiinflammatory arylpropionic acids of type B, in which the aromatic group is substituted by an MAOM moiety. Some of the new compounds. tested in vivo for their antiinflammatory properties by means of the carrageenan-induced paw edema method in rats, exhibited activity indices similar to that shown in the same test by ibuprofen. Compounds 3a.b and 4a,b, for which at least one of the two enantiomers had shown an inhibition value higher than 40% in the in vivo test, were assayed for their in vitro enzymatic inhibitory activity. showing percentage inhibition values between 40 and 50% at a concentration of 10 muM against COX-2: at the same concentration, they appeared to be devoid of any activity towards COX-1. Compounds 3a.b and 4a,b also proved to possess a similar toxicity. The lack of enantioselectivity shown by compounds 3-6 was tentatively explained in terms of a conformational freedom of the enantiomers which allows their quasi-superimposition.
Aldo, Balsamo; Simone, Bertini; Giambattista, Gervasi; Lapucci, Annalina; Nencetti, Susanna; Orlandini, Elisabetta; Rapposelli, Simona; Rossello, Armando; Giulio, Soldani
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11568/67771
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? 3
  • Scopus 8
  • ???jsp.display-item.citation.isi??? 7
social impact