Contributions to the development of new substitution patterns of penicillins: synthesis of new penicillins derivatives and evaluation of their porcine pancreatic elastase inhibitory activity

BOSCHETTI,; MATA, E. G.; MASCARETTI, O. A.; CRICCO, J. A.; GABRIELA COUX; LODEYRO, A. F.; ROVERI, O. A.

Journal of the Brazilian Chemical Society

J. Braz. Chem. Soc.

Año: 1996 vol. 7 p. 1 - 6

0103-5053

The synthesis of 6α-chloropenicillanate sulfone esters 6a-c, 12, the acetate and benzoate of 3α-hydroxymethyl-6α-chloropenam sulfones 8a-b and pivaloyloxymethyl and benzyl esters of several 6α-(sulfonyl)oxypenicillanate sulfones 15, 18a1-a3, 18b1-b3 are reported. When tested as inhibitors of porcine pancreatic elastase, the acetate of 3α-hydroxymethylpenam 8a proved to be more active in comparison with the esters of 3α-carboxylic acid counterparts 6a-c and 12. Compounds with diverse 6α-(sulfonyl)oxy substituents showed elastase inhibitory activity improved over the corresponding 6α-chloro derivatives 6a-c and 12; among those, compounds 18a2 and 18b2 were rather unstable, but compounds 18a1, 18a3, 18b1, 18b3 combined fair activity with better stability.