Contributions to the Development of New Substitutions Patterns of Penicillins: Synthesis of New Penicillins Derivatives and Evaluation of their Porcine Pancreatic Elastase Inhibitory Activity

CARLOS E. BOSCHETTI; ERNESTO G. MATA; ORESTE A. MASCARETTI; JULIA A. CRICCO; GABRIELA COUX; ANABELLA LODEYRO; OSCAR A. ROVERI

JOURNAL OF THE BRAZILIAN CHEMICAL SOCIETY

Sociedad Brasilera de Química

Lugar: Campinhas (Brasil); Año: 1996 vol. 7 p. 285 - 295

The synthesis of 6a-chloropenicillanate sulfone esters 6a-c, 12, the acetate and benzoate of 3a-hydroxymethyl-6a-chloropenam sulfones 8a-b and pivaloyloxymethyl and benzyl esters of several 6a-(sulfonyl)oxypenicillanate sulfones 15, 18a1-a3, 18b1-b3 are reported. When tested as inhibitors of porcine pancreatic elastase, the acetate of 3a-hydroxymethylpenam 8a proved to be more active in comparison with the esters of 3a-carboxylic acid counterparts 6a-c and 12. Compounds with diverse 6a-(sulfonyl)oxy substituents showed elastase inhibitory activity improved over the corresponding 6a-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.