US 4,503,040 A · 6-(Aminoacyloxymethyl)penicillanic acid 1,1-dioxides as beta-lactamase inhibitors

Abstract

Beta-lactamase inhibitors which are aminoacid esters of 6-alpha- and 6-beta-(hydroxymethyl)pencillanic acid 1,1-dioxides; pharmaceutically-acceptable salts thereof; conventional esters thereof which are hydrolyzable in vivo; bis-methanediol esters thereof; or mixed methanediol esters with said beta-lactamase inhibitors and sulbactam. Pharmaceutical compositions comprising said beta-lactamase inhibitors and a conventional beta-lactam antibiotic, said compositions useful in the treatment of bacterial infections. Compounds useful as intermediates in the synthesis of said beta-lactamase inhibitors. Antibacterial mixed bis-methanediol esters of said aminoacyloxymethyl penicillanic acid 1,1-dioxides and ampicillin or amoxicillin, also useful in the treatment of bacterial infections; and intermediates therefor.

Claims57

Dependent claims

A compound having the formula ##STR19## wherein R is ##STR20## R.sup.3, R.sup.4 and R.sup.5 are each independently hydrogen or (C.sub.1 -C.sub.3)alkyl;

R.sup.6 is hydrogen, (C.sub.1 -C.sub.6)alkyl, phenyl or benzyl;
or one of said (C.sub.1 -C.sub.6)alkyl, phenyl or benzyl monosubstituted with --OR.sup.3, --SR.sup.8, --SO.sub.2 R.sup.8, --NR.sup.3 R.sup.4, --NHCOR.sup.3, --CONH.sub.2 or --COOR.sup.3 ;
with the proviso that when said substituent is --COOH, n is 1 and R.sup.1 is hydrogen;
R.sup.7 is hydrogen, hydroxy or --OCOR.sup.3 ;
R.sup.8 is (C.sub.1 -C.sub.3)alkyl;
Y is --(CH.sub.2).sub.m --;
--0--, --S--, ##STR21## m is 0, 1 or 2;
and either n is 1 and R.sup.1 is hydrogen, a radical group forming an ester hydrolyzable under physiological conditions, or 1,1-dioxopenicillanoyloxymethyl;
or
n is 2 and R.sup.1 is --CH.sub.2 --;
a pharmaceutically-acceptable acid addition salt thereof, or a pharmaceutically-acceptable cationic salt thereof when n is 1 and R.sup.1 is hydrogen.

8 more elements

Dependencies are inferred from the claim text.

6-(Aminoacyloxymethyl)penicillanic acid 1,1-dioxides as beta-lactamase inhibitors

Life of this patent

6-(Aminoacyloxymethyl)penicillanic acid 1,1-dioxides as beta-lactamase inhibitors

Life of this patent

Abstract

Claims57