6-substituted penicillanic acid 1,1-dioxide compounds

Claim 2

A penicillanic acid 1,1-dioxide compound selected from the group consisting of ##STR13## and the pharamaceutically-acceptable base salts thereof, and the pharmaceutically-acceptable esters thereof readily hydrolyzable in vivo, wherein R 1 is selected from the group consisting of hydrogen and alkyl having 1 to 4 carbons; X is selected from the group consisting of hydroxy, alkanoyloxy having 2 to 5 carbon atoms and amino; and said pharmaceutically-acceptable esters thereof readily hydrolyzable in vivo are formed from an ester-forming radical selected from the group consisting of 3-phthalidyl, 4-crotonolactonyl, gamma-butyrolacton-4-yl and --CH(R 4 )--O--C(═O)--R 5 , wherein R 4 is hydrogen, methyl or ethyl and R 5 is alkyl of 1 to 5 carbons or alkoxy of 1 to 5 carbons.

Claim 3

A compound according to claim 1 of the formula ##STR14## and said pharmaceutically-acceptable base salts thereof, and the pharmaceutically-acceptable esters thereof readily hydrolyzable in vivo.

Claim 4

A compound according to claim 2, wherein R 1 is said alkyl.

Claim 5

A compound according to claim 3, wherein X is hydroxy.

Claim 6

A compound according to claim 4, wherein R 1 is methyl.

Claim 7

A compound according to claim 3, wherein X is amino.

Claim 8

A compound according to claim 6, wherein R 1 is methyl.

Claim 9

A compound according to claim 1 of the formula ##STR15## and said pharmaceutically-acceptable base salts thereof, and the pharmaceutically-acceptable esters thereof readily hydrolyzable in vivo.

Claim 10

A compound according to claim 8, wherein R 1 is said alkyl.

Claim 11

A compound according to claim 9, wherein X is amino.

Claim 12

A compound according to claim 10, wherein R 1 is ethyl.

Claim 13

In a method of treating a bacterial infection caused by a beta-lactamase producing microorganism in a mammalian subject with a beta-lactam antibiotic selected from the group consisting of penicillin G, penicillin V, ampicillin, amoxicillin, carbenicillin, bacampicillin, cephalothin, cefazolin and cefoperazone, and the pharmaceutically-acceptable salt thereof, the improvement which comprises: co-administering with said beta-lactam antibiotic to said mammalian subject an effective beta-lactamase inhibiting amount of a penicillanic acid 1,1-dioxide compound selected from the group consisting of ##STR16## and the pharmaceutically-acceptable base salts thereof, and the pharmaceutically-acceptable esters thereof readily hydrolyzable in vivo, wherein R 1 is selected from the group consisting of hydrogen and alkyl having 1 to 4 carbons; X is selected from the group consisting of hydroxy, alkanoyloxy having 2 to 5 carbon atoms and amino; and said pharmaceutically-acceptable esters thereof readily hydrolyzable in vivo are formed from an ester-forming radical selected from the group consisting of 3-phthalidyl, 4-crotonolactonyl, gamma-butyrolacton-4-yl and --CH(R 4 )--O--C(═O)--R 5 , wherein R 4 is hydrogen, methyl or ethyl and R 5 is alkyl of 1 to 5 carbons or alkoxy of 1 to 5 carbons.

Claim 14

In a method of treating a bacterial infection caused by a beta-lactamase producing microorganism in a mammalian subject with a beta-lactam antibiotic selected from the group consisting of penicillin G, penicillin V, ampicillin, amoxicillin, carbenicillin, bacampicillin, cephalothin, cefazolin and cefoperazone, and the pharmaceutically-acceptable salt thereof, the improvement which comprises: co-administering with said beta-lactam antibiotic to said mammalian subject an effective beta-lactamase inhibiting amount of a penicillanic acid 1,1-dioxide compound selected from the group consisting of ##STR16## and the pharmaceutically-acceptable base salts thereof, and the pharmaceutically-acceptable esters thereof readily hydrolyzable in vivo, wherein R 1 is selected from the group consisting of hydrogen and alkyl having 1 to 4 carbons; X is selected from the group consisting of hydroxy, alkanoyloxy having 2 to 5 carbon atoms and amino; and said pharmaceutically-acceptable esters thereof readily hydrolyzable in vivo are formed from an ester-forming radical selected from the group consisting of 3-phthalidyl, 4-crotonolactonyl, gamma-butyrolacton-4-yl and --CH(R 4 )--O--C(═O)--R 5 , wherein R 4 is hydrogen, methyl or ethyl and R 5 is alkyl of 1 to 5 carbons or alkoxy of 1 to 5 carbons.

Claim 15

The method according to claim 12, wherein said penicillanic acid 1,1-dioxide compound is of the formula ##STR17## or pharmaceutically-acceptable base salt thereof, or one of said pharmaceutically-acceptable esters thereof readily hydrolyzable in vivo.

Claim 16

The method according to claim 13, wherein R 1 is said alkyl.

Claim 17

The method according to claim 14, wherein X is hydroxy.

Claim 18

The method according to claim 15, wherein R 1 is methyl.

Claim 19

The method according to claim 14, wherein X is amino.

Claim 20

The method according to claim 17, wherein R 1 is methyl.

Claim 21

The method according to claim 12, wherein said penicillanic acid 1,1-dioxide compound is of the formula ##STR18## or a pharmaceutically-acceptable base salt thereof, or one of said pharmaceutically-acceptable esters thereof readily hydrolyzable in vivo.

Claim 22

The method according to claim 19, wherein R 1 is said alkyl.

Claim 23

The method according to claim 20, wherein X is amino.

Claim 24

The method according to claim 21, wherein R 1 is ethyl.

Claim 25

A pharmaceutical composition, which comprises a penicillanic acid 1,1-dioxide compound according to claim 1 and a pharmaceutically-acceptable carrier, wherein the weight ratio of the penicillanic acid 1,1-dioxide compound to the pharmaceutically-acceptable carrier is in the range from 1:4 to 4:1.