US 4,359,473 A · .alpha.-Amino deoxy clavulanic acid antibacterial agents

Abstract

The compounds of the formula (XVII) ##STR1## and their esters wherein R.sub.2 is a hydrogen, fluorine, chlorine or bromine atom or an alkyl group of 1-3 carbon atoms, an alkoxyl group of 1-3 carbon atoms, an acyloxyl group of 1-3 atoms, a hydroxyl group, an alkoxycarbonyl group containing 1-3 carbon atoms in the alkoxy part, or a group --N(R.sub.5)CO.R.sub.6, --N(R.sub.5)SO.sub.2 R.sub.6 or --CO-NR.sub.5 R.sub.6 where R.sub.5 is a hydrogen atom or an alkyl group of 1-3 carbon atoms or a phenyl or benzyl group and R.sub.6 is an alkyl group of 1-3 carbon atoms or a phenyl or benzyl group; R.sub.3 is a hydrogen, fluorine or chlorine atom or an alkyl group of 1-3 carbon atoms, an alkoxyl group of 1-3 carbon atoms; or an acyloxyl group of 1-3 carbon atoms R.sub.4 is a hydrogen fluorine or chlorine atom or an alkyl group of 1-3 atoms or an alkoxyl group of 1-3 carbon atoms; and X is a bond or alkylene group of 1-4 carbon atoms; have been found to be .beta.-lactamase inhibitors and antibacterial agents. Their preparation and use is described.

Claims69

Dependent claims

A compound of the formula (XVII):

##STR22## or an ester thereof of the formula (XVIII) or (XIX):
##STR23## wherein A.sub.1 is alkyl of 1 to 6 carbon atoms unsubstituted or mono-substituted by alkoxyl or alkanoyloxy of 1 to 7 carbon atoms, phthalidyl, ethoxycarbonyloxymethyl or .alpha.-ethoxycarbonyloxyethyl, A.sub.2 is alkenyl or alkynyl of up to 5 carbon atoms or phenyl unsubstituted or mono-substituted by fluoro, chloro, bromo, nitro or alkyl or alkoxyl of up to 4 carbon atoms, A.sub.3 is hydrogen, alkyl of up to 4 carbon atoms or phenyl unsubstituted or mono-substituted by fluoro, chloro, bromo, nitro, or alkyl or alkoxyl of up to 4 carbon atoms, R.sub.2 is hydrogen, fluorine, chlorine, bromine, alkyl of 1 to 3 carbon atoms, alkoxy of 1 to 3 carbon atoms, alkanoyloxy of 1 to 3 carbon atoms, hydroxyl, alkoxycarbonyl of 1 to 3 carbon atoms in the alkoxy part, or a group --N(R.sub.5)CO.R.sub.6, --N(R.sub.5)SO.sub.2 R.sub.6 or --CO--NR.sub.5 R.sub.6 wherein R.sub.5 is hydrogen, alkyl of 1 to 3 carbon atoms, phenyl or benzyl and R.sub.6 is alkyl of 1 to 3 carbon atoms, phenyl or benzyl;
R.sub.3 is hydrogen, fluorine, chlorine, alkyl group of 1 to 3 carbon atoms, alkoxy of 1 to 3 carbon atoms or alkanoyloxy of 1 to 3 carbon atoms;
R.sub.4 is hydrogen, fluorine, chlorine, alkyl group of 1 to 3 carbon atoms or alkoxyl of 1 to 3 carbon atoms;
and X is alkylene of 1 to 4 carbon atoms.

2 more elements

A method of treating bacterial infections in mammals including humans which comprises administering to such a mammal in need thereof an antibacterially effective amount of a compound of the formula (XVIII):

##STR24## wherein A.sub.1 is tetrahydropyranyl, tetrahydrofuranyl or a moiety of the formula
--CHA.sub.5 --OA.sub.6 (c)
--CHA.sub.5 --COA.sub.6 (d)
--CHA.sub.5 --CO.sub.2 A.sub.6 (e)
wherein
A.sub.5 is hydrogen or methyl;
A.sub.6 is alkyl of up to 4 carbon atoms, phenyl, benzyl or phenyl or benzyl substituted by one or two alkyl or alkoxy moieties up to 3 carbon atoms or by fluoro, chloro, bromo or nitro, or A.sub.5 is joined to A.sub.6 to form an ortho-phenylene moiety unsubstituted or substituted by one or two alkyl or alkoxyl moieties of up to 3 carbon atoms or by fluoro, chloro, bromo or nitro,
R.sub.2 is hydrogen, fluorine, chlorine, bromine, alkyl of 1 to 3 carbon atoms, alkoxy of 1 to 3 carbon atoms, alkanoyloxy of 1 to 3 carbon atoms, hydroxyl, alkoxycarbonyl of 1 to 3 carbon atoms in the alkoxy part, or a group --N(R.sub.5)CO.R.sub.6, --N(R.sub.5).SO.sub.2 R.sub.6 or --CO--NR.sub.5 R.sub.6 wherein
R.sub.5 is hydrogen, alkyl of 1 to 3 carbon atoms, phenyl or benzyl and
R.sub.6 is alkyl of 1 to 3 carbon atoms, phenyl or benzyl;
R.sub.3 is hydrogen, fluorine, chlorine, alkyl group of 1 to 3 carbon atoms, alkoxy of 1 to 3 carbon atoms or alkanoyl of 1 to 3 carbon atoms;
R.sub.4 is hydrogen, fluorine, chlorine, alkyl group of 1 to 3 carbon atoms or alkoxyl of 1 to 3 carbon atoms;
and
X is alkylene of 1 to 4 carbon atoms, in combination with a pharmaceutically acceptable carrier.

11 more elements

A pharmaceutical composition useful for treating bacterial infections in mammals including humans which comprises an antibacterially effective amount of a compound of the formula (XVII):

##STR25## or an ester thereof of the formula (XVIII) or (XIX):
##STR26## wherein A.sub.1 is alkyl of 1 to 6 carbon atoms unsubstituted or mono-substituted by alkoxyl or alkanoyloxy of 1 to 7 carbon atoms, phthalidyl, ethoxycarbonyloxymethyl or .alpha.-ethoxycarbonyloxyethyl, A.sub.2 is alkenyl or alkynyl of up to 5 carbon atoms or phenyl unsubstituted or mono-substituted by fluoro, chloro, bromo, nitro or alkyl or alkoxyl of up to 4 carbon aoms, A.sub.3 is hydrogen, alkyl of up to 4 carbon atoms or phenyl unsubstituted or mono-substituted by fluoro, chloro, bromo, nitro, or alkyl or alkoxyl of up to 4 carbon atoms, R.sub.2 is hydrogen, fluorine, chlorine, bromine, alkyl of 1 to 3 carbon atoms, alkoxy of 1 to 3 carbon atoms, alkanoyloxy of 1 to 3 carbon atoms, hydroxyl, alkoxycarbonyl of 1 to 3 carbon atoms in the alkoxy part, or a group --N(R.sub.5)CO.R.sub.6 --N(R.sub.5)SO.sub.2 R.sub.6 or --CO--NR.sub.5 R.sub.6 wherein R.sub.5 is hydrogen, alkyl of 1 to 3 carbon atoms, phenyl or benzyl and R.sub.6 is alkyl of 1 to 3 carbon atoms, phenyl or benzyl;
R.sub.3 is hydrogen, fluorine, chlorine, alkyl group of 1 to 3 carbon atoms, alkoxy of 1 to 3 carbon atoms or alkanoyloxy of 1 to 3 carbon atoms;
R.sub.4 is hydrogen, fluorine, chlorine, alkyl group of 1 to 3 carbon atoms or alkoxyl of 1 to 3 carbon atoms;
and X is alkylene of 1 to 4 carbon atoms as the sole antibacterial agent, in combination with a pharmaceutically acceptable carrier.

2 more elements

A compound of the formula (XVII):

##STR29## or an ester thereof of the formula (XVIII):
##STR30## wherein A.sub.1 is tetrahydropyranyl, tetrahydrofuranyl or a moiety of the formula
--CHA.sub.5 --OA.sub.6 (c)
--CHA.sub.5 --COA.sub.6 (d)
--CHA.sub.5 --CO.sub.2 A.sub.6 (e)
wherein
A.sub.5 is hydrogen or methyl;
A.sub.6 is alkyl of up to 4 carbon atoms, phenyl, benzyl or phenyl or benzyl substituted by one or two alkyl or alkoxy moieties of up to 3 carbon atoms or by fluoro, chloro, bromo or nitro, or A.sub.5 is joined to A.sub.6 to form an ortho-phenylene moiety unsubstituted or substituted by one or two alkyl or alkoxyl moieties of up to 3 carbon atoms or by fluoro, chloro, bromo or nitro,
R.sub.2 is hydrogen, fluorine, chlorine, bromine, alkyl of 1 to 3 carbon atoms, alkoxy of 1 to 3 carbon atoms, alkanoyloxy of 1 to 3 carbon atoms, hydroxyl, alkoxycarbonyl of 1 to 3 carbon atoms in the alkoxy part, or a group --N(R.sub.5)CO.R.sub.6,--N(R.sub.5)SO.sub.2 R.sub.6 or --CO--NR.sub.5 R.sub.6 wherein
R.sub.5 is hydrogen, alkyl of 1 to 3 carbon atoms, phenyl or benzyl and
R.sub.6 alkyl of 1 to 3 carbon atoms, phenyl or benzyl;
R.sub.3 is hydrogen, fluorine, chlorine, alkyl group of 1 to 3 carbon atoms, alkoxy of 1 to 3 carbon atoms or alkanoyl of 1 to 3 carbon atoms;
R.sub.4 is hydrogen, fluorine, chlorine, alkyl group of 1 to 3 carbon atoms or alkoxyl of 1 to 3 carbon atoms;
and
X is alkylene of 1 to 4 carbon atoms.

12 more elements

A pharmaceutical composition useful for treating bacterial infections in mammals including humans which comprises an antibacterially effective amount of the compound of the formula (XVIII):

##STR31## wherein A.sub.1 is tetrahydropyranyl, tetrahydrofuranyl or a moiety of the formula
--CHA.sub.5 --OA.sub.6 (c)
--CHA.sub.5 --COA.sub.6 (d)
--CHA.sub.5 --CO.sub.2 A.sub.6 (e)
wherein
A.sub.5 is hydrogen or methyl;
A.sub.6 is alkyl of up to 4 carbon atoms, phenyl, benzyl or phenyl or benzyl substituted by one or two alkyl or alkoxy moieties of up to 3 carbon atoms or by fluoro, chloro, bromo or nitro, or A.sub.5 is joined to A.sub.6 to form an ortho-phenylene moiety unsubstituted or substituted by one or two alkyl or alkoxyl moieties of up to 3 carbon atoms or by fluoro, chloro, bromo or nitro.
R.sub.2 is hydrogen, fluorine, chlorine, bromine, alkyl of 1 to 3 carbon atoms, alkoxy of 1 to 3 carbon atoms, alkanoyloxy of 1 to 3 carbon atoms, hydroxyl, alkoxycarbonyl of 1 to 3 carbon atoms in the alkoxy part, or a group --N(R.sub.5)CO.R.sub.6 --N(R.sub.5)SO.sub.2 R.sub.6 or --CO--NR.sub.5 R.sub.6 wherein
R.sub.5 is hydrogen, alkyl of 1 to 3 carbon atoms, phenyl or benzyl and
R.sub.6 is alkyl of 1 to 3 carbon atoms, phenyl or benzyl;
R.sub.3 is hydrogrn, fluorine, chlorine, alkyl group of 1 to 3 carbon atoms, alkoxy of 1 to 3 carbon atoms or alkanoyl of 1 to 3 carbon atoms;
R.sub.4 is hydrogen, fluorine, chlorine, alkyl group to 1 to 3 carbon atoms or alkoxyl of 1 to 3 carbon atoms;
and
X is alkylene of 1 to 4 carbon atoms as the sole antibacterial agent, in combination with a pharmaceutically acceptable carrier.

11 more elements

Dependencies are inferred from the claim text.

.alpha.-Amino deoxy clavulanic acid antibacterial agents

Life of this patent

.alpha.-Amino deoxy clavulanic acid antibacterial agents

Life of this patent

Abstract

Claims69