Bis-type penicillins and process for producing the same

Claim 2

A compound represented by the general formula (I), ##EQU13## wherein R is the radical derived from a conventional penicillin acylamido group represented by the formula ##EQU14## in which R 4 represents a substituted or unsubstituted alkyl, cycloalkyl, cycloalkenyl, cycloalkadienyl, aryl, aralkyl, aryloxy, alkylthioalkyl, or a heterocyclic group; and R 5 represents a hydrogen atom; R 4 and R 5 together with the common carbon atom may form a cycloalkyl, cycloalkenyl or cycloalkadienyl ring; R 1 represents a hydrogen atom, a conventional penicillin blocking group or a conventional penicillin saltforming cation R 2 represents a substituted or unsubstituted alkylene, alkenylene, cycloalkylene, arylene, alkylenediaryl group; X and Y are individually an oxygen atom or a sulfur atom.

Claim 3

A compound represented by the general formula (Ia), ##EQU15## wherein R 1 , Y and R 4 and R 5 are defined in claim 1 and R 6 represents a substituted or unsubstituted alkylene, alkenylene, cycloalkylene, arylene or alkylenediaryl group.

Claim 4

A compound according to claim 2, wherein R 6 is a substituted or unsubstituted alkylene, alkenylene or cycloalkylene group.

Claim 5

A compound according to claim 2, wherein R 6 is a substituted or unsubstituted arylene group.

Claim 6

A compound according to claim 2, wherein R 6 is an alkylenediaryl group.

Claim 7

A compound according to claim 1, wherein R 1 is a hydrogen atom.

Claim 8

A compound according to claim 1, wherein R 1 is selected from the group consisting of ester-forming groups capable of being removed by catalytic reduction, chemical reduction or hydrolysis under mild conditions and ester-forming groups capable of being easily removed owing to enzymes in a living body.

Claim 9

A compound selected from the group consisting of N,n'-1-methyl-1-propylmalonyl-bis[6-(D(-)-α-ureidophenylacetamido) penicillanic acid], N,n'-succinyl-bis[6-(D(-)-α-ureidophenylacetamido) penicillanic acid], N,n'-glutaryl-bis[6-(D(-)-α-ureidophenylacetamido) penicillanic acid], N,n'-adipoly-bis[6-(D(-)-α-ureidophenylacetamido) penicillanic acid], N,n'-pimeloyl-bis[6-(D(-)-α-ureidophenylacetamido) penicillanic acid], N,n'-sebacoyl-bis[6-(D(-)-α-ureidophenylacetamido) penicillanic acid], N,n'-dodecanedioyl-bis[6-(D(-)-α-ureidophenylacetamido) penicillanic acid], N,n'-tridecanedioyl-bis[6-(D(-)-α-ureidophenylacetamido) penicillanic acid], N,n'-fumaroyl-bis[6-(D(-)-α-ureidophenylacetamido) penicillanic acid], N,n'-1,4-cyclohexanedioyl-bis[6-(D(-)-α-ureidophenylacetamido) penicillanic acid], N,n'-sebacoyl-bis[6-(D(-)-α-ureido-hydroxyphenylacetamido penicillanic acid], N,n'-sebacoyl-bis[6-(1-ureidocyclohexylcarbonylamido) penicillanic acid], N,n'-terephthaloyl-bis[6-(D(-)-α-ureidophenylacetamido) penicillanic acid], N,n'-isophthaloyl-bis[6-(D(-)-α-ureidophenylacetamido) penicillanic acid], N,n'-terephthaloyl-bis[6-(D(-)-α-thioureidophenylacetamido) penicillanic acid], N,n'-2-nitroterephthaloyl-bis[6-(D(-)-α-ureidophenylacetamido) penicillanic acid], N,n'-2,5-dimethoxyterephthaloyl-bis[6-(D(-)-α-ureidophenylacetamido) penicillanic acid], and N,n'-2,6-naphthalenedioyl-bis[6-(D(-)-α-ureidophenylacetamido) penicillanic acid].

Claim 10

A compound selected from the group consisting of N,n'-1-methyl-1-propylmalonyl-bis[6-(D(-)-α-ureidophenylacetamido) penicillanic acid], N,n'-succinyl-bis[6-(D(-)-α-ureidophenylacetamido) penicillanic acid], N,n'-glutaryl-bis[6-(D(-)-α-ureidophenylacetamido) penicillanic acid], N,n'-adipoly-bis[6-(D(-)-α-ureidophenylacetamido) penicillanic acid], N,n'-pimeloyl-bis[6-(D(-)-α-ureidophenylacetamido) penicillanic acid], N,n'-sebacoyl-bis[6-(D(-)-α-ureidophenylacetamido) penicillanic acid], N,n'-dodecanedioyl-bis[6-(D(-)-α-ureidophenylacetamido) penicillanic acid], N,n'-tridecanedioyl-bis[6-(D(-)-α-ureidophenylacetamido) penicillanic acid], N,n'-fumaroyl-bis[6-(D(-)-α-ureidophenylacetamido) penicillanic acid], N,n'-1,4-cyclohexanedioyl-bis[6-(D(-)-α-ureidophenylacetamido) penicillanic acid], N,n'-sebacoyl-bis[6-(D(-)-α-ureido-hydroxyphenylacetamido penicillanic acid], N,n'-sebacoyl-bis[6-(1-ureidocyclohexylcarbonylamido) penicillanic acid], N,n'-terephthaloyl-bis[6-(D(-)-α-ureidophenylacetamido) penicillanic acid], N,n'-isophthaloyl-bis[6-(D(-)-α-ureidophenylacetamido) penicillanic acid], N,n'-terephthaloyl-bis[6-(D(-)-α-thioureidophenylacetamido) penicillanic acid], N,n'-2-nitroterephthaloyl-bis[6-(D(-)-α-ureidophenylacetamido) penicillanic acid], N,n'-2,5-dimethoxyterephthaloyl-bis[6-(D(-)-α-ureidophenylacetamido) penicillanic acid], and N,n'-2,6-naphthalenedioyl-bis[6-(D(-)-α-ureidophenylacetamido) penicillanic acid].

Claim 11

The compound N,n'-4,4'-ethylenedibenzoyl-bis[6-(D(-)-α-ureidophenylacetamido) penicillanic acid].

Claim 12

The compound N,n'-4,4'-ethylenedibenzoyl-bis[6-(D(-)-α-ureidophenylacetamido) penicillanic acid].

Claim 13

A compound selected from the group consisting of dipivaloyloxymethyl N,N'-terephthaloyl-bis-[6-(D(-)-α-ureidophenylacetamido) penicillanate], and diphthalidyl N,N'-sebacoyl-bis[6-(D(-)-α-ureidophenylacetamido) penicillanate].

Claim 14

A compound selected from the group consisting of dipivaloyloxymethyl N,N'-terephthaloyl-bis-[6-(D(-)-α-ureidophenylacetamido) penicillanate], and diphthalidyl N,N'-sebacoyl-bis[6-(D(-)-α-ureidophenylacetamido) penicillanate].

Claim 15

A compound according to claim 1, wherein R 1 is a cation capable of forming a non-toxic salt.

Claim 16

A non-toxic salt of a compound according to claim 8.

Claim 17

N,N'-succinyl-bis[6-(D(-)-α-ureidophenylacetamido) penicillanic acid] or its non-toxic salt.

Claim 18

N,N'-succinyl-bis[6-(D(-)-α-ureidophenylacetamido) penicillanic acid] or its non-toxic salt.

Claim 19

A pharmaceutical composition containing an active ingredient a compound of claim 1.