# US 4,396,619 A · Cephalosporin betaines

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- Number: US 4,396,619 A
- Document ID: US4396619A
- Status: Granted
- Kind: A
- Application number: 06/300,100
- Filed: 1981-09-08
- Granted: 1983-08-02
- Earliest claimed: 1981-09-08
- Assignees: Eli Lilly and Company
- Inventors: William H. W. Lunn; John K. Shadle
- Web page: https://patentgrep.com/patent/US4396619A

## CPC

- C07D 501/46: with the 7-amino radical acylated by carboxylic acids containing hetero rings
- A61P 31/04: Antibacterial agents
- C07D 501/16: with a double bond between positions 2 and 3
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Broad spectrum cephalosporin betaine antibiotics represented by the formula ##STR1## wherein R' is a heterocyclic ring, e.g. 2-aminothiazol-4-yl, 2-amino-1,3,5-thiadiazol-4-yl, or 2-aminopyridin-6-yl; R" is C.sub.1 -C.sub.4 alkyl, especially methyl, a substituted carbamoyl group, or a carboxy-substituted alkyl or cycloalkyl group; and R.sub.1 is isoquinolinium or a substituted isoquinolinium group are provided. Compounds wherein R.sub.1 is isoquinolinium are preferred especially syn-7-[2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3-(isoquinolinium- 2-ylmethyl)-3-cephem-4-carboxylate. Pharmaceutical formulations and a method for treating infectious diseases comprising the use of the antibiotics are described.

## Claims

### Claim 1

A compound of the formula ##STR21## wherein R' is an amino-substituted heterocyclic ring represented by the formulas ##STR22## R" is C.sub.1 -C.sub.4 alkyl, a carboxy-substituted alkyl or a carboxy-substituted cycloalkyl group represented by the formula ##STR23## wherein a and b independently are hydrogen or C.sub.1 -C.sub.3 alkyl, and a and b when taken together with the carbon atom to which they are bonded form a C.sub.3 -C.sub.7 carbocyclic ring; n is 0-3; and
R"' is hydroxy, amino or C.sub.1 -C.sub.4 alkoxy;
R.sub.1 is isoquinolinium substituted by amino, C.sub.1 -C.sub.4 alkylamino, di-(C.sub.1 -C.sub.4)alkylamino, hydroxy, sulfo, or aminosulfonyl; and the pharmaceutically acceptable non-toxic salts thereof.

### Claim 2 (depends on 1)

The compound of claim 1 wherein R" is C.sub.1 -C.sub.4 alkyl.

### Claim 3 (depends on 1)

The compound of claim 1 wherein R" is a group of the formula ##STR24##

### Claim 4 (depends on 1)

The compound of claim 1 wherein R' is ##STR25##

### Claim 5 (depends on 4)

The compound of claim 4 wherein R' is ##STR26##

### Claim 6 (depends on 5)

The compound of claim 5 wherein R" is C.sub.1 -C.sub.4 alkyl.

### Claim 7 (depends on 4)

The compound of claim 4 wherein R" is a group of the formula ##STR27##

### Claim 8 (depends on 1)

The compound of claim 1 wherein R.sub.1 is an amino-substituted isoquinolinium group.

### Claim 9 (depends on 8)

The compound of claim 8 wherein R' is ##STR28##

### Claim 10 (depends on 9)

The compound of claim 9, wherein R' is ##STR29## and R" is C.sub.1 -C.sub.4 alkyl.

### Claim 11 (depends on 10)

The compound of claim 10 said compound being syn-7-[2-(2-aminothiazol-4-yl)-2-methoxyiminoacetaido]-3-(4-aminoisoquinol inium-2-ylmethyl)-3-cephem-4-carboxylate.

### Claim 12 (depends on 10)

The compound of claim 10 said compound being syn-7-[2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3-(5-aminoisoquino linium-2-ylmethyl)-3-cephem-4-carboxylate.

### Claim 13 (depends on 1)

The compound of claim 1 wherein R.sub.1 is an hydroxy substituted isoquinolinium group.

### Claim 14 (depends on 13)

The compound of claim 13 wherein R' is ##STR30##

### Claim 15 (depends on 14)

The compound of claim 14 said compound being syn-7-[2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3-(8-hydroxyisoqui nolinium-2-ylmethyl)-3-cephem-4-carboxylate.

### Claim 16 (depends on 14)

The compound of claim 14 said compound being syn-7-[2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3-(5-hydroxyisoqui nolinium-2-ylmethyl)-3-cephem-4-carboxylate.

### Claim 17 (depends on 1)

The compound of claim 1 wherein R.sub.1 is isoquinolinium substituted by a sulfo group.

### Claim 18 (depends on 17)

The compound of claim 17 said compound being syn-7-[2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3-(5-sulfoisoquino linium-2-ylmethyl)-3-cephem-4-carboxylate.

### Claim 19 (depends on 1)

A pharmaceutical formulation comprising a therapeutically effective amount of a compound of claim 1 and a pharmaceutically acceptable diluent.

### Claim 20 (depends on 19)

The formulation of claim 19 where in the compound R' is 2-aminothiazol-4-yl or 2-amino-1,3,5-thiadiazol-4-yl and R" is C.sub.1 -C.sub.4 alkyl.

### Claim 21 (depends on 1)

A method for treating bacterial infections in a mammal which comprises administering to said mammal in a dose of between about 100 mg. and about 2000 mg. of a compound of claim 1.

### Claim 22 (depends on 21)

The method of claim 21 where in the compound R' is 2-aminothiazol-4-yl or 2-amino-1,3,5-thiadiazol-4-yl, R" is C.sub.1 -C.sub.4 alkyl, and R.sub.1 is an amino-substituted isoquinolinium or an hydroxy-substituted isoquinolinium group.