# US 4,394,375 A · Cephalosporin derivatives, and compositions containing them

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- Number: US 4,394,375 A
- Document ID: US4394375A
- Status: Granted
- Kind: A
- Application number: 06/271,008
- Filed: 1981-06-05
- Granted: 1983-07-19
- Earliest claimed: 1980-06-06
- Assignees: Beecham Group Limited
- Inventors: Peter H. Bentley; Kenneth D. Hardy; Peter H. Milner
- Web page: https://patentgrep.com/patent/US4394375A

## CPC

- C07D 505/00: Heterocyclic compounds containing 5-oxa-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula: [IMAGE cpc-sch-C07D-0995.gif] , e.g. oxacephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- A61K 31/545: Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula: [IMAGE cpc-sch-A61K-0953.gif] , e.g. cephalosporins, {cefaclor, or cephalexine}
- A61P 31/04: Antibacterial agents
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

A compound of formula (I) or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof: ##STR1## wherein R is phenyl, 4-hydroxyphenyl, or a 5- or 6-membered heterocyclic ring containing up to three heteroatoms selected from oxygen, sulphur or nitrogen, optionally substituted with hydroxy, amino, halogen or C.sub.1-6 alkoxy; R.sup.1 represents hydrogen or C.sub.1-6 alkyl; R.sup.2 and R.sup.3 are the same or different and represent hydrogen, C.sub.1-6 alkyl, halogen, amino, hydroxy, or C.sub.1-6 alkoxy; X represents oxygen or sulphur; and A represents hydrogen, pyridyl, acetoxy, carbamoyloxy or a heterocyclicthio group; Their preparation and use is described.

## Claims

### Claim 1

A compound of formula (I) or a pharmaceutically acceptable salt or in vivo hydrolysable ester thereof: ##STR15## wherein R is phenyl, 4-hydroxyphenyl, or a 5- or 6-membered heterocyclic ring containing up to three heteroatoms selected from oxygen, sulphur or nitrogen, optionally substituted with hydroxy, amino, halogen or C.sub.1-6 alkoxy;
R.sup.1 represents hydrogen or C.sub.1-6 alkyl;
R.sup.2 and R.sup.3 are the same or different and represent hydrogen, C.sub.1-6 alkyl, halogen, amino, hydroxy, or C.sub.1-6 alkoxy;
X represents oxygen or sulphur; and
A represents hydrogen, or acetoxy.

### Claim 2 (depends on 1)

A compound as claimed in claim 1 wherein the carbon atom marked * in formula (I) is in the D configuration.

### Claim 3 (depends on 1)

A compound as claimed in claim 1 wherein X is sulphur.

### Claim 4 (depends on 1)

A compound as claimed in claim 1 wherein R is phenyl or 4-hydroxyphenyl, 2-thienyl, 3-thienyl or 2-amino-4-thiazolyl.

### Claim 5 (depends on 1)

A compound as claimed in claim 1 wherein R.sup.1, R.sup.2 and R.sup.3 may be the same or different and each represents methyl, ethyl, n- and iso- propyl, n-, sec-, iso- and tert-butyl.

### Claim 6 (depends on 1)

A compound as claimed in claim 1 wherein R.sup.1 is ethyl.

### Claim 7 (depends on 1)

A compound as claimed in claim 1 wherein R.sup.2 and R.sup.3 are hydrogen.

### Claim 8 (depends on 1)

A compound as claimed in claim 1 or a pharmaceuticaly acceptable salt or in vivo hydrolysable ester thereof which is:
7.beta.-[2(4-ethyl-2,3-dioxopiperazine-1-carbonylamino)]phenylacetamido-7.a lpha.-hydroxymethylcephalosporanic acid; 7.beta.-[2(4-ethyl-2,3-dioxopiperazine-1-carbonylamino)]phenylacetamido-7. alpha.-formyloxymethylcephalosporanic acid; 7.beta.-[2-(4-ethyl-2,3-dioxopiperazine-1-carbonylamino)-2-(4-hydroxypheny l)acetamido]-7.alpha.-hydroxymethylcephalosporanic acid.

### Claim 9 (depends on 1)

A pharmaceutical composition having antibacterial activity comprising an antibacterially effective amount of a compound as claimed in claim 1 together with a pharmaceutical carrier or excipient.

### Claim 10 (depends on 9)

A pharmaceutical composition according to claim 9 which also comprises a compound of formula (VIII) or a pharmaceutically acceptable salt or ester thereof: ##STR16## wherein Z is hydroxyl, substituted hydroxyl, thiol, substituted thiol, amino, mono- or di-hydrocarbyl-substituted amino, or mono- or di-acylamino.

### Claim 11 (depends on 9)

A method of treating an antibacterial infection in a host in need thereof which comprises the administration to such host of an effective amount of a composition of claim 9.

### Claim 12 (depends on 10)

A method of treating an antibacterial infection in a host in need thereof which comprises the administration to such host of an effective amount of a composition of claim 10.

### Claim 13 (depends on 1)

A compound according to claim 1, wherein R is 4-hydroxyphenyl, R.sup.1 is ethyl, R.sup.2 and R.sup.3 are each hydrogen, X is oxygen and A is acetoxy.