# US 4,395,418 A · Penem-3-carboxylic acid derivatives

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 4,395,418 A
- Document ID: US4395418A
- Status: Granted
- Kind: A
- Application number: 06/271,010
- Filed: 1981-06-05
- Granted: 1983-07-26
- Earliest claimed: 1980-06-06
- Assignees: Sankyo Company, Limited
- Inventors: Eiji Ohki; Sadao Oida; Akira Yoshida; Teruo Hayashi; Shinichi Sugawara
- Web page: https://patentgrep.com/patent/US4395418A

## CPC

- C07D 499/88: Compounds with a double bond between positions 2 and 3 and a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2
- C07D 205/09: with a sulfur atom directly attached in position 4
- C07F 7/1804: {Compounds having Si-O-C linkages (Si-O-acyl linkages C07F7/1896)}
- C07F 9/568: Four-membered rings
- Y02P 20/55: Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- C07F: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM (metal-containing porphyrins C07D487/22)
- Y02P: CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS

## Abstract

Penem-3-carboxylic acid derivatives of formula (I): ##STR1## (wherein: R.sup.1 represents a hydrogen atom, an alkyl group, an alkoxy group, a hydroxyalkyl group, an acyloxyalkyl group, an alkylsulphonyloxyalkyl group, an arylsulphonyloxyalkyl group or a trialkylsilyloxyalkyl group; R.sup.2 represents a hydrogen atom or an alkyl group; R.sup.3 represents a hydrogen atom, an amino-protecting group or a group of formula ##STR2## in which R.sup.5 and R.sup.6 are the same or different and each represents a hydrogen atom or an alkyl group; A represents a branched-chain alkylene group; and R.sup.4 represents a carboxy group or a protected carboxy group) and pharmaceutically acceptable salts thereof, may be prepared by heating a corresponding phosphorus-ylide compound or by reacting a corresponding azetidin-2-one with a suitable phosphorous acid triester or triamide, and have been found to have excellent antibacterial activity accompanied by a very low acute toxicity.

## Claims

### Claim 1

Compounds of formula (I): ##STR28## wherein: R.sup.1 represents a 1-hydroxyethyl group;
R.sup.2 represents a hydrogen atom or a C.sub.1 -C.sub.2 alkyl group;
R.sup.3 represents a hydrogen atom, a formimidoyl group, or an acetimidoyl group;
A represents an ethylene or trimethylene group having one methyl group in the .alpha.-position in its carbon chain; and
R.sup.4 represents a carboxy group or a pivaloyloxymethoxycarbonyl group; and pharmaceutically acceptable salts thereof.

### Claim 2 (depends on 1)

Compounds as claimed in claim 1, in the form of the sodium or potassium salt.

### Claim 3 (depends on 1)

Compounds as claimed in claim 1, wherein the configuration is selected from the (5R,6S) and (5R,6R) configurations.

### Claim 4 (depends on 1)

Compounds as claimed in claim 1, wherein R.sup.1 represents a 1-hydroxyethyl group, whose .alpha.-hydroxy substitutent is in the R configuration.

### Claim 5

In a pharmaceutical composition comprising an antibiotic and a pharmaceutically acceptable carrier or diluent, the improvement which comprises employing as antibiotic a compound of formula: ##STR29## wherein: R.sup.1 represents a hydroxyalkyl group;
R.sup.2 represents a hydrogen atom or a C.sub.1 -C.sub.2 alkyl group;
R.sup.3 represents a hydrogen atom, a formimidoyl group or an acetimidoyl group;
A represents an ethylene or trimethylene group having one methyl group in the .alpha.-position of the carbon chain; and
R.sup.4 represents a carboxy group or a pivaloyloxymethoxycarbonyl group; or a pharmaceutically acceptable salt thereof.

### Claim 6

2-(2-Amino-1-methylethylthio)-6-(1-hydroxyethyl)penem-3-carboxylic acid and pharmaceutically acceptable salts thereof.

### Claim 7

(5R,6S)-(2-Amino-1-methylethylthio)-6-[(R)-1 -hydroxyethyl]penem-3-carboxylic acid and pharmaceutically acceptable salts thereof.

### Claim 8 (depends on 1)

Compounds as claimed in claim 1, wherein:
R.sup.1 represents a 1-hydroxyethyl group,
R.sup.2 and R.sup.3 represent hydrogen atoms,
A represents an ethylene or trimethylene group having one methyl substituent in its .alpha.-position of the carbon chain, and
R.sup.4 represents a carboxy group, and pharmaceutically acceptable salts thereof.