2-oxo-1-azetidine sulfonic acid derivatives as potent .beta.-lactamase inhibitors

• US 5,888,998 A
• Filed: 04/24/1997
• Issued: 03/30/1999
• Est. Priority Date: 04/24/1997
• Status: Expired due to Fees

• Current Assignee: Naeja Pharmaceutical Inc., Taiho Pharmaceutical Company Limited (Otsuka Holdings Company Limited)
• Original Assignee: Taiho Pharmaceutical Company Limited (Otsuka Holdings Company Limited), Synphar Laboratories, Inc.
• Inventors: Nishida, Koichi, Setti, Eduardo L., Uji, Tatsuya, Phillips, Oludotun A., Maiti, Samarendra N., Kunugita, Chieko, Higashitani, Fusahiro, Singh, Rajeshwar, Reddy, Andhe V. Narender, Micetich, Ronald G.
• Primary Examiner(s): Berch, Mark L.
• Application Number:
  US08/840,608
• Time in Patent Office: 705 Days
• Field of Search: 514/210, 540/355
• US Class Current: 514/210.15
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/54 having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: C07D 409/14 containing three or more hetero rings
• CPC Class Codes: C07D 413/14 containing three or more hetero rings
• CPC Class Codes: C07D 417/14 containing three or more hetero rings

Abstract

A compound of formula (I) ##STR1## wherein R₁ is selected from the group consisting of 2-thienyl, 2-furyl, 2-pyrrolyl, 1-methyl-2-pyrrolyl, 2-amino-1-thiazolyl and 5-isothiazolyl;

R₂ is selected from the group consisting of: ##STR2## and M is hydrogen or a pharmaceutically acceptable cation; wherein the oxyimino fragment (═N--OR₂) in formula (I) is in the `anti` orientation.

Claims

1. A compound of formula (I) ##STR70## wherein R₁ is selected from the group consisting of 2-thienyl, 2-furyl, 2-pyrrolyl, 1-methyl-2-pyrrolyl, 2-amino-1-thiazolyl and 5-isothiazolyl;

R₂ is selected from the group consisting of;

##STR71## M is hydrogen or a pharmaceutically acceptable cation;

wherein the oxyimino fragment (═

N--OR₂) in formula (I) is in the `anti` orientation.

2. The compound according to claim 1 where the R₁ is selected from the group consisting of 2-thienyl and 2-amino-4-thiazolyl.

3. The compound according to claim 2, wherein R₁ is 2-thienyl.

4. The compound according to claim 1 where R₂ is hydroxypyridone and its derivatives as represented by the following formula:

##STR72##

5. The compound according to claim 4, wherein when X is N--OH, R₂ is a keto or enol tautomeric isomer of the formula:

##STR73##

6. The method for inhibiting β

-lactamase-mediated inactivation of a β

-lactam antibiotic, which comprises administering to a patient an effective amount of the compound described in claim 1 or a pharmaceutically acceptable salt thereof.

7. The compound according to claim 1, wherein Y is selected from the group consisting of ##STR74##

8. The compound according to claim 1, wherein said compound contains variable amounts of water.

9. The compound according to claim 8, wherein said variable amounts of water result from lyophilization, crystallization or column purification.

10. A pharmaceutical composition suitable for the treatment of bacterial infections in mammals comprising the compound described in claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.

11. A β

-lactamase inhibitor for a β

-lactam antibiotic, which comprises as an active ingredient the compound described in claim 1 or a pharmaceutically acceptable salt thereof in combination with a pharmaceutically acceptable carrier.