3-(Heteroaryl acetamido)-2-oxo-azetidine-1-sulfonic acids derivatives as antibacterial agents

• US 20040019203A1
• Filed: 02/27/2003
• Published: 01/29/2004
• Est. Priority Date: 09/14/2000
• Status: Active Grant

• Current Assignee: Rempex Pharmaceuticals, Inc (Melinta Therapeutics, Inc.)
• Original Assignee: Pantherix Limited
• Inventors: Narender Reddy, Andhe V., Singh, Rajeshwar, Thomas, George, Micetich, Ronald George, Salama, Sameeh M., Fiakpui, Charles, Maiti, Samarendra
• Granted Patent: US 6,916,803 B2
• Time in Patent Office: Days
• US Class Current: 540/355
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: C07D 417/14 containing three or more hetero rings
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present invention relates to novel Syn isomers of racemates and optical isomers of 3-(heteroaryl acetamido)-2-oxo-azetidine-1-sulfonic acids of formula (I) and its use in treating the infections caused by gram-negative pathogenic bacteria.

Claims

1. A compound selected from the group consisting of a Syn isomer of a racemate and an optical isomer of 3-(heteroaryl acetamido)-2-oxo-axetidine-1-sulfonic acid and of formula I

2. A compound of formula I as set forth in claim 1, wherein at least one of R, R₁, R₂, R₃, and R₄ are selected from the group consisting of methyl, ethyl, propyl and isopropyl.

3. A compound of formula I as set forth in claim 1, wherein R₃ and R₄ are independently a saturated alicyclic moiety having 3-6 carbon atoms selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.

4. A compound of formula I as set forth in claim 1, wherein the halogen atom is selected from the group consisting of fluorine, chlorine, and bromine.

5. A compound of formula I as set forth in claim 1, wherein the substitutents are 1, 2 or 3 substituents selected from OH, NH₂, dimethylamino, halogen atom, OCH₃, COOH, CONH₂, NO₂ or CN.

6. A compound of formula I as set forth in claim 1, wherein the pharmaceutically acceptable salt forming cation is selected from the group consisting of alkali metals, alkaline earth metals, organic bases or basic amino acids.

7. A method of producing a zwitterion of the compound of claim 1 wherein M is hydrogen, and wherein said compound is interacted with a basic nitrogen atom present in the molecule of formula I.

9. A pharmaceutical composition suitable for the treatment of bacterial infections in mammals comprising the compound described in claim 1 or claim 8 or pharmaceutically acceptable salt thereof and pharmaceutically acceptable carrier.

10. The use of compounds described in claim 1 or claim 8 for treatment of bacterial infections in warm-blooded animals.

11. A method of treating a bacterial infection in a subject in need of such treatment comprising administering to said subject in need of such treatment a therapeutically effective amount of the compound of claim 1 or claim 8.

12. An oral preparation comprising about 1 to 25 w/w % of the compound of claim 1 or claim 8.

13. A parenteral preparation comprising about 0.1 to 5 w/w % of the compound of claim 1 or claim 8.

14. The method of claim 11, wherein the therapeutically effective amount of the compound of claim 1 or claim 8 comprises an oral dosage of about 50 to 1500 mg/day of the compound of claim 1 or claim 8 for an adult in 24 divided doses.

15. the method of claim 11, wherein the therapeutically effective amount of compound of claim 1 or claim 8 comprises an injection of about 1-100 mg of the compound of claim 1 or claim 8.

16. The method of claim 17, wherein the therapeutically effective amount of the compound of claim 1 or claim 8 is diluted with physiological saline of glucose injection liquid.

17. The method of claim 11, wherein the therapeutically effective amount of the compound of claim 1 or claim 8 comprises a suppository containing about 1-1000 mg of the compound of claim 1 or 8.

19. A compound of formula I as set forth in claim 1, wherein the racemate is the mixture of diastereoisomers having zero optical rotation of the molecule.

20. A compound of formula I as set forth in claim 1, wherein the optical isomer is a pure single R and S diasteroisomer at an asymmetric carbon atom present in the molecule.

8. A compound of formula I

18. A method of producing a compound of formula I comprising (a) reacting a 3-amino-azetidine-2-one sulfonic acid of formula (II) with a heteroaryl carboxylic acid of formula (III) and (b) deprotecting the protecting group.