Oxazolidinone derivatives, process for their preparation and pharmaceutical compositions containing them

• US 6,617,339 B1
• Filed: 12/05/2000
• Issued: 09/09/2003
• Est. Priority Date: 06/05/1998
• Status: Expired due to Fees

• Current Assignee: Astrazeneca AB (Astrazeneca PLC)
• Original Assignee: Syngenta Limited (China National Chemical Corporation)
• Inventors: Gravestock, Michael Barry
• Primary Examiner(s): Huang, Evelyn Mei
• Application Number:
  US09/719,012
• Time in Patent Office: 1,008 Days
• Field of Search: 546/19.22, 546/125, 546/256, 546/209, 546/271.4, 546/269.1, 546/341, 544/124, 544/235, 544/238, 544/364, 544/369, 548/110, 548/182, 548/187, 548/135, 548/232, 514/340, 514/210.2, 514/254.04, 514/376, 514/278, 514/326, 514/362, 514/249, 514/304, 514/369, 514/333, 514/253.1, 514/236.8, 514/252.04
• US Class Current: 514/340
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: C07D 231/12 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 233/56 with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
• CPC Class Codes: C07D 249/08 1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
• CPC Class Codes: C07D 413/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/14 containing three or more hetero rings
• CPC Class Codes: C07D 417/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/14 containing three or more hetero rings
• CPC Class Codes: C07D 451/02 containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
• CPC Class Codes: C07D 487/08 Bridged systems
• CPC Class Codes: C07F 9/59 Hydrogenated pyridine rings
• CPC Class Codes: C07F 9/65583 each of the hetero rings containing nitrogen as ring hetero atom

Abstract

Compounds of formula (I) as defined herein, or a pharmaceutically acceptable salt, or an in-vivo-hydrolysable ester thereof, are useful as antibacterial agents. Processes for their manufacture and pharmaceutical compositions containing them are described.

Claims

1. 5(R)-Isoxazol-3-yloxymethyl-3-(4-(1-(2(S),3-dihydroxypropanoyl)-1,2,5,6-tetrahydropyrid-4-yl)-3,5-difluorophenyl)-oxazolidin-2-one, or a pharmaceutically-acceptable salt or in vivo-hydrolyzable ester thereof.

2. 5(R)-Isoxazol-3-yloxymethyl-3-(4-(1-(2(S)-hydroxy-3-phosphoryl-propanoyl)-1,2,5,6-tetrah dropyrid-4-yl)-3,5-difluorophenyl)oxazolidin-2-one, or a pharmnaceutically-acceptable salt thereof.

3. The disodium salt of 5(R)-isoxazol-3-yloxymethyl-3-(4-(1-(2(S)-hydroxy-3-phosphoryl-propanoyl)-1,2,5,6-tetrahydropyrid-4-yl)-3,5-difluorophenyl)oxazolidin-2-one.

4. A pharmaceutical composition comprising a pharmaceutically-acceptable diluent or carrier and 5(R)-isoxazol-3-yloxymethyl-3-(4-(1-(2(S),3-dihydroxypropanoyl)-1,2,5,6-tetrahydropyrid-4-yl)-3,5-difluorophenyl)-oxazolidin-2-one, or a pharmaceutically-acceptable salt, or in-vivo hydrolysable ester thereof.

5. A pharmaceutical composition comprising a pharmaceutically-acceptable diluent or carrier and 5(R)-isoxazol-3-yloxymethyl-3-(4-(1-(2(S)-hydroxy-3-phosphoryl-propanoyl)-1,2,5,6-tetrahydropyrid-4-yl)-3,5-difluorophenyl)oxazolidin-2-one or a pharmaceutically-acceptable salt thereof.

6. A pharmaceutical composition comprising a pharmaceutically-acceptable diluent or carrier and the disodium salt of 5(R)-isoxazol-3-yloxymethyl-3-(4-(1-(2(S)-hydroxy-3-phosphoryl-propanoyl)-1,2,5,6-tetrahydropyrid-4-yl)-3,5-difluorophenyl)oxazolidin-2-one.

7. A method for producing an antibacterial effect in a warm blooded animal, comprising administering to the said animal in need thereof an effective amount of the compound 5(R)-isoxazol-3-yloxymethyl-3-(4-(1-(2(S),3-dihydroxypropanoyl)-1,2,5,6-tetrahydropyrid-4-yl)-3,5-difluorophenyl)-oxazolidin-2-one or a pharmaceutically-acceptable salt or in vivo-hydrolyzable ester thereof.

8. A method for producing an antibacterial effect in a warm blooded animal, comprising administering to said animal in need thereof an effective amount of the compound 5(R)-isoxazol-3-yloxymethyl-3-(4-(1-(2(S)-hydroxy-3-phosphoryl-propanoyl)-1,2,5,6-tetrahydropyrid-4-yl)-3,5-difluorophenyl)oxazolidin-2-one, or a pharmaceutically-acceptable salt thereof.

9. A method for producing an antibacterial effect in a warm blooded animal, comprising administering to said animal in need thereof an effective amount of the disodium salt of 5(R)-isoxazol-3-yloxymethyl-3-(4-(1-(2(S)-hydroxy-3-phosphoryl-propanoyl)-1,2,5,6-tetrahydropyrid-4-yl)-3,5-difluorophenyl)oxazolidin-2-one.

10. A method for producing an antibacterial effect in a warm blooded animal, comprising administering to said animal in need thereof an effective amount of a pharmaceutical composition comprising the compound 5(R)-isoxazol-3-yloxymethyl-3-(4-(1-(2(S),3-dihydroxypropanoyl)-1,2,5,6-tetrahydropyrid-4-yl)-3,5-difluorophenyl)-oxazolidin-2-one, or a pharmaceutically-acceptable salt, or in vivo-hydrolyzable ester thereof;

and a pharmaceutically-acceptable diluent or carrier.

11. A method for producing an antibacterial effect in a warm blooded animal, comprising administering to said animal in need thereof an effective amount of a pharmaceutical composition comprising the compound 5(R)-isoxazol-3-yloxymethyl-3-(4-(1-(2(S)-hydroxy-3-phosphoryl-propanoyl)-1,2,5,6-tetrahydropyrid-4-yl)-3,5-difluorophenyl)oxazolidin-2-one or a pharmaceutically-acceptable salt thereof;

and a pharmaceutically-acceptable diluent or carrier.

12. A method for producing an antibacterial effect in a warm blooded animal, comprising administering to said animal in need thereof an effective amount of a pharmaceutical composition comprising the disodium salt of 5(R)-isoxazol-3-yloxymethyl-3-(4-(1-(2(S)-hydroxy-3-phosphoryl-propanoyl)-1,2,5,6-tetrahydropyrid-4-yl)-3,5-difluorophenyl)oxazolidin-2-one;

and a pharmaceutically-acceptable diluent or carrier.