Cross-linked glycopeptide-cephalosporin antibiotics

• US 7,279,458 B2
• Filed: 04/17/2006
• Issued: 10/09/2007
• Est. Priority Date: 07/11/2003
• Status: Active Grant

• Current Assignee: Theravance Biopharma Antibiotics IP, LLC (Theravance Biopharma, Inc.)
• Original Assignee: Theravance, Inc
• Inventors: Aggen, James B., Linsell, Martin S., Moran, Edmund J., Fatheree, Paul R., Marquess, Daniel, Trapp, Sean G.
• Primary Examiner(s): Tsang; Cecilia J.
• Assistant Examiner(s): Kosar; Andrew D.
• Application Number:
  US11/405,331
• Publication Number:
  US 20060189517A1
• Time in Patent Office: 540 Days
• Field of Search: None
• US Class Current: 514/2.9
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/02 of urine or of the urinary tract, e.g. urine acidifiers
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 31/00 Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 41/00 Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07D 501/00 Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula: , e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
• CPC Class Codes: C07K 7/64 Cyclic peptides containing only normal peptide links
• CPC Class Codes: C07K 9/008 directly attached to a hetero atom of the saccharide radical, e.g. actaplanin, avoparcin, ristomycin, vancomycin

Abstract

This invention provides cross-linked glycopeptide—cephalosporin compounds and pharmaceutically acceptable salts thereof which are useful as antibiotics. This invention also provides pharmaceutical compositions containing such compounds; methods for treating bacterial infections in a mammal using such compounds; and processes and intermediates useful for preparing such compounds.

Claims

1. A compound of the formula:

2. The compound of claim 1, wherein R⁹ is hydrogen, C_1-4 alkyl or C_3-5 cycloalkyl, where the alkyl group is optionally substituted with —

COOH or 1 to 3 fluoro substituents.

3. The compound of claim 1, wherein R⁹ is hydrogen, methyl, ethyl, 2-fluoroethyl, 2-carboxyprop-2-yl or cyclopentyl.

4. The compound of claim 1, wherein R⁹ is methyl.

5. The compound of claim 1, wherein W is CCl.

6. The compound of claim 1, wherein W is N.

7. The compound of claim 1, wherein n is 0.

8. The compound of claim 1, wherein R¹ and R² are hydrogen.

9. The compound of claim 1, wherein R^c is -(CH²)₄-.

10. The compound of claim 1, wherein R^b is hydrogen.

11. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of any one of claims 1 to 10.

12. A method of treating a bacterial infection in a mammal, the method comprising administering to a mammal a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a compound of any one of claims 1 to 10.