2 substituted cephem compounds

Patent metadata

Field	Value
Publication number	US-10174053-B2
Application number	US-201715490220-A
Country	US
Kind code	B2
Filing date	Apr 18, 2017
Priority date	Oct 29, 2012
Publication date	Jan 8, 2019
Grant date	Jan 8, 2019

Abstract

The compounds of the subject invention are related to 2-substituted cephem compounds, which have a wide antimicrobial spectrum, in particular exhibit potent antimicrobial activity against beta-lactamase producing Gram negative bacteria, and pharmaceutical compositions comprising the same.

First claim

The invention claimed is:

1. A compound which is:

or a pharmaceutically acceptable salt thereof.

2. A compound which is:

3. A pharmaceutical composition, which comprises a compound or a pharmaceutically acceptable salt thereof according to claim 1 and at least one or more pharmaceutically acceptable excipients.

4. A pharmaceutical composition, which comprises a compound according to claim 2 and at least one or more pharmaceutically acceptable excipients.

5. A method of treating bacterial infections, which comprises administering a therapeutically effective amount of a compound or a pharmaceutically acceptable salt thereof according to claim 1 to a subject in need thereof.

6. The method according to claim 5 , wherein the bacterial infections are caused by Gram-Negative bacteria or Gram-Positive bacteria.

7. A method of treating bacterial infections, which comprises administering a pharmaceutical composition according to claim 3 to a subject in need thereof.

8. A method of treating a bacterial infection, which comprises administering a compound or pharmaceutically acceptable salt thereof according to claim 1 to a subject in need thereof.

9. The method according to claim 8 , wherein the bacterial infection is caused by Gram-Negative bacteria or Gram-Positive bacteria.

10. The method according to claim 8 , wherein the compound or a pharmaceutically acceptable salt thereof according to claim 1 exhibits potent antimicrobial activity against beta-lactamase producing Gram negative bacteria.

11. The method according to claim 9 , wherein the Gram negative bacteria is selected from:
Gram negative bacteria of enterobacteria selected from E. coli, Klebsiella, Serratia, Enterobacter, Citrobacter, Morganella, Providencia or Proteus;
Gram negative bacteria colonized in respiratory system selected from Haemophilus, Moraxella;
Gram negative bacteria of glucose non fermentation selected from Pseudomonas aeruginosa, Pseudomonas other than P. aeruginosa, Stenotrophomonas, Burkholderia or Acinetobacter;
Gram negative multidrug-resistant bacteria selected from Class B type metallo-betalactamase producing Gram negative bacteria, and extended-spectrum beta-lactamase (ESBL) producing bacteria; or
Gram beta-lactam drug resistant Gram negative bacteria selected from ESBL producing bacteria.

12. The method according to claim 9 , wherein the Gram positive bacteria is selected from methicillin-resistant Staphylococcus aureus (MRSA) or penicillin-resistant Streptococcus pneumoniae (PRSP).

13. A method for treating biothreat organism(s), which comprises administering a compound or a pharmaceutically acceptable salt thereof according to claim 1 or a pharmaceutically acceptable salt thereof to a subject in need thereof;
wherein:
the biothreat organism(s) is or are selected from Yersinia pestis, Bacillus anthracis, Francisella tularensis, Burkholderia mallei, Burkholderia pseudomallei, Brucella suis, Brucella melitensis or Brucella abortus.

14. A method for treating a biothreat organism or biothreat organisms, which comprises administering a compound according to claim 3 to a subject in need thereof;
wherein the biothreat organism(s) is or are selected from Yersinia pestis, Bacillus anthracis, Francisella tularensis, Burkholderia mallei, Burkholderia pseudomallei, Brucella suis, Brucella melitensis or Brucella abortus.

15. A method for treating a Gram-negative bacteria infection, which comprises administering a compound or a pharmaceutically aceeptable salt thereof according to claim 1 to a subject in need thereof.

16. The method according to claim 15 , wherein the bacterial infection is caused by Gram-Negative bacteria or Gram-Positive bacteria.

17. The method according to claim 16 , wherein the Gram negative bacteria is selected from:
Gram negative bacteria of enterobacteria selected from E. coli, Klebsiella, Serratia, Enterobacter, Citrobacter, Morganella, Providencia or Proteus;
Gram negative bacteria colonized in respiratory system selected from Haemophilus, Moraxella;
Gram negative bacteria of glucose non fermentation selected from Pseudomonas aeruginosa, Pseudomonas other than P. aeruginosa, Stenotrophomonas, Burkholderia or Acinetobacter;
Gram negative multidrug-resistant bacteria selected from Class B type metallo-betalactamase producing Gram negative bacteria, and extended-spectrum beta-lactamase (ESBL) producing bacteria; or
Gram beta-lactam drug resistant Gram negative bacteria selected from ESBL producing bacteria.

18. A method for treating a Gram-negative bacterial infection, which comprises administering a pharmaceutical composition according to claim 3 to a subject in need thereof.

19. A method for treating Gram-positive bacterial infections, which comprises administering a compound or a pharmaceutically acceptable salt thereof according to claim 1 to a subject in need thereof.

20. The method according to claim 19 , wherein the bacterial infection is caused by Gram-Positive bacteria.

21. The method according to claim 20 , wherein the Gram positive bacteria is selected from methicillin-resistant Staphylococcus aureus (MRSA) or penicillin-resistant Streptococcus pneumoniae (PRSP).

22. A method for treating Gram-positive bacterial infections, which comprises administering a pharmaceutical composition according to claim 3 to a subject in need thereof.

23. A method of treating a bacterial infection, which comprises administering a compound according to claim 3 to a subject in need thereof.

Assignees

• Glaxo Group Ltd
• Shionogi & Co
• Shionogi & Co

Inventors

• Aoki Toshiaki
• Kusano Hiroki
• Liao Xiangmin
• Pearson Neil David
• Pendrak Israil
• Sato Jun
• Thalji Reema K
• Yamawaki Kenji
• Yokoo Katsuki

Classifications

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• A61P27/16

  Otologicals · CPC title

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title

• A61P1/00

  Drugs for disorders of the alimentary tract or the digestive system · CPC title