Antimicrobial agents and uses thereof
View Patent ↗The invention features compounds that act as antimicrobial agents and/or antimicrobial enhancer agents, compositions that include the antimicrobial enhancer agents of the invention, and methods for treating microbial infections using those compositions.
1. A compound of formula I:
wherein A 1 and A 2 combine to form a fused ring described by formulas:
X 1 represents an oxygen atom.
R 1 represents H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 -alkynyl, aryl, or heteroalkyl;
R 2 represents OR 3 , SR 3 , a hydrogen atom, or an alkyl group having 1 to 3 carbon atoms;
each R 3 , independently, represents H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 -alkynyl, acyl, aryl, heteroalkyl, S(O) 1-2 —C 1-6 alkyl, S(O) 1-2 -aryl, S(O) 1-2 —C 2-6 alkenyl, or S(O) 1-2 —C 2-6 -alkynyl;
and R 4 represents a group expressed by the formula:
wherein each of R 5 and R 6 is, independently, an alkyl group having 1 to 7 carbon atoms,
or R 4 represents a group expressed by the formula:
in which g represents an integer between 1 and 3; or R 4 represents a group expressed by the formula:
wherein each of R 7 and R 8 is, independently, a hydrogen atom or an alkyl group having 1 to 3 carbon atoms, and X 2 represents an oxygen atom, a sulfur atom, a carbonyl group,
or X 2 represents a group expressed by the formula:
in which each of R 9 and R 10 is, independently, a hydrogen atom, or an alkyl group having 1 to 3 carbon atoms, or R 9 and R 10 , in combination with each other, represent —(CH 2 ) k — in which k represents an integer between 1 and 4;
or X 2 represents a group expressed by the formula:
in which m represents 0 or 1, R 11 represents a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, or —(CH 2 ) n X 3 in which n represents an integer between 1 and 4, and X 3 represents a halogen atom, an alkoxy group having 1 to 3 carbon atoms, a vinyl group, or an ethynyl group,
or X 2 represents a group expressed by the formula:
2. The compound of claim 1 , wherein said compound is of formula II:
wherein
R 1 represents H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 -alkynyl, aryl, or heteroalkyl;
R 2 represents OR 3 , SR 3 , a hydrogen atom, or an alkyl group having 1 to 3 carbon atoms;
Each R 3 , independently, represents C 1-6 alkyl, C 2-6 alkenyl, C 2-6 -alkynyl, acyl, aryl, heteroalkyl, S(O) 1-2 —C- 1-6 alkyl, S(O) 1-2 -aryl, S(O) 1-2 —C 2-6 alkenyl, or S(O) 1-2 —C 2-6 -alkynyl;
each of R 7 and R 8 is, independently, a hydrogen atom or an alkyl group having 1 to 3 carbon atoms;
X 1 represents an oxygen atom;
and X 2 represents a group expressed by the formula:
in which m represents 0 or 1, and R 11 represents a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, or —(CH 2 ) n X 3 in which n represents an integer between 1 and 4, and X 3 represents a halogen atom, an alkoxy group having 1 to 3 carbon atoms, a vinyl group, or an ethynyl group.
3. The compound of claim 1 , wherein said compound is of formula III:
wherein
R 1 represents H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 -alkynyl, aryl, or heteroalkyl;
R 2 represents OR 3 , SR 3 , a hydrogen atom, or an alkyl group having 1 to 3 carbon atoms;
each R 3 , independently, represents C 1-6 alkyl, C 2-6 alkenyl, C 2-6 -alkynyl, acyl, aryl, heteroalkyl, S(O) 1-2 —C 1-6 alkyl, S(O) 1-2 -aryl, S(O) 1-2 —C 2-6 alkenyl, or S(O) 1-2 —C 2-6 -alkynyl;
each of R 7 and R 8 is, independently, a hydrogen atom or an alkyl group having 1 to 3 carbon atoms;
X 1 represents an oxygen atom;
and X 2 represents a group expressed by the formula:
in which m represents 0 or 1, and R 11 represents a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, or —(CH 2 ) n X 3 in which n represents an integer between 1 and 4, and X 3 represents a halogen atom, an alkoxy group having 1 to 3 carbon atoms, a vinyl group, or an ethynyl group.
4. A method of treating an infection of microbes selected from bacteria, fungi, and protozoans, or killing said microbes, said method comprising contacting said microbe or a site susceptible to microbial growth with a compound of claim 1 in an amount sufficient to treat said infection.
5. The method of claim 4 , wherein contacting said microbes comprises administering said compound to a mammal in an amount effective to treat a microbial infection.
6. The method of claim 5 , wherein said compound of claim 1 is administered in parallel with one or more antifungal agents, antibacterial agents, or antiprotozoan agents, or combinations thereof.
7. A method of enhancing the antimicrobial activity of an antimicrobial agent against a microbe, said method comprising:
a. contacting the microbe with the antimicrobial agent; and
b. contacting the microbe with a compound of claim 1 in an amount effective to increase the antimicrobial activity of the antimicrobial agent.
8. A method of treating disease associated with a bacterial infection in a patient, said method comprising administering to said patient a compound of claim 1 in amounts sufficient to treat said disease.
9. The method of claim 8 , wherein said disease in an inflammatory disease.
10. A pharmaceutical composition comprising an effective amount of a compound of claim 1 , or a suitable salt thereof, together with a pharmaceutically acceptable carrier or diluent.
11. The compound of claim 1 , wherein said compound has the structure:
12. The compound of claim 1 , wherein said compound has the structure:
13. The compound of claim 1 , wherein said compound has the structure:
14. The compound of claim 1 , wherein said compound has the structure:
15. The compound of claim 1 , wherein said compound has the structure:
16. The compound of claim 1 , wherein said compound has the structure:
17. The compound of claim 1 , wherein said compound has the structure:
18. The compound of claim 1 , wherein said compound has the structure:
19. The compound of claim 1 , wherein said compound has the structure:
20. The compound of claim 1 , wherein said compound has the structure:
21. The compound of claim 1 , wherein said compound has the structure:
22. The compound of claim 1 , wherein said compound has the structure:
23. The method of claim 4 , wherein said infection of microbes is an infection of bacteria.
24. The method of claim 23 , wherein said compound the structure:
25. The method of claim 23 , wherein said compound has the structure:
26. The method of claim 23 , wherein said compound has the structure:
27. The method of claim 23 , wherein said compound has the structure:
28. The method of claim 23 , wherein said compound has the structure:
29. The method of claim 23 , wherein said compound has the structure:
30. The method of claim 23 , wherein said compound has the structure:
31. The method of claim 23 , wherein said compound has the structure:
32. The method of claim 23 , wherein said compound has the structure:
33. The method of claim 23 , wherein said compound has the structure:
34. The method of claim 23 , wherein said compound has the structure:
35. The method of claim 23 , wherein said compound has the structure:
36. A method of enhancing the antibacterial activity of an antibacterial agent against bacteria, said method comprising:
a. contacting the bacteria with the antibacterial agent; and
b. contacting the bacteria with a compound of claim 1 in an amount effect to increase the antibacterial activity of the antibacterial agent.