Antimicrobial agents and uses thereof

1 . A compound of formula I:

wherein a 1 and a 2 combine to form a fused ring described by formulas:

X 1 represents a sulfur 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 5 and R 6 combine to form a 3-8 membered cyclic system,

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;

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;

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 compound of formula IV:

wherein X 1 represents an oxygen atom or a sulfur atom;

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 1-10 alkyl, C 2-10 alkenyl, S(O) 1-2 —C 1-10 -alkyl, S(O) 1-2 —C 1-10 -aryl, S(O) 1-2 —C 1-10 -heteroaryl, or S(O) 1-2 —C 1-10 -heterocyclyl;

each of R 7 and R 8 is, independently, a hydrogen atom or an alkyl group having 1 to 3 carbon atoms;

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;

R 12 is H, O, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 -alkynyl, acyl, aryl, or heteroalkyl; and

R 13 is H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 -alkynyl, acyl, aryl, heteroalkyl, OH, SH, OR 3 , or SR 3 .

5 . A compound of formula V:

V

wherein X 4 represents an oxygen atom or a sulfur atom;

R 2 represents OR 3 , SR 3 , a hydrogen atom, or an alkyl group having 1 to 3 carbon atoms;

R 3 represents H, C 1-10 alkyl, C 2-10 alkenyl, S(O) 1-2 —C 1-10 -alkyl, S(O) 1-2 —C 1-10 -aryl, S(O) 1-2 —C 1-10 -heteroaryl, or S(O) 1-2 —C 1-10 -heterocyclyl;

each of R 7 and R 8 is, independently, a hydrogen atom or an alkyl group having 1 to 3 carbon atoms;

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;

R 14 is C 1-6 alkyl, C 2-6 alkenyl, C 2-6 -alkynyl, aryl, or heteroalkyl; and

R 15 is H, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 -alkynyl, acyl, aryl, or heteroalkyl.

6 . 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 , 4 , or 5 in an amount sufficient to treat or kill the microbes.

7 . The method of claim 6 , wherein contacting said microbes comprises administering said compound to a mammal in an amount effective to treat a microbial infection

8 . The method of claim 7 , wherein said compound of claim 1 , 4 , or 5 is administered in parallel with one or more antifungal agents, antibacterial agents, or antiprotozoan agents, or combinations thereof.

9 . 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 , 4 , or 5 in an amount effective to increase the antimicrobial activity of the antimicrobial agent.

10 . A method of treating a disease associated with a bacterial infection in a patient, said method comprising administering to said patient a compound of claim 1 , 4 , or 5 in an amount sufficient to treat said disease.

11 . The method of claim 10 , wherein said disease is an inflammatory disease.

12 . A pharmaceutical composition comprising an effective amount of a compound of claim 1 , 4 , 5 , or a suitable salt thereof, together with a pharmaceutically acceptable carrier or diluent.