Bis-indole pyrroles useful as antimicrobials agents

1. A method of treating a microbial infection comprising administering a compound having a structure of Formula I, and pharmaceutically acceptable salts and pro-drug esters thereof:

wherein a ring can include one or more additional hetero-atoms, such as nitrogen, sulfur or oxygen; and can include a non-nitrogen hetero-atom, such as sulfur or oxygen, in place of a nitrogen(s) in Formula I; and

wherein each of a R 1 , a R 2 , five R 3 , five R 4 , a R 5 , and two R 6 is independently selected from the group consisting of a hydrogen atom, a halogen, a sugar, an aminoalkyl, mono-substituted, poly-substituted or unsubstituted variants of the following residues: saturated C 1 –C 24 alkyl, unsaturated C 2 –C 24 alkenyl or C 2 –C 24 alkynyl, acyl, acyloxy, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, heteroaryl, arylalkoxy carbonyl, alkoxy carbonylacyl, amino, aminocarbonyl, aminocarboyloxy, nitro, azido, phenyl, hydroxy, alkylthio, arylthio, oxysulfonyl, carboxy, cyano, and halogenated alkyl including polyhalogenated alkyl, —CO—O—R 7 , carbonyl —CCO—R 7 , —CO—NR 8 R 9 , —(CH 2 ) n —COOR 7 , —CO—(CH 2 ) n —COOR 7 , —(CH 2 ) n —NR 8 R 9 , ester, alkoxycarbonyl, aryloxycarbonyl, wherein n is an integer from 1 to 6,

wherein each R 7 , R 8 and R 9 is separately selected from the group consisting of a hydrogen atom, halogen atom, mono-substituted, poly-substituted or unsubstituted variants of the following residues: saturated C 1 –C 24 alkyl, unsaturated C 2 –C 24 alkenyl or C 2 –C 24 alkynyl, acyl, acyloxy, alkyloxycarbonyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, alkoxy, cycloalkoxy, aryl, heteroaryl, arylalkoxy carbonyl, alkoxy carbonylacyl, amino, aminocarbonyl, aminocarboyloxy, nitro, azido, phenyl, hydroxy, alkylthio, arylthio, oxysulfonyl, carboxy, cyano, and halogenated alkyl including polyhalogenated alkyl, a 5-membered ring, a 6-membered ring, or combination thereof.

2. The method of claim 1 , wherein at least one of the R 1 , R 2 , the five R 3 , the five R 4 , R 5 , and the two R 6 substitutions is asymmetric.

3. The method of claim 1 , wherein the two R 6 substitutions are asymmetric.

4. The method of claim 1 , wherein the five R 4 and the five R 3 substitutions are asymmetric.

5. The method of claim 1 , wherein at least of the five R 3 is a halogen atom and at least one R 4 is a halogen atom, and the indole rings do not include additional hetero-atoms, but do include the indole nitrogen.

6. The method of claim 1 , wherein R 8 is —(CH 2 ) 2 — and R 9 is —(CH 2 ) 2 —, wherein R 8 and R 9 are directly connected to each other so as to form a five membered ring.

7. The method of claim 6 , wherein R 8 is —(CH 2 ) 2 — and R 9 is —(CH 2 ) 2 —, wherein R 8 and R 9 are connected to each other via R 10 so as to form a six membered ring, wherein R 10 is selected from the group consisting of CH 2 , NH, O, and S.

8. The method of claim 5 , wherein

one of the two R 6 is an alkoxy carbonyl;

one of the R 6 is a hydrogen atom;

at least one of the five R 3 is a chloride atom; and

R 1 , R 2 , and R 5 are each hydrogen atoms.

9. The method of claim 8 , wherein the alkoxy carbonyl is a methoxy carbonyl.

10. The method of claim 1 further comprising:

identifying a subject that would benefit from administration of an antimicrobial agent;

administering the compound to the subject.

11. The method of claim 1 , wherein the microbial infection is an infection of at least one a gram positive bacterium.

12. The method of claim 1 , wherein the microbial infection is an infection of at least E. faecalis -Vans.

13. The method of claim 1 , wherein the microbial infection is an infection of at least H. influenzae.