Patent ID: 7994225

Claim:
A method of therapeutic treatment of a gram negative bacterial infection in an eye or ear of a subject, comprising co-administering to the eye or ear infected with a gram negative bacteria having an efflux pump an effective amount of an antimicrobial agent and a compound of formula I: wherein R 1 and R 2 are separately selected from the group consisting of amine and C 1-4 alkylamine; linkers L 1 and L 3 are separately selected from the group consisting of amine and C 1-2 alkylamine or are separately absent; aromatic rings A 1 and A 2 are separately selected from the group consisting of wherein Z 1 -Z 4 are each C, with the proviso that aromaticity of the aromatic rings are maintained; Z 1 -Z 4 that are C are optionally substituted with C 1-4 alkyl, CH 2 NH 2 , halogen, methoxy, CH 2 C(O)NMe 2 , C(O)NH 2 , C(O)NMe 2 , SO 2 Me, or SO 2 NH 2 ; linker L 2 is a 1 to 12 unit chain, wherein each units is independently selected from the group consisting of CH 2 , C(CH 3 ) 2 , O, C(O), S, S(O), S(O) 2 , NH, NR 4 , phenyl, monocyclic 5-membered heteroaryl, monocyclic 6-membered heteroaryl, —CH═CH— cis, —CH═CH— trans, NHC(O)NH, NR 4 C(O)NH, NHC(O)NR 4 , NR 4 C(O)NR 4 , OC(O)NH, NR 4 C(O)O, OC(O)NR 4 , and NHC(O)O with the proviso that L 2 does not contain a C(O)NH, C(O)NR 4 , C(O)O, or C(O)S unit; wherein the 5-membered heteroaryls are selected from the group consisting of imidazole, furane, thiophene, thiazole, isothiazole, oxazole, isoxazole, 1,2,3-oxadiazole, 1,3,4-oxadiazole, 1,2,4-oxadiazole, 1,2,3-triazole, and 1,3,4-triazole; the 6-membered heteroaryls are selected from the group consisting of pyridine, pyrimidine, pyridazine, 1,2,4-triazine, and 1,3,5-triazine; and R 4 is selected from the group consisting of H and C 1-4 alkyl.