Novel inhibitors of bacterial biofilms and related methods

A compound corresponding to the following chemical structure:

• wherein R1 is selected from the group consisting of hydrogen, methyl, halide, lower haloalkyl, nitrile, lower alkyl nitrile, lower alkyl, substituted lower alkyl, lower alkenyl, substituted lower alkenyl, lower alkynyl, substituted lower alkynyl, lower cycloalkyl, lower cycloalkenyl, aryl, substituted aryl, heteroaryl, and substituted heteroaryl;
• wherein R2 is selected from the group consisting of carboxyl, amide, hydroxyamide, methylamide, —CH2N(CH3)2, —CH2NR6R7,
• wherein R3 is selected from the group consisting of hydrogen and methyl;
• wherein one of R4 and R5 is hydrogen and the other is methyl;
• wherein R6 and R7 are independently selected from the group consisting of hydrogen, methyl, ethyl, propyl, isopropyl, and butyl;
• wherein R8 is selected from the group consisting of hydroxyl, amino, —N(CH3)2, and —NHCH3;
• wherein R9 is selected from the group consisting of hydrogen, halide, lower alkyl, lower alkenyl, lower alkynyl, morpholinyl, piperazinyl, lower alkyl piperazinyl, heterocycloalkyl, lower cycloalkyl, lower cycloalkenyl;
• and lower alkyl, lower alkenyl, and lower alkynyl optionally substituted with moieties selected from the group consisting of hydroxyl, amino, lower aminoalkyl, halide, lower alkoxy, lower alkoxyalkyl, lower alkoxycarbonyl, lower alkylcarbonylamino, carboxyl, amide, hydroxyamide, —CONHCH3, —NHCONH2, —SO2NH2, —SO2CH3, —NHCOCH3, —NHCSNH2, and —NHSO2CH3;
• and wherein R10 and R11 together with the carbon atoms to which they are attached form an aromatic N-heterocycle which is substituted or not selected from the group consisting of indole, imidazole, quinoline, isoquinoline, pyridine, triazine, pyrazine, pyrimidine, pyridazine, isoindole, pyrrole, benzimidazole, purine, pyrazole, benzopyrazole, indazole, quinoxaline, acridine, quinazoline, indolizine, carbazole and cinnoline;
• and salts thereof.

A compound according to claim 1, wherein the compound corresponds to the following chemical structure:

• wherein R1 is selected from the group consisting of hydrogen, methyl, halide, lower haloalkyl, nitrile, lower alkyl nitrile, lower alkyl, substituted lower alkyl, lower alkenyl, substituted lower alkenyl, lower alkynyl, substituted lower alkynyl, lower cycloalkyl, lower cycloalkenyl, aryl, substituted aryl, heteroaryl, and substituted heteroaryl;
• wherein R2 is selected from the group consisting of carboxyl, amide, hydroxyamide, methylamide, —CH2N(CH3)2, —CH2NR6R7,
• wherein R3 is selected from the group consisting of hydrogen and methyl;
• wherein one of R4 and R5 is hydrogen and the other is methyl;
• wherein R6 and R7 are independently selected from the group consisting of hydrogen, methyl, ethyl, propyl, isopropyl, and butyl;
• wherein R8 is selected from the group consisting of hydroxyl, amino, —N(CH3)2, and —NHCH3;
• and wherein R9 is selected from the group consisting of hydrogen, halide, lower alkyl, lower alkenyl, lower alkynyl, morpholinyl, piperazinyl, lower alkyl piperazinyl, heterocycloalkyl, lower cycloalkyl, lower cycloalkenyl;
• and lower alkyl, lower alkenyl, and lower alkynyl optionally substituted with moieties selected from the group consisting of hydroxyl, amino, lower aminoalkyl, halide, lower alkoxy, lower alkoxyalkyl, lower alkoxycarbonyl, lower alkylcarbonylamino, carboxyl, amide, hydroxyamide, —CONHCH3, —NHCONH2, —SO2NH2, —SO2CH3, —NHCOCH3, —NHCSNH2, and —NHSO2CH3;
• and salts thereof.

A method for inhibiting or reducing the formation or growth of a biofilm comprising contacting said biofilm or a cell capable of biofilm formation or growth with an effective amount of a compound or a composition comprising the compound corresponding to the following chemical structure:

• wherein R1 is selected from the group consisting of hydrogen, methyl, halide, lower haloalkyl, nitrile, lower alkyl nitrile, lower alkyl, substituted lower alkyl, lower alkenyl, substituted lower alkenyl, lower alkynyl, substituted lower alkynyl, lower cycloalkyl, lower cycloalkenyl, aryl, substituted aryl, heteroaryl, and substituted heteroaryl;
• wherein R2 is selected from the group consisting of carboxyl, amide, hydroxyamide, methylamide, —CH2N(CH3)2, —CH2NR6R7,
• wherein R3 is selected from the group consisting of hydrogen and methyl;
• wherein one of R4 and R5 is hydrogen and the other is methyl;
• wherein R6 and R7 are independently selected from the group consisting of hydrogen, methyl, ethyl, propyl, isopropyl, and butyl;
• wherein R8 is selected from the group consisting of hydroxyl, amino, —N(CH3)2, and —NHCH3;
• wherein R9 is selected from the group consisting of hydrogen, halide, lower alkyl, lower alkenyl, lower alkynyl, morpholinyl, piperazinyl, lower alkyl piperazinyl, heterocycloalkyl, lower cycloalkyl, lower cycloalkenyl;
• and lower alkyl, lower alkenyl, and lower alkynyl optionally substituted with moieties selected from the group consisting of hydroxyl, amino, lower aminoalkyl, halide, lower alkoxy, lower alkoxyalkyl, lower alkoxycarbonyl, lower alkylcarbonylamino, carboxyl, amide, hydroxyamide, —CONHCH3, —NHCONH2, —SO2NH2, —SO2CH3, —NHCOCH3, —NHCSNH2, and —NHSO2CH3;
• and wherein R10 and R11 together with the carbon atoms to which they are attached form an aromatic N-heterocycle which is substituted or not selected from the group consisting of indole, imidazole, quinoline, isoquinoline, pyridine, triazine, pyrazine, pyrimidine, pyridazine, isoindole, pyrrole, benzimidazole, purine, pyrazole, benzopyrazole, indazole, quinoxaline, acridine, quinazoline, indolizine, carbazole and cinnoline;
• and salts thereof.