Antimicrobial compositions and methods of use thereof
AssigneeWisconsin Alumni Research Foundation
InventorsDouglas B. Weibel, Ye Jin Eun, Maoquan Zhou
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Abstract
Described herein is a novel class of inhibitors of bacterial cell division. Several lines of evidence suggest the compounds disclosed herein specifically target the division process and have antibacterial activity in vitro and in vivo. The inhibitors are useful for treating subject in need of treatment for bacterial infections as will as for inhibiting bacterial growth, such as growth on contaminated surfaces.
Claims26
A method of treating a subject in need of treatment for a bacterial infection, comprising
- administering to the subject an effective amount of a cell division inhibitor of Formula Ib, or a pharmaceutically acceptable salt thereof:
- wherein G is
- wherein each instance of A is independently CH or N provided that the total number of N is 0 or 1;
- R1 is hydrogen, hydroxy, amino, halogen, cyano, C1-C6alkyl, C1-C6alkoxy, C1-C6haloalkyl, C1-C6haloalkoxy, aryl, or (aryl)alkyl;
- X1 is N, CR2, O, or S;
- R2 is hydrogen, C1-C6alkyl, C1-C6alkoxy, C1-C6haloalkyl, C1-C6haloalkoxy, aryl, or (aryl)alkyl;
- each instance of R3 independently is hydroxy, sulfate, nitro, amino, halogen, cyano, C1-C4alkyl, C1-C4alkoxy, C3-C7cycloalkyl, mono- and di-(C1-C4alkyl)amino, C2-C6alkoxycarbonyl, C2-C6alkanoyl, C1-C2haloalkyl, C1-C2haloalkoxy, phenyl, pyridyl, heterocycloalkyl, alkylcarboxamide, C2-C4alkenyl, or C2-C4alkynyl;
- n is 0, 1, or 2;
- m is 0 or 1;
- Q is a bond or a C1-C6 hydrocarbon linking group, wherein the linking group is substituted by 0, 1, 2, or 3 substituents independently chosen from hydroxy, sulfate, nitro, amino, cyano, halogen, C1-C4alkyl, C3-C7cycloalkyl, C1-C4alkoxy, mono- and di-(C1-C4alkyl)amino, C2-C6alkoxycarbonyl, C2-C6alkanoyl, C1-C2haloalkyl, C1-C2haloalkoxy, or oxo;
- wherein the 2-hydroxy-1-naphthalenyl group is substituted with 0, 1, or 2 hydroxy substituents.
A method of inhibiting bacterial growth, comprising contacting the bacteria with a cell division inhibitor of Formula Ib or a pharmaceutically acceptable salt thereof:
- wherein G is
- wherein each instance of A is independently CH or N provided that the total number of N is 0 or 1;
- R1 is hydrogen, hydroxy, amino, halogen, cyano, C1-C6alkyl, C1-C6alkoxy, C1-C6haloalkyl, C1-C6haloalkoxy, aryl, or (aryl)alkyl;
- X1 is N, CR2, O, or S;
- R2 is hydrogen, C1-C6alkyl, C1-C6alkoxy, C1-C6haloalkyl, C1-C6haloalkoxy, aryl, or (aryl)alkyl;
- each instance of R3 independently is hydroxy, sulfate, nitro, amino, halogen, cyano, C1-C4alkyl, C1-C4alkoxy, C3-C7cycloalkyl, mono- and di-(C1-C4alkyl)amino, C2-C6alkoxycarbonyl, C2-C6alkanoyl, C1-C2haloalkyl, C1-C2haloalkoxy, phenyl, pyridyl, heterocycloalkyl, alkylcarboxamide, C2-C4alkenyl, or C2-C4alkynyl;
- n is 0, 1, or 2;
- m is 0 or1;
- Q is a bond or a C1-C6 hydrocarbon linking group, wherein the linking group is substituted by 0, 1, 2, or 3 substituents independently chosen from hydroxy, sulfate, nitro, amino, cyano, halogen, C1-C4alkyl, C3-C7cycloalkyl, C1-C4alkoxy, mono- and di-(C1-C4alkyl)amino, C2-C6alkoxycarbonyl, C2-C6alkanoyl, C1-C2haloalkyl, C1-C2haloalkoxy, or oxo;
- wherein the 2-hydroxy-l-naphthalenyl group is substituted with 0, 1, or 2 hydroxy substituents.
Dependencies are inferred from the claim text.