Back to results
US 9,730,913 B2Granted
High affinity beta lactamase inhibitors
AssigneeThe Johns Hopkins University
InventorsErnesto Freire, Rogelio Siles, Patrick C. Ross
Life of this patent
Estimating the term…
Abstract
Inhibitors of beta lactamases and their use in treating bacterial infections are disclosed.
Claims45
A compound of Formula (I):
- wherein:
- each n is independently an integer selected from the group consisting of 1, 2, 3, 4, and 5;
- each R2 is independently selected from the group consisting of:
- R3 is selected from the group consisting of hydrogen, hydroxyl, alkoxyl, and
- p is an integer selected from the group consisting of 1 and 2;
- X1 is selected from the group consisting of N and CR8;
- X2 is selected from the group consisting of S, NR8, and CR8R9;
- Y1 is selected from the group consisting of S, O, and NR8;
- Y2 is selected from the group consisting of N and CR8;
- R1, R4, R5, R6, and R7 are each independently selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, alkoxyl, hydroxyl, hydroxyalkyl, carboxyl, acyl, Cl, Br, NO2, —NH2, F, phenyl, cyclohexyl, benzyloxyl, and —SO3H, including —COOR10, wherein R10 is lower alkyl, carbonyl, carbamoyl, alkylcarbamoyl, halogen, amino, nitro, nitrile, amide, haloalkyl, aryl, cycloalkyl, aralkyloxyl, and —SO3H;
- R8, and R9 are each independently selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, alkoxyl, hydroxyl, hydroxyalkyl, carboxyl, acyl, including —COOR10, wherein R10 is lower alkyl, carbonyl, carbamoyl, alkylcarbamoyl, halogen, amino, nitro, nitrile, amide, haloalkyl, aryl, cycloalkyl, aralkyloxyl, and —SO3H;
- and a pharmaceutically acceptable salt, prodrug, or solvate thereof.
9 more elements
A method for inhibiting a beta lactamase, the method comprising contacting the beta lactamase with a compound of Formula (I) in an amount to inhibit the beta lactamase:
- wherein:
- each n is independently an integer selected from the group consisting of 1, 2, 3, 4, and 5;
- each R2 is independently selected from the group consisting of:
- R3 is selected from the group consisting of:
- hydrogen, hydroxyl, alkoxyl, and
- p is an integer selected from the group consisting of 1 and 2;
- X1 is selected from the group consisting of N and CR8;
- X2 is selected from the group consisting of S, NR8, and CR8R9;
- Y1 is selected from the group consisting of S, O, and NR8;
- Y2 is selected from the group consisting of N and CR8;
- R1, R4,R5,R6, and R7 are each independently selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, alkoxyl, hydroxyl, hydroxyalkyl, carboxyl, acyl, Cl, Br, NO2 , —NH2, F, phenyl, cyclohexyl, benzyloxyl, and —SO3H, including —COOR10, wherein R10 is lower alkyl, carbonyl, carbamoyl, alkylcarbamoyl, halogen, amino, nitro, nitrile, amide, haloalkyl, aryl, cycloalkyl, aralkyloxyl, and —SO3H;
- R8and R9 are each independently selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, alkoxyl, hydroxyl, hydroxyalkyl, carboxyl, acyl, including —COOR10, wherein R10 is lower alkyl, carbonyl, carbamoyl, alkylcarbamoyl, halogen, amino, nitro, nitrile, amide, haloalkyl, aryl, cycloalkyl, aralkyloxyl, and —SO3H;
- and a pharmaceutically acceptable salt, prodrug, or solvate thereof.
10 more elements
A method for treating a bacterial infection in a subject having said infection thereof, the method comprising administering to the subject a therapeutically-effective amount of a beta-lactam antibiotic, optionally in combination with one or more other antibacterial agents, in combination with a therapeutically-effective amount of a compound of Formula (I):
- wherein:
- each n is independently an integer selected from the group consisting of 1, 2, 3, 4, and 5;
- each R2 is independently selected from the group consisting of:
- R3 is selected from the group consisting of:
- hydrogen, hydroxyl, alkoxyl, and
- p is an integer selected from the group consisting of 1 and 2;
- X1 is selected from the group consisting of N and CR8;
- X2 is selected from the group consisting of S, NR8, and CR8R9;
- Y1 is selected from the group consisting of S, O, and NR8;
- Y2 is selected from the group consisting of N and CR8;
- R1,R4,R5,R6,and R7are each independently selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, alkoxyl, hydroxyl, hydroxyalkyl, carboxyl, acyl, Cl, Br, NO2 , —NH2, F, phenyl, cyclohexyl, benzyloxyl, and —SO3H, including —COOR10, wherein R10 is lower alkyl, carbonyl, carbamoyl, alkylcarbamoyl, halogen, amino, nitro, nitrile, amide, haloalkyl, aryl, cycloalkyl, aralkyloxyl, and —SO3H;
- R8 and R9 are each independently selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, alkoxyl, hydroxyl, hydroxyalkyl, carboxyl, acyl, including —COOR10, wherein R10 is lower alkyl, carbonyl, carbamoyl, alkylcarbamoyl, halogen, amino, nitro, nitrile, amide, haloalkyl, aryl, cycloalkyl, aralkyloxyl, and —SO3H;
- and a pharmaceutically acceptable salt, prodrug, or solvate thereof.
10 more elements
A method for overcoming a bacterial resistance in a subject in need of treatment thereof, the method comprising administering to the subject a therapeutically effective amount of a compound of Formula (I):
- wherein:
- each n is independently an integer selected from the group consisting of 1, 2, 3, 4, and 5;
- each R2 is independently selected from the group consisting of:
- R3 is selected from the group consisting of:
- hydrogen, hydroxyl, alkoxyl, and
- p is an integer selected from the group consisting of 1 and 2;
- X1 is selected from the group consisting of N and CR8;
- X2 is selected from the group consisting of S, NR8, and CR8R9;
- Y1 is selected from the group consisting of S, O, and NR8;
- Y2 is selected from the group consisting of N and CR8;
- R1,R4,R5,R6,and R7are each independently selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, alkoxyl, hydroxyl, hydroxyalkyl, carboxyl, acyl, Cl, Br, NO2, —NH2 , F, phenyl, cyclohexyl, benzyloxyl, and —SO3H, including —COOR10, wherein R10 is lower alkyl, carbonyl, carbamoyl, alkylcarbamoyl, halogen, amino, nitro, nitrile, amide, haloalkyl, aryl, cycloalkyl, aralkyloxyl, and —SO3H;
- R8and R9 are each independently selected from the group consisting of hydrogen, substituted or unsubstituted alkyl, alkoxyl, hydroxyl, hydroxyalkyl, carboxyl, acyl, including —COOR10, wherein R10 is lower alkyl, carbonyl, carbamoyl, alkylcarbamoyl, halogen, amino, nitro, nitrile, amide, haloalkyl, aryl, cycloalkyl, aralkyloxyl, and —SO3H;
- and a pharmaceutically acceptable salt, prodrug, or solvate thereof.
10 more elements
Dependencies are inferred from the claim text.