Compounds and methods for treating bacterial infections
The present invention encompasses compounds and methods for treating urinary tract infections.
1. A compound of Formula (I):
wherein:
X is selected from the group consisting of hydrogen, OR 2 , SR 2 , and NR z ;
Z is selected from the group consisting of O, S, CR 3 and NR 4 ;
Y is selected from the group consisting of oxygen, sulfur, CR 3 , NR 4 , —N(R 5 )CO—, —CH 2 N(R 5 )—, —CH 2 N(R 5 )CO—, CO 2 , SO 2 , —CH 2 O—, —CH 2 S—, CO, —CON(R 5 )—, —SO 2 N(R 5 )—, —O(CH 2 ) n —, —S(CH 2 ) n —, —N(CH 2 ) n —, —(CH 2 ) n —, NR 5 , and an optionally substituted alkyl, alkene, alkyne, or heterocycle;
R 2 is independently selected from the group consisting of hydrogen, COR x , CONR x , hydrocarbyl, and substituted hydrocarbyl;
R 3 , R 4 , R 5 are independently selected from the group consisting of hydrogen, hydrocarbyl, and substituted hydrocarbyl;
R z is independently selected from the group consisting of hydrogen hydrocarbyl, substituted hydrocarbyl, —COR x , —CONR x R x SO 2 R x , and —CO 2 R x ;
R x is independently selected from the group consisting of hydrogen, NR 4 R 5 , and an optionally substituted alkyl, cycloalkyl, heterocycle, or aryl;
n is an integer from 1 to 10; and
R 1 is Formula (IV):
wherein:
A is independently selected from the group consisting of CR 6 and N;
R 6 is independently selected from the group consisting of hydrogen, hydrocarbyl, and substituted hydrocarbyl;
R 11 and R 12 are independently selected from the group consisting of OR 15 , —NR 15 R 16 , —NR 15 COR 16 , —NR 15 CO 2 R 16 , —NR 15 CONR 16 , —NR 15 SO 2 R 16 , —COR 15 , —SO 2 R 16 , nitro, cyano, halogen, aryl, heterocycle, —COOR 15 , —CONR 16 R 17 , —SO 2 NR 18 R 19 , alkenyl, alkynyl, hydrocarbyl, and substituted hydrocarbyl;
R 15 , R 16 , R 17 , R 18 , R 19 are independently selected from the group consisting of hydrogen, hydrocarbyl, substituted hydrocarbyl, aryl, and heterocycle, and R 16 and R 17 together can optionally form a ring, and R 18 and R 19 together can optionally form a ring; and
(a) of R 11 is the integer 1 and (a) of R 12 is either the integer 1 or the integer 2.
2. The compound of claim 1 , wherein X is OR 2 and Z is O.
3. The compound of claim 1 , wherein X is OR 2 ; Z is O; R 11 is selected from the group consisting of —OR 15 , methyl, halogen, CO 2 Me, hydrocarbyl, and substituted hydrocarbyl.
4. The compound of claim 3 , wherein Formula (IV) is:
5. The compound of claim 1 , wherein X is OR 2 ; Z is O; Y is selected from the group consisting of oxygen, sulfur, CR 3 , NR 4 , —N(R 5 )CO—, —CH 2 N(R 5 )—, —CH 2 O—, —CON(R 5 )—, —CH 2 N(R 5 )CO, and —(CH 2 ) n — and an optionally substituted alkyl.
6. The compound of claim 1 , wherein X is OR 2 ; Z is O; Y is selected from the group consisting of oxygen, sulfur, NH, —CH 2 O—, —CONH, —CH 2 NHCO—, —(CH 2 ) n — and an optionally substituted alkyl.
7. The compound of claim 5 , wherein Y is selected from the group consisting of oxygen, sulfur, NH, —(CH 2 ) n — and an optionally substituted alkyl; and R 12 is selected from the group consisting of —COOR 15 and —CONR 16 R 17 .
8. The compound of claim 1 , wherein X is OR 2 ; Z is O; Y is selected from the group consisting of oxygen and an optionally substituted alkyl; Formula (IV) is:
R 11 is selected from the group consisting of —OR 15 , methyl, halogen, CO 2 Me, and hydrocarbyl; and R 12 is selected from the group consisting of —COOR 15 and —CONR 16 R 17 .
9. A method of treating a urinary tract infection, the method comprising administering a compound of claim 1 to a subject in need thereof.
10. The method of claim 9 , wherein the subject is further administered a bactericidal composition.
11. A method of reducing the resistance of a bacterium to a bactericidal compound, the method comprising administering a compound of claim 1 to a subject in need thereof.