β-lactamase inhibitors
Disclosed herein inter alia are Boron containing compounds and methods for treating infections related to antibiotic resistant microorganisms.
1. A compound of the formula:
wherein,
L 1 is unsubstituted alkylene;
L 2 is a bond, substituted or unsubstituted alkylene or substituted or unsubstituted heteroalkylene;
R 2 is hydrogen or substituted or unsubstituted C 1 -C 5 alkyl;
R 3 is substituted or unsubstituted aryl.
2. The compound of claim 1 , of the formula:
wherein ring A is, substituted or unsubstituted aryl;
R 5 is independently hydrogen, halogen, CX a 3 , —CN, —SO 2 Cl, —SO p R 14 , —SO q NR 11 R 12 , —NHNH 2 , —ONR 11 R 12 , —NHC═(O)NHNH 2 ,
—NHC═(O)NR 11 R 12 , —N(O) r , —NR 11 R 12 , —C(O)R 13 , —C(O)—OR 13 , —C(O)NR 11 R 12 , —OR 14 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
wherein two adjacent R 5 substituents are optionally joined to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
v is an integer from 0 to 7;
R 11 , R 12 , R 13 , and R 14 are independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
q and r are independently 1 or 2;
p is independently an integer from 0 to 4;
X a is —Cl, —Br, —I, or —F.
3. The compound of claim 1 , having the formula:
wherein ring A is substituted or unsubstituted arylene;
wherein ring B are independently substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 6 is independently hydrogen, halogen, —CX a 3 , —CN, —SO 2 Cl, —SO p1 R 18 , —SO q1 NR 15 R 16 , —NHNH 2 , —ONR 15 R 16 , —NHC═(O)NHNH 2 ,
—NHC═(O)NR 15 R 16 , —N(O) r1 , —NR 15 R 16 , —C(O)R 17 , —C(O)—OR 17 , —C(O)NR 15 R 16 , —OR 18 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
wherein two adjacent R 6 substituents are optionally joined to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 15 , R 16 , R 17 , and R 18 are independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
q1 and r1 are independently 1 or 2;
p1 is an integer from 0 to 4;
X a1 is —Cl, —Br, —I, or —F;
w is an integer from 0 to 7.
4. The compound of claim 1 , of the formula:
wherein,
R 5 is independently hydrogen, halogen, —CX a 3 , —CN, —SO 2 Cl, —SO p R 14 , —SO q NR 11 R 12 , —NHNH 2 , —ONR 11 R 12 , —NHC═(O)NHNH 2 ,
—NHC═(O)NR 11 R 12 , —N(O) r , —NR 11 R 12 , —C(O)R 13 , —C(O)—OR 13 , —C(O)NR 11 R 12 , —OR 14 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
wherein two adjacent R 5 substituents are optionally joined to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 11 , R 12 , R 13 , and R 14 are independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
q and r are independently 1 or 2;
p is independently an integer from 0 to 4;
X a is —Cl, —Br, —I, or —F;
v1 is an integer from 0 to 5.
5. The compound of claim 1 , having the formula:
wherein,
R 5 is independently hydrogen, halogen, —CX a 3 , —CN, —SO 2 Cl, —SO p R 14 , —SO q NR 11 R 12 , —NHNH 2 , —ONR 11 R 12 , —NHC═(O)NHNH 2 ,
—NHC═(O)NR 11 R 12 , —N(O) r , —NR 11 R 12 , —C(O)R 13 , —C(O)—OR 13 , —C(O)NR 11 R 12 , —OR 14 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
wherein two adjacent R 5 substituents are optionally joined to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 6 is independently hydrogen,
halogen, —CX a1 3 , —CN, —C(O)R 17 , —C(O)—OR 17 , —C(O)NR 15 R 16 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 11 , R 12 , R 13 , and R 14 are independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
q and r are independently 1 or 2;
p is independently an integer from 0 to 4;
X a is —Cl, —Br, —I, or —F;
R 15 , R 16 , and R 17 are independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
X a1 is —Cl, —Br, —I, or —F; and
v2 is an integer from 0 to 4.
6. The compound of claim 1 , having the formula:
wherein,
R 5 is independently hydrogen, halogen, —CX a 3 , —CN, —SO 2 Cl, —SO p R 14 , —SO q NR 11 R 12 , —NHNH 2 , —ONR 11 R 12 , —NHC═(O)NHNH 2 ,
—NHC═(O)NR 11 R 12 , —N(O) r , —NR 11 R 12 , —C(O)R 13 , —C(O)—OR 13 , —C(O)NR 11 R 12 , —OR 14 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
wherein two adjacent R 5 substituents are optionally joined to form a substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 6 is independently hydrogen,
halogen, —CX a1 3 , —CN, —C(O)R 17 , —C(O)—OR 17 , —C(O)NR 15 R 16 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 11 , R 12 , R 13 , and R 14 are independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
q and r are independently 1 or 2;
p is independently an integer from 0 to 4;
X a is —Cl, —Br, —I, or —F;
R 15 , R 16 , and R 17 are independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
X a1 is —Cl, —Br, —I, or —F;
v2 is an integer from 0 to 4.
7. The compound of claim 1 , having the formula:
wherein,
R 5 is independently hydrogen, halogen, —CX a 3 , —CN, —SO 2 Cl, —SO p R 14 , —SO q NR 11 R 12 , —NHNH 2 , —ONR 11 R 12 , —NHC═(O)NHNH 2 ,
—NHC═(O)NR 11 R 12 , —N(O) r , —NR 11 R 12 , —C(O)R 13 , —C(O)—OR 13 , —C(O)NR 11 R 12 , —OR 14 , substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
R 11 , R 12 , R 13 , and R 14 are independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;
q and r are independently 1 or 2;
p is independently an integer from 0 to 4;
X a is —Cl, —Br, —I, or —F.
8. The compound of claim 7 , wherein R 5 is halogen.
9. The compound of claim 7 , wherein R 5 is —Cl.
10. The compound of claim 7 , wherein R 5 is —CF 3 .
11. A compound selected from
12. A compound selected from
13. A pharmaceutical composition comprising a pharmaceutically acceptable excipient and a compound of claim 1 .