Compounds and methods

A compound according to Formula (I) or a pharmaceutically acceptable salt thereof:

• wherein:
• m is 0, 1, or 2;
• X1, X2, X3, X4, and X5 are each independently selected from N, N+—O−, CH, and CR6, wherein 0-3 of X1, X2, X3, X4, and X5 are N or N+—O− and 0-3 of X1, X2, X3, X4, and X5 are CR6;
• one of Y1 and Y2 is O or NR8 and the other is a bond;
• or X1 is CR6, Y1 is NR8, Y2 is a bond, and R6 and R8 taken together with the atoms to which they are attached form a five to seven membered ring, optionally containing an additional heteroatom selected from oxygen, nitrogen, and sulfur, which ring is optionally substituted by (C1-C4)alkyl;
• K1, K2, and K3 are each independently selected from N, CH, and CR6, wherein 0-2 of K1, K2, and K3 are N and 0-2 of K1, K2, and K3 are CR6;
• R1 is (C3-C6)alkyl, (C3-C6)haloalkyl, (C3-C8)cycloalkyl, (C3-C6)alkoxy, (C1-C6)alkoxy(C1-C2)alkyl, aryl, heteroaryl, aryl(C1-C6)alkyl, heteroaryl(C1-C6)alkyl, or heterocycloalkyl, each of which is optionally substituted one, two, or three times, independently, by R6;
• R2 is hydrogen, (C1-C6)alkyl, or (C1-C6)haloalkyl;
• or R1 and R2 taken together with the carbon atom to which they are attached form a three to eight membered ring, optionally containing a heteroatom selected from oxygen, nitrogen, and sulfur, which ring is optionally substituted one, two, or three times, independently, by R6;
• R3 and R3a are each independently hydrogen, hydroxyl, (C1-C6)alkyl, (C1-C6)haloalkyl, halogen, (C1-C6)alkoxy, amino, (C1-C4)alkylamino, or ((C1-C4)alkyl)((C1-C4)alkyl)amino;
• R4 is hydroxyl or amino;
• R5 is phenyl or 5- or 6-membered heteroaryl, wherein said phenyl or heteroaryl is optionally substituted one, two, or three times, independently, by (C1-C6)alkyl, (C1-C6)haloalkyl, (C3-C6)cycloalkyl, halogen, cyano, hydroxyl, hydroxy(C1-C6)alkyl, (C1-C6)alkoxy, —((C0-C3)alkyl)CO2R7, —((C0-C3)alkyl)CONR7R8, (C1-C4)alkoxy(C1-C6)alkyl, amino(C1-C6)alkyl, ((C1-C4)alkyl)((C1-C4)alkyl)amino(C1-C6)alkyl, (C1-C4)alkylamino(C1-C6)alkyl, amino, (C1-C4)alkylamino, ((C1-C4)alkyl)((C1-C4)alkyl)amino, aryl, heteroaryl, aryl(C1-C6)alkyl, heteroaryl(C1-C6)alkyl, or heterocycloalkyl;
• each R6 is independently selected from (C1-C6)alkyl, (C1-C6)haloalkyl, (C3-C6)cycloalkyl, halogen, cyano, hydroxyl, hydroxy(C1-C6)alkyl, (C1-C6)alkoxy, (C1-C4)alkoxy(C1-C6)alkyl, amino, (C1-C4)alkylamino, ((C1-C4)alkyl)((C1-C4)alkyl)amino, aryl, heteroaryl, aryl(C1-C6)alkyl, heteroaryl(C1-C6)alkyl, and heterocycloalkyl;
• R7 is hydrogen, (C1-C6)alkyl, (C1-C6)haloalkyl, (C3-C6)cycloalkyl, (C1-C4)alkoxy(C1-C6)alkyl, aryl, heteroaryl, aryl(C1-C6)alkyl, heteroaryl(C1-C6)alkyl, or heterocycloalkyl;
• R8 is hydrogen, (C1-C6)alkyl, or (C1-C6)haloalkyl;
• or R7 and R8 taken together with the nitrogen atom to which they are attached form a four to eight membered ring, optionally containing an additional heteroatom selected from oxygen, nitrogen, and sulfur, which ring is optionally substituted by (C1-C4)alkyl, (C1-C4)haloalkyl, (C3-C6)cycloalkyl, —CO2H, —CO2(C1-C4)alkyl, hydroxyl, hydroxy(C1-C6)alkyl, (C1-C4)alkoxy, (C1-C4)alkoxy(C1-C6)alkyl, amino, (C1-C4)alkylamino, or ((C1-C4)alkyl)((C1-C4)alkyl)amino;
• R9 is (C1-C6)alkyl, (C1-C6)haloalkyl, (C3-C6)cycloalkyl, halogen, oxo, cyano, hydroxyl, hydroxy(C1-C6)alkyl, (C1-C6)alkoxy, —((C0-C3)alkyl)NHCO2R7, —((C0-C3)alkyl)N((C1-C4)alkyl)CO2R7, —((C0-C3)alkyl)NHC(O)R7, —((C0-C3)alkyl)N((C1-C4)alkyl)C(O)R7, —((C0-C3)alkyl)CO2R7, —((C0-C3)alkyl)CONR7R8, —((C0-C3)alkyl)C(O)R7, (C1-C4)alkoxy(C1-C6)alkyl, amino(C1-C6)alkyl, ((C1-C4)alkyl)((C1-C4)alkyl)amino(C1-C6)alkyl, (C1-C4)alkylamino(C1-C6)alkyl, amino, (C1-C4)alkylamino, ((C1-C4)alkyl)((C1-C4)alkyl)amino, aryl, heteroaryl, aryl(C1-C6)alkyl, heteroaryl(C1-C6)alkyl, or heterocycloalkyl;
• and
• Cy taken together with the two carbon atoms of the phenyl or heteroaryl group to which it is fused comprises a five or six membered ring, optionally containing one, two, or three heteroatoms independently selected from oxygen, nitrogen, and sulfur, which ring is optionally substituted one or two times, independently, by R9;
• provided that the compound of Formula (I) is not:
• wherein:
• K1, K2, and K3 are each independently selected from N and CH, wherein 0-2 of K1, K2, and K3 are N;
• R1 is F, Cl, —CH3, or —OCH3;
• R2 is —CH3, —CN, —N(CH3)2, or —OCH3;
• and
• R3 is phenyl or 5- or 6-membered heteroaryl, wherein said phenyl or heteroaryl is optionally substituted one, two or three times, independently, by (C1-C4)alkyl, (C1-C4)haloalkyl, (C3-C6)cycloalkyl, halogen, cyano, hydroxyl, hydroxy(C1-C6)alkyl, (C1-C4)alkoxy, —((C0-C3)alkyl)CO2(C1-C4)alkyl, —((C0-C3)alkyl)CONH2, —((C0-C3)alkyl)CONH(C1-C4)alkyl, —((C0-C3)alkyl)CON((C1-C4)alkyl)((C1-C4)alkyl), or (C1-C4)alkoxy(C1-C6)alkyl.