3-substituted propionic acids as αV integrin inhibitors

A compound of Formula (I):

• or a pharmaceutically acceptable salt thereof, wherein:
• A is CR6b;
• E is CR6b;
• G is N;
• L is C;
• M is N;
• X is a C1-6 alkylene substituted with 0, 1, or 2 R7b;
• Z is a covalent bond;
• R1 is:
• R2 is hydrogen or C1-6 alkyl;
• R3 is hydrogen;
• R4 is NRaRb, ORa, S(O)nR10, C(O)NRaRb, NHC(O)ORa, NHC(O)NRaRb, NHC(O)R10, OC(O)NRaRb, OC(O)R10, NHS(O)nNRaRb, or NHS(O)nR10
• R5 is hydrogen or R5a;
• R5a is C1-6 alkyl, phenyl, or 5- to 7-membered heterocyclyl, wherein the alkyl, phenyl, and heterocyclyl are each independently substituted with 0 to 3 R5d;
• R5d, at each occurrence, is independently halo, OH, alkoxy, oxo, or alkyl;
• R6b is each independently hydrogen, halo, cyano, nitro, amino, OH, C1-6 alkyl, haloalkyl, alkoxy, haloalkoxy, hydroxyalkyl, aminoalkyl, or C3-5 cycloalkyl, wherein the cycloalkyl is substituted with 0, 1, 2, or 3 halo, cyano, nitro, amino, or OH;
• R7b is each independently halo, cyano, hydroxyl, amino, C1-6 alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxy, haloalkoxy, amido, carbamate, or sulfonamide;
• R10 is C1-6 alkyl, 3- to 10-membered carbocyclyl, 3- to 10-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl;
• wherein the alkyl, carbocyclyl, heterocyclyl are each independently substituted with 0, 1, 2, or 3 R11;
• R11 is halo, cyano, nitro, OH, amino, C1-6 alkyl, alkoxy, 3- to 10-membered carbocyclyl, 3- to 10-membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl;
• wherein the aryl, alkyl, and heteroaryl are each independently substituted with 0, 1, 2, or 3 R13;
• R13 and R14, at each occurrence, are independently halo, cyano, nitro, OH, amino, C1-6 alkyl, alkoxy, aminoalkyl, haloalkyl, haloalkoxy, haloaminoalkyl, 3 to 6 membered carbocyclyl, 3 to 6 membered heterocyclyl, 6- to 10-membered aryl, or 5- to 10-membered heteroaryl;
• wherein the aryl and heteroaryl, by themselves or as part of another group, are each independently substituted with one or more groups independently selected from halo, cyano, hydroxyl, amino, C1-6 alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxy, haloalkoxy, amido, carbamate, and sulfonamide;
• and the carbocyclyl and heterocyclyl, by themselves or as part of another group, are each independently substituted with one or more groups independently selected from halo, cyano, hydroxyl, amino, oxo, C1-6 alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxy, haloalkoxy, amido, carbamate, and sulfonamide;
• Ra and Rb, at each occurrence, are independently hydrogen, C1-10 alkyl, 3- to 10-membered carbocyclyl, or 3- to 10-membered heterocyclyl;
• wherein the alkyl, carbocyclyl, heterocyclyl are each independently substituted with 0, 1, 2, or 3 R14;
• Re is OH, C1-4 alkyl, halo, haloalkyl, C1-4 cycloalkyl, amino, amido, carbamate, or sulfonamide;
• Rf is hydrogen, CH3, CH2CH3, or COOCH2CH3;
• Rg is selected from CH3, CH2CH3, CH2CCl3, phenyl, 4-fluorophenyl, 4-methoxyphenyl, benzyl,
• n is 2;
• and
• r is an integer of 0, 1, 2, or 3.