Lysophosphatidic acid receptor antagonists and their use in the treatment fibrosis

The compound of Formula (II):

• wherein:
• R1 is —CO2H, —CO2RD, —C(═O)NHSO2R10, —C(═O)N(R9)2, —C(═O)NH—OH, —C(═O)NH—CN, —P(═O)(OH)2, —P(═O)(ORD)2, —OPO3H2, —SO2NHC(═O)R10, —CN, —C(═NH)—NH2, —C(═NH)—NHC(═O)RD, —C(═O)NHCH2CH2SO3H, tetrazolyl, 5-oxo-2,5-dihydro-[1,2,4]oxadiazol-3-yl, or carboxylic acid bioisostere;
• RD is H or C1-C6alkyl;
• L2 is a substituted or unsubstituted C1-C6alkylene, substituted or unsubstituted C1-C6fluoroalkylene, or substituted or unsubstituted C1-C6heteroalkylene, where if L2 is substituted then L2 is substituted with 1, 2 or 3 R12;
• each R12 is independently F, C1-C4alkyl, C1-C4fluoroalkyl, hydroxyl, C1-C4alkoxy, C1-C4fluoroalkoxy or a substituted or unsubstituted phenyl;
• or L2 is -L3-X1-L4-;
• L3 is absent or a substituted or unsubstituted C1-C4alkylene, where if L3 is substituted then L3 is substituted with 1, 2, or 3 R13;
• each R13 is independently F, C1-C4alkyl, C1-C4fluoroalkyl, hydroxyl, C1-C4alkoxy or C1-C4fluoroalkoxy;
• X1 is absent, —O—, —S—, —S(O)—, —S(O)2—, —NR7—, —C(O)NR8—, —NR8C(═O)—, —NR8C(═O)CH2O—, —NR8C(═O)—CH(CH3)O—, —NR8C(═O)—C(CH3)2O—, —N(R8)S(═O)2—, —S(═O)2N(R8)—, —C(═O)—, —OC(═O)—, —C(═O)O—, —OC(═O)O—, —OC(═O)N(R8)—, —NR8C(═O)O—, or —NR8C(═O)N(R8)—;
• R7 is H, —S(═O)2R16, —S(═O)2N(R9)2, —C(═O)R10, —CO2R9, —C(═O)N(R9)2, C1-C4alkyl, C1-C4fluoroalkyl, or C1-C4heteroalkyl;
• R8 is H, C1-C4alkyl, or C1-C4fluoroalkyl;
• L4 is absent or a substituted or unsubstituted C1-C4alkylene, where if L4 is substituted then L4 is substituted with 1, 2, or 3 R14;
• each R14 is independently F, C1-C4alkyl, C1-C4fluoroalkyl, hydroxyl, C1-C4alkoxy or C1-C4fluoroalkoxy;
• or L2 is -L5-X2-L6-;
• L5 is absent, —C(═O)—, —S—, —S(O)—, —S(O)2—, —N(RD)—, —N(RD)C(═O)—, substituted or unsubstituted C1-C4alkylene, substituted or unsubstituted C1-C4fluoroalkylene, or a substituted or unsubstituted C1-C4heteroalkylene, where if L5 is substituted, then L5 is substituted with 1 or 2 R15, where each R15 is F, C1-C4alkyl, —OH, —OR8, or —N(R8)2;
• X2 is a substituted or unsubstituted cyclic group selected from a substituted or unsubstituted C3-C6cycloalkylene, a substituted or unsubstituted C2-C5heterocycloalkylene, a substituted or unsubstituted monocyclic C1-C5heteroarylene, and a substituted or unsubstituted phenylene, where if X2 is substituted, then X2 is substituted with 1 or 2 R17, each R17 is independently halogen, —CN, —OH, C1-C4alkyl, C1-C4fluoroalkyl, C1-C4fluoroalkoxy, C1-C4alkoxy, or C1-C4heteroalkyl;
• L6 is absent, a substituted or unsubstituted C1-C4alkylene, substituted or unsubstituted C1-C4fluoroalkylene, substituted or unsubstituted C1-C4heteroalkylene, —O—, —S—, —S(O)—, SO2, N(R8)—, or —C(═O)—N(R8)—C1-C4alkylene-, where if L6 is substituted, then L6 is substituted with 1 or 2 R16, where each R16 is independently F, C1-C4alkyl, —OH, —OR8, or —N(R8)2;
• RA and RB are independently halogen, —CN, —OH, C1-C4alkyl, C1-C4alkoxy, C1-C4fluoroalkyl, C1-C4fluoroalkoxy, or C3-C6cycloalkyl;
• Each Rc is independently halogen, —OH, —CH3, —CH2CH3, —CF3, —OCF3, —OCH3 and —OCH2CH3;
• A is phenyl, furanyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, imidazolyl, pyrazolyl, triazolyl, isothiazolyl, oxadiazolyl, pyridinyl, pyrimidinyl, pyrazinyl pyridazinyl, thiophenyl, isoquinolinyl, or thiadiazolyl;
• R3 is H or C1 to C4 alkyl;
• each R9 is independently H, C1-C6heteroalkyl, C1-C6fluoroalkyl, a substituted or unsubstituted C3-C10cycloalkyl, a substituted or unsubstituted C2-C10heterocycloalkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, a substituted or unsubstituted —C1-C4alkylene-C3-C10cycloalkyl, a substituted or unsubstituted —C1-C4alkylene-C2-C10heterocycloalkyl, a substituted or unsubstituted —C1-C4alkylene-aryl, or a substituted or unsubstituted —C1-C4alkylene-heteroaryl;
• or two R9 groups attached to the same N atom are taken together with the N atom to which they are attached to form a substituted or unsubstituted heterocycle;
• R10 is C1-C6alkyl, C1-C6heteroalkyl, C1-C6fluoroalkyl, a substituted or unsubstituted C3-C10cycloalkyl, a substituted or unsubstituted C2-C10heterocycloalkyl, a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, a substituted or unsubstituted —C1-C4alkylene-C3-C10cycloalkyl, a substituted or unsubstituted —C1-C4alkylene-C2-C10heterocycloalkyl, a substituted or unsubstituted —C1-C4alkylene-aryl, or a substituted or unsubstituted —C1-C4alkylene-heteroaryl;
• m is 0, 1, or 2;
• n is 0, 1, or 2;
• and
• p is 0, 1, or 2.