Heterocyclic compounds useful in the treatment of disease

A method for treating a lysophosphatidic acid-dependent disease or condition in a subject in need thereof, the method comprising:

• administering to the subject a therapeutically effective amount of a compound having the structure of Formula I:
• or a pharmaceutically acceptable salt thereof,
• wherein Ring A is a 5 membered heteroarene selected from one of:
• wherein the dashed line indicates the point of attachment of Ring A to Ring B;
• Ring B is:
• wherein A1, A2 and A3 are independently ═CH— or —CH═;
• Ring C is absent;
• wherein RA is —CO2H;
• L1 is —UV—Z—, wherein —UV— is defined by
• —WO—, —WN(RJ)—, or —C(═O)N(RJ)—,
• wherein W is C1-C3 alkylene, and
• wherein Z is C1-C6 alkylene, C3-C6 cycloalkylene, —C(RL)2-, or —CHRL—;
• L2 is absent;
• wherein RC is —F, —Cl, —Br, —I, —OC1-C4 alkyl, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 fluoroalkyl, —CN or —H;
• and RD is —N(RF)—C(═O)XCH2—CY, —N(RF)—C(═O)XCH(RG)—CY, —N(RF)C(═O)XC(RG)2—CY, wherein X is —O—;
• RE is —H, —C1-C4 alkyl;
• RF is —H or C1-C4 alkyl;
• RG is —C1-C4 alkyl;
• CY is substituted or unsubstituted C6-C10 aryl, wherein if CY is substituted then CY is substituted with 1, 2, or 3 independently selected RH;
• wherein each RH is independently selected from —H, halogen, —OH, —ORJ, —SRJ, C1-C4 alkyl, C1-C4 fluoroalkyl, C1-C4 fluoroalkoxy, C1-C4 alkoxy;
• wherein each RJ is independently —H or C1-C6 alkyl;
• and
• wherein RL is —H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —C1-C4 alkylene-(substituted or unsubstituted cycloalkyl), —C1-C4 alkylene-(substituted or unsubstituted heterocycloalkyl), —C1-C4 alkylene(substituted or unsubstituted aryl), or —C1-C4 alkylene-(substituted or unsubstituted heteroaryl).

A method for reducing signal transduction through a lysophosphatidic acid receptor (LPAR), the method comprising:

• contacting the LPAR with a compound having the structure of Formula I:
• or a pharmaceutically acceptable salt thereof,
• wherein Ring A is a 5 membered heteroarene selected from one of:
• wherein the dashed line indicates the point of attachment of Ring A to Ring B;
• Ring B is:
• wherein A1, A2 and A3 are independently ═CH— or —CH═;
• Ring C is absent;
• wherein RA is —CO2H;
• L1 is —UV—Z—, wherein —UV— is defined by —WO—, —WN(RJ)—, or —C(═O)N(RJ)—,
• wherein W is C1-C3 alkylene, and
• wherein Z is C1-C6 alkylene, C3-C6 cycloalkylene, —C(RL)2-, or —CHRL—;
• L2 is absent;
• wherein RC is —F, —Cl, —Br, —I, —OC1-C4 alkyl, C1-C4 alkyl, C3-C6 cycloalkyl, C1-C4 fluoroalkyl, —CN or —H;
• and RD is —N(RF)—C(═O)XCH2—CY, —N(RF)—C(═O)XCH(RG)—CY,
• N(RF)C(═O)XC(RG)2—CY, wherein X is —O—;
• RE is —H, —C1-C4 alkyl;
• RF is —H or C1-C4 alkyl;
• RG is —C1-C4 alkyl;
• CY is substituted or unsubstituted C6-C10 aryl, wherein if CY is substituted then CY is substituted with 1, 2, or 3 independently selected RH;
• wherein each RH is independently selected from —H, halogen, —OH, —ORJ, —SRJ, C1-C4 alkyl, C1-C4 fluoroalkyl, C1-C4 fluoroalkoxy, C1-C4 alkoxy;
• wherein each RJ is independently —H or C1-C6 alkyl;
• and
• wherein RL is —H, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C1-C6 heteroalkyl, substituted or unsubstituted C1-C6 fluoroalkyl, substituted or unsubstituted C3-C6 cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, —C1-C4 alkylene-(substituted or unsubstituted cycloalkyl), —C1-C4 alkylene-(substituted or unsubstituted heterocycloalkyl), —C1-C4 alkylene(substituted or unsubstituted aryl), or —C1-C4 alkylene-(substituted or unsubstituted heteroaryl).