Acid and ester compounds and methods of using the same

A compound of Formula II:

• wherein:
• Z is CH or N;
• Q is phenyl or monocyclic Het;
• wherein said phenyl and monocyclic Het are optionally unsubstituted or substituted with one or more groups independently selected from halo, cyano, nitro, C1-C6 alkyl, C3-C6 alkenyl, C3-C6 alkynyl, —C0-C4 alkyl-CO2R11, —C0-C4 alkyl-C(O)SR11, —C0-C4 alkyl-CONR12R13, —C0-C4 alkyl-COR14, —C0-C4 alkyl-NR12R13, —C0-C4 alkyl-SR11, —C0-C4 alkyl-OR11, —C0-C4 alkyl-SO3H, —C0-C4 alkyl-SO2NR12R13, —C0-C4 alkyl-SO2R11, —C0-C4 alkyl-SOR14, —C0-C4 alkyl-OCOR14, —C0-C4 alkyl-OC(O)NR12R13, —C0-C4 alkyl-OC(O)OR14, —C0-C4 alkyl-NR12C(O)OR14, —C0-C4 alkyl-NR12C(O)NR12R13, and —C0-C4 alkyl-NR12COR14, where said C1-C6 alkyl is optionally unsubstituted or substituted by one or more halo substituents, p is 0-4;
• k is 0, 1 or 2;
• n is 2-4;
• q is 0 or 1;
• W1 and W2 are each independently C3-C6 cycloalkyl or aryl;
• each R1 and R2 is independently selected from H, C1-C4 alkyl, —OH, —O—C1-C4 alkyl, —SH, and —S—C1-C4 alkyl;
• each R3 is the same or different and is independently selected from halo, cyano, C1-C6 alkyl, —C0-C4 alkyl-NR12R13, —C0-C4 alkyl-OR11, —C0-C4 alkyl-SO2NR12R13, and —C0-C4 alkyl-CO2H, wherein said C1-C6 alkyl is optionally unsubstituted or substituted by one or more halo substituents;
• each R4 and R5 is independently H or C1-C4 alkyl;
• R6 and R7 are each independently H or C1-C4 alkyl;
• R8 and R9 are each independently H or C1-C4 alkyl;
• R10 is selected from H, C1-C6 alkyl, —C0-C4 alkyl-Ar, —C0-C4 alkyl-Het and —C0-C4 alkyl-C3-C6 cycloalkyl;
• R11 is selected from H, C1-C6 alkyl, —C0-C4 alkyl-Ar, —C0-C4 alkyl-Het and —C0-C4 alkyl-C3-C7 cycloalkyl;
• each R12 and each R13 are independently selected from H, C1-C6 alkyl, —C0-C4 alkyl-Ar, —C0-C4 alkyl-Het and —C0-C4 alkyl-C3-C7 cycloalkyl, or R12 and R13 together with the nitrogen to which they are attached form a 4-7 membered heterocyclic ring which optionally contains one or more additional heteroatoms selected from N, O, and S;
• and
• R14 is selected from C1-C6 alkyl, —C0-C4 alkyl-Ar, —C0-C4 alkyl-Het and —C0-C4 alkyl-C3-C7 cycloalkyl;
• provided that R10 is not H or methyl when p is 1 and R1 and R2 are each H, k is 0, n is 3 and each R4 and R5 are H, q is 1 and R8 and R9 are each H, Q is unsubstituted phenyl or 4-methoxyphenyl or 2-chloro-3-trifluoromethyl-phenyl, R6 and R7 are each H, W1 is unsubstituted phenyl and W2 is unsubstituted phenyl or unsubstituted cyclohexyl;
• or a pharmaceutically acceptable salt or solvate thereof.

A method for the prevention or treatment of an LXR mediated disease or condition comprising administering a therapeutically effective amount of a compound having Formula I-A:

• wherein:
• Z is CH, CR3 or N;
• wherein when Z is CH or CR3, k is 0-4 and when Z is N, k is 0-3;
• p is 0-8;
• n is 2-8;
• q is 0 or 1;
• Q is selected from C3-C8 cycloalkyl, phenyl, and monocyclic Het;
• wherein said C3-C8 cycloalkyl, phenyl and monocyclic Het are optionally unsubstituted or substituted with one or more groups independently selected from halo, cyano, nitro, C1-C6 alkyl, C3-C6 alkenyl, C3-C6 alkynyl, —C0-C6 alkyl-CO2R11, —C0-C6 alkyl-C(O)SR11, —C0-C6 alkyl-CONR12R13, —C0-C6 alkyl-COR14, —C0-C6 alkyl-NR12R13, —C0-C6 alkyl-SR11, —C0-C6 alkyl-OR11, —C0-C6 alkyl-SO3H, —C0-C6 alkyl-SO2NR12R13, —C0-C6 alkyl-SO2R11, —C0-C6 alkyl-SOR14, —C0-C6 alkyl-OCOR14, —C0-C6 alkyl-OC(O)NR12R13, —C0-C6 alkyl-OC(O)OR14, —C0-C6 alkyl-NR12C(O)OR14, —C0-C6 alkyl-NR12C(O)NR12R13, and —C0-C6 alkyl-NR12COR14, where said C—C6 alkyl is optionally unsubstituted or substituted by one or more halo substituents;
• W1 and W2 are each independently C3-C8 cycloalkyl or aryl;
• each R1 and R2 is independently selected from H, C1-C6 alkyl, —OH, —O—C1-C6 alkyl, —SH, and —S—C1-C6 alkyl;
• each R3 is the same or different and is independently selected from halo, cyano, nitro, C1-C6 alkyl, C3-C6 alkenyl, C3-C6 alkynyl, —C0-C6 alkyl-Ar, —C0-C6 alkyl-Het, —C0-C6 alkyl-C3-C7 cycloalkyl, —C0-C6 alkyl-CO2R11, —C0-C6 alkyl-C(O)SR11, —C0-C6 alkyl-CONR12R13, —C0-C6 alkyl-COR14, —C0-C6 alkyl-NR12R13, —C0-C6 alkyl-SR11, —C0-C6 alkyl-OR11, —C0-C6 alkyl-SO3H, —C0-C6 alkyl-SO2NR12R13, —C0-C6 alkyl-SO2R11, —C0-C6 alkyl-SOR14, —C0-C6 alkyl-OCOR14, —C0-C6 alkyl-OC(O)NR12R13, —C0-C6 alkyl-OC(O)OR14, —C0-C6 alkyl-NR12C(O)OR14, —C0-C6 alkyl-NR12C(O)NR12R13, and —C0-C6 alkyl-NR12COR14, wherein said C1-C6 alkyl is optionally unsubstituted or substituted by one or more halo substituents;
• each R4 and R5 is independently H or C1-C4 alkyl;
• R6 and R7 are each independently H or C1-C4 alkyl;
• R8 and R9 are each independently H or C1-C4 alkyl;
• R10 is selected from H, C1-C8 alkyl, C3-C8 alkenyl, C3-C8 alkynyl, —C0-C6 alkyl-Ar, —C0-C6 alkyl-Het and —C0-C6 alkyl-C3-C7 cycloalkyl;
• R11 is selected from H, C1-C6 alkyl, C3-C6 alkenyl, C3-C6 alkynyl, —C0-C6 alkyl-Ar, —C0-C6 alkyl-Het and —C0-C6 alkyl-C3-C7 cycloalkyl;
• each R12 and each R13 are independently selected from H, C1-C6 alkyl, C3-C6 alkenyl, C3-C6 alkynyl, —C0-C6 alkyl-Ar, —C0-C6 alkyl-Het and —C0-C6 alkyl-C3-C7 cycloalkyl, or R13 and R14 together with the nitrogen to which they are attached form a 4-7 membered heterocyclic ring which optionally contains one or more additional heteroatoms selected from N, O, and S;
• and
• R14 is selected from C1-C6 alkyl, C3-C6 alkenyl, C3-C6 alkynyl, —C0-C6 alkyl-Ar, —C0-C6 alkyl-Het and —C0-C6 alkyl-C3-C7 cycloalkyl;
• provided that R10 is not H when p is 1 and R1 and R2 are each H, k is 0, n is 3 and each R4 and R5 are H, q is 1 and R8 and R9 are each H, Q is unsubstituted phenyl or 4-methoxyphenyl or 2-chloro-3-trifluoromethyl-phenyl, R6 and R7 are each H, W1 is unsubstituted phenyl and W2 is unsubstituted phenyl or unsubstituted cyclohexyl;
• or a pharmaceutically acceptable salt or solvate thereof.

A method for the prevention or treatment of an LXR mediated disease or condition comprising administering a therapeutically effective amount of a compound having Formula II-A:

• wherein:
• Z is CH or N;
• Q is phenyl or monocyclic Het;
• wherein said phenyl and monocyclic Het are optionally unsubstituted or substituted with one or more groups independently selected from halo, cyano, nitro, C1-C6 alkyl, C3-C6 alkenyl, C3-C6 alkynyl, —C0-C4 alkyl-CO2R11, —C0-c4 alkyl-C(O)SR11, —C0-C4 alkyl-CONR12R13, —C0-C4 alkyl-COR14, —C0-C4 alkyl-NR12R13, —C0-C4 alkyl-SR11, —C0-C4 alkyl-OR11, —C0-C4 alkyl-SO3H, —C0-C4 alkyl-SO2NR12R13, —C0-C4 alkyl-SO2R11, —C0-C4 alkyl-SOR14, —C0-C4 alkyl-OCOR14, —C0-C4 alkyl-OC(O)NR12R13, —C0-C4 alkyl-OC(O)OR14, —C0-C4 alkyl-NR12C(O)OR14, —C0-C4 alkyl-NR12C(O)NR12R13, and —C0-C4 alkyl-NR12COR14, where said C1-C6 alkyl is optionally unsubstituted or substituted by one or more halo substituents,
• p is 0-4;
• k is 0, 1 or 2;
• n is 2-4;
• q is 0 or 1;
• W1 and W2 are each independently C3-C6 cycloalkyl or aryl;
• each R1 and R2 is independently selected from H, C1-C4 alkyl, —OH, —O—C1-C4 alkyl, —SH, and —S—C1-C4 alkyl;
• each R3 is the same or different and is independently selected from halo, cyano, C1-C6 alkyl, —C0-C4 alkyl-NR12R13, —C0-C4 alkyl-OR11, —C0-C4 alkyl-SO2NR12R13, and —C0-C4 alkyl-CO2H, wherein said C1-C6 alkyl is optionally unsubstituted or substituted by one or more halo substituents;
• each R4 and R5 is independently H or C1-C4 alkyl;
• R6 and R7 are each independently H or C1-C4 alkyl;
• R8 and R9 are each independently H or C1-C4 alkyl;
• R10 is selected from H, C1-C6 alkyl, —C0-C4 alkyl-Ar, —C0-C4 alkyl-Het and —C0-C4 alkyl-C3-C6 cycloalkyl;
• R11 is selected from H, C1-C6 alkyl, —C0-C4 alkyl-Ar, —C0-C4 alkyl-Het and —C0-C4 alkyl-C3-C7 cycloalkyl;
• each R12 and each R13 are independently selected from H, C1-C6 alkyl, —C0-C4 alkyl-Ar, —C0-C4 alkyl-Het and —C0-C4 alkyl-C3-C7 cycloalkyl, or R12 and R13 together with the nitrogen to which they are attached form a 4-7 membered heterocyclic ring which optionally contains one or more additional heteroatoms selected from N, O, and S;
• and
• R14 is selected from C1-C6 alkyl, —C0-C4 alkyl-Ar, —C0-C4 alkyl-Het and —C0-C4 alkyl-C3-C7 cycloalkyl;
• provided that R10 is not H when p is 1 and R1 and R2 are each H, k is 0, n is 3 and each R4 and R5 are H, q is 1 and R8 and R9 are each H, Q is unsubstituted phenyl or 4-methoxyphenyl or 2-chloro-3-trifluoromethyl-phenyl, R6 and R7 are each H, W1 is unsubstituted phenyl and W2 is unsubstituted phenyl or unsubstituted cyclohexyl;
• or a pharmaceutically acceptable salt or solvate thereof.