Modulators of orphan nuclear receptors for NASH and other metabolic disorders

A method for treatment of disease selected from the group consisting of non-alcoholic steatohepatitis (NASH), alcoholic steatohepatitis (ASH), non-alcoholic fatty liver disease (NAFLD) comprising administering an effective treatment amount of a compound of Formula A to a patient in need of treatment thereof,

• wherein:
• wherein Z is C(O), and X and Y are selected from the group consisting of —NH—, —N(NH2)—, —NH(OH)—, N(C1-10 alkyl)-, —N(C3-10 cycloalkyl)-, —N(C2-10 alkenyl)-, —N(C2-10 alkynyl)-, —N(aryl)-, or —N(heteroaryl)
• A and B are phenyl;
• u and v are independently 0, 1, 2, 3 or 4;
• with the proviso that at least one of u and v is 1, 2, 3, or 4;
• each R1 and R2 are independently R3, OH, OR3, SR3, S(O)R3, SO2R3, C(O)R3, C(O)OR3, OC(O)R3, OC(O)OR3, NH2, NHR3, NHC(O)R3, NR3C(O)R3, NHS(O)2R3, NR3S(O)2R3, NHC(O)OR3, NR3C(O)OR3, NHC(O)NH2, NHC(O)NHR3, NHC(O)N(R3)2, NR3C(O)N(R3)2, C(O)NH2, C(O)NHR3, C(O)N(R3)2, C(O)NHOH, C(O)NHOR3, C(O)NHSO2R3, C(O)NR3SO2R3, SO2NH2, SO2NHR3, SO2N(R3)2, COOH, C(O)H, C(N)NH2, C(N)NHR3, C(N)N(R3)2, C(N)OH, C(N)OCH3, CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, halo (F, Cl, Br, or I), —CH2-phosphonate, —CH2O-phosphate, CH2P(O)(OH)2, CH2P(O)(OR3)2, CH2P(O)(OR3)(NR3), CH2P(O)(NR3)2, CH2P(O)(OH)(OC1-10 alkyl-O—C1-20 alkyl), or CH2-cycloSal monophosphate prodrug,
• wherein the term phosphate includes monophosphate, diphosphate, triphosphate, and stabilized phosphate prodrugs, and the term phosphonate includes the same prodrugs that are present in the phosphate prodrugs,
• and when R1 and R2 are on adjacent carbon, they can come together to form an saturated or unsaturated alkyl, an aromatic or a heteroaromatic ring
• each R3 is, independently, aryl, heteroaryl, C3-10 cycloalkyl, C3-10 cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, C1-10 alkyl, C2-10 alkenyl or C2-10 alkynyl, each of which is unsubstituted or independently substituted with one or more substituents selected from the group consisting of R4, OH, OR4, SR4, S(O)R4, SO2R4, C(O)R4, C(O)OR4, OC(O)R4, OC(O)OR4, NH2, NHR4, NHC(O)R4, NR4C(O)R4, NHS(O)2R4, NR4S(O)2R4, NHC(O)OR4, NR4C(O)OR4, NHC(O)NH2, NHC(O)NHR4, NHC(O)N(R4)2, NR4C(O)N(R4)2, C(O)NH2, C(O)NHR4, C(O)N(R4)2, C(O)NHOH, C(O)NHOR4, C(O)NHSO2R4, C(O)NR4SO2R4, SO2NH2, SO2NHR4, SO2N(R4)2, COOH, C(O)H, C(N)NH2, C(N)NHR4, C(N)N(R4)2, C(N)OH, C(N)OCH4, CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, halo (F, Cl, Br, or I), P(O)(OH)2, P(O)(OR4)2, P(O)(OR4)(NR4), P(O)(NR4)2, P(O)(OH)(OC1-10 alkyl-O—C1-20 alkyl), cycloSal monophosphate prodrugs, CH2P(O)(OH)2, CH2P(O)(OR4)2, CH2P(O)(OR4)(NR4), CH2P(O)(NR4)2, CH2P(O)(OH)(OC1-10 alkyl-O—C1-20 alkyl), and CH2-cycloSal monophosphate prodrugs, each R4 are independently selected from aryl, heteroaryl, arylalkyl, alkylaryl, C3-10 cycloalkyl, C3-10 cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, C1-10 alkyl, C2-10 alkenyl or C2-10 alkynyl, each of which is unsubstituted or independently substituted with one or more substituents selected from the group consisting of R5, OH, OR5, SR5, S(O)R5, SO2R5, C(O)R5, C(O)OR5, OC(O)R5, OC(O)OR5, NH2, NHR5, NHC(O)R5, NR5C(O)R5, NHS(O)2R5, NR5S(O)2R5, NHC(O)OR5, NR5C(O)OR5, NHC(O)NH2, NHC(O)NHR5, NHC(O)N(R5)2, NR5C(O)N(R5)2, C(O)NH2, C(O)NHR5, C(O)N(R5)2, C(O)NHOH, C(O)NHOR5, C(O)NHSO2R5, C(O)NR5SO2R5, SO2NH2, SO2NHR5, SO2N(R5)2, COOH, C(O)H, C(N)NH2, C(N)NHR5, C(N)N(R5)2, C(N)OH, C(N)OCH3, CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, halo (F, Cl, Br, or I), P(O)(OH)2, P(O)(OR4)2, P(O)(OR4)(NR4), P(O)(NR4)2, P(O)(OH)(OC1-10 alkyl-O—C1-20 alkyl), and cycloSal monophosphate prodrugs,
• each R5 are independently aryl, heteroaryl, C3-10 cycloalkyl, C3-10 cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, C1-10 alkyl, C2-10 alkenyl or C2-10 alkynyl, each of which is unsubstituted or independently substituted with one or more substituents selected from the group consisting of R6, OH, OR6, SR6, S(O)R6, SO2R6, C(O)R6, C(O)OR6, OC(O)R6, OC(O)OR6, NH2, NHR6, NHC(O)R6, NR6C(O)R6, NHS(O)2R6, NR6S(O)2R6, NHC(O)OR6, NR6C(O)OR6, NHC(O)NH2, NHC(O)NHR6, NHC(O)N(R6)2, NR6C(O)N(R6)2, C(O)NH2, C(O)NHR6, C(O)N(R6)2, C(O)NHOH, C(O)NHOR6, C(O)NHSO2R6, C(O)NR6SO2R6, SO2NH2, SO2NHR6, SO2N(R6)2, COOH, C(O)H, C(N)NH2, C(N)NHR6, C(N)N(R6)2, C(N)OH, C(N)OCH3, CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, F, Cl, Br, I, P(O)(OH)2, P(O)(OR4)2, P(O)(OR4)(NR4), P(O)(NR4)2, P(O)(OH)(OC1-10 alkyl-O—C1-20 alkyl), and cycloSal monophosphate prodrugs, each R6 are independently aryl, heteroaryl, C3-10 cycloalkyl, C3-10 cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, C1-10 alkyl, C2-10 alkenyl or C2-10 alkynyl, each of which is unsubstituted or independently substituted with one or more substituents selected from the group consisting of C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, OH, NH2, C(O)NH2, C(O)NHOH, SO2NH2, COOH, C(O)H, C(N)NH2, C(N)OH, C(N)OCH3, CN, N3, NO2, CF3, CF2CF3, OCF3, OCF2CF3, halo (F, Cl, Br, or I), P(O)(OH)2, P(O)(OR4)2, P(O)(OR4)(NR4), P(O)(NR4)2, P(O)(OH)(OC1-10 alkyl-O—C1-20 alkyl), and cycloSal monophosphate prodrugs,
• or a pharmaceutically-acceptable salt thereof.