Fused-aryl and heteroaryl derivatives as modulators of metabolism and the prophylaxis and treatment of disorders related thereto

A compound of Formula (I):

• or a pharmaceutically acceptable salt, hydrate or solvate thereof;
• wherein:
• A and B are each independently C1-3 alkylene optionally substituted with 1 to 4 substituents selected from the group consisting of C1-3 alkyl, C1-4 alkoxy, carboxy, cyano, C1-3 haloalkyl and halogen;
• D is N—R2;
• E is N, C or CR3, wherein R3 is H or C1-8 alkyl;
• is a single bond when E is N or CR3, or a double bond when E is C;
• K is a C3-6 cycloalkylene or C1-3 alkylene wherein each are optionally substituted with 1 to 4 substituents selected from the group consisting of C1-3 alkyl, C1-4 alkoxy, carboxy, cyano, C1-3 haloalkyl and halogen;
• or K is a bond;
• Q is O, S, S(O) or S(O)2;
• T is N or CR5;
• M is N or CR6;
• J is N or CR7;
• U is C;
• V is a bond;
• W is C;
• X is N;
• Y is O;
• Z is C;
• R5, R6, and R7 are each independently selected from the group consisting of H, C1-5 acyloxy, C2-6 alkenyl, C1-4 alkoxy, C1-8 alkyl, C1-4 alkylcarboxamide, C2-6 alkynyl, C1-4 alkylsulfonamide, C1-4 alkylsulfinyl, C1-4 alkylsulfonyl, C1-4 alkylthio, C1-4 alkylureyl, amino, C1-4 alkylamino, C2-8 dialkylamino, carboxamide, cyano, C3-6 cycloalkyl, C2-6 dialkylcarboxamide, C2-6 dialkylsulfonamide, halogen, C1-4 haloalkoxy, C1-4 haloalkyl, C1-4 haloalkylsulfinyl, C1-4 haloalkylsulfonyl, C1-4 haloalkylthio, hydroxyl, hydroxylamino and nitro;
• wherein said C2-6 alkenyl, C1-8 alkyl, C2-6 alkynyl and C3-6 cycloalkyl are optionally substituted with 1, 2, 3 or 4 substituents selected from the group consisting of C1-5 acyl, C1-5 acyloxy, C1-4 alkoxy, C1-4 alkylamino, C1-4 alkylcarboxamide, C1-4 alkylthiocarboxamide, C1-4 alkylsulfonamide, C1-4 alkylsulfinyl, C1-4 alkylsulfonyl, C1-4 alkylthio, C1-4 alkylthioureyl, C1-4 alkylureyl, amino, carbo-C1-6-alkoxy, carboxamide, carboxy, cyano, C2-8 dialkylamino, C2-6 dialkylcarboxamide, C1-4 dialkylthiocarboxamide, C2-6 dialkylsulfonamide, C1-4 alkylthioureyl, C1-4 haloalkoxy, C1-4 haloalkyl, C1-4 haloalkylsulfinyl, C1-4 haloalkylsulfonyl, C1-4 haloalkylthio, halogen, hydroxyl, hydroxylamino and nitro;
• Ar1 is aryl or heteroaryl each optionally substituted with R13, R14, R15, R16, and R17;
• wherein R13 is selected from the group consisting of C1-5 acyl, C1-6 acylsulfonamide, C1-5 acyloxy, C2-6 alkenyl, C1-4 alkoxy, C1-8 alkyl, C1-4 alkylamino, C1-6 alkylcarboxamide, C1-4 alkylthiocarboxamide, C2-6 alkynyl, C1-4 alkylsulfonamide, C1-4 alkylsulfinyl, C1-4 alkylsulfonyl, C1-4 alkylthio, C1-4 alkylthioureyl, C1-4 alkylureyl, amino, arylsulfonyl, carbamimidoyl, carbo-C1-6-alkoxy, carboxamide, carboxy, cyano, C3-7 cycloalkyl, C3-7 cycloalkyloxy, C2-6 dialkylamino, C2-6 dialkylcarboxamide, C2-6 dialkylthiocarboxamide, guanidinyl, halogen, C1-4 haloalkoxy, C1-4 haloalkyl, C1-4 haloalkylsulfinyl, C1-4 haloalkylsulfonyl, C1-4 haloalkylthio, heterocyclic, heterocyclic-oxy, heterocyclicsulfonyl, heterocyclic-carbonyl, heteroaryl, heteroarylcarbonyl, hydroxyl, nitro, C4-7 oxo-cycloalkyl, phenoxy, phenyl, sulfonamide, sulfonic acid, and thiol, and wherein said C1-5 acyl, C1-6 acylsulfonamide, C1-4 alkoxy, C1-8 alkyl, C1-4 alkylamino, C1-6 alkylsulfonamide, C1-4 alkylsulfonyl, C1-4 alkylthio, arylsulfonyl, carbamimidoyl, C2-6 dialkylamino, heterocyclic, heterocyclic-carbonyl, heteroaryl, phenoxy and phenyl are optionally substituted with 1 to 5 substituents selected independently from the group consisting of C1-5 acyl, C1-5 acyloxy, C2-6 alkenyl, C1-4 alkoxy, C1-7 alkyl, C1-4 alkylamino, C1-4 alkylcarboxamide, C2-6 alkynyl, C1-4 alkylsulfonamide, C1-4 alkylsulfinyl, C1-4 alkylsulfonyl, C1-4 alkylthio, C1-4 alkylureyl, carbo-C1-6-alkoxy, carboxamide, carboxy, cyano, C3-7 cycloalkyl, C3-7 cycloalkyloxy, C2-6 dialkylamino, C2-6 dialkylcarboxamide, halogen, C1-4 haloalkoxy, C1-4 haloalkyl, C1-4 haloalkylsulfinyl, C1-4 haloalkylsulfonyl, C1-4 haloalkylthio, heteroaryl, heterocyclic, hydroxyl, nitro, phenyl, and phosphonooxy, and wherein said C1-7 alkyl and C1-4 alkylcarboxamide are each optionally substituted with 1 to 5 substituents selected from the group consisting of C1-4 alkoxy and hydroxy;
• or
• R13 is a group of Formula (A):
• wherein:
• “p” and “r” are independently 0, 1, 2 or 3;
• and
• R18 is H, C1-5 acyl, C2-6 alkenyl, C1-8 alkyl, C1-4 alkylcarboxamide, C2-6 alkynyl, C1-4 alkylsulfonamide, carbo-C1-6-alkoxy, carboxamide, carboxy, cyano, C3-7 cycloalkyl, C2-6 dialkylcarboxamide, halogen, heteroaryl or phenyl, and wherein said heteroaryl or phenyl optionally substituted with 1 to 5 substituents selected independently from the group consisting of C1-4 alkoxy, amino, C1-4 alkylamino, C2-6 alkynyl, C2-8 dialkylamino, halogen, C1-4 haloalkoxy, C1-4 haloalkyl and hydroxyl;
• R14, R15, R16, and R17 are each independently selected form the group consisting of H, C1-5 acyl, C1-5 acyloxy, C2-6 alkenyl, C1-4 alkoxy, C1-8 alkyl, C1-4 alkylcarboxamide, C2-6 alkynyl, C1-4 alkylsulfonamide, C1-4 alkylsulfinyl, C1-4 alkylsulfonyl, C1-4 alkylthio, C1-4 alkylureyl, carbo-C1-6-alkoxy, carboxamide, carboxy, cyano, C3-7 cycloalkyl, C2-6 dialkylcarboxamide, halogen, C1-4 haloalkoxy, C1-4 haloalkyl, C1-4 haloalkylsulfinyl, C1-4 haloalkylsulfonyl, C1-4 haloalkylthio, hydroxyl and nitro;
• or
• two adjacent R14, R15, R16 and R17 together with the atoms to which they are attached form a 5, 6 or 7 member cycloalkyl, cycloalkenyl or heterocyclic group fused with Ar1 wherein the 5, 6 or 7 member group is optionally substituted with halogen;
• and
• R2 is selected from the group consisting of C1-8 alkyl, C2-6 alkynyl, amino, aryl, carboxamide, carboxy, cyano, C3-6-cycloalkyl, C1-4 haloalkoxy, C1-4 haloalkyl, halogen, heteroaryl and hydroxyl;
• and wherein said C1-8 alkyl, aryl and heteroaryl are each optionally substituted with 1 to 5 substituents selected from the group consisting of C1-5 acyl, C1-5 acyloxy, C1-4 alkoxy, C1-8 alkyl, C1-4 alkylamino, C1-4 alkylcarboxamide, C1-4 alkylthiocarboxamide, C1-4 alkylsulfonamide, C1-4 alkylsulfinyl, C1-4 alkylsulfonyl, C1-4 alkylthio, C1-4 alkylthioureyl, C1-4 alkylureyl, amino, carbo-C1-6-alkoxy, carboxamide, carboxy, cyano, C3-6-cycloalkyl, C3-6-cycloalkyl-C1-3-heteroalkylene, C2-8 dialkylamino, C2-6 dialkylcarboxamide, C2-6 dialkylthiocarboxamide, C2-6 dialkylsulfonamide, C1-4 alkylthioureyl, C1-4 haloalkoxy, C1-4 haloalkyl, C1-4 haloalkylsulfinyl, C1-4 haloalkylsulfonyl, C1-4 haloalkylthio, halogen, heterocyclic, hydroxyl, hydroxylamino and nitro;
• or
• R2 is —Ar2—Ar3 wherein Ar2 and Ar3 are each independently aryl or heteroaryl each optionally substituted with 1 to 5 substituents selected from the group consisting of H, C1-5 acyl, C1-5 acyloxy, C1-4 alkoxy, C1-8 alkyl, C1-4 alkylcarboxamide, C1-4 alkylthiocarboxamide, C1-4 alkylsulfinyl, C1-4 alkylsulfonyl, C1-4 alkylthio, amino, C1-4 alkylamino, carbo-C1-6-alkoxy, carboxamide, carboxy, cyano, C3-6-cycloalkyl, C2-8 dialkylamino, C2-6 dialkylcarboxamide, C1-4 haloalkoxy, C1-4 haloalkyl, halogen, hydroxyl and nitro;
• or
• R2 is a group of Formula (B):
• wherein:
• R19 is H, C1-8 alkyl, C3-7 cycloalkyl, aryl, heteroaryl or OR21;
• and R20 is F, Cl, Br, CN or NR22R23;
• where R21 is H, C1-8 alkyl or C3-7 cycloalkyl, and R22 and R23 are independently H, C1-8 alkyl, C3-7 cycloalkyl, aryl or heteroaryl;
• or
• R2 is a group of Formula (C):
• wherein:
• G is:
• i) —C(O)—, —C(O)NR25—, —NR25C(O)—, —NR25—, —NR25C(O)O—, —OC(O)NR25—, —CR25R26NR27C(O)—, —CR25R26C(O)NR27—, —C(O)O—, —OC(O)—, —C(S)—, —C(S)NR25—, —C(S)O—, —OC(S)—, —CR25R26—, —O—, —S—, —S(O)—, —S(O)2— or a bond when D is CR2R3;
• or
• ii) —CR25R26C(O)—, —C(O)—, —CR25R26C(O)NR27—, —C(O)NR25—, —C(O)O—, —C(S)—, —C(S)NR25—, —C(S)O—, —CR25R26—, —S(O)2—, or a bond when D is NR2;
• wherein R25, R26 and R27 are each independently H or C1-8 alkyl;
• and R24 is C1-8 alkyl, C3-7 cycloalkyl, phenyl, heteroaryl, or heterocyclic each optionally substituted with 1 to 5 substituents selected from the group consisting of C1-5 acyl, C1-5 acyloxy, C2-6 alkenyl, C1-4 alkoxy, C1-7 alkyl, C1-4 alkylamino, C1-4 alkylcarboxamide, C1-4 alkylthiocarboxamide, C1-4 alkylsulfonamide, C1-4 alkylsulfinyl, C1-4 alkylsulfonyl, C1-4 alkylthio, C1-4 alkylthioureyl, C1-4 alkylureyl, amino, carbo-C1-6-alkoxy, carboxamide, carboxy, cyano, C3-7 cycloalkyl, C2-8 dialkylamino, C2-6 dialkylcarboxamide, C2-6 dialkylthiocarboxamide, C2-6 dialkylsulfonamide, C1-4 alkylthioureyl, C1-4 haloalkoxy, C1-4 haloalkyl, C1-4 haloalkylsulfinyl, C1-4 haloalkylsulfonyl, C1-4 haloalkylthio, halogen, heteroaryl, heterocyclic, hydroxyl, hydroxylamino, nitro, phenyl, phenoxy, and sulfonic acid, wherein said C1-4 alkoxy, C1-7 alkyl, C1-4 alkylamino, heteroaryl, phenyl and phenoxy are each optionally substituted with 1 to 5 substituents selected from the group consisting of C1-5 acyl, C1-5 acyloxy, C1-4 alkoxy, C1-8 alkyl, C1-4 alkylamino, C1-4 alkylcarboxamide, C1-4 alkylthiocarboxamide, C1-4 alkylsulfonamide, C1-4 alkylsulfinyl, C1-4 alkylsulfonyl, C1-4 alkylthio, C1-4 alkylthioureyl, C1-4 alkylureyl, amino, carbo-C1-6-alkoxy, carboxamide, carboxy, cyano, C3-7 cycloalkyl, C2-8 dialkylamino, C2-6 dialkylcarboxamide, C2-6 dialkylthiocarboxamide, C2-6 dialkylsulfonamide, C1-4 alkylthioureyl, C1-4 haloalkoxy, C1-4 haloalkyl, C1-4 haloalkylsulfinyl, C1-4 haloalkylsulfonyl, C1-4 haloalkylthio, halogen, heterocyclic, hydroxyl, hydroxylamino, nitro, and phenyl.