Azinone-substituted azapolycycle MCH-1 antagonists, methods of making, and use thereof

A compound of Formula (I):

• wherein
• R1 is selected from the group consisting of H, —S(O)qR8, —C(O)R8, —C(O)NR7R8, C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, and C2-C6 alkynyl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C1-C3 alkyl, halogen, —CN, —OR10, —NR10R11, and phenyl which is optionally substituted 1-3 times with halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, —OR10, or —NR10R11;
• R2 and R4 are each individually selected from the group consisting of H, —S(O)qR8, —C(O)R8, —C(O)NR7R8, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, heterocyclyl, aryl, and heteroaryl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C1-C3 alkyl, halogen, —CN, —OR10, —NR10R11, and phenyl which is optionally substituted 1-3 times with halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, —OR10, or —NR10R11;
• R2 and R3 can combine to form a 3- to 7-membered heterocycle or R3 and R4 can combine to form a 3- to 7-membered heterocycle, wherein at least one of R2 and R3 or R3 and R4 combine to form a 3- to 7-membered heterocycle and wherein the 3-7-membered heterocycle comprises from 1 to 2 heteroatoms selected from the group consisting of N, O, and S and is optionally substituted with from 1 to 10 substituents independently selected at each occurrence thereof from H, halogen, —OR7, —NR7R8, —NR7C(O)R8, —NR7C(O)2R8, —NR8C(O)NR8R9, —S(O)qR8, —CN, —C(O)R8, —C(O)NR7R8, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, heterocyclyl, aryl, and heteroaryl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C1-C3 alkyl, halogen, —CN, —OR10, —NR10R11, and phenyl which is optionally substituted 1-3 times with halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, —OR10, or —NR10R11;
• with the proviso that, when n is 0 and R3 and R4 combine to form a 3- to 7-membered heterocycle, R2 cannot be C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, heterocyclyl, aryl, or heteroaryl;
• R5 is independently selected at each location from the group consisting of H, halogen, —NR7R8, —NR7C(O)2R8, —NR8C(O)NR8R9, —S(O)qR8, —CN, —C(O)R8, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, heterocyclyl, aryl, and heteroaryl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C1-C3 alkyl, halogen, —CN, —OR10, —NR10R11, and phenyl which is optionally substituted 1-3 times with halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, —OR10, or —NR10R11;
• R6 is selected from the group consisting of H, halogen, —OR7, —NR7R8, —NR7C(O)2R8, —NR8C(O)NR8R9, —S(O)qR8, —CN, —C(O)R8, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, heterocyclyl, aryl, and heteroaryl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C1-C3 alkyl, halogen, —CN, —OR10, —NR10R11, and phenyl which is optionally substituted 1-3 times with halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, —OR10, or —NR10R11;
• R7 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R9, phenyl, or benzyl, wherein phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy;
• R8 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, phenyl, or benzyl, wherein phenyl or benzyl is optionally substituted 1 to 3 times with halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, or C1-C4 alkoxy;
• R9 is C1-C4 alkyl, C1-C4 haloalkyl, or phenyl;
• R10 and R11 are each independently H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxyalkyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, —C(O)R9, phenyl, or benzyl, wherein phenyl or benzyl is optionally substituted from 1 to 3 times with a substituent selected independently at each occurrence thereof from the group consisting of halogen, cyano, C1-C4 alkyl, C1-C4 haloalkyl, and C1-C4 alkoxy;
• R12 is selected from the group consisting of H, halogen, —OR7, —NR7R8, —NR7C(O)R8, —NR7C(O)2R8, —NR8C(O)NR8R9, —S(O)qR8, —CN, —C(O)R8, —C(O)NR7R8, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, heterocyclyl, aryl, and heteroaryl, wherein each of C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C4-C7 cycloalkylalkyl, heterocyclyl, aryl, and heteroaryl is optionally substituted with from 1 to 3 substituents independently selected at each occurrence thereof from C1-C3 alkyl, halogen, —CN, —OR10, —NR10R11, and phenyl which is optionally substituted 1-3 times with halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy, —CN, —OR10, or —NR10R11;
• X is CR12, C(R12)2, N, or NR12;
• Y is CR12, C, or N;
• Z is C, CH, or N;
• L is —(CH2)p—O—, —(CH2)p—, —CH═CH—, or a bond;
• B is aryl, heteroaryl, heterocyclyl, or cycloalkyl, wherein each of the aryl, heteroaryl, heterocyclyl, or cycloalkyl is optionally substituted with from 1 to 3 substituents selected from the group consisting of H, alkoxy, —S-alkyl, optionally substituted C1-C6 alkyl, halogen, —CF3, and —CN;
• n is 0 or 1 and m is 0 or 1, wherein n+m=1;
• s is 0, 1, 2, or 3;
• p is from 1 to 4;
• q is 0, 1, or 2;
• and
• represents an optional double bond,
• or an oxide thereof, a pharmaceutically acceptable salt thereof, a solvate thereof, or prodrug thereof.