Spirocyclic compounds as farnesoid X receptor modulators

A compound of Formula (I):

• or a stereoisomer, a tautomer, a pharmaceutically acceptable salt, or a solvate thereof;
• wherein:
• the
• moiety is
• E ring is a 4- to 6-membered carbocyclyl or heterocyclyl, wherein the carbocyclyl and heterocyclyl are each independently substituted with 0 to 3 R3;
• * denotes a spiro carbon atom;
• Y is CR7 or N;
• m and n are each independently an integer of 0, 1, or 2;
• f is an integer of 0, 1, 2, or 3;
• Z is 6- to 10-membered aryl, 5- to 10-membered heteroaryl containing 1 to 3 heteroatoms independently selected from N, O, and S, 3- to 10-membered carbocyclyl, or 4- to 10-membered heterocyclyl containing 1 to 3 heteroatoms independently selected from N, O, and S, wherein the aryl, heteroaryl carbocyclyl, and heterocyclyl are independently substituted with 0 to 5 R8;
• L1 is a covalent bond, O, S, —NR16—, —S(O)2—, C1-3 alkylene, C1-3 heteroalkylene, C2-4 alkenylene, C2-4 alkynylene, aryl, or a 5- to 6-membered heteroaryl containing 1 to 3 heteroatoms independently selected from N, O, and S;
• wherein the alkylene, alkenylene, aryl, heteroalkylene, and heteroaryl are each independently substituted with 0 to 3 R11;
• L2 is a covalent bond, O, S, —NR17—, C1-3 alkylene, or C1-3 heteroalkylene, wherein the alkylene and heteroalkylene are independently substituted with 0 to 3 R15;
• RX is -L3-RZ;
• L3 is a covalent bond, C1-3 alkylene, —C(O)NR12—CH2—, or —OCH2—, wherein the C1-3 alkylene is substituted with 0 to 3 R4;
• RZ is —CN, —C(O)OR13, —C(O)NR14aR14b,
• Re is C1-6 alkyl, C3-6 cycloalkyl, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, or aryl;
• RY is each independently hydrogen, halo, cyano, hydroxyl, amino, C1-6 alkyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy;
• or alternatively two RY, together with the carbon atoms to which they are attached, form a bridge moiety;
• and with the proviso that when Y is N and RY is attached to a carbon atom adjacent to Y, then RY is not halo, cyano, hydroxyl, amino, alkoxy, or haloalkoxy;
• R1 is C1-6 alkyl, C3-5 cycloalkyl, or C4-6 heterocyclyl, wherein the alkyl, cycloalkyl, and heterocyclyl are each substituted with 0 to 3 R9;
• R2 is 6- to 10-membered aryl, 5- to 10-membered heteroaryl containing 1 to 3 heteroatoms independently selected from N, O, and S, 3- to 10-membered carbocyclyl, or 4- to 10-membered heterocyclyl containing 1 to 3 heteroatoms independently selected from N, O, and S, wherein the aryl, heteroaryl, carbocyclyl, and heterocyclyl are independently substituted with 0 to 5 R10;
• R3, R5, and R7 are each independently hydrogen, halo, cyano, hydroxyl, amino, C1-6 alkyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy;
• R4 is each independently halo, oxo, cyano, hydroxyl, amino, alkyl, alkoxy, or alkylamino;
• or alternatively, two R4, taken together with the atom(s) to which they are attached, form a carbocyclyl or heterocyclyl moiety;
• R6, R16 and R17 are each independently hydrogen, C1-6 alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, or haloalkoxyalkyl;
• R8 and R10 are each independently halo, cyano, hydroxyl, amino, oxo, —ORa, —SRa, ═S, NRcRc, ═NH, ═N—OH, ═NRa, ═N—ORa, —NO2, —S(O)2Ra, —S(O)2NHRb, —S(O)2NRcRc, —S(O)2ORb, —OS(O)2Rb, —OS(O)2ORb, —P(O)(ORb)(ORb), —C(O)Rb, —C(NRb)Rb, —C(O)ORb, —C(O)NRcRc, —C(NRb)NRcRc, —OC(O)Rb, —NRbC(O)Rb, —OC(O)ORb, —NRbC(O)ORb, —NRbC(O)NRcRc, —NRbC(NRb)Rb, —NRbC (NRb)NRcRc, C1-6 alkyl, C1-6 haloalkyl, aryl, arylalkyl, heteroaryl, carbocyclyl, or heterocyclyl;
• wherein the alkyl, aryl, heteroaryl, carbocyclyl, and heterocyclyl, by themselves or as part of another group, are each independently substituted with 0 to 5 Rd;
• Ra is each independently C1-6 alkyl, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, carbocyclyl, carbocyclylalkyl, heterocyclyl, or heterocyclylalkyl;
• Rb is each independently hydrogen or Ra;
• Rc is each independently Rb or alternatively, the two Rc are taken together with the nitrogen atom to which they are bonded form a 4-, 5-, 6- or 7-membered heterocyclyl containing 1 to 3 heteroatoms independently selected from N, O, and S;
• Rd is each independently Ra, alkoxy, haloalkoxy, alkylamino, cycloalkylamino, heterocyclylamino, haloalkyl, hydroxyalkyl, aminoalkyl, cycloalkoxy, heterocyclyloxy, haloalkoxy, alkoxyalkoxy, haloalkylamino, alkoxyalkylamino, haloalkoxyalkylamino, arylamino, aralkylamino, aryloxy, aralkyloxy, heteroaryloxy, heteroarylalkyloxy, alkylthio, halo, cyano, hydroxyl, amino, oxo, —ORa, —SRa, ═S, —NRcRc, ═NH, ═N—OH, ═NRa, ═N—ORa, —NO2, —S(O)2Ra, —S(O)2NHRb, —S(O)2NRcRc, —S(O)2ORb, —OS(O)2Rb, —OS(O)2ORb, —P(O)(oRb)(ORb), —C(O)Rb, —C(NRb)Rb, —C(O)ORb, —C(O)NRcRc, —C(NRb)NRcRc, —OC(O)Rb, —NRbC(O)Rb, —OC(O)ORb, —NRbC(O)ORb, —NRbC(O)NRcRc, —NRbC(NRb)Rb, or —NRbC(NRb)NRcRc;
• R9 is each independently halo, cyano, hydroxyl, amino, or C1-6 alkyl;
• R11 and R15 are each independently halo, oxo, cyano, hydroxyl, amino, C1-6 alkyl, C3-6 cycloalkyl, C4-6 heterocyclyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy;
• R12 is hydrogen or C1-4 alkyl;
• R13 is hydrogen, C1-10 alkyl, glycosyl, or carboxy(trihydroxy)tetrahydropyranyl;
• and
• R14a and R14b are each independently hydrogen, C1-6 alkyl, C3-6 cycloalkyl, C4-6 heterocyclyl, alkylamino, haloalkyl, hydroxyalkyl, aminoalkyl, alkoxyalkyl, haloalkoxyalkyl, alkoxy, or haloalkoxy.