Gpr40 agonists

A compound of Formula (I):

• or a pharmaceutically acceptable salt, solvate, stereoisomer, or prodrug thereof, wherein:
• Z is —P(═O)(H)OR6, —P(═O)(R5)OR6, —P(═O)(OR6)2, —S(═O)(OR6), —SO2OR6, —C(═O)NHSO2R5, —C(═O)NHSO2N(R6)2, —N(R6)SO2N(R6)2, —N(R6)C(═O)NHSO2(R5), —N(R6)C(═O)NHSO2N(R6)2, —N(R6)C(═NH)NH2, —C(═O)NHNHC(═O)N(R6)2, or —B(OR6)2;
• R5 is C1-C6 alkyl, C3-C6 cycloalkyl, phenyl, or —(C1-C6 alkyl)-phenyl;
• wherein each alkyl, cycloalkyl, and phenyl is independently unsubstituted or substituted with 1, 2, or 3 substituents selected from the group consisting of halogen, —CN, —OH, —O—(C1-C6 alkyl), C1-C6 alkyl, C1-C6 fluoroalkyl, C1-C6 hydroxyalkyl, —O—(C1-C6 fluoroalkyl), C3-C6 cycloalkyl, and 3- to 6-membered heterocycloalkyl;
• each R6 is independently hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl, phenyl, or —(C1-C6 alkyl)-phenyl;
• wherein each alkyl, cycloalkyl, and phenyl is independently unsubstituted or substituted with 1, 2, or 3 substituents selected from the group consisting of halogen, —CN, —OH, —O—(C1-C6 alkyl), C1-C6 alkyl, C1-C6 fluoroalkyl, C1-C6 hydroxyalkyl, —O—(C1-C6 fluoroalkyl), C3-C6 cycloalkyl, and 3- to 6-membered heterocycloalkyl;
• R1, R2, and R3 are each independently hydrogen, halogen, —OH, —O—(C1-C6 alkyl), C1-C6 alkyl, C3-C6 cycloalkyl, or 3- to 6-membered heterocycloalkyl;
• wherein each alkyl, cycloalkyl, and heterocycloalkyl is independently unsubstituted or substituted with 1, 2, or 3 substituents selected from the group consisting of halogen, —CN, —OH, —O—(C1-C6 alkyl), and C1-C6 alkyl;
• R4 is C1-C6 alkyl, C3-C6 cycloalkyl, or 3- to 6-membered heterocycloalkyl;
• wherein each alkyl, cycloalkyl, and heterocycloalkyl is independently unsubstituted or substituted with 1, 2, or 3 substituents selected from the group consisting of halogen, —CN, —OH, —O—(C1-C6 alkyl), and C1-C6 alkyl;
• Y1, Y2, Y3, and Y4 are each independently N, CH, or C—RY;
• each RY is independently halogen, —CN, —OH, —O—(C1-C6 alkyl), —NH2, —NH—(C1-C6 alkyl), —N(C1-C6 alkyl)2, C1-C6 alkyl, C3-C6 cycloalkyl, or 3- to 6-membered heterocycloalkyl;
• wherein each alkyl, cycloalkyl, and heterocycloalkyl is independently unsubstituted or substituted with 1, 2, or 3 substituents selected from the group consisting of halogen, —CN, —OH, —O—(C1-C6 alkyl), and C1-C6 alkyl;
• L1 is —O—, —NR7—, *—O—CH2—, *—CH2—O—, *-NR7—CH2—, *—CH2—NR7—, *-NR7—C(O)—, *-C(O)—NR7—, or *-C(O)—CH2—;
• wherein * represents the connection to Ring B;
• R7 is hydrogen, C1-C6 alkyl, or C3-C6 cycloalkyl;
• Ring B is arylene or heteroarylene;
• wherein the arylene or heteroarylene is unsubstituted or substituted with 1, 2, 3, or 4 RB substituents;
• Ring A is carbocycle or heterocycle;
• wherein the carbocycle or heterocycle is unsubstituted or substituted with 1, 2, 3, 4, or 5 RA substituents;
• L2 is a bond, C1-C6 alkylene, or —(C1-C6 alkylene)-O—;
• wherein the alkylene is unsubstituted or substituted with 1, 2, or 3 substituents selected from the group consisting of halogen, —CN, —OH, C1-C6 alkyl, and —O—(C1-C6 alkyl);
• each RA is independently halogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C1-C10 fluoroalkyl, -LA-CN, -LA-OH, -LA-OR10, -LA-NR11R11, -LA-C(═O)R10, -LA-C(═O)OR11, -LA-OC(═O)R11, -LA-C(═O)NR11R11, -LA-NR11C(═O)R11, -LA-NR11C(═O)NR11R11, -LA-OC(═O)NR11R11, -LA-NR11C(═O)OR10, -LA-OC(═O)OR10, -LA-aryl, -LA-heteroaryl, -LA-(C3-C10 cycloalkyl), or -LA-(3- to 10-membered heterocycloalkyl);
• wherein each alkyl, alkenyl, alkynyl, fluoroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl is independently unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of halogen, —CN, —OH, C1-C6 alkyl, C1-C6 fluoroalkyl, C1-C6 hydroxyalkyl, —O—(C1-C6 alkyl), and —O—(C1-C6 fluoroalkyl);
• each RB is independently halogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C1-C10 fluoroalkyl, -LB-CN, -LB-OH, -LB-OR10, -LB-NR11R11, -LB-C(═O)R10, -LB-C(═O)OR11, -LB-OC(═O)R11, -LB-C(═O)NR11R11, -LB-NR11C(═O)R11, -LB-NR11C(═O)NR11R11, -LB-OC(═O)NR11R11, -LB-NR11C(═O)OR10, -LB-OC(═O)OR10, -LB-aryl, -LB-heteroaryl, -LB-(C3-C10 cycloalkyl), or -LB-(3- to 10-membered heterocycloalkyl);
• wherein each alkyl, alkenyl, alkynyl, fluoroalkyl, aryl, heteroaryl, cycloalkyl, and heterocycloalkyl is independently unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of halogen, —CN, —OH, C1-C6 alkyl, C1-C6 fluoroalkyl, C1-C6 hydroxyalkyl, —O—(C1-C6 alkyl), and —O—(C1-C6 fluoroalkyl);
• each LA and LB is independently a bond or C1-C6 alkylene;
• wherein the alkylene is unsubstituted or substituted with 1, 2, or 3 substituents selected from the group consisting of halogen, —CN, —OH, —O—(C1-C6 alkyl), and C1-C6 alkyl;
• each R10 is independently C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, 3- to 10-membered heterocycloalkyl, phenyl, or monocyclic heteroaryl;
• wherein each alkyl, alkenyl, alkynyl, phenyl, heteroaryl, cycloalkyl, and heterocycloalkyl is independently unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of halogen, —CN, —OH, C1-C6 alkyl, C1-C6 fluoroalkyl, C1-C6 hydroxyalkyl, —O—(C1-C6 alkyl), and —O—(C1-C6 fluoroalkyl);
• and
• each R11 is independently hydrogen, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, 3- to 10-membered heterocycloalkyl, phenyl, or monocyclic heteroaryl;
• wherein each alkyl, alkenyl, alkynyl, phenyl, heteroaryl, cycloalkyl, and heterocycloalkyl is independently unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of halogen, —CN, —OH, C1-C6 alkyl, C1-C6 fluoroalkyl, C1-C6 hydroxyalkyl, —O—(C1-C6 alkyl), and —O—(C1-C6 fluoroalkyl);
• or two R11 on the same nitrogen atom are taken together with the nitrogen to which they are attached to form a 3- to 10-membered N-heterocycloalkyl;
• wherein the heterocycloalkyl is unsubstituted or substituted with 1, 2, 3, 4, or 5 substituents selected from the group consisting of halogen, —CN, —OH, C1-C6 alkyl, C1-C6 fluoroalkyl, C1-C6 hydroxyalkyl, —O—(C1-C6 alkyl), and —O—(C1-C6 fluoroalkyl).