Thiazolidinone compounds and use thereof

A compound of formula (I):

• wherein
• X is S, Y is —CH2—, W is —C(O)—, ring A is
• U is C6-14 aryl or C1-13 heteroaryl,
• and V is
• in which
• R1 is halo, C1-6 alkyl, or C2-6 alkenyl;
• each of R2, R4, and R5, independently, is H, C1-6 alkyl, C3-8 cycloalkyl, C2-8 heterocycloalkyl, C1-6 alkoxy, C6-14 aryl, or C1-13 heteroaryl;
• and
• R3 is halo, CN, C1-6 alkyl, C1-6 alkoxy, C1-13 heteroaryl, —C(O)OR, —C(O)NRR′, —C(O)R, —C(O)NRS(O)2R′, —C(O)NRS(O)2NR′R″, —C(═NH)NRR′, —NRC(O)R′, —NRR′, or —NRS(O)2R′, each of R, R′, and R″, independently, being H, halo, OH, CN, COOH, mono-, di-, or tri-alkylsubstitutes silyl, acetyl, acetamide, dialkylamino, alkylamino, C1-6 alkyl, C1-6 multihaloalkyl, C1-6 alkoxy, C1-6 multihaloalkoxy, C3-8 cycloalkyl, C2-8 heterocycloalkyl, C6-14 aryl, or C1-13 heteroaryl,
• wherein
• each of C1-6 alkyl, C3-8 cycloalkyl, C2-8 heterocycloalkyl, C1-6 alkoxy, C6-14 aryl, and C1-13 heteroaryl, independently, either is optionally mono-, di-, or tri-substituted with halo, OH, CN, CF3, NH2, NO2, SO2, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C3-8 cycloalkyl, C2-8 heterocycloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 alkylamino, C2-6 dialkylamino, C7-12 aralkyl, C1-12 heteroaralkyl, C6-14 aryl, C1-13 heteroaryl, —C(O)OR, —C(O)NRR′, —NRC(O)R′, —S(O)2R, —S(O)2NRR′, —NRS(O)2R′, —C(O)R, —C(O)NRS(O)2R′, —C(O)NRS(O)2NR′R″, or —NRS(O)2NR′R″;
• or is optionally fused with C3-8 cycloalkyl, C2-8 heterocycloalkyl, C6-14 aryl, or C1-13 heteroaryl;
• and
• the compound has an enantiomeric excess of greater than 90%.

A compound of formula (I):

• wherein
• X is S, Y is —CH2—, W is —C(O)—, ring A is
• U is C6-14 aryl or C1-13 heteroaryl, and V is
• in which
• R1 is halo, C1-6 alkyl, or C2-6 alkenyl;
• each of R2, R4, and R5, independently, is H, C1-6 alkyl, C3-8 cycloalkyl, C2-8 heterocycloalkyl, C1-6 alkoxy, C6-14 aryl, or C1-13 heteroaryl;
• R3 is halo, CN, C1-6 alkyl, C1-6 alkoxy, C1-13 heteroaryl, —C(O)OR, —C(O)NRR′, —C(O)R, —C(O)NRS(O)2R′, —C(O)NRS(O)2NR′R″, —C(═NH)NRR′, —NRC(O)R′, —NRR′, or —NRS(O)2R′, each of R, R′, and R″, independently, being H, halo, OH, CN, COOH, mono-, di-, or tri-alkylsubstitutes silyl, acetyl, acetamide, dialkylamino, alkylamino, C1-6 alkyl, C1-6 multihaloalkyl, C1-6 alkoxy, C1-6 multihaloalkoxy, C3-8 cycloalkyl, C2-8 heterocycloalkyl, C6-14 aryl, or C1-13 heteroaryl;
• and
• at least one of R1, Y, and the carbon U attached to is mono-, di-, or tri-substituted with deuterium,
• wherein
• each of C1-6 alkyl, C3-8 cycloalkyl, C2-8 heterocycloalkyl, C1-6 alkoxy, C6-14 aryl, and C1-13 heteroaryl, independently, either is optionally mono-, di-, or tri-substituted with halo, OH, CN, CF3, NH2, NO2, SO2, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C3-8 cycloalkyl, C2-8 heterocycloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 alkylamino, C2-6 dialkylamino, C7-12 aralkyl, C1-12 heteroaralkyl, C6-14 aryl, C1-13 heteroaryl, —C(O)OR, —C(O)NRR′, —NRC(O)R′, —S(O)2R, —S(O)2NRR′, —NRS(O)2R′, —C(O)R, —C(O)NRS(O)2R′, —C(O)NRS(O)2NR′R″, or —NRS(O)2NR′R″;
• or is optionally fused with C3-8 cycloalkyl, C2-8 heterocycloalkyl, C6-14 aryl, or C1-13 heteroaryl.

A method of treating an opioid receptor-associated condition, the method comprising administering to a subject in need thereof a mu-opioid receptor antagonist and an effective amount of a compound of Formula (I):

• wherein
• U is C1-6 alkyl, C3-8 cycloalkyl, C2-8 heterocycloalkyl, C6-14 aryl, or C1-13 heteroaryl;
• V is C1-6 alkyl, C3-8 cycloalkyl, C2-8 heterocycloalkyl, -L-C6-14 aryl, or -L-C1-13 heteroaryl, L being a bond or NR;
• X is S, SO2, CRR′, O, or N;
• Y is CRR′, O, or N;
• and
• W is —C(O)—, —CH═, —CH2—, N, or O,
• in which
• each of the C1-6 alkyl, C3-8 cycloalkyl, C2-8 heterocycloalkyl, C6-14 aryl, and C1-13 heteroaryl, independently, either is optionally mono-, di-, or tri-substituted with halo, OH, CN, CF3, NH2, NO2, SO2, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C3-8 cycloalkyl, C2-8 heterocycloalkyl, C1-6 alkoxy, C1-6 haloalkoxy, C1-6 alkylamino, C2-6 dialkylamino, C7-12 aralkyl, C1-12 heteroaralkyl, C6-14 aryl, C1-13 heteroaryl, —C(O)OR, —C(O)NRR′, —C(O)R, —C(O)NRS(O)2R′, —C(O)NRS(O)2NR′R″, —C(═NH)NRR′, —S(O)2R, —S(O)2NRR′, —NRR′, —NRC(O)R′, —NRS(O)2R′, or —NRS(O)2NR′R″;
• or is optionally fused with C3-8 cycloalkyl, C2-8 heterocycloalkyl, C6-14 aryl, or C1-13 heteroaryl;
• each of R, R′, and R″, independently, being H, halo, OH, CN, COOH, mono-, di-, or tri-alkylsubstitutes silyl, acetyl, acetamide, dialkylamino, alkylamino, C1-6 alkyl, C1-6 multihaloalkyl, C1-6 alkoxy, C1-6 multihaloalkoxy, C3-8 cycloalkyl, C2-8 heterocycloalkyl, C6-14 aryl, or C1-13 heteroaryl;
• and is either a single bond or a double bond,
• or a pharmaceutically acceptable salt of the compound.