Modulator for promoting binding of butyrophilin 3a1/2a1

A compound of formula (I), or a pharmaceutically acceptable salt, an enantiomer, a diastereomer, a solvate, a hydrate, a polymorph or an isotopic variant thereof:

• wherein,
• ring A is C6-10 aryl or 5- to 10-membered heteroaryl;
• Ra is selected from H, halogen, C1-6 alkyl, C1-6 haloalkyl, —OR″, NR″R″, C2-6 alkenyl and C2-6 alkynyl;
• m=1, 2, 3, 4, or 5;
• X is O or CRR′;
• R1 is selected from H, F, Cl, CN and methyl, wherein the methyl is substituted with 1 to 3 substituents independently selected from halogen, CN, OH and NH2;
• R2 is selected from C1-6 hydroxyalkyl, C5-6 alkyl, C5-6 haloalkyl, C5-6 alkenyl, C5-6 alkynyl, C0-6 alkylene-C3 12 cycloalkyl and C0-6 alkylene-4- to 12-membered heterocyclyl, wherein the C1-6 hydroxyalkyl, C5-6 alkyl, C5-6 haloalkyl, C5-6 alkenyl, C5-6 alkynyl, C0-6 alkylene-C312 cycloalkyl and C0-6 alkylene-4- to 12-membered heterocyclyl are optionally substituted with one or more substituents selected from halogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C2-6 alkenyl, C2-6 alkynyl, 3- to 10-membered cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-10 aryl, 5- to 10-membered heteroaryl, —C(O)—C1-6 alkyl, —C(O)—C1-6 hydroxyalkyl, —C(O)—C1-6 haloalkyl, —C(O)—C2-6 alkenyl, —C(O)—C2-6 alkynyl, —C(O)-3- to 10-membered cycloalkyl, —C(O)-4- to 10-membered heterocycloalkyl, —C(O)—C6-10 aryl, —C(O)-5- to 10-membered heteroaryl, —CN and oxo group;
• R3 is selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl and C2-6 alkynyl;
• wherein,
• R and R′ are independently selected from H and halogen;
• R″ is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3-7 cycloalkyl, 3- to 7-membered heterocyclyl, C6-10 aryl and 5- to 10-membered heteroaryl.

A compound of formula (VI), or a pharmaceutically acceptable salt, an enantiomer, a diastereomer, a solvate, a hydrate, a polymorph or an isotopic variant thereof:

• wherein,
• ring A is C6-12 aryl or 5- to 12-membered heteroaryl;
• Ra is selected from halogen, C1-6 alkyl, C1-6 haloalkyl, —OR″, NR″R″, C2-6 alkenyl and C2-6 alkynyl;
• m=1, 2, 3, 4, or 5;
• X is O or CRR′;
• R1 is selected from H, F, Cl, CN and methyl, wherein the methyl is optionally substituted with 1 to 3 substituents independently selected from halogen, CN, OH and NH2;
• R2 is selected from C1-6 hydroxyalkyl, C5-6 alkyl, C5-6 haloalkyl, C5-6 alkenyl, C5-6 alkynyl, C0-6 alkylene-C3-12 cycloalkyl, C0-6 alkylene-4- to 12-membered heterocyclyl and C0-6 alkylene-5- to 10-membered heteroaryl, wherein the C1-6 hydroxyalkyl, C5-6 alkyl, C5-6 haloalkyl, C5-6 alkenyl, C5-6 alkynyl, C0-6 alkylene-C3-12 cycloalkyl, C0-6 alkylene-4- to 12-membered heterocyclyl and C0-6 alkylene-5- to 10-membered heteroaryl are optionally substituted with one or more substituents selected from halogen, C1-6 alkyl, C1-6 haloalkyl, C1-6 hydroxyalkyl, C2-6 alkenyl, C2-6 alkynyl, 3- to 10-membered cycloalkyl, 4- to 10-membered heterocycloalkyl, C6-10 aryl, 5- to 10-membered heteroaryl, —C(O)—C1-6 alkyl, —C(O)—C1-6 hydroxyalkyl, —C(O)—C1-6 haloalkyl, —C(O)—C2-6 alkenyl, —C(O)—C2-6 alkynyl, —C(O)-3- to 10-membered cycloalkyl, —C(O)-4- to 10-membered heterocycloalkyl, —C(O)—C6-10 aryl, —C(O)-5- to 10-membered heteroaryl, —CN and oxo group;
• R3 and R3′ are each independently selected from C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl and C2-6 alkynyl;
• wherein,
• R and R′ are independently selected from H and halogen;
• R″ is independently selected from H, C1-6 alkyl, C1-6 haloalkyl, C2-6 alkenyl, C2-6 alkynyl, C3 7 cycloalkyl, 3- to 7-membered heterocyclyl, C6-10 aryl and 5- to 10-membered heteroaryl.