Dihydropyrimidine compounds and uses thereof in medicine

A compound having Formula (I) or Formula (Ia), a stereoisomer, a tautomer, an N-oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof,

• wherein each R1 is independently H, deuterium, F, Cl, Br or I;
• each R2 is independently C1-6 alkyl or C1-6 haloalkyl;
• each R3 is independently 5 membered heteroaryl unsubstituted or substituted with methyl;
• each W is N;
• each X1 is C(═O)— or —CH2—;
• each R4 is independently —(CR7R8)j—R5-L-R6;
• R5 is 3-12 membered heterocyclyl, C3-7 cycloalkyl, C2-12 alkynyl, 5-12 membered heteroaryl or C6-10 aryl, wherein each of the 3-12 membered heterocyclyl, C3-7 cycloalkyl, C2-12 alkynyl, 5-12 membered heteroaryl and C6-10 aryl is independently unsubstituted or substituted with one, two, three, four or five substituents independently selected from deuterium, F, Cl, Br, OH, CN, C1-6 alkoxy, C1-6 alkyl, HOOC-(CR7R8)h— and C1-6 alkoxy-C(═O)—;
• R6 is 3-12 membered heterocyclyl, C3-7 cycloalkyl, C2-12 alkynyl, 5-12 membered heteroaryl or C6-10 aryl, wherein each of the 3-12 membered heterocyclyl, C3-7 cycloalkyl, C2-12 alkynyl, 5-12 membered heteroaryl and C6-10 aryl is independently unsubstituted or substituted with one, two, three, four or five Rw;
• L is a single bond, —O—, —S(═O)t—, —C(═O)—, —NH—, —(CR7R8)j— or —O—(CR7R8)n—;
• each Rw is independently deuterium, F, Cl, Br, OH, CN, HOOC—(CR7R8)h—, R11C(═O)—, RcRdP(═O)—, R10—S(═O)t—, R3O—, R12—(CR7R8)j—, amino, C1-12 alkoxy, C3-7 cycloalkyl, C1-8 alkoxy-(CR7R8)n—O—, C1-8 alkyl, hydroxy-C1-8 alkyl, C2-12 alkynyl, C6-10 aryl, 3-10 membered heterocyclyl or 5-10 membered heteroaryl, wherein each of the amino, C1-12 alkoxy, C3-7 cycloalkyl, C1-8 alkoxy of C1-8 alkoxy-(CR7R8)n—O—, C1-8 alkyl, hydroxy-C1-8 alkyl, C2-12 alkynyl, C6-10 aryl, 3-10 membered heterocyclyl and 5-10 membered heteroaryl is independently unsubstituted or substituted with one, two, three, four or five Rx;
• each R10 and R11 is independently RaRbN—, C1-8 alkyl, C1-8 alkoxy, C3-7 cycloalkyl, 3-12 membered heterocyclyl, C6-10 aryl or 5-10 membered heteroaryl, wherein each of the C1-8 alkyl, C1-8 alkoxy, C3-7 cycloalkyl, 3-12 membered heterocyclyl, C6-10 aryl and 5-10 membered heteroaryl is independently unsubstituted or substituted with one, two, three, four or five Ry;
• each R12 is independently OH, HOOC—, C1-8 alkyl, C1-8 alkoxy, C3-7 cycloalkyl, 3-12 membered heterocyclyl, C6-10 aryl or 5-10 membered heteroaryl, wherein each of the C1-8 alkyl, C1-8 alkoxy, C3-7 cycloalkyl, 3-12 membered heterocyclyl, C6-10 aryl and 5-10 membered heteroaryl is independently unsubstituted or substituted with one, two, three, four or five Rz;
• each R3 is independently C1-8 alkyl, C3-7 cycloalkyl, 5-10 membered heteroaryl, C6-10 aryl or 5-10 membered heterocyclyl, wherein each of the C1-8 alkyl, C3-7 cycloalkyl, 5-10 membered heteroaryl, C6-10 aryl and 5-10 membered heterocyclyl is independently unsubstituted or substituted with one, two, three, four or five Rg;
• each Rx, Ry, Rz and Rg is independently deuterium, F, Cl, Br, OH, CN, HOOC—(CR7R8)h—, R14C(═O)—, RcRdP(═O)—, R1—S(═O)t—, R16O—, R17-(CR7R8)j—, amino, C1-12 alkoxy, C3-7 cycloalkyl, C1-8 alkoxy-(CR7R8)n—O—, C1-8 alkyl, hydroxy-C1-8 alkyl, C2-12 alkynyl, C6-10 aryl, 3-12 membered heterocyclyl or 5-10 membered heteroaryl, wherein each of the amino, C1-12 alkoxy, C3-7 cycloalkyl, C1-8 alkoxy of C1-8 alkoxy-(CR7R8)n—O—, C1-8 alkyl, hydroxy-C1-8 alkyl, C2-12 alkynyl, C6-10 aryl, 3-12 membered heterocyclyl and 5-10 membered heteroaryl is independently unsubstituted or substituted with one, two, three, four or five substituents independently selected from deuterium, F, Cl, Br, OH, C1-8 alkoxy, C1-8 alkyl, hydroxy-C1-8 alkyl, HOOC—(CR7R8)h— and C1-8 alkoxy-(CR7R8)n—;
• each R14 and R15 is independently RaRbN—, C1-8 alkyl, C1-8 alkoxy, C3-7 cycloalkyl, 3-12 membered heterocyclyl, C6-10 aryl or 5-10 membered heteroaryl, wherein each of the C1-8 alkyl, C1-8 alkoxy, C3-7 cycloalkyl, 3-12 membered heterocyclyl, C6-10 aryl and 5-10 membered heteroaryl is independently unsubstituted or substituted with one, two, three, four or five substituents independently selected from deuterium, F, Cl, Br, OH, C1-8 alkoxy, C1-8 alkyl, HOOC—(CR7R8)h— and C1-8 alkoxy-(CR7R8)n—;
• each R7 is independently OH, HOOC—, C1-8 alkyl, C1-8 alkoxy, C3-7 cycloalkyl, 3-12 membered heterocyclyl, C6-10 aryl or 5-10 membered heteroaryl, wherein each of the C1-8 alkyl, C1-8 alkoxy, C3-7 cycloalkyl, 3-12 membered heterocyclyl, C6-10 aryl and 5-10 membered heteroaryl is independently unsubstituted or substituted with one, two, three, four or five substituents independently selected from deuterium, F, Cl, Br, OH, C1-8 alkoxy, C1-8 alkyl, HOOC—(CR7R8)h— and C1-8 alkoxy-(CR7R8)nO—;
• each R16 is independently C1-8 alkyl, C3-7 cycloalkyl, 5-10 membered heteroaryl, C6-10 aryl or 5-10 membered heterocyclyl, wherein each of the C1-8 alkyl, C3-7 cycloalkyl, 5-10 membered heteroaryl, C6-10 aryl and 5-10 membered heterocyclyl is independently unsubstituted or substituted with one, two, three, four or five substituents independently selected from deuterium, F, Cl, Br, OH, C1-8 alkoxy, C1-8 alkyl, HOOC—(CR7R8)h— and C1-8 alkoxy-(CR7R8)n—O—;
• each Ra, Rb, Rc and Rd is independently H, deuterium, C1-8 alkyl, C2-8 alkynyl, C1-8 alkoxy, C3-7 cycloalkyl, HOOC—(CR7R8)h—, C6-10 aryl-C1-4 alkylene or 3-12 membered heterocyclyl, wherein each of the C1-8 alkyl, C2-8 alkynyl, C1-8 alkoxy, C3-7 cycloalkyl, C6-10 aryl of C6-10 aryl-C1-4 alkylene and 3-12 membered heterocyclyl is independently unsubstituted or substituted with one, two, three, four or five substituents independently selected from deuterium, F, Cl, Br, OH, C1-8 alkyl, (C1-6 alkyl)2NC(═O)—, C1-8 alkoxy, HOOC—(CR7R8)h— and C1-8 alkoxy-(CR7R8)—O—;
• each R7 and R8 is independently H, deuterium, F, Cl, Br, C1-6 alkyl, NH2C(═O)—, C1-6 alkyl-OC(═O)—, carboxy, carboxy-C1-6 alkylene, hydroxy-C1-6 alkyl or C1-6 haloalkyl, or R7 and R8, together with the carbon atom to which they are attached, form C3-6 cycloalkyl or carbonyl;
• each R9 is independently H, deuterium or C1-6alkyl;
• each f, m and h is independently 0, 1, 2, 3, or 4;
• each n is independently 1, 2, 3 or 4;
• each t is independently 0, 1 or 2;
• each j is independently 0, 1, 2 or 3.