Dihydropyrimidine compounds and uses thereof in medicine

1. 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 R 1 is independently H, deuterium, F, Cl, Br or I;

each R 2 is independently C 1-6 alkyl or C 1-6 haloalkyl;

each R 3 is independently 5 membered heteroaryl unsubstituted or substituted with methyl;

each W is N;

each X 1 is C(═O)— or —CH 2 —;

each R 4 is independently —(CR 7 R 8 ) j —R 5 -L-R 6 ;

R 5 is 3-12 membered heterocyclyl, C 3-7 cycloalkyl, C 2-12 alkynyl, 5-12 membered heteroaryl or C 6-10 aryl, wherein each of the 3-12 membered heterocyclyl, C 3-7 cycloalkyl, C 2-12 alkynyl, 5-12 membered heteroaryl and C 6-10 aryl is independently unsubstituted or substituted with one, two, three, four or five substituents independently selected from deuterium, F, Cl, Br, OH, CN, C 1-6 alkoxy, C 1-6 alkyl, HOOC-(CR 7 R 8 ) h — and C 1-6 alkoxy-C(═O)—;

R 6 is 3-12 membered heterocyclyl, C 3-7 cycloalkyl, C 2-12 alkynyl, 5-12 membered heteroaryl or C 6-10 aryl, wherein each of the 3-12 membered heterocyclyl, C 3-7 cycloalkyl, C 2-12 alkynyl, 5-12 membered heteroaryl and C 6-10 aryl is independently unsubstituted or substituted with one, two, three, four or five R w ;

L is a single bond, —O—, —S(═O) t —, —C(═O)—, —NH—, —(CR 7 R 8 ) j — or —O—(CR 7 R 8 ) n —;

each R w is independently deuterium, F, Cl, Br, OH, CN, HOOC—(CR 7 R 8 ) h —, R 11 C(═O)—, R c R d P(═O)—, R 10 —S(═O) t —, R 3 O—, R 12 —(CR 7 R 8 ) j —, amino, C 1-12 alkoxy, C 3-7 cycloalkyl, C 1-8 alkoxy-(CR 7 R 8 ) n —O—, C 1-8 alkyl, hydroxy-C 1-8 alkyl, C 2-12 alkynyl, C 6-10 aryl, 3-10 membered heterocyclyl or 5-10 membered heteroaryl, wherein each of the amino, C 1-12 alkoxy, C 3-7 cycloalkyl, C 1-8 alkoxy of C 1-8 alkoxy-(CR 7 R 8 ) n —O—, C 1-8 alkyl, hydroxy-C 1-8 alkyl, C 2-12 alkynyl, C 6-10 aryl, 3-10 membered heterocyclyl and 5-10 membered heteroaryl is independently unsubstituted or substituted with one, two, three, four or five R x ;

each R 10 and R 11 is independently R a R b N—, C 1-8 alkyl, C 1-8 alkoxy, C 3-7 cycloalkyl, 3-12 membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein each of the C 1-8 alkyl, C 1-8 alkoxy, C 3-7 cycloalkyl, 3-12 membered heterocyclyl, C 6-10 aryl and 5-10 membered heteroaryl is independently unsubstituted or substituted with one, two, three, four or five R y ;

each R 12 is independently OH, HOOC—, C 1-8 alkyl, C 1-8 alkoxy, C 3-7 cycloalkyl, 3-12 membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein each of the C 1-8 alkyl, C 1-8 alkoxy, C 3-7 cycloalkyl, 3-12 membered heterocyclyl, C 6-10 aryl and 5-10 membered heteroaryl is independently unsubstituted or substituted with one, two, three, four or five R z ;

each R 3 is independently C 1-8 alkyl, C 3-7 cycloalkyl, 5-10 membered heteroaryl, C 6-10 aryl or 5-10 membered heterocyclyl, wherein each of the C 1-8 alkyl, C 3-7 cycloalkyl, 5-10 membered heteroaryl, C 6-10 aryl and 5-10 membered heterocyclyl is independently unsubstituted or substituted with one, two, three, four or five R g ;

each R x , R y , R z and R g is independently deuterium, F, Cl, Br, OH, CN, HOOC—(CR 7 R 8 ) h —, R 14 C(═O)—, R c R d P(═O)—, R 1 —S(═O) t —, R 16 O—, R 17 -(CR 7 R 8 ) j —, amino, C 1-12 alkoxy, C 3-7 cycloalkyl, C 1-8 alkoxy-(CR 7 R 8 ) n —O—, C 1-8 alkyl, hydroxy-C 1-8 alkyl, C 2-12 alkynyl, C 6-10 aryl, 3-12 membered heterocyclyl or 5-10 membered heteroaryl, wherein each of the amino, C 1-12 alkoxy, C 3-7 cycloalkyl, C 1-8 alkoxy of C 1-8 alkoxy-(CR 7 R 8 ) n —O—, C 1-8 alkyl, hydroxy-C 1-8 alkyl, C 2-12 alkynyl, C 6-10 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, C 1-8 alkoxy, C 1-8 alkyl, hydroxy-C 1-8 alkyl, HOOC—(CR 7 R 8 ) h — and C 1-8 alkoxy-(CR 7 R 8 ) n —;

each R 14 and R 15 is independently R a R b N—, C 1-8 alkyl, C 1-8 alkoxy, C 3-7 cycloalkyl, 3-12 membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein each of the C 1-8 alkyl, C 1-8 alkoxy, C 3-7 cycloalkyl, 3-12 membered heterocyclyl, C 6-10 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, C 1-8 alkoxy, C 1-8 alkyl, HOOC—(CR 7 R 8 ) h — and C 1-8 alkoxy-(CR 7 R 8 ) n —;

each R 7 is independently OH, HOOC—, C 1-8 alkyl, C 1-8 alkoxy, C 3-7 cycloalkyl, 3-12 membered heterocyclyl, C 6-10 aryl or 5-10 membered heteroaryl, wherein each of the C 1-8 alkyl, C 1-8 alkoxy, C 3-7 cycloalkyl, 3-12 membered heterocyclyl, C 6-10 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, C 1-8 alkoxy, C 1-8 alkyl, HOOC—(CR 7 R 8 ) h — and C 1-8 alkoxy-(CR 7 R 8 ) n O—;

each R 16 is independently C 1-8 alkyl, C 3-7 cycloalkyl, 5-10 membered heteroaryl, C 6-10 aryl or 5-10 membered heterocyclyl, wherein each of the C 1-8 alkyl, C 3-7 cycloalkyl, 5-10 membered heteroaryl, C 6-10 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, C 1-8 alkoxy, C 1-8 alkyl, HOOC—(CR 7 R 8 ) h — and C 1-8 alkoxy-(CR 7 R 8 ) n —O—;

each R a , R b , R c and R d is independently H, deuterium, C 1-8 alkyl, C 2-8 alkynyl, C 1-8 alkoxy, C 3-7 cycloalkyl, HOOC—(CR 7 R 8 ) h —, C 6-10 aryl-C 1-4 alkylene or 3-12 membered heterocyclyl, wherein each of the C 1-8 alkyl, C 2-8 alkynyl, C 1-8 alkoxy, C 3-7 cycloalkyl, C 6-10 aryl of C 6-10 aryl-C 1-4 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, C 1-8 alkyl, (C 1-6 alkyl) 2 NC(═O)—, C 1-8 alkoxy, HOOC—(CR 7 R 8 ) h — and C 1-8 alkoxy-(CR 7 R 8 )—O—;

each R 7 and R 8 is independently H, deuterium, F, Cl, Br, C 1-6 alkyl, NH 2 C(═O)—, C 1-6 alkyl-OC(═O)—, carboxy, carboxy-C 1-6 alkylene, hydroxy-C 1-6 alkyl or C 1-6 haloalkyl, or R 7 and R 8 , together with the carbon atom to which they are attached, form C 3-6 cycloalkyl or carbonyl;

each R 9 is independently H, deuterium or C 1-6 alkyl;

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.

2. The compound of claim 1 having Formula (II) or Formula (IIa),

wherein each R 1 and R 1a is independently H, deuterium, F, Cl, Br or I.

3. The compound of claim 1 , wherein each R 2 is independently methyl, ethyl, n-propyl, i-propyl or C 1-4 haloalkyl;

R 3 is furyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, oxazolyl, oxadiazolyl, thiazolyl or thienyl, wherein each of the furyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, oxazolyl, oxadiazolyl, thiazolyl, and thienyl is independently unsubstituted or substituted with methyl;

each R 7 and R 8 is independently H, deuterium, F, Cl, Br, methyl, ethyl, n-propyl, i-propyl, NH 2 C(═O)—, C 1-4 alkyl-OC(═O)—, carboxy, carboxy-C 1-3 alkylene, hydroxy-C 1-4 alkyl or C 1-4 haloalkyl, or R 7 and R 8 , together with the carbon atom to which they are attached, form cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or carbonyl; and

each R 6 independently H, deuterium, methyl, ethyl, n-propyl or i-propyl.

4. The compound of claim 1 , wherein R 5 is 5-10 membered heterocyclyl, C 3-6 cycloalkyl, C 2-8 alkynyl, 5-10 membered heteroaryl, phenyl or naphthyl, wherein each of the 5-10 membered heterocyclyl, C 3-6 cycloalkyl, C 2-8 alkynyl, 5-10 membered heteroaryl, phenyl and naphthyl is independently unsubstituted or substituted with one, two, three, four or five substituents independently selected from deuterium, F, Cl, Br, OH, CN, C 1-4 alkoxy, C 1-4 alkyl, HOOC—(CR 7 R 8 ) h — and C 1-4 alkoxy-C(═O)—;

R 6 is 5-10 membered heterocyclyl, C 3-6 cycloalkyl, C 2-8 alkynyl, 5-10 membered heteroaryl, phenyl or naphthyl, wherein each of the 5-10 membered heterocyclyl, C 3-6 cycloalkyl, C 2-8 alkynyl, 5-10 membered heteroaryl, phenyl and naphthyl is independently unsubstituted or substituted with one, two, three, four or five R w .

5. The compound of claim 1 , wherein R 5 is 5-6 membered heterocyclyl, C 3-6 cycloalkyl, C 2-6 alkynyl, 5-6 membered heteroaryl, 9-10 membered heteroaryl, phenyl or naphthyl, wherein each of the 5-6 membered heterocyclyl, C 3-6 cycloalkyl, C 2-6 alkynyl, 5-6 membered heteroaryl, 9-10 membered heteroaryl, phenyl and naphthyl is independently unsubstituted or substituted with one, two, three, four or five substituents independently selected from deuterium, F, Cl, Br, OH, CN, C 1-3 alkoxy, C 1-3 alkyl, HOOC—(CR 7 R 8 ) h — and C 1-3 alkoxy-C(═O)—;

R 6 is 5-6 membered heterocyclyl, C 3-6 cycloalkyl, C 2-6 alkynyl, 5-6 membered heteroaryl, phenyl or naphthyl, wherein each of the 5-6 membered heterocyclyl, C 3-6 cycloalkyl, C 2-6 alkynyl, 5-6 membered heteroaryl, phenyl and naphthyl is independently unsubstituted or substituted with one, two, three, four or five R w .

6. The compound of claim 1 , wherein R 5 is pyrrolidyl, pyrazolidyl, imidazolidinyl, tetrahydrofuryl, tetrahydrothienyl, tetrahydropyranyl, tetraphydrothiopyranyl, piperidyl, morpholinyl, thiomorpholinyl, piperazinyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, ethynyl, propargyl, propynyl, butynyl, pentynyl, pyridyl, 1,3,5-triazinyl, pyrazinyl, pyridazinyl, pyrimidinyl, furyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, thienyl, benzothiazolyl, benzimidazolyl, benzofuranyl, benzothienyl, indolyl, purinyl, quinolyl, isoquinolyl, phenyl or naphthyl, wherein each of the pyrrolidyl, pyrazolidyl, imidazolidinyl, tetrahydrofuryl, tetrahydrothienyl, tetrahydropyranyl, tetraphydrothiopyranyl, piperidyl, morpholinyl, thiomorpholinyl, piperazinyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, ethynyl, propargyl, propynyl, butynyl, pentynyl, pyridyl, 1,3,5-triazinyl, pyrazinyl, pyridazinyl, pyrimidinyl, furyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, thienyl, benzothiazolyl, benzimidazolyl, benzofuranyl, benzothienyl, indolyl, purinyl, quinolyl, isoquinolyl, phenyl and naphthyl is independently unsubstituted or substituted with one, two, three, four or five substituents independently selected from deuterium, F, Cl, Br, CN, OH, C 1-3 alkoxy, C 1-3 alkyl, HOOC—(CR 7 R 8 ) h — and C 1-3 alkoxy-C(═O)—;

R 6 is pyrrolidyl, pyrazolidyl, imidazolidinyl, tetrahydrofuryl, tetrahydrothienyl, tetrahydropyranyl, tetraphydrothiopyranyl, piperidyl, morpholinyl, thiomorpholinyl, piperazinyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, ethynyl, propargyl, propynyl, butynyl, pentynyl, pyridyl, 1,3,5-triazinyl, pyrazinyl, pyridazinyl, pyrimidinyl, furyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, thienyl, phenyl or naphthyl, wherein each of the pyrrolidyl, pyrazolidyl, imidazolidinyl, tetrahydrofuryl, tetrahydrothienyl, tetrahydropyranyl, tetraphydrothiopyranyl, piperidyl, morpholinyl, thiomorpholinyl, piperazinyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, ethynyl, propargyl, propynyl, butynyl, pentynyl, pyridyl, 1,3,5-triazinyl, pyrazinyl, pyridazinyl, pyrimidinyl, furyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, thienyl, phenyl and naphthyl is independently unsubstituted or substituted with one, two, three, four or five R w .

7. The compound of claim 1 , wherein each R w is independently deuterium, F, Cl, Br, OH, CN, HOOC—(CR 7 R 8 ) h —, R 11 C(═O)—, R c R d P(═O)—, R 10 —S(═O) t —, R 13 O—, R 12 —(CR 7 R 8 ) j —, amino, C 1-6 alkoxy, C 3-6 cycloalkyl, C 1-6 alkoxy-(CR 7 R 8 ) n —O—, C 1-6 alkyl, hydroxy-C 1-6 alkyl, C 2-6 alkynyl, phenyl, naphthyl, 5-6 membered heterocyclyl or 5-6 membered heteroaryl, and wherein each of the amino, C 1-6 alkoxy, C 3-6 cycloalkyl, C 1-6 alkoxy of C 1-6 alkoxy-(CR 7 R 8 ) n —O—, C 1-6 alkyl, hydroxy-C 1-6 alkyl, C 2-6 alkynyl, phenyl, naphthyl, 5-6 membered heterocyclyl and 5-6 membered heteroaryl is independently unsubstituted or substituted with one, two, three, four or five R x .

8. The compound of claim 1 , wherein each R w is independently deuterium, F, Cl, Br, OH, CN, HOOC—(CR 7 R 8 ) h —, R 11 C(═O)—, R c R d P(═O)—, R 10 —S(═O) t —, R 13 O—, R 12 —(CR 7 R 8 ) j —, amino, C 1-4 alkoxy, C 3-6 cycloalkyl, C 1-4 alkoxy-(CR 7 R 8 ) n —O—, C 1-4 alkyl, hydroxy-C 1-4 alkyl, C 2-4 alkynyl, phenyl, pyridyl, 1,3,5-triazinyl, pyrazinyl, pyridazinyl, pyrimidinyl, furyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, thienyl, pyrrolidyl, pyrazolidyl, imidazolidinyl, tetrahydrofuryl, tetrahydrothienyl, tetrahydropyranyl, tetraphydrothiopyranyl, piperidyl, morpholinyl, thiomorpholinyl or piperazinyl, and wherein each of the amino, C 1-4 alkoxy, C 3-6 cycloalkyl, C 1-4 alkoxy-(CR 7 R 8 ) n —O—, C 1-4 alkyl, hydroxy-C 1-4 alkyl, C 2-4 alkynyl, phenyl, pyridyl, 1,3,5-triazinyl, pyrazinyl, pyridazinyl, pyrimidinyl, furyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, thienyl, pyrrolidyl, pyrazolidyl, imidazolidinyl, tetrahydrofuryl, tetrahydrothienyl, tetrahydropyranyl, tetraphydrothiopyranyl, piperidyl, morpholinyl, thiomorpholinyl and piperazinyl is independently unsubstituted or substituted with one, two, three, four or five R x .

9. The compound of claim 1 , wherein each R 10 and R 11 is independently R a R b N—, C 1-6 alkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, 5-6 membered heterocyclyl, phenyl, naphthyl or 5-6 membered heteroaryl, and wherein each of the C 1-6 alkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, 5-6 membered heterocyclyl, phenyl, naphthyl and 5-6 membered heteroaryl is independently unsubstituted or substituted with one, two, three, four or five R 1 ;

each R 12 is independently OH, HOOC—, C 1-6 alkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, 4 membered heterocyclyl, 5-6 membered heterocyclyl, phenyl, naphthyl or 5-6 membered heteroaryl, and wherein each of the C 1-6 alkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, 4 membered heterocyclyl, 5-6 membered heterocyclyl, phenyl, naphthyl and 5-6 membered heteroaryl is independently unsubstituted or substituted with one, two, three, four or five R z ;

each R 3 is independently C 1-6 alkyl, C 3-6 cycloalkyl, 5-6 membered heteroaryl, phenyl, naphthyl or 5-6 membered heterocyclyl, and wherein each of the C 1-6 alkyl, C 3-6 cycloalkyl, 5-6 membered heteroaryl, phenyl, naphthyl and 5-6 membered heterocyclyl is independently unsubstituted or substituted with one, two, three, four or five R 1 .

10. The compound of claim 1 , wherein each R 10 and R 11 is independently R a R b N—, C 1-4 alkyl, C 1-4 alkoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, pyrrolidyl, pyrazolidyl, imidazolidinyl, tetrahydrofuryl, tetrahydrothienyl, tetrahydropyranyl, tetraphydrothiopyranyl, piperidyl, morpholinyl, thiomorpholinyl, piperazinyl, phenyl, pyridyl, 1,3,5-triazinyl, pyrazinyl, pyridazinyl, pyrimidinyl, furyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl or thienyl, and wherein each of the C 1-4 alkyl, C 1-4 alkoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, pyrrolidyl, pyrazolidyl, imidazolidinyl, tetrahydrofuryl, tetrahydrothienyl, tetrahydropyranyl, tetraphydrothiopyranyl, piperidyl, morpholinyl, thiomorpholinyl, piperazinyl, phenyl, pyridyl, 1,3,5-triazinyl, pyrazinyl, pyridazinyl, pyrimidinyl, furyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl and thienyl is independently unsubstituted or substituted with one, two, three, four or five R y ;

each R 12 is independently OH, HOOC—, C 1-4 alkyl, C 1-4 alkoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, azetidinyl, oxetanyl, thietanyl, pyrrolidyl, pyrazolidyl, imidazolidinyl, tetrahydrofuryl, tetrahydrothienyl, tetrahydropyranyl, tetraphydrothiopyranyl, piperidyl, morpholinyl, thiomorpholinyl, piperazinyl, phenyl, pyridyl, 1,3,5-triazinyl, pyrazinyl, pyridazinyl, pyrimidinyl, furyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl or thienyl, and wherein each of the C 1-4 alkyl, C 1-4 alkoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, azetidinyl, oxetanyl, thietanyl, pyrrolidyl, pyrazolidyl, imidazolidinyl, tetrahydrofuryl, tetrahydrothienyl, tetrahydropyranyl, tetraphydrothiopyranyl, piperidyl, morpholinyl, thiomorpholinyl, piperazinyl, phenyl, pyridyl, 1,3,5-triazinyl, pyrazinyl, pyridazinyl, pyrimidinyl, furyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl and thienyl is independently unsubstituted or substituted with one, two, three, four or five R z ;

each R 13 is independently C 1-4 alkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, pyrrolidyl, pyrazolidyl, imidazolidinyl, tetrahydrofuryl, tetrahydrothienyl, tetrahydropyranyl, tetraphydrothiopyranyl, piperidyl, morpholinyl, thiomorpholinyl, piperazinyl, phenyl, pyridyl, 1,3,5-triazinyl, pyrazinyl, pyridazinyl, pyrimidinyl, furyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl or thienyl, and wherein each of the C 1-4 alkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, pyrrolidyl, pyrazolidyl, imidazolidinyl, tetrahydrofuryl, tetrahydrothienyl, tetrahydropyranyl, tetraphydrothiopyranyl, piperidyl, morpholinyl, thiomorpholinyl, piperazinyl, phenyl, pyridyl, 1,3,5-triazinyl, pyrazinyl, pyridazinyl, pyrimidinyl, furyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl and thienyl is independently unsubstituted or substituted with one, two, three, four or five R g .

11. The compound of claim 1 , wherein each R x , R y , R z and R g is independently deuterium, F, Cl, Br, OH, CN, HOOC—(CR 7 R 8 ) h —, R 14 C(═O)—, R c R d P(═O)—, R 15 —S(═O) t —, R 16 O—, R 17 —(CR 7 R 8 ) j —, amino, C 1-6 alkoxy, C 3-6 cycloalkyl, C 1-6 alkoxy-(CR 7 R 8 ) n —O—, C 1-6 alkyl, hydroxy-C 1-6 alkyl, C 2-6 alkynyl, phenyl, naphthyl, 5-6 membered heterocyclyl or 5-6 membered heteroaryl, wherein each of the amino, C 1-6 alkoxy, C 3-6 cycloalkyl, C 1-6 alkoxy of C 1-6 alkoxy-(CR 7 R 8 ) n —O—, C 1-6 alkyl, hydroxy-C 1-6 alkyl, C 2-6 alkynyl, phenyl, naphthyl, 5-6 membered heterocyclyl and 5-6 membered heteroaryl is independently unsubstituted or substituted with one, two, three, four or five substituents independently selected from deuterium, F, Cl, Br, OH, C 1-6 alkoxy, C 1-6 alkyl, hydroxy-C 1-6 alkyl, HOOC—(CR 7 R 8 ) h — and C 1-6 alkoxy-(CR 7 R 8 ) n —.

12. The compound of claim 1 , wherein each R x , R y , R z and R g is independently deuterium, F, Cl, Br, OH, CN, HOOC—(CR 7 R 8 ) h —, R 14 C(═O)—, R c R d P(═O)—, R 15 —S(═O) t —, R 16 O—, R 17 —(CR 7 R 8 ) j —, amino, C 1-4 alkoxy, C 3-6 cycloalkyl, C 1-4 alkoxy-(CR 7 R 8 ) n —O—, C 1-4 alkyl, hydroxy-C 1-4 alkyl, C 2-4 alkynyl, phenyl, pyridyl, 1,3,5-triazinyl, pyrazinyl, pyridazinyl, pyrimidinyl, furyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, thienyl, pyrrolidyl, pyrazolidyl, imidazolidinyl, tetrahydrofuryl, tetrahydrothienyl, tetrahydropyranyl, tetraphydrothiopyranyl, piperidyl, morpholinyl, thiomorpholinyl or piperazinyl, and wherein each of the amino, C 1-4 alkoxy, C 3-6 cycloalkyl, C 1-4 alkoxy-(CR 7 R 8 ) n —O—, C 1-4 alkyl, hydroxy-C 1-4 alkyl, C 2-4 alkynyl, phenyl, pyridyl, 1,3,5-triazinyl, pyrazinyl, pyridazinyl, pyrimidinyl, furyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, thienyl, pyrrolidyl, pyrazolidyl, imidazolidinyl, tetrahydrofuryl, tetrahydrothienyl, tetrahydropyranyl, tetraphydrothiopyranyl, piperidyl, morpholinyl, thiomorpholinyl and piperazinyl is independently unsubstituted or substituted with one, two, three, four or five substituents independently selected from deuterium, F, Cl, Br, OH, C 1-4 alkoxy, C 1-4 alkyl, hydroxy-C 1-4 alkyl, HOOC—(CR 7 R 8 ) h — and C 1-4 alkoxy-(CR 7 R 8 ) n —.

13. The compound of claim 1 , wherein each R 14 and R 15 is independently R a R b N—, C 1-6 alkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, 5-6 membered heterocyclyl, phenyl, naphthyl or 5-6 membered heteroaryl, wherein each of the C 1-6 alkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, 5-6 membered heterocyclyl, phenyl, naphthyl and 5-6 membered heteroaryl is independently unsubstituted or substituted with one, two, three, four or five substituents independently selected from deuterium, F, Cl, Br, OH, C 1-6 alkoxy, C 1-6 alkyl, HOOC—(CR 7 R 8 ) h — and C 1-6 alkoxy-(CR 7 R 8 ) n —O—;

each R 7 is independently OH, HOOC—, C 1-6 alkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, 5-6 membered heterocyclyl, phenyl, naphthyl or 5-6 membered heteroaryl, wherein each of the C 1-6 alkyl, C 1-6 alkoxy, C 3-6 cycloalkyl, 5-6 membered heterocyclyl, phenyl, naphthyl and 5-6 membered heteroaryl is independently unsubstituted or substituted with one, two, three, four or five substituents independently selected from deuterium, F, Cl, Br, OH, C 1-6 alkoxy, C 1-6 alkyl, HOOC—(CR 7 R 8 ) h — and C 1-6 alkoxy-(CR 7 R 8 ) n —;

each R 16 is independently C 1-6 alkyl, C 3-6 cycloalkyl, 5-6 membered heteroaryl, phenyl, naphthyl or 5-6 membered heterocyclyl, wherein each of the C 1-6 alkyl, C 3-6 cycloalkyl, 5-6 membered heteroaryl, phenyl, naphthyl and 5-6 membered heterocyclyl is independently unsubstituted or substituted with one, two, three, four or five substituents independently selected from deuterium, F, Cl, Br, OH, C 1-6 alkoxy, C 1-6 alkyl, HOOC—(CR 7 R 8 ) h — and C 1-6 alkoxy-(CR 7 R 8 ) n —O—.

14. The compound of claim 1 , wherein each R 14 and R 15 is independently R a R b N—, C 1-4 alkyl, C 1-4 alkoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, pyrrolidyl, pyrazolidyl, imidazolidinyl, tetrahydrofuryl, tetrahydrothienyl, tetrahydropyranyl, tetraphydrothiopyranyl, piperidyl, morpholinyl, thiomorpholinyl, piperazinyl, phenyl, pyridyl, 1,3,5-triazinyl, pyrazinyl, pyridazinyl, pyrimidinyl, furyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl or thienyl, and wherein each of the C 1-4 alkyl, C 1-4 alkoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, pyrrolidyl, pyrazolidyl, imidazolidinyl, tetrahydrofuryl, tetrahydrothienyl, tetrahydropyranyl, tetraphydrothiopyranyl, piperidyl, morpholinyl, thiomorpholinyl, piperazinyl, phenyl, pyridyl, 1,3,5-triazinyl, pyrazinyl, pyridazinyl, pyrimidinyl, furyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl and thienyl is independently unsubstituted or substituted with one, two, three, four or five substituents independently selected from deuterium, F, Cl, Br, OH, C 1-4 alkoxy, C 1-4 alkyl, HOOC—(CR 7 R 8 ) h — and C 1-4 alkoxy-(CR 7 R 8 )—O—;

each R 17 is independently OH, HOOC—, C 1-4 alkyl, C 1-4 alkoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, pyrrolidyl, pyrazolidyl, imidazolidinyl, tetrahydrofuryl, tetrahydrothienyl, tetrahydropyranyl, tetraphydrothiopyranyl, piperidyl, morpholinyl, thiomorpholinyl, piperazinyl, phenyl, pyridyl, 1,3,5-triazinyl, pyrazinyl, pyridazinyl, pyrimidinyl, furyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl or thienyl, and wherein each of the C 1-4 alkyl, C 1-4 alkoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, pyrrolidyl, pyrazolidyl, imidazolidinyl, tetrahydrofuryl, tetrahydrothienyl, tetrahydropyranyl, tetraphydrothiopyranyl, piperidyl, morpholinyl, thiomorpholinyl, piperazinyl, phenyl, pyridyl, 1,3,5-triazinyl, pyrazinyl, pyridazinyl, pyrimidinyl, furyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl and thienyl is independently unsubstituted or substituted with one, two, three, four or five substituents independently selected from deuterium, F, Cl, Br, OH, C 1-4 alkoxy, C 1-4 alkyl, HOOC—(CR 7 R 8 ) h — and C 1-4 alkoxy-(CR 7 R 8 ) n —O—;

each R 16 is independently C 1-4 alkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, pyrrolidyl, pyrazolidyl, imidazolidinyl, tetrahydrofuryl, tetrahydrothienyl, tetrahydropyranyl, tetraphydrothiopyranyl, piperidyl, morpholinyl, thiomorpholinyl, piperazinyl, phenyl, pyridyl, 1,3,5-triazinyl, pyrazinyl, pyridazinyl, pyrimidinyl, furyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl or thienyl, and wherein each of the C 1-4 alkyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, pyrrolidyl, pyrazolidyl, imidazolidinyl, tetrahydrofuryl, tetrahydrothienyl, tetrahydropyranyl, tetraphydrothiopyranyl, piperidyl, morpholinyl, thiomorpholinyl, piperazinyl, phenyl, pyridyl, 1,3,5-triazinyl, pyrazinyl, pyridazinyl, pyrimidinyl, furyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl and thienyl is independently unsubstituted or substituted with one, two, three, four or five substituents independently selected from deuterium, F, Cl, Br, OH, C 1-4 alkoxy, C 1-4 alkyl, HOOC—(CR 7 R 8 ) h — and C 1-4 alkoxy-(CR 7 R 8 ) n —O—.

15. The compound of claim 1 , wherein each R a , R b , R c and R d is independently H, deuterium, C 1-6 alkyl, C 2-6 alkynyl, C 1-6 alkoxy, C 3-6 cycloalkyl, HOOC—(CR 7 R 8 ) h —, phenyl-C 1-3 alkylene or 5-6 membered heterocyclyl, wherein each of the C 1-6 alkyl, C 2-6 alkynyl, C 1-6 alkoxy, C 3-6 cycloalkyl, phenyl-C 1-3 alkylene and 5-6 membered heterocyclyl is independently unsubstituted or substituted with one, two, three, four or five substituents independently selected from deuterium, F, Cl, Br, OH, C 1-6 alkyl, (C 1-4 alkyl) 2 NC(═O)—, C 1-6 alkoxy, HOOC—(CR 7 R 8 ) h — and C 1-6 alkoxy-(CR 7 R 8 ) n —O—.

16. The compound of claim 1 , wherein each R a , R b , R c and R d is independently H, deuterium, C 1-4 alkyl, C 2-4 alkynyl, C 1-4 alkoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, HOOC—(CR 7 R 8 ) h —, phenyl-methylene, pyrrolidyl, pyrazolidyl, imidazolidinyl, tetrahydrofuryl, tetrahydrothienyl, tetrahydropyranyl, tetraphydrothiopyranyl, piperidyl, morpholinyl, thiomorpholinyl or piperazinyl, and wherein each of the C 1-4 alkyl, C 2-4 alkynyl, C 1-4 alkoxy, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl-methylene, pyrrolidyl, pyrazolidyl, imidazolidinyl, tetrahydrofuryl, tetrahydrothienyl, tetrahydropyranyl, tetraphydrothiopyranyl, piperidyl, morpholinyl, thiomorpholinyl and piperazinyl is independently unsubstituted or substituted with one, two, three, four or five substituents independently selected from deuterium, F, Cl, Br, OH, C 1-4 alkyl, (CH 3 ) 2 NC(═O)—, (CH 2 CH 3 ) 2 NC(═O)—, CH 3 CH 2 N(CH 3 )C(═O)—, C 1-4 alkoxy, HOOC—(CR 7 R 8 ) h — and C 1-4 alkoxy-(CR 7 R 8 ) n —O—.

17. The compound of claim 1 having one of the following structures:

a stereoisomer, a tautomer, an N-oxide, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof.

18. A pharmaceutical composition comprising the compound of claim 1 and one or more pharmaceutically acceptable adjuvants.

19. The pharmaceutical composition of claim 18 , further comprising one or more other anti-HBV drugs selected from the group consisting of lamivudine, telbivudine, tenofovir, entecavir, adefovir dipivoxil, alfaferone, alloferon, celmoleukin, clevudine, emtricitabine, famciclovir, feron, hepatect CP, intefen, interferon α-1b, interferon α, interferon α-2a, interferon β-1a, interferon α-2, interleukin-2, mivotilate, nitazoxanide, peginterferon alfa-2a, ribavirin, roferon-A, sizofiran, Euforavac, rintatolimod, Phosphazid, Heplisav, interferon α-2b, levamisole, and propagermanium.

20. A method of managing, treating or lessening a virus disease comprising administering the compound of claim 1 to a patient in need thereof, wherein

the virus disease is hepatitis B infection or a disease caused by hepatitis B infection, and

the disease caused by hepatitis B infection is hepatic cirrhosis or hepatocellular carcinogenesis.

21. A method of managing, treating or lessening a virus disease comprising administering the pharmaceutical composition of claim 18 to a patient in need thereof, wherein

the virus disease is hepatitis B infection or a disease caused by hepatitis B infection, and

the disease caused by hepatitis B infection is hepatic cirrhosis or hepatocellular carcinogenesis.