Thienopyrimidine derivative and use thereof in medicine

1. A compound having Formula (I) or a stereoisomer, a geometric isomer, a tautomer, a hydrate, a solvate, or a pharmaceutically acceptable salt thereof,

wherein:

Het is —C(═O)NR a R b , —C(═NR)NR a R b , —NH—C(═NR)NR a R b , 3-10 membered heterocyclyl or 5-10 membered heteroaryl; wherein each of 3-10 membered heterocyclyl and 5-10 membered heteroaryl is independently and optionally substituted with H, oxo (═O), F, Cl, Br, I, hydroxy, amino, nitro, cyano, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 haloalkyl, carboxy and —C(═O)NH 2 ;

R 1 is H, F, Cl, Br, I, hydroxy, amino, nitro, cyano, C 1-6 alkyl, C 1-6 alkoxy or C 1-6 haloalkyl;

R 2 is —OR or —NR a R b ;

each of R 3 and R 4 is independently H, C 1-6 alkyl, C 1-6 hydroxyalkyl or C 1-6 haloalkyl;

L is —O—, —O-methylene-, —O-ethylene-, —S— or —NH—;

R 5 is C 6-10 aryl or 5-10 membered heteroaryl, wherein each of C 6-10 aryl and 5-10 membered heteroaryl is independently and optionally substituted with 1, 2 or 3 R 6 ; wherein R 6 is H, F, Cl, Br, I, hydroxy, amino, nitro, cyano, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 haloalkyl, C 1-6 haloalkoxy, C 1-6 cyanoalkyl or C 1-6 hydroxyalkyl; and

W is fused cyclyl, bridged cyclyl or spiro cyclyl, wherein fused cyclyl, bridged cyclyl or spiro cyclyl is saturated or partially unsaturated 6-12 membered cyclyl containing 0, 1, 2, 3 or 4 heteroatoms independently selected from N, O or S; and wherein W is optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from oxo (═O), F, Cl, Br, I, hydroxy, amino, nitro, cyano, —C(═O)OR, —C(═O)NR a R b , —C(═NR)NR a R b , —NH—C(═NR)NR a R b , —SO 2 R, —SO 2 NR a R b , C 1-6 alkyl, C 3-6 cycloalkyl, C 1-6 alkoxy, C 1-6 haloalkoxy, C 1-6 alkylamino, C 1-6 haloalkyl, C 1-6 cyanoalkyl and C 1-6 hydroxyalkyl;

wherein each R, R a and R b is independently H, C 1-6 alkyl, C 1-6 haloalkyl or C 3-8 cycloalkyl; or R a and R b , together with the N atom to which they are attached, form 3-10 membered heterocyclyl; and wherein 3-10 membered heterocyclyl is optionally substituted with oxo (═O), F, Cl, Br, I, hydroxy, amino, nitro, cyano, C 1-6 alkyl, C 1-6 alkoxy and C 1-6 haloalkyl.

2. The compound of claim 1 , wherein Het is 5-6 membered heterocyclyl or 5-6 membered heteroaryl; and wherein each of 5-6 membered heterocyclyl and 5-6 membered heteroaryl is independently and optionally substituted with H, oxo (═O), F, Cl, Br, I, hydroxy, amino, nitro, cyano, C 1-3 alkyl, C 1-3 alkoxy, C 1-3 haloalkyl, carboxy and —C(═O)NH 2 .

3. The compound of claim 1 , wherein Het is pyrrolidyl, tetrahydrofuryl, imidazolidinyl, pyrazolidyl, tetrahydropyranyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl, pyrrolyl, furyl, thienyl, pyrazolyl, imidazolyl, oxazolyl, thiazolyl, triazolyl, tetrazolyl, pyridyl, pyrimidinyl, pyridazinyl or pyrazinyl, wherein each of pyrrolidyl, tetrahydrofuryl, imidazolidinyl, pyrazolidyl, tetrahydropyranyl, piperidyl, piperazinyl, morpholinyl, thiomorpholinyl, pyrrolyl, furyl, thienyl, pyrazolyl, imidazolyl, oxazolyl, thiazolyl, triazolyl, tetrazolyl, pyridyl, pyrimidinyl, pyridazinyl and pyrazinyl is independently and optionally substituted with H, oxo (═O), F, Cl, Br, I, hydroxy, amino, nitro, cyano, methyl, ethyl, isopropyl, methoxy, ethoxy, isopropoxy, trifluoromethyl, difluoromethyl, carboxy and —C(═O)NH 2 .

4. The compound of claim 1 , wherein R 1 is H, F, Cl, Br, I, hydroxy, amino, nitro, cyano, C 1-3 alkyl, C 1-3 alkoxy or C 1-3 haloalkyl; and

R 2 is —OR or —NR a R b ;

wherein each R, R a and R b is independently H, C 1-3 alkyl, C 1-3 haloalkyl or C 3-6 cycloalkyl; or R a and R b , together with the N atom to which they are attached, form 4-6 membered heterocyclyl; and wherein 4-6 membered heterocyclyl is optionally substituted with oxo (═O), F, Cl, Br, I, hydroxy, amino, nitro, cyano, C 1-3 alkyl, C 1-3 alkoxy and C 1-3 haloalkyl; and

each of R 3 and R 4 is independently H, C 1-3 alkyl, C 1-3 hydroxyalkyl or C 1-3 haloalkyl.

5. The compound of claim 1 , wherein R 1 is H, F, Cl, Br, I, hydroxy, amino, nitro, cyano, methyl, ethyl, methoxy, ethoxy, isopropoxy, trifluoromethyl, difluoromethyl or trifluoroethyl; and

R 2 is —OR or —NR a R b ;

wherein each R, R a and R b is independently H, methyl, ethyl, n-propyl, isopropyl, trifluoromethyl, difluoromethyl, trifluoroethyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl;

or R a and R b , together with the N atom to which they are attached, form heterocyclyl selected from heterocyclyl groups represented by formulae (I-a) to (I-k):

wherein the heterocyclyl groups represented by formulae (I-a) to (I-k) are optionally substituted with oxo (═O), F, Cl, Br, I, hydroxy, amino, nitro, cyano, methyl, ethyl, isopropyl, methoxy, ethoxy, trifluoromethyl, difluoromethyl or trifluoroethyl; and

each of R 3 and R 4 is independently H, methyl, ethyl, n-propyl, hydroxymethyl, hydroxyethyl, trifluoromethyl or 2-fluoroethyl.

6. The compound of claim 1 , wherein R 5 is phenyl, naphthyl, 1,2,3,4-tetrahydronaphthyl or 5-6 membered heteroaryl, wherein each of phenyl, naphthyl, 1,2,3,4-tetrahydronaphthyl and 5-6 membered heteroaryl is independently and optionally substituted with 1, 2 or 3 R 6 ; and wherein R 6 is H, F, Cl, Br, I, hydroxy, amino, nitro, cyano, C 1-3 alkyl, C 1-3 alkoxy, C 1-3 haloalkyl, C 1-3 haloalkoxy, C 1-3 cyanoalkyl or C 1-3 hydroxyalkyl.

7. The compound of claim 1 , wherein R 5 is phenyl, naphthyl, 1,2,3,4-tetrahydronaphthyl, imidazolyl, pyrazolyl, furyl, thienyl, oxazolyl, oxadiazolyl, thiazolyl, thiadiazolyl, triazolyl, tetrazolyl, pyridyl, pyrimidinyl, pyranyl or pyridazinyl, wherein each of phenyl, naphthyl, 1,2,3,4-tetrahydronaphthyl, imidazolyl, pyrazolyl, furyl, thienyl, oxazolyl, oxadiazolyl, thiazolyl, thiadiazolyl, triazolyl, tetrazolyl, pyridyl, pyrimidinyl, pyranyl and pyridazinyl is independently and optionally substituted with 1, 2 or 3 R 6 ; and wherein R 6 is H, F, Cl, Br, I, hydroxy, amino, nitro, cyano, methyl, ethyl, n-propyl, isopropyl, methoxy, ethoxy, isopropoxy, trifluoromethyl, difluoromethyl, trifluoromethoxy, difluoromethoxy, hydroxymethyl, hydroxyethyl, cyanomethyl or cyanoethyl.

8. The compound of claim 1 , wherein W has one of the following structures:

each of X 1 , X 2 and X 3 is independently a bond, —CH 2 —, —O—, —S— or —NH—;

Y is CH or N;

each r, s, t and n is independently 0, 1, 2, or 3; and

each W is optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from oxo (═O), F, Cl, Br, I, hydroxy, amino, nitro, cyano, —C(═O)OH, —C(═O)NH 2 , —C(═NH)NH 2 , —NH—C(═NH)NH 2 , —SO 2 CH 3 , —SO 2 C 2 H 5 , C 1-3 alkyl, C 3-6 cycloalkyl, C 1-3 alkoxy, C 1-3 haloalkoxy, C 1-3 alkylamino, C 1-3 haloalkyl, C 1-3 cyanoalkyl and C 1-3 hydroxyalkyl.

9. The compound of claim 1 , wherein W has one of the following structures:

wherein each W is optionally substituted with 1, 2, 3, 4 or 5 substituents independently selected from oxo (═O), F, Cl, Br, I, hydroxy, amino, nitro, cyano, —C(═O)OH, —C(═O)NH 2 , —C(═NH)NH 2 , —NH—C(═NH)NH 2 , —SO 2 CH 3 , —SO 2 C 2 H 5 , methyl, ethyl, isopropyl, n-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, trifluoromethyl, difluoromethyl, methoxy, ethoxy, isopropoxy, trifluoromethoxy, difluoromethoxy, methylamino, cyanomethyl and hydroxymethyl.

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

or a stereoisomer, a geometric isomer, a tautomer, an N oxide, a hydrate, a solvate, or a pharmaceutically acceptable salt thereof.

11. A pharmaceutical composition comprising the compound of claim 1 .

12. The pharmaceutical composition of claim 11 further comprising a pharmaceutically acceptable carrier, excipient, diluent, adjuvant, vehicle or a combination thereof.

13. A method of treating or lessening a disorder or disease regulated by acetyl-CoA carboxylase in a patient comprising administering to the patient a therapeutically effective amount of the compound of claim 1 , wherein the disorder or disease is obesity, metabolic syndrome, diabetes, non-alcoholic steatohepatitis, breast cancer, colorectal cancer or prostate cancer.

14. A method of treating or lessening a disorder or disease regulated by acetyl-CoA carboxylase in a patient comprising administering to the patient a therapeutically effective amount of the pharmaceutical composition of claim 11 , wherein the disorder or disease is obesity, metabolic syndrome, diabetes, non-alcoholic steatohepatitis, breast cancer, colorectal cancer or prostate cancer.