Imidazole derivative used as antiviral agent and use therof in preparation of medicament

A chemical compound having the following formula or the pharmaceutical acceptable salt thereof:

• wherein
• each of X1, X2, and X4 independently represents CH, or substituted CH;
• X3 represents CH, N, or substituted CH;
• R2 is a C1-6 alkyl group or a C2-6 alkenyl group that are optionally substituted by 0-3 halogen atoms, CN or OH, and wherein optionally one of —C(═O)—, —S(═O)— or —S(═O)2— is inserted into the chain of the alkyl or alkenyl group;
• Z represents C═O;
• one of D1-4 is —C(Rd1)(Rd2)— or —C(═O)—, and the remaining three are CH2;
• each of Rd1 and Rd2 is independently selected from H, OH, or CH3.

A chemical compound or a pharmaceutical acceptable salt thereof, the chemical compound being selected from the group consisting of the following compounds:

• 62) Isopropyl 1′-((1-(4-hydroxybutyl)-4,5,6,7-tetrahydro-1H-benzo[d]imidazol-2-yl)methyl)-2′-oxospiro[azetidine-3,3′-indoline]-1-carboxylate;
• 64) Isopropyl 1′-((1-(4,4-difluorobutyl)-4,5,6,7-tetrahydro-1H-benzo[d]imidazol-2-yl)methyl)-2′-oxospiro[azetidine-3,3′-indoline]-1-carboxylate;
• 65) Isopropyl 2′-oxo-1′-((1-(4,4,4-trifluorobutyl)-4,5,6,7-tetrahydro-1H-benzo[d]imidazol-2-yl)methyl)-spiro[azetidine-3,3′-indoline]-1-carboxylate;
• 66) Isopropyl 2′-oxo-1′-((1-(2,2,4-trifluorobutyl)-4,5,6,7-tetrahydro-1H-benzo[d]imidazol-2-yl)methyl)spiro[azetidine-3,3′-indoline]-1-carboxylate;
• 67) Isopropyl 1′-((1-(2,2-difluorobutyl)-4,5,6,7-tetrahydro-1H-benzo[d]imidazol-2-yl)methyl)-2′-oxospiro[azetidine-3,3′-indoline]-1-carboxylate;
• 68) Isopropyl1′-((1-(3-methyl-2-oxobutyl)-4,5,6,7-tetrahydro-1H-benzo[d]imidazol-2-yl)methyl)-2′-oxospiro[azetidine-3,3′-indoline]-1-carboxylate;
• 69) Isopropyl1′-((1-(2,2-difluoro-3-methylbutyl)-4,5,6,7-tetrahydro-1H-benzo[d]imidazol-2-yl)methyl)-2′-oxospiro[azetidine-3,3′-indoline]-1-carboxylate;
• 70) (Z)-isopropyl 1′-((1-(2-fluoro-3-methylbut-1-en-1-yl)-4,5,6,7-tetrahydro-1H-benzo[d]imidazol-2-yl)methyl)-2′-oxospiro[azetidine-3,3′-indoline]-1-carboxylate;
• 71) Isopropyl 1′-((1-(2-fluoro-3-methylbut-2-en-1-yl)-4,5,6,7-tetrahydro-1H-benzo[d]imidazol-2-yl)methyl)-2′-oxospiro[azetidine-3,3′-indoline]-1-carboxylate;
• 72) Ethyl 1′-((1-isopentyl-4,5,6,7-tetrahydro-1H-benzo[d]imidazol-2-yl)methyl)-2′-oxospiro[azetidine-3,3′-indoline]-1-carboxylate;
• 73) Ethyl 1′-((1-(3-fluorobutyl)-4,5,6,7-tetrahydro-1H-benzo[d]imidazol-2-yl)methyl)-2′-oxospiro[azetidine-3,3′-indoline]-1-carboxylate;
• 74) Ethyl 1′-((1-(3-cyanopropyl)-4,5,6,7-tetrahydro-1H-benzo[d]imidazol-2-yl)methyl)-2′-oxospiro[azetidine-3,3′-indoline]-1-carboxylate;
• 75) Ethyl 2′-oxo-1′-((1-(4,4,4-trifluorobutyl)-4,5,6,7-tetrahydro-1H-benzo[d]imidazol-2-yl)methyl)spiro[azetidine-3,3′-indoline]-1-carboxylate;
• 76) Ethyl 1′-((1-(3-(methylsulfonyl)propyl)-4,5,6,7-tetrahydro-1H-benzo[d]imidazol-2-yl)methyl)-2′-oxospiro[azetidine-3,3′-indoline]-1-carboxylate;
• 77) Cyclopentyl 1′-((1-(3-hydroxybutyl)-4,5,6,7-tetrahydro-1H-benzo[d]imidazol-2-yl)methyl)-2′-oxospiro[azetidine-3,3′-indoline]-1-carboxylate;
• 78) Isopropyl 5′-bromo-1′-((1-(4-hydroxybutyl)-4,5,6,7-tetrahydro-1H-benzo[d]imidazol-2-yl)methyl)-2′-oxospiro[azetidine-3,3′-indoline]-1-carboxylate;
• 79) Isopropyl 5′-bromo-2′-oxo-1′-((1-(4,4,4-trifluorobutyl)-4,5,6,7-tetrahydro-1H-benzo[d]imidazol-2-yl)methyl)spiro[azetidine-3,3′-indoline]-1-carboxylate;
• 80) Isopropyl 5′-chloro-2′-oxo-1′-((1-(4,4,4-trifluorobutyl)-4,5,6,7-tetrahydro-1H-benzo[d]imidazol-2-yl)methyl)spiro[azetidine-3,3′-indoline]-1-carboxylate;
• 81) Isopropyl 6′-chloro-2′-oxo-1′-((1-(4,4,4-trifluorobutyl)-4,5,6,7-tetrahydro-1H-benzo[d]imidazol-2-yl)methyl)spiro[azetidine-3,3′-indoline]-1-carboxylate;
• 82) Isopropyl 6′-fluoro-2′-oxo-1′-((1-(4,4,4-trifluorobutyl)-4,5,6,7-tetrahydro-1H-benzo[d]imidazol-2-yl)methyl)spiro[azetidine-3,3′-indoline]-1-carboxylate;
• 83) Ethyl 6′-fluoro-2′-oxo-1′-((1-(4,4,4-trifluorobutyl)-4,5,6,7-tetrahydro-1H-benzo[d]imidazol-2-yl)methyl)spiro[azetidine-3,3′-indoline]-1-carboxylate;
• 84) 1-(Cyclopropanecarbonyl)-6′-fluoro-1′-((1-(4,4,4-trifluorobutyl)-4,5,6,7-tetrahydro-1H-benzo[d]imidazol-2-yl)methyl)spiro[azetidine-3,3′-indoline]-2′-one;
• 85) Isopropyl 4′-chloro-1′-((1-(4-hydroxybutyl)-4,5,6,7-tetrahydro-1H-benzo[d]imidazol-2-yl)methyl)-2′-oxospiro[azetidine-3,3′-indoline]-1-carboxylate;
• 86) Isopropyl 4′-chloro-2′-oxo-1′-((1-(4,4,4-trifluorobutyl)-4,5,6,7-tetrahydro-1H-benzo[d]imidazol-2-yl)methyl)spiro[azetidine-3,3′-indoline]-1-carboxylate;
• 87) Ethyl 2′-oxo-1′-((1-(4,4,4-trifluorobutyl)-4,5,6,7-tetrahydro-1H-benzo[d]imidazol-2-yl)methyl)-1′,2′-dihydrospiro[azetidine-3,3′-pyrrolo[2,3-c]pyridine]-1-carboxylate;
• 88) Isopropyl 2′-oxo-1′-((1-(4,4,4-trifluorobutyl)-4,5,6,7-tetrahydro-1H-benzo[d]imidazol-2-yl)methyl)-1′,2′-dihydrospiro[azetidine-3,3′-pyrrolo[2,3-c]pyridine]-1-carboxylate;
• 89) 1-(Cyclopropanecarbonyl)-1′-((1-(4,4,4-trifluorobutyl)-4,5,6,7-tetrahydro-1H-benzo[d]imidazol-2-yl)methyl)spiro[azetidine-3,3′-pyrrolo[2,3-c]pyridin]-2′(1′H)-one;
• 90) 2′-Oxo-1′-((1-(4,4,4-trifluorobutyl)-4,5,6,7-tetrahydro-1H-benzo[d]imidazol-2-yl)methyl)spiro[azetidine-3,3′-indoline]-1-carbaldehyde;
• 91) 1-(1-Methylcyclopropanecarbonyl)-1′-((1-(4,4,4-trifluorobutyl)-4,5,6,7-tetrahydro-1H-benzo[d]imidazol-2-yl)methyl)spiro[azetidine-3,3′-pyrrole[2,3-c]pyridine]-2′-one;
• 92) 1-Acetyl-1′-((1-(4,4,4-trifluorobutyl)-4,5,6,7-tetrahydro-1H-benzo[d]imidazol-2-yl)methyl)spiro[azetidine-3,3′-indoline]-2′-one;
• 93) 1-(Cyclopropanecarbonyl)-1′-((1-(4,4,4-trifluorobutyl)-4,5,6,7-tetrahydro-1H-benzo[d]imidazol-2-yl)methyl)spiro[azetidine-3,3′-indoline]-2′-one;
• 94) 1-Propionyl-1′-((1-(4,4,4-trifluorobutyl)-4,5,6,7-tetrahydro-1H-benzo[d]imidazol-2-yl)methyl)spiro[azetidine-3,3′-indoline]-2′-one;
• 95) 1-Isobutyryl-1′-((1-(4,4,4-trifluorobutyl)-4,5,6,7-tetrahydro-1H-benzo[d]imidazol-2-yl)methyl)spiro[azetidine-3,3′-indoline]-2′-one;
• 96) 1-(2,2-Difluoroacetyl)-1′-((1-(4,4,4-trifluorobutyl)-4,5,6,7-tetrahydro-1H-benzo[d]imidazol-2-yl)methyl)spiro[azetidine-3,3′-indoline]-2′-one;
• 97) 1-(Methylsulfonyl)-1′-((1-(4,4,4-trifluorobutyl)-4,5,6,7-tetrahydro-1H-benzo[d]imidazol-2-yl)methyl)spiro[azetidine-3,3′-indoline]-2′-one;
• 98) 1-(Cyclopropylsulfonyl)-1′-((1-(4,4,4-trifluorobutyl)-4,5,6,7-tetrahydro-1H-benzo[d]imidazol-2-yl)methyl)spiro[azetidine-3,3′-indoline]-2′-one;
• 99) 1-(Isopropylsulfonyl)-1′-((1-(4,4,4-trifluorobutyl)-4,5,6,7-tetrahydro-1H-benzo[d]imidazol-2-yl)methyl)spiro[azetidine-3,3′-indoline]-2′-one;
• 102) Isopropyl 2′-oxo-1′-((1-(4,4,4-trifluorobutyl)-1,4,5,6-tetrahydrocyclopenta[d]imidazol-2-yl)methyl)spiro[azetidine-3,3′-indoline]-1-carboxylate;
• 103) Isopropyl 1′-((1-(4-hydroxybutyl)-1,4,5,6-tetrahydrocyclopenta[d]imidazol-2-yl)methyl)-2′-oxospiro[azetidine-3,3′-indoline]-1-carboxylate;
• 104) Ethyl 2′-oxo-1′-((1-(4,4,4-trifluorobutyl)-1,4,5,6-tetrahydrocyclopenta[d]imidazol-2-yl)methyl)spiro[azetidine-3,3′-indoline]-1-carboxylate;
• 105) 1-Isobutyryl-1′-((1-(4,4,4-trifluorobutyl)-1,4,5,6-tetrahydrocyclopenta[d]imidazol-2-yl)methyl)spiro[azetidine-3,3′-indoline]-2′-one;
• 106) 1-(Methylsulfonyl)-1′-((1-(4,4,4-trifluorobutyl)-1,4,5,6-tetrahydrocyclopenta[d]imidazol-2-yl)methyl)spiro[azetidine-3,3′-indoline]-2′-one;
• 107) Isopropyl 1′-((1-(but-3-en-1-yl)-4,5,6,7-tetrahydro-1H-benzo[d]imidazol-2-yl)methyl)-6′-chloro-2′-oxospiro[azetidine-3,3′-indoline]-1-carboxylate;
• 108) Isopropyl 2′-oxo-1′-((7-oxo-1-(4,4,4-trifluorobutyl)-4,5,6,7-tetrahydro-1H-benzo[d]imidazol-2-yl)methyl)spiro[azetidine-3,3′-indoline]-1-carboxylate;
• 109) Isopropyl 1′-((7-hydroxy-1-(4,4,4-trifluorobutyl)-4,5,6,7-tetrahydro-1H-benzo[d]imidazol-2-yl)methyl)-2′-oxospiro[azetidine-3,3′-indoline]-1-carboxylate;
• and
• 110) Ethyl 1′-((4-methyl-1-(4,4,4-trifluorobutyl)-4,5,6,7-tetrahydro-1H-benzo[d]imidazol-2-yl)methyl)-2′-oxospiro[azetidine-3,3′-indoline]-1-carboxylate.