Claims
- 1. A compound of formula I, or a pharmaceutically acceptable salt thereof wherein,X is Cl, Br, F, CN or NO2; G is (a) C1-4alkyl which is fully saturated or partially unsaturated and is substituted by hydroxy, or (b) C1-4alkyl substituted by NR1R2 or 4-tetrahydropyran; R1 is C2-7alkyl substituted by hydroxy, C1-4alkoxy, aryl, or heteroaryl; R2 is hydrogen or C1-7alkyl; or R1 and R2 together with the nitrogen to which they are attached form (a) a morpholine which may be optionally substituted by aryl or C1-7alkyl, or (b) a pyrrolidine ring substituted by hydroxy; W is a heterocycle of formula W1A is CR4 or nitrogen; B is CR5 or nitrogen; D is (a) —(CR13R14)a—, where a is 2 or 3 (b) —(CR15R16)4—, (c) —Y—CR13R14—CR13R14—, (d) —CR13R14—Y—CR13R14—, (e) —Y—CR13R14—Y—, (f)—CR13R14—CR13R14—Y—, (g) —Y—(CR15R16)n—, (h) —Y—CR15═CR15—, (i) —Y—CR15═N—, (j) —CR15═CR15—Y—, (k) —N═CR15—Y—, (l) —(CR15R16)b—N═CR15—, where b is 0 or 1 (m) —CR15═N—(CR15R16)b—, where b is 0 or 1 (n) —N═N—, (o) —N═CR15—(CR15R16)b—, where b is 0 or 1 (p) —CR15═CR15—, (q) —N═N—Y—, (r) —Y—N═N—, (s) —Y—N═CR15—, or (t) —CR15R16—Y—CR15R16—CR15R16—; Y is oxygen, S(O)m, or NR7; with the provisos that:when G is C1-4 alkyl which is fully saturated and is substituted by hydroxy or morpholinyl, in which morpholinyl is attached through nitrogen; A is CR4; B is CR5; and R8 is hydrogen then at least one of R13, R14, or R7 is not hydrogen or C1-7alkyl; when A is CR4, B is CR5, D is —Y—CR13R14—CR13R14—, and R8 is hydrogen or C1-7 alkyl then Y is not oxygen; when A is CR4, and B is CR5 then D is not —CR15l═CR15—; R4 is H, halogen, or C1-4alkyl optionally substituted by one to three halogens; R5 is (a) H, (b) halo, (c) OR12, (d) SR12, (e) C1-7alkyl which may be partially unsaturated and optionally substituted by one or more substituents selected from OR12, SR12, NR10R11, or halo, (f) C3-8cycloalkyl which may be partially unsaturated and is optionally substituted by one or more substituents selected from halogen, OR12, SR12, or NR10R11, (g) (C═O)R9, (h) S(O)mR9, (i) (C═O)OR2, (j) NHSO2R9, (k) nitro, or (l) cyano; R7 is (a) H, (b) C1-7alkyl which may be partially unsaturated and optionally substituted by one or more substituents selected from OR12, SR12,NR10R11, or halo, (c) C3-8cycloalkyl which may be partially unsaturated and is optionally substituted by one or more substituents selected from halogen, OR12, SR12, or NR10R11, (d) aryl, (e) het, (f) (C═O)R9, or (g) S(O)mR9; R8 is (a) H, (b) C1-7 alkyl which may be partially unsaturated and optionally substituted by one or more substituents selected from OR12, SR12, NR10R11, or halo, (c) OR12, or (d) SR12; R9 is (a) C1-7alkyl optionally substituted by OR12 or NR2R2, (b) C3-8cycloalkyl optionally substituted by OR12 or NR2R2, (c) NR10R11, (d) aryl, or (e) het, wherein said het is bound through a carbon atom; R10 and R11 are independently (a) H, (b) aryl, (c) C1-7alkyl which may be partially unsaturated and is optionally substituted by one or more substituents selected from CONR2R2, CO2R2, het, aryl, cyano, or halo, (d) C2-7alkyl which may be partially unsaturated and is substituted by one or more substituents selected from NR2R2, OR2, or SR2, (e) C3-8cycloalkyl which may be partially unsaturated and is optionally substituted by one or more substituents selected from halogen, OR2, SR2, or NR2R2, or (f) R10 and R11 together with the nitrogen to which they are attached form a het; R12 is (a) H, (b) aryl, (c) het (d) C1-7alkyl optionally substituted by aryl, or halogen, (e) C2-7alkyl substituted by OR2, SR2, or NR2R2, or (f) C3-8cycloalkyl which may be partially unsaturated and is optionally substituted by one or more substituents selected from halogen, OR2, SR2, or NR2R2; R13, R14, R15, and R16 are independently (a) H (b) C1-7alkyl which may be partially unsaturated and optionally substituted by one or more OR12, SR12, NR10R11, or halo groups, (c) C3-8cycloalkyl which may be partially unsaturated and is optionally substituted by one or more substituents selected from halogen, OR12, SR12, or NR10R11, (d) aryl, (e) het, wherein said het is bound through a carbon atom, (f) OR12, (g) SR12, (h) NR10R11; (i) (C═O)OR2, or (j) R13 and R14 or R15 and R16 together with the carbon to which they are attached form (C═O); each m is independently 0, 1 or 2; each n is independently 1 or 3; aryl is a phenyl radical or an ortho-fused bicyclic carbocyclic radical wherein at least one ring is aromatic, and aryl may be optionally substituted with one or more substituents selected from halo, OH, cyano, NR2R2, CO2R2, CF3, C1-6alkoxy, and C1-6 alkyl which maybe further substituted by one to three SR2, NR2R2, OR2, or CO2R2 groups; het is a four- (4), five- (5), six- (6), or seven- (7) membered saturated or unsaturated heterocyclic ring having 1, 2, or 3 heteroatoms selected from oxygen, sulfur, or nitrogen, which is optionally fused to a benzene ring, or any bicyclic heterocycle group, and het may be optionally substituted with one or more substituents selected from halo, OH, cyano, phenyl, CO2R2, CF3, C1-6alkoxy, oxo, oxime, and C1-6 alkyl which may be further substituted by one to three SR2, NR2R2, OR2, or CO2R2 groups; halo or halogen is F, Cl, Br, I; 1 represents the point of attachment between W and G; 2 represents the point of attachment between W and the carbonyl group of Formula (I).
- 2. A compound of claim 1 wherein W1 is of the formula W1.1
- 3. A compound of claim 1 wherein W1 is of the formula W1.3
- 4. A compound of claim 1 wherein W1 is of the formula W1.5
- 5. A compound of claim 1 wherein W1 is of the formula W1.6
- 6. A compound of claim 1 wherein W1 is of the formula W1.7
- 7. A compound of claim 1 wherein W1 is of the formula W1.8
- 8. A compound of claim 1 wherein W1 is of the formula W1.9
- 9. A compound of claim 1 wherein W1 is of the formula W1.10
- 10. A compound of claim 1 wherein W1 is of the formula W1.11
- 11. A compound of claim 1 wherein W1 is of the formula W1.14
- 12. A compound of claim 1 wherein W1 is of the formula W1.15
- 13. A compound of claim 1 wherein W1 is of the formula W1.17
- 14. A compound of claim 1 wherein W1 is of the formula W1.18
- 15. A compound of claim 1 wherein W1 is of the formula W1.19
- 16. A compound of claim 1 wherein W1 is of the formula W1.20
- 17. A compound of claim 1 wherein W is of the formula W1.23
- 18. A compound of claim 1 wherein W is of the formula W1.24
- 19. A compound of claim 1 wherein W is of the formula W1.25
- 20. A compound of claim 1 wherein W is of the formula W1.26
- 21. A compound of claim 1 wherein W is of the formula W1.52
- 22. A compound according to claim 1 wherein X is Cl.
- 23. A compound according to claim 1 wherein G is 4-morpholinylmethyl.
- 24. A compound according to claim 1 wherein G is 3-hydroxypropyl.
- 25. A compound according to claim 1 wherein G is 3-hydroxy-1-propynyl.
- 26. A compound according to claim 1 wherein G is tetrahydro-2H-pyran-4-ymethyl.
- 27. A compound of claim 1 wherein R8 hydrogen.
- 28. A compound of claim 27 where A is CR4 and B is CR5.
- 29. A compound 28 where R4 is hydrogen and R5 is hydrogen.
- 30. A compound of formula I according to claim 1 wherein W is selected from W1.2, W1.4, W1.12, W1.13, W1.16, W1.21, W1.22, W1.27, W1.30, W1.31, W1.32, W1.33, W1.34, W1.35, W1.36, W1.37, W1.38, W1.39, W1.40, W1.41, W1.42, W1.43, W1.44, W1.45, W1.46, W1.47, W1.48, W1.49, W1.50, W1.51, W1.52, W1.53, W1.54, W1.55, W1.56, W1.57, W1.58, W1.59, W1.60, W1.61, W1.62, W1.63, W1.64, or W1.65
- 31. A compound according to claim 1 which isN-(4-chlorobenzyl)-8-(4-morpholinylmethyl)-6-oxo-6H-imidazo[4,5,1-ij]quinoline-5-carboxamide, N-(4-chlorobenzyl)-8-(3-hydroxy-1-propynyl)-6-oxo-6H-imidazo[4,5,1-ij]quinoline-5-carboxamide; N-(4-chlorobenzyl)-8-(3-hydroxypropyl)-6-oxo-6H-imidazol[4,5,1-ij]quinoline-5-carboxamide; 1-amino-N-(4-chlorobenzyl)-8-(3-hydroxy-1-propynyl)-6-oxo-1,2-dihydro-6H-pyrrolo[3,2,1-ij]quinoline-5-carboxamide; 1-amino-N-(4-chlorobenzyl)-8-(3-hydroxypropyl)-6-oxo-1,2-dihydro-6H-pyrrolo[3,2,1-ij]quinoline-5-carboxamide; 1-amino-N-(4-chlorobenzyl)-8-(4-morpholinylmethyl)-6-oxo-1,2-dihydro-6H-pyrrolo[3,2,1-ij]quinoline-5-carboxamide; N-(4-chlorobenzyl)-2-(hydroxymethyl)-8-(3-hydroxy-1-propynyl)-6-oxo-1,2-dihydro-6H-pyrrolo[3,2,1-ij]quinoline-5-carboxamide; N-(4-chlorobenzyl)-8-(3-hydroxyprop-1-ynyl)-2,2-dimethyl-6-oxo-1,2-dihydro-6H-pyrrolo[3,2,1-ij]quinoline-5-carboxamide; 3-benzyl-N-(4-chlorobenzyl)-9-(3-hydroxy-1-propynyl)-7-oxo-2,3-dihydro-7H-[1,3,4]oxadiazino[6,5,4-ij]quinoline-6-carboxamide; 3-benzyl-N-(4-chlorobenzyl)-9-(3-hydroxypropyl)-7-oxo-2,3-dihydro-7H-[1,3,4]-oxadiazino[6,5,4-ij]quinoline-6-carboxamide; 3-benzyl-N-(4-chlorobenzyl)-9-(4-morpholinylmethyl)-7-oxo-2,3-dihydro-7H-[1,3,4]oxadiazino[6,5,4-ij]quinoline-6-carboxamide; 3-benzyl-N-(4-chlorobenzyl)-9-(tetrahydro-2H-pyran-4-ylmethyl)-7-oxo-2,3-dihydro-7H-[1,3,4]oxadiazino[6,5,4-ij]quinoline-6-carboxamide; N-(4-chlorobenzyl)-9-(3-hydroxyprop-1-ynyl)-3-methyl-7-oxo-2,3-dihydro-7H-[1,3,4]oxadiazino[6,5,4-ij]quinoline-6-carboxamide; 3-benzyl-N-(4-chlorobenzyl)-9-(3-hydroxy-1-propynyl)-7-oxo-2,3-dihydro-7H-[1,3,4]thiadiazino[6,5,4-ij]quinoline-6-carboxamide; 3-benzyl-N-(4-chlorobenzyl)-9-(3-hydroxypropyl)-7-oxo-2,3-dihydro-7H-[1,3,4]-thiadiazino[6,5,4-ij]quinoline-6-carboxamide; 3-benzyl-N-(4-chlorobenzyl)-9-(4-morpholinylmethyl)-7-oxo-2,3-dihydro-7H-[1,3,4]thiadiazino[6,5,4-ij]quinoline-6-carboxamide; 3-benzyl-N-(4-chlorobenzyl)-9-(tetrahydro-2H-pyran-4-ylmethyl)-7-oxo-2,3-dihydro-7H-[1,3,4]thiadiazino[6,5,4-ij]quinoline-6-carboxamide; N-(4-chlorobenzyl)-3-methyl-9-(morpholin-4-ylmethyl)-7-oxo-7H-[1,4]thiazino[2,3,4-ij]quinoline-6-carboxamide; N-(4-chlorobenzyl)-3-methyl-7-oxo-9-(tetrahydro-2H-pyran-4-ylmethyl)-7H-[1,4]thiazino[2,3,4-ij]quinoline-6-carboxamide; N-(4-chlorobenzyl)-9-(3-hydroxypropyl)-3-methyl-7-oxo-7H-[1,4]thiazino[2,3,4-ij]quinoline-6-carboxamide; N-(4-chlorobenzyl)-9-(3-hydroxyprop-1-ynyl)-3-methyl-7-oxo-7H-[1,4]thiazino[2,3,4-ij]quinoline-6-carboxamide; N-(4-chlorobenzyl)-9-(morpholin-4-ylmethyl)-7-oxo-2-pyridin-3-yl-7H-[1,4]thiazino[2,3,4-ij]quinoline-6-carboxamide; N-(4-chlorobenzyl)-9-(3-hydroxy-1-propynyl)-7-oxo-3-phenyl-1H,7H-[1,3]oxazino[5,4,3-ij]quinoline-6-carboxamide; N-(4-chlorobenzyl)-9-(3-hydroxypropyl)-7-oxo-3-phenyl-1H,7H-[1,3]oxazino[5,4,3-ij]quinoline-6-carboxamide; N-(4-chlorobenzyl)-7-oxo-3-phenyl-9-(tetrahydro-2H-pyran-4-ylmethyl)-1H,7H-[1,3]oxazino [5,4,3-ij]quinoline-6-carboxamide; N-(4-chlorobenzyl)-9-(4-morpholinylmethyl)-7-oxo-3-phenyl-1H,7H-[1,3]oxazino[5,4,3-ij]quinoline-6-carboxamide; N-(4-chlorobenzyl)-9-(3-hydroxy-1-propynyl)-1-methyl-7-oxo-3-phenyl-2,3-dihydro-1H,7H-pyrido[1,2,3-de]quinoxaline-6-carboxamide; N-(4-chlorobenzyl)-9-(3-hydroxypropyl)-1-methyl-7-oxo-3-phenyl-2,3-dihydro-1H,7H-pyrido[1,2,3-de]quinoxaline-6-carboxamide; N-(4-chlorobenzyl)-9-(tetrahydro-2H-pyran-4-ylmethyl)-1-methyl-7-oxo-3-phenyl-2,3-dihydro-1H,7H-pyrido[1,2,3-de]quinoxaline-6-carboxamide; N-(4-chlorobenzyl)-9-(4-morpholinylmethyl)-1-methyl-7-oxo-3-phenyl-2,3-dihydro-1H,7H-pyrido[1,2,3-de]quinoxaline-6-carboxamide; N-(4-chlorobenzyl)-9-(3-hydroxy-1-propynyl)-2,3,7-trioxo-2,3-dihydro-1H,7H-pyrido[1,2,3-de]quinoxaline-6-carboxamide; N-(4-chlorobenzyl)-9-(3-hydroxypropyl)-2,3,7-trioxo-2,3-dihydro-1H,7H-pyrido[1,2,3-de]quinoxaline-6-carboxamide; N-(4-chlorobenzyl)-9-(4-morpholinylmethyl)-2,3,7-trioxo-2,3-dihydro-1H,7H-pyrido[1,2,3-de]quinoxaline-6-carboxamide; N-(4-chlorobenzyl)-9-(3-hydroxy-1-propynyl)-2,7-dioxo-2,3-dihydro-1H,7H-pyrido[1,2,3-de]quinoxahne-6-carboxamide; N-(4-chlorobenzyl)-9-(3-hydroxypropyl)-2,7-dioxo-2,3-dihydro-1H,7H-pyrido[1,2,3-de]quinoxaline-6-carboxamide; N-(4-chlorobenzyl)-9-(3-hydroxy-1-propynyl)-3,7-dioxo-2,3-dihydro-1H,7H-pyrido[1,2,3-de]quinoxaline-6-carboxamide; N-(4-chlorobenzyl)-9-(3-hydroxypropyl)-3,7-dioxo-2,3-dihydro-1H,7H-pyrido[1,2,3-de]quinoxaline-6-carboxamide; N-(4-chlorobenzyl)-9-(4-morpholinylmethyl)-3,7-dioxo-2,3-dihydro-1H,7H-pyrido[1,2,3-de]quinoxaline-6-carboxamide; N-(4-chlorobenzyl)-9-(4-morpholinylmethyl)-2,7-dioxo-2,3-dihydro-1H,7H-pyrido[1,2,3-de]quinoxaline-6-carboxamide; N-(4-chlorobenzyl)-9-(3-hydroxy-1-propynyl)-1-methyl-2,7-dioxo-2,3-dihydro-1H,7H-pyrido[1,2,3-de]quinoxaline-6-carboxamide; 3-benzyl-N-(4-chlorobenzyl)-9-(3-hydroxy-1-propynyl)-1-methyl-7-oxo-2,3-dihydro-1H,7H-[1,2,4]triazino[5,6,1-ij]quinoline-6-carboxamide; 3-benzyl-N-(4-chlorobenzyl)-9-(3-hydroxypropyl)-1-methyl-7-oxo-2,3-dihydro-1H,7H-[1,2,4]triazino[5,6,1-ij]quinoline-6-carboxamide; 3-benzyl-N-(4-chlorobenzyl)-9-(4-morpholinylmethyl)-1-methyl-7-oxo-2,3-dihydro-1H,7H-[1,2,4]triazino[5,6,1-ij]quinoline-6-carboxamide; 3-benzyl-N-(4-chlorobenzyl)-9-(tetrahydro-2H-pyran-4-ylmethyl)-1-methyl-7-oxo-2,3-dihydro-1H,7H-[1,2,4]triazino[5,6,1-ij]quinoline-6-carboxamide; 1-benzyl-N-(4-chlorobenzyl)-5-(3-hydroxy-1-propynyl)-2,7-dioxo-2,3-dihydro-1H,7H-pyrido[3,2,1-ij]cinnoline-8-carboxamide; 1-benzyl-N-(4-chlorobenzyl)-5-(3-hydroxypropyl)-2,7-dioxo-2,3-dihydro-1H,7H-pyrido[3,2,1-ij]cinnoline-8-carboxamide; 1-benzyl-N-(4-chlorobenzyl)-5-(4-morpholinylmethyl)-2,7-dioxo-2,3-dihydro-1H,7H-pyrido[3,2,1-ij]cinnoline-8-carboxamide; 1-benzyl-N-(4-chlorobenzyl)-5-(tetrahydro-2H-pyran-4-ylmethyl)-2,7-dioxo-2,3-dihydro-1H,7H-pyrido[3,2,1-ij]cinnoline-8-carboxamide; N-(4-Chlorobenzyl)-5-(3-hydroxyprop-1-ynyl)-1-methyl-7-oxo-2,3-dihydro-1H,7H-pyrido[3,2,1-ij]cinnoline-8-carboxamide; N-(4-chlorobenzyl)-9-(3-hydroxy-1-propynyl)-7-oxo-3-phenyl-1H,7H-[1,3]thiazino[5,4,3-ij]quinoline-6-carboxamide; N-(4-chlorobenzyl)-9-(3-hydroxypropyl)-7-oxo-3-phenyl-1H,7H-[1,3]thiazino[5,4,3-ij]quinoline-6-carboxamide; N-(4-chlorobenzyl)-9-(tetrahydro-2H-pyran-4-ylmethyl)-7-oxo-3-phenyl-1H,7H-[1,3]thiazino[5,4,3-ij]quinoline-6-carboxamide; N-(4-chlorobenzyl)-9-(4-morpholinylmethyl)-7-oxo-3-phenyl-1H,7H-[1,3]thiazino[5,4,3-ij]quinoline-6-carboxamide; N-(4-chlorobenzyl)-9-(3-hydroxypropyl)-2-methyl-7-oxo-3-phenyl-2,3-dihydro-1H,7H-pyrido[3,2,1-ij]quinazoline-6-carboxamide; N-(4-chlorobenzyl)-9-(3-hydroxy-1-propynyl)-2-methyl-7-oxo-3-phenyl-2,3-dihydro-1H,7H-pyrido[3,2,1-ij]quinazoline-6-carboxamide; N-(4-chlorobenzyl)-9-(4-morpholinylmethyl)-2-methyl-7-oxo-3-phenyl-2,3-dihydro-1H,7H-pyrido[3,2,1-ij]quinazoline-6-carboxamide; N-(4-chlorobenzyl)-9-(tetrahydro-2H-pyran-4-ylmethyl)-2-methyl-7-oxo-3-phenyl-2,3-dihydro-1H,7H-pyrido[3,2,1-ij]quinazoline-6-carboxamide; 2-benzyl-N-(4-chlorobenzyl)-9-(4-morpholinylmethyl)-7-oxo-2,3-dihydro-1H,7H-pyrido[3,2,1-ij]quinazoline-6-carboxamide; 2-benzyl-N-(4-chlorobenzyl)-9-(4-morpholinylmethyl)-3,7-dioxo-2,3-dihydro-1H,7H-pyrido[3,2,1-ij]quinazoline-6-carboxamide; N-(4-chlorobenzyl)-9-(3-hydroxy-1-propynyl)-2-(4-morpholinyl)-7-oxo-7H-[1,3,4]-thiadiazino[6,5,4-ij]quinoline-6-carboxamide, N-(4-chlorobenzyl)-9-(3-hydroxypropyl)-2-(4-morpholinyl)-7-oxo-7H-[1,3,4]thiadiazino[6,5,4-ij]quinoline-6-carboxamide; N-(4-chlorobenzyl)-2-(4-morpholinyl)-9-(4-morpholinylmethyl)-7-oxo-7H-[1,3,4]-thiadiazino[6,5,4-ij]quinoline-6-carboxamide; N-(4-chlorobenzyl)-2-(4-morpholinyl)-7-oxo-9-(tetrahydro-2H-pyran-4-ylmethyl)-7H-[1,3,4]thiadiazino[6,5,4-ij]quinoline-6-carboxamide; N-(4-chlorobenzyl)-9-(3-hydroxypropyl)-7-oxo-2,3-dihydro-1H,7H-pyrazino[3,2,1-ij][1,7]naphthyridine-6-carbaxmide; N-(4-chlorobenzyl)-9-(4-morpholinylmethyl)-7-oxo-2,3-dihydro-1H,7H-pyrazino[3,2,1-ij][1,7]naphthyridine-6-carboxamide; N-(4-chlorobenzyl)-9-(3-hydroxy-1-propynyl)-7-oxo-2,3-dihydro-1H,7H-pyrazino[3,2,1-ij][1,7]naphthyridine-6-carboxamide; N-(4-chlorobenzyl)-9-(3-hydroxypropyl)-7-oxo-2,3-dihydro-7H-[1,4]thiazino[2,3,4-ij][1,7]naphthyridine-6-carboxamide; N-(4-chlorobenzyl)-9-(4-morpholinylmethyl)-7-oxo-2,3-dihydro-7H-[1,4]thiazino[2,3,4-ij][1,7]naphthyridine-6-carboxamide; N-(4-chlorobenzyl)-9-(3-hydroxy-1-propynyl)-7-oxo-2,3-dihydro-7H-[1,4]thiazino[2,3,4-ij][1,7]naphthyridine-6-carboxamide; N-(4-chlorobenzyl)-9-(3-hydroxy-1-propynyl)-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij][1,7]naphthyridine-6-carboxamide; N-(4-chlorobenzyl)-9-(4-morpholinylmethyl)-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij][1,7]naphthyridine-6-carboxamide; N-(4-chlorobenzyl)-9-(3-hydroxypropyl)-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij][1,7]naphthyridine-6-carboxamide; N-(4-chlorobenzyl)-9-(3-hydroxypropyl)-3,7-dioxo-3H,7H-pyrido[1,2,3-de]quinoxaline-6-carboxamide; N-(4-chlorobenzyl)-9-(3-hydroxy-1-propynyl)-3,7-dioxo-3H,7H-pyrido[1,2,3-de]quinoxaline-6-carboxamide; N-(4-chlorobenzyl)-9-(4-morpholinylmethyl)-3,7-dioxo-3H,7H-pyrido[1,2,3-de]quinoxaline-6-carboxamide; N-(4-chlorobenzyl)-2-[(4-chlorobenzyl)amino]-9-(4-morpholinylmethyl)-7-oxo-3H,7H-pyrido[1,2,3-de]quinoxaline-6-carboxamide; 2-(benzylamino)-N-(4-chlorobenzyl)-9-(4-morpholinylmethyl)-7-oxo-3H,7H-pyrido[1,2,3-de]quinoxaline-6-carboxamide; N-(4-chlorobenzyl)-10-(3-hydroxypropyl)-2,4,8-trioxo-1,2,3,4-tetrahydro-8H-[1,4]-diazepino [3,2,1-ij]quinoline-7-carboxamide; N-(4-chlorobenzyl)-10-(3-hydroxy-1-propynyl)-2,4,8-trioxo-1,2,3,4-tetrahydro-8H-[1,4]diazepino[3,2,1-ij]quinoline-7-carboxamide; N-(4-chlorobenzyl)-10-(4-morpholinylmethyl)-2,4,8-trioxo-1,2,3,4-tetrahydro-8H-[1,4]diazepino[3,2,1-ij]quinoline-7-carboxamide; N-(4-chlorobenzyl)-10-(4-morpholinylmethyl)-2,8-dioxo-1,2,3,4-tetrahydro-8H-[1,4]diazepino[3,2,1-ij]quinoline-7-carboxamide; N-(4-chlorobenzyl)-8-(4-morpholinylmethyl)-2,6-dioxo-1,2-dihydro-6H-imidazo[4,5,1-ij]quinoline-5-carboxamide; N-(4-chlorobenzyl)-8-(3-hydroxy-1-propynyl)-2,6-dioxo-1,2-dihydro-6H-imidazo[4,5,1-ij]quinoline-5-carboxamide; N-(4-chlorobenzyl)-8-(3-hydroxypropyl)-2,6-dioxo-1,2-dihydro-6H-imidazo[4,5,1-ij]quinoline-5-carboxamide; N-(4-chlorobenzyl)-8-(4-morpholinylmethyl)-2,6-dioxo-1-[2-(1-piperidinyl)ethyl]-1,2-dihydro-6H-imidazo[4,5,1-ij]quinoline-5-carboxamide; N-(4-chlorobenzyl)-1-[2-(4-methyl-1-piperazinyl)ethyl]-8-(4-morpholinylmethyl)-2,6-dioxo-1,2-dihydro-6H-imidazo[4,5,1-ij]quinoline-5-carboxamide; N-(4-chlorobenzyl)-10-(4-morpholinylmethyl)-8-oxo-3,4-dihydro-2H,8H-[1,4]oxazepino[2,3,4-ij]quinoline-7-carboxamide; N-(4-chlorobenzyl)-3-methyl-9-(morpholin-4-ylmethyl)-7-oxo-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxamide; N-(4-chlorobenzyl)-3-methyl-7-oxo-9-(tetrahydro-2H-pyran-4-ylmethyl)-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxamide; N-(4-chlorobenzyl)-9-(3-hydroxypropyl)-3-methyl-7-oxo-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxamide; N-(4-chlorobenzyl)-9-(3-hydroxyprop-1-ynyl)-3-methyl-7-oxo-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxamide; N-(4-chlorobenzyl)-9-(morpholin-4-ylmethyl)-7-oxo-2-pyridin-3-yl-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxamide; 2-benzyl-N-(4-chlorobenzyl)-10-(4-morpholinylmethyl)-3,8-dioxo-1,2,3,4-tetrahydro-8H-[1,4]diazepino[6,7,1-ij]quinoline-7-carboxamide; or a pharmaceutically acceptable salt thereof.
- 32. A compound according to claim 1 which isN-(4-chlorobenzyl)-10-(4-morpholinylmethyl)-8-oxo3,4-dihydro-2H,8H-[1,4]oxazepino [2,3,4-ij]quinoline-7-carboxamide; N-(4-chlorobenzyl)-8-(4-morpholinylmethyl)-2,6-dioxo-1,2-dihydro-6H-imidazo[4,5,1-ij]quinoline-5-carboxamide; N-(4-chlorobenzyl)-9-(4-morpholinylmethyl)-2,7-dioxo-2,3-dihydro-1H,7H-pyrido[1,2,3-de]quinoxaline-6-carboxamide; N-(4-chlorobenzyl)-2-[(4-chlorobenzyl)amino]-9-(4-morpholinylmethyl)-7-oxo-3H,7H-pyrido[1,2,3-de]quinoxaline-6-carboxamide; N-(4-chlorobenzyl)-2-(hydroxymethyl)-8-(3-hydroxy-1-propynyl)-6-oxo-1,2-dihydro-6H-pyrrolo[3,2,1-ij]quinoline-5-carboxamide; N-(4-chlorobenzyl)-8-(3-hydroxyprop-1-ynyl)-2,2-dimethyl-6-oxo-1,2-dihydro-6H-pyrrolo[3,2,1-ij]quinoline-5-carboxamide; N-(4-chlorobenzyl)-10-(4-morpholinylmethyl)-2,8-dioxo-1,2,3,4-tetrahydro-8H-[1,4]diazepino[3,2,1-ij]quinoline-7-carboxamide; 2-(benzylamino)-N-(4-chlorobenzyl)-9-(4-morpholinylmethyl)-7-oxo-3H,7H-pyrido[1,2,3-de]quinoxaline-6-carboxamide; N-(4-chlorobenzyl)-9-(3-hydroxy-1-propynyl)-1-methyl-2,7-dioxo-2,3-dihydro-1H,7H-pyrido[1,2,3-de]quinoxaline-6-carboxamide; 2-benzyl-N-(4-chlorobenzyl)-9-(4-morpholinylmethyl)-7-oxo-2,3-dihydro-1H,7H-pyrido[3,2,1-ij]quinazoline-6-carboxamide; 2-benzyl-N-(4-chlorobenzyl)-9-(4-morpholinylmethyl)-3,7-dioxo-2,3-dihydro-1H,7H-pyrido[3,2,1-ij]quinazoline-6-carboxamide; 2-benzyl-N-(4-chlorobenzyl)-10-(4-morpholinylmethyl)-3,8-dioxo-1,2,3,4-tetrahydro-8H-[1,4]diazepino[6,7,1-ij]quinoline-7-carboxamide; N-(4-chlorobenzyl)-9-(3-hydroxyprop-1-ynyl)-3-methyl-7-oxo-2,3-dihydro-7H-[1,3,4]oxadiazino[6,5,4-ij]quinoline-6-carboxamide; N-(4-chlorobenzyl)-5-(3-hydroxyprop-1-ynyl)-1-methyl-7-oxo-2,3-dihydro-1H,7H-pyrido[3,2,1-ij]cinnoline-8-carboxamide; or a pharmaceutically acceptable salt thereof.
- 33. A compound according to claim 1 which isN-(4-chlorobenzyl)-10-(4-morpholinylmethyl)-8-oxo-3,4-dihydro-2H,8H-[1,4]oxazepino [2,3,4-ij]quinoline-7-carboxamide; N-(4-chlorobenzyl)-9-(4-morpholinylmethyl)-2,7-dioxo-2,3-dihydro-1H,7H-pyrido[1,2,3-de]quinoxaline-6-carboxamide; N-(4-chlorobenzyl)-10-(4-morpholinylmethyl)-2,8-dioxo-1,2,3,4-tetrahydro-8H-[1,4]diazepino[3,2,1-ij]quinoline-7-carboxamide; 2-(benzylamino)-N-(4-chlorobenzyl)-9-(4-morpholinylmethyl)-7-oxo-3H,7H-pyrido[1,2,3-de]quinoxaline-6-carboxamide; N-(4-chlorobenzyl)-9-(3-hydroxy-1-propynyl)-1-methyl-2,7-dioxo-2,3-dihydro-1H,7H-pyrido[1,2,3-de]quinoxaline-6-carboxamide; or a pharmaceutically acceptable salt thereof.
- 34. A compound according to claim 1 which is N-(4-chlorobenzyl)-9-(4-morpholinylmethyl)-2,7-dioxo-2,3-dihydro-1H,7H-pyrido[1,2,3-de]quinoxaline-6-carboxamide; or a pharmaceutically acceptable salt thereof.
- 35. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
- 36. A method of treating herpes virus infections comprising administering to a mammal in need of such treatment a compound of claim 1.
- 37. The method according to claim 36 wherein said mammal is a human.
- 38. The method according to claim 36 wherein said mammal is a livestock or companion animal.
- 39. The method according to claim 36 wherein the herpes virus infection is herpes simplex virus type 1 or 2, human herpes virus type, 6, 7, or 8, varicella zoster virus, human cytomegalovirus, or Epstein-Barr virus.
- 40. The method according to claim 36 wherein the infection is herpes simplex virus type 1 or 2, human herpes virus type 8, varicella zoster virus, human cytomegalovirus, or Epstein-Barr virus.
- 41. The method according to claim 36 wherein a compound of formula I is administered from about 0.1 to about 300 mg/kg of body weight.
- 42. The method according to claim 41 wherein a compound of formula I is administered from about 1 to about 30 mg/kg of body weight.
- 43. The method according to claim 36 wherein the compound is administered parenterally, topically, intravaginally, orally, or rectally.
- 44. A method for inhibiting a herpes viral DNA polymerase, comprising contacting the polymerase with an effective inhibitory amount of a compound of claim 1.
- 45. The method of claim 44 wherein the polymerase and the compound are contacted in vitro.
- 46. The method of claim 44 wherein the polymerase and the compound are contacted in vivo.
CROSS REFERENCE TO RELATED APPLICATIONS
This application claims the benefit of the following provisional applications: U.S. Ser. No: 60/217,559, filed Jul. 12, 2000, and U.S. Ser. No: 60/272,143, filed Feb. 28, 2001, under 35 USC 119(e)(i).
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Provisional Applications (2)
|
Number |
Date |
Country |
|
60/217559 |
Jul 2000 |
US |
|
60/272143 |
Feb 2001 |
US |