This invention relates to compounds which can act as inhibitors of viral polymerases, especially the hepatitis C virus (HCV) polymerase, to uses of such compounds in the treatment and prevention of infection by hepatitis C virus, and to their preparation. The hepatitis C virus (HCV) is the major causative agent of parenterally-transmitted and sporadic non-A, non-B hepatitis (NANB-H). Some 1% of the human population of the planet is believed to be affected. Infection by the virus can result in chronic hepatitis and cirrhosis of the liver, and may lead to hepatocellular carcinoma. Currently no vaccine nor established therapy exists, although partial success has been achieved in a minority of cases by treatment with recombinant interferon-α, either alone or in combination with ribavirin. There is therefore a pressing need for new and broadly-effective therapeutics. Several virally-encoded enzymes are putative targets for therapeutic intervention, including a metalloprotease (NS2-3), a serine protease (NS3), a helicase (NS3), and an RNA-dependent RNA polymerase (NS5B). Of these, the polymerase plays an essential role in replication of the virus and is therefore an important target in the fight against hepatitis C. Certain naphthalimide derivatives have been disclosed in the art but none are disclosed as being useful as inhibitors of hepatitis C virus (HCV) polymerase. Published International application WO 00/32577 (Merck Patent GmbH) discloses the compounds of formula (A):

where R, R1 and R2 are as defined therein, as glycoprotein IbIX antagonists. Published International application WO 00/01672 (Taiho Pharmaceutical Co., Ltd.) discloses the compounds of formula (B):

where X1, Y, A1, R1, R2 and e are as defined therein. These compounds are disclosed as being useful as antitumour agents. 4-alkylamino-N-alkylnaphthalic-l,8-imides are also disclosed in, for instance, Alexiou et al. J. Chem. Research (S), 2000, 208-210; Ghorbanian et al. J. Chem. Technol. BiotechnoL, 75:1127-1134 (2000); and Qian et al. Dyes and Pigments, 11(1989), 13-20. However none of these disclosures relate to the treatment of hepatitis C virus infections. It has now surprisingly been found that certain naphthalimide derivatives, including certain of the known compounds referred to above, act as inhibitors of the hepatitis C virus (HCV) polymerase enzyme. Thus, in one aspect, there is provided the use of a compound of formula (I):

or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for the treatment or prevention of infection by hepatitis C virus, wherein A and B are each independently CH2, C=O or C=S, with the proviso that A and B are not both CH2; R1 is Ci-6alkyl, C2-6alkenyl, C2-6alkynyl, (CH2)0-3C3-7cycloalkyl, (CH2)0-3Het, (CH2)0-3aryl or (CH2)0-3heteroaryl, optionally substituted by halogen, hydroxy, Ci-6alkyl, Ci-6alkoxy, C2-6alkenyl, CN, (CH2)0-3θ(CH2)o-3aryl, S(Ci-6alkyl), S(O)(Ci-6alkyl), S(O)2(Ci-6alkyl), S-heteroaryl, S(O)heteroaryl, S(O)2heteroaryl, S-aryl, S(O)aryl, S(O)2aryl, SO2NR4R5, CO2R4, CONR4R5, NR4COR5, NR4SO2R5 or NR4CONR5 where said Ci-6alkyl, (CH2)0-3Het, (CH2)0-3aryl and (CH2)0-3heteroaryl groups, either by themselves or as part of other substituents, may optionally be substituted by 1 to 8 halogen atoms, and where said (CH2)0-3Het, (CH2)0-3aryl and (CH2)0-3heteroaryl groups may optionally be further substituted with one or two groups selected from hydroxy, Ci-6alkoxy, Ci-6alkyl, (CH2)0-3CO2H, (CH2)0-3CO2Ci.6alkyl and C(O)NR24R25, and where said (CH2)0-3aryl group may be fused to C3-7cycloalkyl; R4, R5 and R21 are each independently selected from hydrogen, Ci-6alkyl, (CH2)0-3Het, (CH2)o-3aryl, (CH2)0-3heteroaryl and SO2(Ci-6alkyl), optionally substituted by 1 to 5 halogen atoms and/or 1 or 2 groups selected from hydroxy, Ci-6alkyl, NH2 and Ci-6alkoxy; R2 is halogen, hydroxy, Ci-6alkyl, C2-6alkenyl, C2-6alkynyl, Ci-6alkoxy, (CH2)0-3C3-8cycloalkyl, (CH2)o-3aryl, CN, NO2, NR6R7, OR8, C(O)C i-6alkyl, CO2H, CO2R8, CONR8R20, NR21COR8, NR21SO2R8, NR8CONR20, SR8, SOR8, SO2R8 or SO2NR8R20, where said Ci-6alkyl, C2-6alkenyl, Ci-6alkoxy and aryl groups are optionally substituted by 1 or 2 groups selected from halogen, hydroxy, Ci-6alkyl, Ci-6alkoxy, NH2, SO2NR6R7, CO2R6 and CONR6R7; R6 and R7 are each independently selected from hydrogen, Ci-6alkyl, C2-6alkenyl, C2-6alkynyl, (CH2)o-3C3-7cycloalkyl, (CH2)0-3Het, (CH2)0-3aryl, (CH2)0-3heteroaryl, (CH2)0-3OR9, (CH2)0-3SR9, (CH2)O-3NR10R11, -C(CH2OH)3, COR22, C(O)C(O)OCi-6alkyl, CO2R22, CONR22R23, SO2R22 and SO2NR22R23, where said Ci-6alkyl, C2-6alkenyl, C2-6alkynyl, cycloalkyl, Het, aryl and heteroaryl groups are optionally substituted by 1 or 2 groups selected from halogen, hydroxy, Ci-6alkyl, CF3, NH2, N(Ci-6alkyl)2, SO2aryl, SO2NR18R19, (CH2)0-3aryl, (CH2)0-3heteroaryl, C(O)C i-6alkyl, C(O)(CH2)0-3aryl, (CH2)O-3CO2R18, (CH=CH)CO2R18, CONR18R19 and O(CH2)0-3aryl, which optional aryl substituents are further optionally substituted by CO2H or Het; R18 and R19 are each independently selected from hydrogen, Ci-6alkyl, C2-6alkenyl, (CH2)0-3C3-7cycloalkyl, (CH2)0-3Het, (CH2)0-3aryl, (CH2)0-3heteroaryl, (CH2)0-3OR9, (CH2)0-3SR9, (CH2)O-3NR10R11, -C(CH2OH)3, where said Ci-6alkyl, C2-6alkenyl and Ci-6alkoxy groups are optionally substituted by halogen or hydroxy; R9, R10 and R11 are each independently selected from hydrogen, Ci-6alkyl, C2-6alkenyl, C(O)Ci-6alkyl and aryl; or R6, R7 and the nitrogen atom to which they are attached form a heteroaliphatic ring of 4 to 7 ring atoms, which ring optionally contains 1, 2 or 3 additional heteroatoms selected from O and S or a group S(O), S(O)2 or NR12, where R12 is hydrogen, Ci-6alkyl, C2-6alkenyl or aryl, and which ring is optionally substituted by halogen, hydroxy, Ci-6alkyl, C2-6alkenyl, Ci-6alkoxy, oxo, SO2NR18R19, COR18, CO2R18 or CONR18R19 , and which ring is optionally bridged by -CH2- or -CH2CH2-; R8, R20, R22 and R23 are each independently selected from hydrogen, Ci-6alkyl, (CH2)i-3OR13, (CH2)1-3NR14R15, (CH2)o-3aryl and (CH2)0-3heteroaryl; R13, R14 and R15 are each independently selected from hydrogen, Ci-6alkyl, C2-6alkenyl, aryl, C(O)R16 and C(O)OR17; R16, R17 and R24 are independently selected from hydrogen, Ci-6alkyl and aryl; R25 is hydrogen, Ci-6alkyl, (CH2)i-3CO2H, (CH2)0-3C3-8cycloalkyl, (CH2)0-3phenyl or SO2(Ci-6alkyl), where C3-8cycloalkyl and phenyl are optionally substituted by 1 to 3 groups selected from halogen, hydroxy or CO2H; n is O or 1 or 2, and when n is 2, the R2 groups may be the same or different; Ra is hydrogen, o orr R R22 a anndd R Raa a arree joined to form a 5- to 8-membered carbocyclic ring. In one embodiment of the present invention, there is provided the use of a compound of formula (Ii):

(Ii) or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for the treatment or prevention of infection by hepatitis C virus, wherein A and B are each independently CH2, C=O or C=S, with the proviso that A and B are not both CH2; R1 is Ci-6alkyl, C2-6alkenyl, C2-6alkynyl, (CH2)0-3C3-7cycloalkyl, (CH2)0-3Het, (CH2)0-3aryl or (CH2)0-3heteroaryl, optionally substituted by halogen, hydroxy, Ci-6alkyl, Ci-6alkoxy, C2-6alkenyl, CN, S(Ci-6alkyl), S(O)(Ci-6alkyl), S(O)2(Ci-6alkyl), S-heteroaryl, S(O)heteroaryl, S(O)2heteroaryl, S-aryl, S(O)aryl, S(O)2aryl, SO2NR4R5, CO2R4, CONR4R5, NR4COR5, NR4SO2R5 or NR4CONR5 where said Ci-6alkyl and (CH2)0-3aryl groups, either by themselves or as part of other substituents, may optionally be substituted by 1 to 8 halogen atoms; R4, R5 and R21 are each independently selected from hydrogen, Ci-6alkyl, (CH2)0-3Het, (CH2)0-3aryl and (CH2)0-3heteroaryl; R2 is halogen, hydroxy, Ci-6alkyl, C2-6alkenyl, Ci-6alkoxy, CN, NO2, NR6R7, OR8, CO2H, CO2R8, CONR8R20, NR21COR8, NR21SO2R8, NR8CONR20, SR8, SOR8, SO2R8 or SO2NR8R20, where said Ci-6alkyl, C2-6alkenyl and Ci-6alkoxy groups are optionally substituted by halogen, hydroxyl, SO2NR6R7, CO2R6 or CONR6R7; R6 and R7 are each independently selected from hydrogen, Ci-6alkyl, C2-6alkenyl, (CH2)O-3C3-7CyClOaIlCyI, (CH2)0-3Het, (CH2)0-3aryl, (CH2)0-3heteroaryl, (CH2)0-3OR9, (CH2)0-3SR9, (CH2)O-3NR10R11, -C(CH2OH)3, COR22, CO2R22, CONR22R23, SO2R22 and SO2NR22R23, where said Ci-6alkyl, C2-6alkenyl, cycloalkyl, Het, aryl and heteroaryl groups are optionally substituted by halogen, hydroxy, SO2NR18R19, CO2R18 or CONR18R19; R18 and R19 are each independently selected from hydrogen, Ci-6alkyl, C2-6alkenyl, (CH2)o-3C3-7cycloalkyl, (CH2)0-3Het, (CH2)0-3aryl, (CH2)0-3heteroaryl, (CH2)0-3OR9, (CH2)0-3SR9, (CH2)O-3NR10R11, -C(CH2OH)3, where said Ci-6alkyl, C2-6alkenyl and Ci-6alkoxy groups are optionally substituted by halogen or hydroxy; R9, R10 and R11 are each independently selected from hydrogen, Ci-6alkyl, C2-6alkenyl, C(O)Ci-6alkyl and aryl; or R6, R7 and the nitrogen atom to which they are attached form a heteroaliphatic ring of 4 to 7 ring atoms, which ring optionally contains 1, 2 or 3 additional heteroatoms selected from O and S or a group S(O), S(O)2 or NR12, where R12 is hydrogen, Ci-6alkyl, C2-6alkenyl or aryl, and which ring is optionally substituted by halogen, hydroxy, Ci-6alkyl, C2-6alkenyl or Ci-6alkoxy, carboxyl, SO2NR18R19, COR18, CO2R18 or CONR18R19; R8, R20, R22 and R23 are each independently selected from Ci-6alkyl, (CH2)i-3OR13, (CH2)1-3NR14R15, (CH2)o-3aryl and (CH2)0-3heteroaryl; R13, R14 and R15 are each independently selected from hydrogen, Ci-6alkyl, C2-6alkenyl, aryl, C(O)R16 and C(O)OR17; R16 and R17 are independently selected from hydrogen, Ci-6alkyl and aryl; n is O or 1. In one embodiment of the present invention, one of A or B is C=O and the other is CH2 or C=O, preferably A is C=O and B is CH2 or C=O, more preferably A and B are C=O. In another embodiment, R1 is (CH2)0-3aryl, preferably (CH2)0-3phenyl, more preferably phenyl or benzyl, most preferably phenyl, optionally substituted by halogen, hydroxy, Ci-6alkyl, Ci-6alkoxy, C2-6alkenyl, CN, S(CX-6 alkyl), S(O)(Ci-6alkyl), S(O)2(Ci-6alkyl), SO2NR4R5 where R4 and R5 are as hereinbefore defined, preferably halogen, Ci-6alkyl or Ci-6alkoxy, more preferably, fluorine, chlorine, bromine, most preferably bromine. When R1 is substituted, it is preferably mono- or di-substituted, more preferably mono- substituted. When R1 is phenyl and substituted, preferably it is substituted at the 3-position of the phenyl group, especially when it is mono-substituted. In another embodiment, R2 is NR6R7 where R6 and R7 are as hereinbefore defined. Preferably, R6 and R7 are independently selected from hydrogen, Ci-6alkyl, (CH2)0-3C3.7cycloalkyl, (CH2)0-3θR9 where R9 is as hereinbefore defined. More preferably, one of R6 and R7 is hydrogen and the other is selected from Ci-6alkyl, (CH2)o-3C3-7cycloalkyl or (CH2V3OR9, especially (CH2)2OR9. Preferably, R9 is selected from hydrogen, C^alkyl and aryl, more preferably hydrogen. In another embodiment, when n is 1, preferably the R2 group is at the 4-position of the naphthalimide moiety. In a further embodiment of the present invention, there is provided the use of a compound of formula (Ia):

or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for the treatment or prevention of infection by hepatitis C virus, wherein R1 and R2 are as defined in relation to formula (Ii). Preferably, R1 is (CH2)0-3aryl, more preferably phenyl, optionally substituted by halogen, hydroxy, Ci-6alkyl, Ci-6alkoxy, C2-6alkenyl, CN, S(Ci-6alkyl), S(O)(Ci-6alkyl), S(O)2(Ci-6alkyl), SO2NR4R5 where R4 and R5 are as defined in relation to formula (Ii), preferably halogen, Ci-6alkyl or Ci-6alkoxy, more preferably halogen, especially fluorine, chlorine and bromine. When R1 is phenyl, preferably it is mono- or di-substituted, more preferably monosubstituted, especially at the 3-position of the phenyl group. Preferably, R2 is NR6R7 where R6 and R7 are as hereinbefore defined. Preferably, one of R6 and R7 is hydrogen and the other is selected from Ci-6alkyl, (CH2)0-3C3.7cycloalkyl or (CH2)0-3θR9, especially (CH2)o-3θR9. Preferably, R9 is selected from hydrogen and Ci-4alkyl, more preferably hydrogen. In particular, NR6R7 may be NH(CH2)2OH. In a further embodiment, there is provided the use of a compound of formula (Ib):

or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for the treatment or prevention of infection by hepatitis C virus, wherein R2 is as defined in relation to formula (I), and R1 is phenyl substituted by bromine and/or CO2H, optionally further substituted by halogen, hydroxy, C2-6alkyl, Ci-6alkoxy or CH2CO2H. In a further embodiment, there is provided the use of a compound of formula (Ic):

or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for the treatment or prevention of infection by hepatitis C virus, wherein R1 is as defined in relation to formula (I), and R2 is C3-8cycloalkyl, (CH2)1-6OH, C2-8alkoxy, phenyl, NH(CH2)0-3Het substituted by C(O)(CH2)0-3aryl, C(O)(Ci-6alkyl), C(O)C3-8cycloalkyl, SO2aryl, (CH2)i-3aryl (optionally substituted by CO2Ci-6alkyl or (CH2)0-3CO2H), (CH2)i-3heteroaryl or (CH2)i-3C(O)OCi-6alkyl, NH(CH2)0-3C3.8cycloalkyl substituted by CO2H or CO2(Ci-6alkyl), NHC(O)Ci-6alkyl, NHC(0)(CH2)o-3aryl, NH(CH2)2O(CH2)1-3aryl, 3-oxo-2-azabicyclo[2.2.2]oct-2-yl, NH(CH2)o-3aryl substituted by CO2H, CO2Ci-6alkyl, Het or CH=CHC(O)OC i-6alkyl, CO2H, or C(0)NH(CH2)o-3aryl, where phenyl is optionally substituted by 1 to 3 groups selected from halogen, Ci-6alkyl, NH2, Ci-6alkoxy or CO2H. In a further embodiment, there is provided the use of a compound of formula (Id):

or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for the treatment or prevention of infection by hepatitis C virus, wherein R2 is as defined in relation to formula (I), and R1 is C3-8alkyl substituted by CO2H, C(O)NHCi-4alkyl, C(O)NHS(O)2(Ci-6alkyl), C(O)NH(CH2)0-3heteroaryl, C(O)NH(CH2)0-3Het, C(O)NHCH(CH3)phenyl or 0(CH2)o-3aryl, (CH2)i-3C3-8cycloalkyl, (CH2)3aryl, (CH2)1-2Het, (CH2)3heteroaryl, phenyl substituted by SH, SCi-6alkyl or SO2C2-6alkyl, C(O)NH(CH2)1-3aryl, C(O)NH(CH2)1-3CO2H, or C(O)NH(C3-8cycloalkyl) substituted by CO2H or C(O)NHSO2(C i-6alkyl), where the Het groups of (CH2)i-2Het and C(O)NH(CH2)0-3Het are optionally substituted by Ci-4alkyl, OH or NH2, and where the aryl group of C(O)NH(CH2)i-3aryl is optionally substituted by CO2H, halogen, Ci-4alkyl or and where the heteroaryl group of C(O)NH(CH2)0-3heteroaryl is optionally substituted by Ci-4alkyl. When any variable occurs more than one time in formula (I) or in any substituent, its definition on each occurrence is independent of its definition at every other occurrence. As used herein, the term "alkyl" or "alkoxy" as a group or part of a group means that the group is straight or branched. Examples of suitable alkyl groups include methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl and t-butyl. Examples of suitable alkoxy groups include methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, s-butoxy and t-butoxy. The cycloalkyl groups referred to herein may represent, for example, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl. As used herein, the term "alkenyl" and "alkynyl" as a group or part of a group means that the group is straight or branched. Examples of suitable alkenyl groups include vinyl and allyl. Suitable alkynyl groups are ethynyl and propargyl. When used herein, the term "halogen" means fluorine, chlorine, bromine and iodine. When used herein, the term "aryl" as a group or part of a group means a carbocyclic aromatic ring. Examples of suitable aryl groups include phenyl and naphthyl. When used herein, the term "heteroaryl" as a group or part of a group means a 5- to 10-membered heteroaromatic ring system containing 1 to 4 heteroatoms selected from N, O and S. Particular examples of such groups include pyrrolyl, furanyl, thienyl, pyridyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazolyl, oxadiazolyl, thiadiazolyl, triazinyl, tetrazolyl, indolyl, benzimidazolyl, benzothienyl and quinolinyl. When used herein, the term "Het" as a group or part of a group means a heteroaliphatic ring of 4 to 7 ring atoms, which ring may contain 1, 2 or 3 heteroatoms selected from N, O or S or a group S(O), S(O)2, NH orNCi_4alkyl. Where a compound or group is described as "optionally substituted", one or more substituents may be present. Optional substituents may be attached to the compounds or groups which they substitute in a variety of ways, either directly or through a connecting group of which the following are examples: amine, amide, ester, ether, thioether, sulfonamide, sulfamide, sulfoxide, urea, thiourea and urethane. As appropriate an optional substituent may itself be substituted by another substituent, the latter being connected directly to the former or through a connecting group such as those exemplified above. Specific compounds within the scope of this invention include those compounds named in the Examples and Tables below and their pharmaceutically acceptable salts. Preferred compounds of the present invention are those of Group (II) as defined below:

Group (IT): lH-benz[fife]isoquinoline-l,3(2H)-dione, 2-(3-bromophenyl)-6-[(2-hydroxyethyl)amino], 2-(3-chlorophenyl)-6-[(2-hydroxyethyl)amino]- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 2-butyl-6-[(2-hydroxyethyl)amino]- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 2-(3-bromophenyl)-6-[(2-hydroxyethyl)thio]- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 2-(3-bromophenyl)-7-[(2-hydroxyethyl)amino]-2,3-dihydro-lH-b enzo[fife]isoquinolin-l-one, 2-(3-chlorophenyl)-6-(3-hydroxypropyl)-lΗ-benzo[cfe]isoquin oline-l,3(2Η)-dione, 2-(3-chlorophenyl)-6-(lH-pyrazol-3-yl)-lH-benzo[cfe]isoquino line-l,3(2H)-dione, 3-[6-[(benzylamino)carbonyl]-l,3-dioxo-lH-benzo[fife]isoquin olin-2(3H)-yl]hexanoic acid, 6-[(2-hydroxyethyl)amino]-2-[(5-methylisoxazol-3-yl)methyl]- lH-benzo[fife]isoquinoline-l,3(2H)-dione, cis-4- { [2-(3-chlorophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6- yljamino} cyclohexanecarboxylic acid, 2-(3-bromophenyl)-6-[(2-hydroxyethyl)amino]- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 2-(3-bromophenyl)-6-[(2-methoxyethyl)amino]- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 2-(3-bromophenyl)-6-(propylamino)- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 2-(3-bromophenyl)-6-[(3-hydroxypropyl)amino]-lH-benzo[fife]i soquinoline-l,3(2H)-dione, 6-amino-2-(3-bromophenyl)- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 2-(3-bromophenyl)-6-[(2-hydroxyethyl)thio]- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 2-(3-bromophenyl)-6-(methylamino)- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 2-(3-bromophenyl)-6- { [2-(dimethylamino)ethyl]amino} - lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 2-(3-bromophenyl)-6-(isobutylamino)-lH-benzo[fife]isoquinoli ne-l,3(2H)-dione, 2-(3-bromophenyl)-6-(ethylamino)- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 6-(benzylamino)-2-(3-bromophenyl)- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 2-(3-bromophenyl)-6-[(2-phenylethyl)amino]- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 2-(3-bromophenyl)-6-[(2-phenoxyethyl)amino]-lH-benzo[fife]is oquinoline-l,3(2H)-dione, 2-(3-bromophenyl)-6-[(2-hydroxyethyl)(methyl)amino]- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 2-(3-bromophenyl)-6-[(tetrahydroftαran-2-ylmethyl)amino]- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 2-(3-bromophenyl)-6-(cyclopentylamino)- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 2-(3-bromophenyl)-6-(cyclohexylamino)- lH-benzo[de]isoquinoline- 1 ,3(2H)-dione, 2-(3-bromophenyl)-6-(isopropylamino)- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 2-(3-bromophenyl)-6- { [2-(methylthio)ethyl]amino} - lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 2-(3-bromophenyl)-6-methoxy- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, N-(2- { [2-(3-bromophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6-yl]amino} ethyl)acetamide, 2-(3-bromophenyl)-6- { [2-(methylamino)ethyl]amino} - lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 2-(3-bromophenyl)-6-(2-hydroxyethoxy)- lH-benzo[de]isoquinoline- 1 ,3(2H)-dione, 6-[(2-aminoethyl)amino]-2-(3-bromophenyl)-lH-benzo[fife]isoq uinoline-l,3(2H)-dione, 2-(3-bromophenyl)-6-[(cyclopropylmethyl)amino]- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 2-(3-bromophenyl)-6-[(pyridin-2-ylmethyl)amino]- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, benzyl (2- { [2-(3-bromophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6- yljamino} ethyl)carbamate, 6-[(l-benzylpiperidin-4-yl)amino]-2-(3-bromophenyl)-lH-benzo [fife]isoquinoline-l,3(2H)-dione, 4-( { [2-(3-bromophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6-yl]amino}methyl)benzoic acid, trans-4- { [2-(3-bromophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6- yljamino} cyclohexanecarboxylic acid, cis-4- { [2-(3-bromophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6- yljamino} cyclohexanecarboxylic acid, 4- { [2-(3-bromophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6-yl]amino}piperidinium trifluoroacetate, 6-[(2-hydroxyethyl)amino]-2-phenyl-lH-benzo[fife]isoquinolin e-l,3(2H)-dione, 2-benzyl-6-[(2-hydroxyethyl)amino]- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 2-butyl-6-[(2-hydroxyethyl)amino]- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 2-cyclohexyl-6-[(2-hydroxyethyl)amino]- lH-benzo[de]isoquinoline- 1 ,3(2H)-dione, 6-[(2-hydroxyethyl)amino]-2-isobutyl-lH-benzo[fife]isoquinol ine-l,3(2H)-dione, 3-[6-[(2-hydroxyethyl)amino]-l,3-dioxo-lH-benzo[fife]isoquin olin-2(3H)-yl]benzonitrile, 6-[(2-hydroxyethyl)amino]-2-(3-methoxyphenyl)-lH-benzo[fife] isoquinoline-l,3(2H)-dione, 6-[(2-hydroxyethyl)amino]-2-(3-methylphenyl)-lH-benzo[fife]i soquinoline-l,3(2H)-dione, 6-[(2-hydroxyethyl)amino]-2-[3-(methylthio)phenyl]-lH-benzo[ fife]isoquinoline-l,3(2H)-dione, 2-(4-bromophenyl)-6-[(2-hydroxyethyl)amino]- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione 6-[(2-hydroxyethyl)amino]-2-[3-(trifluoromethyl)phenyl]-lH-b enzo[fife]isoquinoline-l,3(2H)-dione, 2-(3-fluorophenyl)-6-[(2-hydroxyethyl)amino]- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 6-[(2-hydroxyethyl)amino]-2-[3-(methylsulfonyl)phenyl]-lH-be nzo[fife]isoquinoline-l,3(2H)-dione, 2-(5-bromopyridin-3-yl)-6-[(2-hydroxyethyl)amino]- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 3-[6-[(2-hydroxyethyl)amino]-l,3-dioxo-lH-benzo[fife]isoquin olin-2(3H)-yl]benzenesulfonamide, 2-(2-bromophenyl)-6-[(2-hydroxyethyl)amino]-lH-benzo[fife]is oquinoline-l,3(2H)-dione, 2-(3,5-dichlorophenyl)-6-[(2-hydroxyethyl)amino]-lH-benzo[fi fe]isoquinoline-l,3(2H)-dione, 2-(2,3-dichlorophenyl)-6-[(2-hydroxyethyl)amino]-lH-benzo[fi fe]isoquinoline-l,3(2H)-dione, 2-(2,5-dichlorophenyl)-6-[(2-hydroxyethyl)amino]-lH-benzo[fi fe]isoquinoline-l,3(2H)-dione, 2-(3-chloro-4-fluorophenyl)-6-[(2-hydroxyethyl)amino]-lH-ben zo[fife]isoquinoline-l,3(2H)-dione, 2-(3-chloro-4-methoxyphenyl)-6-[(2-hydroxyethyl) amino]- lH-benzo[cfe]isoquinoline-l,3(2H)-dione, 6-[(2-aminoethyl)amino]-2-phenyl- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, methyl { [2-(3-chlorophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6-yl]amino} (oxo)acetate, 6-[(l-benzoylpiperidin-4-yl)amino]-2-(3-chlorophenyl)-lH-ben zo[fife]isoquinoline-l,3(2H)-dione, 6-[(l-acetylpiperidin-4-yl)amino]-2-(3-chlorophenyl)-lH-benz o[fife]isoquinoline-l,3(2H)-dione, 2-(3-chlorophenyl)-6- { [ 1 -(cyclohexylcarbonyl)piperidin-4-yl]amino} - lH-benzo[cfe]isoquinoline- 1 ,3(2H)- dione, 2-(3-chlorophenyl)-6- { [ 1 -(phenylsulfonyl)piperidin-4-yl]amino} - lH-benzo[cfe]isoquinoline- 1 ,3(2H)- dione, N-[2-(3-chlorophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6-yl]glycine, 4-( { [2-(3-chlorophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6- yl]amino}methyl)cyclohexanecarboxylic acid, 2-(3-chlorophenyl)-5-[(2-hydroxyethyl)amino]- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 2-[(4- { [2-(3-chlorophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6-yl]amino}piperidin- 1 - yl)carbonyl]benzoic acid, 4-[(4- { [2-(3-chlorophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6-yl]amino}piperidin- 1 - yl)carbonyl]benzoic acid, N-[2-(3-chlorophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-5-yl]acetamide, 4-chloro-2-[6-[(2-hydroxyethyl)amino]-l,3-dioxo-lH-benzo[fif e]isoquinolin-2(3H)-yl]benzoic acid, N-[2-(3-chlorophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6-yl]-2-phenylacetamide, 2-(3-chlorophenyl)-5-(methylamino)- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 2-(3-chlorophenyl)-5-(dimethylamino)- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 2-( { [2-(3-chlorophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-5-yl]amino}methyl)pyridinium trifluoroacetate, trans-A- { [2-(3-chlorophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6- yljamino} cyclohexanecarboxylic acid, 2-(3-chlorophenyl)-6-(2-oxopyrrolidin-l-yl)-lH-benzo[fife]is oquinoline-l,3(2H)-dione, 5- { [2-(3-chlorophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6-yl]amino}pentanoic acid, 1 -benzyl-4- { [2-(2-carboxy-5-chlorophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6- yl]amino}piperidinium trifluoroacetate, (25)-2-[6-[(2-hydroxyethyl)amino]-l,3-dioxo-lH-benzo[fife]is oquinolin-2(3H)-yl]pentanoic acid, 4- { [2-(3-carboxyphenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6-yl]amino}piperidinium trifluoroacetate, 3-[6-[(l-acetylpiperidin-4-yl)amino]-l,3-dioxo-lH-benzo[fife ]isoquinolin-2(3H)-yl]-5-bromobenzoic acid, 1 -benzyl-4-( {2-[(l S)- 1 -carboxybutyl]- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6- yl}amino)piperidinium trifluoroacetate, ethyl 2-(6-bromo- 1 ,3-dioxo- lH-benzo[cfe]isoquinolin-2(3H)-yl)- 1 ,3-thiazole-5-carboxylate, 6- { [2-(benzyloxy)ethyl]amino} -2-[(5-methylisoxazol-3-yl)methyl]- lH-benzo[cfe]isoquinoline- 1 ,3(2H)- dione, 6-[(2-hydroxyethyl)amino]-2-[(5-methylisoxazol-3-yl)methyl]- lH-benzo[fife]isoquinoline-l,3(2H)-dione, 3-[6-[(2-hydroxyethyl)amino]-l,3-dioxo-lH-benzo[fife]isoquin olin-2(3H)-yl]benzoic acid, 4-[6-[(2-hydroxyethyl)amino]-l,3-dioxo-lH-benzo[fife]isoquin olin-2(3H)-yl]benzoic acid, 2-[6-[(2-hydroxyethyl)amino]-l,3-dioxo-lH-benzo[fife]isoquin olin-2(3H)-yl]-4-methylpentanoic acid, methyl cis-4- { [2-(3-chlorophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6- yljamino} cyclohexanecarboxylate, 2-(3-chlorophenyl)-6-(3-oxo-2-azabicyclo[2.2.2]oct-2-yl)-lH- benzo[fife]isoquinoline-l,3(2H)-dione, 2-[6-[(2-hydroxyethyl)amino]-l,3-dioxo-lH-benzo[fife]isoquin olin-2(3H)-yl]benzoic acid, cis-4- { [2-(3-chlorophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6- yljamino} cyclohexanecarboxylic acid, 4- { [2-(3-chlorophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6-yl]amino} - 1 - methylpiperidinium trifluoroacetate, 4- { [2-(3-chlorophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[de]isoquinolin-6-yl]amino} - 1 -(2- phenylethyl)piperidinium trifluoroacetate, 4- { [2-(3-chlorophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6-yl]amino} - 1 - propylpiperidinium trifluoroacetate, 4- { [2-(3-chlorophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6-yl]amino} - 1 -(1 ,3-thiazol-2- ylmethyl)piperidinium trifluoroacetate, 4- { [2-(3-chlorophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6-yl]amino} - 1 -[4- (methoxycarbonyl)benzyl]piperidinium trifluoroacetate, 4- { [2-(3-chlorophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6-yl]amino} - 1 - isopropylpiperidinium trifluoroacetate, l-benzyl-4-({2-[3-bromo-5-(ethoxycarbonyl)phenyl]-l,3-dioxo- 2,3-dihydro-lH-benzo[fife]isoquinolin-6- yl}amino)piperidinium trifluoroacetate, 4- { [2-(3-chlorophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6-yl]amino} - 1 -(2-ethoxy-2- oxoethyl)piperidinium trifluoroacetate, l-(4-carboxybenzyl)-4- { [2-(3-chlorophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6- yl]amino}piperidinium trifluoroacetate, 6-anilino-2-(3-chlorophenyl)- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 2-(3-chlorophenyl)-6-(4-methoxyphenyl)- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 3-[2-(3-chlorophenyl)-l,3-dioxo-2,3-dihydro-lH-benzo[cfe]iso quinolin-6-yl]benzoic acid, 4-[2-(3-chlorophenyl)-l,3-dioxo-2,3-dihydro-lH-benzo[cfe]iso quinolin-6-yl]benzoic acid, 2-(3-chlorophenyl)-6-(3-fluoro-4-methoxyphenyl)- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 2-(3-chlorophenyl)-6-(2-fluoro-4-methoxyphenyl)- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 2-(3-chlorophenyl)-6-(4-fluoro-3-methylphenyl)- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 2-(3-chlorophenyl)-6-(5-fluoro-2-methoxyphenyl)- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 3-[2-(3-chlorophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6-yl]- lH-pyrazol- 1 -ium trifluoroacetate, 2-(3-chlorophenyl)-6-(3-thienyl)- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 4-[2-(3-chlorophenyl)-l,3-dioxo-2,3-dihydro-lH-benzo[cfe]iso quinolin-6-yl]pyridinium trifluoroacetate, 2-(3-chlorophenyl)-6-(3-furyl)- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 3-[2-(3-chlorophenyl)-l,3-dioxo-2,3-dihydro-lH-benzo[cfe]iso quinolin-6-yl]pyridinium trifluoroacetate, 2-(3-chlorophenyl)-6-pyrimidin-5-yl- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 3-[2-(3-chlorophenyl)-l,3-dioxo-2,3-dihydro-lH-benzo[fife]is oquinolin-6-yl]benzenaminium trifluoroacetate, 2-(3-chlorophenyl)-6-cyclohexyl- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, l-(carboxymethyl)-4-{[2-(3-chlorophenyl)-l,3-dioxo-2,3-dihyd ro-lH-benzo[cfe]isoquinolin-6- yl]amino}piperidinium trifluoroacetate, 1 -benzyl-3- { [2-(3-chlorophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6- yl]amino}pyrrolidinium trifluoroacetate, methyl 4- { [2-(3-chlorophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6-yl]amino}benzoate, 4- { [2-(3-chlorophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6-yl]amino}benzoic acid, 2-(3-chlorophenyl)-6-(pyridin-2-ylamino)- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 2-(3-chlorophenyl)-6-(pyridin-3-ylamino)- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 3-[6-[(2-hydroxyethyl)amino]-l,3-dioxo-lH-benzo[fife]isoquin olin-2(3H)-yl]hexanoic acid, 3-bromo-5-[6-[(2-hydroxyethyl)amino]-l,3-dioxo-lH-benzo[fife ]isoquinolin-2(3H)-yl]-N,N- dimethylbenzamide, 3- { [2-(3-chlorophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6-yl]amino}benzoic acid, 2-(3-chlorophenyl)-6-[(4-morpholin-4-ylphenyl)amino]- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 6- { [3-(benzyloxy)phenyl]amino} -2-(3-chlorophenyl)- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 2-(3-chlorophenyl)-6-(quinolin-3-ylamino)- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 2-(3-chlorophenyl)-6-(isoquinolin-7-ylamino)- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, ethyl (2£)-3-(4- { [2-(3-chlorophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6- yl]amino}phenyl)acrylate, 2-(3-chlorophenyl)-6- { [3-(trifluoromethyl)phenyl]amino} - lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 6-[(4-,yec-butylphenyl)amino]-2-(3-chlorophenyl)-lH-benzo[fi fe]isoquinoline-l,3(2H)-dione, 2-(3-chlorophenyl)-6- { [4-(trifluoromethyl)phenyl]amino} - lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 3-bromo-5-[6-[(2-hydroxyethyl)amino]-l,3-dioxo-lH-benzo[fife ]isoquinolin-2(3H)-yl]-N- methylbenzamide, N- {3-bromo-5-[6-[(2-hydroxyethyl)amino]- 1 ,3-dioxo- lH-benzo[cfe]isoquinolin-2(3H)-yl]benzoyl} -β- alanine, 4-[({3-bromo-5-[6-[(2-hydroxyethyl)amino]-l,3-dioxo-lH-benzo [fife]isoquinolin-2(3H)- yljbenzoyl} amino)methyl]benzoic acid, c/.y-4-({3-bromo-5-[6-[(2-hydroxyethyl)amino]-l,3-dioxo-lH-b enzo[fife]isoquinolin-2(3H)- yljbenzoyl} amino)cyclohexanecarboxylic acid, 3-({3-bromo-5-[6-[(2-hydroxyethyl)amino]-l,3-dioxo-lH-benzo[ fife]isoquinolin-2(3H))- yljbenzoyl} amino)cyclohexanecarboxylic acid, 3- { [2-(3-chlorophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6-yl]amino} -NN- dimethylbenzenaminium trifluoroacetate, 3-bromo-5-[6-[(2-hydroxyethyl)amino]-l,3-dioxo-lH-benzo[fife ]isoquinolin-2(3H)-yl]-N- (methylsulfonyl)benzamide, 2-(6-anilino- 1 ,3-dioxo- lH-benzo[cfe]isoquinolin-2(3H)-yl)pentanoic acid, 4- { [2-(3-chlorophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6-yl]amino} -2- methylquinolinium trifluoroacetate, ethyl 3-(6-anilino- 1 ,3-dioxo- lH-benzo[cfe]isoquinolin-2(3H)-yl)-5-chlorobenzoate, 3-(6-anilino- 1 ,3-dioxo- lH-benzo[cfe]isoquinolin-2(3H)-yl)-5-chlorobenzoic acid, 4- { [2-(3-carboxy-5-chlorophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6-yl]amino} - 1 - isopropylpiperidinium trifluoroacetate, 4- { [2-(3-carboxy-5-chlorophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6-yl]amino} - 1 -(2- phenylethyl)piperidinium trifluoroacetate, 4-[(4- { [2-(3-carboxy-5-chlorophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6- yl]amino}piperidinium- 1 -yl)methyl]pyridinium bis(trifluoroacetate), 1 -benzyl-4-[(2- {3-bromo-5-[(methylamino)carbonyl]phenyl} - 1 ,3-dioxo-2,3-dihydro- IH- benzo[fife]isoquinolin-6-yl)amino]piperidinium trifluoroacetate, 6-amlino-2-butyl- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 4-[(2-butyl- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6-yl)amino]- 1 -isopropylpiperidinium trifluoroacetate, 3-(6-anilino- 1 ,3-dioxo- lH-benzo[cfe]isoquinolin-2(3H)-yl)hexanoic acid, 4-( {2-[ 1 -(carboxymethyl)butyl]- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6-yl} amino)- 1 - isopropylpiperidinium trifluoroacetate, 2-(3-bromophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinoline-6-carboxylic acid, 2-[ 1 -(carboxymethyl)butyl]- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinoline-6-carboxylic acid, 3-[6-[(benzylamino)carbonyl]-l,3-dioxo-lH-benzo[fife]isoquin olin-2(3H)-yl]hexanoic acid, 2-(5-chloro-2-methoxyphenyl)-6-[(2-hydroxyethyl)amino]- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 3-(6-anilino- 1 ,3-dioxo- lH-benzo[cfe]isoquinolin-2(3H)-yl)-N-(methylsulfonyl)hexanam ide, 1 -isopropyl-4-( {3-[6-[( 1 -isopropylpiperidinium-4-yl)amino]- 1 ,3-dioxo- lH-benzo[cfe]isoquinolin-2(3H)- yljhexanoyl} amino)piperidinium bis(trifluoroacetate), 1 -isopropyl-4-[(2- { 1 -[2-(methylamino)-2-oxoethyl]butyl} - 1 ,3-dioxo-2,3-dihydro- IH- benzo[fife]isoquinolin-6-yl)amino]piperidinium trifluoroacetate, 2-(5-chloro-2-hydroxyphenyl)-6-[(2-hydroxyethyl)amino]- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 2-(2,3-dihydro-lh-inden-4-yl)-6-[(2-hydroxyethyl)amino]-lH-b enzo[fife]isoquinoline-l,3(2H)-dione, 2-(3-chloro-2-fluorophenyl)-6-[(2-hydroxyethyl)amino]-lH-ben zo[fife]isoquinoline-l,3(2H)-dione, 2-(3-bromo-2-methylphenyl)-6-[(2-hydroxyethyl)amino]-lH-benz o[fife]isoquinoline-l,3(2H)-dione, 6-[(2-hydroxyethyl)amino]-2-(4-methylpyridin-2-yl)-lH-benzo[ fife]isoquinoline-l,3(2H)-dione, 3-( { [2-(3-chlorophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6-yl]amino}methyl)benzoic acid, 3-[6-[(2-hydroxyethyl)amino]-l,3-dioxo-lH-benzo[fife]isoquin olin-2(3H)-yl]-N-l,3,4-thiadiazol-2- ylhexanamide, 2- { 1 -[2-(3-amino- lH-pyrazol- 1 -yl)-2-oxoethyl]butyl} -6-[(2-hydroxyethyl)amino]- IH- benzo[fife]isoquinoline- 1 ,3(2H)-dione, 2-( {3-[6-[(2-hydroxyethyl)amino]- 1 ,3-dioxo- lH-benzo[cfe]isoquinolin-2(3H)-yl]hexanoyl} amino)- 1 ,3- thiazol-3-ium trifluoroacetate, 3-[({3-[6-[(2-hydroxyethyl)amino]-l,3-dioxo-lH-benzo[fife]is oquinolin-2(3H)- yljhexanoyl} amino)methyl]pyridinium trifluoroacetate, 2-[({3-[6-[(2-hydroxyethyl)amino]-l,3-dioxo-lH-benzo[fife]is oquinolin-2(3H)- yljhexanoyl} amino)methyl]pyridinium trifluoroacetate, 4-[({3-[6-[(2-hydroxyethyl)amino]-l,3-dioxo-lH-benzo[fife]is oquinolin-2(3H)- yljhexanoyl} amino)methyl]pyridinium trifluoroacetate, 3-[2-({3-[6-[(2-hydroxyethyl)amino]-l,3-dioxo-lH-benzo[fife] isoquinolin-2(3H)- yljhexanoyl} amino)ethyl]pyridinium trifluoroacetate, 5-[2-({3-[6-[(2-hydroxyethyl)amino]-l,3-dioxo-lH-benzo[fife] isoquinolin-2(3H)- yljhexanoyl} amino)ethyl]- lH-imidazol-3-ium trifluoroacetate, 2-(3-chlorophenyl)-6-(3-hydroxypropyl)- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 6-[(2-hydroxyethyl)amino]-2-(3-methylcyclohexyl)-lH-benzo[fi fe]isoquinoline-l,3(2H)-dione, N-(2,6-difluorobenzyl)-3-[6-[(2-hydroxyethyl)amino]- 1 ,3-dioxo- lH-benzo[cfe]isoquinolin-2(3H)- yljhexanamide, 3-[6-[(2-hydroxyethyl)amino]-l,3-dioxo-lH-benzo[fife]isoquin olin-2(3H))-yl]-N-[2-(lH-l,2,4-triazol-5- yl)ethyl]hexanamide, 3-[6-[(2-hydroxyethyl)amino]-l,3-dioxo-lH-benzo[fife]isoquin olin-2(3H)-yl]-N-(2-pyridin-4- ylethyl)hexanamide, 3-[6-[(2-hydroxyethyl)amino]-l,3-dioxo-lH-benzo[fife]isoquin olin-2(3H)-yl]-N-(lH-indol-6- ylmethyl)hexanamide, N-benzyl-3-[6-[(2-hydroxyethyl)amino]-l,3-dioxo-lH-benzo[fif e]isoquinolin-2(3H)-yl]hexanamide, N-(2,6-dimethoxybenzyl)-3-[6-[(2-hydroxyethyl)amino]-l,3-dio xo-lH-benzo[fife]isoquinolin-2(3H)- yljhexanamide, N-(2,6-difluorobenzyl)-3-[6-[(2-hydroxyethyl)amino]- 1 ,3-dioxo- lH-benzo[cfe]isoquinolin-2(3H)- yljhexanamide, N-(2,6-difluorobenzyl)-3-[6-[(2-hydroxyethyl)amino]- 1 ,3-dioxo- lH-benzo[cfe]isoquinolin-2(3H)- yljhexanamide, {3-bromo-5-[6-[(2-hydroxyethyl)amino]-l,3-dioxo-lH-benzo[fif e]isoquinolin-2(3H)-yl]phenyl}acetic acid, 3-[6-[(2-hydroxyethyl)amino]-l,3-dioxo-lH-benzo[fife]isoquin olin-2(3H)-yl]-N-[(lR)-l- phenylethyljhexanamide, 3-[6-[(2-hydroxyethyl)amino]-l,3-dioxo-lH-benzo[fife]isoquin olin-2(3H)-yl]-N-[(lR)-l- phenylethyljhexanamide, N-[(37?,47?)-4-hydroxy- 1 , 1 -dioxidotetrahydro-3-thienyl]-3-[6-[(2-hydroxyethyl)amino]- 1 ,3-dioxo- IH- benzo[fife]isoquinolin-2(3H)-yl]hexanamide, 3-[6-[(2-hydroxyethyl)amino]-l,3-dioxo-lH-benzo[fife]isoquin olin-2(3H)-yl]-N-[(l-methyl-lh-pyrazol-4- yl)methyl]hexanamide, N-(2-chloro-6-methylbenzyl)-3-[6-[(2-hydroxyethyl)amino]- 1 ,3-dioxo- lH-benzo[fife]isoquinolin-2(3H)- yljhexanamide, N-(2-fluorobenzyl)-3-[6-[(2-hydroxyethyl)amino]- 1 ,3-dioxo- lH-benzo[fife]isoquinolin-2(3H)- yljhexanamide, 3-[6-[(2-hydroxyethyl)amino]-l,3-dioxo-lH-benzo[fife]isoquin olin-2(3H)-yl]-N-[(15)-l- phenylethyljhexanamide, 3-[6-[(2-hydroxyethyl)amino]-l,3-dioxo-lH-benzo[fife]isoquin olin-2(3H)-yl]-N-[(15)-l- phenylethyljhexanamide, 2-butyl-6-(butylamino)- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 2-[({3-[6-[(2-hydroxyethyl)amino]-l,3-dioxo-lH-benzo[fife]is oquinolin-2(3H)- yljhexanoyl} amino)methyl]-5,7-dimethyl[ 1 ,2,4]triazolo[ 1 ,5-a]pyrimidin- 1 -ium trifluoroacetate, 1 -benzyl-4-( { 1 ,3-dioxo-2-[ 1 -(2-oxo-2- { [(75)- 1 -phenylethyljamino} ethyl)butyl]-2,3-dihydro- IH- benzo[cfe]isoquinolin-6-yl}amino)piperidinium trifluoroacetate, 1 -benzyl-4-( { 1 ,3-dioxo-2-[ 1 -(2-oxo-2- { [(75)- 1 -phenylethyljamino} ethyl)butyl]-2,3-dihydro- IH- benzo[cfe]isoquinolin-6-yl}amino)piperidinium trifluoroacetate, cis-4-( { 1 ,3-dioxo-2-[ 1 -(2-oxo-2- { [(75)- l-phenylethyl]amino} ethyl)butyl]-2,3-dihydro- IH- benzo[cfe]isoquinolin-6-yl} amino)cyclohexanecarboxylic acid, cis-4-( { 1 ,3-dioxo-2-[ 1 -(2-oxo-2- { [(75)- l-phenylethyl]amino} ethyl)butyl]-2,3-dihydro- IH- benzo[cfe]isoquinolin-6-yl} amino)cyclohexanecarboxylic acid, 2- { 1 -[(benzyloxy)methyl]butyl} -6-[(2-hydroxy ethyl) amino]- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, trans- 1 -benzyl-4- { [2-(3-chlorophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6- yljamino} cyclohexanecarboxylic acid, 2-(3-chlorophenyl)-6- { [ 1 -(phenylacetyl)piperidin-4-yl]amino} - lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione, 3-bromo-5-[6-[(2-hydroxyethyl)amino]-l,3-dioxo-lH-benzo[cfe] isoquinolin-2(3H)-yl]benzoic acid, 1 -benzyl-4- { [2-(3-bromo-5-carboxyphenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6- yl]amino}piperidinium trifluoroacetate, 4-[(4- { [2-(3-chlorophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6-yl]amino}piperidinium- 1 - yl)methyl]pyridinium bis(trifluoroacetate), 4- { [2-(3-chlorophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6-yl]amino} - 1 -(3- thienylmethyl)piperidinium trifluoroacetate, c/.y-4-[(2-{3-methyl-5-[(methylamino)carbonyl]phenyl}-l,3-di oxo-2,3-dihydro-lH-benzo[fife]isoquinolin- 6-yl)amino]cyclohexanecarboxylic acid, cis- l-benzyl-4- { [2-(3-chlorophenyl)- 1 ,3-dioxo-2,3-dihydro- lH-benzo[cfe]isoquinolin-6- yljamino} cyclohexanecarboxylic acid, 6-bromo-2-butyl- lH-benzo[cfe]isoquinoline- 1 ,3(2H)-dione,

and their pharmaceutically acceptable salts. For use in medicine, the salts of the compounds of formula (I) will be non-toxic pharmaceutically acceptable salts. Other salts may, however, be useful in the preparation of the compounds according to the invention or of their non-toxic pharmaceutically acceptable salts. Suitable pharmaceutically acceptable salts of the compounds of this invention include acid addition salts which may, for example, be formed by mixing a solution of the compound according to the invention with a solution of a pharmaceutically acceptable acid such as hydrochloric acid, fumaric acid, p-toluenesulfonic acid, maleic acid, succinic acid, acetic acid, citric acid, tartaric acid, carbonic acid, phosphoric acid or sulfuric acid. Salts of amine groups may also comprise quaternary ammonium salts in which the amino nitrogen atom carries a suitable organic group such as an alkyl, alkenyl, alkynyl or aralkyl moiety. Furthermore, where the compounds of the invention carry an acidic moiety, suitable pharmaceutically acceptable salts thereof may include metal salts such as alkali metal salts, e.g. sodium or potassium salts; and alkaline earth metal salts, e.g. calcium or magnesium salts. The salts may be formed by conventional means, such as by reacting the free base form of the product with one or more equivalents of the appropriate acid in a solvent or medium in which the salt is insoluble, or in a solvent such as water which is removed in vacuo or by freeze drying or by exchanging the anions of an existing salt for another anion on a suitable ion exchange resin. The present invention includes within its scope prodrugs of the compounds of formula (I) above. In general, such prodrugs will be functional derivatives of the compounds of formula (I) which are readily convertible in vivo into the required compound of formula (I). Conventional procedures for the selection and preparation of suitable prodrug derivatives are described, for example, in "Design of Prodrugs", ed. Η. Bundgaard, Elsevier, 1985. A prodrug may be a pharmacologically inactive derivative of a biologically active substance (the "parent drug" or "parent molecule") that requires transformation within the body in order to release the active drug, and that has improved delivery properties over the parent drug molecule. The transformation in vivo may be, for example, as the result of some metabolic process, such as chemical or enzymatic hydrolysis of a carboxylic, phosphoric or sulfate ester, or reduction or oxidation of a susceptible functionality. The present invention includes within its scope solvates of the compounds of formula (I) and salts thereof, for example, hydrates. The present invention also includes within its scope any enantiomers, diastereomers, geometric isomers and tautomers of the compounds of formula (I). It is to be understood that all such isomers and mixtures thereof are encompassed within the scope of the invention. In another aspect of the invention, there is provided a method of inhibiting hepatitis C virus polymerase and/or of treating or preventing an illness due to hepatitis C virus, the method involving administering to a human or animal (preferably mammalian) subject suffering from the condition a therapeutically or prophylactically effective amount of the pharmaceutical composition described above or of a compound of formula (I) as defined above, or a pharmaceutically acceptable salt thereof. "Effective amount" means an amount sufficient to cause a benefit to the subject or at least to cause a change in the subject's condition. In a further embodiment of the present invention, there is provided the use of a compound of formula (I), or a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for the treatment or prevention of infection by hepatitis C virus, in combination with one or more other agents for the treatment of viral infections such as an antiviral agent, and/or an immunomodulatory agent such as α-, β- or γ-interferon, particularly α-interferon. Suitable antiviral agents include ribavirin and inhibitors of hepatitis C virus (HCV) polymerase, such as inhibitors of metalloprotease (NS2-3), serine protease (NS3), helicase (NS3) and RNA-dependent RNA polymerase (NS5B). A further aspect of the invention provides a pharmaceutical composition comprising a compound of formula (Ic) or (Id) as defined above or a compound selected from Group (II) as defined above, or a pharmaceutically acceptable salt thereof, in association with a pharmaceutically acceptable carrier. The composition may be in any suitable form, depending on the intended method of administration. It may for example be in the form of a tablet, capsule or liquid for oral administration, or of a solution or suspension for administration parenterally. The composition may be prepared by admixing at least one active ingredient, or a pharmaceutically acceptable salt thereof, with one or more pharmaceutically acceptable adjuvants, diluents or carriers and/or with one or more other therapeutically or prophylactically active agents. A further aspect of the invention provides a compound of formula (Ic) or (Id) as defined above or a compound selected from Group (II) as defined above, or a pharmaceutically acceptable salt thereof for use in therapy. A further aspect of the invention provides a compound of formula (Ic) or (Id) as defined above or a compound selected from Group (II) as defined above, or a pharmaceutically acceptable salt thereof. The dosage rate at which the compound is administered will depend on a variety of factors including the activity of the specific compound employed, the metabolic stability and length of action of that compound, the age of the patient, body weight, general health, sex, diet, mode and time of administration, rate of excretion, drug combination, the severity of the particular condition and the host undergoing therapy. For the treatment or prevention of infection by hepatitis C virus, suitable dosage levels may be of the order of 0.02 to 5 or 10 g per day, with oral dosages two to five times higher. For instance, administration of from 10 to 50 mg of the compound per kg of body weight from one to three times per day may be in order. Appropriate values are selectable by routine testing. The compound may be administered alone or in combination with other treatments, either simultaneously or sequentially. For instance, it may be administered in combination with effective amounts of antiviral agents, immunomodulators, anti-infectives or vaccines known to those of ordinary skill in the art. It may be administered by any suitable route, including orally, intravenously, cutaneously and subcutaneously. It may be administered directly to a suitable site or in a manner in which it targets a particular site, such as a certain type of cell. Suitable targeting methods are already known. Compounds of general formula (I) may be prepared by methods disclosed in the documents hereinbefore referred to and by methods known in the art of organic synthesis as set forth below. According to a general process (a), compounds of formula (I) may be prepared by the reaction of a compound of formula (II) with a compound of formula (III):

(II) (III)

where R1, R2, A, B and n are as defined for formula (I). The reaction is conveniently performed in the presence of a suitable solvent, such as NMP, ethanol or DMF, at a raised temperature, such as the reflux temperature of the solvent, and optionally under microwave irradiation. Compounds of formula (I) may also be prepared by the reaction of a compound of formula (IV) with a compound of formula (V):

(IV) (V)

where R1, R2, A and B are as defined for formula (I), and L is a suitable leaving group such as chlorine, bromine or nitro. The reaction is conveniently performed in the presence of a suitable solvent, such as NMP, at a raised temperature, optionally under microwave irradiation. Alternatively, the compounds of formula (I) may be prepared by the reaction of the compound of formula (IV) with a compound of formula (VI): R2— B(OH)2 (VI)

where R2 is as defined for formula (I). The reaction is conveniently performed in the presence of a suitable catalyst, such as palladium triphenylphosphine, in a suitable solvent, such as a dimethyl ether/ethanol mixture, at raised temperature. Where they are not commercially available, the starting material of formulae (II), (III), (IV) and (V) may be prepared by methods analogous to those described in the accompanying Examples, or by standard methods well known from the art. It will be understood that any compound of formula (I) initially obtained from any of the above processes may, where appropriate, subsequently be elaborated into a further compound of formula (I) by techniques known from the art. For instance, a compound of formula (I) where B is C=O may be transformed into a compound of formula (I) where B is CH2 by reduction with a suitable reducing agent, such as sodium borohydride, in a suitable solvent, such as an ethanol/water mixture. Many of the compounds of the present invention were prepared using the general method (A):

Method A

1,8-naphthalimides were prepared by condensation reaction of naphthalic anhydrides with primary amines under microwave irradiation. The 6-amino analogues were synthesised by treatment of 6-bromo- 1,8-naphthalimides with primary or secondary amines under microwave irradiation. General method (A) is illustrated by Example 1 below. Where a mixture of products is obtained from any of the processes described above for the preparation of compounds according to the invention, the desired product can be separated therefrom at an appropriate stage by conventional methods such as preparative HPLC; or column chromatography utilising, for example, silica and/or alumina in conjunction with an appropriate solvent system. During any of the above synthetic sequences it may be necessary and/or desirable to protect sensitive or reactive groups on any of the molecules concerned. This may be achieved by means of conventional protecting groups, such as those described in Protective Groups in Organic Chemistry, ed. J.F.W. McOmie, Plenum Press, 1973; and T. W. Greene & P.G.M. Wuts, Protective Groups in Organic Synthesis, John Wiley & Sons, 3rd edition, 1999. The protecting groups may be removed at a convenient subsequent stage using methods known from the art. The following Examples are illustrative of the invention. The compounds of the invention were tested for inhibitory activity against the HCV RNA dependent RNA polymerase (NS5B) in an enzyme inhibition assay (example i)). The compounds have IC50's below 30μM in the enzyme assay.

i) In-vitro HCV NS5B Enzyme Inhibition Assay The HCV-BK cDNA sequence coding for the NS5B protein lacking of the 21 C-terminal residues (residues 1-570) was cloned in the pT7.7 vector downstream of the T7 promoter and in frame with the first ATG of the gene 10 protein of the T7 phage. A C-terminal HisTag was added to simplify purification procedure. Expression in E.coli BL21(DE3) was performed as described (Tomei et al., JGV (2000), 81, 759). Bacteria were grown at 37°C in standard LB medium up to an absorbance of 0.8 at 600 nm. The temperature of the culture was then lowered to 18°C and expression induced with 0.4 mM IPTG for further 23 hrs. All the subsequent purification steps were performed at 4°C. Cells were harvested, washed with PBS (20 mM Na-phosphate [pH 7.5], 150 mM NaCl), resuspendend in 100 ml of lysis buffer/liter of culture, and disrupted with a model HOS Microfluidizer. Lysis buffer contained 10 mM Tris [pH 8.0], 1 mM EDTA, 0.5 M NaCl, 50% glycerol, 10 mM β-mercaptoethanol, 0.1% n-octyl-β-D- glucopyranoside (Inalco; n-OG), Complete™ protease inhibitor cocktail (Roche). After addition of 10 mM MgCl2, the extract was incubated with 0.5 units/ml of DNaseI for 30 min. The insoluble material was pelletted by centrifugation for 60 min at 15,000 rpm in a Sorvall SS34 rotor. The clarified supernatant was incubated batchwise for 45 min with 50 ml/liter of culture of DEAE-Sepharose FF resin equilibrated in lysis buffer lacking glycerol. The flow-through from the DEAE-Sepharose was diluted to 0.3 M NaCl and loaded on a Ni-NTA Superflow column (Qiagen; 3 ml/liter of culture) equilibrated with A buffer + 10 mM Imidazole (A buffer: 10 mM Tris [pH 8.0], 20% glycerol, 0.3 M NaCl, 0.1% n-OG, 10 mM β-mercaptoethanol) and eluted with a 50 to 500 mM imidazole gradient in A buffer. Peak fraction were collected, dialysed vs D buffer (10 mM Hepes [pH 8.0], 20% glycerol, 0.2% n-OG, 1 mM EDTA, 5 mM DTT) containing 0.15 M NaCl and loaded on HiTrap Heparin column (Amersham) equilibrated with D buffer and eluted with a 0.15 to 0.8M NaCl gradient in D buffer. The protein was stored in aliquots in liquid nitrogen. The purified enzyme was shown to possess in vitro RNA polymerase activity using RNA as template according to a description in Journal of General Virology 81:759-767 (2000). The reference describes a polymerisation assay using poly(A) and oligo(U) as a template/primer. Incorporation of tritiated UTP is quantified by measuring acid-insoluble radioactivity. The present inventors have employed this assay to screen the various compounds described above as inhibitors of HCV RdRp. Incorporation of radioactive UMP was measured as follows. The standard reaction (50 μl) was carried out in a buffer containing 20 mM Tris/HCl pH 7.5, 5 mM MgCl2, 1 mM DTT, 10 mM NaCl, 0.01% Triton X-100, 1 μCi [3H]-UTP (40 Ci/mmol, NEN), 10 μM UTP and 10 μg/ml poly(A) /Oligo(U)i2 (1 μg/ml, Genset) as a template/primer. The final NS5B ΔC21 enzyme concentration was 5 nM. The order of assembly was: 1) compound, 2) enzyme, 3) template/primer, 4) NTP. After 1 h. incubation at 22°C the reaction was stopped by adding 50 μl of 20% TCA and applying samples to DE81 filters. The filters were washed thoroughly with 5% TCA containing IM Na2HPO4ZNaH2PO4, pH 7.0, rinsed with water and then ethanol, air dried, and the filter-bound radioactivity was measured in the scintillation counter. Carrying out this reaction in the presence of various concentrations of each compound set out above allowed determination Of IC50 values by utilising the formula:

% Residual activity = 100/(l+[I]/IC50)s

where [I] is the inhibitor concentration and "s" is the slope of the inhibition curve.

ii) General Procedures AU solvents were obtained from commercial sources (Fluka, puriss.) and were used without further purification. With the exception of routine deprotection and coupling steps, reactions were carried out under an atmosphere of nitrogen in oven dried (110 °C) glassware. Organic extracts were dried over sodium sulfate, and were concentrated (after filtration of the drying agent) on rotary evaporators operating under reduced pressure. Flash chromatography was carried out on silica gel following published procedure (W.C. Still et al., J. Org. Chem. 1978, 43, 2923) or on semi-automated flash chromatography systems utilising pre-packed columns. Reagents were usually obtained directly from commercial suppliers (and used as supplied) but a limited number of compounds from in-house corporate collections were utilised. In the latter case the reagents are readily accessible using routine synthetic steps that are either reported in the scientific literature or are known to those skilled in the art. 1H nmr spectra were recorded on Bruker AM series spectrometers operating at (reported) frequencies between 300 and 600 MHz. Chemical shifts (δ) for signals corresponding to non- exchangeable protons (and exchangeable protons where visible) are recorded in parts per million (ppm) relative to tetramethylsilane and are measured using the residual solvent peak as reference. Signals are tabulated in the order: multiplicity (s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet; br, broad, and combinations thereof); coupling constant(s) in hertz; number of protons. Mass spectral (MS) data were obtained on a Perkin Elmer API 100 operating in negative (ES") or positive (ES+) ionization mode and results are reported as the ratio of mass over charge (m/z) for the parent ion only. Preparative scale HPLC separations were carried out on a Waters Delta Prep 4000 separation module, equipped with a Waters 486 absorption detector or on a Gilson preparative system. In all cases compounds were eluted with linear gradients of water and acetonitrile both containing 0.1% TFA using flow rates between 15 and 25 mL/min. The following abbreviations are used in the examples: AcOH: acetic acid; BINAP: 2,2'-bis(diphenylphosphino)-l,r-binaphthyl; BoC2O: di-tert-butyl dicarbonate; DIPEA: NN-diisopropylethylamine; DMAP: 4-(dimethylamino)pyridine; DME: 1,2- dimethoxyethane; DMF: dimethylformamide; DMSO: dimethylsulfoxide; eq.: equivalents); EtOH: ethanol; H2O: water; Et2O: ethyl ether; EtOAc: ethyl acetate; h: hour(s); HCl: hydrogen chloride; M: molar; MeCN: acetonitrile; MeOH: methanol; min: minutes; ΝMP: l-methyl-2-pyrrolidinone; RP-HPLC: reversed phase high-pressure liquid chromatography; RT: room temperature; TFA: trifluoroacetic acid.

Example 1: lH-benz[cfe]isoquinoline-l,3(2H)-dione, 2-(3-bromophenyl)-6-[(2-hydroxyethyl)amino]

Step 1 : 6-bromo-2-(3-bromophenyiy lH-benzo[<fe]isoquinoline- 1 ,3(2H)-dione 3-bromoaniline (1.3 eq.) was added to a solution (0.3 M) of 4-bromo-l,8-naphthalic anhydride in ΝMP. The reaction mixture was heated at 145°C for 24 h and then cooled at RT. The resulting precipitate was filtered, washed subsequently with EtOH and Et2O and dried to afford the title compound (42%) as a pale brown solid; MS (ES+) m/z 430, 432 (M+Η)+.

Step 2: 2-(3-bromophenyl)-6-[(2-hvdroxyethyl)aminol- lH-benz[<felisoquinoline-1.3(2H)-dione A solution (0.2 M) of 6-bromo-2-(3-bromophenyl)-lH-benzo[cfe]isoquinoline-l,3(2H)- dione (from Step 1) and ethanolamine (10 eq.) in ΝMP was heated at 200°C under microwave irradiation for 30 min. After addition of water the resulting precipitate was filtered and washed subsequently with EtOH and Et2O. Crystallization from acetone afforded the title compound (27%) as a yellow solid. 1H ΝMR (400 MHz, DMSO-d6, 400 K) δ 3.51 (m, 2H), 3.73 (m, 2H), 4.91 (t, / 5.19, IH), 6.87 (d, / 8.57, IH), 7.38 (d, / 7.67, IH), 7.48 (t, / 7.75, IH), 7.65 (m, 2H), 7.73 (t, / 7.76, IH), 8.27 (d, / 8.48, IH), 8.45 (d, /7.13, IH), 8.77 (d, / 8.30, IH); MS (ES+) m/z 411, 413 (M+H)+ .

Example 2: 2-(3-chlorophenyl)-6-[(2-hydroxyethyl)amino]-lH-benzo[fife]i soquinoline-l,3(2H)-dione A solution (0.09 M) of 4-bromo-l,8-naphthalic anhydride in EtOH was treated with 3-chloroaniline (1.5 eq.). The reaction mixture was heated to reflux for 15 h. After cooling down, filtration and washing with EtOH afforded a solid that was a mixture (1.2:1) of starting material and 6-bromo-2-(3-chlorophenyl)-lH- benzo[fife]isoquinoline-l,3(2H)-dione (MS (ES+) m/z 386, 388, 390 (M+Η)+). This crude was dissolved in ΝMP. The resulting solution (0.15 M) was treated with 2-aminoethanol (2.0 eq.). The reaction mixture was heated at 200°C under microwave irradiation for 30 min. After cooling down, the reaction mixture was diluted with MeCΝ/DMSO (3:1) and it was purified by RP-HPLC (Conditions: Waters X-TERRA MS C18, 5 micron, 19 x 150 mm; flow: 20 mL/min; Gradient: A: H2O + 0.1% TFA; B: MeCN + 0.1% TFA; 99% A isocratic for 2 min, linear to 1% A in 10 min, 1% A isocratic for 5 min) to afford the title compound (20%) as a solid. 1H NMR (400 MHz, DMSO-d6, 300 K) δ 3.50 (m, 2H), 3.72 (t, 2H, / 6.2), 6.86 (d, IH, / 8.6), 7.33 (m, IH), 7.52 (m, 3H), 7.72 (dd, IH, / 7.2, 8.3), 7.80 (m, IH), 8.26 (d, IH, / 8.6), 8.44 (d, IH, / 7.2), 8.75 (d, IH, / 7.9); MS (ES+) m/z 367, 369 (M+H)+.

Example 3: 2-butyl-6-[(2-hydroxyethyl)amino]-lH-benzo[fife]isoquinoline -l,3(2H)-dione

Step 1: 6-bromo-2-butyl-lH-benzo[(Je1isoquinoline-1.3(2H)-dione A solution (0.32 M) of 4-bromo-l,8-naphthalic anhydride in EtOH was treated with w-butylamine (1.1 eq.). The reaction mixture was heated at 150°C under microwave irradiation for 1 h. After addition of MeOH the resulting precipitate was filtered and dried to afford a first crop of the title compound (62%) as a solid. The filtrate was concentrated, and the residue was treated with EtOHZH2O (1:4) to afford a second crop of the title compound (35%). This compound was used as such in the next step; MS (ES+) m/z 332, 334 (M+H)+.

Step 2: 2-butyl-6-[(2-hvdroxyethyl)aminol-lH-benzo[(Je1isoquinoline- l,3(2H)-dione A solution (0.15 M) of 6-bromo-2-butyl-lH-benzo[cfe]isoquinoline-l,3(2H)-dione (from Step 1) in NMP was treated with 2-aminoethanol (1.2 eq.). The reaction mixture was heated at 200°C under microwave irradiation for 30 min. After cooling down, the reaction mixture was diluted with EtOAc and water was added. The organic layer was separated and the aqueous layer was extracted with EtOAc. The combined organic layers were dried and evaporated to give a residue that was purified by RP-ΗPLC (Conditions: Waters X-TERRA MS C 18, 5 micron, 19 x 150 mm; flow: 20 mL/min; Gradient: A: H2O + 0.1% TFA; B: MeCN + 0.1% TFA; 99% A isocratic for 2 min, linear to 1% A in 10 min, 1% A isocratic for 5 min) to afford the title compound (53%) as a solid. 1H NMR (400 MHz, DMSO-d6, 300 K) δ 0.91 (t, 3H, /7.2), 1.33 (m, 2H), 1.58 (m, 2H), 3.46 (m, 2H), 3.70 (t, 2H, / 6.1), 4.04 (t, 2H, / 7.4), 6.81 (d, IH, / 8.8), 7.67 (dd, IH, / 7.4, 8.3), 7.70 (bs, IH), 8.25 (d, IH, / 8.6), 8.42 (d, IH, /6.8), 8.68 (d, IH, / 7.6); MS (ES+) m/z 313 (M+H)+.

Example 4: 2-(3-bromophenyl)-6-[(2-hydroxyethyl)thio]-lH-benzo[cfe]isoq uinoline-l,3(2H)-dione A solution (1.0 M) of 6-[(2-hydroxyethyl)thio]-lH, 3H-benzo[cfe]isochromene-l,3-dione in NMP was treated with 3-bromoaniline (1.5 eq.). The reaction mixture was heated at 200°C under microwave irradiation for 30 min. Then more 3-bromoaniline (0.75 eq) was added, and the reaction was heated under microwave irradiation for another 15 min. After cooling down, water and EtOAc were added. The layers were separated, and the aqueous layer was extracted with EtOAc. The gummy residue that remained on the reaction vessel gave a solid after addition of EtOH. This solid was filtered off and washed with EtOH to afford 39% of recovered starting material. After drying, combined EtOAc layers were joint with the EtOH filtrate and evaporated. The residue was purified by RP-ΗPLC (Conditions: Waters X-TERRA MS C 18, 5 micron, 19 x 150 mm; flow: 20 mL/min; Gradient: A: H2O + 0.1% TFA; B: MeCN + 0.1% TFA; 99% A isocratic for 2 min, linear to 1% A in 10 min, 1% A isocratic for 5 min) to afford the title compound (11%) as a solid. 1H NMR (400 MHz, DMSO-d6, 300 K) δ 3.39 (t, 2H, /6.4), 3.77 (t, 2H, /6.4), 5.14 (bs, IH), 7.43 (d, IH, /7.9), 7.50 (t, IH, / 7.9), 7.68 (d, IH, / 7.9), 7.70 (d, IH, / 1.5), 7.85 (d, IH, / 8.1), 7.93 (dd, IH, / 7.4, 8.3), 8.38 (d, IH, / 7.9), 8.55 (d, IH, /7.2), 8.65 (d, IH, / 8.5); MS (ES+) m/z 428, 430 (M+H)+.

Example 5: 2-(3-bromophenyl)-7-[(2-hydroxyethyl)amino]-2,3-dihydro-lH-b enzo[fife]isoquinolin-l- one A solution (0.02 M) of 2-(3-bromophenyl)-6-[(2-hydroxyethyl)amino]-lH-benz[cfe]isoq uinoline-l,3(2H)- dione (from Example 1) in EtOΗ/water (10: 1) was treated with sodium borohydride (5 eq.). The reaction was stirred overnight at RT. After quenching with aqueous HCl (1 N), the reaction mixture was extracted with EtOAc and the combined organic layers were dried and concentrated. The residue was purified by RP-ΗPLC (Conditions: Waters X-TERRA MS C 18, 5 micron, 19 x 150 mm; flow: 20 mL/min; Gradient: A: H2O + 0.1% TFA; B: MeCN + 0.1% TFA; 90% A isocratic for 2 min, linear to 30% A in 10 min, then linear to 0% A in 2 min) to afford the title compound (26%) as a solid. 1H NMR (300 MHz, DMSO-d6, 300 K) δ 3.41 (m, 2H), 3.70 (m, 2H), 4.83 (t, / 5.53, IH), 5.29 (s, 2H), 6.68 (d, / 8.40, IH), 6.91 (m, IH), 7.35-7.55 (m, 5H), 7.74 (s, IH), 8.06 (d, / 8.41, IH), 8.15 (m, IH); MS (ES+) m/z 397, 399 (M+H)+.

Example 6: 2-(3-chlorophenyl)-6-(3-hydroxypropyl)-lH-benzo[cfe]isoquino line-l,3(2H)-dione

Step 1: 2-(3-chlorophenyl)-6-[(lJD-3-hvdroxyprop-l-en-l-yl1-lH-benzo [(Je1isoquinoline-1.3(2H)-dione A solution (0.1 M) of 6-bromo-2-(3-chlorophenyl)-lH-benzo[cfe]isoquinoline-l,3(2H) -dione (prepared as in Example 2) in DMF was treated with prop-2-en-l-ol (10 eq.), palladium acetate (0.05 eq.), triphenylphosphine (0.1 eq.) and silver acetate (1.0 eq.). The reaction mixture was heated at 80°C for 12 h. After cooling down, the reaction mixture was diluted with EtOAc and aqueous HCl (IN) was added. The organic layer was separated and the aqueous layer was extracted with EtOAc. The combined organic layers were dried and evaporated to give a yellow solid as residue that was used as such in the next step; MS (ES+) m/z 364, 366 (M+Η)+.

Step 2: 2-(3-chlorophenyl)-6-(3-hvdroxypropyl)- lH-benzo[<fe1isoquinoline- 1 ,3(2H)-dione A solution (0.1 M) of 2-(3-chlorophenyl)-6-[(l£)-3-hydroxyprop-l-en-l-yl]-lH-benz o[cfe]isoquinoline- l,3(2H)-dione (from step 1) in MeOΗ/EtOAc (1:1) was treated with ZnBr2 (0.2 eq.), 10% Pd on carbon (50% w/w) and stirred under H2 (g) for 12 h. The catalyst was then deactivate by bubbling N2 for 10 min, filtered off and washed with hot MeOH and EtOAc. The solution was evaporated to give a residue that was purified by RP-HPLC (Conditions: Waters Symmetry C 18, 5 micron, 19x300 mm; flow: 20 mL/min; Gradient: A: H2O + 0.1 %TFA; B: MeCN + 0.1% TFA; 60 % A isocratic for 3 min, linear to 10 % A in 23 min, 10 % A isocratic for 2 min) to afford the title compound (6% over two steps) as a solid. 1H NMR (400 MHz, DMSO-d6, 300 K) δ 1.81-1.92 (m, 2H), 3.20-3.35 (m, 2H), 3.49-3.58 (m, 2H), 4.60- 4.70 (m, IH), 7.38-7.44 (m, IH), 7.52-7.62 (m, 3H), 7.77 (d, / 7.5, IH), 7.93 (t, / 7.9, IH), 8.44 (d, / 7.5, IH), 8.52 (d, / 7.2, IH), 8.67 (d, / 8.40, IH); MS (ES+) m/z 366, 368 (M+H)+.

Example 7: 2-(3-chlorophenyl)-6-(lH-pyrazol-3-yl)-lH-benzo[cfe]isoquino line-l,3(2H)-dione A solution (0.1 M) of 6-bromo-2-(3-chlorophenyl)-lH-benzo[cfe]isoquinoline-l,3(2H) -dione (prepared as in Example 2) in DME/EtOΗ (2.6/1) was treated with lH-pyrazol-3-yl boronic acid (1.2 eq.), aqueous Na2CO3 (2M solution) and Pd(PPh3)4 (0.1 eq.). The reaction mixture was heated at 80°C for 2 h. After cooling down, the reaction mixture was acidified with aqueous HCl (IN) and filtered. The precipitate was washed sequentially with water, a small portion Of Et2O and dried to give a residue that was purified by RP-ΗPLC (Conditions: Waters X-TERRA C18, 5 micron, 19x100 mm; flow: 20 mL/min; Gradient: A: H2O + 0.1 %TFA; B: MeCN + 0.1% TFA; 50 % A isocratic for 1 min, linear to 0 % A in 9 min, 0 % A isocratic for 2 min) to afford the title compound (25%) as a solid. 1H NMR (400 MHz, DMSO-d6, 300 K) δ 6.96 (d, /2.2, IH), 7.41-7.50 (m, IH), 7.55-7.65 (m, 3H), 7.97 (dd, /7.5, 8.56, IH), 8.02 (d, /2.2, IH), 8.16 (d, /7.7, IH), 8.54-8.60 (m, 2H), 9.30-9.45 (bs, IH); MS (ES+) m/z 374, 376 (M+H)+.

Example 8: 3-[6-[(benzylamino)carbonyl]-l,3-dioxo-lH-benzo[fife]isoquin olin-2(3H)-yl]hexanoic acid

Step 1: l,3-dioxo-lH,3H-benzo[(Je1isochromene-6-carboxylic acid A solution (0.4 M) of l^-dihydroacenaphthylene-S-carboxylic acid in glacial AcOH was treated with Na2Cr2O7 (4.0 eq.). After the spontaneous exothermic reaction was finished the reaction mixture was heated at reflux for 10 min. The reaction mixture was then cooled down, acidified with aqueous HCl (IN) and the precipitate formed was filtered, washed with water and dried to give the title compound (50%) as a solid; MS (ES+) m/z 243 (M+Η)+.

Step 2: 3-[6-[(benzylamino)carbonyl1-l,3-dioxo-lH-benzo[de1isoquinol in-2(3H)-yllhexanoic acid A solution (0.4 M) of l,3-dioxo-lH,3H-benzo[cfe]isochromene-6-carboxylic acid (from step 1) in CH2Cl2 was treated with DMF (0.05 eq.) and cooled to 00C. Oxalyl chloride (2M solution in CH2Cl2, 2.0 eq.) was added and the reaction mixture was stirred at 0°C for 1 h., then at 25°C for 1 h. The solvent was removed in vacuo and the residue was dissolved in toluene/DMF (1/1). The resulting solution (0.1 M) was treated with benzylamine (0.98 eq.) and a catalytic amount of DMAP. The reaction mixture was stirred at 25°C for 1 h., then at 60°C for 6 h. After cooling down, the reaction mixture was diluted with EtOAc and aqueous HCl (IN) was added. The organic layer was separated and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with brine, dried and evaporated to give a brown solid as residue that was used as such after dilution in EtOH. The resulting solution (0.14 M) was treated with β-norvaline (3.0 eq.). The reaction mixture was heated at 150°C under microwave irradiation for 30 min. After cooling down, the solvent was evaporated and the residue was purified by RP-HPLC (Conditions: Waters X-TERRA C 18, 5 micron, 19x100 mm; flow: 20 mL/min; Gradient: A: H2O + 0.1 %TFA; B: MeCN + 0.1% TFA; 50 % A isocratic for 1 min, linear to 0 % A in 9 min, 0 % A isocratic for 2 min) to afford the title compound (22%) as a solid. 1H NMR (400 MHz, DMSO-d6, 300 K) δ 0.86 (t, / 7.32, 3H), 1.19-1.31 (m, 2H), 1.69-1.81 (m, IH), 2.10- 2.22 (m, IH), 2.90 (dd, / 6.9, 16.0, IH), 3.08 (dd, / 7.7, 16.0, IH), 4.59 (d, / 5.9, 2H), 5.42-5.53 (m, IH), 7.27-7.33 (m, IH), 7.36-7.46 (m, 4H), 7.92 (t, /7.9, IH), 7.97 (d, / 7.5, IH), 8.49-8.57 (m, 2H), 8.59 (d, / 8.4, IH), 9.37 (bt, / 5.94, IH), 12.0-12.4 (bs, IH); MS (ES+) m/z 445 (M+H)+.

Example 9: 6-[(2-hydroxyethyl)amino]-2-[(5-methylisoxazol-3-yl)methyl]- lH- benzo[fife]isoquinoline-l,3(2H)-dione

Step 1: feft-butyl 6-bromo-1.3-dioxo-lH-berizo[<fe]isoquinoline-2(3H)-carbox ylate A solution (0.9 M) of 6-bromo-lH,3H-benzo[cfe]isochromene-l,3-dione in EtOH and ammonia (32% aqueous solution, 1 eq.) were mixed in an Ace tube. The tube was well closed and heated at 80°C for 3 h. After cooling down, a precipitate was formed. The precipitate was isolated by filtration and washed with small portions of EtOH. The resulting solid was dissolved in dioxane. The resulting solution (0.2 M) was treated with BoC2O (1.2 eq.) and catalytic amount of DMAP. The reaction mixture was stirred at RT for Ih. Then, the solvent was evaporated and the residue was diluted with EtOAc and washed with aqueous HCl (IN), NaHCO3 (saturated solution), brine and dried. Evaporation of the solvent afforded the title compound (85%) as pale yellow powder; m/z 276,278 (M+H)+.

Step 2: 6- { [2-(benzyloxy)ethyl]amino| - lH-benzo[<fe1isoquinoline- 1 ,3(2H)-dione A solution (0.5 M) of tert-butyl 6-bromo-l,3-dioxo-lH-benzo[cfe]isoquinoline-2(3H)-carboxylat e (from step 1) and 2-(benzyloxy)ethanamine (3 eq.) in NMP (0.5 M) was heated at 180°C under microwave irradiation for 30 min. Then, the reaction was treated with water and kept at 4°C overnight. The resulting precipitate was isolated by filtration giving the title compound (70%) as a solid; m/z 347 (M+Η)+.

Step 3: 6-[(2-hydroxyethyl)amino]-2-[(5-methylisoxazol-3-yl)methyl]- lH-benzo[<fe]isoquinoline- 1.3f2H)-dione A solution (0.4 M) of 6-{[2-(benzyloxy)ethyl]amino}-lH-benzo[cfe]isoquinoline-l,3( 2H)-dione in DMF was treated with KOΗ (1.1 eq.) and stirred for 30 min at 0°C. Then, 3-(chloromethyl)-5-methylisoxazole (1.2 eq.) was added and the reaction was stirred overnight. The reaction was treated with NH4Cl (saturated solution) and extracted with EtOAc. The recombined organic layers were washed with NH4Cl (saturated solution), water, brine and dried. Evaporation of the solvent afforded a crude that was dissolved in MeOH. 10% Pd on carbon (50% w/w) was added to the resulting solution (0.1 M). The reaction was stirred under H2 for 2 h. at RT. Then, the catalyst was filtered off and washed with EtOAc. After evaporation of the solvent the resulting residue was diluted with MeCN/DMSO (3:1) and purified by RP-HPLC (Conditions: Waters X-TERRA MS C 18, 5 micron, 19 x 100 mm; flow: 20 mL/min; Gradient: A: H2O + 0.1% TFA; B: MeCN + 0.1% TFA; 80% A isocratic for 1 min, linear to 20% A in 9 min, 20% A isocratic for 2 min) affording the title compound (37%) as a solid. 1H NMR (300 MHz, DMSO-d6, 300 K) δ 2.32 (s, 3H), 3.50 (m, 2H), 3.70 (m, 2H), 4.88 (t, / 5.5, IH), 5.21 (s, 2H), 6.85 (d, / 8.6, IH), 7.70 (t, / 8.0, 1 H), 7.80 (m, IH), 7.99 (m, IH), 8.29 (d, / 8.6, IH), 8.46 (d, /7.1, IH), 8.74 (d, / 8.2 ,1H); m/z 353 (M+H)+.

Example 10: d.y^-IP-CS-chloropheny^-l^-dioxo^^-dihydro-lH-benzotfifeliso quinolin-ό- yl]amino}cyclohexanecarboxylic acid

Step 1: methyl cis-4-{[2-(3-chlorophenyl)-l,3-dioxo-2,3-dihydro-lH-benzo[(J e1isoquinolin-6- yl]amino| cyclohexanecarboxylate A solution (0.1 M) of 6-bromo-2-(3-chlorophenyl)-lH-benzo[cfe]isoquinoline-l,3(2H) -dione (prepared as in Example 2), methyl cώ-4-aminocyclohexanecarboxylate hydrochloride (1.2 eq.) and DIPEA (1.5 eq.) in dry and degassed toluene was treated sequentially with BINAP (0.03 eq.), Pd(OAc)2 (0.02 eq.), and NaOf-Bu (1.4 eq.). The reaction was stirred at 80°C for 2 h., then additional amounts of reagents: BINAP (0.06 eq.), Pd(OAc)2 (0.08 eq.), and NaOf-Bu (1.4 eq.) were added. The reaction was stirred for another 3 h. and then diluted with EtOAc and water. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic layers were dried and concentrated to give a residue that was purified by chromatography on silica gel (petroleum ether/EtOAc (7:3) to EtOAc) to afford the title compound (43%) as a solid; MS (ES+) m/z 463, 465 (M+Η)+.

Step 2: cis-4- { [2-(3-chlorophenvD- 1 ,3-dioxo-2,3-dihydro- lH-benzo[<fe1isoquinolin-6- yl]amino| cyclohexanecarboxylic acid A solution (0.075 M) of methyl ri.y-4-{[2-(3-chlorophenyl)-l,3-dioxo-2,3-dihydro-lH- beiizo[de]isoquinolin-6-yl]amino} cyclohexanecarboxylate in MeOH was treated with NaOH (2M aqueous solution, 2 eq.). The reaction mixture was heated at 60°C for 8 h. Then the solvent was evaporated under reduced pressure and the residue was taken up with EtOAc and aqueous HCl (IN) was added. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic layers were dried and concentrated. The residue was purified by RP-ΗPLC (Conditions: Waters Symmetry Prep C18, 7 micron, 19 x 300 mm; flow: 15 mL/min; Gradient: A: H2O + 0.1% TFA; B: MeCN + 0.1% TFA; 90% A to 0% A linear in 15 min) to afford the title compound (47%) as a solid. 1H NMR (400 MHz, DMSO-d6, 300 K) δ 1.69 (m, 4H), 1.87 (m, 2H), 2.10 (m, 2H), 2.59 (m, IH), 3.75 (m, IH), 6.89 (d, / 8.8, IH), 7.32 (m, IH), 7.40 (d, / 6.6, IH), 7.51 (m, 3H), 7.68 (t, /7.8, IH), 8.24 (d, / 8.5, IH), 8.42 (dd, /7.2, IH), 8.85 (d, / 8.5, IH); MS (ES+) m/z 449, 451 (M+H)+.

The following table shows additional examples which were prepared using procedures analogous to the general methods or specific examples described above, or which are commercially available, as indicated in the final column.

Table 1

Table 2

Sources of commercially available compounds: comm1: Asinex (Russia); comm2: Interchim Intermediates (France); comm3: Maybridge (UK); comm4: Labotest (Germany) ; comm5 : Chembridge (San Diego, USA).