MXPA04010617A

MXPA04010617A - Inhibitors of checkpoint kinases (wee1 and chk1).

Info

Publication number: MXPA04010617A
Application number: MXPA04010617A
Authority: MX
Inventors: Lorna Helen Mitchell
Original assignee: Warner Lambert Co
Priority date: 2002-04-26
Filing date: 2003-04-15
Publication date: 2004-12-13
Also published as: BR0309783A; JP2006504632A; EP1501831A1; WO2003091255A1; CA2483496A1; AU2003224341A1

Abstract

This invention relates to pyrrolocarbazole derivatives according formula (I) wherein R1, R2, r7, R8 R9, X and Y are as defined in the specification wherein said derivatives specifically inhibit one or both of the checkpoint kinases Wee1 and Chk1.

Description

KINASE INHIBITORS OF CONTROL POINTS (Wee1 and Chk1) FIELD OF THE INVENTION This invention relates to small chemical molecules that specifically inhibit one or both of the checkpoint kinases Wee1 and Chk1.

BACKGROUND OF THE INVENTION The proper organization of the steps required for the orderly progression of the cell through the cell cycle requires several signaling pathways within the cells. Many of these routes use protein kinases to perform the transmission of crucial signals at the appropriate time and in the intracellular location. The kinases of the cell cycle are enzymes, natural implied in the regulation of the cell cycle that is generally divided into four segments: Gi (gap 1 (resting phase 1)), S (DNA synthesis), G2 (gap 2 (phase of rest 2)) and M (mitosis). Some of these kinases are responsible for inhibiting the normal progression of cells through cell division, while others are normally active in promoting the progression of cells through the cell cycle producing cell division. It has been shown that increased activity or temporarily abnormal activation of these kinases causes the development of tumors and other proliferative disorders. One of the protein kinases involved is a tyrosine-specific kinase, Wee1, which has as substrate another complex with kinase activity called Cdc2 / cyclinB. Wee1 kinase is a regulatory kinase that has Cdc2 / cyclinB as substrate and when Wee1 is active, it phosphorylates a specific tyrosine (Tyr15) in Cdc2 that causes inactivation of the Cdc2 / cyclinB complex, which in turn results in a pause or control point in the cell cycle in the transition between G2 and M. The kinase activity of Cdc2 / cyclinB is absolutely required for cells to progress through the G2 phase of the cell division cycle to the M (or mitotic) phase, where two daughter cells are formed by the division of the mother cell. Under normal circumstances, when the cells progress through the cell cycle, the Cdc2 / cyclinB complex is assembled in the last part of the S phase and along G2. Normally, Wee1 is active and thus phosphorylates the Cdc2 / cyclinB complex until the end of G2, at which time all the necessary components for the entry of cells into the M phase have been synthesized. Weei, a phosphotase removes the inhibitory phosphorylation of Tyr15 from Cd2 / cyclinB, the complex is reactivated and the cells enter the M phase, where the replicated DNA divides and the daughter cells are formed. The inhibition of Wee1 results in the absence of the inhibitory phosphorylation of Tyr15 on Cdc2 / c1clAnaB and the potentially inappropriate and premature entry of the cell into mitosis. In addition to regulating the transition of cells between the different phases of the cell cycle under normal conditions, cell cycle transitions are regulated in response to DNA damage, providing opportunities allegedly for cells to repair potentially genotoxic DNA lesions before replication using a damaged DNA template or to permanently exit the cell cycle and die. Another kinase of interest called Chk1 participates in this signaling pathway dependent on DNA lesions by phosphorylation of a phosphatase called Cdc25C which when activated by itself and colocalized with Cdc2 / cyclinB in the nucleus, dephosphorylates Tyr15 and causes the activation of the Cdc2 / cyclinB complex. The phosphorylation of Cdc25C mediated by Chk1 causes Cdc2C to be exported from the nucleus, where it can no longer dephosphorylate and thus activate the Cdc2 / cyclinB complex. Therefore, if Chk1_ is active (in response to lesions in the -DNA) it will indirectly contribute to the inactivation of Cdc2 / cyclinB (whose activity is required for progression to the M phase) by means of the preservation of the inactivating phosphorylation of Tyr15 on Cdc2 / cyclinB. Conversely, inhibition of Chk1 would result in the dephosphorylation of Cdc2 / cyclinB by the Cdc25C phosphatase in the nucleus (which has not been exported to the cytoplasm since it has not been phosphorylated by Chk1) and the subsequent activation of Cd2 / cyclinB with the associated entry of cells into mitosis.

Inhibition of Wee1 or Chk1 or the two kinases in the presence of DNA damaged by conventional DNA-directed chemotherapeutic agents or by radiation presents an opportunity to use cellular regulatory pathways to cause cells to progress to M-phase inappropriately and inappropriately. . Such cells may be less likely to survive and to divide further, since the dedication to the M phase was performed in the presence of the damaged DNA in a potentially catastrophic manner (Alan J. Kraker and Robert N. Booher, "New Cell Cycle Targets" , Ann. Rep. Med. Chem., 1999; 34: 247-256). Small molecule inhibitors of the Wee1 kinase, WO 0119825 and Cancer Res. (2001), 61 (22), 821 1 8217, have been published. Small molecule inhibitors of the Chk1 kinase have also been reported in W00016781, Cancer Res. (2000), 60 (3), 566572. It is known that certain pyrrolocarbazole derivatives have inhibitory activity of Protein kinase .c and. antitumor activity (U.S. Patent No. 4,912,107), but in comparison to the compounds of the present invention, the compounds described in U.S. Patent No. 4,912,107 have very little activity of knockout kinases. It is also known that certain pyrrolocarbazole derivatives stimulate the production of platelets (document W096128447) and promote thrombopoiesis (document W09809967). EP 0695755 discloses another pyrrolocarbazole derivative having activity on Protein kinase c. U.S. Patent No. 5,166,204 discloses anti-tumor isoindol derivatives having a bond or a lower alkylene group attached to positions 2 and 3 or 3 and 4 of the carbazole backbone. U.S. Patent No. 5,728,709 discloses pyrrolocarbazole derivatives that stimulate platelet production. WO 01 185686 also describes pyrrolocarbazole derivatives. However, there are no reports that any type of pyrrolocarbazole inhibits Wee1 kinase or Chk1 kinase. There have also been no reports that any type of pyrrolocarbazole inhibits both Wee1 kinase and Chk1 kinase.

BRIEF DESCRIPTION OF THE INVENTION The claimed compounds are of the general structure described by Formula 1 wherein each dashed line represents an optional link; R1 is hydrogen, halogen, C8 alkyl, NR5R6 or an aryl or heteroaryl ring optionally substituted with up to five substituents selected from halogen, alkyl, haloalkyl, hydroxyl, nitro, cyano, C (0) R3, OR3, S (0) mR3 , NR3R4, OC (0) R3, NR3 (CO) OR4, CH2NR3R4, CH2OR3, COOR3, CONR3R4, NR3COR4, S02NR R4, CONHS02R3, NR3S (0) mR4, NHCONR3R4, NR3CONHR4; or a cycloalkyl or cycloalkenyl ring optionally substituted with up to five substituents selected from halogen, alkyl, haloalkyl, hydroxyl, nitro, cyano, C (0) R3, OR3, S (0) mR3, NR3R4, OC (0) R3, NR3 ( CO) OR4, CH2NR3R4, CH2OR3, COOR3, CONR3R4, NR3COR4, S02NR3R4, CONHS02R3, NR3S (0) mR4, NHCONR3R4, NR3CONHR4; or a heterocyclic ring optionally substituted with up to five substituents selected from halogen, alkyl, haloalkyl, hydroxyl, nitro, cyano, C (0) R3, OR3, S (0) mR3, NR3R4, OC (0) R3, NR3 (CO) OR4, CH2NR3R4, CH20R3, COOR3, CONR3R4, NR3COR4, S02NR3R4, CONHS02R3, NR3S (0) mR4, NHCONR3R4, NR3CONHR4; . . _ ._ m is 0-2; X is hydrogen or halogen; Y1 is O, S (0) m or NR10, R9 is hydrogen, hydroxyl, halogen, NR3C (0) R4, NHCONR3R4, (C = NR3) NHR4, NH (C = NR3) NHR4, NH (C = NH) NR3R4, NH (C = 0) OR3, NR5R6, (CR5R6) r-Z; r is 0-6; R2, R7, R8 and R10 in each case are independently selected from ((CR5R6) nT) to (C11R12) b) -Z, where the sum of n, a and b is in each case less than 10; T may be absent or, when present, in each case 3 is independently selected from O, CONR3, CONHS02, S (0) m, NR3, NR30, OS (0) m, S (0) mO, NR3S (0 >2 or S (0) 2NR3; n is independently in each case 0-6, a is independently in each case 0-6; b is independently in each case 0-6; Z is selected from hydrogen, halogen, alkyl, haloalkyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, heteroaryl, cyano, nitro, hydroxy, C (0) R3, CONHS02R3, OR3, S (0) mR3, OS02R3, NR3R4, C02R3, CONR3R4, NR3COR4, S02NR3R4, OPO (OR3) (OR4), CH = CR3R4, CCR3, (C = NR3) NHR4, NH (C = NR3) NHR4, NH (C = NH) NR3R4, where the alkyl group, cycloalkyl, cycloalkenyl, heterocyclyl, aryl or heteroaryl may be substituted with up to four groups independently selected from halogen, alkyl, hydroxyl, nitro, cyano, OR3, S (O) mR3, NR3R4, OC (O) R3, NR3 (CO) OR4 , C (O) R3, COOR3, CONR3R4, NR3COR4, S02NR3R4, CONHS02R3, NR3S (0) mR4, CH2NR3R4, CH2OR3, NHCONR3R4, NR3CONHR4; R5, R6, R11 and R12 are independently selected in each case from hydrogen, hydroxyl, alkyl, haloalkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, halogen, cyano, nitro, CH2NR3R4, CH2OR3, C (0) R3, OR3, S (0) mR3, NR3R4, COOR3, CONR3R4, S02NR3R4, NHCONR3R4, NR3CONHR4; wherein the alkyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl or heteroaryl group may be substituted with up to four groups independently selected from halogen, alkyl, hydroxyl, nitro, cyano, OR3, S (0) mR3, NR3R4, OC (0) R3, NR3 (CO) OR4, C (0) R3, COOR3, CONR3R4, NR3COR4, S02NR3R4, CONHS02R3, NR3S (0) mR4, NHCONR3R4, NR3CONHR4; R5 and R6 or R1 and R12 together with the carbon atom to which they are attached can form a carbonyl group; or together with the carbon or heteroatom to which they are attached can form a cycloalkyl or heterocyclyl group, wherein said carbonyl, cycloalkyl or heterocyclyl group can be substituted with up to four groups independently selected from halogen, hydroxyl, nitro, cyano, alkyl, haloalkyl, halogen , alkyl, nitro, cyano, OR3, S (0) mR3, NR3R4, OC (0) R3, NR3 (CO) OR4, C (0) R3, COOR3, CONR3R \ NR3COR4, S02NR3R4, ONHS02R3, NR3S (0) mR4 , NHCONR3R4, NR3CONHR4; R3 and R4 are independently selected from hydrogen, alkyl, haloalkyl or a substituted or unsubstituted carbocyclic group selected from cycloalkyl, cycloalkenyl, heterocyclyl, aryl and heteroaryl, wherein said alkyl, or a substituted carbocyclic group may be substituted with up to 4 groups selected from halogen, hydroxyl, nitro, cyano, alkyl, haloalkyl, alkyloxy, carboxy, COOH, CONH2 > NHCOCH3, N (CH3) 2, NHCH3, thiomethyl, thioethyl, SOCH3, S02CH3; R3 and R4 together with the carbon atom or heteroatom to which they are attached can form a cycloalkyl or heterocyclyl group with up to four groups independently selected from halogen, hydroxyl, nitro, cyano, alkyl, haloalkyl, alkyloxy, formyl, carboxy, acetyl, CH2NH2 , CH2OH, COOH, CONH2, NHCOCH3, N (CH3) 2, thiomethyl, thioethyl, SOCH3, SO2CH3, alkoxycarbonyl, alkylcarbonyl, alkynylamino, aminoalkyl, aminoalkylcarbonyl, amino, mono- or dialkylamino, or R3 and R4 together with the nitrogen to which they are joined can form a heterocyclic ring containing 3-8 members, up to four of which are optionally carbonyl groups or heteroatoms independently selected from oxygen, sulfur, S (O), S (0) 2 and nitrogen, where the carbocyclic group is unsubstituted or substituted with up to four groups independently selected from halogen, hydroxy, hydroxyalkyl, alkyl,. haloalkyl, alkoxy, alkoxycarbonyl, -alkylcarbonyl, alkynylamino, aminoalkyl, aminoalkylcarbonyl, amino, mono- or dialkylamino. Unless the context clearly requires otherwise, throughout the description and claims, the words "comprises", "comprising" and the like are constructed in an inclusive sense against an exclusive or exhaustive sense; that is, in the sense of "including, but without limitation".

BRIEF DESCRIPTION OF THE FIGURES Figure 1 depicts a Western blot of tumor cells treated in vivo with ciplastin and Compound of Example 80. Figure 2 depicts a Western blot of cells treated in vitro with Adriamycin and the Compound of Example 80. Figure 3 represents a Western blotting of tumor cells treated in vivo with cpt-1 1 and Compound of Example 362. Figure 4 depicts a graph of the increase in lifespan in animals treated with the Compound of Example 80.

DETAILED DESCRIPTION OF THE INVENTION The compounds of the present invention are of the general structure described by Formula 1 wherein each dashed line represents an optional link; R1 is hydrogen, halogen, C ^ cs alkyl, NR5R6 or an aryl or heteroaryl ring optionally substituted with up to five substituents selected from halogen, alkyl, haloalkyl, hydroxyl, nitro, cyano, C (0) R3, OR3, S (0) mR3, NR3R4, OC (0) R3, NR3 (CO) OR4, CH2NR3R4, CH2OR3, COOR3, CONR3R4, NR3COR4, S02NR3R4, CONHS02R3, NR S (0) mR4, NHCONR3R4, NR3CONHR4, or a cycloalkyl or cycloalkenyl ring optionally substituted with up to five substituents selected from the group consisting of halogen, alkyl, haloalkyl, hydroxyl, nitro, cyano, C (0) R3, OR3, S (0) mR3, NR3R4, OC (0) R3, NR3 (CO) OR3, CH2NR3R4 , CH2OR3, COOR3, CONR3R4, NR3COR4, S02NR3R4, CONHS02R3, NR3S (0) mR4, NHCONR3R4, NR3C0NHR4; or a heterocyclic ring optionally substituted with up to five substituents selected from halogen, alkyl, haloalkyl, hydroxyl, nitro, cyano, C (0) R3, OR3, S (0) mR3, NR3R4, OC (0) R3, NR3 (C0) 0R4, CH2NR3R4, CH20R3, COOR3, C0NR3R4, NR3COR4, S02NR3R4, C0NHS02R3, NR3S (0) mR4, NHC0NR3R4, NR3C0NHR4; . . . . . .. m is 0-2; X is hydrogen or halogen; Y1 is O, S (0) m or NR10; R9 is hydrogen, hydroxyl, halogen, NR3C (0) R4, NHCONR3R4, (C = NR3) NHR4, NH (C = NR3) NHR4, NH (C = NH) NR3R4, NH (C = 0) OR3, NR5R6, (CR5R6) r-Z; r is 0-6; R2, R7, R8 and R10 in each case are independently selected from ((CR5 R6) nT) to (CR1 R12) b) -Z, where the sum of n, a and b is in each case less than 10; T may be absent or, when present, in each case it is independently selected from O, CONR3, CONHS02, S (0) m, NR3, NR3-0, 0-S (0) m, S (0) m-0 , NR3-S (0) 2 or S (0) 2-NR3; n is independently in each case 0-6; a is independently in each case 0-6; b is independently in each case 0-6; Z is selected from hydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, heteroaryl, cyano, nitro, hydroxy, C (0) R3, CONHSO2R3, OR3, S (0) mR3, OS02R3, NR3R4, C02R3, CONR3R4, NR3COR4, S02NR3R4, OPO (OR3) (OR4), CH = CR3R4, CCR3, (C = NR3) NHR4, NH (C = NR3) NHR4, NH (C = NH) NR3R4, where the alkyl, cycloalkyl, cycloalkenyl group, heterocyclyl, aryl or heteroaryl may be substituted with up to four groups- selected, independently from halogen, -alkyl, hydroxyl, nitro, cyano, OR3, S (O) mR3, NR3R4, OC (O) R3, NR3 (CO) OR4, C (0) R3, COOR3, CONR3R4, NR3COR4, S02NR3R4, CONHSO2R3, NR3S (O) mR4, CH2NR3R2, CH2OR3, NHCONR3R4, NR3CONHR4; R5, R6, R11 and R12 are independently selected in each case from hydrogen, hydroxyl, alkyl, haloalkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, halogen, cyano, nitro, CH2NR3R4, CH2OR3, C (0) R3, OR3, S (0) mR3, NR3R4, COOR3, CONR3R4, S02NR3R4, NHCONR3R4, NR3CONHR4; wherein the alkyl, cycloalkio, cycloalkenyl, heterocyclyl, aryl or heteroaryl group can be substituted with up to four groups independently selected from halogen, alkyl, hydroxyl, nitro, cyano, OR3, S (O) mR3, NR3R4, OC (O) R3, NR3 (CO) OR4, C (0) R3, COOR3, CONR3R4, NR3COR4, SO2NR3R4, CONHSO2R3, NR3S (O) mR4, NHCONR3R4, NR3CONHR4; R5 and R6 or R11 and R12 together with the carbon atom to which they are attached can form a carbonyl group; or together with the carbon or heteroatom to which they are attached can form a cycloalkyl or heterocyclyl group, wherein said carbonyl, cycloalkyl or heterocyclyl group can be substituted with up to four groups independently selected from halogen, hydroxyl, nitro, cyano, alkyl, haloalkyl, halogen , alkyl, nitro, cyano, OR3, S (O) mR3, NR3R4, OC (O) R3, NR3 (CO) OR4, C (O) R3, COOR3, CONR3R4, NR3COR4 ,. SO2NR3R4, CONHSO2R3, NR3S (O) mR4, CH2NR3R4, -CH2OR3NHCONR3R4, NR3CONHR4; R3 and R4 are independently selected from hydrogen, alkyl, haloalkyl or a substituted or unsubstituted carbocyclic group selected from cycloalkio, cycloalkenyl, heterocyclyl, aryl and heteroaryl, wherein said alkyl, or a substituted carbocyclic group may be substituted with up to 4 groups selected from halogen, hydroxyl, nitro, cyano, alkyl, haloalkyl, alkyloxy, carboxy, COOH, CONH2, NHCOCH3, N (CH3) 2, NHCH3, thiomethyl, thioethyl, SOCH3, S02CH3; R3 and R4 together with the carbon atom or heteroatom to which they are attached can form a cycloalkyl or heterocyclyl group with up to four groups independently selected from halogen, hydroxyl, nitro, cyano, alkyl, haloalkyl, alkyloxy, formyl, carboxy, acetyl, CH2NH2 , CH2OH, COOH, CONH2, NHCOCH3, N (CH3) 2, thiomethyl, thioethyl, SOCH3, S02CH3, alkoxycarbonyl, alkylcarbonyl, alkynylamino, aminoalkyl, aminoalkylcarbonyl, amino, mono- or dialkylamino, or R3 and R4 together with the nitrogen to which they are joined can form a heterocyclic ring containing 3-8 members, up to four of which are optionally carbonyl groups or heteroatoms independently selected from oxygen, sulfur, S (O), S (0) 2 and nitrogen, where the carbocyclic group is unsubstituted or substituted with up to four groups independently selected from halogen, hydroxy, hydroxyalkyl, alkyl, haloalkyl,. alkoxy, alkoxycarbonyl, alkylcarbonyl, alkynylamino, -aminoalkyl, aminoalkylcarbonyl, amino, mono- or dialkylamino. In a preferred embodiment of the invention the compound of Formula I is selected from the group consisting of: 4- (2-chlorophenyl) -6- (3-hydroxypropyl) -9-methoxypyrrolo [3,4-c] carbazole-1, 3- (2H, 61 -1) -dione; 4- (5-Amino-2-methoxyphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 9-Hydroxy-4- (2-hydroxyphenyl) -6- (3-hydroxypropyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chloro-6-methoxyphenyl) -9-hydroxy-6- [2- (4-morpholin) ethyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 6-Benzyl-4- (2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 9-Hydroxy-6- (3-hydroxypropyl) -4-phenylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 9-Hydroxy-6- (6-hydroxyethyl) -4-phenylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 9-Hydroxy-6-methyl-4-phenylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (5-Amino-2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; Acid 3-. { [3- (4- (2-chlorophenyl-9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1 H) -yl] propyl] amino] benzoic acid; Acid-. - - - 2- { [3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 ( 1 H) -yl] propyl] amino] benzoic acid 4- { [3- (4- (2-chlorophenyl-9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] ] carbazole-6 (1 H) -yl] propyl] amino] benzoic acid 4- (2-chlorophenyl) -6-. {3 - [(cis) -3,5-dimethyl-piperazinyl] propyl} -9- hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2,6-Dichlorophenyl) -6-. {3 - [(cis) -3,5-dimethylpiperazinyl]] propyl.}. -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 6- (2-aminoethyl) -9-hydroxy-4-phenylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 9-hydroxy-6- [2- (methylamino) ethyl] -4-phenylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 6- (3-aminopropyl) -9-hydroxy-4-phenylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 9-hydroxy-4-phenyl-6- [3- (1-pyrrolidinyl) propyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 6- [3- (diethylamino) propyl] -9-hydroxy-4-phenylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 9-hydroxy-4-phenyl-6- [3- (1-piperidinyl) propyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione, 9-hydroxy-6- [3 - (4-methyl-1-piperazinyl) propyl] -4-phenylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 6- [6- (dimethylamino) hexyl] -9-hydroxy-4-phenylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; . . - -. . 9-hydroxy-6- [6- (4-methyl-1-piperazinyl) hexyl] -4-phenylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 6- (2-aminoethyl) -4- (2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazol-1, 3- (2H.6H) -dione; 4- (2-chlorophenyl) -9-hydroxy-6- [3- (dimethylamino) ethyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenol) -9-hydroxy-6- [2- (1 H-imidazol-1-yl) etl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -done; 4- (2-chlorophenyl) -9-hydroxy-6- [2- (4-morpholinyl) ethyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -9-hydroxy-6- [2- (4-methyl-1-piperazinyl) ethyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -diona; 6- (2-anilinoethyl) -4- (2-chlorophenol) -9-hydroxy-pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2,6-dichlorophenyl) -9-hydroxy-6- [3- (dimethylamine) etl] pyrrolo [3,4-c] carbazole-1, 3- ( 2H, 6H) -dione; 4- (2,6-dichlorophenol) -9-hydroxy-6- [2- (4-morpholinyl) ethyl] pyrrolo [3,4-c] carbazole-, 3- (2H, 6H) -dione; 4- (2,6-dichlorophenyl) -9-hydroxy-6- [2- (4-methyl-1-piperazinyl) ethyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) - diona; 6- (2-anilinoetheyl) -4- (2,6-dichlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; . .. .. .. 4- (2-chlorophenol) -9-hydroxy-6- [3- (methylamino) propyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H )-Mrs; 4- (2-chlorophenyl) -6- [3- (dimethyllamido) propyl] -9-hydroxypyrrolo [3,4-c] carbazol-1, 3- (2H, 6H) -dione; 4- (2-chlorophenol) -9-hydroxy-6- [3- (4-morpholinyl) propyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenol) -9-hydroxy-16- [3- (4-methyl-1-piperazinyl) propyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 6- (3-aninlinopropyl) -4- (2-chlorophenol) -9-hydroxypropyl [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2,6-dichlorophenol) -9-hydroxy-6- [3- (methylamino) propyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2,6-dichlorophenyl) -6- [3- (dimethylamine) propyl] -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -diona; 4- (2,6-dichlorophenyl) -9-hydroxy-6- [3- (1 H -amidazol-1-yl) propyl] pyrrolo [3,4-c] carbazole-1 , 3- (2H, 6H) -dione; 4- (2,6-dichlorophenol) -9-hydroxy-6- [3- (4-morpholinyl) propyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) - diona; 4- (2,6-dichlorophenyl) -9-hydroxy-6- [3- (4-methyl-1-piperazinyl) propyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H ) -diona; 6- (3-anilinopropyl) -4- (2,6-dichlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; . -. . - · .. 9-Hydroxy-6- [3- (4-morpholinyl) propyl] -4-phenypyrrolo [3,4-c] carbazl-1, 3- (2H, 6H) -dione; 9-Hydroxy-6- [2- (4-morpholinyl) etl] -4-phenylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 9-Hydroxy-6- [3- (1 H -imidazol-1-yl) propyl] -4-phenylfrolo [3,4-c] carbazole-1, 3- (2H, 6H) -diona; 9-Hydroxy-6- [2- (1 H -imidazol-1-yl) propyl] -4-phenylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 9-Hydroxy-6- [3- (methylamino) propyl] -4-phenylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 9-Hydroxy-4-phenyl-6- [3- (1-p-piperazinyl) propyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 6- [3- (Benzylamino) propyl] -9-hydroxy-4-phenylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 6- (3-Anilnopropyl) -9-hydroxy-4-phenylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chloro-6-methoxyphenyl) -6-. { 3- [cis-3,5-dimethyl-piperazinyl] propyl} -9-hydroxy-pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -9-hydroxy-6- [2- (phenylsulfanyl) et!] Pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazQl-6 (1 H) -l) -N- [ 2- (diethylamine) ethyl] -N-methylpropanamide; . 3- (4- (2-chlorophenol) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) -N - (2,2,6,6-tetramethyl-4-piperidinyl) propanamide (XIII; Ar = 2-chlorophenyl, n = 2, R 3 = H; R 4 = 2,2,6,6- tetramethyl-4-p-pentydinyl); 4- (2-chlorophenyl) -6-. { 3- [cis-3,5-dimethylpiperazinyl] -3-oxopropyl} -9-methoxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -l) -N- [2- (1 H-imidazol-5-yl) ethyl] propanamide (XIII; Ar = 2-chlorophenyl, n = 2, R 3 = H, R 4 = (1 H-imidazol-5-yl) etllo); 3- (4- (2,6-Dichlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) propanoic acid; N- [2- (Dimethylamino) ethyl] -3- (9-hydroxy-1,3-dioxo-4-phenyl-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) propanamide; N- [2- (Dimethylamino) ethyl] -3- (9-hydroxy-4- (2-methoxyphenyl) -1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H ) -yl) propanamide; 3,9-dihydroxy-4-phenyl-3,6-dihydropyrrolo [3,4-c] carbazole-1 (2H) -one; 4- (2-chlorophenyl) -1,9-dihydroxy-6- (3-hydroxypropyl) -1,6-dihydropyrrolo [3,4-c] carbazol-3 (2H) -one; 4- (2-chlorophenyl) -3,9-dihydroxy-6- (3-hydroxypropyl) -3,6-dihydropyrrolo [3,4-c] carbazol-3 (2H) -one; 4- (2-chlorophenyl) -9-hydroxy-6- (3-hydroxypropyl) -4,5,6,10c-tetrahydropyrrolo [3,4-c] carbazole-1, 3- (2H, 3aH) -dione; 8-Hydroxy-4-phenylcyclopenta [c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -8-hydroxy-6-methylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -6- [3- (cis-3,5-dimethyl-1-piperazinyl) -2-hydroxypropyl] -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -6- [3- (dimethylamino) -2-hydroxypropyl] -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -9-hydroxy-6-propylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -9-hydroxy-6-pentylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 6-Allyl-4- (2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -9-hydroxy-6- (2-phenylethyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -9-hydroxy-6- (2-propynyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -9-hydroxy-6-isopentyl-pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -9-hydroxy-6- (2,2,2-tnfluoroethyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -9-hydroxy-6- (4-pentenyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; . . . 2- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl-acetamide; Butenyl) -4- (2-chlorophenyl) -9- idroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -9-hydroxy-6-isobutylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenol) -9-hydroxy-6- (4,4,4-trifluorobutyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -done; 6-Sec-butyl-4- (2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -6-cyclopentyl-9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -8- [4- (dimethyl) butyl] -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -9-hydroxy-8- [4- (1-pyrrolidinyl) butyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) - diona; 4- (2-chlorophenyl) -9-hydroxy-6,8-bis (2-hydroxyethyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -9-hydroxy-6- (2-hydroxyethyl) -8- [3- (4-morpholinyl) propoxy] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H )-Mrs; 9-Hydroxy-8- (3-hydroxypropyl) -6-methyl-4-phenylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; . 8-Ethyl-9-hydroxy-6-methyl-4-phenylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 8- (2,3-D-Hydroxypropyl) -9-hydroxy-6-methyl-4-phenypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -d Ona; 4- (2-chlorophenyl) -8-ethyl-9-hydroxy-6-methylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 9-Hydroxy-8- (2-hydroxyethyl) -6-methyl-4-phenylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -9-hydroxy-8- (2-hydroxyethyl) -6-methylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 8- [3- (Dimethylamino) propyl] -9-hydroxy-6-methyl-4-phenylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 8- [2- (Dimethylamino) ethyl] -9-hydroxy-6-methyl-4-phenylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 9-Hydroxy-5-methyl-4-phenylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 9-Hydroxy-4,5-diphenyl-pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -8- (3-hydroxypropoxy) -9-methoxy-6-methylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -8- [3- (dimethylamino) propoxy] -9-methoxy-6-methylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -8- [3- (dimethylamino) propoxy] -9-hydroxy-6-methylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -done; - - - - 8- [3- (Dimethylamino) propoxy] -9-hydroxy-6-methyl-4-phenylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) - diona; 4- (2-chlorophenyl) -9-hydroxy-6-methyl-8- [3- (4-morpholinyl) propoxy] pyrrolo [3,4c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -9-hydroxy-6-methyl-8- [3- (1-pyrrolidinyl) propoxy] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -8- (2-hydroxyethyl) -6-methylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -8- (1, 2-dihydroxyethyl) -6-methylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -8- (hydroxymethyl) -6-methylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -8- (3-hydroxypropoxy) -6-methylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -8- [3- (dimethylamino) propoxy] -6-methylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -6-methyl-8- [3- (methylamino) propoxy] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -8- [3- (cs-3,5-d-methyl-1-piperazinyl) propoxy] -6-methylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -8- (2-hydroxyethoxy) -6-methylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; - - - ·. 4- (2-chlorophenyl) -8- (2,3-dihydroxypropoxy) -6-methylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 9-Hydroxy-4- (2-methoxyphenyl) -6- [2- (4-morpholinyl) ethyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 1,3-Dioxo-4-phenyl-1, 2,3,6-tetrahydropyrrolo [3,4c] carbazol-9-yl dihydrogen phosphate; 4- (2-chlorophenyl) -8- (3-dimethyl-propoxy) -9-hydroxy-6- (3-hydroxypropyl) 6H-pyrrolo [3,4-c] ] carbazole-1,3-dione; 6- (3-Bromo-propyl) -4- (2-chlorophenyl) -8- (3-dimethylamino-propoxy) -9-hydroxy-6H-pyrrolo [3,4-c] carbazole-1, 3- diona; 4- (2-chlorophenyl) -8- (4-dimethylamino-3-hydroxy-butoxy) -6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-chlorophenyl) -8-hydroxy-6- (3-hydroxy-propyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-chlorophenol) -8- (4-dimethylamino-butyl) -6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-chlorophenyl) -6-methyl-8- (4-pyrrolidin-1-N-butyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-chlorophenyl) -6-methyl-8- (4-methylamino-butyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-chlorophenyl) -9-hydroxy-6- (3-hydroxy-propyl) -8- (3-pyrrolidin-1-H-propoxy) -6H-pyrrolo [3,4; C] carbazole- 1,3-dione; . .. .... 4- (2-chlorophenyl) -9-hydroxy-8- (4-hydroxy-butyl) -6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 8-. { 3- [Bis- (2-hydroxyethyl) -amino] -propoxy} -4- (2-chlorophenyl) -9-hydroxy-6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-chloro-phenyl) -9-hydroxy-6- (3-hydroxy-propyl) -8- [3- (4-methyl-piperazin-1-yl) -propoxy] -6H-pyrrolo [3, 4-c] carbazole-1,3-dione; 9-Amino-4- (2-chloro-phenyl) -6- (3-hydroxy-propyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione, 3- [4-acid] - (2-Chloro-phenyl) -9-nitro-1,3-dioxo-2,3-dihydro-1 H-pyroolo [3,4-c] carbazol-6-yl] -propionic acid; 4- (2-chloro-phenyl) -9-hydroxyl-8- (4-hydroxy-butoxy) -6-methyl-6H-pyrrolo [3,4-c] carbazole-1, 3 -diona; 4- (2-chloro-phenyl) -6- (3-hydroxy-propyl) -8-methoxy-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-chloro-phenyl) -9-fluoro-8-methoxy-6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-chloro-phenyl) -9-fluoro-8-hydroxy-6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-chloro-phenyl) -8- (3-dimethylamino-propoxy) -6- (3-hydroxy-propyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-chloro-phenyl) -6- (3-hydroxy-propyl) -8- (3-pyrrolidin-1H-propoxy) -6H.-pyrrolo [3,4-c] carbazok1, 3-dione; 4- (2-chloro-phenyl) -9-fluoro-8- (3-hydroxy-propoxy) -6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-chloro-phenyl) -9-fIuoro-6-methyl-8- (3-methylamino-propoxy) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-chloro-phenyl) -9-hydroxy-6-methyl-8- (4-morpholin-4-yl-butyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-chloro-phenyl) -9-fluoro-6-methyl-8- (3-pyrrolidin-1H-propoxy) -6H-pyrrolo [3,4-c] carbazole-1, 3- diona; 4- (2-chloro-phenyl) -9-hydroxy-6- (2-hydroxy-ethyl) -8- [3- (4-methyl-piperazin-1-yl) propoxy] -6H-pyrrolo [3,4 -c] carbazole-1,3-dione; 4- (2-chloro-phenyl) -8- (3-diethylamino-propoxy) -9-hydroxy-6- (2-hydroxy-ethyl) -6H-pyrrolo [3,4-c] carbazole-1, 3- diona; 4- (2-chloro-phenyl) -8- (3-dimethylamino-propoxy) -9-fluoro-6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; N- [4- (2-chloro-phenyl) -6- (3-hydroxy-propyl) -1, 3-dioxo-1, 2,6-tetrahydropyrrolo [3,4-c] carbazol-9-yl] - formamide; 4- (2-chloro-phenyl) -9-hydroxy-6- (3-hydroxy-propyl) -8-piperidin-4-yl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-chloro-phenyl) -6-methyl-8-piperidin-4-yl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 7- (2-Amino-1-h idroxy-ethyl) -4- (2-chlorophen-yl) -9-h idroxy-6-oxa-2-aza-cyclopenta [c] fluorene-1,3-dione; 4- (2-chloro-phenyl) -9-hydroxy-7- (1-hydroxy-2-methylamino-ethyl) -6-oxa-2-aza-cyclopenta [c] fluorene-1,3-dione; 4- (2-chloro-phenyl) -9-hydroxy-7- (1-hydroxy-2-piperazin-1-yl-ethyl) -6-oxa-2-aza-cyclopenta [c] fluorene-1, 3- diona; 4- (2-chloro-phenyl) -9-hydroxy-7- (1-hydroxy-2-morpholin-4-yl-ethyl) -6-oxa-2-aza-cyclopenta [c] fluorene-1, 3- diona; 4- (2-chloro-phenyl) -9-hydroxy-7- [1-hydroxy-2- (2-methoxy-ethoxy) -ethyl] -6-oxa-2-aza-cyclopenta [c] fluorene-1, 3-dione; 7- (2-Amino-1-hydroxy-ethyl) -4- (2-chlorophenyl) -6-oxa-2-aza-cyclopenta [c] fluorene-1,3-dione; 4- (2-chlorophenyl) -6-methyl-8-piperidin-3-yl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-chlorophenyl) -6-methyl-8-piperidin-4-yl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-chlorophenyl) -8- (4-hydroxy-piperidin-3-yl) -6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 8- (1-Aminomethyl-2-hydroxy-ethyl) -4- (2-chlorophenyl) -6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-chlorophenyl) -6- (3-hydroxy-propyl) -8-pipendin-3-yl-6H-pyrrolo [3,4-c] carbazole-, 3-dione; 4- (2-chlorophenyl) -8- (4-hydroxy-piperidin-3-yl) -6- (3-hydroxy-propyl) -6H-pyrro | or [3,4-c] carbazole-1., 3 -diona; 4- (2-chlorophenyl) -9-hydroxy-8- [4- (methylamino) butyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -9-hydroxy-8- [3- (methylamino) propoxy] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -8- [3- (dimethylamino) propoxy] -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -8- [3- (dimethylammono) propoxy] -9-hydroxy-6- (2-hydroxyethyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -9-hydroxy-6- (2-hydroxyethyl) -8- [3- (methylamino) propoxy] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) - diona; 4- (2-chlorophenyl) -9-hydroxy-6- (2-hydroxyethyl) -8- [4- (methylamino) butyl] pyrrolo [3,4-c] carbazole-1, 3- ( 2H, 6H) -dione; 4- (2-chlorophenyl) -8- [4- (dimethylamino) butyl] -9-hydroxy-6- (2-hydroxyethyl) pyrrolo [3,4-c] carbazole-1, 3 - (2H, 6H) -dione; 4- (2-chlorophenol) -8- [4- (dimethylamino) butyl] -9-hydroxy-6- (3-hydroxypropyl) pyrrolo [3,4-c] carbazole- 1, 3- (2H, 6H) -dione; 4- (2-chlorophenol) -8- [4- (dimethylammon) butyl] -9-hydroxy-6- (3-hydroxypropyl) pyrrolo [3,4-c] carbazole-1,3 - (2H, 6H) -dione; 4- (2-chlorophenyl) -9-hydroxy-6- (3-hydroxypropyl) -8- [3- (methylamino) propoxy] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-Chloro-thiyl) -8- [3- (dimethylamino) propoxy] -9-hydroxy-6- (3-hydroxypropyl) pyrrolo [3,4-c] carbazole-1, 3r (2H, 6H) -dione; 4- (2-chlorophenyl) -9-hydroxy-6- (3-hydroxypropyl) -8- [3- (1-pyrrolidinyl) propoxy] pyrrolo [3,4-c] carbazole -1, 3- (2H, 6H) -dione; 4- (2-chlorophenol) -9-hydroxy-6-methyl-8- [4- (methylamino) butyl] pyrrolo [3,4-c] carbazole-1, 3- (2H) , 6H) -dione; 4- (2-chlorophenyl) -9-hydroxy-6-methyl-8- [3- (methylamino) propoxy] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenol) -8- [4- (dimethylamino) butyryl] -9-hydroxy-6-methylpyrrolo [3,4-c] carbazole-1, 3 - (2H, 6H) -dione; 4- (2-chlorophenyl) -8-. { 3 - [(3,5-dimethylpiperazinyl) propoxy] -9-hydroxy-6-methylpyrrolo [3,4-c] carbazole-, 3- (2H, 6H) -dione; -Butyl-4- (2-chlorophenyl) -8- [4- (dimethylamino) butyl] -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) - dione; 4- (2-chlorophenol) -9-hydroxy-8- [4- (methylamino) butyl] -6-propylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 6-Butyl-4- (2-chlorophenyl) -9-hydroxyl-8- [3- (methylamine) propoxy] pyrrolo [3,4-c] carbazole -1, 3- (2H, 6H) -dione; 6-Butyl-4- (2-chlorophenyl) -8- [3- (dimethylamino) propoxy] -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 6-Butyl-4- (2-chlorophenol) -9-hydroxy-8- [4- (1-pyrrolidinyl) butyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; . 4- (2,6-Dichlorophenyl) -9-hydroxy-8- [4- (methylamino) butyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; . 4- (2-chloro-6-methoxyphenyl) -9-hydroxy-8- [4- (methylamino) butyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -diona; 4- (2-Bromophenyl) -9-hydroxy-8- [4- (methylamino) butyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-Bromophenyl) -8- [4- (dimethylamino) butyl] -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-Chloro-6-methoxyphenyl) -8- [4- (dimethylamino) butyl] -9-hydroxy-pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -d Ona; 4- (2-Chloro-6-methoxyphenyl) -8- [3- (dimethylamino) propoxy] -9-hydroxy-pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) - diona; 4- (2,6-Dichlorophenol) -8- [3- (dimethylamino) propoxy] -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -d ona; 4- (2-Bromophenyl) -8- [3-. { dimethylamino) propoxy] -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-Bromophenyl) -9-hydroxy-8- [3- (methylamino) propoxy] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chloro-6-methoxyphenyl) -9-hydroxy-8- [3- (methylamino) propoxy] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -d Ona; 4- (2-loro-6-methoxyphenyl) -9-hydroxy-6-methyl-8- [3- (methylamino) propoxy] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) - diona; 4- (2,6-Dichlorophenyl) -9-hydroxy-6-methyl-8- [3- (methylamino) propoxy] pyrrolo. { 3,4-p] carbazole: 1, 3- (2H, 6H) -dione; 4- (2-Bromophenyl) -9-hydroxy-6-methyl-8- [3- (methylamino) propoxy] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -diona; 4- (2-Bromophenyl) -8- [3- (dimethylamine) propoxy] -9-hydroxy-6-methylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H )-Mrs; 4- (2,6-Dichlorophenyl) -8- [4- (dimethylamino) butl] -9-hydroxy-6-methylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H ) -diona; 4- (2-Chloro-6-methoxyphenyl) -8- [4- (dimethylamino) butyl] -9-hydroxy-6-methylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chloro-6-methoxy-phenol) -8- [3- (dimethylamino) propoxy] -9-hydroxy-6-methyl-pyrrolo [3,4-c] carbazole-1, 3- (2H) , 6H) -dione; 6-Butyl-4- (2-chloro-6-methoxyphenyl) -8- [3- (dimethylamino) propoxy] -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- ( 2H, 6H) -dione; 6-Butyl-4- (2-chloro-6-methoxyphenyl) -9-hydroxy-8- [3- (methylamino) propoxy] pyrrolo [3,4-c] carbazole-1, 3- ( 2H, 6H) -dione; 6-Butyl-4- (2-chloro-6-methoxy-phenol) -8- [4- (dimethylammono) butyl] -9-hydroxypyrrolo [3,4-c] carbazole-1, 3 - (2H, 6H) -dione; 6-Butyl-4- (2 > 6-dichlorophenol) -8- [4- (dimethylamino) butyl] -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H) , 6H) -dione; 6-Butyl-4- (2,6-dichlorophenyl) -8- [3- (dimethylamino) propoxy] -hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) - Mrs; 6-Butyl-4- (2,6-dichlorophenyl) -9- idroxy-8- [3- (methylamino) propoxy] pyrrolo [3,4-c] carbazor-1, 3- (2H, 6H) - didha; 6-Butyl-4- (2,6-dichlorophenyl) -9-hydroxy-8- [4- (methylamino) butyl] pyrrolo [3,4-c] carbazole-1, 3- ( 2H, 6H) -dione; 4- (2-chlorophenol) -9-hydroxy-8- [4- (1-pyrrolidinyl) butl] -1 H- [1] benzofuro [3,2-e] ¡lsoindole-1, 3 - (2H) -dione; 8- (4-Aminobutyl) -4- (2-chlorophenyl) -9-hydroxy-1 H- [1] benzofuro [3,2-e] isoindol-1, 3- (2H) -dione; 8- (4-Aminobutyl) -4- (2-chlorophenol) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 8- (4-Aminobutyl) -4- (2-chlorophenyl) -9-hydroxy-6-methylpyrrolo [3,4-c] carbazol-1, 3- (2H-6H) -dione; 4- (2-chlorophenyl) -9- (hydroxymethyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -9- (trifluoromethyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 9- (2-Amino-1-hydroxyethyl) -4- (2-chlorophenyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -9- [1-hydroxy-2- (methylamino) ethyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -9- [2- (dimethylariino) -1-hydroxyethyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; . , - ..-. - - - --- - '4- (2-chlorophenyl) -9- [1-hydroxy-2- (1-pipéridinyl) ethyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H )-Mrs; 4- (2-chlorophenol) -9- [1-hydroxy-2- (4-morpholinyl) etl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) - diona; 4- (2-chlorophenyl) -8- (4-hydroxybutoxy) -6-methyl-pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -8- (3,4-dihydroxybutoxy) -6-methylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -6-methyl-8- [4- (methylamino) butoxy] pyrrolo [3,4- c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -8- [4- (dimethylamino) -3-hydroxybutoxy] -6-methylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -8- [3-hydroxy-4- (methylamino) butoxy] -6-methylpyrrolo [3,4-c] carbazol-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -8- [3-hydroxy-4- (1-pyrrolidinyl) butoxy] -6-methylpyrrolo [3,4-c] carbazol-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -8 - [(1 E) -4- (dimethylamino) -1-butenyl] -6-methylpyrrolo [3,4c] carbazole-1, 3- (2H, 6H) -dione; 4 (2-chlorophenyl) -6-methyl-8 - [(1 E) -4- (methylamino) -1-butenyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -6-methyl-8- [4- (methylamino) butyl] pyrrolo [3) 4- c] carbazole-1, 3- (2H, 6H) -dione; _ .. ^ .. ... |- ~~~ "4r (2-chlorophenyl) -8- [4- (dimethylmethyl) butyl] -6-methylpyrrolo [3,4-c] carbazole -1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -8 - [(1 E) -4-hydroxy-1-butenyl] -6-methylpyrrolo [3,4- c] carbazole- 1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -8 - [(1 E) -4-hydroxy-1-butenyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -8- (4-hydroxybutyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -8- [4- (methylamino) butyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -8 - [(1 E) -4- (methylamino) -1-butenyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -6- (3-hydroxypropyl) -8- [3- (methylamino) propoxy] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) - diona; 4- (2-chlorophenyl) -8- [3- (methylamino) propoxy] -6- [3- (methylamino) propyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -diona; 4- (2-chlorophenyl) -8- (3-hydroxypropoxy) -8- [3- (methylamino) propyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -9-fluoro-8- [3- (methylamino) propoxy] -6- [3- (methylamino) propyl] pyrrolo [3,4-c] carbazole-1, 3- ( 2H, 6H) -dione; 4- (2-chlorophenyl) -9-fluoro-8- (3-hydroxypropoxy) -6- [3- (methylamino) propyl] pyrrolo [3,4-c] cart) azolTjl, 3- (2H-, 6H) -diona; ~ '~' _ .. ... - 4- (2-chlorophenyl) -9-fluoro-6- (3-hydroxypropyl) -8- [4- (methylamino) but!] Pyrrolo [3 , 4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenol) -9-fluoro-8- (4-hydroxybutoxy) -6-methylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -9-fluoro-6-methyl-8- [3- (methylamino) propoxy] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenol) -9-fiuoro-8- (3-hydroxypropoxy) -6-methylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chloro-3-hydroxyphenyl) -8- [4- (methylamino) butyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chloro-3-hydroxy-phenyl) -9-fluoro-8- [3- (methylamino) propoxy] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chloro-3-hydroxyphenyl) -9-fluoro-8- [3- (methylamino) butyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chloro-3-hydroxyphenyl) -9-fluoro-6- (3-hydroxypropyl) -8- [4 (methylamino) butyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H ) -diona; 4- (3-Amino-2-chlorophenyl) -9-fluoro-6- (3-hydroxypropyl) -8- [4 (methylamino) butyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (3-Ami-2-chlorof in I) -9-fl uoro-8- [4- (methylamino) butyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H ) -diona; 4- (3-Amino-2-chlorophenyl) -9-fluoro-8- [3- (methylamino) propoxy] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dionea 4- (2-chlorophenyl) -9-fIuoro-6-methylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 3- (4- (2-chlorophenyl) -9- (formylamino) -1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -N- [2- (dimethylamino ) ethyl] propanamide; 3- (9-Amino-4- (2-chlorophenyl) -1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) -N - [2- (dimethylamino) ethyl] propanamide; 4- (2-chlorophenyl) -6-methyl-9- { [3- (1-piperidinyl) propyl] amino} pyrrolo [3,4c] carbazole- 1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -9-fluoropyrrolo [3,4-c] carbazol-1, 3- (2Hl 6H) -dione; 9-Amino-4- (2-chlorophenyl) -6- (3-hydroxypropyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -6- (3-hydroxypropyl) -1,3-dioxo-1, 2,3,6-tetrahydropyrrolo [3,4-c] carbazol-9-ylformamide; 4- (2-chlorophenyl) -9-. { [4- (dimethylamino) butyl] amino} -6-methylpyrrolo [3,4-c] carbazol-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -6-methylene-9-. { [4- (methalamine) butl] amino} pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenol) -9-. { [3- (1-piperidinyl) propyl] amino} pyrrolo [3,4-G] carbazole-1, 3- (2H, 6H) -dione; 4- (2-ethoxyphenyl) -6-methyl-1,3-d-oxo-1, 2,3,6-tetrahydropyrrolo [3,4-c] carbazol-9-ylformamide; 4- (2-Methoxyphenyl) -6-methyl-9- (methylamino) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; "4- (2-chlorophenyl) -6-methyl-8- [3- (methylamino) propoxy] -1,3-dioxo-1, 2,3,6-tetrahydropyrrolo [3,4-c] carbazole- 9-ylformamide: 4- (2-chlorophenyl) -9-hydroxy-6-methyl-8- [4- (methylamino) butanoyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenol) -8- [4- (dimethylamine) butanoyl] -9-hydroxy-6-methylpyrrolo [3,4c] carbazole- 1, 3- (2H, 6H) -dione; 4- (2-chlorophenol) -8- [3- (dimethylamino) propoxy] -6-methyl-1,3-dioxo-1, 2, 3,6-tetrahydropyrrolo [3,4-c] carbazole-9-lformamide; 4- (2-chlorophenyl) -8-. { [3- (dimethylammon) propyl] sulfinyl} -9-Hydrpxy-6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; and 4- (2-chlorophenyl) -9-hydroxy-6-methyl-8-. { [3 (methylamino) propyl] sulfonyl} pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione. In another preferred embodiment of the present invention, R in the compounds according to Formula I is aryl. A preferred embodiment are compounds according to Formula I wherein R is selected from an unsubstituted aryl ring or an aryl ring substituted with up to 3 substituents selected from the group consisting of halogen, haloalkyl, alkoxy, hydroxyl, nitro or NR3R4. A more preferred embodiment are compounds according to Formula I wherein R 1 is an aryl ring substituted with up to 2 halogens or alkoxy groups. Another preferred embodiment of the present invention comprises -compounds according to Formula I wherein R1 is selected from Me and I. In a preferred embodiment of the present invention, R9 in the compounds according to Formula I is hydrogen, hydroxyl, halogen or a NHCHO group. Another preferred embodiment are compounds according to Formula I wherein at least one of X, R7, R8 and R9 is not hydrogen. In another embodiment, when three of X, R7, R8 and R9 are hydrogen and R1 is lower alkyl, then R2 must be hydrogen.

In a more preferred embodiment of the present invention, R9 in the compounds according to Formula I is a hydroxyl group. In a more preferred embodiment of the present invention, R9 in the compounds according to Formula I is a fluorine group. A more preferred embodiment of the present invention are compounds according to Formula I wherein R9 is hydroxyl and R1 is aryl, such as, but not limited to: 4- (2-chloro-3-hydroxyphenyl) -9-hydroxypyrrolo [ 3,4-c] carbazole-1, 3- (2H, 6H) -dione; 9-Hydroxy-4- (2-iodophenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-chloro-6-methoxyphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2,6-Dichloro-3-hydroxyphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; _ "- ._ 4- (4-Amino-2-bromophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (3-Amino-2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chloro-4-hydroxyphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-Bromophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 9-Hydroxy-4- (2-methoxyphenyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (4-Amino-2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2,6-Dimethoxyphenyl) -9-hydroxy-pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2,6-Dichlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, dione; 4- (2,3-Dichlorophenol) -9-hydroxypi rrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chloro-5-hydroxyphenyl) -9-hydroxypyrrolo [3,4-c] carbazole- 1, 3- (2H, 6H) -dione; 9-Hydroxy-4- [2- (methylsulfanyl) phenyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -done; : - | - - - "- ... 4- (2,6-Dibromophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 9-Hydroxy-4- (3-thienyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chloro-6-hydroxy-phenyl) -9-hydroxypyrrolo [3 , 4-c] carbazole-1, 3- (2H, 6H) -dione; 9-Hydroxy-4- (2-nitrophenyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2,6-Dichloro-4-hydroxy-phenyl) -9-hydroxypyrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (3-chlorophenol) -9-hydroxy-pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 9-Hydroxy-4- (2-hydroxy-phenyl) -pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 9-Hydroxy-4- (4-hydroxyphenyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (3-Aminophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2,6-Dimethylphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 9-Hydroxy-4- (3-hydroxyphenyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (5-Amino-2-methoxyphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 9-Hydroxy-4- (3-hydroxy-4-methoxyphenyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; .. ..- · - | - 9-Hydroxy-4- (2-thienyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (4-Aminophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 2- (9-Hydroxy-1,3-dioxo-1, 2,3,6-tetrahydropyrrolo [3,4-c] carbazole-4-l) benzonitrile; 4, (2-Aminophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-Bromo-4-nitrophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 9-Hydroxy-4- [2- (methylsufinfin) phenyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -done; 4- (2-Ethoxyphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 9-Hydroxy-4- (3-nitrophenol) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-Ethylphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 9-Hydroxy-4- [2- (hydroxymethyl) phenyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -done; 4- (2-chloro-4-nitrophenol) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 9-Hydroxy-4- (2-trifluoromethylphenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- [1, 1 '-Bifenl] -2-yl-9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (4-chlorophenyl) -9-hydroxypyrrold [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 9-Hydroxy-4- (4-hydroxyethylphenyl) pyrrolo [3-4-c] carbazole-1, 3- (2H, 6H) -done; 9-Hydroxy-4-o-tolyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 3- (9-Hydroxy-1,3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazol-4-yl) benzonitrile; 4- Furan-2-H-9-hydroxy-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 9-Hydroxy-4-m-tolyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 9-Hydroxy-4- (2-methylsulfanyl-phenyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 9-Hydroxy-4- (3-trifluoromethoxy-phenyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 9-Hydroxy-4- (3-Hydroxymethyl-phenyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 9-Hydroxy-4- (4-trifluoromethoxy-phenyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 9-Hydroxy-4- (3-Hydroxy-phenyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; Y 4- (2-Acetyl-phenyl) -9-Hydroxy-6H-pyrrolo [3,4-c] carbazole-1,3-dione. Still another preferred embodiment of the present invention are compounds according to Formula I wherein Y 1 is oxygen, such as, but not limited to: 4- (2-chlorophenyl) -7- (1,2-dihydroxyethyl) -9- hydroxy-1 H- [1] benzofuro [3,2-e] isoindol-1, 3- (2H) -dione; 4- (2-chlorophenyl) -9-hydroxy-1 H- [1] ben-dione; 4- (2-chlorophenyl) -8-ethyl-9-hydroxy-1 H- [1] benzofuro [3,2-e] isoindol-1, 3- (2H) -dione; 4- (2-chlorophenyl) -7-ethyl-9-hydroxy-1 H- [1] benzofuro [3,2-e] isoindol-1, 3- (2H) -dione; 9-Hydroxy-4-phenyl-1 H- [1] benzofuro [3,2-e] isoindol-1, 3- (2H) -dione; 4- (2-chlorophenyl) -8- [3- (dimethylamino) propoxy] -9-hydroxy-1 H- [1] benzofuro [3,2-e] isoindol-1,3 (2H) -dione; 4- (2-chlorophenyl) -9-hydroxy-8- (4-hydroxybutyl) -1 H- [1] benzofuro [3,2-e] isondol-1, 3- (2H) -dione. Another preferred embodiment of the present invention are compounds according to Formula I wherein Y 1 is sulfur, such as, but not limited to: 4- (2-chlorophenyl) -9-Hydroxy-1 H- [1] benzothieno [3 , 2-e] isoindol-1,3 (2H) -dione. Another preferred embodiment of the present invention are compounds according to Formula I wherein R9 is hydroxyl and Y1 is NR10. Another preferred embodiment of the present invention are compounds according to Formula I wherein R9 is NR5R6, R1 is aryl and Y1 is NR10 such as, but not limited to, the compounds selected from the group consisting of: r - r - 9 -Amino-4- (2-methoxyphenyl) -6,6-methylpyrrolp [3,4-c] carbazole 1,3 (2H, 6H) -dione; '' "· - -.. 9-Amino-4- (2-chlorophenyl) -6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 9- (Dimethylamino) -4- (2-methoxyphenyl) -6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 9-Amino-4- (2-chlorophenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-chlorophenyl-6-methyl-1,3-dioxo-1, 2,3,6-tetrahydropyrrolo [3,4-c] carbazol-9-ylformamide; 4- (2-chlorophenyl) -1,3-dioxo-1, 2,3,6-tetrahydropyrrolo [3,4-c] carbazol-9-ylformamide; 4- (2-chlorophenyl) -6-methyl-9- (methylamino) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 5 N- [4- (2-chlorophenyl) -6-methyl-1,3-dioxo-1, 2,3,6-tetrahydropyrrolo [3,4-c] carbazol-9-yl] acetamide; 4- (2-chlorophenyl) -9- (ethylamino) -6-methylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; and N- [4- (2-chlorophenyl) -6-methyl-1,3-dioxo-1, 2,3,6-tetrahydropyrrolo [3,4- 10 c] carbazol-9-yl] 3- (1 - piperidinyl) propanamide. Another preferred embodiment of the present invention are compounds according to Formula I wherein R9 is hydroxyl and Y1 is NR10. Another preferred embodiment of the present invention are compounds according to Formula 1. wherein R9 is hydroxyl and Y1 is NR10, and T may be absent or be OR, CONR3 or CONHS02. compounds shown below: 9-Methoxy-4- (2-methoxy-5-nitrophenyl) -4,5,6,10c-tetrahydropyrrolo [3,4-c] carbazole-1, 3- (2H, 3aH) - dione; 20 N- [3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) propanoyl ] benzenesulfonamide; 4- (2,6-Dichlorophenyl) -9-hydroxy-6- (3-hydroxypropyl) pyrrolo [3,4-c] carbazole-, 3- (2H, 6H) -dione; 4 4- (2,6-Dichlorophenyl) -9-hydroxy-6- (2-hydroxyethyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 3- (4- (2-chlorophenyl) -9-Hydroxy-1,3-d-oxo-2,3-d -hydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) -N- (1 H-tetrazol-5-yl) propanamide; 4- (2-chlorophenyl) -9-hydroxy-6- [2- (1 H-1, 2,4-triazol-5-ylsulfinyl) ethyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 6- (3-Bromopropyl) -4- (2-chlorophenol) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 3- (4- (2-Chlorophenyl) -9-hydroxy-1,3-d-oxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) propanoic acid; N- [3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) propanoyl] -2 - (dimethylamino) ethanesulfonamide; 4- (2-chlorophenyl) -9-Hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; N- [3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) propanoyl ] methanesulfonamide; 4- (4- (2-chlorophenyl) -9-hydroxyl-1,3: dioxo-2,3-d-hydropropyrrolo [3,4- c] carbazole-6 (1 H) -yl) butanoic acid; N- [4- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) butanoyl] methanesulfonamide; 6-Acetyl-4- (2-chlorophenyl) -9-Hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 3- (4- (2,6-Dichlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) -N- [2- (dimethylamino) etl] propanamide; 3- (4- (2-chlorophenyl) -9-hydroxy-1,3-d-oxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) -propanonitrile; 4- (2-chlorophenyl) -9-hydroxy-6- [3- (1 H -tetrazol-5-yl) propyl] pyrroio [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -9-hydroxy-6- [2- (1 H-imidazol-2-ylsulfanyl) ethyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; N- [4- (2- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1 H) -yl) butanoyl] benzenesulfonamide; 4- (2-chlorophenyl) -9-hydroxy-6- [2- (1 H-1, 2,4-triazol-5-ylsulfonyl) ethyl] pyrrolo [3,4-c] carbazole-1, 3- ( 2H, 6H) -dione; 4- (2-chlorophenyl) -9-hydroxy-6- [2- (1 H-imidazol-2-Nsulfinyl) ethyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -9-hydroxy-6- [2- (1 H -tetrazol-5-yl) ethyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; -3- (9-Hydroxy-1, 3-dioxo-4-phene) 6 (1 H) il) propanamide; "- -. 4- (2-chlorophenyl) -9-idroxy-6- [2- (1 H -imidazol-2-ylsulfonyl) ethyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 3- (9-hydroxy-1,3-dioxo-4-phenyl-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) propanoic acid; 4- ( 2-chlorophenyl) -6- (2,3-dihydroxypropyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 2- (4- (2,6-Dichlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) ethyl methanesulfonate; 4- (2-chlorophenyl) -9-hydroxy-6- [2- (4H-1, 2,4-triazol-3-ylsulfanyl) ethyl] pyrrolo [3,4-c] carbazole-1, 3- (2H , 6H) -dione; 9-Hydroxy-6- (2-hydroxyethyl) -4-phenylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 6- (3-Bromopropyl) -4- (2,6-dichlorophenyl) -9-hydroxypyrrolo [3,4- c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -9-hydroxy-6- (3-methoxypropyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -9-hydroxy-6- (2-hydroxypropyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -9-hydroxy-6 - [(2S) -3-hydroxy-2-methylpropyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; - - - - - 3 ^ (4- (2-chlorophenyl) -9-H | drpxi-, 3-dioxp-2,3-dihydropyrrolo [3I4-c] carbazole-6 (1 H) -yl) -N- [2- (1 H-imidazol-5-ii ethyl] propanamide; * - - 9-Hydroxy-6- (3-hydroxypropyl) -4- (2-methoxyphenyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 3- (4- (2-chlorophenyl) -9-Hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1H) - il) methyl propanoate: 3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) - N- [2- (4-morpholinyl) ethyl] propanamide; 4- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) butanonitrile; 4- (2-chloro-6-methoxyphenyl) -9-hydroxy-6- (2-hydroxyethyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; . 3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) -N- [2- ( dimethylamino) ethyl] propanamide; 4- (2-chlorophenyl) -6- (3,4-dihydroxybutyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 3- (4- (2-chloro-6-methoxyphenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) -N- [2- (dimethylamino) ethyl] propanamide; 4- (2-chlorophenyl) -9-Hydroxy-6 - [(2R) -3-Hydroxy-2-methylpropyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 2- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) ethyl ethanesulfonate; - - 4- (2-chloro-6-methoxyphenij) -9-hydroxy-6- (3-hydroxypropyl) pi c] carbazole-1, 3- (2H, 6H) -dione; * '- - "9-Hydroxy-6- (2-hydroxyethyl) -4- (2-methoxyphenyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2 -chlorophenyl) -6- (2-hydroxyethyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -9-hydroxy-6- [3- (methylsulfanyl) propyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -6-etl-9-H, -droxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (V !; Ar = 2-chlorophenyl, R = CH2CH3); 4- (2-chlorophenyl) -9-hydroxy-6-ysopropyl-pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenol) -9-hydroxy-6- [3- (1 H-imidazol-1-yl) propyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -diona; 4- (2-chloro-6-methoxy-phenyl) -9-hydroxy-6- [3- (4-morpholinyl) propyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H ) -diona; 6- (2-chloroethyl) -4- (2-chlorophenyl) -9-hydroxy-pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 6- (3-Bromopropyl) -4- (2-chloro-6-methoxyphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -9-hydroxy-6- [2-hydroxy-3- (methylamino) propyl] pyrrolo [3,4-c] carbazole-, 3- (2H, 6H) -d ona; , 4- (2-chlorophenol) -9-hydroxy-6H) -dione; "~" | "* '" · - - 4- (2-chlorophenyl) -9-hydroxy-6- [2-hydroxy-3- (4-morpholinyl) propyl] pyrrolo [3,4-c] carbazole-1 , 3- (2H, 6H) -dione; 4- (2,6-Dichlorophenyl) -9-hydroxy-6- [3- (1 H -imidazol-1-yl) propyl] pyrrolo [3,4-c] carbazole-1, 3 - (2H, 6H) -dione; and 6-ButyI-4- (2-chlorophenyl) -9-Hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione.

A more preferred embodiment of the present invention are compounds according to Formula I wherein R9 is hydroxyl and Y1 is NR10 and the bond represented by dashed line (C-O) is absent. An especially preferred embodiment of the present invention are compounds according to Formula I wherein R9 is hydroxyl and R8 is not hydrogen. Another preferred embodiment of the present invention are compounds according to Formula I wherein R9 is hydroxyl and Y1 is NR10 and R1 is aryl. Another especially preferred embodiment of the present invention are compounds according to Formula I wherein R8 is not hydrogen and R9 is hydrogen. Another especially preferred embodiment of the present invention are compounds according to Formula I wherein R8 is not hydrogen, R9"is hydrogen and Y- is NR10.,., Another especially preferred embodiment of the present invention-- comprises compounds of according to Formula I wherein R9 is hydrogen and R8 is ((CR5R6) nT) a (CR1R2) b) -Z, where T may be absent or be O and Z is NR3R4. present invention comprises compounds according to Formula I wherein R9 is selected from halogen or hydroxyl and R8 is ((CR5R6) nT) a (CR1 R12) b) Z where T is absent and Z is hydrogen.

Following are definitions of terms used in this specification. The initial definition provided for a group or term in this document applies to that group or term throughout the present specification, individually or as part of another group, unless otherwise indicated. When there are stereoisomers or enantiomers, all possible combinations are claimed. The terms "halogen" and "halo" refer to fluorine, chlorine, bromine and iodine. The term "unsaturated ring" includes partially unsaturated and aromatic rings. The term "alkyl" in the present invention refers to a linear or branched hydrocarbon radical having from 1 to 8 carbon atoms and includes, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl ^ r - isobutyl tere-butyl, n-pentyl, Jso-pentyl, n ^ -hexyl and the like. The term "aryl" refers to an aromatic carbocyclic group having a single ring (e.g., phenyl), multiple rings (e.g., biphenyl) or multiple fused rings wherein at least one is aromatic (e.g. , 3,4-tetrahydronaphthyl, naphthyl, anthryl or phenanthryl). The term "heteroaryl" means an aromatic group "heterocycle", "heterocyclic" or "heterocyclyl" as defined below, comprising at least one heteroatom.

The aryl or heteroaryl ring may be optionally substituted with up to five substituents selected from NH (C6 alkyl), N (Ci-C6 alkyl) 2, C1-C6 thioalkyl, C1-C6 alkoxy, hydroxy, carboxy, C1-C6 alkoxycarbonyl, halo, nitrile and cycloalkyl. By "alkoxy" are meant straight or branched chain alkoxy groups having from 1 to 10 carbon atoms, such as, for example, methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, sec-butoxy, tert-butoxy, pentoxy , 2-pentyloxy, isopentoxy, neopentoxy, hexoxy, 2-hexoxy, 3-hexoxy and 3-methylpentoxy. "Alkynyl" refers to straight or branched hydrocarbon radicals having from 2 to 8 carbon atoms and a triple bond and include ethynyl, 3-butyne-1-yl, propynyl, 2-butyne-1-yl, 3-pentyl- 1 -ilo and similar. The terms "cycloalkyl" and "cycloalkenyl" refer to cyclic hydrocarbon groups of 3 to 8 carbon atoms and include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, and the like. "-" - "Acyl" refers to an alkyl, aryl, cycloalkyl, heterocycle, heterocyclic, or heteryl cyclyl group bonded through a carbonyl group, i.e., Rc (O) - Typical acyl groups include acetyl, benzoyl and the like having 1-10 carbon atoms, preferably 1-6 carbon atoms The term "haloalkyl" refers to an alkyl group substituted with 1 to 6 halogen atoms and includes trifluoromethyl, trichloromethyl, tribromomethyl, trifluoroethyl, trifluoropropyl , trifluorobutyl, pentafluoroethyl and the like.

The alkyl, alkenyl, alkoxy and alkynyl groups described above are optionally substituted, preferably with 1 to 3 groups selected from NH (Ci-c6 alkyl), N (Ci-c6 alkyl) 2, phenyl, substituted phenyl, C6 cycloalkyl, alkoxy Ci-c6, hydroxy, carboxy, C] C6 alkoxycarbonyl, halo, nitrile, cycloalkyl and a 4 or 6 membered carbocyclic ring or a heterocyclic ring having 1 or 2 heteroatoms selected from nitrogen, substituted nitrogen, oxygen and sulfur. "Substituted nitrogen" refers to a nitrogen having Ci-c6 alkyl or (CH2) PP where p is 1, 2 or 3. Perhalo and polyhalo substitution are also included. The term "heteroatom" refers to an oxygen, nitrogen, sulfur or phosphorus atom. The terms "heterocycle", "heterocyclic" or "heterocyclyl" refer to fully saturated or unsaturated groups, including aromatic or non-aromatic cyclic (heteroaryl) groups, for example, monocyclic 4- to 7-membered, bicyclic ring systems. of 7 to 11 members or tricyclics of 10 to 15 members, having at least one heteroatom in at least one ring containing a carbon atom Each ring of heterocyclic group containing heteroatoms may have 1, 2, 3 or 4 selected heteroatoms between nitrogen atoms, oxygen atoms and / or sulfur atoms, where the nitrogen and sulfur heteroatoms can optionally be oxidized and the nitrogen heteroatoms optionally quaternized.The heterocyclic group can be attached to any heteroatom or carbon atom of the ring or system of rings Monocyclic heterocyclic groups include, but are not limited to, pyridine, 2,6-dimethylpiperazine, piperazine, n-methylpiperazine, pyrrolidinyl, pyrrolyl, pyrazolyl, oxetanyl, pyrazolinyl, imidazolyl, imidazolinyl, S (0) -imidazoles, S (0) 2 -imidazoles, oxazolyl, oxazolidinyl, isoxazolinyl, isoxazolyl, thiazolyl, thiazolyl, thiazolidinyl, isothiazolyl, isothiazolidinyl, morpholine and dimethylmorpholine, 2-thiophene, thiophene, 1-imidazole, 2-imidazole, furyl, tetrahydrofuryl, thienyl, oxadiazole, piperidinyl, piperazinyl , 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolidinyl, 2-oxoazepinyl, 2-azepinyl, 4-piperidonyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, tetrahydropyranyl, morpholinyl, thiamorpholinyl, thiamorpholinyl sulfoxide, thiamorpholinisulfone, 1,3-dioxolane and tetrahydro-1,1,1-dioxothianyl, tetrazole, SO-triazole, S02-triazole and the like. Bicyclic heterocyclic groups include, but are not limited to, indolyl, benzothiazolyl, benzoxazolyl, benzodioxolyl, benzothienyl, quinuclidinyl, quinolinyl, tetra-hydroisoquinolinyl, isoquinolinyl, -benzimidazolyl, -benzopjranyl ,. indolizinyl, benzopral, chromonyl, courmarinyl, benzopyranyl, cinolinyl, quinoxalinyl, indazolyl, pyrrolopyridyl, furopyridyl (such as furo [2,3-c] pyridinyl, furo [3,2-b] pyridinyl or furo [2,3b] pyridinyl), dihydroisoindolyl, dihydroquinazolinyl (such as 3,4-dihydro-4-oxoquinazolinyl), tetrahydroquinolinyl and the like Tricyclic heterocyclic groups include, but are not limited to, carbazolyl, benzoindolyl, phenanthrolinyl, acridinyl, phenanthridinyl, xanthenyl and the like. "cancer" includes, but is not limited to, the following cancers: cancers of the breast, ovaries, cervix, prostate, testes, esophagus, stomach, skin, lung, bone, colon, pancreas, thyroid, bile ducts, oral cavity, and pharynx (oral), lips, tongue, mouth, pharynx, small intestine, colon-rectum, large intestine, rectum, brain and central nervous system, glioblastoma, neuroblastoma, keratoacantroma, squamous cell carcinoma, gram cell carcinoma ndes, adenocarcinoma, adenoma, follicular carcinoma, undifferentiated carcinoma, papillary carcinoma, seminoma, melanoma, sarcoma, bladder carcinoma, liver carcinoma, kidney carcinoma, myeloid disorders, lymphoid disorders, Kodgkin's lymphoma, tricholeukemia and leukemia. The expression "sales"Pharmaceutically acceptable esters, amides and prodrugs", as used herein, refers to the carboxylate salts, amino acid addition salts, esters, amides and prodrugs of the compounds of the present invention which are, within the scope of a reasonable medical judgment, suitable for use in contact with tissues, of patients without inducing toxicity, irritation, allergic responses and the like "in proportion to a reasonable benefit / risk ratio, and effective for the use for which they are intended, as well as the zwitterionic forms, when possible, of the compounds of the invention. The term "salts" refers to non-toxic organic and inorganic acid addition salts of the compounds of the present invention. These salts can be prepared in situ during the final isolation and purification of the compounds or by separately reacting the purified compound in the form of its free base with a suitable organic or inorganic acid and isolating the salt formed in this manner. Representative salts include the hydrobromide, hydrochloride, sulfate, bisulfate, nitrate, acetate, oxalate, valerate, oleate, palmitate, stearate, laurate, borate, benzoate, lactate, phosphate, tosylate, citrate, maleate, fumarate, succinate, tartrate, naphthylate, mesylate, glucoheptonate, lactobionate and laurylsulfonate, and the like. These may include cations based on alkali and alkaline earth metals, such as sodium, lithium, potassium, calcium, magnesium and the like, as well as non-toxic ammonium, quaternary ammonium and amine cations including, but not limited to, ammonium, tetramethylammonium, tetraethylammonium , methylamine, dimethylamine, trimethylamine, triethylamine, ethylamine and the like. (See, for example, Berge S.M. et al., "Pharmaceutical Salts," J. Pharm. Sci., 1977; 66: 1-19 which is incorporated herein by reference). The compounds of Formula I may furthermore form pharmaceutically acceptable formulations comprising salts, including but not limited to addition of acids and / or bases, solvates and N-oxides of a compound of Formula I. This invention also provides pharmaceutical formulations which comprise a compound of Formula I together with a pharmaceutically acceptable carrier, diluent or excipient therefor. All these forms are within the present invention. Pharmaceutically acceptable acid addition salts of the compounds of Formula I include salts derived from inorganic acids such as hydrochloric, nitric, phosphoric, sulfuric, hydrobromic, hydroiodic, phosphorous and the like, as well as salts derived from organic acids such as mono acids. - and aliphatic dicarboxylic acids, phenyl-substituted alkanoic acids, hydroxy-alkanoic acids, alkanedioic acids, aromatic acids, aliphatic and aromatic sulfonic acids, etc. Thus, such salts include sulfate, pyrosulfate, bisulfate, sulfite, bisulfite, nitrate, phosphate, monohydrogen phosphate, dihydrogen phosphate, metaphosphate, pyrophosphate, chloride, bromide, iodide, acetate, propionate, caprylate, isobutyrate, oxalate, malonate, succinate, , sebacate, fumarate, maleate, mandelate, benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, phthalate, benzenesulfonate, toluenesulfonate, phenylacetate, citrate, lactate, maleate, tartrate, methanesulfonate and the like. Also contemplated are amino acid salts such as arginate, gluconate, galacturonate and the like; see, for example, Berge et al., "Pharmaceutical Salts", J. of Pharmaceutical Science, 1977; 66: 1 -19. The acid addition salts of the basic compounds are prepared by putting in. contact the free base form with a sufficient quantity of the desired acid to produce the salt in the conventional manner. The free base form can be regenerated by contacting the salt form with a base and isolating the free base in the conventional manner. The free base forms differ from their respective salt forms to some extent in certain physical properties such as solubility in polar solvents, but otherwise the salts are equivalent to their respective free bases for the purposes of the present invention.

The pharmaceutically acceptable base addition salts are formed with metals or amines, such as alkali and alkaline earth metal hydroxides, or organic amines. Examples of metals used are cations sodium, potassium, magnesium, calcium and the like. Examples of suitable amines?,? '- dibenzylethylenediamine, chloroprocaine, choline, diethanolamine, ethylenediamine, N-methylglucamine and procaine; see, for example, Berge et al., supra., 1977. The base addition salts of acidic compounds are prepared by contacting the free acid form with a sufficient amount of the desired base to produce the salt in the conventional manner . The free acid form can be regenerated by contacting the salt form with an acid and isolating the free acid in a conventional manner. The free acid form differs from its respective salt forms to some extent in certain physical properties such as solubility in polar solvents, but otherwise lasks are equivalent to their respective free acids for the purposes of the present invention: Examples of non-toxic pharmaceutically acceptable esters of the compounds of this invention include C1-C6 alkyl esters in which the alkyl group is a straight or branched chain. Acceptable esters also include C5-C7 cycloalkyl esters as well as arylalkyl esters such as, but not limited to, benzyl. Preferred are C1-C4 alkyl esters. The esters of the compounds of the present invention can be prepared according to conventional methods "March's Advanced Organic Chemistry, 5th Edition". M.B. Smith & J. March, John Wiley & Sons, 2001. Examples of pharmaceutically acceptable non-toxic amides of the compounds of this invention include amides derived from ammonia, alkyl dC6-primary amines and dialkyl dC6-secondary amines in which the alkyl groups are linear or branched In the case of the secondary amines, the amine may also be in the form of a 5- or 6-membered heterocycle containing a nitrogen atom. Amides derived from ammonia, alkyl d-C3-primary amines and dialkyl Ci-C2-secondary amines are preferred. Amides of the compounds of the invention can be prepared according to conventional methods such as "March's Advanced Organic Chemistry, 5th Edition", M.B. Smith & J. March, John Wiley & Sons, 2001. The term "prodrug" refers to compounds that are rapidly transformed in vivo to produce the parent compound of the above formulas, "for example, by hydrolysis in the blood." A thorough discussion is provided. in T. Higuchi and V. Stella, "Pro-drugs as Novel Delivery Systems", Vol. 14 of the ACS Symposium Series, and in Bioreversible Carriers in Drug Design, ed. Edward B. Roche, American Pharmaceutical 20 Association and Pergamon Press , 1987, both incorporated herein by reference.The present invention also includes isotope-stained compounds, which are identical to those indicated in Formula I except for the fact that one or more atoms have been replaced by an atom having one or more atoms. atomic mass or mass number different from the atomic mass or mass number normally found in nature Examples of isotopes that can be incorporated into the compounds of the present invention include 5 isos moles of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine and chlorine, such as 2 H, 3 H, 13 C, 1 C, 14 C, 15 N, 80, 70, 3 P, 32 P, 35 S, 18 F and 36 C, respectively. Within the scope of this invention are the compounds of the present invention, their prodrugs and the pharmaceutically acceptable salts of said compounds or of said prodrugs TO containing the aforementioned isotopes and / or other isotopes of other atoms. Certain isotopically-labeled compounds of the present invention, for example, those in which radioactive isotopes such as 3H and 14C have been incorporated., are useful in the distribution assays of drugs and / or substrates in tissues. Particularly preferred are tritium, that is, 3H and carbon-14, that is, 14C, for their ease of preparation and detectability. In addition, replacing it with heavier isotopes such as deuterium, ie, 2H, can produce certain therapeutic advantages due to greater metabolic stability, for example a longer half-life in vivo or the need for lower doses and, therefore, can Prefer in some circumstances. The compounds of Formula I labeled with isotopes of this invention and their prodrugs can generally be prepared by performing the procedures described in the Schemes and / or in the Examples and Preparations shown below. replacing a non-isotope-labeled reagent with an easily available isotope-labeled reagent. Compounds of Formula I and their pharmaceutically acceptable salts can be administered to mammals orally, parenterally (such as subcutaneously, intravenously, intramuscularly, intraestemally and infusion techniques), rectally, intranasally or topically. In general, it is most desirable to administer these compounds in doses ranging from about 10 to about 10,000 mg per day, in single or divided doses (ie from 1 to 4 doses per day), although there will necessarily be variations depending on the species , weight and condition of the subject to be treated and of the particular administration route selected. However, it is most desirable to employ a dosage level that is in the range of about 0.15 mg to about 150 mg per kg of body weight per day. However, variations may arise depending on the species of animal to be treated and its individual response to said medicament, as well as the type of pharmaceutical formulation selected and the period and time interval in which such administration is performed. In some cases, dosage levels below the lower limit of the range mentioned above may be more than adequate, while in other cases even higher doses may be used without producing any harmful side effects, provided that such higher dosage levels are first divided into several small doses. for administration throughout the day.

The compounds of the present invention can be administered alone or together with pharmaceutically acceptable carriers or diluents by any of the routes indicated above, and such administration can be carried out in single or multiple doses. More particularly, the novel therapeutic agents of this invention can be administered in a wide variety of different dosage forms, that is, they can be combined with various inert pharmaceutically acceptable carriers in the form of tablets, capsules, dragees, troches, hard candies, powders, sprays, creams, ointments, suppositories, jellies, gels, pastes, lotions, ointments, aqueous suspensions, injectable solutions, elixirs, syrups and the like. Such vehicles include solid diluents or fillers, sterile aqueous media and various non-toxic organic solvents, etc. In addition, oral pharmaceutical compositions can be conveniently sweetened and / or flavored. In general, the therapeutically effective compounds of the present invention are present in such dosage forms at concentrations ranging from about 5.0% to about 70% by weight. For oral administration, tablets containing various excipients such as microcrystalline cellulose, citrate may be employed.

Sodium, calcium carbonate, dicalcium phosphate and glycine, together with various disintegrants such as starch (and preferably corn starch, potato or tapioca), alginic acid and certain complex silicates, together with granulation binders such as polyvinylpyrrolidone, sucrose, gelatin and gum arabic.

In addition, lubricating agents such as magnesium stearate, sodium lauryl sulfate and talc are often very useful for compression. Solid compositions of a similar type may also be employed as fillers in gelatin capsules; Preferred materials in this regard also include lactose or milk sugar, as well as high molecular weight polyethylene glycols. When aqueous suspensions and / or elixirs are desired for oral administration, the active ingredient may be combined with various sweetening or flavoring agents, coloring substances or dyes and, if desired, emulsifying and / or suspending agents, together with diluents such as water. , ethanol, propylene glycol, glycerin and various similar combinations thereof. For parenteral administration, solutions of a compound of the present invention may be employed in sesame or peanut oil or in aqueous propylene glycol. The aqueous solutions should be buffered conveniently (preferably at a pH of about 3 to about "8) if necessary and the liquid diluent first" should --- -. . "Become isotonic. These aqueous solutions are suitable for intravenous injection purposes. Oily solutions are suitable for intra-articular, intramuscular and subcutaneous injection purposes. The preparation of all these solutions under sterile conditions is easily accomplished by conventional pharmaceutical techniques well known to those skilled in the art.

In addition, it is also possible to administer the compounds of the present invention topically when skin cell proliferation conditions are treated and this can be done by means of creams, jellies, gels, pastes, patches, ointments and the like, in accordance with pharmaceutical practice. conventional. The activity of the compounds of the present invention is determined by their ability to act as checkpoint overriders. The control point cancellers inhibit the kinases involved in the regulation of the G2 / M control point, resulting in the inversion of the imposed control point. Wee1 or Chk1 are examples of such kinases. The use in cells having DNA lesions, for example, but without limitation, DNA lesions by chemotherapeutic agents directed to conventional DNA or by radiation of cells with undamaged DNA presents an opportunity to use the cellular regulatory pathways for causing the cells to progress improperly and prematurely to the M-phase. These cells may be less likely to survive-and divide further, since dedication to the M-phase was performed in the presence of damaged DNA in a potentially catastrophic manner. In the case of undamaged cells that do not have detectable DNA damage, treatment of these cells with the checkpoint overriders of the present invention can force these cells to enter the M phase prematurely with similar cytotoxic effects. (Alan J. Kraker and Robert N.

Booher, "New Cell Cycle Targets", Ann. Rep. Med. Chem., 1999; 34: 247-256). The control point overriders of the present invention can be identified by measuring the activity in the assays described in Examples 483 (Wee1), 484 (Chk1) and 486 (PKC) and selecting the compounds having at least 10-fold lower activity in the PKC assay that they have in the Wee1 assay or an activity at least 5 times lower in the PKC assay than they have in the Chk1 assay. The present invention is illustrated by the following examples. However, it will be understood that the invention is not limited to the specific details of these examples. The melting points are uncorrected. The proton nuclear magnetic resonance spectra (1H MN) and 13C nuclear magnetic resonance spectra were measured for solutions in deuterochloroform (CDCI3) or in CD3OD or CD3SOCD3, and the positions of the peaks are expressed in parts per million (ppm) downfield of tetramethylsilane (TMS). The shapes of the peaks are indicated as follows: s, singlet, d, doublet, t, triplet, c, quadruplet, m, multiplet, a, width, etc. The compounds of the present invention can exist in unsolvated forms as well as in Solvated forms, including hydrated forms In general, solvated forms, including hydrated forms, are equivalent to unsolvated forms and are intended to be included within the scope of the present invention.

The term "animal" refers to mammals, including rodents, cows, horses, dogs, cats and humans. The compounds of the present invention are useful for treating cancer (e.g., leukemia and cancer of the lung, breast, prostate and skin such as melanoma) and other proliferative diseases including, but not limited to, psoriasis, HSV (herpes virus) infections simple) or HIV (human immunodeficiency virus), restenosis and atherosclerosis in combination with other conventional therapies. To use a compound of the present invention to treat a cancer, the patient in need of such treatment, such as one having cancer or another cell proliferation disease, is administered with an effective amount of the compound of the invention. In addition, the compounds of the present invention are useful for treating cancers when combined with adjuvant therapy with other treatment agents and clinical modalities such as, but without limitation, X-ray irradiation, beam therapy, conventional chemotherapeutic agents such as gemcitabine, paclitaxel, docetaxel, cisplatin, carboplatin, etoposide, adriamycin, topotecan, CPT-1 1, capecitabine or ionizing radiation alkylating agents, antimetabolites, antibodies, DNA intercalators or other anti-proliferative agents that eventually cause DNA damage. As new agents or antineoplastic modalities continue to be discovered, the use of Wee1 and / or Chk1 inhibitors together with these other agents or therapeutic modalities is contemplated.

Although the in vivo assays described herein teach the administration of the compounds according to Formula I simultaneously or after administration of the conventional agent, it is contemplated that the compound of the present invention may also be administered prior to the conventional chemotherapeutic agent or agents. . The following examples illustrate particular embodiments of the invention and are not intended to limit the specification, including the claims, in any way. Those skilled in the art will appreciate that numerous changes and modifications may be made to the preferred embodiments of the invention and that such changes and modifications may be made without departing from the spirit of the invention. Therefore, all these equivalent variations must be considered within the true spirit and scope of the invention. The chemical synthesis schemes provided below exemplify the best mode for preparing the compounds of the present invention. This patent describes various synthetic reactions known to those skilled in the art. In each case, alternative conditions known to one skilled in the art and described in the literature may also lead to the desired product, for example, in Advanced Organic Chemistry 5th Edition, Author: Jerry March, m. b. Smith & J. March, John Wiley & Sons 2001; Comprehensive Organic Transformation, Author: Richard C. Larock, The Journal of Organic Chemistry, published by the American Chemical Society, and the references cited in that document).

Known transformations include, but are not limited to: alkylation, dealkylation, oxidation, reduction, Curtius rearrangement, Suzuki reaction, esterification, Wittig reaction, amide formation, hydrogenation, protection, deprotection, hydrolysis, dehydroxylation, ozonolysis, acetylation and hydroboration. .

SCHEME 1 Preparation of 4-aryl-pyrrolo [3,4-c] substituted carbazoles EXAMPLE 1 Preparation of benzyl (2E) -3- (5-methoxy-1 H-indol-2-yl) -2-propenoate (2) Benzyl (triphenylphosphoranylidene) acetate (49.2 g, 0. 120 moles) was added to a stirred solution of 5-methoxy-1H-indole-2-carbaldehyde (1) (20.0 g, 0.14 mole) in CH2Cl2 (500 mg) and the solution was stirred at room temperature for 4 h. The solvent was removed in vacuo and the residue was suspended with methanol (200 ml), after which the crystallization of the product occurred. The mixture was filtered, washed with several portions of cold methanol and dried to give (2E) -3- (5-methoxy-1H-indol-2-yl) -2-benzyl propenoate (2) in a yield of 30.46 g, 87% in the form of pale yellow plates; p.f. 155-157 ° C. 1 H NMR d (CDCl 3) 8.28 (s, 1 H), 7.69 (d, J = 16.1 Hz, 1 H), 7.43-2.3 Hz, 1 H), 6.74 (d, J = 1.8 Hz, 1 H), 6.24 (d, J = 16.1 Hz, 1 H), 5.26 (s, 2H), 3.84 (s, 3H). Found: C, 74.45; H, 5.62; N, 4.58. C19H17NO3 requires C, 74.25; H, 5.57; N, 4.56.

EXAMPLE 2 The preparation of 9-methoxy-1,3-dioxo-1.2.3.3a.4.5.6.10c- octah¡dropirrolof3.4-c] carbazole-4-carboxylic acid benzyl (3) Maleimide (4.82 g, 0.050 mol) was added to a solution of (2E) 3- (5-methoxy-1 H -indole-2-yl) -2-propenoate benzyl (12.71 g, 0.041 mole) prepared as in example 1 in THF (150 ml) in a bottom flask 250 ml plane and the mixture was stirred until it became homogeneous. The THF was removed in vacuo and the residue was dried at high vacuum for 30 min. The flask was immersed in an oil bath at 175 ° C and the mixture was stirred at this temperature for 3 h. The solid melt was cooled to room temperature and ethyl acetate (100 ml) was added thereto. The solid mass was partially broken up with a spatula and the mixture was stirred vigorously overnight, after which time the product (3) was present as a cream precipitate. The followed-layered filtration with diethyl ether gave 9-methoxy-1 .S.dioxo-I ^ .S.Sa ^ .SGI Oc-octahydropyrrolotS ^ -clcarbazole ^ -benzylcarboxylate (13.76 g, 83%), mp 179-181 ° C. 1 H NMR d [(CD3) 2 SO] 10.98 (br s, 1 H), 10.87 (s, 1 H), 7.45-7.32 (m, 5H), 7.20 (d, J = 2.4 Hz, 1 H), 7.17 (d , J = 8.7 Hz, 1 H), 6.69 (dd, J = 8.7, 2.4 Hz, 1 H), 5.21 (s, 1 H), 4.22 (day, J = 7.8 Hz, 1 H), 4.14 (dd, J = 7.8, 4.2 Hz, 1 H), 3.75 (s, 3H), 3.19-3.13 (m, 1 H), 3.00 (dd, J = 16.5, 4.8 Hz, 1 H), 2.79-2.70 (m, 1 H).

EXAMPLE 3 The preparation of 9-Methoxy-1,3-dioxo-1,2,3,6-tetrahydropyrrolo [3-4-c] carbazole-4-carboxylic acid benzyl ester (4) Activated manganese dioxide (69 g) was added to a solution of 9-methoxy-1,3-dioxo-1, 2,3,3a, 4,5,6,10c-octahydropyrrolo [3,4-c] carbazole 4-benzyl carboxylate, (13.76 g, 0.034 mole), prepared as in example 2, in p-dioxane (300 ml) and the mixture was heated to reflux with vigorous stirring for 0.5-2 h. The mixture was filtered while hot through a pad of Celite, which was thoroughly washed with a 1: 1 mixture of MeOH / p-dioxane until the washings became colorless. The combined washings and filtrate were concentrated to dryness and the residue was triturated several times with diethyl ether to give 9-methoxy-1,3-dioxo-1, 2,3,6-tetrahydropyrrolo [3,4-c] carbazole- Benzyl 4-carboxylate (4) in the form of a: 5. "powder-yellow / orange (12.47 g, 91.5% mp" 245 ° C. A small sample was recrystallized from EtOAc to give 9-methoxy). 1, 3-dioxo-1, 2,3,6-tetrahydropyrrolo [3,4-c] carbazole-4-carboxylic acid benzyl in the form of orange cubes, mp 289-292 ° C. 1H NMR d [(CD3) 2SO ] 12.1 1 (sa, 1 H), 1 1.27 (sa, 1 H), 8.45 (d, 20 J = 2.6 Hz, 1 H), 7.98 (s, 1 H), 7.59 (d, J = 8.9 Hz, 1 H), 7.55-7.51 (m, 2H), 7.44-7.34 (m, 3H), 7.27 (dd, J = 8.9, 2.6 Hz, 1 H), 5.41 (s, 2H), 3.88 (s, 3H) Found: C, 68.99, H, 4.09, 6.91, C23H16N205 requires C, 69.00, H, 4.03, N, 6.99.

EXAMPLE 4 The preparation of 9-methoxy-1,3-dioxo-1,2,3,6-tetrahydropyrrolo [3,4-c] carbazole-4-carboxylic acid (5) A solution of benzyl 9-methoxy-1,3-dioxo-1, 2,3,6-tetrahydropyrrolo [3,4-c] carbazole-4-carboxylate (2.00 g), prepared as in Example 3, in DMF / MeOH (4: 1) (50 ml) containing 5% Pd-c (0.50 g) was hydrogenated at 60 psi (413,685 kPa) for 2 h (Parr apparatus). The solution was filtered through a pad of Celite, which was washed 6 times with net DMF followed by MeOH? (several cycles). The filtrate and the combined washings were concentrated to dryness in vacuo and the residue was suspended with diethyl ether to give 9-methoxy-1,3-dioxo-1, 2,3,6-tetrahydropyrrolo [3,4-c] carbazole acid. 4-carboxylic acid (5) in the form of a grayish solid. The reaction was repeated 5 times on this scale and the products were combined to give the acid 9-methoxy-1,3-dioxo-1, 2,3,6-5-tetrahydropyrrolo [3,4-c] carbazole-4- carboxylic acid (8: 1 g, 84%). A portion of the product was purified by adsorption on silica, followed by chromatography on silica, eluting with EtOAc. The product was triturated with diethyl ether to give 9-methoxy-1,3-dioxo-1, 2,3,6-tetrahydropyrrolo [3,4-c] carbazole-4-carboxylic acid as an orange solid; p.f. > 300 ° C. 0 1 H NMR d [(CD 3) 2 SO] 12.15 (s, 1 H), 8.42 (d, J = 2.5 Hz, 1 H), 7.97 (s, 1 H), 7.57 (d, J = 8.8 Hz, 1 H), 7.25 (dd, J = 8.8, 2.5 Hz, 1 H), 3.82 (s, 3H), 3.40 (a, 2H).

Found: C, 58.69; H, 3.55; N, 8.40. C16HioN205. H20 requires C, 58.54; H, 3.68; N, 8.53.

EXAMPLE 5 The preparation of 4-amino-9-methoxypyrrolo [3,4-c] carbazole-1-3 (2H-6H) -dione (6) Diphenylphosphoryl azide (1.81 ml, 8.38 mmol) was added to a mixture of 9-methoxy-1,3-dioxo-1, 2,3,6-tetrahydropyrrolo [3,4-c] carbazole-4-carboxylic acid ( 2.55 g, 8.22 mmol), prepared as in Example 4, and Et3N (1.17 mL, 8.38 mmol) in anhydrous t-butanol (300 mL) and the mixture was refluxed under a nitrogen atmosphere for 16 h. The solution was concentrated in vacuo and the residue was partitioned between EtOAc and NaHCC > 3 saturated aqueous. The insoluble material was removed by filtration of the two layers through Celite, _.15: - washing thoroughly with ^ more EtOAc: The organic phase was dried, the drying agent was removed and the solution was concentrated to dryness and gave a yellow solid. This material was dissolved in CH2Cl2 / trifluoroacetic acid (1: 1) (200 ml) and the solution was kept at room temperature for 1 h. After concentration in vacuo, the residue was partitioned between EtOAc and an aqueous saturated solution of NaHCO 3. The EtOAc solution was dried, the drying agent was removed and the solution was concentrated to dryness to give an orange solid which was adsorbed on silica gel and chromatographed. Elution with ethyl acetate / petroleum ether (1: 1) followed by ethyl acetate and then methanol / ethyl acetate (1: 9) gave 4-amino-9-methoxypyrrolo [3,4-c] carbazole-1 , 3- (2H, 6H) -dione (6) in the form of an orange powder (2.16 g, 93%), mp 342-345 ° C. H MN d [(CD3) 2 SO] 1 1.18 (s, 1 H), 10.78 (sa, 1 H), 8.18 (d, J = 2.5 Hz, 1 H), 7.29 (d, J = 8.7 Hz, 1 H ), 7.01 (dd, J = 8.7, 2.5 Hz, 1 H), 6.83 (s, 1 H), 6.28 (sa, 2H), 3.82 (s, 3H). Found: C, 63.05; H, 3.99; N, 14.05. C15HH 3O3. 1 / 2H20 requires C, 63.04; H, 4.06; N, 14.7.

EXAMPLE 6 The preparation of 4-iodo-9-methoxypyrrolo [3,4-c] carbazole-1.3- (2H.6H) dione (7) Concentrated H2SO4 (10 mL) was added at room temperature to 4-amino-9-methoxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione powder (0.50 g, 1.78 mmol), prepared as in Example 5, and the mixture was stirred for 5 min and then cooled in an ice bath. An ice-water suspension (approximately 40 ml) was added in one portion with vigorous stirring and the mixture was stirred for a further 15 min to give a brown precipitate. When the internal temperature reached 3 ° C, a solution of NaN02 (0.18 g, 2.65 mmol) in cold water (1 ml) was added dropwise over 30 seconds and the mixture was stirred for a further 3 minutes. Powdered urea (74 mg, 1.23 mmol) was added and the mixture was stirred for a further 3 min. Finally, a suspension of Kl (1.46 g, 8.79 mmol) and Cul (1.46 g, 7.66 mmol) in cold water (10 ml) was added, the mixture was stirred vigorously for 5 min, then slowly heated to 70 ° C and it was kept at this temperature for 1 h. Ethyl acetate was added and the two phase mixture was filtered through a pad of Celite, washing thoroughly with more EtOAc. The combined organic portions were washed with a 0.5N aqueous sodium sulfite solution and dried, the drying agent was removed and the solution was concentrated to dryness to give an oil which was chromatographed on silica. Elution with EtOAc and then crystallization of the product from THF / petroleum ether gave the compound 4-iodo-9-methoxypyrrolo [3,4-10 c] carbazole-1, 3- (2H, 61-1) -dione ( 7) (0.32 g, 46%) in the form of a yellow powder; p.f. 322-325 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.89 (s, 1 H), 11.29 (s, 1 H), 8.40 (s, J = 2.6 Hz, 1 H), 8.18 (s, 1 H), 7.54. (d, J = 8.9 Hz, 1 H), 7.24 (dd, J = 8.9, 2.6 Hz, 1 H), 3.87 (s, 3H). -15-- - ---- · - · - "- Found: -C, 45.49G ?, -2.36; Nr6: 92: Cí5H lN¿03 ~. -f / 4H¿0" - '~ " 'requires C, 45.42; H, 2.41; N, 7.06.

EXAMPLE 7 The preparation of 9-hydroxy-iodopyrrolo [3,4-c] carbazole-1.3- (2H-6H) -dione (8) 4-Iodo-9-methoxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione (0.50 g, 1.27 mmol) prepared as in Example 6 was added to dry pyridine hydrochloride in a portion. freshly prepared melt at 200 ° C in a CaCl2 drying tube and the mixture was stirred at this temperature for 15 min. Water was added and the mixture was extracted with EtOAc. The EtOAc extracts were dried, the drying agent was removed and the solution was concentrated to dryness to give a solid which was chromatographed on silica. Elution with EtOAc gave 9-hydroxy-4-iodopyrrolo [3,4-c] carbazole-1,3 (2H-6H) -dione (8) (0.43 g, 89%) as an orange powder; p.f. > 350 ° C. 1 H NMR d [(CD 3) 2 SO] 1 1.76 (br s, 1 H), 11 .24 (br s, 1 H), 9.29 (br s, 1 H), 8.27 (d, J = 2.4 Hz, 1 H), 8.13 (s, 1 H), 7.44 (d, J = 8.7 Hz, 1 H), 7.08 (dd, J = 8.7, 2.4 Hz, 1 H). Found: C, 44.90; H, 1.79; N, 7.14. C 14 H 7 IN 2 O 3 requires C, 44.47; H, 1.87; N, 7.40.

EXAMPLE 8 - The preparation of 4- (2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbonazole-1.3- (2H.6H) -dione (9) (I. Ar = 2-chlorophenyl) A mixture of the compound 9-hydroxy-4-iodopyrrolo [3,4-c] carbazole-1, 3- (2H-6H) -dione (41.8 mg, 0.1 10 mmol) prepared as in Example 7 and acid 2 -chlorobenzeneboronic acid (52 mg, 0.332 mmol) in p-dioxane (3 mL) and Na 2 CO 2 N (0.5 mL) was purged with nitrogen. Pd (dppf) CI2 (35 mg, 0.01 1 mmol) was added and the mixture was heated to reflux in an N2 atmosphere for 4 h and then partitioned between EtOAc and water. The organic layer was dried, the drying agent was removed and the solution was concentrated to dryness, adsorbed on silica and chromatographed. Elution with EtOAc / petroleum ether (1: 4) followed by EtOAc / petroleum ether (2: 3) gave the solid carbazole (50) which crystallized from EtOAc / petroleum ether to yield 4- (2-chlorophenyl) - 9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (9) (I, Ar = 2-chlorophenyl) (33.1 mg, 83%) as a yellow powder, mp 215-220 ° C (dec). 1 H NMR d [(CD3) 2 SO] 1 1.83 (sa, 1 H), 1 1 .01 (sa, 1 H), 9.27 (sa, 1 H), 8.32 (d, J = 2.4 Hz, 1 H ), 7.65-7.40 m, 5H), 7.08 (dd, J = 8.7, 2.4 Hz), 1 H). Found: C, 65.72; H. 3.50, N, 6.97. C20H11CIN2O3. 1 / 4EtOAc requires C, 65.54; H, 3.40; N, 7.28.

EXAMPLE 9 The preparation of 9-hydroxy-4- (3-hydroxy-4-methoxyphenyl) pyrrolo [3,4-clcarbazole-1.3- (2H.6H) -dione (10) (1. Ar = 3-hydroxy ^ 4) -methoxyphenyl6V ~ ~ The reaction of 9-hydroxy-4-iodopyrrolo [3I4-c] carbazole-1, 3- (2H, 6H) -dione, prepared as in Example 7, with 3-hydroxy-4-methoxybenzeneboronic acid according to the procedure described in Example 8 gave 9-hydroxy-4- (3-hydroxy-4-methoxyphenyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione (10) (I, Ar = 3-hydroxy-4-methoxyphenyl) (51%), mp 265 ° C (dec). 1 H NMR d [(CD 3) 2 SO] 11.67 (s, 1 H), 10.96 (s, 1 H), 9.22 (s, 1 H), 9.15 (s, 1 H), 8.33 (d, J = 2.4 Hz, 1 H), 7.57 (s, 1H), 7.41 (d, J = 8.7 Hz, 1H), 7.22 (d, J = 2.0 Hz, 1H), 7.06-6.99 (m, 2H), 6.85 (d, J = 8.1 Hz, 1H) 3.81 (s, 3H). EIMS found M +: 374.0900. C2iHi4N205 requires 374.0903.

EXAMPLE 10 The preparation of 9-hydroxy-4- (3-thienyl) pyrrolo [3,4-c] carba2ol-1.3 (2H.6H) -dione (12) (I. Ar = 3-thienyl) The reaction of 9-hydroxy-4-iodopyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione, prepared as in Example 7, with 3-thienylboronic acid according to the procedure described in Example 8 gave 9-hydroxy-4- (3-thienyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (12) (I, Ar = 3-thienyl) in a yield of 74%; p.f.247 ° C (dec). .- ..:. =. - · 1 H NMR-d [(CD.i) 2 SO] 11.73 (br s, 1 H), 11.05 (br s, 1 H); 9.24 (s, '= 1H), 9.15 (s, 1H), 8.34 (d, J = 2.4 Hz, 1H), 7.92 (dd, J = 5.0, 2.7 Hz, 1H), 7.70 (s, 1H), 7.61 (dd, J = 5.0, 2.7 Hz, 1H), 7.51 (dd, J = 5.0, 0.9 Hz, 1H), 7.42 (d, J = 8.7 Hz, 1H), 7.06 (dd, J = 8.7, 2.4 Hz, 1?). Found: C, 61.05; H, 2.96; N, 7.60. C18HioN2S03. H20 requires C, 61.36; H, 3.43; N, 7.95.

EXAMPLE 11 The preparation of 4- (3-aminophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (15) (I. Ar = 3-aminophenyl) The reaction of 9-hydroxy-4-iodopyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione, prepared as in Example 7, with 3-aminobenzeneboronic acid according to the procedure described in Example 8 gave 4- (3-aminophenyl) -9-Hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (15) (I, Ar = 3-aminophenyl) with a 62% yield; p.f. 279-284 ° C. 1 H NMR d [(CD3) 2 SO] 1 .70 (s, 1 H), 10.96 (s, 1 H), 9.22 (s, 1 H), 8.33 (d, J = 2.4 Hz, 1 H), 7.50 ( s, 1 H), 7.42 (d, J = 8.7 Hz, 1 H), 7.10-7.03 (m, 2H), 6.77-6.74 (m, 1 H), 6.72-6.68 (m, 1 H), 6.61 ( dd, J = 8.1, 2.3 Hz), 1 H), 5.1 1 (sa, 2H). Found: C, 69.41; H, 4.12; N, 10.73. C20H13N3O3 requires C, -69.96; ?, 3.82; N, 12.24. "- - - - ^ - - - - - - - EXAMPLE 12 The preparation of 4- (4-aminophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (16) (1. Ar = 4-aminophenyl) The reaction of 9-hydroxy-4-iodopyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione prepared as in Example 7 with 4- (4,4,5,5-tetramethyl) 11, 3,2-dioxoborolan-2-yl) phenylamine according to the procedure described in Example 8 gave 4- (4-amniphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione (16) (I, Ar = 4-aminophenyl) with a yield of 57%; p.f. 256-258 ° C. 1H RN d [(CD3) 2SO] 11.60 (s, 1 H), 10.92 (s, 1 H), 9.19 (s, 1 H), 8.31 (d, J = 2.3 Hz, 1 H), 7.48 (s, 1 H), 7.39 (d, J = 8.6 Hz, 1 H), 7.30 (d, J = 8.4 Hz, 2 H), 7.02 (dd, J = 8.6, 2.3 Hz, 1 H), 6.62 (d, J = 8.4 Hz, 2H), 5.29 (sa, 2H). Found: C, 68.09; H, 4.34; N, 1.03. C20H13N3O3. 1 / 2H20 requires C, 68.17; H, 4.00; N, 1 1.92.

EXAMPLE 13 The preparation of 4- (2,6-D-methylphenyl) -9-hydroxy-pyrrolo [3,4-c] carbazole-1.3- (2H.6H) -dione (17) (I. Ar = 2,6-dimethylphenyl) The reaction of 9-hydroxy-4-iodopyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione prepared as in Example 7 with 2,6-dimethylbenzeneboronic acid according to the procedure described in -r- ~ ~ -example 8 gave 4- (2,6-dimethylphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione (17) (I , Ar = 2,6-dimethylphenyl) with a yield of 62%; p.f. 230-238 ° C (dec). H NMR d [(CD3) 2 SO] 1 1.72 (s, 1 H), 10.95 (s, 1 H), 9.25 (s, 1 H), 8.32 (d, J = 2.3 Hz, 1 H), 7.44 (d , J = 8.7 Hz, 1 H), 7.35 (s, 1 H), 7.20 (t, J = 7.5 Hz, 1 H), 7.12 (d, J = 7.5 Hz, 2H), 7.06 (dd, J = 8.7 , 2.3 Hz, 1 H), 1.93 (s, 6H). EIMS found M +: 356.1159. C22H16N2O3 requires 356.1161.

EXAMPLE 14 The preparation of 4- (2,3-dichlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1.3 (2H-6H) -dione (18) (I. Ar = 2,3-dichlorophenyl) The reaction of 9-hydroxy-4-iodopyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione prepared as in Example 7 with 2,3-dichlorobenzeneboronic acid according to the procedure described in Example 8 he gave 4- (2,3-dichlorophenyl) -9-hydroxypyrrolo [3,4-c] carba-2-l, 3- (2H, 6H) -dione (18) (I, Ar = 2,3- dichlorophenyl) with a yield of 27%; p.f. 233- 10 235 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.87 (a, 1 H), 1.05 (a, 1 H), 9.29 (a, 1 H), 8.31 (d, J = 2.5 Hz, 1 H), 7.74- 7.70 (m, 1 H), 7.55 (s, 1 H), 7.48-7.45 (m, 3H), 7.09 (dd, J = 8.7, 2.5 Hz, 1 H). Found: C, 59.19; H, 3.04; N, 6.56. C2oHioCI2N203. 1 / 2H20 -. .-15 r requires C,: 59.13; Hr-2: 73; Np6.89. - * - ^ - - '- "- - | - EXAMPLE 15 The preparation of 4- (2,6-dimethoxyphenyl) -9-hydroxypyrrolo [3,4-c] carbazole- 1.3- (2H-6H-dione (19) (I. Ar = 2,6-dimethoxyphenyl) 20 The reaction of 9-hydroxy -4-iodopyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione prepared as in Example 7 with 2,6-dimethoxybenzeneboronic acid according to the procedure described in Example 8 gave 4- (2,6-dimethoxy-phenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione (19) (I, Ar = 2.6 -dimethoxyphenyl) with a yield of 43%, mp 275-277 ° C (dec). 1 H NMR d [(CD3) SO] 1 1.62 (sa, 1 H), 10.83 (sa, 1 H), 9.21 (sa, 1 H), 8.29 (d, J = 2.4 Hz, 1 H), 7.42 (s, 1 H), 7.41 (d, J = 8.4 Hz, 1 H), 7.35 (t, J = 8.4 Hz, 1 H) , 7.04 (dd, J = 8.4, 2.4 Hz, 1 H), 6.75 (d, J = 8.4 Hz, 2H), 3.63 (s, 6H) Found: C, 66.31, H, 4.50, N, 6.70, C22H16N2O5 1 / 2H20 requires C, 66.49; H, 4.31; N, 7.04.

EXAMPLE 16 The preparation of 9-hydroxy-4- (2-methoxyphenyl) pyrrolo [3,4-c] carbazole-1.3- The reaction of 9-hydroxy-4-iodopyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione,: prepared - as in "-example -7, with 2-methoxybenzeneboronic acid in accordance with the procedure described in Example 8 gave 9-hydroxy-4- (2-methoxyphenyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione (20) (I, Ar = 2 -methoxyphenyl) with a yield of 75%, mp 216 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.70 (s, 1 H), 10.90 (s, 1 H), 9.23 (s, 1 H), 8.31 (d, J = 2.4 Hz, 1 H), 7.50 (s, 1 H), 7.43 (d, J = 8.0 Hz, 1 H), 7.43-7.38 (m, 1 H), 7.31 (dd, J = 8.0 , 2.4 Hz, 1 H), 7.11-7.01 (m, 3H), 3.68 (s, 3H) Found: C, 69.21; H, 3.80; N, 7.58, C2iH14N204, 1 / 4H20 requires C, 69.51; H, 4.03; N, 7.72.

EXAMPLE 17 The preparation of 9-hydroxy-4- (4-hydroxymethylphenyl) pyrrolo [3,4-c] carbazole-1-3 (2H.6H) -dione (21) (I. Ar = 4-hydroxymethylphenyl) The reaction of 9-hydroxy-4-iodopyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione, prepared as in Example 7, with 4-hydroxymethylbenzeneboronic acid according to the procedure described in Example 8 gave 9-hydroxy-4- (4-hydroxymethylphenyl) pyrrolo [3,4-c] carbazole-, 3- (2H, 6H) -dione (21) (I, Ar = 4-hydroxymethylphenyl) in a yield of 34%; p.f. 266-271 ° C. 1 H NMR d [(CD 3) 2 SO] 1 1 .74 (br s, 1 H), 1 .00 (br s, 1 H), 9.25 (br s, 1 H), 8.34 (d, J = 2.4 Hz, 1 H) , 7.56 (d, J = 8.3 Hz, 2H), 7.56 (s, 1 H), 7.43 (d, J = 8.7 Hz, 1 H), 7.40 (d, J = 8.3 Hz, 1 H), 7.06 (dd) , J = 8.7, 2.4 Hz, 1 H), 5.27 (t, J = 5.7 Hz, 1 H), 4.59 (d, J = 5.7 Hz, 2H). ,. r = -.- Found: C, - 69:74; "H- 4:04; N; 7v57 e2íH¾N¿0." 1 / 4H20 requires C, 69.51; H, 4.02; N, 7.72.

EXAMPLE 18 The preparation of 9-hydroxy-4- (2-trifluoromethylphenyl) pyrrolo [3,4-c] carbazole-1.3- (2H.6H) -dione (22) (I. Ar = 2-trifluoromethylphenyl) The reaction of 9-hydroxy-4-iodopyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione, prepared as in Example 7, with 2-trifluoromethylbenzeneboronic acid according to the procedure described in Example 8 gave 9-hydroxy-4- (2-trifluoromethylphenyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione (22) (I, Ar = 2-trifluoromethylphenyl) with a 47% yield, mp 210 ° C (dec). H NMR d [(CD3) 2 SO] 1 1.81 (s a, 1 H), 1.01 (s a, 1 H), 9.30 (s a, 1 H), 8.31 (d, J = 2.4 Hz, 1 H), 7.86 (day, J = 7.2 Hz, 1 H), 7.75-7.64 (m, 2H), 7.51 (s, 1 H), 7.49 (day , J = 7.6 Hz, 1 H), 7.46 (d, J = 8.7 Hz, 1 H), 7.09 (dd, J = 8.7, 2.4 Hz, 1 H). EIMS found M +: 396.0721. C21 H11 F3N2O3 requires 396.0722.

EXAMPLE 19 The preparation of 9-hydroxy-4- (4-hydroxy-3-methoxyphenyl) pyrrolo [3,4-c] carbazole 1-3 (2H.6H) -dione (23) (I. Ar = 4-hydroxy) 3-methoxyphenol) The reaction of 9-Hydroxy-4-iodopyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione, prepared as in Example 7, with 2-methoxy-4- (4,4,5) , 5-tetramethyl-1, 3,2-dioxoborolan-2-yl) phenol according to the procedure described in Example 8 gave 9-hydroxy-4- (4-hydroxy-3-methoxyphenyl) pyrrolo [3,4- c] carbazole-1, 3- (2H, 6H) -dione (23) (I, Ar = 4-hydroxy-3-methoxyphenyl) with a yield of 58%; p.f. 290-295 ° C (dec). 1 H NMR d [(CD3) 2 SO] 11.67 (br s, 1H), 10.97 (br s, 1H), 9.22 (br, 1H), 9.15 (s, 1H), 8.33 (d, J = 2.4 Hz, 1H), 7.57 (s, 1H), 7.41 (d, J = 8.6 Hz, 1H), 7.23 (d, J = 2.0 Hz, 1H), 7.04 (m, 2H), 6.86 (d, J = 8.1 Hz, 1H), 3.82 (s, 3H). FABMS found [+ H] +: 375.0973. C21H15N2O5 requires 375.0981 EXAMPLE 20 The preparation of 4- (2-ethylphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (501) (I: Ar = 2-ethylphenyl) The reaction of 9-hydroxy-4-iodopyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione, prepared as in Example 7, with 2-ethylbenzeneboronic acid according to the procedure described in Example 8 gave 4- (2-ethylphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (501) (I; Ar = 2-ethylphenyl) in a yield of 69%; p.f. (MeGH / CH2Cl2 / hexane) ^ 273 ^ 275 ° C. 1 H NMR [(CD 3) 2 SO] d 11.73 (br s, 1 H), 10.95 (br s, 1 H), 9.25 (s, 1 H), 8.32 (d, J = 2.4 Hz, 1 H), 7.44 (s, 1 H), 7.44 (d, J = 8.6 Hz, 1H), 7.36 (td, J = 7.2, 1.5 Hz, 1H), 7.33 (dd, J = 8.1, 2.2 Hz, 1H), 7.25 (td, J = 7.0, 1.8 Hz, 1H), 7.20 (dd, J = 7.5, 1.2 Hz, 1H), 7.07 (dd, J = 8.7, 2.5 Hz, 1H), 2.42 (m, 2H), 0.96 (t, J = 7.6 Hz, 3H). Found: C, 73.83; H, 4.46; N, 7.82. C 22 H 16 N 2 O 3 requires C, 74.15; H.4.53; N, 7.86.

EXAMPLE 21 The preparation of 9-hydroxy-4- [2- (hydroxymethyl) phenyl] pyrrolo [3,4-c] carbazole- 1.3- (2H.6m-dione (503) (I: Ar = 2- (hydroxymethyl) phenyl) The reaction of 9-hydroxy-4-iodopyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione, prepared as in Example 7, with cyclic monoester of 2- (hydoxymethyl) benzeneboronic acid of according to the procedure described in example 8 gave 9-hydroxy-4- [2- (hydroxymethyl) phenyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione (503) (I; Ar = 2- (hydroxymethyl) phenyl) with a yield of 57%, mp (THF / CH2Cl2 / hexane) 270-280 ° C (dec). H NMR [(CD3) 2 SO] d 1 1.76 (br s, 1 H), 10.96 (br s, 1 H), 9.25 (br s, H), 8.32 (d, J = 2.4 Hz, 1 H), 7.57 (d, J = 7.6 Hz, 1 H), 7.47 (s, 1 H), 7.44 (d, J = 8.5 Hz, 1 H), 7.43 (td, J = 7.6, 1.2 Hz, 1 H), 7.31 (td, J = 7.4, 0.9 Hz, 1 H), 7.23 (dd, J = 7.5, 1.0 Hz, H), 7.06 (dd, J = 8.7, 2.5 Hz, 1 H), 5.00 (t, J = 5.4 Hz, 1 H ), 4.33 (ddrJ-1-3.6, 5.2 Hz, 1 H) r4.24 (ddrJ = 13.5, 5.3 ??, H): - ^ ~ '- - Found: C, 68.41; H, 4.29; N, 7.59. C2iH14N204. 1 / 2H20 requires C, 68.66; H, 4.12; N, 7.63.

EXAMPLE 22 The preparation of 4- (2-ethoxyphenyl) -9-hydroxypyrrolo [3.4-c] carbazole-1.3- (2H.6H) -dione (504) (I. Ar = 2-ethoxyphenyl > The reaction of 9-hydroxy-4-iodopyrrolo [3,4-c] carbazole-1,3- (2H, 6H) -dione, prepared as in Example 7, with 2-ethoxybenzeneboronic acid according to the procedure described in Example 8 gave 4- (2-ethoxyphenol) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (504) (I; Ar = 2-ethoxyphenyl) with a 74% yield; p.f. (THF / CH2CI2 / hexane) 190-193 ° C (dec). 1 H NMR [(CD3) 2 SO] d 11.71 (br s, 1H), 10.91 (br,?), 9.23 (s, 1H), 8.31 (d, J = 2.4 Hz, 1H), 7.51 (s, 1H), 7.43 (d, J = 8.7 Hz, 1H), 7.38 (td, J = 7.8, 1.7 Hz, 1H), 7.33 (dd, J = 7.5, 1.7 Hz, 1H), 7.07 (day, J = 6.7 Hz, 1H) , 7.05 (dd, J = 8.7, 2.3 Hz, 1H), 7.02 (dd, J = 7.3, 6.6 Hz, 1H), 3.97 (c, J = 6.7 Hz, 2H), 1: (t, J = 6.9Hz , 3H). - -; · ~ '' "··" '' '' '' Found: C, 70.63; H, 4.74; N, 6.88. C22H16N2O4. 1 / 4THF requires C, 70.76; H, 4.65; N, 7.18.

EXAMPLE 23 The preparation of 9-hydroxy-4- (2-thienyl) pyrrolo [3,4-c] carbazole-1.3- (2H.6H) -dione (505) (I: Ar-2-thienyl) The reaction of 9-hydroxy-4-iodopyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione, prepared as in example 7, with 2-thiophenoboronic acid according to the procedure described in Example 8 gave 9-hydroxy-4- (2-thienyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (505) (I; Ar = 2-thienyl) with a yield of 69%; p.f. (THF / CH 2 Cl 2 / hexane) 179-184 ° C (dec). 1 H NMR [(CD 3) 2 SO] d 1 1.75 (br s, 1 H), 11.11 (br s, 1 H), 9.26 (br s, 1 H), 8.34 (d, J = 2.4 Hz, 1 H), 7.75 (s) , 1 H), 7.73 (dd, J = 3.6, 1.0 Hz, 1 H), 7.68 (dd, J = 5.1, 1 .3 Hz, 1 H), 7.43 (d, J = 8.7 Hz, 1 H), 7.20 (dd, J = 5.1, 3.6 Hz, 1 H), 7.07 (dd, J = 8.7, 2.5 Hz, 1 H). Found: C, 62.38; H, 3.11; N, 7.74. Ci8H10N2O3S. 3 / 4H20 requires 62 15G ?, 3:33; ? ~ 8.05: ~ - EXAMPLE 24 The preparation of 3- (9-hydroxy-1,3-dioxo-1.2.3.6-tetrahydro-pyrrolo [3,4-c] carbazol-4-yl) benzaldehyde (507) (I: Ar = 3-formylphenyl) The reaction of 9-hydroxy-4-iodopyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione, prepared as in Example 7, with 3-formylbenzeneboronic acid according to the procedure described in Example 8 gave 3- (9-hydroxy-1,3-dioxo-1, 2,3,6-tetrahydropyrrolo [3,4-c] carbazol-4-yl) benzaldehyde (507) (I; Ar = 3- formylphenyl) with a yield of 69%; p.f. (THF / CH2Cl2 / hexane) 280-286 ° C (dec). H NMR [(CD3) 2 SO] d 1 1.82 (br s, 1 H), 11.07 (br s, 1 H), 10.11 (s, 1 H), 9.27 (br s, 1 H), 8.35 (d, J = 2.4 Hz , 1 H), 8.14 (t, J = 1.4 Hz, 1 H), 7.97 (m, 2H), 7.70 (t, J = 7.7 Hz, 2H), 7.65 (s, 1 H), 7.46 (d, J = 8.7 Hz, 1 H), 7.08 (dd, J = 8.7, 2.5 Hz, 1 H). FABMS found [M + H] +: 357.0857. C2iH13N204 requires 357. 0875 EXAMPLE 25 The preparation of 9-hydroxy-4- [2- (methylsulfanyl) phenyl] pyrrolo [3,4-c] carbazole-1.3- (2H.6H) -dione (508) (I; Ar = 2- (methylsulfanyl) phenol ) r - ~ ~ - The reaction of * 9: hydroxy-4-iodopyrrolo [3,4-c] carbazoi-1, 3- (2H, 6H) -dione, prepared as in example 7, with 2- (methylthio) acid ) benzeneboronic acid according to the procedure described in Example 8 gave 9-hydroxy-4- [2- (methylsulfanyl) phenyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione (508) ) (I; Ar = 2- (methylsulfanyl) phenyl) with a yield of 72%, mp (MeOH / CH 2 Cl 2 / hexane) 208-216 ° C. 1 H NMR [(CD 3) 2 SO] d 1 1.76 (br s, 1 H), 10.95 (br s, 1 H), 9.25 (br s, 1 H), 8.31 (d, J = 2.5 Hz, 1 H), 7.47 (s) , 1 H), 7.44 (d, J = 8.6 Hz, 1 H), 7.43 (td, J = 7.3, 2.2 Hz, 1 H), 7.38 (day, J = 7.5 Hz, 1 H), 7.27 (dd, J = 7.8, 2.2 Hz, 1 H), 7.24 (td, J = 7.3, 1 .3 Hz, 1 H), 7.07 (dd, J = 8.7, 2.5 Hz, 1 H), 2.32 (s, 3H). Found: C, 66.55; H, 3.88; N, 7.38. C21H14N2O3S. 1 / 4H20 requires C, 66.57; H, 3.86; N, 7.39.

EXAMPLE 26 The preparation of 4- (9-hydroxy-3-dioxo-1, 2.3.6-tetrahydro-pyrrolo [3,4-c] carbazol-4-yl) benzaldehyde (509) (I: Ar = 4-formylphenyl) The reaction of 9-hydroxy-4-iodopyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione, prepared as in Example 7, with 4-formylbenzeneboronic acid according to the procedure described in Example 8 gave 4- (9-hydroxy-1,3-dioxo-1, 2,3,6-tetrahydropyrrolo [3,4-c] carbazol-4-yl) benzaldehyde (509) (I; Ar = 4-formylphenyl) with a yield of 52%; p.f. (THF / eH2CI2 / hexane) 276-280C.- ····································································································· H), 10.1 1 (s, 1 H), 9.28 (sa, 1 H), 8.34 (d, J = 2.3 ??, 1 H), 8.00 (d, J = 8.2 Hz, 2H), 7.85 (d, J = 8.1 Hz, 2H), 7.65 (s, 1 H), 7.46 (d, J = 8.7 Hz, 1 H), 7.08 (dd, J = 8.7, 2.4 Hz, 1 H) Found: C, 68.43; H, 4.16; N, 7.26, C2iH12N204.3 / 4H20 requires C, 68.20, H, 3.68, N, 7.57, FABMS found [M + H] +: 357.0841, C2iH13N204 requires 357.0875, EXAMPLE 27 The preparation of 9-hydroxy-4 - [2- (Methylsulfanyl) phenyl] pyrrolof3.4-c1carbazole-1.3- (2H.6H) -dione (510) (I: Ar = 2- (methylsuffinyl) phenyl) A mixture of the compound 9-hydroxy-4- [2- (methylsulfanyl) phenyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (508) (34.5 rng, 0.092 mmoles), prepared according to Example 25, and 2-phenylsulfonyl-3-phenyloxaziridine (Davis reagent) (26.5 mg, 0.102 mmol) in THF (10 mL) was stirred at 20 ° C for 2.5 h, then adsorbed. on silica gel and chromatographed. Elution with 0-3% MeOH / CH2CI2 and then 3-4% MeOH / CH2CI2 gave (after crystallization in THF / CH2Cl2 / pentane) the compound 9-hydroxy4- [2- (methylsulfanyl) phenyl] pyrrolo [ 3,4-c] carbazole-1, 3- (2H, 6H) -dione (510) (I; Ar = 2 (methylsulfinyl) phenyl) in a yield of 86% as a yellow solid; p.f. 321 -323 ° C. - - · -H- NMR [(CD3) 2SO] d 1 1 -.86, 1 1.85 (2 sa, 1 H), 11.09 (sa, 1?), · - - - 9.30 (sa, 1 H), 8.32 (d, J = 2.4 Hz, 1 H), 8.04, 7.97 (2d, J = 7.6 Hz, 1 H), 7.74 (t, J = 7.6 Hz, 1 H), 7.65, 7.62 (2t, J = 7.4) Hz, 1 H), 7.62, 7.54 (2 s, 1 H), 7.47 (d, J = 9.1 Hz, 1 H), 7.44 (d, J = 8.4 Hz, 1 H), 7.09 (dd, J = 8.7, 2.5 Hz, 1 H), 2.43, 2.31 (2s, 3H). Found: C, 64.60; H, 3.88; N, 6.87. C2iH14N204S requires C, 64.61; H, 3.61; N, 7.18.

EXAMPLE 28 The preparation of 9-hydroxy-4- (4-hydroxyphenyl) pyrrolo [3,4-c] carbazole-1.3- (2H-6H) -dione (24) (I: Ar = 4-hydroxyphenol) The reaction of 9-hydroxy-4- (4-methoxyphenyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione prepared as described in Example 34 with BBr3 using the procedure described in Example 80 of Scheme 2 gave 9-hydroxy-4- (4-hydroxyphenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (24) (I, Ar = 4 -hydroxyphenyl) with a yield of 92%; p.f. 230 ° C (dec). 1 H R N d [(CD3) 2 SO] 1 1.67 (s, 1 H), 10.96 (s, 1 H), 9.59 (s, 1 H), 9. 22 (s, 1 H), 8.32 (d, J = 2.4 Hz, 1 H), 7.51 (s,?), 7.43 (d, J = 8.7 Hz, 1 H), 7.41 (d, J = 8.6 Hz, 2H), 7.04 (dd, J = 8.7, 2.4 Hz, 1 H), 6.84 (d, J = 8.6 Hz, 2H). FABMS found [+ H] +: 345.0875. C2oH13 204 requires 3. 4. 5. 0875 EXAMPLE 29 The preparation of 9-hydroxy-4- (3-hydroxyphenyl) pyrrolo [3,4-c] carbazole-1-3 (2H.6H) -dione (25) (I: Ar = 3-hydroxyphenyl) 9-Hydroxy-4- (3-methoxyphenyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione (prepared as described in Example 35) was reacted with BBr3 using the procedure described in the procedure described in Example 80 of Scheme 2 to give 9-hydroxy-4- (3-hydroxyphenyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione (25) ( I, Ar = 3-hydroxyphenyl) with a yield of 88%; p.f.282-285 ° C (dec). 1 H NMR d [(CD3) 2 SO] 11.73 (br s, 1H), 11.00 (br s, 1H), 9.48 (br s, H), 9.24 (s, 1H) .8.34 (d, J = 2.4 Hz, 1H), 7.54 (s, 1H), 7.43 (d, J = 8.7 Hz, 1H), 7.24 (dd, J = 7.7, 7.7 Hz, 1H), 7.05 (dd, J = 8.7, 2.4 Hz, 1H), 7.01-6.96 ( m, 2H), 6.82 (dd, J = 8.2, 2.1 Hz, 1H). FABMS found [M + H] +: 345.0875. C2oH13 204 requires 3. 4. 5. 0875 EXAMPLE 30 The preparation of 4- (2-chloro-6-hydroxyphenyl) -9-hydroxypyrrolo [3,4-c1carbazole-1.3- (2H.6H) -dione (26) (I: Ar = 2-chloro-6- hydroxyphenyl) 4- (2-Chloro-6-methoxyphenyl) -9; hydroxypyrrolo [3; 4- "'c] carbazole-1; 3- (2H, 6H) -dione prepared as in Example 33 was reacted with BBr3 using the procedure described in Example 80 of Scheme 2 to give 4- (2-chloro-6-hydroxyphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (26) (I , Ar = 2-chloro-6-hydroxyphenyl) with a yield of 70%; pf228-235 ° C. 1H NMR d [(CD3) 2SO] 11.73 (s, 1H), 10.94 (s, 1H), 9.75 ( sa, 1H), 9.25 (s, 1H), 8.30 (d, J = 2.4 Hz, 1H), 7.45 (s, 1H), 7.44 (d, J = 8.7 Hz, 1H), 7.23 (dd, J = 8.1 , 8.1 Hz, 1H), 7.07 (dd, J = 8.7, 2.4 Hz, 1H), 6.99 (d, J = 8.1 Hz, 1H), 6.90 (d, J = 8.1 Hz, 1H).

FABMS found [M + H] +: 381.0461, 379.0479. C20H12CIN2O4 requires 381 .0456, 379.0486. The compounds described in Examples 31-35 were prepared in an orderly manner by reaction of the iodide (8) prepared as described in Example 7 with the appropriate substituted arylboronic acid using the procedure described in Example 8.

EXAMPLE 31 The preparation of 4- (3-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1.3- (2H.6H) -dione (I; Ar = 3-chlorophenyl) (866) by reaction with 3-chlorobenzeneboronic acid. Found [M + H] +: 363.

(I; Ar = 4-chlorophenyl) (867) by reaction with 4-chlorobenzeneboronic acid. Found [M + H] +: 363.

EXAMPLE 33 The preparation of 4- (2-chloro-6-methoxyphenyl) -9-hydroxypyrrolo [3,4-clcarbazole-1.3- (2H.6H) -dione (I; Ar = 2-chloro-6-methoxy-phenyl) (868) by reaction with 2-chloro-6-methoxybenzeneboronic acid. Found [+ H] +: 393.

EXAMPLE 34 The preparation of 9-hydroxy-4- (4-methoxyphenyl) pyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (I; Ar = 4-methoxyphenyl) (870) by reaction with 4-methoxybenzeneboronic acid. Found [M + H] + = 359 , ·. - - EXAMPLE 35"^ The preparation of 9-hydroxy-4- (3-methoxyphenyl) pyrrolo [3,4-c] carbazole-1.3f2H.6H) -dione (I; Ar = 4-methoxyphenyl) by reaction with 4-methoxybenzeneboronic acid. Found [M + H] +: 359 EXAMPLE 36 The preparation of a series of compounds using multiple synthetic, parallel techniques from the compound 9-hydroxy-4-iodopyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione prepared as in Example 7 Combichem procedure 1 In a vial with an 8 ml screw cap was added a solution of 9-hydroxy-4-iodo-6H-pyrrolo [3, 4-c] carbazole-1,3-dione (0.1 mmol) prepared as in Example 7 in dioxane (1 mL), a solution of Reagent 1 (see Table 1) (0.1 mmol) in 1: 1 dioxane / K2C03 2.5 M (1 ml) and complex of [1, 1 'Bis (diphenylphosphino) ferrocene] -dichloropolylate (II) with dichloromethane (0.003 g, 0.0037 mmol). The vial was capped and the reaction mixture was stirred for 4 hours at 90 ° C. After cooling to room temperature, the solution was removed in vacuo. Purification was carried out by reverse phase HPLC (3% n-propanol. In 3% acetonitrile y-n-propanol in water as eluent; column C-18). The "products were characterized by mass spectral analysis (See table 1 )· Combichem procedure 2 In a vial with a screw cap of 8 ml, a solution of 9-hydroxy-4-iodo-6H-pyrrolo [3,4-c] carbazole-1,3-dione (0.1 mmol) prepared as in Example 7 in anhydrous toluene (1 mL), a solution of Reagent 1 (see Table 1) in 1: 1 anhydrous toluene / dimethylformamide (1 mL) and a solution of palladium (II) diacetate 0.05 M plus or- 0.2 M dicyclohexylphosphinobiphenyl in anhydrous toluene (20 μm) and 40 mg of K3PO4.2H2O in an H2 atmosphere. The vial was capped and the reaction mixture was stirred for 20 hours at 100 ° C. After cooling to room temperature, the solution was removed in vacuo. Purification was carried out by reverse phase HPLC (3% n-propanol in acetonitrile and 3% n-propanol in water as eluent: column C-18). The products were characterized by mass spectral analysis (See table 1 ).

CUADR0 1 Reagent Procedure 1 Product Analytical Data MS-APCI [M + H] + Acid procedure 2- 4- (2-Acetylphenyl) -9- 371.2 Combichem 1 acetylphenylboronic hydroxy-6H-pyrrolo [3,4-c] carbazole-1,3-dione Acid Procedure. 4- (4-Fluorophenyl) -9 ÷ ÷ - "- - - 347.2 'Combichem 1 fluoro-phenylboronic hydroxy-6H-pyrrolo [3,4- c] carbazole-1,3-dione Acid Process 3,4- 4 - (1, 3-Benzodioxo1 -5- 373.2 Combichem 1 methylenedioxybenzene-9-hydroxy-6H-noboronic pyrrolo [3,4-c] carbazole-1,3-dione Acid Process 2-9-Hydroxy-4-naphthalene- 2- 379.2 Combichem 1 naphthalenoboronic il-6H-pyrrolo [3,4-c] carbazole-1,3-dione Process Acid 4-methylthio- 9-Hydroxy-4- (4- 375.2 Combichem 1 phenyl boronic methylsulfanylphenyl) - 6H- pyrrolo [3,4-c] carbazole-1,3-dione Process acid 4-4-biphenyl-4-yl-9-hydroxy- 405.2 Combichem 1 biphenylboronic acid 6H-pyrrolo [3,4-c] carbazole-1 , 3-dione Acid procedure 3-9-Hydroxy-4- (3-413.2 Combichem 1 (trifluoromethoxy) ben trifluoromethyl-phenyl) -6H-cenoboronic pyrrolo [3,4-c] carbazole-1,3-dione Acid Procedure 3 - 9-Hydroxy-4- (3- 359.2 Combichem 1 methoxyphenylmethoxyphenyl) -6H-boronic pyrrolo [3,4-c] carbazole-1,3-dione Procedure Acid 3- 3- (9-Hydroxy-1,3-dioxo-354.2 Combichem 1 cyanophenylboronic acid 1, 2,3,6-tetrahydropyrrolo [3,4-c] carbazole-44) -benzonitrile Acid procedure 2,5 - 4- (2,5-Dichlorophenyl) -9- 398.2 Combichem 1 dichlorophenylboronic hydroxy-6H-pyrrolo [3,4-c] carbazole-1,3-dione Acid procedure 4-9-Hydroxy-4- (4-413.2 Combichem 1 trifluoromethoxytrifluoromethoxy-phenyl) -phenyl boronic acid 6H-pyrrolo [3,4-c] carbazole-1,3-dione Process Acid 3-9-Hydroxy-4- (3- 359.2 Combichem 1 Hydroxymethylphenylbor hydroxymethylphenyl) - 6H- onic pyrrolo [3,4-c] carbazole-1,3-dione Acid Procedure ~ furan-3- 4-Furan 2-yl-9 hydroxy- 319.2 Combichem 1 boronic. - - · 6H-pyrrolo [3; 4 - c] carbazole-1,3-dione Process Acid pyridine-3-9-Hydroxy-4-pyridin-3-yl-330.2 Combichem 1 boronic 6H-pyrrolo [3,4 - c] carbazole-1,3-dione Procedure 2,4-4- (2,4-Dimethoxy-391.2 Combichem 1-dimethoxypyrimidin-pyrimidin-5-yl) -9-hydroxy-5-boronic acid 6H-pyrrolo [3, 4- c] carbazole-1,3-dione Process Acid 4- 4- (9-Hydroxy-1,3-dioxo-354.2 Combichem 1 cyanophenylboronic 1, 2,3,6-tetrahydropyrrolo [3,4-c] carbazole-1,3-dione Process Acid 4-9-Hydroxy-4- (4-397.2 Combichem 1 (trifluoromethyl) phenyltrifluoromethylphenyl) -6H-boronic pyrrolo [3,4-c] carbazole-1,3-dione Procedure 3-9-Hydroxy-4- (3-397.2) Combichem 1 (trifluoromethyl) phenyltrifluoromethylphenyl) -6H-boronic pyrrolo [3,4-c] carbazole-1,3-dione Acid procedure 4-9-Hydroxy- 4- (4- 407.2 Combichem 1 (methylsulfonyl) phenyl-methylsulfonylphenyl) -6H-boronic pyrrolo [3,4-c] carbazole-1,3-dione Acid procedure 3- N- [3- (9-Hydroxy-1, 3- 386.2 Combichem 1 acetamidof enylboron dioxo-, 2,3,6- nico tetrahydro-pyrrolo [3,4- c] carbazol-4-yl) -phenyl] acetamide Process acid 4- 4- (4-Dimethylaminophenyl) - 372.2 Combichem 2 dimethylamino-phenyl- 9-hydroxy-6H-boronic pyrrolo [3,4-c] carbazole-1,3-dione Process acid 3-acetylphenyl-4- (3-Acetylphenyl) -9- 371.2 Combichem 2 boronic hydroxy-6H-pyrrolo [3, 4- c] carbazole-1,3-dione Acid procedure 3-9-Hydroxy-4- (3- 345.2 Combichem 2 hydroxyphenylboronic hydroxyphenyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione , " Process; acid: - - "3-9-Hydroxy-4-m-tolyl-6H-343.2 Combichem 2 methylbenzeneboron pyrrolo [3,4-c] carbazole-1,3-dione O-9-Hydroxy-4-o acid -tolyl-6H- 343.2 Combichem 2 tolylboronic pyrrolo [3,4-c] carbazole-1,3-dione Procedure Trans-2- 9-Hydroxy-4 - ((E) -styryl) - 355.2 Combichem 2 phenylvinyl boronic acid 6H-pyrrole [3,4-c] carbazole-1,3-dione Acid procedure 2- 2- (9-Hydroxy-1,3-dioxo-357.2 Combichem 2 formylphenylboronic 1, 2,3,6-tetrahydropyrrolo [ 3,4-c] carbazol-4-yl) -benzaldehyde Acid procedure 2,5- 4- (2,5-Dimethylphenyl) -9-357.2 Combichem 2 dimethylphenylboronic hydroxy-6H-pyrrolo [3,4- c] carbazole- 1,3-dione Process Acid 4-9-Hydroxy-4- (2- 375.2 Combichem 2 methylsulfanyl-methylsulfaniphenyl) -6H-benzeneboronic pyrrolo [3,4-c] carbazole-1,3-dione Acid Procedure 4- 9-H id roxi-4-p-toli I-6H-343.2 Combichem 2 methylbenzene-pyrrolo [3,4-c] carbazolboronic 1,3-dione SCHEME2 Scheme 2 procedures Representative procedure for method 2 of scheme 2 EXAMPLE 37 The preparation of 2- [2- (2-chlorophenyl) ethenyl] -5-methoxy-1 H-indole (II: Ar = 2-chlorophenyl) (27) Lithium diisopropylamide (34.4 ml of a 1.5 N solution, 0.052 mole) was added dropwise under a nitrogen atmosphere to a suspension of benzyl (triphenyl) phosphonium chloride (20.17 g, 0.048 mole) in dry THF (200 g. mi) and the solution was stirred at room temperature for 15 min. A solution of 5-methoxy-1 H-indole-2-carbaldehyde (1) (6.99 g, 0.040 mol) in THF (30 ml) was added and stirring was continued at room temperature for 15 min and then the mixture gave a reaction. it was heated to reflux for 6 h. The cooled solution was diluted with water, extracted with EtOAc, the organic phase was dried, the drying agent was removed and the solution was concentrated to dryness to give an oil which was adsorbed on silica and chromatographed on silica. Elution with ethyl acetate / petroleum ether (1: 1) gave 2- [2- (2-chlorophenyl) ethenyl] -5-methoxy-1 H-indole (27) as a mixture of E / Z isomers with a yield of 9.76 g, 87%. Crystallization of a small sample in methanol yielded pure isomer E, m.p. 135-137 ° C. 1 4 1 H RN d (CDCl 3) 1 1.39 (s, 1 H), 7.86 (dd, J = 7.8, 1.5 Hz, 1 H), 7.49 (dd, J = 8.0, 1.2 Hz, 1 H), 7.43 (d , J = 16.4 Hz, 1 H), 7.37 (m, 1 H), 7.31-7.23 (m, 3H), 7.01 (d, J = 2.4 Hz, 1 H), 6.77 (dd, J = 8.7, 2.4 Hz , 1 H), 6.56 (s, 1 H), 3.75 (s, 3H). Found: C, 72.01; H, 5.03; N, 4.98. C17H 4CINO requires C, 71. 96; H. 4.79; N, 4.94.

Representative procedure for method 3 of scheme 2 EXAMPLE 38 The preparation of 1- (3- {[tert-butyl (dimethyl) silyl] oxy} propyl) -2- [2- (2-chlorophenyl) ethenyl] -5-methoxy-1H-indole (III: Ar 2-chlorophenyl R 10 - CH CH 2 CH 2 OSiMe 2 t-Bu) (28) - - "Sodium hydride" was added (1.05 g of a 50% dispersion - in mineral oil, 0.022 mol) to a solution of the compound 2- [2- (2-chlorophenyl) ethenyl] -5-methoxy-1 H -indole prepared according to example 37 (4.13 g, 0.014 mol) in DMF (30 ml) and the solution was stirred at room temperature for 5 min.Thromopropyl tert-butyl (dimethyl) silyl ether (4.04 g, 0.016 moles) and the stirring was continued for 2 h.The solution was diluted with water, extracted with EtOAc which was well washed with brine, the organic phase was dried, the drying agent was removed and the solution was concentrated to dryness to give 1 - (3- {[tert-Butyl (dimethyl) silyl] oxy} propyl) -2- [2 (2-chlorophenyl) ethenyl] -5-methoxy-1 H-indole (28) in the form of an oily solid (4.98 g) (in the form of a mixture of E / Z isomers) which was used without further purification.

EXAMPLE 39 The preparation of 6- (3- {[tert-butyl (dimethyl) silyl] oxo} propyl) -4- (2-chlorophenyl) -9-methoxypyrrolor3.4-c] carbazole-1.3 (2H -6H) -dione (V; Ar = 2-chlorophenyl R10 = CH2CH2CHzOSiMe, t-Bu) (29) 1- (3. {[[Tert-Butyl (dimethyl) silyl] oxy} propyl) -2- [2- (2-chlorophenyl) ethenyl] -5-methoxy-1H-indole prepared from according to example 38 with maleimide according to the procedure described in example 68 with the exception that the reaction time was 16 h. The resulting product was reacted with nC > 2 according to the procedure described in Example 81 with the exception that the reaction time was 8 h After chromatography on silica, the product was triturated with diethyl ether to give 6- ( 3-. {[[Tert-butyl (dimethyl) silyl] oxy} propyl) -4- (2-chlorophenyl) -9-methoxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione (29) with a yield of 4.87 g, 61%, in the form of a yellow solid, mp 199-201 ° C. H NMR d [(CD3) 2SO 1 1.12 (a, 1 H), 8.52 (d, J = 2.6Hz, 1 H), 7.75 (s, 1 H), 7.66 (d, J = 8.9 Hz, 1 H), 7.57 (dd, J = 8.3 Hz, 1 H), 7.5-7.4 (m, 3H ), 7.30 (dd, J = 8.9, 2.6 Hz, 1 H), 4.53 (t, J = 6.4 Hz, 2H), 3.90 (s, 3H), 3.55 (t, J = 5.8 Hz, 2H), 1. 94 (m, 2H), 0.77 (s, 9H), -0.06 (s, 3H).

Found: C, 65.72; H, 6.09; N, 5.19. C30H32CIS1N2O4 requires C, 65.74; H, 5.88; N, 5.1 1.

EXAMPLE 40 The preparation of 4- (2-chlorophenyl) -6- (3-hydroxypropyl) -9-methoxypyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (V: Ar = 2-chlorophenyl, R10-CH? CH2CH2OH) (31) 3 N HCl (50 ml) was added to a solution of 6- (3. {[[Tert-butyl (dimethyl) silyl] oxy} propyl) -4- (2-chlorophenyl) -9-methoxypyrrolo [3]. , 4-c] carbazole-1, 3- (2H, 6H) -dione (4.87 g, 8.85 mmol) prepared according to example 39 in 1: 1 THF / methanol (200 ml). After stirring at room temperature for 2 h, most of the solvents were removed in vacuo, the residue was extracted with ethyl acetate, washed well with water and the organic portion was concentrated to a volume of 60 ml. "Petroleum ether was added to precipitate the product, which was removed by filtration and triturated several times with diethyl ether.The solid was crystallized from THF / petroleum ether and gave 4- (2-chlorophenyl) -6- (3- hydroxypropyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (V; Ar = 2-chlorophenyl, R10 = CH2CH2CH2OH) (31) with a yield of 3.77 g, 88% in the form of a yellow powder, mp 228-230 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.12 (sa, 1 H), 8.52 (d, J = 2.5 Hz, 1 H), 7.80 (s) , 1 H), 7.70 (d, J = 8.9 Hz, 1 H), 7.58 (dd, J = 8.1, 2.2 Hz, 1 H), 7.53-7.42 (m, 3H), 7.31 (dd, J = 8.9, 2.5 Hz, 1 H), 4.63 (a, 1 H), 4.53 (t, J = 6.9 Hz, 2H), 3.91 (s, 3H), 3.40 (m, 2H), 1.91 (m, 2H). C, 66.00; H, 4.23; N, 6.55, C24H19CIN204 requires C, 66.29; H, 4.40; N, 6.44.

EXAMPLE 41 The preparation of 2-. { 2- [2- (2-Chlorofertil) ethenyl] -5-methoxy-1H-indol-1-yl} ethanol (III: Ar = 2-chlorophenol, R10 = CH2CH3OH) (44) The alkylation of 2- [2- (2-dorophenyl) ethenyl] -5-methoxy-1 H-indole (27) prepared according to Example 37 with 2-bromoethyl tetrahydro-2H-pyran-2-yl ether using the procedure described in Example 38 followed by reaction of the crude product with 2 N HCl in methanol gave 2-. { 2- [2- (2-chlorophenyl) ethenyl] -5-methoxy-1 H-indol-1-yl} ethanol (III; Ar = 2-chlorophenyl, R10 = CH2CH2OH) (44) with a yield of 86% in the form of a mixture of E / Z isomers, which was used without further purification.

EXAMPLE 42 The preparation of 4- (2-chlorophenyl) -6- (2-hydroxyethyl) -9-methoxy-4.5.6.10-tetrahydropyrrolo [3,4-c] carbazole-1.3 (2H.3aH) -dione (V: Ar = 2-chlorophenyl R10 = CH CH, OH) (45) The reaction of 2-. { 2- [2- (2-chlorophenyl) ethenyl] -5-methoxy-1 H-indol-1-yl} ethanol (III; Ar = 2-chlorophenyl, R10 = CH2CH2OH) (44) prepared according to example 41 with maleimide according to the procedure described in Example 68 gave 4- (2-chlorophenyl) -6- (2- hydroxyethyl) -9-methoxy-4,5,6,10c-tetrahydropyrrolo [3,4-c] carbazole-1, 3- (2H, 3aH) -dione (V; Ar = 2-chlorophenyl, R 0 = CH 2 CH 2 OH) (45) with a yield of 79% in the form of an oily solid, which was used without further purification.

EXAMPLE 43 · The preparation of 4- (2-chlorophenyl) -6- (2-hydroxyethyl) -9-methoxy-fluoro [3,4- c1carbazole-1.3 (2H.6H) -dione (V: Ar = 2-chlorophenyl) R10 = CH, CH, OH) (461 Reacted 4- (2-chlorophenyl) -6- (2-hydroxyethyl) -9-methoxy-4,5,6,10c-tetrahydropyrrolo [3,4-c] carbazole-1,3 (2H, 3aH) - dione (V; Ar = 2-chlorophenyl, R 0 = CH 2 CH 2 OH) (45) prepared according to Example 42 with Mn 02 using the procedure described in Example 79 with the exception that the reaction time was 18 h, 4- (2-chlorophenyl) -6-. { 2-hydroxyethyl) -9-methoxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione (V; Ar = 2-chlorophenyl, R = CH2CH2OH) (46) with a yield of 72% in the form of a yellow powder, mp 255-257 ° C. 1 H NMR d [(CD 3) 2 SO] 11.10 (br s, 1 H), 8.52 (d, J = 2.6 Hz, 1 H), 7.80 (s, 1 H), 7.71 (d, J = 9.0 Hz, 1 H) , 7.59-7.56 (m, 1 H), 7.52-7.43 (m, 4H), 7.29 (dd, J = 9.0, 2.2.6 Hz, 1 H), 4.84 (t, J = 5.0 Hz, 1 H), 4.53 (t, J = 5.2 Hz, 2H), 3.90 (s, 3H), 3.77 (m, 2H). Found: C, 65.50; H, 4.07; N, 6.59. C23H17CIN204 requires C, 65.64; H, 4.07; N, 6.66.

EXAMPLE 44 The preparation of. 4- (2-chlorophenyl) -6- (2-hydroxyethyl) -9-hydroxypyrrolo [3,4-c1carbazole-1.3 (2H. 6H) -dione (VI: Ar = 2-chlorophenyl, R10-CH2CH2QH) (47) The reaction of 4- (2-chlorophenyl) -6- (2-hydroxyethyl) -9-methoxy-6H) -dione "(V; Ar = 2-chlorophenyl, R10 = CH2CH2OH) (46) prepared according to Example 43 with BBr3 using the procedure described in Example 80 gave the compound 4- (2-chlorophenyl) -6- (2-hydroxyethyl) -9-hydroxypyrrolo [3,4-c ] carbazole-1, 3- (2H, 6H) -dione (VI; Ar = 2-chlorophenyl, R10 = CH2CH2OH) (47) with a yield of 87% in the form of a yellow / orange powder; p.f. 265 ° C (dec). 1 H NMR d [(CD 3) 2 SO] 1 1 .04 (br s, 1 H), 9.33 (br s, 1 H), 8.38 (d, J = 2.4 Hz, 1 H), 7.75 (s, 1 H), 7.60 -7.56 (m, 2H), 7.52-7.43 (m, 4H), 7.12 (dd, 1 J = 8.8, 2.4 Hz, 1 H), 4.83 (t, J = 5.5 Hz, 1 H), 4.49 (t, J = 5.2 Hz, 2H), 3.77 (dt, J = 5.5, 5.2 Hz, 2H). Found: C, 63.41; H, 4.11; N, 6.32. CaaH ^ CINzCU. 1 / 2H20 requires C, 63.54; H, 3.87; N, 6.73.

EXAMPLE 45 The preparation of 5-methoxy-2- [2- (2-methoxy-5-nitrophenyl) ethenyl] -1 H -indole (II; Ar = 2-methoxy-5-nitrophenyl) (35) Reaction of 5-methoxy-1 H-indole-2-carbaldehyde (1) with 2-methoxy-5-nitrobenzyltriphenylphosphonium chloride using the procedure described in Example 37 gave 5-methoxy-2- [2- (2-methoxy -5-nitrophenyl) ethenyl] -1H-indole (II; Ar = 2-methoxy-5-nitrophenyl) (35) with a yield of 76% in the form of an orange solid (a mixture of E / Z isomers) it was used without further purification.

EXAMPLE 46 The preparation of 5-methoxy-2- [2- (3,5-dinitrophenyl) ethenyl] -1 H-indole (II: Ar = 3,5-dinitrophenyl) (40) Reaction of 5-methoxy-1H-indole-2-carbaldehyde (1) with 3,5-dinitrobenzyltriphenylphosphonium bromide using the procedure described in Example 37 gave 5-methoxy-2- [2- (3,5- dinitrophenyl) ethenyl] -1H-indole (II; Ar = 3,5-dinitrophenyl) (40) with a yield of 26% as an orange solid (a mixture of E / Z isomers) which was used without additional purification.

EXAMPLE 47 The preparation of 4- (3T5-dinitrophenyl) -9-methoxy-4.5.6.10-tetrahydropyrrolo [3.4-c] carbazole-1.3 (2H. 3aH) -dione (IV; Ar-3,5-dinitrophenyl; R10 = H ) (41) The reaction of 5-methoxy-2- [2- (3,5-dinitrophenyl) ethenyl] -H-indole (II; Ar = 3,5-dinitrophenyl (40) prepared as described in Example 46 with maleimide using the procedure described in Example 69 gave 4- (3,5-dinitrophenyl) -9-methoxy-4,5,6,10c-tetrahydropyrrolo [3,4-c] carbazole-1> 3- (2H, 3aH) - dione (IV; Ar = 3,5-dinitrophenyl, R10 = H) (41) with a yield of 89% as a glassy solid which was used without further purification. EXAMPLE 48 The preparation of 4- (3,5-dinitrophenyl) -9-methoxypyrrolo [3,4-c] carbazole-1.3- (2H.6H) -dione (V: Ar = 3,5-dinitrophenyl, R10 = H) (42) The reaction of 4- (3,5-dinitrophenyl) -9-methoxy-4,5,6,10c-tetrahydropyrrolo [3,4-c] carbazol-1, 3- (2HI3aH) -dione (IV; Ar = 3,5-dinitrophenyl, R = H) (41) prepared as described in Example 47 with DDQ according to the procedure described in Example 70 gave 4- (3,5-dinitrophenyl) -9-methoxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione (V; Ar = 3,5-dinitrophenyl, R 10 = H) (42) with a yield of 42% in the form of a reddish solid that was used without further purification.

EXAMPLE 49 The preparation of 4- (3,5-dinitrophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1.3- (2H.6H) -dione (V: Ar = 3,5-dinitrophenyl, R 0 = H) (43) The reaction of 4- (3,5-dinitrophenyl) -9-methoxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione (V; Ar = 3,5-dinitrophenyl, R10 = H ) (42) prepared as described in Example 48 with pyridinium hydrochloride according to the procedure described in Example 81 gave 4- (3,5-dinitrophenyl) -9- hydroxypyrrolo [3,4-c] carbazole- 1, 3 (2H, 6H) -dione (V; Ar = 3,5-dinitrophenyl, R10 = H) (43) with a yield of 57% in the form of an orange powder, mp. > 330 ° C. ·.. - -- -- - - -- ·1? NMR d [(CD3) 2 SO] 1 1.94"(s ~ a, 1 H), 11.18 (s a, 1 H), .9.32 (s a, 1 H), 8.91 (s, 3H), 8.35 (d, J = 2.3 Hz, 1 H), 7.83 (s, 1 H), 7.49 (d, J = 8.7 Hz, 1 H), 7.11 (dd, J = 8.7, 2.3 Hz, 1 H).

EXAMPLE 50 The preparation of 5-methoxy-2- [2- (2-methoxyphenyl) ethenyl] -1 l-Uindol (II: Ar = 2-methoxyphenyl) (97) Reaction of 5-methoxy-1H-indole-2-carbaldehyde (1) with 2-methoxybenzyltriphenylphosphonium chloride using the procedure described in Example 37 gave 5-methoxy-2- [2- (2-methoxyphenyl) ethenyl] - 1 H-indole (II; Ar = 2-methoxyphenyl) (97) with a yield of 98% in the form of a yellow solid (a mixture of E / Z isomers) which was used without further purification.

EXAMPLE 51 The preparation of 1- (3- [tert-butyl (dimethyl) siMI] oxy] propyl) -5-methoxy-2- [2- (2-methoxyphenyl) ethenyl] -1H-indole ( III: Ar = 2-ethoxyphenyl, R10 = CH2CH2OSiMezt-Bu) (98) The reaction of 5- ethoxy-2- [2- (2-methoxyphenyl) ethenyl] -1H-indole (II; Ar 2-methoxyphenyl) (97) prepared as in example 50 with tert-butyl (dimethyl) silyl ether of 3-bromopropyl using the procedure described in Example 38 gave 1- (3. {[[tert-butyl (dimethyl) silyl] oxy} propyl) -5-methoxy-2- [2- (2-methoxyphenyl) ) ethenyl] -1 H-indole (III; Ar = 2-methoxyphenyl, R10 = CH2CH2CH2OSiMe2tBu) (98) with a yield of 97% which was used without further purification.

EXAMPLE 52 The preparation of 6- (3- [tert-butyl (dimethyl] silyl] oxy] propyl) -9-methoxy-4- (2-methoxyphenyl) -1,56.10c-tetrahydropyrrolof3-c1carbazole- 1.3- (2H-3aH) -dione (IV: Ar = 2-methoxyphenyl, R 10 CH, CH, CH, OsiMe &tt-Bu) The reaction of 1- (3- {[tert-butyl (dimethyl) silyl] oxy} propyl) -5-methoxy-2- [2- (2-methoxyphenyl) ethenyl] -1H-indole (III; Ar 2-methoxyphenyl, R 10 CH 2 CH 2 CH 20 SiMe 2 t -Bu) (98) prepared as described in Example 51 with maleimide using the procedure described in Example 68 gave 6- (3. {[Tert-butyl (dimethyl) silyl]] oxy, propyl) -9-methoxy-4- (2-methoxyphenyl) -4,5,6,10c-tetrahydropyrrolo [3,4-c] carbazole-1,3 (2H, 3aH) -dione (IV; Ar = 2-methoxyphenyl; R10 = CH2CH2CH2OSi e2t-Bu) (99) with a yield of 89% in the form of a chestnut powder, which was used without further purification.

- - - · | - ~ - 'EXAMPLE 53 ~: = _ The preparation of 6- (3-hydroxypropyl) -9-methoxy-4- (2-methoxyphenyl) pyrrolo 3.4-c] carbazole-1.3- (2H.6H ) -dione (V: Ar = 2-methoxyphenyl, R10 = CH CH, CHgOH) (100) The reaction of 6- (3. {[[Tert-butyl (dimethyl) silyl] oxy} propyl) -9-methoxy-4- (2-methoxyphenyl) -4,5,6,10 tetrahydropyrrolo [3,4-c] carbazole-1, 3- (2H, 3aH) -dione (IV; Ar = 2-methoxyphenyl; R10 = CH2CH2CH2OSilvle2t-Bu) prepared as described in example 52 with DDQ using the procedure described in Example 70 followed by reaction with 2 N HCl in THF / methanol gave 6- (3-hydroxypropyl) -9-methoxy-4- (2-methoxyphenyl) pyrrolo [3,4-c] carbazole-1, 3 (2H, 6H) -dione (V; Ar = 2-methoxyphenyl, R10 = CH2CH2CH2OH) (100) with a yield of 72% in the form of an orange powder; p.f. 223-225X. 1 H NMR d [(CD3) 2 SO] 10.99 (br s, 1 H), 8.53 (d, 2.6 Hz, 1 H), 7.74 (s, 1 H), 7.67 (d, J = 8.9 Hz, 1 H), 7.45-7.40 (m, 1 H), 7.36 (dd, J = 7.4, 1.7 Hz, 1 H), 7.29 (dd, J = 8.9, 2.7 Hz, 1 H), 7.1 1 (d, J = 8.1 Hz, 1 H), 7.06 (dd, J = 7.2, 7.2 Hz, 1 H), 4.63 (t, J = 4.8 Hz, 1 H ), 4.52 (t, J = 6.9 Hz, 2H), 3.90 (s, 3H), 3.69 (s, 3H), 3.40 (m, 2H), 1.91 (m, 2H). Found: C, 69.55; H, 5.31; N, 6.30. C25H22N205 requires C, 69. 76; H, 5.15; N, 6.51.

EXAMPLE 54 The preparation of 9-hydroxy-4- (2-hydroxyphenyl) -6- (3-hydroxyphenyl, R10 = CH2CH CH2OH) (101) The reaction of 6- (3-hydroxypropyl) -9-methoxy-4- (2-methoxyphenyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione (V; Ar = 2- methoxyphenyl, R10 = CH2CH2CH2OH) (100) prepared as described in Example 53 with BBr3 using the procedure described in Example 80 gave 9-hydroxy-4- (2-hydroxyphenyl) -6- (3- hydroxypropyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione (VI; Ar = 2-hydroxyphenyl, R10 = CH2CH2CH2OH) (101) with a yield of 82% in the form of a powder orange, pf 306-309 ° C. 1 H NMR d [(CD3) 2 SO] 10.90 (a, 1 H), 9.40 (a, 1 H), 8.38 (d, J = 2.4 Hz, 1 H), 7.67 (s, 1 H), 7.56 (d, J = 8.8 Hz, 1 H), 7.30-7.23 (m, 2H), 7.13 (dd, J = 8.8, 2.4 Hz, 1 H), 6.94-6.88 (m, 2H), 4.78 (a, 2H), 4.47 (t, J = 6.8 Hz, 2H), 3.41 (t, J = 6.0 Hz, 2H), 1.91 (m, 2H). Found: C, 66.85; H, 4.61; N, 6.63. C23H18 205. 1 / 2H20 requires C, 67.14; H, 4.65; N, 6.80.

EXAMPLE 55 The preparation of 2- [2- (2-chloro-6-methoxyphenyl) ethenyl] -5-methoxy-1-indole (II Ar = 2-chloro-e-methoxyphenyl) (102) Reaction of 5-methoxy-1 H-indole-2-carbaldehyde (1) with "2-chloro-6-methoxybenzyl-eosilphosphonium bromide using the procedure described in Example 37 gave 2- [2- (2-chloro- 6-methoxyphenyl) ethenyl] -5-methoxy-1 H-indole (II; Ar = 2-chloro-6-methoxyphenyl) (102) in a yield of 92% as a yellow solid (a mixture of E / isomers) Z) that was used without further purification.

EXAMPLE 56 The preparation of 1- (3-1- [tert -butyl (dimethylsilyl] oxy} propyl) -2- [2- (2-chloro-6-methoxyphenyl) ethenyl-5-methoxy-1H- indole (III: Ar = 2-chloro-6-methoxyphenyl) R10 = CH2CH CH2OSiMe? t-Bul M03 The reaction of 2- [2- (2-chloro-6-methoxyphenyl) ethenyl] -5-methoxy-1 H -indole (II; Ar = 2-chloro-6-methoxyphenyl) (102) prepared as described in Example 55 with tert-butyl (dimethyl) silyl 3-bromomethyl ether using the procedure described in Example 38 gave 1- (3. {[[tert-butyl (dimethyl) silyl] oxy] .}. propyl) -2- [2- (2-chloro-6-methoxyphenyl) ethenyl] -5-methoxy-1 H-indole (III; Ar = 2-chloro-6-methoxyphenyl, R10 = CH2CH2CH2OSiMe2t-Bu) (103) with a 91% yield that was used without further purification.

EXAMPLE 57 The preparation of 6- (3. {[[Tert-butyl (dirnethyl-methoxyphenyl) -9-methoxy-4,5-6.10c-tetrahydropyrrolo [3f4-c] carbazole-1.3 (2H.3aH) -dione (IV : Ar = 2-chloro-6-methoxyphenyl- R 0 = CH2CH CH2OSiMe2t-Bu) (104) The reaction of 1- (3- {[tert-butyl (dimethyl) silyl] oxy} propyl) -2- [2- (2-chloro-6-methoxy-phenol) ethenyl] -5-methoxy- 1 H-indole (III; Ar = 2-chloro-6-methoxyphenyl, R10 = CH2CH2CH2OSiMe2t-Bu) (103) prepared as described in Example 56 with maleimide using the procedure described in Example 68 gave 6- (3 - { [tert -Butyl (dimethyl) silyl] oxy} propyl) -4- (2-chloro-6-methoxyphenyl) -9-methoxy 4,5,6,10-tetrahydropyrrolo [3,4-c] ] carbazole-1, 3 (2H, 3aH) -dione (IV; Ar = 2-chloro-6-methoxyphenyl, R 0 = CH 2 CH 2 CH 2 OSiMe 2 t -Bu) (104) with a yield of 77% in the form of a cream powder, which it was used without further purification.

EXAMPLE 58 The preparation of 4- (2-chloro-6-methoxyphenyl) -6- (3-hydroxypropyl) -9-methoxyDirrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (V: Ar = 2- chloro-6-methoxyphenyl, R 10 = CH 2 CH, CH 2 OH) (105) The reaction of 6- (3. {[[Tert-butyl (dimethyl) silyl] oxy} propyl) -4- (2-chloro-6-methoxyphenyl) -9-methoxy-4,5,6,10 c -tetrahydropyrrolo [3,4-c] carbazole-1, 3- (2H, 3aH) -dione (IV; Ar = 2-chloro-6-methoxyphenyl, R10 = CH2CH2CH20SiMe2t-Bu) (104) prepared as described in Example 57 with DDQ using the procedure described in Example 70 followed by reaction with 2 N HCl in THF / methanol gave 4- (2-chloro-6-methoxyphenyl) -6- (3-hydroxypropyl) -9- methoxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione (V; Ar = 2-chloro-6-methoxyphenyl, R 0 = CH 2 CH 2 CH 2 OH) (105) with a yield of 76% in the form of an orange powder, mp 224-227 ° C. H NMR d [(CD3) 2 SO] 1 1.05 (a, 1 H), 8.51 (d, J = 2.6 Hz, 1 H), 7.75 (s, 1 H), 7.69 (d, J = 8.9 Hz, 1 H), 7.44 (dd, J = 8.2, 8.2 Hz, 1 H), 7.31 (dd, J = 8.9, 2.6 Hz, 1 H), 7.18 (d, J = 8.2 Hz, 1 H), 7.13 (d, J = 8.2 Hz, 1 H), 4.63 (t, J = 4.9 Hz, 1 H), 4.51 (t, J = 6.8 Hz, 2H) , 3.91 (s, 3H), 3.68 (s, 3H), 3.41 (m, 2H), 1.89 (m, 2H). Found: C, 69.71; H, 4.53; N, 6.43. C 25 H 22 N 2 O 5 requires C, 69.76; H, 5.15; N, 6.51.

EXAMPLE 59 The preparation of 4- (2-chloro-6-methoxyphenyl) -9-hydroxy-6- (3-hydroxypropyl) pyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (VI: Ar = 2-chloro-6-methoxyphenyl, R10 = CH? CH2CH2OH) (106) The reaction of 4- (2-chloro-6-methoxyphenyl) -6- (3-hydroxypropyl) -9-methoxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione (V; Ar = 2-chloro-6-methoxyphenyl, R10 = CH2CH2CH2OH) (105) prepared as described in example 58 with BBr3 using the procedure described in example 80 and with a reaction time of 90"" minutes " dio ~ 4- (2-chloro-6-methoxyphenyl) -9-hydroxy-6- (3-hydroxypropyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = 2-chloro-6-methoxyphenyl, R 10 = CH 2 CH 2 CH 2 OH) (106) with a yield of 64% in the form of an orange powder, mp 270-273 ° C. 1 H NMR d [(CD 3) 2 SO] 1.01 (br s, 1 H ), 9.35 (sa, 1 H), 8.37 (d, J = 2.4 Hz, 1 H), 7.70 (s, 1 H), 7.58 (d, J = 8.7 Hz, 1 H), 7.44 (dd, J = 8.3, 8.3 Hz, 1 H), 7.20-7.1 1 (m, 3H), 4.61 (ta, 1 H), 4.47 (t, J = 6.9 Hz, 2H), 3.68 (s, 3H), 3.42 (m, 2H), 1.88 (m, 2H).

Found: C, 64.16; H, 4.55; N, 6.01. C24HigCIN205 requires C, 63.93; H, 4.25; N. 6.21.

EXAMPLE 60 The preparation of 9-hydroxy-6- (3-hydroxypropyl) -4- (2-methoxyphenyl) pyrrolo [3,4-c] carbazole-1.3 (2H. 6H) -dione (VI: Ar = 2-methoxyphenyl) R10 = CH2CH? CH2OH) (107) Reacted were 4- (2-chloro-6-methoxyphenyl) -9-hydroxy-6- (3-hydroxypropyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar; = 2-chloro-6-methoxyphenyl, R 10 = CH 2 CH 2 CH 2 OH) (106) (0.20 g, 0.44 mmole) prepared as described in example 59, potassium acetate (0.20 g) and 5% Pd / C in a solution 1 1: ethyl acetate (25 ml) and methanol (25 ml) in a hydrogen atmosphere at 60 psi (413,685 kPa) for 7 h. The catalyst was removed-or filtered-and filtered off to dryness. The residue was partitioned between ethyl acetate and water, the organic solution was dried, the drying agent was removed and the solution was concentrated to dryness and chromatographed on silica. Elution with ethyl acetate / petroleum ether (21) gave 9-hydroxy-6- (3-hydroxypropyl) -4- (2-methoxyphenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = 2-methoxyphenyl, R10 = CH2CH2CH2OH) (107) with a yield of 51% in the form of an orange powder (from THF / petroleum ether), m.p. 296-300 ° C. 1 H NMR d [(CD3) 2 SO] 10.93 (br s, 1 H), 9.31 (br s, 1 H), 8.38 (d, J = 2.4 Hz, 1 H), 7.69 (s, 1 H), 7.55 (d, J = 8.8 Hz, 1 H), 7.42 (m, 1 H), 7.35 (dd, J = 7.5, 1.7 Hz, 1 H), 7.13-7.08 (m, 2H), 7.05 (dd, J = 7.2, 7.2 Hz, 1 H), 4.62 (t, J = 4.8 Hz, 1 H), 4.48 (t, J = 6.8 Hz, 2H), 3.68 (s, 3H), 3.40 (m, 2H), 1.90 (m , 2H). Found: C, 69.29; H, 4.90; N, 6.54. C 24 H 20 2 O 5 requires C, 69.22; H, 4.84; N, 6.73.

EXAMPLE 61 The preparation of 2-. { 2- [2- (2-chloro-6-methoxyphenyl) ethenyl] -5-methoxy-1 H-indol-1-yl-ethanol (III .- Ar = 2-chloro-6-methoxyphenyl- R10 = CH2CH2OH) (109) The reaction of 2- [2- (2-chloro-6-methoxyphenyl) ethenyl] -5-methoxy-1 H-indole (II; Ar = 2-chloro-6-methoxyphenyl) (102) prepared as described in Example 55 with 2-bromoethyl tetrahydro-2H-pyran-2-yl ether using the procedure described in Example 38 followed by reaction of the crude product with 2 N HCl in methanol gave 2-. { 2- [2- (2-Chloro-6-methoxyphenyl) ethenyl] -5-methoxy-1 H-indole-1-yl} e ^ R10 = CH2CH2OH) (109) with a yield of 91% in the form of a mixture of E / Z isomers, which was used without further purification.

EXAMPLE 62 The preparation of 4- (2-cioro-6-methoxyphenyl) -6- (2-hydroxyethyl) -9-methoxy-4.5.6.10c-tetrahydropyrrolo [3,4-c] carbazole-1.3- (2H-3aH) - dione (IV: Ar 2-chloro-6-methoxyphenyl, R 10 = CH 2 CH 9 OH) (110) The reaction of 2-. { 2- [2- (2-Chloro-6-methoxyphenyl) ethenyl] -5-methoxy-1 H-indol-1-yl} ethanol (III; Ar = 2-chloro-6-methoxyphenyl, R10 = CH2CH2OH) (109) prepared as described in Example 61 with maleimide using the procedure described in example 68 gave 4- (2-chloro-6-) methoxyphenyl) -6- (2-hydroxyethyl) -9-methoxy-4,5,6,10c-tetrahydropyrrolo [3,4-c] carbazole-1, 3- (2H, 3aH) -dione (IV; Ar = 2-chloro -6-methoxyphenyl, R10 = CH2CH2OH) (10) with a yield of 72% in the form of a cream powder, which was used without further purification.

--- ----- --- -; - - ~ EXAMPLE 63 '' ~ The preparation of 4- (2-cyclo-6-methoxyphenyl) -6- (2-hydroxyethyl) -9-methoxypyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione ( V: Ar = 2-chloro-6-methoxyphenyl, R 10 = CH, CH 0 OH) (111) The reaction of 4- (2-chloro-6-methoxyphenyl) -6- (2-hydroxyethyl) -9-methoxy-4,5,6,10c-tetrahydropyrrolo [3,4-c] carbazole-1,3 (2H , 3aH) -dione (IV; Ar = 2-chloro-6-methoxyphenyl, R10 = CH2CH2OH) (10) prepared as described in Example 62 with Mn02 using the procedure described in Example 79 with the exception that the reaction time was 8 h gave 4- (2-chloro-6-methoxyphenyl) -6- (2-hydroxyethyl) -9-methoxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione (V; Ar = 2-chloro-6-methoxyphenyl, R10 = CH2CH2OH) (III) with a yield of 75% in the form of a yellow / orange powder; p.f. 264-268 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.04 (s a, 1 H), 8.50 (d, J = 2.6 Hz, 1 H), 7. 75 (s, 1 H), 7.69 (d, J = 9.0 Hz, 1 H), 7.44 (dd, J = 8.3, 8.3 Hz, 1 H), 7.28 (dd, J = 9.0, 2.6 Hz, 1 H) , 7.18 (d, J = 8.3 Hz, 1 H), 7.13 (d, J = 8.3 Hz, 1 H), 4.83 (t, J = 5.5 Hz, 1 H), 4.51 (t, J = 5.3 Hz, 2H ), 3.90 (s, 3H), 3.75 (m, 2H), 3.67 (s, 3H). Found: C, 63.84; H, 4.32; N, 5.97. C24Hi9CIN205 requires C, 63.93; H, 4.25; N, 6.21.

EXAMPLE 64 The preparation of 4- (2-chloro-6-methoxyphenyl) -9-hydroxy-6- (2-hydroxyethyl) pyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (VI: Ar 2 chlorine-6 ---- - - ^ - ~ m efox if eni I or R10 = CH? CH? Ó H) (í 12) ".

The reaction of 4- (2-chloro-6-methoxyphenyl) -6- (2-hydroxyethyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (V; Ar = 2-chloro-6-methoxyphenyl, R10 = CH2CH2OH) (III) prepared as described in Example 63 with BBr3 using the procedure described in Example 80 with the exception that the reaction conditions were 2 h at 0 ° C. 4- (2-Chloro-6-methoxyphenyl) -9-hydroxy-6- (2-hydroxyethyl) -pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione 1 (VI; Ar = 2-chloro-6-methoxyphenol, R10 = CH2CH2OH) (112) with a yield of 56% in the form of a yellow powder (56%); p.f. 275-278 ° C. H NMR d [(CD3) 2 SO] 10.98 (br s, 1 H), 9.30 (br s, 1 H), 8.36 (d, J = 2.4 Hz, 1 H), 7.70 (s, 1 H), 7.57 (d, J = 8.7 Hz, 1 H), 7.43 (dd, J = 8.3, 8.3 Hz, 1 H), 7.17 (d, J = 7.9 Hz, 1 H), 7.14-7.09 (m, 2H), 4.81 (t, J = 5.5 Hz, 1 H), 4.46 (t, J = 5.3 Hz, 2H), 3.74 (dt, J = 5.5, 5.3 Hz, 2H), 3.66 (s, 3H). FABMS found [M + H] +: 439.0882, 437.0889. C23H18CIN2O5 requires 439.0875, 437.0904.

EXAMPLE 65 The preparation of 9-hydroxy-6- (2-hydroxyethyl) -4- (2-methoxyphenyl) pyrrolo [3,4-c] carbazole-1.3- (2H.6H) -dione (VI: Ar = 2-methoxyphenyl. R 0 = CHZCH20H) 013.}.

'-' ~~ · - - "" - "-" The "reaction of" 4- (2-chloro-6-methoxyphenyl) -9-hydroxy-6: (2-hydroxyethyl) pyrrolo [3,4-c ] carbazole-1, 3 (2H, 6H) -dione (VI; Ar = 2-chloro-6-methoxyphenyl, R 10 = CH 2 CH 2 OH) (1 12) prepared as described in Example 64 with hydrogen gas, using a Pd / C catalyst, according to the procedure of Example 60 gave 9- hydroxy-6- (2-hydroxyethyl) -4- (2-methoxyphenyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione (VI; Ar = 2-methoxyphenyl, R 0 = CH 2 CH 2 OH) (13) with a yield of 77% as a yellow solid; p.f. 285-289 ° C. 1 H NMR d [(CD3) 2 SO] 10.91 (br s, 1 H), 9.29 (br s, 1 H), 8.37 (d, J = 2.4 Hz, 1 H), 7.70 (s, 1 H), 7.55 (d, J = 8.8 Hz, 1 H), 7.42 (m, 1 H), 7.33 (dd, J = 8.8, 2.4 Hz, 1 H), 7.12-7.02 (m, 3H), 4.84 (t, J = 5.5 Hz, 1 H), 4.73 (t, J = 5.3 Hz, 2H), 3.76 (dt, J = 5.5, 5.3 Hz, 2H), 3.68 (s, 3H). Found: C, 67.30; H, 4.47; N, 6.79. C23H18N2O5. 1 / 2H20 requires C, 67.15; H, 4.65; N, 6.81.

EXAMPLE 66 The methanesulfonate preparation of 2- (4- (2-chloro-6-methoxyphenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-clcarbazole-6 (H) -yl) ethyl (VII: Ar = 2-chloro-6-methoxyphenyl. n = 2. mesylate) (114) The reaction of 4- (2-chloro-6-methoxyphenyl) -6- (2-hydroxyethyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (V; Ar = 2-chloro-6-methoxyphenyl, R10 = CH2CH20H) (11 1) prepared as "described in" Example 63 with methanesulfonyl chloride, followed by reaction with BBr3 using the procedure described in Example 170 of the Scheme 3 gave 2- (4- (2-chloro-6-methoxyphenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (H) -yl methanesulfonate ethyl (VII; Ar = 2-chloro-6-methoxyphenyl, n = 2, mesylate) (14) as a white solid, which was used without further purification.

EXAMPLE 67 The preparation of 4- (2-chloro-6-methoxyphenyl) -9-hydroxy-6- [2- (4-morpholinyl) etinpyrrolor3.4-c carbazole-1.3 i2H-6H) -dione (HIV: Ar = 2-chloro-6-methoxyphenyl, n = 2.Z = 4-morpholinyl) (115) The methanesulfonate reaction of 2- (4- (2-chloro-6-methoxyphenyl) -g-hydroxy-1 .S-dioxo ^. S-dihydropyrrololS ^ -chlorcarbazole-ethyl-1-ethyl (VII; Ar = 2-chloro -6-methoxyphenyl, n = 2, mesylate) (114) prepared as described in Example 66 with morpholine using the procedure described in Example 179 of Scheme 3 gave 4- (2-chloro-6-methoxyphenyl) -9 -hydroxy-6- [2- (4-morpholinyl) ethyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione (VIII; Ar = 2-chloro-6-methoxyphenyl, n = 2, Z = 4-morpholinyl) (15) with a yield of 81% in the form of a yellow powder, mp 185 ° C. 1 H NMR d [(CD3) 2 SO] 10.99 (sa, 1 H), 9.34 ( sa, 1 H), 8.37 (d, J = 2.4 Hz, -1 H), 7.69 (s, -1 H), 7.57 (d, J = 8, 8 Hz, 1?), 7.44 (dd, J = 8; 3, 8: 3 Hz, 1 H), 7.17 (d, J = 8.3 Hz, 1 H), 7.14-7.10 (m, 2H), 4.53 (t, J = 6.1 Hz, 2H), 3.66 (s) , 3H), 3.41 (t, J = 4.5 Hz, 4H), 2.64 (t, J = 6.1 Hz, 2H), 2.37 (m, 4H) Found: C, 63.57, H, 4.71, N, 8.06, C27H24CI N3O5.1 / 4H20 requires C, 63.53; H, 4.84; N, 8.03.

Representative procedure for method 4 of scheme 2 EXAMPLE 68 The preparation of 4- (2-chlorophenyl) -9-methoxy-4,5-6-0-tetrahydropyrrolo [3,4-c] carbazole-1.3 (2H.3aH) -dione (IV: Ar = 2-chlorophenyl) R10 = H) (32) A solution of 2- [2- (2-chlorophenyl) ethenyl] -5-methoxy-1 H-indole (II; Ar 2-chlorophenyl) (27) (1.5 g, 5.29 mmol) prepared according to example 37, maleimide (0.61 g, 6.34 mmol) and SnCl 2 (0.20 g, 1.05 mmol) in toluene (25 mL) was heated to reflux for 6 h. After dilution with ethyl acetate, the solution was washed with water, the organic phase was dried, the drying agent was removed and the solution was concentrated to dryness to give 4- (2-chlorophenyl) -9-methoxy-4, 5,6,10c-tetrahydropyrrolo [3,4-c] carbazole-1,3 (2H, 3aH) -dione (IV; Ar = 2 -ophophenyl,, R1 ° = H) (32) with-a yield of 1.98 g, 98% in the form of a yellow --solid (in the form of a mixture of diastereomers), which was used without further purification.

Representative procedure for method 5 of scheme 2 EXAMPLE 69 The preparation of 9-methoxy-4- (2-methoxy-5-nitrophenyl) -4.5.6.10-tetrahydropyrrolo [3,4-c] carbazole-1.3- (2H-3aH) -dione (IV: Ar = 2- methoxy-5-nitrophenyl-R10 = H) (185) A solution of 5-methoxy-2- [2- (2-methoxy-5-nitrophenyl) ethenyl] -1H-indole (II, Ar = 2-methoxy-5-nitrophenyl) (0.437 g, 1.35 mmole) prepared as it was described in example 45 and maleimide (0.156 g, 1.62 mmol) in THF (10 ml) was concentrated to dryness in a 25 ml flask. The resulting solid was placed in an oil bath at 180 ° C and the resulting melt was maintained at this temperature for 4 h. The residue was cooled and triturated with diethyl ether to give 9-methoxy-4- (2-methoxy-5-nitrophenyl) -4,5,6,10c-tetrahydropyrrolo [3,4-c] carbazole-1, 3- (2H, 3aH) -dione, (IV; Ar = 2-methoxy-5-nitrophenyl, _R 0 = H) (185) with a yield of 6.51 g, 90% in the form of a chestnut powder, which was used without further purification in the next stage.

Representative procedure for method 6 of scheme 2 EXAMPLE 70 The preparation of 9-methoxy-4- (2-methoxy-5-nitrophenyl) pyrrolo [3,4-clcarbazole-1.3 (2H-6H) -dione (V: Ar = 2-methoxy-5-nitrophenyl) R 0 = H) (36) A solution of 9-methoxy-4- (2-methoxy-5-nitrophenyl) -4,5,6,10-tetrahydropyrrolo [3,4-c] carbazole-1,3 (2H, 3aH) -dione (IV; Ar = 2-methoxy-5-nitrophenyl, R10 = H) (185) (0.51 g, 1.21 mmol) prepared according to Example 69 and DDQ (0.82 g, 3.63 mmol) in dioxane (30 mL) was heated to reflux for 2 h. After dilution with water, the solution was extracted with dichloromethane. The organic extracts were washed with a saturated aqueous solution of NaHCO 3 (3 x). The organic phase was dried, the drying agent was removed and the solution was concentrated to dryness to give a solid which was chromatographed on silica. The elution: with ethyl acetate / petroleum ether (3: 7) followed ethyl acetate / petroleum ether (II) gave a solid which when triturated with diethyl ether to give 9-methoxy-4- (2-methoxy-5-nitrophenyl) pyrrolo [3,4-c] carbazole-1 , 3- (2H, 6H) -dione (V; Ar 2-methoxy-5-nitrophenyl, R 10 = H) (36) with a yield of 0.42 g, 82%; p.f. 302-304 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.95 (br s, 1 H), 11.06 (br s, 1 H), 8.46 (d, J = 2.6 Hz, 1 H), 8.37 (dd, J = 9.2, 3.0 Hz, 1 H), 8.22 (d, J = 3.0 Hz, 1 H), 7.69 (s, 1 H), 7.57 (d, J = 8.8 Hz, 1 H), 7.36 (d, J = 9.2 Hz, 1 H), 7.24 (dd, J = 8.8, 2.6 Hz, 1 H), 3.89 (s, 3H), 3.85 (s, 3H).

Found: C, 63.90; H, 3.79; N, 9.52. C 22 H 15 N 3 O 6 requires C, 63.61; H, 3.62; N, 10.07.

EXAMPLE 71 The preparation of 9-hydroxy-4- (2-hydroxy-5-nitrophenyl) pyrrolo [3,4-c] carbazole-1.3- (2H.6H) -dione (VI: Ar = 2- hydroxy-5-nitrophenyl, R10 = H) (37) The compound 9-methoxy-4- (2-methoxy-5-nitrophenyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione (V; Ar = 2-methoxy) 5-nitrophenyl, R = H) (36) prepared according to Example 70 was reacted using the procedure described in Example 81 by reaction at 210 ° C for 30 min, to give 9-hydroxy-4- (2- hydroxy-5-nitrophenyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione (VI; Ar = 2-hydroxy-5-nitrophenyl, R10 = H) (37) with a 82% yield in the form of a yellow / orange powder; p.f. > 330 ° C. - - - "~ '* JH NMR 5 [(CD3) 2SO] 11, 78 (s, 1 H), 10.99 (s, 1 H); 9.26 (s /?), 8.32 (d, J = 2.4 Hz , 1 H), 8.21 -8.16 (m, 2H), 7.63 (s, 1 H), 7.45 (d, J = 8.7 Hz, 1 H), 7.08 (m, 2H).

EXAMPLE 72 The preparation of 9-hydroxy-4- (2-methoxy-5-nitrophenyl) pyrrolo [3,4-clcarbazole-1.3 (2H.6m-dione (VI: Ar = 2-methoxy-5-nitrophenyl, R10 = H) (38) The compound 9-methoxy-4- (2-methoxy-5-nitrophenyl) pyrrolo [3,4c] carbazole-1, 3- (2H, 6H) -dione (V; Ar = 2-methoxy) 5-nitrophenyl, R 10 = H) (36) prepared according to Example 70 was reacted using the procedure described in Example 80 to give 9-hydroxy-4- (2-methoxy-5-nitrophenyl) pyrrolo [ 3,4-c] carbazole-1, 3- (2H, 6H) -dione (VI; Ar = 2-methoxy-5-nitrophenyl, R10 = H) (38) with a yield of 76% in the form of a powder yellow; p.f. 265-273 ° C (dec). H NMR d [(CD3) 2 SO] 11 .86 (a, 1 H), 1 1 .01 (a, 1 H), 8.38 (dd, J = 9.3, 2.8 Hz, 1 H), 8.31 (d, J = 2.4 Hz, 1 H). 8.20 (d, J = 2.8 Hz, 1 H), 7.65 (1 H), 7.48 (d, J = 8.7 Hz, 1 H), 7.36 (d, J = 9.3 Hz, 1 H), 7.10 (dd) , J = 8.7, 2.4 Hz, 1 H), 3.84 (s, 3?) '. ~ ~ "" _. . . . EIMS found M +: 403.0794. C21 H13N3O6 requires 403.0804.

EXAMPLE 73 The preparation of 4- (5-amino-2-methoxyphenyl) -9-hydroxypiranium [3,4-c] carbazole-1.3 (2H.6H) -dione (VI: Ar = 5-amino-2-methoxyphenyl) R10 = H) (39) To a solution of 9-hydroxy-4- (2-methoxy-5-nitrophenyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione (VI; Ar = 2-methoxy-5) -nitrophenyl, R10 = H) (38) (64 mg, 0.159 mmol) prepared according to example 72 in methanol (10 mL) and THF (1 mL) was added 2N HCl (1 mL). Freshly prepared nickel boride (-0.50 g) was added and the mixture was heated to 60 ° C. Then, 1 N HCl (1 mL) and Ni2B (-0.50 g) were added and the reaction mixture was maintained at 60 ° C for a total of 4 h. The solvents were removed in vacuo and the residue was partitioned between ethyl acetate and 2N HCl. The aqueous layer was basified with a conc. Ammonia solution. and extracted with ethyl acetate. The organic phase was dried, the drying agent was removed and the solvent was concentrated to dryness to give a solid which when crystallized from THF / petroleum ether gave 4- (5-amino-2-methoxyphenyl) -9-hydroxypyrrolo [3, 4-c] carbazole-1, 3- (2H, 6H) -dione (VI; Ar = 5-amino-2-methoxyphenyl, R10 = H) (39) with a yield of 49.7 mg, 84% as a yellow powder; p.f. 246-250 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.67 (s, 1 H), 10.87 (s, 1 H), 9.21 (s, 1 H), 8.30) d, J = 2.4 Hz, 1 H), 7.44 (s) , 1 H), 7.42 (d, J = 8.7 Hz, 1 H), 7.05 (dd, J = 8.6, 2.5 Hz,?), 6.¾0 '(d, ~ J = 8.7 Hz, 1 H), 6.61 (dd, J = 8.6, 2.7 Hz, 1 H), 6.55 (d ... J = 2.8 Hz, 1 H), 4.68 (a, 2H), 3.53 (s, 3H). FABMS found [M + H] +: 373.1056. C21 H15 3O4 requires 373. 1062 EXAMPLE 74 The preparation of 2 - [(E) -2- (2-bromo-4-nitrophenol) ethenyl] -5-methoxy-1 H-indole (II: Ar = 2-bromo-4-nitrophenyl) (49) Reaction of 5-methoxy-1 H-indole-2-carbaldehyde (1) with 2-bromo-4-nitrobenzyltriphenylphosphonium bromide using the procedure described in Example 37 gave the diene 2 - [(E) -2- (2 -Bromo-4-nitrophenyl) ethenyl] -5-methoxy-1 H-indole (II; Ar = 2-bromo-4-nitrophenyl) (49) with a yield of 98% in the form of a red solid which was used without additional purification.

EXAMPLE 75 The preparation of 4- (2-bromo-4-nitrophenyl) -9-methoxy-4-5-6.10-tetrahydropyrrolo [3,4-c] carbazole-1.3 (2H.3aH) -dione (IV: Ar = 2 -bromo-4-nitrophenyl R10-H) (50) '' ~ '' The reaction of 2 - [(E) -2- (2-bromo-4-nitrophenyl) ethenyl] -5-methoxy-1 H- indole (II; Ar = 2-bromo-4-nitrophenyl) (49) prepared as described in Example 74 with maleimide using the procedure described in Example 69 gave 4- (2-bromo-4-nitrophenyl) -9 -methoxy-4,5,6,10c-tetrahydropyrrolo [3,4-c] carbazole-1, 3- (2H, 3aH) -dione (IV; Ar = 2-bromo-4-nitrophenyl, R 10 = H) ( 50) with a yield of 54% in the form of a chestnut powder; p.f. 272 ° C (dec), which was used without further purification.

EXAMPLE 76 The preparation of 4- (2-bromo-4-nitrophenyl) -9-methoxypyrrolo [3,4-c1carba2ol-1.3 (2H-6H) -dione (V: Ar = 2-bromo-4-nitrophenyl, R10 = H) (51) The reaction of 4- (2-bromo-4-nitrophenyl) -9-methoxy-4,5,6,10c-tetrahydropyrrolo [3,4-c] carbazole-1, 3- (2H, 3aH) -dione (IV; Ar = 2-bromo-4-nitrophenyl, R10 = H) (50) prepared as described in Example 75 with DDQ using the procedure described in Example 70 gave 4- (2-bromo-4-nitrophenyl) - 9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (V; Ar = 2-bromo-4-nitrophenyl, R10 = H) (51) with a yield of 67% in the form of a yellow powder, mp 288-292 ° C (dec). 1 H NMR d [(CD3) 2 SO] 12.07 (a, 1 H), 1 1.18 (a, 1 H), 8.56 (d, J = 2.3 Hz, 1 H), 8.46 (d, J = 2.6 Hz, 1 H ), 8.33 (dd, J = 8.5, 2.6 Hz, 1 H), 7.80 (d, J = 8.5 Hz, 1 H), 7.63 (s, H), 7.59 (d, J = 8.8 Hz, 1 H), 7.27 (dd, J = 8.8, 2.3 Hz, 1 H), 3.90 (s, 3H). "" ", ~ _ - Found: C, 54.06; H, 2.59; N, 8.72. C2iH 2BrN305 requires C, 54.10; H, 2.59; N, 9.01.

EXAMPLE 77 The preparation of 4- (2-bromo-4-nitrophenyl) -9-hydroxypyrrolo [3-4c] carbazole-1.3 (2H.6H) -dione (VI: Ar = 2-bromo-4-nitrophenyl) R10 = H) (52) The reaction of 4- (2-bromo-4-nitrophenyl) -9-methoxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione (V; Ar = 2-bromo- 4-nitrophenyl, R10 = H) (51) prepared as described in Example 76 with pyridinium hydrochloride using the procedure described in Example 81 gave 4- (2-bromo-4-nitrophenyl) -9-hydroxypyrrolo [3 , 4-c] carbazole-1, 3- (2H, 6H) -dione (VI; Ar 2-bromo-4-nitrophenyl, 10 10 = H) (52) with a yield of 92% in the form of a yellow powder , pf > 330 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.94 (s, 1 H), 1 1.13 (s, 1 H), 9.32 (s, 1 H), 8.55 (d, J = 2.3 Hz, 1 H), 8.34 ( d, J = 2.4 Hz, 1 H), 8.31 (m, 2H), 7.79 (d, J = 8.5 Hz, 1 H), 7.58 (s, 1 H), 7.48 (d, J = 8.7 Hz, 1 H ), 7.11 (dd, J = 8.7, 2.4 Hz, 1 H). "15" "'"' ~ "" ~ _. EXAMPLE 78 The preparation of 4- (4-amino-2-bromophenyl) -9-hydroxy-pyrrolo [3,4-c] carbazole-1.3- (2H.6H) -dione (VI: Ar = 4-amino-2-bromophenyl R10 = H) (53) 20 Freshly prepared nickel (5.00 g, 0.039 mol) was added in portions to a solution of 4- (2-bromo-4-nitrophenyl) -9 -hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar 2-bromo-4-nitrophenyl, R 10 = H) (52) (0.50 g, 1.10 mmol) prepared as described in example 77 in methanol (80 ml) and 2N HCl (5.0 ml) at 60 ° C. After 2 h, the mixture was cooled, diluted with water, basified with conc. Ammonia. aqueous and extracted with ethyl acetate. The extract was treated to give a solid which was chromatographed on silica. Elution with ethyl acetate gave 4- (4-amino-2-bromophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = 4-amino- 2-bromophenyl, R10 = H) (53) with a yield of 0.47 g, 97% which was crystallized from ethyl acetate / petroleum ether as a yellow powder, mp. 324-326 ° C. H NMR d [(CD3) 2 SO] 1 1.71 (br s, 1 H), 10.93 (br s, 1 H), 9.23 (br s, 1 H), 8.30 (d, J = 2.4 Hz, 1 H), 7.43 (d, J = 8.6 Hz, 1 H), 7.42 (s, 1 H), 7.09-7.03 (m, 2H), 6.89 (d, J = 2.1 Hz, 1 H), 6.61 (dd, J = 8.6, 2.4 Hz, 1 H), 5.48 (sa, 2H). Found: C, 56.79; H, 3.26; N, 8.77. C2oH12BrN303 1/3 EtOAc requires C, 56.67; H, 3.46; N, 9.01.

Representative procedure for method 7 of scheme 2 EXAMPLE 79 The preparation of 4- (2-chlorophenyl) -9-methoxypyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione IV: Ar = 2-chlorophenyl. R10 = m (33) Manganese dioxide (12.0 g) was added to a solution of 4- (2-chlorophenyl) -9-methoxy-4,5,6,10c-tetrahydropyrrolo [3,4-c] carbazole-1, 3- (2H, 3aH) -dione (IV; Ar = 2-chlorophenyl, R10 = H) (32) prepared as described in example 68 (2.1 g, 5.51 mmol) in dioxane (100 ml) and the mixture was heated to reflux with stirring for 16 h. The mixture was filtered hot through a pad of Celite, washing thoroughly with more dioxane and then with 5% methanol / dioxane. The filtrate and the combined washings were concentrated to dryness and the residue was adsorbed on silica and chromatographed. Elution with ethyl acetate / petroleum ether (3: 7) gave 4- (2-chlorophenyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (V; Ar = 2-chlorophenyl, R10 = H) (33) with a yield of 1.66 g, 79% which crystallized in THF / petroleum ether 10 in the form of a yellow powder, mp. 170-175 ° C (dec). H NMR d [(CD3) 2 SO] 1 1.96 (br s, 1 H), 1.08 (sa, 1 H), 8.46 (d, J = 2.6 Hz, 1 H), 7.60-7.55 (m, 3H), 7.51 -7.42 (m, 3H), 7.24 (dd, J = 8.9, 2.6 Hz, H), 3.89 (s, 3H). Found: C, 65.64; H, 3.63; N, 7.12. C21 H13CIN2O3. 1 / 2H20"" 15"requires C, 65:37; H, 3.66; N, 7.26. ' "" ~ "~~ Representative procedure for method 8 of scheme 2 EXAMPLE 80 The preparation of 4- (2-chlorophenyl) -9-hydroxy-6- (3-hydrox »propyl) pyrrolo [3,4-clcarbazole-1.3 (2H.6H) -dione (VI: Ar = 2-chlorophenyl. 0 = CH2CH2CH OH) (34) A solution of 1N BBr3 in CH202 (11.5 ml, 0.011 mole) was added to a solution of 4- (2-chlorophenyl) -6- (3-hydroxypropyl) -9-methoxy-pyrrolo [3,4-c] carbazole -1, 3- (2H, 6H) -dione (V; Ar = 2-chlorophenyl, R10 = CH2CH2CH2OH) (31) prepared as described in Example 40 (1.00 g, 2.30 mmol) in CH2Cl2 under an atmosphere of nitrogen and the reaction mixture was stirred at room temperature for 3 h. A saturated aqueous solution of NaHCO 3 was added and the solution was diluted with water and extracted with ethyl acetate-acetate. The organic phase was dried, drying agent was removed and the solution was concentrated to dryness, adsorbed on silica and dried. It was chromatographed. Elution with ethyl acetate / petroleum ether (1: 1) followed by ethyl acetate gave 4- (2-chlorophenyl) -9-hydroxy-6- (3-hydroxypropyl) pyrrolo [3,4-c] carbazole- 1, 3- (2H, 6H) -dione (VI; Ar = 2-chlorophenyl, R10 = CH2CH2CH2OH) (34) with a yield of 0.90 g, 93%, which crystallized from THF / petroleum ether as a powder yellow / orange, mp 291-294 ° C. 1 H NMR d [(CD 3) 2 SO] 1 1 .05 (br s, 1 H), 9.36 (s, 1 H), 8.38 (d, J = 2.5 Hz, 1 H), 7.74 (s, 1 H), 7.59 -7.54 (m, 2H), 7.52-7.42 (m, 3H), 7.14 (dd, J = 8.7, 2.5 Hz, 1 H), 4.62 (ta, 1 H), 4.49 (t, J = 6.8 Hz, 2H ), 3.41 (m, 2H), 1.90 (m, 2H). Found: C, 64.99; H, 4.13; N, 6.43. C23H17CIN204. 1 / 4H20 5 requires C, 64.94; H, 4.15; N, 6.58.

Representative procedure for method 9 of scheme 2 EXAMPLE 81 10 The preparation of 4- (2-chlorophenyl) -9-hydroxypyrrolo [3r4-c] carbazole-1.3- (2H-6H) -dione (VI: Ar = 2-chlorophenyl R 0 = H) (9) 4- (2-chlorophenyl) -9-methoxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione (V; Ar = 2-chlorophenyl, R10 = H) (33) was added as it has been described in Example 5 ~ (0.'5"12 g, 1.36" mmoles) to pyridinium hydrochloride melted at 200 ° C and the mixture was stirred at this temperature for 20 min. The resulting precipitate was filtered off, washed well with water, adsorbed on silica and chromatographed, elution with ethyl acetate / petroleum ether (II) gave 4- (2-chlorophenyl) -9-hydroxypyrrolo [3.4 -c] carbazole-1, 3- (2H, 6H) -20 dione (VI; Ar = 2-chlorophenyl, R10 = H) (9) with a yield of 0.42 g, 85%, mp 215-220 ° C ( dec). H NMR d [(CD3) 2SO] 1 1.83 (sa, 1 H), 11.01 (sa, 1 H), 9.27 (sa, 1 H), 8.32 (d, J = 2.4 Hz, 1H) , 7.65-7.40 (m, 5H), 7.08 (dd, J = 8.7, 2.4 Hz, 1 H).

Found: C, 65.72; H, 3.50; N, 6.97. C20H11CIN2O3. I / 4CH3COOCH2CH3 requires C, 65.54; H, 3.40; N, 7.28.

EXAMPLE 82 The preparation of 6- (2-hydroxyethyl) -9-methoxy-4-phenylpyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (V: Ar = phenyl, R 0 = ( CH,) 2OH) (201) Reacted 5-methoxy-2 - [(E, Z) -2-phenylethenyl] -1H-indole (II; Ar = phenyl) (1.93 g, 7.74 mmole) with 2- (2-bromoethoxy) tetrahydro -2H-pyran using the procedure described in Example 38. This material was reacted directly with maleimide (0.79 g) using the procedure described in method 4. The product obtained was reacted using the procedure described in Example 70 to give The crude material was then dissolved in methanol (100 ml) to which p-toluenesulfonic acid (30 mg) was added before the solution was heated at 5 ° C for 3 h. Then, the solution was diluted with water and extracted with ethyl acetate. The organic phase was dried, the drying agent was removed and the solution was concentrated to dryness before being adsorbed on silica and chromatographed eluting with ethyl acetate / hexane (from 1: 2 to 1: 1) to give 6- (2- hydroxyethyl) -9-methoxy-4-phenylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione (V; Ar = phenyl, R10 = (CH2) 20H) (201) with a yield of 0.51 g, 17% in the form of a yellow powder; p.f. 262-264 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.09 (br s, 1 H), 8.56 (d, J = 2.6 Hz, 1 H), 7.83 (s, 1 H), 7.66 (m, 3H), 7.47 (m, 3H), 7.28 (dd, J = 9.0, 2.6 Hz, 1 H), 4.86 (t, J = 5.5 Hz, 1 H), 4.55 (t, J = 5.3 Hz, 2H), 3.90 (s, 3H), 3.78 (m, 2H). Found: C, 71.47; H, 4.77; N, 7.32. C23H18N2O4 requires: C, 71.49; H. 4.70; N, 7.25.

EXAMPLE 83 The preparation of 6- (3-hydroxypropyl) -9-methoxy-4-phenylpyrrolo [3,4-c1carbazole-1.3 (2H-6H) -dione (V: Ar = phenyl, R10 = (CH,) jOH) (202) -methoxy-2 - [(E, Z) -2-phenylethenyl] -1H-indole (II; Ar = phenyl) (6.85 g, 27.5 mmol) was reacted with tert-butyl (dimethyl) silyl ether -bromopropyl using the procedure described in Example 38. The isolated product was reacted directly with maleimide (5.2 g) using the procedure described in Example 68. The 'aromatization' of the crude Diels-Alder adduct using the procedure described in Example 79 gave the crude material which was then dissolved in methanol (300 ml) to which 1 N hydrochloric acid (50 ml) was added.This solution was stirred at rt for 3 h before being diluted with water and extracted with ethyl acetate. The organic layer was dried, the drying agent was removed and the solution was concentrated to dryness The residue was adsorbed on silica and chromatographed eluting with dichloromethane for ethyl acetate / dichloromethane (7: 3). gave the alcohol (202) in the form of a yellow powder (2.55 g, 23%), mp 241 -243X. 1 H NMR d [(CD 3) 2 SO] 1 1.10 (br s, 1 H), 8.56 (d, J = 2.6 Hz, 1 H), 7.82 (s, 1 H), 7.67 (m, 3 H), 7.47 (m, 3H), 7.30 (dd, J = 9.0, 2.6 Hz, 1 H), 4.66 (t, J = 4.9 Hz, 1 H), 4.55 (t, J = 6.9 Hz, 2H), 3.90 (s, 3H), 3.39 (m, 2H), 1.93 (m, 2H). Found: C, 71.95; H, 5.09; N, 6.93. C24H20B2O4 requires: C, 71.99; H, 5.03; N, 6.99.

EXAMPLE 84 The preparation of 6- (6-hydroxyhexyl) -9-methoxy-4-phenylpyrrolo [3,4-c1carbazole-1.3 (2H-6H) -dione (V: Ar = phenyl R10 = (CHz) gOH) (203) The alkylation of 5-methoxy-2 - [(E, Z) -2-phenylethyl] -1H-indole (II; Ar = phenyl) (0.30 g, 0.71 mmole)) with 6-bromohexyl-tert-butyl (dimethyl) Silyl ether according to the procedure described in Example 38 gave the crude material which was reacted directly with maleimide (0.14 g) following Method 4a. The aromatization of crude crude Diels-Alder adduct using the procedure described in Example 79 gave the crude material which was then dissolved in methanol (100 ml) to which 1 N hydrochloric acid (15 ml) was added. This solution was stirred at rt for 2 h before it was diluted with water and extracted with ethyl acetate, the organic layer was dried, the drying agent was removed and the solution was concentrated to dryness chromatography on silica eluting with dichloromethane. to ethyl acetate / hexane (41) followed by trituration with diethyl ether gave the alcohol (203) as a yellow powder (0.31 g, 98%), mp 170-173 ° C. H NMR d [(CD3) 2SO] 1 1.10 (sa, 1 H), 8.56 (d, J = 2.6 Hz, 1 H), 7.82 (s, 1 H), 7.67 (m, 3H), 7.47 (m, 3H), 7.29 (dd, J = 8.9, 2.6 Hz, 1 H), 4.50 (t, J = 7.0 Hz, 2H), 4.28 (t, J = 5.1 Hz, 1 H), 3.90 (s, 3H), 3.32 (t, J = 6.4 Hz, 2H), 1.76 (m, 2H), 1.36-1.26 (m, 6H) Found: C, 73.57, H, 6.17, N, 6.39, C27H26N2O4 requires: C, 73.28; 5.92; N, 6.33.

EXAMPLE 85 The preparation of 4- (2,6-Dichlorophenyl) -6- (2-hydroxyethyl) -9-methioxypyrrolo [3,4-c] carbazole-1.3- (2H.6H) -dione (V: Ar = 2-6-dichlorophenyl) R10 = (CH2) 2OH) (230) "" '· ~ "R" The pure "trans-diene alqylation" (512) (3.0 g, 10.6 ~ mmoles) prepared as described in Example 103 with 2- (2-bromoethoxy) tetrahydro-2H-pyran according to the procedure described in Example 38 gave a crude material which was dissolved in methanol / tetrahydrofuran (41.250 ml) and to this 2 N hydrochloric acid (20 ml) was added before stirring the solution at room temperature for 2 hours. The solution was then diluted with saturated sodium bicarbonate and concentrated under reduced pressure to precipitate the crude product which was collected by filtration and dried in vacuo This solid was reacted directly with maleimide (1.26 g) following the procedure described in Example 68. The aromatization of the Diels-Alder adduct chromatographed using the procedure described in Example 70 gave the material which was then triturated in methanol to give the alcohol (230) as a yellow powder (2.14 g, 44% ), mp 229-231 ° C. 1 H NMR d [(CD3) 2 SO] 1.17 (br s, 1 H), 8.50 (d, J = 2.6 Hz, 1 H), 7.86 (s, 1 H), 7.72 (d, J = 9.0 Hz, 1 H) , 7.62 (m, 2H), 7.51 (dd, J = 8.9, 7.4 Hz, 1 H), 7.31 (dd, J = 9.0, 2.6 Hz, 1 H), 4.83 (t, J = 5.3 Hz, 1 H) , 4.54 (t, J = 5.2 Hz, 2H), 3.91 (s, 3H), 3.77 (m, 2H). Found: C, 60.61; H, 3.85; N, 5.88. C 23 H 16 Cl 2 N 2 O 4 requires: C. 60.66: H, 3.54; N. 6.15.

EXAMPLE 86 The preparation of 4- (2,6-dichlorophenyl) -6- (3-hydroxypropyl) -9-methoxypyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (V; Ar-2,6-dichlorophenyl) - '- "" R10 = (CH2 ÓH) (232) ~ ~ "' Alkylation of the diene (512) (3.0 g, 9.43 mmol) prepared as described in Example 103 with 3-bromopropyl tert-butyl (dimethyl) silyl ether according to the procedure described in Example 38 gave the crude material which was dissolved in methanol / dichloromethane (31, 300 ml) to which 1N hydrochloric acid (60 ml) was added. This solution was stirred at rt for 2 h before being diluted with saturated sodium bicarbonate and concentrated under reduced pressure to precipitate the crude product which was collected by filtration and dried in vacuo. This solid was reacted with maleimide (1.20 g) following the procedure described in example 68. The aromatization of the crude Diels-Alder adduct using the procedure described in example 70 gave the material which was then chromatographed on silica eluting with methanol / dichloromethane (from 2:98 to 5:95) to give the alcohol (232) (2.4 g, 54%) as a yellow powder, mp 254-256 ° C. H NMR d [(CD3) 2 SO] 1 1 .18 (br s, 1 H), 8.51 (d, J = 2.6 Hz, 1 H), 7.86 (s, 1 H), 7.72 (d, J = 9.0 Hz, 1 H), 7.63 (m, 2 H), 7.51 (dd, J = 8.8, 7.4 Hz, 1 H), 7.34 (d, J = 9.0, 2.6 Hz, 1 H), 4.62 (t, J = 5.0 Hz, 1 H), 4.54 (t, J = 6.9 Hz, 2H), 3.91 (s, 3H), 3.42 (m, 2H), 1.90 (m, 2H). FABMS found M +: 468.0630, 470.0628, 472.0626. C24H18CI2 2O4 requires 468.0644, 472.0585.

EXAMPLE 87"The preparation of 4- (4 (2-morphine) -9-methoxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-e] carbazole-6 (1 H) -yl) butanoic acid (V; Ar = 2 -chlorophenyl, R10 = (CH,) 3COOH) (262) Alkylation of the diene (27) (0.40 g, 1.41 mmol) prepared as described in Example 37 with ethyl bromobutyrate according to the procedure described in Example 38 gave the crude material which was reacted with maleimide (0.27 g). ) following the procedure described in example 68. The aromatization of the Diels-Alder adduct using the procedure described in example 70 gave the crude material which was then dissolved in methanol (100 ml) to which 2 N potassium hydroxide was added ( 2 mi). This solution was stirred at rt for 2 h before it was diluted with water and acidified by the addition of 1 N hydrochloric acid to precipitate the product as a yellow solid, which was collected by filtration and washed with water before being dried at room temperature. empty. Chromatography on silica eluting with ethyl acetate followed by trituration with diethyl ether / hexane gave the acid (262) as a yellow powder (0.10 g)., 16%), p.f. 251-254 ° C. 1 H NMR d [(CD 3) 2 SO] 12.12 (br s, 1 H), 1 1.12 (br s, 1 H), 8.53 (d, J = 2.6 Hz, 1 H), 7.85 (s, 1 H), 7.72 (d , J = 9.0 Hz, 1 H), 7.58 (m, 1 H), 7.53-7.45 (m, 3H), 7.32 (d, J = 9.0, 2.6 Hz, 1 H), 4.50 (t, J = 7.3 Hz , 2H), 3.91 (s, 3H), 2.30 (m, 2H), 1.97 (m, 2H). FABMS found [M + H] +: 463.1025, 465.1034. C25H19CIN205 requires 463.1061, 465.1031.

EXAMPLE 88 The preparation of 4- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) butanoic acid (VI: Ar = 2) -chlorophenyl, R10 = (CH) OOH) (263) Demethylation of acid (262) (32 mg, 0.07 mmol) prepared as described in Example 87 using the procedure described in Example 80 gave phenol (263) (6 mg, 19%) as an orange powder , pf 274-277 ° C. 1 H NMR d [(CD3) 2 SO] 12 (s very a, 1 H), 1.06 (sa, 1 H), 9.38 (sa, 1 H), 8.38 (d, J = 2.4 Hz, 1 H), 7.80 (s, 1 H), 7.60 (d, J = 8.9 Hz, 1 H), 7.58 (m, 1 H), 7.52-7.43 (m, 3H), 7.14 (dd, J = 8.9, 2.4 Hz, 1 H ), 4.45 (t, J = 7.5 Hz, 2H), 2.27 (m, 2H), 1.95 (m, 2H). FABMS found [M + H] +: 449.0874, 451.0879. C24H17CIN205 requires 449.0904, 451 .0875.

EXAMPLE 89 The preparation of 9-hydroxy-6- (2-hydroxyethyl) -4-phenylpyrrolo [3,4-c] carbazole- The demethylation of the alcohol (201) (135 mg, 0.35 mmol) "prepared as described in Example 82 followed by the procedure described in example 81 gave the alcohol (220) (90 mg, 69%) in the form of a orange powder, pf 298-301 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.04 (br s, 1 H), 9.31 (br s, 1 H), 8.40 (d, J = 2.5 Hz, 1 H), 7.79 (s, 1 H), 7.64 (m , 2H), 7.55 (d, J = 8.8 Hz, 1 H), 7.47 (m, 3H), 7.10 (dd, J = 8.8, 2.5 Hz, 1 H), 4.85 (t, J = 5.3 Hz, 1 H ), 4.51 (t, J = 5.4 Hz, 2H), 3.77 (m, 2H). Found: C, 68.88; H, 4.43; N, 6.76. C22H16N204. 3 / 4H20 requires: C, 68.48; H, 4.57; N, 7.26.

EXAMPLE 90 The preparation of 9-hydroxy-6- (3-hydroxypropyl) -4-phenylpyrrolof3.4-c] carbazole-1.3f2H.6H) -dione (VI: Ar = phenyl- R10 = (CH2) 2OH) (221 ) Demethylation of the alcohol (202) prepared as described in Example 83 (60 mg, 0.15 mmol) using the procedure described in Example 80 gave the alcohol (221) (45 mg, 78%) as an orange powder , pf 274-276 ° C. 1 H NMR d [(CD 3) 2 SO] 1 1 .05 (br s, 1 H), 9.33 (s, 1 H), 8.41 (d, J = 2.4 Hz, 1 H), 7.77 (s, 1 H), 7.64 (m, 2H), 7.56 (d, J = 8.8 Hz, 1 H), 7.46 (m, 3H), 7.12 (dd, J = 8.8, 2.4 Hz, 1 H), 4.64 (t, J = 4.9 Hz, 1 H), 4.51 (t, J = 6.9 Hz, 2H), 3.39 (m, 2H), 1.92 (m, 2H). Found: C, 71.59; H, 4.74; N, 7.57. C23H18N204 requires: C, 71 .49; H. 4.70; N, 7.25.

EXAMPLE 91 The preparation of 9-hydroxy-6- (6-hydroxyethyl) -4-phenylpyrrolo [3,4-c] carbazole-1.3-y2H.6-dione (VI: Ar = phenyl, R10 = (CHAjOH) (222) Demethylation of the alcohol (203) prepared as described in Example 84 (55 mg, 0.12 mmol) using the procedure described in Example 80 gave the alcohol (222) (12 mg, 23%) as an orange powder , pf 132-140 ° C. 1 H NMR d [(CD3) 2 SO] 1 .04 (br s, 1 H), 9.33 (s, 1 H), 8.41 (d, J = 2.5 Hz, 1 H), 7.77 (s, 1 H), 7.64 ( m, 2H), 7.54 (d, J = 8.8 Hz, 1 H), 7.46 (m, 3H), 7.12 (dd, J = 8.8, 2.5 Hz, 1 H), 4.46 (t, J = 7.1 Hz, 2H ), 4.29 (t, J = 5.1 Hz, 1 H), 3.31 (m, 2H), 1.75 (m, 2H), 1.36-1 .26 (m, 6H). FABMS found +: 428.1730. C26H24N2O4 requires 428. 1736 EXAMPLE 92 The preparation of 9-methoxy-6-methyl-4-phenylpyrrolo [3,4-c] carbazole-1.3- (2H.6H) -dione (V: Ar = phenyl, R10 = CH-.) (223) The alkylation of pure trans-5-methoxy-2 - [(E) -2-phenylethenyl] -1H-indole (II; Ar = phenyl) (0.20 g, 0.80 mmole) with methyl iodide according to the procedure described in Example 38 gave the crude material that was reacted with maleimide (92 mg) following "Method 4a, with the exception that the reaction time was 24 h. Aromatization of the crude Diels-Alder adduct using the procedure described in Example 79 gave the crude material which was chromatographed on silica eluting with ethyl acetate / dichloromethane (1: 3). Trituration in methanol gave carbazole (223) (0.20 g, 70%) as a yellow powder, m.p. 286-291 ° C. 1 H NMR d [(CD 3) 2 SO] 1 1.11 (br s, 1 H), 8.53 (d, J = 2.6 Hz, 1 H), 7.80 (s, 1 H), 7.66 (m, 3 H), 7.47 (m, 3H), 7.30 (dd, J = 9.0, 2.6 Hz, 1 H), 3.96 (s, 3H), 3.90 (s, 3H).

Found: C, 74.29; H, 4.67; N, 7.86. C22H16N2O3 requires: C, 74.15; H, 4.53; N, 7.86.

EXAMPLE 93 The preparation of 9-hydroxy-6-metal-4-phenylpyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (VI: Ar = phenyl, R10 = CH2) (224) The demethylation of the alcohol (223) prepared as described in Example 92 (180 mg, 0.51 mmol) using the procedure described in Example 81, was followed by chromatography on silica eluting with ethyl acetate / dichloromethane (1: 2) . Trituration in dichloromethane / hexane gave the alcohol (224) (155 mg, 90%) as an orange powder, m.p. 297-300 ° C. 1 H NMR d [(CD 3) 2 SO] 1 1 .05 (br s, 1 H), 9.34 (s, 1 H), 8.39 (d, J = 2.5 Hz, 1 H), 7r76- (s, 1 H), 7.65 (m, 2H), 7.54 (d, J = 8.8 Hz. 1 H), 7.46 (m, 3H), 7.13 (dd, J = 8.8, 2.5 Hz, 1 H), 3.93 (s, 3H). Found: C, 69.96; H, 4.58; N, 7.70. C21 H14N2O3. H20 requires: C, 69.99; H, 4.48; N, 7.77.

EXAMPLE 94 The preparation of 4- (2,6-dichlorophenyl) -9-hydroxy-6- (2-hydroxyethyl) pyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (Vi: Ar-2,6-dichlorophenyl) R10 = (CH?), OH) (234) Demethylation of the alcohol (230) (0.10 g, 0.22 mmol) prepared as described in Example 85 using the procedure described in Example 80 gave the phenol (234) (49 mg, 50%) as an orange powder / yellow, pf 254-257 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.10 (br s, 1 H), 9.35 (s, 1 H), 8.36 (d, J = 2.4 ??,?), 7.80 (s, 1 H), 7.61 (m, 3H), 7.50 (dd, J = 8.7, 7.3 Hz, 1 H), 7.13 (dd, J = 8.8, 2.4 Hz, 1 H), 4.82 (t, J = 5.5 Hz, 1 H), 4.49 (t, J = 5.2 Hz, 2H), 3.75 (m, 2H). Found: C, 58.76; H, 3.34; N, 6.25. C22H14Cl2N2O4. 1 / 2H20 requires: C, 58.67; H, 3.36; N, 6.22.

EXAMPLE 95 The preparation of 4- (2,6-dichlorophenyl) -9-hydroxy-6- (3-hydroxypropyl) pyrrolo [3,4-clcarbazole-1.3 (2H.6H) -dione (VI: Ar = 2,6-dichlorophenyl) R10 = (CH2) jOH) (235) Demethylation of the alcohol (232) (0.36 g, 0.77 mmol) prepared as described in Example 86 using the procedure described in Example 80 gave the phenol (235) (0.32 g, 92%) as an orange powder / yellow, pf. 2 5-218 ° C. 1 H NMR d [(CD 3) 2 SO] 11.12 (br s, 1 H), 9.39 (s, 1 H), 8.37 (d, J = 2.5 Hz, 1 H), 7.80 (s, 1 H), 7.61 (m, 3H), 7.51 (dd, J = 8.7, 7.2 Hz, 1 H), 7.16 (dd, J = 8.8, 2.5 Hz, 1 H), 4.61 (t, J = 5.0 Hz, 1 H), 4.49 (t, J = 6.9 Hz, 2H), 3.42 (m, 2H), 1.88 (m, 2H). Found: C, 60.36; H, 3.47; N, 6.08. C23H 6CIN204 requires: C, 60.66; H, 3.54; N, 6.15.

EXAMPLE 96 The preparation of 3- 2 - [(E) -2- (2-chlorophenyl) ethenyl] -5-methoxy-1H-indol-1-ylpropanenitrile (NI.Ar = 2-chlorophenyl) R 0 = CH? CH , CN) (236 To a solution of trans-diene (27) prepared as described in example = 37 (1: 5 g 5: 25-mmoles) in acetonitrile- (30 ml) was added acrylonitrile (2.42 ml, 36.8 mmol) and 1,8-diazabicyclo [5.4.0] undec-7-ene (20 drops). The resulting solution was stirred at room temperature under a nitrogen atmosphere for 18 h before it was diluted with water and extracted with ethyl acetate. The organic layer was dried, the drying agent was removed and the solution was concentrated to dryness. Chromatography on silica eluting with ethyl acetate / hexane (II), followed by trituration in methanol gave the diene (236) (1.36 g, 77%) as an off-white solid, m.p. 136-138 ° C. 1 H NMR d [(CD 3) 2 SO] 8.05 (dd, J = 7.9, 1.5 Hz, 1 H), 7.50 (m, 4 H), 7.41 (m, 1 H), 7.33 (m, 1 H), 7.04 (d , J = 2.4 Hz, 1 H), 6.90 (s, 1 H), 6.81 (dd, J = 9.0, 2.4 Hz, 1 H), 4.68 (t, J = 6.6 Hz, 2 H), 3.77 (s, 3 H) ), 2.93 (t, J = 6.6 Hz, 2H). Found: C, 71.32; H, 5.14; N, 8.51. C20H17CIN2O requires: C, 5 71.31; H, 5.09; N, 8.31.

EXAMPLE 97 The preparation of 3- (4- (2-chlorophenyl) -9-methoxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) propanenitrile (V: Ar = 2- Chlorophenyl 10 R10 = (CH CH2CN) (237) The diene (236) (1.30 g, 3.86 mmol) prepared as described in Example 96 was reacted with maleimide (0.49 g) following the procedure described in example 68 and then flavored with the procedure. described in-example ^ 70: to: give the crude material which was chromatographed on silica eluting with ethyl acetate / hexane (1: 1). Trituration in methanol gave the nitrile (237) (1.33 g, 80%) as of a yellow powder, mp 287-288 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.16 (br s, 1 H), 8.53 (d, J = 2.6 Hz, 1 H), 8.02 (s, 1 H) ), 7.83 (d, J = 9.0 Hz, 1 H), 7.59 (m, 1 H), 7.49 (m, 3H), 7.33 (dd, J = 9.0, 2.6 Hz, 1 H), 4.86 (t, J) = 6.7 Hz, 2H), 3.91 (s, 3H), 3.04 (t, J = 6.7 Hz, 2H) Found: C, 65.32, H, 4.15, N, 9.60, C24H16CIN303, 3 / 4H20 requires: C, 65.01; H, 3.98; N, 9.47.

EXAMPLE 98 The preparation of 3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolof3.4-c] carbazole-6 (1 H) -yl) propanenitrile (VI: Ar = 2- chlorophenyl, R10 = CH2CH, CN) (238) Demethylation of the nitrile (237) (0.15 g, 0.35 mmol) prepared as described in Example 97 using the procedure described in Example 80 followed by trituration in methanol gave the phenol (238) (0.13 g, 89%) in the form of an orange / yellow powder, mp 332-336X. 1 H NMR d [(CD3) 2 SO] 1 1 .10 (s a, 1 H), 9.42 (s a, 1 H), 8.39 (d, J = 2.4 Hz, 1 H), 7.96 (s, 1 H), 7.69 (d, J = 8.8 Hz, 1 H), 7.58 (m, 1 H), 7.48 (m, 3H), 7.15 (dd, j = 8.8, 2.4 Hz, 1 H), 4.82 (t, J = 6.7 Hz, 2H), 3.02 (t, J = 6.7 Hz, 2H). Found: C, 66.24; H, 3.66; N, 9.93. C23H14CIN3O3 requires: C, 66.43; H, 3.39; N, 10.10.

EXAMPLE 99 The preparation of 6-benzyl-4- (2-chlorophenyl) -9-methoxypyrrolo [3,4-c] carbazole-1.3 (2H-6H) -dione (V: Ar = 2-chlorophenyl, R10 = CH? Ph) (239) Alkylation of the pure trans-diene (27) (0.20 g, 0.70 mmol) prepared as described in Example 37 with benzyl bromide according to the procedure described in Example 38 gave the crude material which was reacted directly with maleimide (103 mg) following the procedure described in example 68, with the exception that the reaction time was 24 h. Aromatization of the crude Diels-Alder adduct using the procedure described in Example 70 gave the crude material which was chromatographed on silica eluting with ethyl acetate / hexane (1: 2). Trituration in ethyl acetate / hexane gave the carbazole (239) (0.15 g, 46%) as a yellow powder, m.p. 234-237 ° C. H NMR d [(CD3) 2 SO] 1 1.15 (br s, 1 H), 8.55 (d, J = 2.6 Hz, 1 H), 7.91 (s, 1 H), 7.69 (d, J = 9.0 Hz, 1 H ), 7.56 (m, H), 7.46 (m, 3H), 7.25 (m, 4H), 7.16 (m, 2H), 5.79 (s, 2H), 3.90 (s, 3H). Found: C, 71.78; H, 4.39; N, 6.18. C28H19CIN2O3 requires: C, 72.02; H, 4.10; N, 6.00.

EXAMPLE 100 The preparation of 6-benzyl-4- (2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1 3- (2H.6H) -dione (VI: Ar = 2-chlorophenyl) R10- = CH2Ph ) (240), Demethylation of carbazole (239) (0.10 g, 0.21 mmol) prepared as described in Example 99 using the procedure described in Example 80, followed by chromatography on silica eluting with ethyl acetate / hexane (1: 2) and of trituration in ethyl acetate / hexane, gave the carbazole (240) (87 mg, 91%) as an orange / yellow powder, mp 260-271 ° C.

H NMR d [(CD3) 2 SO] 1 1.09 (br s, 1 H), 9.40 (s, 1 H), 8.40 (d, J = 2.5 Hz, 1 H), 7.86 (s, 1 H), 7.56 (m , 2H), 7.45 (m, 3H), 7.25 (m, 3H), 7.16 (m, 2H), 7.1 1 (dd, J = 8.9, 2.5 Hz, 1 H), 5.75 (s, 2H). Found: C, 72.06; H, 4.18; N, 6.20. C27H17CIN2O3 requires: C, 71.60; H, 3.78; N, 6.18.

EXAMPLE 101 The preparation of methyl 3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1H) -yl) propanoate (VI; Ar = 2 - chlorophenyl R10 fCH COOCH3) (264) Gaseous hydrochloric acid was bubbled through a stirred solution of the acid (117) (35 mg, 0.08 mmol) prepared as described in Example 230 in methanol (10 mL) for 30 seconds. The solution was stirred for 30 minutes at room temperature before being diluted with water and extracted with ethyl acetate, the organic layer was dried, the drying agent was removed and the solution was concentrated to dryness. silica eluting with ethyl acetate / hexane (1: 1) followed by crystallization from ethyl acetate / hexane gave the ester (264) (25 mg, 70%) as an orange powder, mp 218-220 ° C. NMR d [(CD3) 2 SO] 11.07 (br s, 1 H), 9.39 (br s, 1 H), 8.38 (d, J = 2.5 Hz, 1 H), 7.79 (s, 1 H), 7.57 (m, 2H ), 7.51 -7.44 (m, 3H), 7.14 (dd, J = 8.8, 2.5 Hz, 1 H), 4.71 (t, J = 6.8 Hz, 2H), 3.48 (s, 3H), 2.83 (t, J) = 6.8 Hz, 2H).

Found: C, 62.18; H, 4.04; N, 5.99. C24H17CIN205. 3 / 4H20 requires: C, 62.34; H, 4.03; N, 6.06.

Representative procedure for method 10a of scheme 2 EXAMPLE 102 The preparation of (2,6-dichlorobenzyl) (triphenyl) phosphonium bromide (511) A mixture of 2,6-dichlorotoluene (20.1 g, 0.125 mol), N-bromosuccinimide (24.6 g, 0.138 mmol) and 2,2'-azobissobutyronitrile (0.41 g, 2.50 mmol) in dry benzene (300 ml) in an N2 atmosphere was stirred at reflux temperature for 6H with continuous irradiation of a 100 W lamp. The resulting reaction mixture was concentrated in vacuo (to 50 mL), cooled and filtered, washing with dry benzene. The filtrate (containing the crude benzyl bromide-7) was treated directly with triphenylphosphine (49.3 g, 0.188 mmol), stirring at reflux temperature for 17 h. After cooling, the precipitate was collected by filtration, washed thoroughly with dry benzene, then with pentane, and dried under vacuum at 50 ° C to give the phosphonium salt (51) as a cream powder (62.1 g, 99%). %), pf (benzene) 247-250 ° C. H NMR (CDCl 3) d 7.76 (m, 9H), 7.64 (m, 6H), 7.18 (s, 3H), 5.50 (d, J = 14.3 Hz, 2H).

Found: C, 60.03; H, 3.76. C25H2oBrCl2P requires C, 59.79; H, 4.01.

EXAMPLE 103 The preparation of 2 - [(E) -2- (2,6-dichlorophenyl) ethenyl] -5-methoxy-1H-indole (512) (H: Ar = 2,6-dichlorophenyl) The 5-methoxy-1 H-indole-2-carbaldehyde (1) was reacted with (2,6-dichlorobenzyl) (triphenyl) phosphonium bromide (511) prepared as described in Example 102 using the procedure described in Example 37, with the exception that the LDA and the aldehyde were added (sequentially) at 0 ° C, the ratio of LDA: aldehyde was 1.37: 1 and the reaction time was 5 h, to give (after crystallization in Ch ^ C ^ / hexane) the diene (512) as a yellow solid (the pure E-isomer) (97%), mp 144-147? C. · -. 1 H NMR (CDCl 3) d 8.20 (br s, 1 H), 7.36 (d, J = 8.1 Hz, 1?), 7: 27- - - (m, 1 H), 7.25 (d, J = 16.8 Hz, 1 H), 7.11 (t, J = 8.0 Hz, 1 H), 7.03 (d, J = 2.4 Hz, 1 H), 6.93 (d, J = 16.8 Hz, 1 H), 6.88 (dd, J = 8.7, 2.5 Hz, 1 H), 6.61 (d, J = 1.8 Hz, 1 H), 3.86 (s, 3H). Found: C, 64.04; H, 4.13; N, 4.39. Ci7H13CI2NO requires C, 64. 17; H. 4.12; N, 4.40.

EXAMPLE 104 The preparation of 4- (2,6-dichlorophenol) -9-methoxy-4,5-6,10-tetrahydropyrrolo [3,4-clcarbazole-1.3- (2H.3aH) -done (513) (IV. Ar = 2,6-dichlorophenyl) The pure Diene E (512) prepared as described in Example 103 was reacted with maleimide according to the procedure described in Example 68 in a sealed vial covered with aluminum foil, with the exception that the diene ratio : maleimide: SnCl2 was 1: 4: 0.075 and the reaction time was 3 h, to give a crude solid containing the adduct (513), which was used without further purification.

EXAMPLE 105"The preparation of 4- (2,6-dichlorophenyl) -9-methoxypyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (514) (V. R10 = H. Ar = 2,6-dichlorophenyl) The crude adduct (513) prepared as described in Example 104 was aromatized with DDQ (5 equiv.) Using the procedure described in Example 70, with the exception that the solvent was 1: 1 toluene / dioxane and the reaction time was 48 h, to give (after crystallization from MeOH / Ch C / hexane) the product (514) (78%) as a yellow crystalline solid, mp 299-301 ° C. 1 H NMR [(CD 3) 2 SO] d 12.02 (br s, 1 H), 1 1.15 (br s, 1 H), 8.45 (d, J = 2.6 Hz, 1 H), 7.61 (d, J = 7.7 Hz, 2H) , 7.61 (s, 1 H), 7.59 (d, J = 8.9 Hz, 1 H), 7.50 (dd, J = 8.8, 7.4 Hz, 1 H), 7.26 (dd, J = 8.9, 2.7 Hz, 1H) 3.90 (s, 3H). Found: C, 61.26; H, 2.92; N, 6.65. C21 H12Cl2N2O3 requires 5 C, 61.33; H, 2.94; N, 6.81.

EXAMPLE 106 The preparation of 4- (2,6-dichlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (515) (VI: R1Q = H. Ar = 2,6-dichlorophenyl) 10 The ether methyl (514) prepared as described in Example 105 was demethylated with BBr2 using the procedure described in Example 80 to give (after crystallization in MeOH / CH2Cl2 / hexane) phenyl (515) (98%) as of an orange solid, mp 205-215 ° C (dec). Δ5 ~ "- H NMR [(CD3) 2SO] d 1-1.89 (sa, 1 H), 1.08 (sa, 1 H), 9.32 (sa, 1 H), 8.30 (d, J = 2.4 Hz, 1 H), 7.61 (d, J = 7.9 Hz, 2H), 7.55 (s, 1 H), 7.50 (dd, J = 8.7, 7.4 Hz, 1 H), 7.47 (d, J = 8.7 Hz, 1 H) 7.10 (dd, J = 8.7, 2.4 Hz, 1 H) Found: C, 58.98, H, 2.99, N, 6.68, C20H10Cl2N2O3, 1 / 2H20 requires C, 59.13, H, 2.73, N, 6.90.

EXAMPLE 107 Bromide (2,6-dibromobenzyl) (trephenyl) phosphonium (516) Bromination of 2,6-dibromotoluene with NBS / AIBN, followed by reaction of the crude bromide with triphenylphosphine, using the procedure described in Example 102, with the exception that the reaction time for bromination was 3 h, the phosphonium salt (516) (95%) in the form of a cream powder, mp (CH2Cl2 / benzene) 241-243 ° C. H NMR (CDCl 3) d 7.78 (m, 9H), 7.64 (m, 6H), 7.40 (da, J = 7.9 Hz, 2H), 6.99 (td, J = 8.0, 2.5 Hz, 1 H), 5.58 (d , J = 14.1 Hz, 2H). Found: C, 47.06; H, 3.37. C25H2oBr3P. 3 / 4CH2Cl2 requires C, 47.23; H, 3.31.

EXAMPLE 108 The preparation de2 - [(E) -2- (2,6-dibromophenyl) ethenyl] -5-methoxy-1 H-indole (517) (II. Ar = 2,6-dibromophenyl) The 5-methoxy-1 H-indole-2-carbaldehyde (1) was reacted with (2,6-dibromobenzyl) (triphenyl) phosphonium bromide (516) prepared as described in Example 107 using the procedure described in Example 37, with the exception that the ratio of LDA: aldehyde was 1.37: 1 and the reaction time was 5 h, to give (after crystallization in CH2Cl2 / hexane) the diene (517) in the form of a yellow solid (pure E-isomer) (80%), mp 140-141 ° C. 1 H NMR (CDCl 3) d 8.20 (br s, 1 H), 7.60 (d, J = 8.1 Hz, 1 H), 7.27 (d, J = 8.2 Hz, 1 H), 7.05 (sa, 1 H), 7.03 (d, J = 16.7 Hz, 1 H), 6.96 (t, J = 8.0 Hz, 1 H), 6.88 (d, J = 8.7, 2.5 Hz, 1 H), 6.82 (d, J = 16.7 Hz, 1 H), 6.61 (d, J = 1 .9 Hz, 1 H), 3.86 (s, 3H). Found: C, 50.37; H, 3.24; N, 3.37. Ci7H 3Br2NO requires C, 50.16; H, 3.22; N, 3.44.

EXAMPLE 109 The preparation of 4- (2,6-dibromophenyl) -9-methoxy-4.5.6.10-tetrahydropyrrolo [3,4-c1carbazole-1.3 (2H-3aH) -dione 518) (IV: R 0 = H. Ar = 2.6- dibromophenyl) "" "" The pure Diene E "(517) prepared as described in example 108 was reacted with maleimide according to the. .. .._ procedure described in example 68 in a sealed vial covered with aluminum foil, with the exception that the ratio of diene: maleimide: SnCl2 was 1: 5: 0.075 and the reaction time was 3.5 h, to give the crude solid containing the adduct (518), which was used without further purification.

EXAMPLE 110 The preparation of 4- (2,6-dibromophenyl) -9-methoxypyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (519) (V. R10 = H. Ar = 2,6-dibromophenyl) The crude adduct (518) prepared as described in Example 109 was aromatized with DDQ (5 equiv.) Using the procedure described in Example 70, with the exception that the solvent was 1: 1 toluene / dioxane and the reaction time was 24 h, to give (after crystallization in MeOH / CH2Cl2 / hexane) the product (519) (68%) as orange crystalline solid ur, mp 329-331 ° C. 1 H NMR [(CD 3) 2 SO] d 12.02 (br s, 1 H), 1 1.13 (br s, 1 H), 8.45 (d, J = 2.6 Hz, 1 H), 7.80 (d, J = 8.1 Hz, 2H) , 7.59 (d, J = 8.3 Hz, 1 H), 7.54 (s, 1 H), 7.33 (t, J = 8.0 Hz, 1 H), 7.26 (dd, J = 8.8, 2.6 Hz, 1 H), 3.90 (s, 3H). Found: C, 50.29; H, 2.32; N, 5.69. C2iHi2Br2N203 requires C, 50.43; H, 2G42; N, 5.60. "- - ^ _-_ - - - _ EXAMPLE 111 The preparation of 4- (2,6-dibromophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (520) (VI: R10 = H. Ar = 2,6-dibromophenyl) The methyl ether (519) prepared as described in Example 10 was demethylated with BBr3 using the procedure described in Example 80, with the exception that the reaction time was 1.5 h, to give (after crystallization from MeOH / CH2Cl2 / EtOAc / hexane) phenyl (520) (98%) as a yellow-orange solid, mp 180-190 ° C (dec). 1 H NMR [(CD 3) 2 SO] d 11 .90 (br s, 1 H), 1.08 (sa, 1 H), 9.35 (br s, 1 H), 8.30 (d, J = 2.3 Hz, 1 H), 7.80 (d, J = 8.1 Hz, 2H), 7.49 (s, 1 H), 7.48 (d, J = 8.9 Hz, 1 H), 7.33 (t, J = 8.1 Hz, 1 H), 7.11 (dd, J = 8.7, 2.5 Hz, 1 H). Found: C, 49.13; H, 2.29; N, 6.05. C2oHioBr2N203 requires C, 49.42; H, 2.07; N, 5.76.

Representative procedure for method 10b of scheme 2 EXAMPLE 112 Preparation of (2,6-dichloro-4-methoxybenzyl) (triphenyl) phosphonium bromide (521) - * One * solution of (2,6-dichloro-4-methoxy-spheryl) methanol (3.00 g, 14.5 mmol) in 30% HBr in acetic acid (45 ml) was stirred at 20 ° C for 3 h and then poured into water cooled with ice (120 ml) and extracted with pentane (6 x 100 ml). The extracts were washed with water (3 x 200 ml) and extracted again with pentane (100 ml). Removal of the solvent gave the crude bromide as white crystals which were immediately redissolved in benzene (80 ml) and treated with triphenylphosphine (5.70 g, 21.7 mmol), stirring at reflux temperature for 15 h. After cooling, the precipitate was collected by filtration, washed thoroughly with dry benzene and then with pentane, and dried under vacuum at 50 ° C to give the phosphonium salt (521) as a white solid (7.75 g, 100% ), pf (CH2Cl2 / benzene) 188-190 ° C. 1 H NMR (CDCl 3) d 7.83-7.60 (m, 15H), 6.74 (s, 2H), 5.37 (d, J = 13.5 H2, 2H), 3.76 (s, 3H). Found: C, 58.40; H, 4.35. C26H22BrCI2OP requires C, 58.67; H, 4.17.

EXAMPLE 113 The preparation of 2 - [(E) -2- (2,6-dlchloro-4-methoxyphenyl) ethenyl] -5-methoxy-1 H indole (5221 II. Ar = 2,6-diclo-4-methoxyphenyl) The compound 5-methoxy-1 H -indole-2-carbaldehyde (1) was reacted with (2,6-dichloro-4-methoxybenzyl) (trifhenyl) phosphonium bromide (521), prepared as described in the example? 12, "using the procedure described in Example 37, with the exception that the aldehyde was added at 0 ° C, the ratio of LDA: aldehyde was 1, 37: 1 and the reaction time was 5, to give ( after crystallization from CH 2 Cl 2 / hexane) the diene (522) as a cream solid (pure E-isomer) (70%), mp 128-129 ° C. 1 H NMR (CDCl 3) d 8.17 (br s, 1 H ), 7.25 (d, J = 8.7 Hz, 1 H), 7.17 (d, J = 16.8 Hz, 1 H), 7.04 (d, J = 2.4 Hz, 1 H), 6.93 (s, 2H), 6.88 (d, J = 16.8 Hz, 1 H), 6.86 (dd, J = 8.7, 2.5 Hz, 1 H), 6.57 (day, J = 1.7 Hz, 1 H), 3.85 (s, 3H), 3.82 (s, 3H).

Found: C, 62.01; H, 4.23; N, 4.21. Ci8H15CI2N02 requires C, 62.09; H, 4.34; N, 4.02.

EXAMPLE 114 The preparation of 4- (2,6-detoxy-4.5.6. 0c-tetrahydropyrrolo [3,4-c] carbazole-1.3 (2H.3aH) -dione (IV: R10 = H. Ar = 2,6-dichloro-4-methoxyphen the) The pure Diene E (522) prepared as described in Example 1 13 was reacted with maleimide according to the procedure described in Example 68 in a sealed vial covered with aluminum foil, with the exception that the ratio of diene: maleimide: SnCl2 was 1: 6: 0.05 and the reaction time was 1.5 hours, to give a crude solid containing the adduct (523), which was used without further purification.

EXAMPLE 115 The preparation of 4- (2,6-dichloro-4-methoxyphenyl) -9-methoxypyrrolo [3,4-clcarbazole-1.3 (2H.6H) -dione (524) (V. R10 = H. Ar = 2.6-dichloro-4 - methoxyphenyl) The crude adduct (523) prepared as described in Example 1 14 was aromatized with DDQ (6 equiv.) Using the procedure described in Example 70, with the exception that the solvent was 1: 1 toluene / dioxane and the reaction time was 24 h, to give (after crystallization in MeOH / CH2Cl2 / hexane) the product (524) (74%) as a yellow-orange crystalline solid, mp. 272-274 ° C. 1 H NMR [(CD 3) 2 SO] d 1 1.98 (br s, 1 H), 11.12 (br s, 1 H), 8.44 (d, J = 2.6 Hz, 1 H), 7.58 (d, J = 8.7 Hz, 1 H ), 7.57 (s, 1 H), 7.26 (dd, J = 8.8, 2.6 Hz, 1 H), 7.23 (s, 2H), 3.89 (2 s, 2 x 3H). Found: C, 56.89; H, 3.18; N, 5.94. C22H14Cl2N204. 5 / 4H20 requires C, 56.97; H, 3.59; N, 6.04.

EXAMPLE 16 The preparation of 4- (2-6-dichloro-4-hydroxyphenyl) -9-hydroxypyrrolo [3,4-clcarbazole-1.3 (2H.6H) -dione (525) (VI, R 0 = H. Ar = 2,6-dichloro- 4- hydroxyphenyl) - ~ -| - - The ether-methyl (524) "" prepared as described in Example 15 was bis-demethylated with BBr3 using the procedure described in Example 80, except that the reaction time was of 4 h with 10 equiv. of G3 and then 9 h more with 10 equiv. more of BBr3, to give (after crystallization in MeOH / CH2CI2 / hexane) phenyl (525) (95%) in the form of a yellow-orange solid, mp 300-308 ° C. 1 H NMR [(CD3) 2 SO] d 11.82 (br s, 1 H), 1.03 (br s, 1 H), 10.47 (br s, 1 H), 9.28 (br , 1 H), 8.29 (d, J = 2.4 Hz, 1 H), 7.50 (s, 1 H), 7.46 (d, J = 8.7 Hz, 1 H), 7.08 (dd, J = 8.7, 2.5 Hz, 1 H), 6.96 (s, 2H).Found: C, 56.28; H, 2.94; N, 6.16. C20H10Cl2N2O4. 3/4 H20 requires C, 56.29; H, 2.72; N, 6.56.

EXAMPLE 117 The preparation of (2,6-dichloro-3-methoxybenzyl) (triphenyl) phosphonium bromide (526) Bromination of (2,6-dichloro-3-methoxyphenyl) methanol with 30% HBr in acetic acid followed by reaction of the crude bromide with triphenylphosphine, using the procedure described in Example 112, with the exception that the time of reaction for displacement was 36 h, gave the phosphonium salt (526) (97%) as a white solid, mp (CH2Cl2 / benzene) 242-244 ° C. 1 H NMR (CDCl 3) d 7.83-7.60 (m, 15H), 7.15 (dd, J = 9.1, 0.8 Hz, 1 H), 6.88 (dd, J = 9.0, -2.4 Hz, 1 H), 5.41 (d, J = 14.3 Hz, 2H), 3.84 (s, '3H). 'G' Found: C, 58.68; H, 4.16, C26H22BrCI2OP requires C, 58.67; H. 4.17.

EXAMPLE 118 The preparation of 2 - [(E) -2- (2,6-dichloro-3-methoxyphenyl) ethenyl] -5-methoxy-1 H-indole (527) (II. Ar-2,6-dichloro-3-methoxyphenyl) The compound 5-methoxy-1H-indole-2-carbaldehyde (1) was reacted with (2,6-dichloro-3-methoxybenzyl) (triphenyl) phosphonium bromide (526), prepared as described in the example 117, using the procedure described in Example 37, with the exception that the aldehyde was added to TC, the ratio of LDA: aldehyde was 1.55: 1 and the reaction time was 5 h, to give (after crystallization in CH 2 Cl 2 / hexane) the diene (527) in the form of a cream solid (the pure E-isomer) (76%), mp 138-140 ° C. 1 H NMR (CDCl 3) d 8.21 (sa, 1 H), 7.32 (d, J = 8.9 Hz, 1 H), 7.26 (d, J = 8.7 Hz, 1 H), 7.22 (d, J = 16.8 Hz, 1 H), 7.04 (d, J = 2.4 Hz, 1 H), 6.92 (d, J = 16.8 Hz, 1 H), 6.87 (dd, J = 8.8, 2.5 Hz, 1 H), 6.80 (d, J = 8.9 Hz, 1 H), 6.61 (d, J = 1.7 Hz, 1 H), 3.92 (s, 3 H); 3.85 (s, 3H). - --- -| · - - · = - - - 's - ~ - Found: C, 61 .29; H, 4.52; N, 3.91. C18H15Cl2N02 requires C, 62.09; H, 4.34; N, 4.02.

EXAMPLE 119 The preparation of 4- (2,6-dichloro-3-methoxyphenyl) -9-methoxy-4.5.6-10-tetrahydropyrrolo [3,4-c] carbazole-1.3 (2H.3aH) -dione (528) (IV : R10 = H. Ar = 2,6-dichloro-3-methoxyphenyl) The pure Diene E (527) prepared as described in Example 118 was reacted with maleimide according to the procedure described in Example 68 in a sealed vial covered with aluminum foil, with the exception that the ratio of diene: maleimide: SnCl2 was 1: 5: 0.03 and the reaction time was 2.5 h, to give a crude solid containing the adduct (528) that was used without further purification.

EXAMPLE 120 The preparation of 4- (2,6-dichloro-3-methoxyphenyl) -9-methoxypyrrolo [3.4"clcarbazole-1.3 (2H.6H) -dione (529) (V. R10 = H. Ar = 2.6-dichloro-3 - methoxyphenyl The crude adduct (528) prepared as described in Example 119 was aromatized with DDQ (5 equiv.) Using the procedure described in Example 70, with the exception that the solvent was 1: 1 toluene / dioxane and the reaction time was 24 h, to give (after crystallization in CH2Cl2 / hexane) the product (529) (70%) as an orange crystalline solid, mp240-242 ° C. HRN [(CD3) 2SO) d 12.00 (br s, 1H), 11.13 (br s, 1H), 8.45 (d, J = 2.6 Hz, 1H), 7.58 (d, J = 8.2 Hz, 1H), 7.56 (s, 1H), 7.56 (d, J = 8.7 Hz, 1H), 7.28 (d, J = 9.3 Hz, 1 H), 7.26 (dd, J = 9.0, 2.4 Hz, 1 H), 3.94 (s, 3H), 3.90 (s, 3H). Found: C, 60.11; H, 3.16; N, 6.30. C22H14Cl2N204 requires C, 59.88; H, 3.20; N, 6.35.

EXAMPLE 121 The preparation of 4- (2,6-dichloro-3-hydroxyphenyl) -9-hydroxypyrrolo [3,4-clcarbazole-1.3 (2H.6H) -dione (530) (VI: R10 = H. Ar = 2.6-dichloro-3 - hydroxyphenyl The methyl ether (529) prepared as described in Example 120. was bis-demethylated with BBf3 using the procedure described in Example 80, with the exception that the reaction time was 6 h with 10 equiv. of BBr3l to give (after crystallization in MeOH / CH2Cl2 / hexane) phenyl (530) 91%) as an orange crystalline solid, m.p.313-318 ° C. 1H NMR [(CD3) 2SO] 5 1.84 (br s, 1H), 11.05 (br s, 1H), 10.56 (br s, 1H), 9.29 (sa, 1H), 8.30 (d, J = 2.4 Hz, 1H), 7.48 (s, 1H), 7.46 (d, J = 8.7 Hz, 1H), 7.36 (d, J = 8.8 Hz, 1H), 7.09 (dd, J = 8.8, 2.6 Hz, 1H), 7.06 (d, J = 8.9 Hz, 1H).

Found: C, 57.21; H, 2.65; N, 6.58. C20H10Cl2N2O4. 1/2 MeOH requires C, 57.36; H, 2.82; N, 6.53.

EXAMPLE 122 The preparation of 2 - [(E) -2- (2-bromophenyl) ethenyl] -5-methoxy-1 H-indole (531) (II: Ar-2-bromophenyl) The compound 5-methoxy-H-indole-2-carbaldehyde (1) was reacted with (2-bromobenzyl) (triphenyl) phosphonium bromide using the procedure described in Example 37, with the exception that the aldehyde was added at 0 ° C, the ratio of LDA: aldehyde was 1.46: 1 and the reaction time was 5 h, to give (after crystallization in CH2Cl2 / hexane) the diene (531) as a yellow solid ( pure isomer E) (88%), mp 120-123 ° C. . 1 H NMR (CDCl 3) d.8.21 (s a, 1 H), 7.66: (dd, J = 7: 9, 1.5 Hz, 1 H), 7. 59 (dd, J = 8.1, 1.0 Hz, 1 H), 7.32 (ta, J = 7.1 Hz, 1 H), 7.27 (d, J = 8.3 Hz, 1 H), 7.22 (d, J = 16.4 Hz, 1 H), 7.12 (td, J = 7.6, 1.5 Hz, 1H), 7.05 (d, J = 16.4 Hz, 1 H), 7.04 (d, J = 2.4 Hz, 1 H), 6.88 (dd, J = 8.8, 2.4 Hz, 1 H), 6.59 (d, J = 1 .7 Hz, 1 H), 3.86 (s, 3 H). Found: C, 61.97; H, 4.30; N, 4.17. C17H14BrNO requires C, 62. twenty-one; H. 4.30; N, 4.27.

Representative procedure to combine method 4a and method 6 of scheme 2 EXAMPLE 123 The preparation of 4- (2-bromophenyl) -9-methoxypyrrolo [3,4-c] carbazole-11.3 (2H.6H) -dione (532) (V: R10 = H. Ar = 2-bromophenyl) A foil-coated mixture of pure Diene E (531) (1.00 g, 3.05 mmol) prepared as described in Example 122 and maleimide (1.48 g, 5.2 mmol) in dry toluene (10 mL) was stirred in a sealed vial at reflux temperature for 24 h. The resulting slurry was transferred to a flask using more toluene (30 mL) and dioxane (40 mL) and then treated with DDQ (3.49 g, 15.4 mmol), stirring at reflux temperature for 24 h. The resulting mixture was treated with a saturated aqueous solution of NaHCO 3 (250 mL) and the product was extracted with 15% MeOH / CH 2 Cl 2. These extracts were washed with an aqueous solution of NaHCO 3 and water. The aqueous NaHC03 solution and water were extracted several times with 15% MeOH / CH2CI2 and then the combined extracts were concentrated to dryness. The residue was adsorbed on silica gel and chromatographed. Elution with 0-0.75% MeOH / CH 2 Cl 2 and then with 0.75% MeOH / CH 2 Cl 2 gave the crude product (532) which was crystallized pure in MeOH / CH 2 Cl 2 / hexane as an orange crystalline solid (1.23 g, 96%), pf 273-275 ° C. 1 H NMR [(CD 3) 2 SO] d 11.96 (br s, 1H), 11.08 (br s, 1H), 8.46 (d, J = 2.6 Hz, 1H), 7.74 (d, J = 7.8 Hz, 1H), 7.58 (d , J = 8.9 Hz, 1H), 7.55 (s, 1H), 7.48 (m, 2H), 7.39 (m, 1H), 7.25 (dd, J = 8.9, 2.7 Hz, 1H), 3.89 (s, 3H) . Found: C, 60.08; H, 3.02; N, 6.68. C2iH13BrN203 requires C, 59.88; H, 3.1; N, 6.65.

EXAMPLE 124 The preparation of 4- (2-bromophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (533) (VI: R10 = H. Ar = 2-bromophenyl) The methyl ether (532) prepared as described in Example 123 was demethylated with BBr3 using the procedure described in Example 80, with the exception that the reaction time was 4 h. Crystallization in MeOH / CH 2 Cl 2 / hexane gave the phenyl (533) with a yield of 89% in the same way. yellow-orange solid, p.f .; 244-246 ° C: "| '1H NMR [(CD3) 2SO] d 11.83 (br s, 1H), 11.01 (br s, 1H), 9.29 (br s, 1H), 8.31 (d, J = 2.4 Hz, 1H) 7.73 (da, J = 7.9 Hz, 1H), 7.47 (m, 4H), 7.38 (m, 1H), 7.08 (dd, J = 8.7, 2.5 Hz, 1H) Found: C, 57.82; H, 2.90 N, 6.72, C20HnBrN2O3, 1 / 2H20 requires C, 57.71, H, 2.91, N, 6.73.

EXAMPLE 125 The preparation of 4- [1,1'-biphenin-2-yl-9-methoxypyrrolo [3,4-c] carbazole 1.3 (2H.6H) -dione (534) (V. R10 = H. Ar = 2- biphenyl) A mixture of the bromo derivative (532) (85.5 mg, 0.203 mmol) prepared as described in example 123, [1,1-bis (diphenylphosphino) ferrocene] dichloropalladium (11), CH2Cl2 (85 mg, 0.104) mmoles) and tetraphenyltin (0.451, 1.06 mmol) in dry DMF (2.5 ml) was stirred in a sealed vial at 130 ° C for 4 d. The resulting mixture was added to NaHCC >3 aqueous (100 ml) and then extracted with 2: 1 CH 2 Cl 2 / EtOAC (5 x 80 ml). The extracts were washed with water: The water was extracted with 2: 1 CH2Cl2 / EtOAc and then the combined organic extracts were concentrated to dryness. The residue was chromatographed several times on silica gel (eluting with CH 2 Cl 2) to give the crude product (44 5 mg, 54%). combined with "material-like" reactions and "purified by preparative reverse phase C18 HPLC (using a gradient of 65-99% CH3CN / aqueous HC02NH4 buffer, pH 3.45) to give (after crystallization in MeOH / CH 2 Cl 2 / hexane) the product (534) (total 21%) as a yellow solid, mp 220-223 ° C. 1 H NMR [(CD 3) 2 SO] d 11.76 (br s, 1 H), 10.87 (br , 1 H), 8.39 (d, J = 2.6 Hz, 1 H), 7.50 (m, 5H), 7.38 (s, 1 H), 7.20 (dd, J = 8.9, 2.6 Hz, 1 H), 7.10 (m, 5H), 3.86 (s, 3H).

Found: C, 77.37; H, 4.21; N, 6.88. C27H18N203 requires C, 77.50; H, 4.34; N, 6.69.

EXAMPLE 126 The preparation of 4- [1,1'-biphenyl] -2-yl-9-hydroxypyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (535) (VI.R10 = H. Ar = 2- biphenyl) The methyl ether (534) prepared as described in Example 125 was demethylated with BBr3 using the procedure described in Example 80, with the exception that the reaction time was 4 h, to give (after crystallization in MeOH / CH2Cl2 / hexane) phenyl (535) (98%) as a yellow solid, mp 198-203 ° C (dec). 1H MN [(CD3) 2SO] d 1 1.61 (sa, 1 H), 10.82 (sa, 1 H), 9.22 (sa, 1 H), 8.24 (d, J = 2.4 Hz, 1H), 7.52 (m, 1 H), 7.45 (m, 3H), 7.37 (d, J = 8.7 Hz, 1 H), 7.31 (s, 1 H), 7.11 (m, 5H) "7.03 (ddr J = 8: 7, 2: 5 Hz, 1 H).; r w ~ ~: "" "" "Found: C, 76.38; H, 3.94; N, 6.99, C26H16N2O3, 1 / 4H20 requires C, 76.37; H, 4.07; N, 6.85.

EXAMPLE 127 The preparation of 5-methoxy-2 - [(E) -2-nitrophenyl) ethenyl-1 H-indole (536) (11. Ar = 2-nitrophenyl) The compound 5-methoxy-1H-indole-2-carbaldehyde (1) was reacted with (2-nitrobenzyl) (triphenyl) phosphonium chloride using the procedure described in Example 37, with the exception that the ratio of LDA: aldehyde was 1.37: 1 and the reaction time was 5 h, to give (after crystallization in CH2Cl2 / hexane) the diene (536) as red-orange crystals (the pure E-isomer) ( 47%), mp136-138 ° C. H NMR (CDCl 3) d 8.25 (sa, 1H), 7.98 (dd, J = 8.2, 1.2 Hz, 1H), 7.78 (dd, J = 7.9, 1.0 Hz, 1H), 7.61 (td, J = 7.6, 0.9 Hz, 1H), 7.41 (d, J = 16.3 Hz, 1H), 7.39 (td, J = 7.8, 1.3 Hz, 1H), 7.27 (m, 1H), 7.13 (d, J = 16.3 Hz, 1H), 7.04 (d, J = 2.4 Hz, 1H), 6.90 (dd, J = 8.8, 2.5 Hz, 1H), 6.62 (d, J = 1.8 Hz, 1H), 3.86 (s, 3H). . ·. · - · .. · ---. - ----- ': r ~' "" Found: C, 69.44; H, 4.49; N, 9.70. Ci7H14N203 requires C, 69. 38; H, 4.79; N, 9.52.

EXAMPLE 128 The preparation of 9-methoxy-4- (2-nitrophenyl) pyrrolo [3,4-c] carbazole-1.3 (2H-6H) -dione (537) (V. R 10 = H. Ar = 2-nitrophenyl) The pure Diene E (536) prepared as described in Example 127 was subjected to successive reactions with maleimide and then with DDQ according to the above representative procedure described in Example 123, to give (after crystallization in MeOH / EtOAc / CH 2 Cl 2 / hexane) the product (537) (97%) as a yellow-orange solid, mp 294-298 ° C. 1 H NMR [(CD 3) 2 SO] d 12.01 (br s, 1 H), 1 1 .10 (br s, 1 H), 8.44 (d, J = 2.5 Hz, 1 H), 8.21 (dd, J = 8.1, 1.0 Hz, 1 H), 7.86 (td, J = 7.5, 1.4 Hz, 1 H), 7.74 (td, J = 7.8, 1 .3 Hz, 1 H), 7.67 (s, 1 H), 7.65 (dd, J = 7.6, 1.4 Hz, 1 H), 7.59 (d, J = 8.9 Hz, 1 H), 7.25 (dd, J = 8.7, 2.6 Hz, 1 H), 3.90 (s, 3H). Found: G, 64.99; ·?; ·· 3: 42; ?, - 0.79;? 2 ?? ? 307 requires C, 65. 12; H, 3.38; N, 10.85. ' "'" EXAMPLE 129 The preparation of 9-hydroxy-4- (2-nitrophenyl) pyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (538) (VI.R10 = H. Ar = 2-nitrophenyl The methyl ether (537) prepared as described in Example 128 was demethylated with BBr3 using the procedure described in Example 80, with the exception that the reaction time was 5 h with 5 equiv. of BBr3, and then 21 h more with 5 equiv. more than BBr3, to give (after crystallization in MeOH / CH2Cl2 / hexane) phenyl (538) (53%) as an orange solid, m.p. 322-330 ° C. 1 H NMR [(CD 3) 2 SO] d 1 1. 88 (br s, 1 H), 11.05 (br s, 1 H), 9.29 (br s), 1 H), 8.30 (d, J = 2.4 Hz, 1 H), 8.20 (dd, J = 8.2, 1.1 Hz, 1 H), 7.85 (td, J = 7.5, 1.2 Hz, 1 H), 7.73 (td) , J = 7.9, 1.4 Hz, 1 H), 7.63 (dd, J = 7.6, 1.4 Hz, 1 H), 7.61 (s, 1 H), 7.47 (d, J = 8.7 Hz, 1 H), 7.09 ( dd, J = 8.7, 2.5 Hz, 1 H). Found: C, 63.03; H, 3.27; N, 10.59. C2oHiiN305. 1/2 MeOH requires C, 63.24; H, 3.37; N, 10.79.

EXAMPLE 130 The preparation of 4- (2-aminophenyl) -9-methoxypyrrolo [3,4-c] carbazole-1.3 (2H-6H) -dione (539) (V. R 0 = H. Ar = 2-aminophenyl) A solution of the nitro derivative (537) (71 mg, 0.183 mmol) prepared as described in example 128 in 2: 1 THF / MeOH (45 ml) containing 10% Pd wet C (71 mg) ) was hydrogenated at 413,685 kPa (60 psi) for 7 h. The solution was filtered through celite, the celite and the catalyst were washed thoroughly with MeOH and THF and then the filtrate was concentrated to dryness. Crystallization of the residue in MeOH / CH2Cl2 / hexane gave the amine (539) (67 mg, 97%) as a yellow solid, m.p. > 320 ° C.

H NMR [(CD3) 2 SO] d 1 1.80 (br s, 1 H), 10.94 (br s, 1 H), 8.47 (d, J = 2.6 Hz, 1 H), 7.54 (d, J = 8.8 Hz, 1 H ), 7.51 (s, 1 H), 7.21 (dd, J = 8.8, 2.6 Hz, 1 H), 7.08 (td, J = 7.7, 1.5 Hz, 1 H), 7.01 (dd, J = 7.6, 1.5 Hz , 1 H), 6.73 (dd, J = 8.1, 0.6 Hz, H), 6.61 (td, J = 7.4, 0.9 Hz, 1 H), 4.70 (s, 2H), 3.89 (s, 3H). Found: C, 67.22; H, 4.50; N, 1 1 .03. C2iH15N303. H20 requires C, 67.19; H, 4.56; N, 11.19.

EXAMPLE 131 The preparation of 4- (2-aminophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1.3 (2H.6m-dione (5401 (VI, R10 = H-Ar = 2-aminophenyl)) A solution of the nitro derivative (538) (81 mg, 0.217 mmol) prepared as described in Example 129 in 2: 1 THF / MeOH (60 mL) containing 10% Pd wet C (81 mg) it was hydrogenated at 413.685 kPa _ (60- The solution was filtered through celite, the celite and the catalyst were washed thoroughly with MeOH and THF and then the filtrate was concentrated to dryness. CH 2 Cl 2 / hexane gave the amine (540) (60 mg, 81%) as a brown solid, mp> 330 ° C. 1 H NMR [(CD 3) 2 SO] d 1 1.67 (br s, 1 H), 10.88 ( sa, 1 H), 9.21 (s, 1 H), 8.32 (d, J = 2.4 Hz, 1 H), 7.46 (s, 1 H), 7.42 (d, J = 8.6 Hz, 1 H), 7.08 (td, J = 7.9, 1.5 Hz, 1 H), 7.05 (dd, J = 8.7, 2.4 Hz, 1 H), 7.00 (dd, J = 7.6, 1.4 Hz, 1 H), 6.72 (ad, J = 8.1 Hz, 1 H), 6.60 (td, J = 7.4, 0.9 Hz, 1 H), 4.69 (s, 2H).

Found: C, 66.35; H, 4.06; N, 1 1.76. C20H13N3O3. H20 requires C, 66.48; H, 4.18; N, 1.63.

EXAMPLE 132 The preparation of 4- (2-hydroxyphenyl) -9-methoxypyrrolo [3,4-c] carbazole-1.3 (2H.6m-dione (541 WV, R10 = H. Ar = 2-hydroxyphenyl) A solution of the amine (539) (129 mg, 0.361 mmol) prepared as described in Example 130 in 90% H2SO4 (7.5 mL) was cooled to -10 ° C and diluted with ice-cold water. (20 mi). After stirring at -10 ° C for 10 min, the resulting suspension was treated dropwise with a solution of NaNÜ2 (38 mg, 0.551 mmol) in cold water (2 x 1 mL) and stirred at -10 to - 5 ° C for 30 min. A solution of urea (13 mg, 0.216 mmol) in cold water (2 x 0.75 ml) was added and the mixture was stirred at -5 ° C for 5 min. Finally, a suspension of? G (400 mg ~, 2.41 mmol) and Cul (402 mg, 2.1 1 mmol) in cold water (2 x 2.5 ml) was added and then the cooling bath was removed and the mixture was stirred for 10 min, then at 60-65 ° C for 2 h. An aqueous solution of sodium metabisulfite (100 ml of 5%) was added, then the pH was adjusted to pH = 3 with NaHCO 3 and the mixture was extracted with EtOAc (5 x 100 mL). The extracts were washed with water (200 ml), the water was extracted with EtOAc and the combined organic extracts were concentrated to dryness. The residue was adsorbed on silica gel and chromatographed. Elution with 0-0.5% MeOH / CH2CI2 followed by 0.5% MeOH / CH2CI2 yielded a mixture of crude iodides (534.544) (24 mg, see the experiment shown below for analytical data). Elution with 1% MeOH / CH 2 Cl 2 gave (after crystallization in THF / CH 2 Cl 2 / pentane) phenyl (541) (31 mg, 24%) as a strong yellow solid, m.p. 264-267 ° C. 1 H NMR [(CD 3) 2 SO] d 11.82 (br s, 1 H), 10.95 (br s, 1 H), 9.41 (br s, H), 8.47 (d, J = 2.6 Hz, 1 H), 7.56 (s, 1 H), 7.54 (d, J = 8.9 Hz, 1 H), 7.25 (dd, J = 7.4, 1.6 Hz, 1 H), 7.23 (td, J = 7.9, 1.7 Hz, 1 H), 7.22 (dd, J = 8.7, 2.6 Hz, 1 H), 6.91 (day, J = 7.5 Hz, 1 H), 6.87 (td, J = 7.4, 0.9 Hz, 1 H), 3.89 (s, 3H). Found: C, 70.40; H, 4.06; N, 7.95. C2iH14N204 requires C, 70.39; H, 3.94; N, 7.82.

EXAMPLE 133 The preparation of 9-hydroxy-4- (2-hydroxyphenyl) pyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (542) (VI, R10 = H-Ar = 2-hydroxyphenyl) The methyl ether (541) prepared as described in Example 132 was demethylated with BBr3 using the procedure described in Example 80, with the exception that the reaction time was 4 h, to give (after crystallization in MeOH / THF / CH2Cl2 / hexane) phenyl (542) (73%) as a yellow-orange solid, mp 291-296 ° C. H NMR [(CD3) 2 SO] d 1 1.67 (br s, 1 H), 10.88 (br s, 1 H), 9.37 (br, 1 H), 9.22 (br, 1 H), 8.31 (d, J = 2.4 Hz , 1 H), 7.51 (s, 1 H), 7.42 (d, J = 8.7 Hz, 1 H), 7.24 (dd, J = 7.5, 1.5 Hz, 1 H), 7.22 (td, J = 7.7, 1.8 Hz, 1 H), 7.05 (dd, J = 8.7, 2.5 Hz, 1 H), 6.91 (day, J = 8.0 Hz, 1 H), 6.86 (td, J = 7.4, 0.9 Hz, 1 H). Found: C, 66.61; H, 3.67; N, 7.70. C2oH12N204. H20 requires C, 66.30; H, 3.89; N, 7.73.

EXAMPLE 134 The preparation of 4- (2-iodophenyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H-6H) -dione (543) (V. R 10 = H-Ar = 2-iodophenyl) A solution of the amine (539) (46 mg, 0.129 mmol) prepared as dibed in Example 130 in 90% H2SO4 (2.5 mL) was cooled to -5 ° C, diluted with ice-cold water (2.5 ml) and then allowed to warm to 7 ° C. The resulting suspension was treated dropwise with a solution of NaN02 (13.6 mg, 0.197 mmol) in cold water (2 x 0.5 ml) and stirred at 70 ° C for 8 min. A solution of.urea ^ S-mg, 0: 083 mmoles) was added in cold water - (2 x 0.4 ml) and the mixture was stirred at 7 ° C for 4 min. Finally, a solution of Kl (140 mg, 0.843 mmol) and Cul (140 mg, 0.735 mmol) in cold water (2 x 1 mL) was added, then the cooling bath was removed and the mixture was stirred for 10 min and then at 60-65 ° C for 2 h. An aqueous solution of sodium metabisulfite (100 ml of 0.5%) was added and then the mixture was extracted with 20% THF / EtOAc (5 x 100 mL). The extracts were washed with water (200 ml), the water was extracted with EtOAc and the combined organic extracts were concentrated to dryness. The residue was adsorbed on silica gel and chromatographed. Elution with 0-0.5% MeOH / CH2Cl2 followed by 0.5% MeOH / CH2Cl2 gave the crude product (22 mg). This was purified by chromatography on silica gel (eluting with 1% EtOH / CHCl3) to yield the crude main iodide (543) (18 mg, 30%) which was combined with similar reaction material, rechromatographed (eluting with EtOAc petroleum ether) and crystallized from MeOH / THF / CH2Cl2 / hexane in the form of yellow-orange crystals, mp 311-315 ° C. 1 H NMR [(CD 3) 2 SO] d 1 1.95 (br s, 1 H), 11.07 (br s, 1 H), 8.46 (d, J = 2.6 Hz, 1 H), 7.97 (dd, J = 7.7, 0.9 Hz, 1 H), 7.58 (d, J = 8.8 ??,??), 7.50 (td, J = 7.6, 0.9 Hz, 1 H), 7.48 (s, 1 H), 7.44 (dd, J = 7.6, 1.8 Hz, 1 H), 7.25 (dd, J = 8.9, 2.7 Hz, 1 H), 7.19 (td, J = 7.6, 1.8 Hz, 1 H), 3.89 (s, 3H). Found: C, 53.87; H, 2.76; N, 5.98. C2iH13IN203 requires C, 53.87; H, 2.80; N, 5.98. FABMS found [M + H] +: 469.0046. C21 H14I N2O3 requires 469.0049. · · · · - | "- · ·" '·: "' ~ EXEMPLQ.135 The preparation of 9-hydroxy-4- (2-iodophenyl) pyrrolo [3,4-c] carbazole-1.3 (2H.6H) - diona (545) (VI.R10) = H. Ar = 2-iodophenyl) The methyl ether (543) prepared as dibed in Example 134 was demethylated with BBr3 using the procedure dibed in Example 80, to give (after crystallization in MeOH / CH2CI2 / hexane) phenyl (545) (88% ) in the form of a yellow-orange solid, mp 217-223 ° C. 1 H NMR [(CD 3) 2 SO] d 1 1.82 (br s, 1 H), 11.01 (br s, 1 H), 9.28 (br s, 1 H), 8.32 (d, J = 2.4 Hz, 1 H), 7.96 (da , J = 7.8 Hz, 1 H), 7.49 (ta, J = 7.7 Hz, 1 H), 7.46 (d, J = 8.9 Hz, 1 H), 7.42 (s, 1 H), 7.42 (dd, J = 7.4, 1.7 Hz, 1 H), 7.19 (td, J = 7.6, 1.7 Hz, 1 H), 7.08 (dd, J = 8.7, 2.5 Hz, 1 H). Found: C, 52.93; H, 2.55; N, 6.07. C20HHIN2O3 requires C, 52. 89; H, 2.44; N, 6.17. FABMS found [+ H] +: 454.9889. C20H12IN2O3 requires 454.9893.

EXAMPLE 136 The preparation of (2-cyanobenzyl) (triphenyl) phosphonium bromide Bromination of o-tolunitrile with NBS / AIBN, followed by reaction of the crude bromide with triphenylphosphine (1.2 equiv.), Using the procedure dibed in Example 102, with the exception that the reaction time for bromination was 2 hr.dio ~ salt. Phosphonium: (547) (70%) in- "" form of a light brown powder, mp. (CH ^ C ^ / benzene) 237-241 ° C. 1 H NMR (CDCl 3) 7.90 (dd, J = 7.8, 2.3 Hz, 1 H), 7.85-7.63 (m, 15H), 7.52 (ta, J = 7.7 Hz, 1 H), 7.44 (da, J = 7.5 Hz , 1 H), 7.38 (tdd, J = 7.6, 2.1, 1.0 Hz, 1 H), 5.86 (d, J = 14.7 Hz, 2H). Found: C, 67.88; H, 4.42; N, 3.09. C26H2iBrNP requires C, 68. 13; H. 4.62; N, 3.06.

EXAMPLE 137 The preparation of 2 - [(E) -2- (5-Methoxy-1 H -indol-2-yl) ethenyl] benzonitrile (548) (II: Ar 2-cyanophenyl) The compound 5-methoxy-1 H -indole-2-carbaldehyde (1) was reacted with (2-cyanobenzyl) (triphenyl) phosphonium bromide (547) prepared as dibed in Example 136 using the procedure dibed in Example 37, with the exception that the LDA and the aldehyde were added (sequentially) at 0 ° C, the ratio of LDA: aldehyde was 1.55: 1 and the reaction time was 5 h, to give (after crystallization in CH2Cl2 hexane) the diene (548) in the form of a yellow solid (the pure E-isomer) (60%), mp 192-196 ° C. 1 H NMR (CDCl 3) d 8.40 (br s, 1 H), 7.79 (d, J = 8.1 Hz, 1 H), 7.66 (dd, J = 8.1, 0.9 Hz, 1 H), 7.58 (td, J = 7.9, 1.3 Hz, 1 H), 7.32 (td, J = 8.0, 0.9 Hz, 1 H), 7.29 (d, J 8.5 Hz, .1 H), 7.28 (d, J = 16.9 Hz, 1 H), 7.18- (d, J = 16.4 ??, 1 H), ~ -7.04 (d, J = 2.4 Hz, 1 H), 6.91 (dd, J = 8.9, 2.4 Hz, 1 H), 6.64 (d, J = 1.8) Hz, 1 H), 3.86 (s, 3H). Found: C, 79.05; H, 5.16; N, 10.31. C18H1 N20 requires C, 78.81; H, 5.14; N, 10.21.

EXAMPLE 138 The preparation of 2- (9-methoxy-1,3-dioxo-1, 2.3.6-tetrahydropyrrolo [3,4-c1carbazol-4-yl] benzonitrile (549) (V. R10 = N. Ar = 2-cyanophenyl) The diene E (548) prepared as described in example 137 was subjected to successive reactions with maleimide and then with DDQ according to the above representative procedure described in example 123, with the exception that most of the final product Slightly soluble was obtained by filtration of the diluted product solution and then washing thoroughly with an aqueous solution of NaHCC > 3, 15% MeOH / CH2Cl2 and water, the remainder being obtained by extraction of the water phase with ethyl acetate. The organic layer was dried, the drying agent was removed and the solution was concentrated to dryness. Crystallization from THF / Ch C / hexane gave the product (549) (96%) as a yellow solid, m.p. 348-350 ° C. H NMR [(CD3) 2 SO] d 12.06 (s a, -1 H), 1 1 .19 (s a, 1 H), 8.48 (d; - - - " J = 2.6 Hz, 1 H), 7.96 (dd, J = 7 ~ .7, 1.0 Hz, 1 H), 7.82 (td, J = 7.7, 1 .4 Hz, 1 H), 7.71 (day, J = 7.4 Hz, 1 H), 7.71 (s, 1 H), 7.66 (td, J = 7.6, 1.1 Hz, 1 H), 7.60 (d, J = 8.9 Hz, 1 H), 7.27 (dd, J = 8.8, 2.6 Hz, 1 H), 3.90 (s, 3H): EIMS found M +: 367.0956. C22H13N3O3 requires 367.0957.

EXAMPLE 139 The preparation of 2- (9-hydroxy-1,3-dioxo-1.2.3.6-tetrahydropyrrolo [3,4-clcarbazol-4-yl] benzonitrile (550) (VI, R1Q = H. Ar = 2-cyanofertil) The methyl ether (549) prepared as described in Example 138 was demethylated with BBr3 using the procedure described in Example 80, with the exception that the reaction time was 5 h with 5 equiv. of BBr3 and then it was 4 h more with 5 equiv. more than BBr3, to give (after crystallization in THF / CH2CI2 / hexane) phenyl (550) (83%) as a yellow solid, m.p.199-204 ° C (dec). 1H RN [(CD3) 2SO] 611.93 (sa, 1H), 11.13 (sa, 1H), 9.31 (sa, 1H), 8.34 (d, J = 2.4 Hz, 1H), 7.96 (dd, J = 7.6, 0.9 Hz, 1H), 7.82 (td, J = 7.7, 1.4 Hz, 1H), 7.70 (day, J = 7.5 Hz, 1H), 7.65 (s, 1H), 7.65 (td, J = 7.7, 1.0 Hz, 1H ), 7.48 (d, J = 8.7 Hz, 1H), 7.10 (dd, J = 8.7, 2.5 Hz, 1H). Found: C, 70.17; H, 3.46; N, 11.49. C21HHN3O3. 1 / 4H20 requires Cr70.49; H, 3.24; N; 11:74. '' - - - EXAMPLE 140 The preparation of 5-methoxy-2 - [(E) -2- (3-nitrophenyl) ethenyl] -1H-indole (551) (II. Ar = 3-nitrophenyl) The compound 5-methoxy-1 H -indole-2-carbaldehyde (1) was reacted with (3-nitrobenzyl) (triphenyl) phosphonium bromide using the procedure described in Example 37, with the exception that the LDA and the Aldehyde were added sequentially at 0 ° C, the ratio of LDA: aldehyde was 1.51 and the reaction time was 5 h, to give (after crystallization in MeOH / CH2Cl2 / hexane) the diene (551) in of an orange-red solid (the pure E-isomer) (51%), mp 178-182 ° C. 1 H NMR [(CD 3) 2 SO] d 1 1.27 (br s, 1 H), 8.34 (t, J = 1.9 Hz, 1 H), 8.09 (dd, J = 8.1, 1.8 Hz, 1 H), 7.99 (d, J = 7.9 Hz, 1 H), 7.67 (t, J = 8.0 Hz, 1 H), 7.47 (d, J = 16.5 Hz, 1 H), 7.26 (d, J = 8.6 Hz, 1 H), 7.25 ( d, J = 16.6 Hz, 1 H), 7.03 (d, J = 2.4 Hz, 1 H), 6.77 (dd, J = 8.8, 2.5 Hz, 1 H), 6.61 (d, J = 1.6 Hz, 1 H), 3.76 (s, 3H). Found: C, 69.36; H, 4.77; N, 9.78. C17H14N2O3 requires C, 69.38; H, 4.79; N, 9.52. 1. 3 (2H.6H¾-dione (552) (V.R10 = H. Ar = 3-nitrophenyl.

The pure Diene E (551) prepared as described in Example 140 was subjected to successive reactions with maleimide and then with DDQ according to the above representative procedure described in Example 123, with the exception that the poorly soluble end product it was obtained by filtration of the solution of the diluted product and then washing thoroughly with an aqueous solution of NaHCO 3, 15% MeOH / CH 2 Cl 2 and water, followed by crystallization in eOH / THF, to give the product (552) (81%) in form of a brown solid, mp > 340 ° C. 1 H NMR [(CD3) 2 SO] d 11.99 (br s, 1H), 11.18 (br s, 1H), 8.50 (d, J = 2.5 Hz, 1H), 8.48 (t, J = 1.9 Hz, 1H), 8.31 (dd , J = 8.1, 1.7 Hz, 1H), 8.11 (day, 5 J = 7.8 Hz, 1 H), 7.78 (t, J = 8.0 Hz, 1 H), 7.75 (s, 1 H), 7.58 (d, J = 8.8 Hz, 1 H), 7.25 (dd, J = 8.8, 2.6 Hz, 1H), 3.90 (s, 3H). Found: C, 62.17; H, 3.52; N, 10.33. C21H13N3O5. H20 requires C, 62.22; H, 3.73; N, 10.37. 0 EXAMPLE 1414 Preparation of 9-hydroxy-4- (3-nitrophenol) pyrrolo [3,4-c] carbazole-11.3 (2H.6m-dione (553) (VI, R10 = H. Ar = 3-nitrophenyl) _ .. _ E [methyl ether (552). prepared as described in Example: 142 was demethylated with pyridinium hydrochloride using the procedure described in Example 81, to give (after crystallization in THF / hexane) phenyl (553) (74%) in the form of an orange-brown solid, mp 300-310 ° C (dec). 1 H NMR [(CD 3) 2 SO] d 11.86 (br s, 1 H), 11.11 (br s, 1 H), 9.29 (br s, 0 1 H), 8.46 (t, J = 1.9 Hz, 1 H), 8.35 (d, J = 2.4 Hz, 1H), 8.30 (ddd, J = 8.2, 2.5, 0.8 Hz, 1H), 8.10 (dt, J = 7.8, 1.2 Hz, 1H), 7.77 (t, J = 8.0 Hz, 1H), 7.70 (s) , 1H), 7.47 (d, J = 8.7 Hz, 1H), 7.09 (dd, J = 8.7, 2.5 Hz, 1H).

FABMS found M +: 373.0692. 02 ??? -.? 305 requires 373. 0699 EXAMPLE 143 The preparation of (2-chloro-3-nitrobenzyl) (triphenyl) phosphonium bromide (554) Bromination of 2-chloro-3-nitrotoluene with NBS / AIBN, followed by reaction of the crude bromide with triphenylphosphine, using the procedure described in Example 102, with the exception that the reaction time for bromination was 2 h the displacement reaction was carried out at 70 ° C for 1 d, gave the phosphonium salt (554) (44%) as a light brown solid, mp (CH2Cl2 / hexane) 224-228 ° C. ______ 1H NMR_ (CDCI3) d 8.09 (d a, J = 8.3 Hz, 1 H), 7.86-7.63 (m, 16H) 7. 34 (t, J = 8.1 ??,??). 5.95 (d, J = 14.6 Hz, 2H). Found: C, 58.68; H, 4.12; N, 2.79. C25H2oBrCIN02P requires C, 58.56; H, 3.93; N, 2.73.

EXAMPLE 144 The preparation of 2 - [(E) -2- (2-chloro-3-nitrophenyl) ethenyl] -5-methoxy-1 H-indole (555) (II. Ar = 2-chloro-3-nitrophenyl) The compound 5-methoxy-1-indole-2-carbaldehyde (1) was reacted with (2-chloro-3-nitrobenzyl) (triphenyl) phosphonium bromide (554) prepared as described in example 143 using the procedure described in Example 37, with the exception that the LDA and the aldehyde were added (sequentially) at 0 ° C, the ratio of LDA: aldehyde was 1.5: 1 and the reaction time was 5 h, to give (after of the crystallization in Ch C / pentane) the diene (555) in the form of an orange crystalline solid (the pure E-isomer) (50%), mp 131 -133 ° C. 1H RN (CDCl3) d 8.24 (sa, 1 H), 7.86 (dd, J = 8.0, 1.4 Hz, 1 H), 7.63 (dd, J = 7.9, 1 .4 Hz, _J H), 7.40 Jt , J = 8.0_Hz, JH), 7.28 (d, J = 8.5 Hz, 1 H),, · - 7.25 (d, J = 15.8 Hz, 1 H), 7.15 (d, J = 16.4 Hz, 1 H) , 7.05 (d, J = 2.4 ??, 1 H), 6.91 (dd, J = 8.9, 2.4 Hz, 1 H), 5.65 (d, J = 1 .7 Hz, 1 H), 3.86 (s, 3H ). Found: C, 61.97; H, 3.92; N, 8.50. C17Hi3CIN203 requires C, 62.11; H, 3.99; N, 8.52.

EXAMPLE 145 The preparation of 4- (2-chloro-3-nitrophenih-9-methoxypyrrolo [3,4-c] carbazole-1.3 (2H-6H) -dione (556) (V. R10 = H. Ar = 2- chloro-3-nitrophenyl) The pure Diene E (555) prepared as described in Example 144 was subjected to successive reactions with maleimide and then with DDQ according to the procedure described in Example 123, to give (after crystallization in THF / pentane) the product (556) (93%) as a yellow-brown solid, mp 315-320 ° C (dec). 1 H NMR [(CD 3) 2 SO] d 12.07 (s a, 1 H), 1 1 .16 (s a, 1 H), 8.46 (d, J = 2.6 Hz, 1 H), 8. 1 (dd, J = 8.1, 1.5 Hz, 1 H), 7.82 (dd, J = 7.7, 1.6 Hz, 1 H), 7.69 (t, J = 7.9 Hz, 1 H), 7.69 (s, H), 7.59 (d, J = 8.9 Hz, 1 H), 7.26 (dd, J = 8.8, 2.6 Hz, 1 H), 3.90 (s, 3H). _, "Found: C, 60.47; H, 3.17; . N, 9.78, C 1Hi2CIN305. 1 / 4THF-. , requires C, 60.08; H, 3.21; N, 9.55.

EXAMPLE 146 The preparation of 4- (2-chloro-3-nitrophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (5571 (VI.R10 = H. Ar = 2- chloro-3-nitrophenyl) The methyl ether (556) prepared as described in Example 145 was demethylated with BBr3 using the procedure described in Example 80, with the exception that the reaction time was 5 min with 10 equiv. of BBr3, to give (after crystallization in THF / CH2Cl2 / pentane) phenyl (557) (84%) as a yellow solid, m.p. 304-308 ° C. 1 H NMR [(CD 3) 2 SO] d 1 1.92 (br s, 1 H), 1 1.1 1 (br s, 1 H), 9.30 (s, 1 H), 8.31 (d, J = 2.4 Hz, 1 H), 8.1 1 (dd, J = 8.2, 1.5 Hz, 1 H), 7.81 (dd, J = 7.6, 1.5 Hz, 1 H), 7.68 (t, J = 7.9 Hz, 1 H), 7.63 (s, 1 H) , 7.47 (d, J = 8.7 Hz, 1 H), 7.10 (dd, J = 8.7, 2.5 Hz, 1 H). Found: C, 58.70; H, 2.72; N, 10.10. C2oH10CIN305 requires C, 58.91; H, 2.47; N, 10.30.

EXAMPLE 147 The preparation of 4- (3-amino-2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (558) (VI, R 0 = H. Ar = 3- amino-2-chlorophenyl) '"A mixture of the derivative" of nitro (557) (66 mg, 0.162 mmol) prepared as described in example 146 and recently prepared (wet) nickel boride (202 mg) in MeOH (4.8 ml) and HCl 1 M (1.2 ml) was stirred at reflux temperature for 100 min. Aqueous concentrated ammonia and aqueous NaHCO3 (100 mL) were added and the mixture was extracted with EtOAc (8 x 100 mL). The extracts were concentrated, adsorbed on silica gel and chromatographed. Elution with 0-1% MeOH / CH 2 Cl 2 and then with 1.5% MeOH / CH 2 Cl 2 and THF gave (after crystallization in THF / CH 2 Cl 2 / pentane) the amine (558) (83%) as a yellow solid -angel, pf 348-352 ° C. 1 H NMR [(CD 3) 2 SO] d 1 1 .76 (br s, 1 H), 10.96 (br s, 1 H), 9.25 (br s, 1 H), 8.31 (d, J = 2.4 Hz, 1 H), 7.45 (s, 1 H), 7.44 (d, J = 8.7 Hz, 1 H), 7.08 (t, J = 7.8 Hz, 1 H), 7.07 (dd, J = 8.7, 2.5 Hz, 1 H), 6.86 ( dd, J = 8.11, 1.5 Hz, 1 H), 6.60 (dd, J = 7.4, 1 .3 Hz, 1 H), 5.39 (s, 2H). Found: C, 63.79; H, 3.47; N, 10.37. C20H12CIN3O3. 1 / 2THF requires C, 63.85; H, 3.90; N, 10.15.

EXAMPLE 148 The preparation of (2-chloro-4-nitrobenzyl) (triphenyl) phosphonium bromide (559) The bromination of 2-chloro: 4-nitrotqluenp; with NBS / AIBN, followed by the reaction of the crude bromide with triphenylphosphine, using the procedure described in Example 102, with the exception that the reaction time for the bromination was 24 h and the displacement reaction was carried out at 20 ° C for 7 d, gave the crude phosphonium salt (559) (34%) as a light brown solid, mp (benzene) 70-75 ° C (dec). 1 H NMR [(CD 3) 2 SO] d 8.21 (d, J = 2.5 Hz, 1 H), 8.13 (dd, J = 8.7, 2.5 Hz, 1 H), 7.94 (td, J = 7.5, 1.6 Hz, 3H) , 7.80-7.66 (m, 12H), 7.43 (dd, J = 8.5, 2.6 Hz, 1 H), 5.33 (d, J = 15.7 Hz, 2H).

FABMS found M + = 432.0916, 434.0904. C25H20CINO2P requires 432.0921, 434.0891.

EXAMPLE 149 The preparation of 2 - [(E) -2- (2-chloro-4-nitrophenyl) etenin-5-methoxy-1 H-indole (560) (II. Ar-2-chloro-4-nitrophenyl) The compound 5-methoxy-1H-indole-2-carbaldehyde (1) was reacted with (2-chloro-4-nitrobenzyl) (triphenyl) phosphonium bromide (559) prepared as described in the example 148 using the procedure described in Example 37, with the exception that the LDA and the aldehyde were added (sequentially) at 0 ° C, the ratio of LDA: aldehyde was 1.51 and the reaction time was 5 h, to give (after crystallization from CH2Cl2 / hexane) the diene (560) as a red-dark-brown solid (the pure E-isomer) (46%); p.f. 239-241 ° C. 1 H NMR [(CD 3) 2 SO] d 11 .57 (br s, 1 H), 8.32 (d, J = 2.0 Hz, 1 H), 8.18 (dd, J = 8.8, 2.1 Hz, 1 H), 8.15 (d , J = 8.9 Hz, 1 H), 7.59 (d, J = 16.3 Hz, 1 H), 7.47 (d, J = 16.3 Hz, 1 H), 7.29 (d, J = 8.9 Hz, 1 H), 7.05 (d, J = 2.4 Hz, 1 H), 6.82 (dd, J = 8.7, 2.5 Hz, 1 H), 6.70 (s, 1 H), 3.76 (s, 3H). Found: C, 62.14; H, 3.91; N, 8.52. Ci7H13CIN203 requires C, 62.1 1; H, 3.99; N, 8.52.

EXAMPLE 150 The preparation of 4- (2-chloro-4-nitrophenyl) -9-methoxypyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (561) (V. R10 = H. Ar = 2-chloro -4-nitrophenyl) The pure Diene E (560) prepared as described in Example 149 was subjected to successive reactions with maleimide and then with DDQ according to the procedure described in Example 123, to give (after crystallization in THF / hexane) the product (561) (98%) in the form of an orange solid, mp 279-282 ° C. 1 H NMR [(CD 3) 2 SO] d 12.06 (br s, 1 H), 1 1.20 (br s, 1 H), 8.46 (d, J = 2.6 Hz, 1 H), 8.43 (d, J = 2.2 Hz, 1 H ), 8.29 (dd, J = 8.4, 2.4 Hz, 1 H), 7.83 (d, J = 8.4 Hz, 1 H), 7.66 (s, 1 H), 7.59 (d, J = 8.9 Hz, 1 H) , 7.27 (dd, J = 8.8, 2.6 Hz, 1 H), 3.90 (s, 3H). Found: C, 59.83; H, 3.6.1; N, 9.57. C21H12CIN3O5. 1/4 THF ~ requires C, 60.08; H, 3.21; N, 9.55 EXAMPLE 151 The preparation of 4- (2-chloro-4-nitrophenyl) -9-hydroxypyrrolo [3,4-clcarbazole-1.3 (2H-6H) -dione (562) (VI.R10 = H. Ar = 2-chloro-4 -nitrophenyl The methyl ether (561) prepared as described in Example 150 was demethylated with BBr3 using the procedure described in Example 80, with the exception that the reaction time was 5 h with 5 equiv. of BBr3 and then it was 5 h more with 5 equiv. more than BBr3 > to give (after crystallization in THF / CH2Cl2 / pentane) phenyl (562) (85%) as a red-orange solid, m.p. 301 -305 ° C. H NMR [(CD3) 2 SO] d 11.94 (br s, 1 H), 11.13 (br s, 1 H), 9.32 (br s, 1 H), 8.43 (d, J = 2.3 Hz, 1 H), 8.32 (d. J = 2.4 Hz, 1 H), 8.29 (dd, J = 8.5, 2.3 Hz, 1 H), 7.82 (d, J = 8.4 Hz, 1 H), 7.61 (s, 1 H), 7.48 (d, J) = 8.7 Hz, 1 H), 7.10 (dd, J = 8.7, 2.5 Hz, 1 H). Found: C, 58.81; H, 2.35; N, 10.05. C2oH10CIN305 requires C, 58.91; H, 2.47; N, 10.30.

EXAMPLE 152 The preparation of 4- (4-amino-2-chlorophenyl) -9-hydroxypyrrolo [3.4-c] carbazole-1.3 (2H.6H) -dione (563) (VI.R10 = H. Ar = 4-amino -2-chlorophenyl) A mixture of the nitro derivative (562) (90 mg, 0.221 mmol) prepared as described in example 151 and recently prepared (wet) nickel boride (277 mg) in MeOH (7.2 ml) and 1M HCl (1.8 ml) ) was stirred at reflux temperature for 1 h. Ammonia conc. aqueous and NaHCO3 (1220 mL) and the mixture was extracted with EtOAc (6 x 80 mL). The extracts were concentrated, adsorbed on silica gel and chromatographed. Elution with 0-2% MeOH / CH2Cl2 and then elution with THF gave (after crystallization in THF / CH2Cl2 / pentane) the amine (563) (100%) as an orange solid, m.p. 293-303 ° C (dec). 1H RN [(CD3) 2SO] d 1 1.70 (sa, 1 H), 10.92 (sa, 1 H), 9.23 (sa, 1 H), 8.30 (d, J = 2.4 Hz, 1 H), 7.44 (s) , 1 H), 7.43 (d, J = 87 Hz, 1 H), 7.09 (d, J = 8.2 Hz, 1 H), 7.05 (dd, J = 8.7, 2.5 Hz, 1 H), 6.71 (d, J = 2.2 Hz, 1 H), 6.58 (dd, J = 8.1, 2.2?, 1 H), 5.51 (s, 2H). Found: C, 60.42; H, 3.64; N, 10.05. C20H12CIN3O3. 5 / 4H20 requires C, 60.01; H, 3.65; N, 10.50.

EXAMPLE 153 The preparation of (2-chloro-5-nitrobenzyl) (triphenyl) phosphonium bromide (564) The bromination of 2- (chloro-5-nitrophenyl) methanol with 30% HBr in acetic acid, followed by the reaction of the crude bromide with triphenylphosphine, using the de-tone method. Example 12 gave the phosphonium salt (564). (63%) in the form of a blaheo solid, m.p. (CH2Cl2 / benzene) 239-243 ° C "~ 1 H NMR (CDCl 3) d 8.22 (sa, 1 H), 8.07 (da, J = 8.7 Hz, 1 H), 7.87-7.65 (m, 15H), 7.41 (d, J = 8.9 Hz, 1 H), 5.80 (d, J = 14.8 Hz, 2H) Found: C, 58.56, H, 3.93, N, 2.73, C25H2oBrCIN02P requires C, 58.47, H, 3.98, N, 2.66.

EXAMPLE 154 The preparation of 2 - [(E) -2- (2-chloro-5-nitrophenyl) ethenyl] -5-methoxy-1H-indole (565) (II. Ar-2-chloro-5-nitrophenyl) The compound 5-methoxy-1 H-indole-2-carbaldehyde (1) was reacted with (2-chloro-5-nitrobenzyl) (triphenyl) phosphonium bromide (564) prepared as described in example 153 using The procedure described in Example 37, with the exception that the LDA and the aldehyde were added sequentially at 0 ° C, the ratio of LDA: aldehyde was 1.51 and the reaction time was 5 h, to give (after crystallization in CH2Cl2 / pentane) the diene (565) as an orange solid (the pure E-isomer) (57%), mp 191 -193 ° C. 1H RN (CDCI3) d 8.54 (d, J = 2.6 Hz, 1 H), 8.25 (sa, 1 H), 8.02 (dd, J = 8.8, 2.6 Hz, 1 H), 7.56 (dd, J = 8.9 Hz , 1 H), 7.28 (d, J = 8.7 Hz, _1 H), 7.26 - - -15 (d, J = 16.4 Hz, 1 H), 7.20 (d, J = 16.5 Hz, 1 H), 7.06 (d, J = 2.4 Hz, 1 H), 6.91"(dd, 'J = 8.8, 2.5 Hz, 1 H), 6.70 (sa, 1 H), 3.86 (s, 3H) Found: C, 61.44; H, 3.92; N, 8.55, C17H13CIN2O3, 1 / 4H20 requires C, 61.27, H, 4.08, N, 8.4.

EXAMPLE 155 The preparation of 4- (2-chloro-5-nitrophenyl) -9-methoxypyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (566) (V. R10 = H. Ar = 2-chloro -5-nitrophenyl) The pure Diene E (565) prepared as described in Example 154 was subjected to successive reactions with maleimide and then with DDQ according to the above representative procedure described in Example 123, to give (after crystallization in THF / CH2Cl2 / pentane) the product (566) (95%) as a yellow-orange solid, mp 285-287 ° C. H NMR [(CD3) 2 SO] d 12.06 (s a, 1 H), 1.1.1 (s a, 1 H), 8.46 (d, J = 2.6 Hz, 1 H), 8.36 (d, J = 2.8 Hz, 1 H), 8.33 (d, J = 8.7, 2.7 Hz, 1 H), 7.91 (d, J = 8.7 Hz, 1 H), 7.71 (s, 1 H), 7.60 (d, J = 8.9 Hz, 1 H), 7.27 (dd, J = 8.9, 2.6 Hz, 1 H), 3.90 (s, 3H). Found; C, 57.3¿; .H, 2.68; N, 9.38. C2iH12CIN305. 1 / 4CH2Cl2 requires C, 57.61; H, '2 84; N 9.48.

EXAMPLE 156 The preparation of 4- (2-chloro-6-nitrophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (567) (VI.R10 = H. Ar = 2-chloro -5-nitrophenyl) The methyl ether (566) prepared as described in Example 155 was demethylated with BBr3 using the procedure described in Example 80, with the exception that the reaction time was 6 h with 10 equiv. of BBr3 and then was 4 h more with 10 equiv. more than ?? G3, to give (after crystallization in THF / CH2Cl2 / pentane) phenyl (567) (88%) as an orange yellow solid, m.p. 268 ° C (dec). 1 H NMR [(CD 3) 2 SO] d 1 1.94 (br s, 1 H), 11 .1 1 (br s, 1 H), 9.31 (br s, 1 H), 8.35 (d, J = 2.6 Hz, 1 H), 8.32 (dd, J = 8.6, 2.9 Hz, 1 H), 8.32 (d, J = 2.4 Hz, 1 H), 7.91 (d, J = 8.7 Hz, 1 H), 7.66 (s, 1 H), 7.48 (d, J = 8.7 Hz, 1 H), 7.10 (dd, J = 8.7, 2.5 Hz, 1 H). Found: C, 58.31; H, 2.45; N, 9.98. C20H10CIN3O5. 1 / 4H20 requires C, 58.27; H, 2.57; N, 10.19.

EXAMPLE 157 The preparation of 4- (5-amino-2-chlorophenyl) -9-hydroxypyrrolo [3,4-clcarbazole-1.3 (2H.6H) -dione (568) (VI.R10 = H. Ar = 5-amino-2 -chlorophenilol A mixture of the nitro derivative (567) (70 g, 0.172 mmol) prepared as described in example 156 and freshly prepared (wet) nickel boride (266 mg) in MeOH (5.6 ml) and HCl 1 (1.4 ml) ) was stirred at reflux temperature for 3 h. Ammonia conc. aqueous and NaHCO3 (100 mL) and the mixture was extracted with EtOAc (5 x 70 mL). The extracts were washed with water, concentrated, adsorbed on silica gel and chromatographed. Elution with 0-2% MeOH / CH 2 Cl 2 and then with 3% MeOH / CH 2 Cl 2 gave (after crystallization in THF / CH 2 Cl 2 / pentane) the amine (568) (97%) as an orange solid, m.p. 301-306 ° C (dec). 1 H NMR [(CD 3) 2 SO] d 11.78 (br s, 1 H), 10.97 (br s, 1 H), 9.26 (br s, 1 H), 8.31 (d, J = 2.4 Hz, 1 H), 7.45 (s, 1 H), 7.45 (d, J = 8.7 Hz, 1 H), 7.13 (d, J = 8.3 Hz, 1 H), 7.07 (dd, J = 8.7, 2.5 Hz, 1 H), 6.62 (dd, J = 8.2, 2.8 Hz, 1 H), 6.60 (d, J = 2.3 Hz, 1 H), 5.29 (s, 2H). Found: C, 63.09; H, 3.17; N, 10.91. C20H12CIN3O3. 1 / 4H20 requires C, 62.84; H, 3.30; N, 10.99.

EXAMPLE 158 The preparation of (2-chloro-3-methoxybenzyl) (triphenyl) phosphonium bromide (569) La_ ^ .bromation. of 2-chloro-1-methoxy-3-methylbenzene - with NBS / AIBN, followed by reaction of the crude bromide with triphenylphosphine, using the procedure described in Example 102, with the exception that the reaction time for the bromination was 5 h, gave a mixture of phosphonium salts containing (569) (20%) as a light brown solid which was used without further purification. A small amount of the pure salt (569) was obtained by crystallization of the mother liquor in the form of white needles, m.p. (CH2Cl2 / benzene) 228-231 ° C. 1 H NMR (CDCl 3) d 7.81-7.60 (m, 15H), 7.17 (dt, J = 7.8, 2.0 Hz, 1 H), 7.1 1 (t, J = 8.0 Hz, 1 H), 6.87 (dt, J = 8.2, 1.8 Hz, 1 H), 5.65 (d, J = 14.4 Hz, 2H), 3.81 (s, 3H). Found: C, 62.88; H, 4.64. C26H23BrCIOP requires C, 62.73; H, 4.66.

EXAMPLE 159 The preparation of 2 - [(E) -2- (2-chloro-3-methoxyphenyl) ethenyl] -5-methoxy-1H-indole (570) (II. Ar = 2-chloro-3-methoxyphenyl) and 2-chloro-3 - [(E) -2- (5-methoxy-1 H -indole-2-ethethylphenol (571) (II. Ar = 2-chloro-3-hydroxyphenyl) The compound 5-methoxy-1 H-indole-2-carbaldehyde (1) was reacted with very crude (2-chloro-3-methoxybenzyl) (triphenyl) phosphonium bromide (569) prepared, as, has: described in -example "- 158 'using * the procedure described in Example 37, with the exception that the LDA and the aldehyde were added sequentially at 0 ° C, the ratio of LDA: aldehyde was 1 1 .51 and the time reaction time was 5 h, to give a crude mixture of dienes, which was chromatographed on silica gel Elution with 0-50% CH 2 Cl 2 / petroleum ether and then elution with 60% CH 2 Cl 2 / petroleum ether diene (after crystallization from CH2Cl2 / pentane) the main diene product (570) as a pale yellow solid (the pure E-isomer) (31%), mp 179-183 ° C. 1 H NMR (CDCl 3) d 8.22 (sa, 1H), 7.32 (d, J = 16.4 Hz, 1H), 7.31 (dd, J = 8.2, 1.4 Hz, 1H), 7.26 (d, J = 8.7 Hz, 1H) , 7.23 (t, J = 8.0 Hz, 1H), 7.09 (d, J = 16.5 Hz, 1H), 7.04 (d, J = 2.4 Hz, 1H), 6.87 (dd, J = 8.7, 2.5 Hz, 1H) , 6.85 (dd, J = 7.8, 1.3 Hz, 1H), 6.58 (d, J = 1.6 Hz, 1H), 3.93 (s, 3H), 3.85 (s, 3H). Found: C, 68.79; H, 5.22; N, 4.51. Ci8H 6CIN02 requires C, 68. 90; H, 5.14; N, 4.46. Another elution of the column with 60% CH 2 Cl 2 / petroleum ether and CH 2 Cl 2 gave (after crystallization in CH 2 Cl 2 / pentane) the diene minor product (571) as a pale yellow solid (the isomer, pure E) (25). %), mp172-175 ° C. 1 H NMR (CDCl 3) d 8.20 (br s, 1 H), 7.27 (m, 1 H), 7.26 (d, J = 8.7 Hz, 1H), 7.19 (t, J = 7.9 Hz, 1H), 7.18 (d, J = 16.4 Hz, 1H), 7.10 (d, J = 16.4 Hz, 1H), 7.04 (d, J = 2.4 Hz, 1H), 6.95 (dd, J = 8.1, 1.5 Hz, 1H), 6.88 (dd, J = 8.8, 2.5 Hz, 1H), 6.60 (d, J = 1.7 Hz, - H), 5.65 (s, 1H), 3.86 (s, 3H): ---- - - "r" ~ 1 Found: C , 67.23; H, 4.72; N, 4.72. C17H14CIN02. 1 / 4H2O requires C, 67.11; H, 4.80; N, 4.60.

EXAMPLE 160 The preparation of 4- (2-chloro-3-hydroxyphenyl) -9-methoxypyrrolo [3,4-c] carbazole-1.3 (2H.6H) -done (572) (V R10 = H- Ar = 2-chloro- 3- hydroxyphenyl) A mixture covered with aluminum foil of pure Diene E (571) (1 10 mg, 0.367 mmol) prepared as described in example 159 and maleimide (180 mg, 1.85 mmol) in dry toluene (2 ml) was stirred in a sealed vial at reflux temperature for 24 h (Method 4a). The resulting slurry was transferred to a flask using dioxane (5 ml) and then treated with manganese dioxide (738 mg, 8.49 mmol), stirring at reflux temperature under a N2 atmosphere for 22 h (as described in US Pat. the procedure of Example 79), after addition of water and extraction with distilled acetate. The organic phase was dried, the drying agent was removed and the solvent was concentrated to dryness. Chromatography and crystallization from THF / CH2Cl2 / pentane gave the product (572) (34%) as an orange-brown solid, m.p. 280-290 ° C (dec). 1 H NMR [(CD 3) 2 SO] d 11.92 (br s, 1 H), 11.04 (br s, 1 H), 10.23 (br s, 1 H), 8.46 (d, J = 2.6 Hz, 1 H), 7.57 (d, J = 8.8 Hz, 1 H), 7.52 (s, 1 H), 7.24 (dd, J = 8.9, 2.6 Hz, 1 H), 7.21 (t, J = 7.8 Hz, 1 H), 7.05 (dd, J = 8.2, 1.5 Hz, 1 H), 6.88 (dd, J = 7.5, 1 .4 Hz, 1 H), 3.89 (s, 3H). Found: C, 64.09; H, 3.48; N, 7.25. C2iH13CIN204 requires C, 64.21; H, 3.34; N, 7.13.

EXAMPLE 161 The preparation of 4- (2-chloro-3-hydroxyphenyl) -9-hydroxypyrrolof3.4 »c1carbazole-1.3 (2H-6H) -dione (573) (VI.R10 = H. Ar = 2-chloro-3 - hydroxyphenyl) The methyl ether (572) prepared as described in Example 160 was demethylated with BBr3 using the procedure described in Example 80, to give (after crystallization in THF / CH2Cl2 / pentane) phenyl (573) (91% ) in the form of a yellow-orange solid, mp 197-203 ° C (dec). 1 H NMR [(CD 3) 2 SO] d 1 1.78 (br s, 1 H), 10.98 (br s, 1 H), 10.17 (br s, 1 H), 9.26 (s, 1 H), 8.31 (d, J = 2.4 Hz , 1 H), 7.47 (s, 1 H), 7.45 (d, J = 8.7 Hz, 1 H), 7.20 (t, J = 7.8 Hz, 1 H), 7.07 (dd, J = 8.7, 2.5 Hz, 1 H), 7.04 (dd, J = 8.3, 1.5 Hz, 1_H), 6.87 (dd, J = 7.5, 1.4 Hz, 1 H). .. - ... - - - - '' Found: C, 62.06, H, 3.29, N, 7.36, C20H11CIN2O4, 1 / 2H20 requires C, 61.95, H, 3.12, N, 7.22.

EXAMPLE 162 The preparation of (2-chloro-4-methoxybenzyl) (tra-phenyl) phosphonium bromide (574) Bromination of (2-chloro-4-methoxyphenyl) methanol with 30% HBr in acetic acid, followed by reaction of the crude bromide with triphenylphosphine, using the procedure described in Example 12, with the exception that the reaction for the bromination was 4 h and the reaction time for the displacement was 28 h, gave the phosphonium salt (574) (100%) as a white solid, mp (CH2Cl2 / benzene) 223-226 ° C. 1 H NMR (CDCl 3) d 7.82-7.61 (m, 15 H), 7.53 (dd, J = 8.4, 2.7 Hz, 1 H), 6.72 (d, J = 2.8 Hz, 1 H), 6.70 (dd, J = 8.9 , 2.5 Hz, 1 H), 5.57 (d, J = 13.6 Hz, 2H), 3.74 (s, 3H). Found: C, 63.05; H, 4.74. C ^^ BrClOP requires C, 62.73; H, 4.66.

EXAMPLE 163 The preparation of 2 - [(E) -2- (2-chloro-4-methoxyphenyl) ethenyl] -5-methoxy-1 H-indole (575) (II. Ar = 2-chloro-4-methoxyphenyl) The compound 5-methoxy-1 H-indole-2-carbaldehyde (1) was reacted with (2-chloro-4-methoxybenzyl) (trifhenyl) phosphonium bromide (574) prepared as described in Example 162 using the procedure described in Example 37, with the exception that the LDA and the aldehyde were added sequentially at 0 ° C, the ratio of LDA: aldehyde was 1.51 and the reaction time was 5 h, to give (after crystallization from CH2Cl2 / pentane) diene, (575) as a pale yellow solid (pure E-isomer) (64%), mp 127-132 ° C. 1 H NMR (CDCb) d 8.17 (sa, 1 H), 7.60 (d, J = 8.8 Hz, 1 H), 7.25 (d, J = 8.3 Hz, 1 H), 7.19 (d, J = 16.5 Hz, 1 H), 7.03 (d, J = 2.4 Hz, 1 H), 6.96 (d, J = 17.3 Hz, 1 H), 6.94 (d, J = 2.4 Hz, 1 H), 6.86 (dd, J = 8.7, 2.6 Hz, 1 H), 6.85 (dd, J = 8.7, 2.8 Hz, 1 H), 6.54 (d, J = 1.7 Hz, H), 3.85 (s, 3H), 3.83 (s, 3H). Found: C, 69.05; H, 5.41; N, 4.68. C18H16CIN02 requires C, 68. 90; H, 5.14; N. 4.46.

EXAMPLE 164 The preparation of 4- (2-chloro-4-methoxyphenyl) -9-methoxypyrrolo [3,4-c1carbazole-1.3 (2H.6H) -dione (576) (V. R10 = H. Ar = 2-chloro-4 -methoxyphenyl) The pure Diene E (575) prepared as described in Example 163 was subjected to successive reactions with maleimide and then with DDQ according to the above representative procedure described "in Example 123, to give (after crystallization) in THF / pentane) the product (576) (86%) as a yellow-orange solid, mp 284-286 ° C. H NMR [(CD3) 2 SO] d 1.93 (sa, 1 H), 11.06 ( sa, 1 H) P, 8.46 (d, J = 2.6 Hz, 1 H), 7.56 (d, J = 8.9 Hz, 1 H), 7.54 (s, 1 H), 7.41 (d, J = 8.5 Hz, 1H), 7.24 (dd, J = 8.9, 2.6 Hz, 1 H), 7.15 (d, J = 2.6 Hz, H), 7.01 (dd, J = 8.5, 2.6 Hz, 1 H), 3.89 (s, 3H ), 3.86 (s, 3H) Found: C, 65.30, H, 4.79, N, 5.82, C22H15CIN204, THF requires C, 65.20, H, 4.84, N, 5.85.

EXAMPLE 165 The preparation of 4- (2-chloro-4-hedroxyphenyl) -9-hydroxypyrrolo [3,4-c1carbazole-1.3 (2H.6H) -dione (577) (VI.R10 = H- Ar = 2-chloro -4- hydroxyphenyl) The methyl ether (576) prepared as described in Example 164 was bis-demethylated with BBr3 using the procedure described in Example 80, with the exception that the reaction time was 5 h with 10 equiv. of BBr3, to give (after crystallization in THF / CH2Cl2 / pentane) phenyl (577) (90%) as a yellow-orange solid, m.p. 330-340 ° C (dec). 1 H NMR [(CD 3) 2 SO] d 11.75 (br s, 1 H), 10.97 (br s, 1 H), 10.00 (br s, 1 H), 9.25 (s, 1 H), 8.31 (d, J = 2.4 Hz, 1 H), 7.47 (s, 1 H), 7.44 (d, J = 8.7 Hz, 1 H), 7.27, (d,: J = 8.4 Hz, -1 H) --7: 06 (dd, J = 8.7, 2.5 Hz, 1 H) r6.93 (d ~ J = 2: 5 Hz, 1 H); "6.82 (dd, J = 8.3, 2.4 Hz, 1 H) Found: C, 62.63; H, 3.44 N, 7.10, C2oHnCIN204, 1 / 4H20 requires C, 62.68, H, 3.02, N, 7.31.

EXAMPLE 166 The preparation of (2-Chloro-5-methoxybenzyl) (triphenyl) phosphonium bromide (578) Bromination of 1-chloro-4-methoxy-2-methylbenzene with NBS / AIBN, followed by reaction of the crude bromide with triphenylphosphine, using the procedure described in Example 102, with the exception that the reaction time for bromination was 4 h, gave the phosphonium salt (578) (76%) as a light brown solid, mp (CH2Cl2 / benzene) 189-190.5 ° C. 1 H NMR (CDCl 3) d 7.82-7.61 (m, 15H), 7.21 (t, J = 2.8 Hz, 1 H), 7.04 (dd, J = 8.8, 0.8 Hz, 1 H), 6.76 (dt, J = 8.9 , 2.7 Hz, 1 H), 5.59 (d, J = 14.4 Hz, 2H), 3.58 (s, 3H). Found: C, 62.75; H, 4.70. C26H23BrCIOP requires C, 62.73; H. 4.66. - | | || || · · · · - · - · - - - - - EXAMPLE 167 The preparation of 2 - [(E) -2- (2-chloro-5-methoxyphenyl) ethenyl] -5-methoxy-1H-indole (579) (II. Ar-2-chloro-5-methoxyphenyl) The compound 5-methoxy-1H-indole-2-carbaldehyde (1) was reacted with (2-chloro-5-methoxybenzyl) (triphenyl) phosphonium bromide (578) prepared as described in example 166 using the procedure described in Example 37, with the exception that the LDA and the aldehyde were added sequentially at 0 ° C, the ratio of LDA: aldehyde was 1.51 and the reaction time was 5 h, to give (after crystallization in CHaC / exano) the diene (579) as a pale yellow solid (the pure E-isomer) ( 85%), pf 1 19-121 ° C. 1 H NMR (CDCl 3) d 8.22 (br s, 1 H), 7.29 (d, J = 8.9 Hz, 1 H), 7.26 (da, J = 8.7 Hz, 1 H), 7.22 (d, J = 16.5 Hz, 1 H), 7.18 (d, J = 3.0 Hz, 1 H), 7.06 (d, J = 16.7 Hz, 1 H), 7.04 (sa, 1 H), 6.88 (dd, J = 8.7, 2.5 Hz, 1 H ), 6.77 (dd, J = 8.8, 3.0 Hz, 1 H), 6.59 (d, J = 1.8 Hz, 1 H), 3.86 (s, 3H), 3.85 (s, 3H). Found: C, 68.70; H, 5.11; N, 4.37. C18Hi6CIN02 requires C, 68.90; H, 5.14; N, 4.46.

EXAMPLE 168 The preparation of 4- (2-chloro-5-methoxyphenyl) -9-methoxypyrrolo [3,4-clcarbazole-1.3 (2H.6H) -dione (580) (V. R10 = H. Ar-2) -chlorine-5-methoxypheniido) The pure Diene E (579) prepared as described in example 167 was subjected to successive reactions with maleimide and then with DDQ according to the previous representative procedure described in example 123, to give (after crystallization in MeOH / CH2Cl2 / hexane) product (580) (84%) as a bright orange solid, m.p. 284-286 ° C. 1 H NMR [(CD 3) 2 SO] d 1 1.96 (br s, 1 H), 11.08 (br s, 1 H), 8.46 (d, J = 2.6 Hz, 1 H), 7.58 (s, 1 H), 7.57 (m , 1 H), 7.46 (d, J = 8.7 Hz, 1 H), 7.25 (dd, J = 8.8, 2.6 Hz, 1 H), 7.07 (d, J = 2.9 Hz, 1 H), 7.04 (dd, J = 8.7, 3.1 Hz, 1 H), 3.89 (s, 3 H), 3.80 (s, 3 H). Found: C, 62.50; H, 3.77; N, 6.54. C22Hi5CIN204. H20 requires C, 62.20; H, 4.03; N, 6.59.

EXAMPLE 169 The preparation of 4- (2-chloro-5-hydroxy-phenyl) -9-hydroxypyrrolo [3,4-c1carbazole-1.3 (2H.6H) -dione (581) (VI, R10 = H. Ar = 2-chloro -5-hydroxyphenyl) The methyl ether (580) prepared as described in Example 168 was bis-demethylated with BBr3 using the procedure described in Example 80, with the exception that the reaction time was 6.5 h with 10 equiv. of BBr3 to give (after crystallization in -MeOH / CH2GI2 / hexane) -phenyl (581) (90%) ren form of a crystalline solid-orange-red, m.p. 335-340 ° C. 1 H NMR [(CD 3) 2 SO] d 11.80 (br s, 1 H), 1 1.00 (br s, 1 H), 9.78 (br s, 1 H), 9.27 (br s, 1 H), 8.31 (d, J = 2.4 Hz , 1 H), 7.49 (s, 1 H), 7.45 (d, J = 8.7 Hz, 1 H), 7.32 (d, J = 8.5 Hz, 1 H), 7.07 (dd, J = 8.7, 2.5 Hz, 1 H), 6.84 (dd, J = 8.5, 2.9 Hz, 1 H), 6.82 (d, J = 2.8 Hz, 1 H). Found: C, 63.25; H, 3.63; N, 6.73. C20H1 CIN2O4. 1 / 2H20. 1 / 4Hexano requires C, 63.09; H, 3.82; N, 6.84.

SCHEME 3 Scheme 3 procedures Representative procedure for method 1 1 of scheme 3 EXAMPLE 170 The preparation of 2- (4- (2-chlorophenyl) -9-methoxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) ethyl methanesulfonate (V. Ar = 2-chlorophenyl R10 = CH £CH2OSOzCH3) (228) The alcohol (46) prepared as described in Example 43 (1.10 g, 2.61 mmol) was dissolved in dry tetrahydrofuran (80 m) under a nitrogen atmosphere. The resulting solution was cooled to 0 ° C and triethylamine (2.0 ml) was added dropwise followed by methanesulfonyl chloride (263 ml, 3.40 mmol). After 30 minutes, an additional portion of methanesulfonyl chloride (50 ml) was added and after 30 more minutes the reaction was diluted with saturated sodium bicarbonate and extracted with ethyl acetate. The organic layer was dried, the drying agent was removed and the solution was concentrated to dryness. Crystallization from ethyl acetate / hexane gave the mesylate (228) (0.96 g, 74%) as a yellow solid, m.p. 254 ° C (dec). 1 H NMR d [(CD3) 2 SO] 1 1.15 (s, 1 H), 8.53 (d, J = 2.6 Hz, 1 H), 7.90 (s, 1 H), 7.74 (d, J = 9.0 Hz, 1 H ), 7.58 (m, 1 H), 7.48 (m, 3H), 7.33 (dd, J = 9.0, 2.6 Hz, 1 H), 4.89 (t, J = 5.0 Hz, 2H), 4.56 (m, 2H) , 3.91 (s, 3H), 2.94 (s, 3H). FABMS found [M + H] +: 499.0694, 501.0696. C24Hi9CIN206S requires 499.073, 501.0701.

EXAMPLE 171 - The methanesulfonate preparation of 2- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolor-3,4-clcarbazole-6 (1 H) -yl) ethyl (VII. Ar = 2 - chlorophenyl, n = 2. mesylate) (229) The mesylate (228) (.23 g, 2.48 mmol) prepared as described in Example 170 was reacted according to the procedure described in Example 80, with the exception that the reaction time was 7 hours, after which chromatography on silica eluting with ethyl acetate / hexane (from 1: 1 to 3: 1) and trituration in ethyl acetate / hexane yielded phenyl (229) (1.05 g, 87%) as a yellow solid, mp 266 ° C (dec). 1 H NMR d [(CD3) 2 SO] 1 1.09 (br s, 1 H), 9.40 (s, 1 H), 8.39 (d, J = 2.5 Hz, 1 H), 7.84 (s, 1 H), 7.62 (d , J = 8.9 Hz, 1 H), 7.58 (m, 1 H), 7.48 (m, 3H), 7.14 5 (dd, J = 8.9, 2.5 Hz, 1 H), 4.85 (t, J = 5.0 Hz, 2H), 4.54 (m, 2H), 2.93 (s, 3H). Found: C, 58. 13; H, 3.74; N, 5.72. C ^ H ^ CINaOeS. 1 / 4hexane requires C, 58.10; H, 4.08; N, 5.53.

EXAMPLE 172 0 The preparation of 6- (3-bromopropyl) -4- (2-chlorophenyl) -9-hydroxypyrrolo [3,4- c] carbazole-1.3 (2H-6H) -dione (VII: Ar = 2-chlorophenyl) n = 3. bromide) (58) The reaction of the alcohol (31) prepared as described in Example 40 with methanesulfonyl chloride followed by demethylation with 5 BBr3 following the procedure described in Example 170 gave the bromide (58) (81%). ), orange powder, mp 278 ° C (dec). 1 H NMR d [(CD3) 2 SO] 1 1.08 (s, 1 H), 9.39 (s, 1 H), 8.39 (d, J = 2.4 Hz, 1 H ), 7.81 (s, 1 H), 7.60 (d, J = 8.7 Hz, 1 H), 7.60-7.58 (m, 1 H), 7.53-7.43 (m, 3H), 7.16 (dd, J = 8.7, 2.4 Hz, 1 H), 4.55 (t, J = 6.9 Hz, 2H), 3.56-3.49 (m, 2H), 0 2.34-2.24 (m, 2H) Found: C, 56.94; H, 3.45, N, 5.69 C23Hi6BrCIN203 requires C, 57.10; H, 3.33; N, 5.79.

EXAMPLE 173 The preparation of 6- (3-bromopropyl) -9-hydroxy-4-phenylpyrrolof3.4-c1carbazole-1.3 (2H.6H) -dione (II. Ar = phenyl, n = 3-bromide (204) The alcohol (202) prepared as described in example 83 (0.50 g, 1.25 mmol) was reacted according to the procedure described in example 170 followed by the procedure described in example 80. Chromatography on silica eluting with acetate ethyl acetate / hexane (from 1: 1 to 4: 1) followed by crystallization from ethyl acetate / hexane gave the bromide (204) (0.54 g, 97%) as an orange powder, mp280-282 ° C. 1 H NMR d [(CD3) 2 SO] 11.07 (s, 1H), 9.36 (s, 1H), 8.41 (d, J = 2.2 Hz, 1H), 7.83 (s, 1H), 7.66 (m, 2H), 7.58 (d, J = 8.8 Hz, 1H), 7.47 (m, 3H), 7.14 (dd, J = 8.8, 2.2 Hz, 1H), 4.57 (t, J = 6.9 Hz, 2H), 3.53 (t, J = 6.5 Hz, 2H), 2.32 (m, 2H). · "- - - ^ --- =.; -, - r, - · .... Found: C, 61.87; H, 3.69; N, 6.59, requires: C, 61.48; H, 3.81; N, 6.23 .

EXAMPLE 174 The methanesulfonate preparation of 2- (9-hydroxy-1,3-dioxo-4-phenyl-2,3-dihydroDirrolo [3,4-clcarbazole-6 (1 H) -M) ethyl (VII. Ar = phenyl. mesylate) (205) The alcohol (201) (0.21 g, 0.53 mmol) prepared as described in Example 82 was reacted according to the procedure described in Example 170 followed by the procedure described in Example 80. Chromatography on silica eluting with ethyl acetate / hexane (from 1: 1 to 4: 1) followed by crystallization from ethyl acetate / hexane gave the mesylate (205) (0.19 g, 80%) as a solid yellow, pf 271-276 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.08 (s, 1 H), 9.37 (sa, 1 H), 8.40 (d, J = 2.4 Hz, 1 H), 7.86 (s, 1 H), 7.67. (m, 2H), 7.60 (d, J = 8.8 Hz, 1 H), 7.46 (m, 3H), 7.13 ~ r ~ ~ (dd J = 8: 8,: 2: 4-Hz, 1 H); 4.86 (t, - J = 4.8 Hz, 2H), 4.57 (t, J = 4.8 Hz, 2H), 2.97 (s, 5 3H). "- | FABMS found [M + H] +: 451.0958. C23Hi8N206S required 451 .0964.

EXAMPLE 175 The preparation of 6- (6-bromohexyl) -9-hydroxy-4-phenylpyrrolo [3,4-clcarbazole-1.3 (2H.6H) -dione (VII: Ar = phenyl, n = 6. bromide) (206) The alcohol (203) (0.30 g, 0.67 mmol) prepared as described in Example 84 was reacted according to the procedure described in Example 170 followed by the use of the procedure described in Example 80. Chromatography on silica eluting with ethyl acetate / hexane (from 1: 4 to 4: 1) followed by crystallization from ethyl acetate / hexane gave the bromide (206) (0.29 g, 88%) as an orange solid, mp 214-216X. 1 H NMR d [(CD3) 2 SO] 1 1.04 (s, 1 H), 9.33 (s, 1 H), 8.41 (d, J = 2.4 Hz, 1 H), 7.78 (s, 1 H), 7.65 (m , 2H), 7.56 (d, J = 8.8 Hz, 1 H), 7.46 (m, 3H), 7.13 (dd, J = 8.8, 2.4 Hz, 1 H), 4.46 (t, J = 7.1 Hz, 2H) , 3.46 (t, J = 6.7 Hz, 2H), 1.74 (m, 4H), J .41-1.29 (m, 4H). _ _ _ " . '"." "Found: C, 63.75; H, 4.72; N, 5.94, C26H23BrN203 requires: C, 63.66; H, 4.73; N, 5.71.

EXAMPLE 176 The preparation of 6- (3-bromophenyl) - - (2-chloro-6-methoxyphenyl) -9-hydroxypyrrolo [3,4-c1carba2ol-1.3f2H.6H) -dione (VII: Ar = 2-chloro-6-) methoxyphenyl, n = 3. bromide) (207) The alcohol (105) (0.20 g, 0.43 mmol) prepared as described in Example 58 was reacted according to the procedure described in Example 170 followed by the use of the procedure described in Example 80, with the exception that the reaction with boron tribromide was carried out at 0 ° C for 2 h and the subsequent crude treatment was dissolved in ethyl acetate (100 ml) to which lithium bromide (1.0 g) was added. This solution was heated at 50 ° C for 2 h before being absorbed on silica and chromatographed eluting with ethyl acetate / hexane (from 1: 3 to 1: 1) to give the bromide (207) (132 mg, 60%) in shape of a yellow solid, mp 286-288 ° C. "" "" _ _. * .. ~ .. ". * 1 H NMR d [(CD3) 2 SO] 1 1.03 (s, 1 H), 9.38 (s, 1 H), 8.38 (d, J = 2.4 Hz, 1 H), 7.77 (s, 1 H), 7.58 (d, J = 8.8 Hz, 1 H), 7.44 (t, J = 8.8 Hz, 1 H), 7.18 (d, J = 8.8 Hz, 1 H), 7.14 (m, 2H), 4.54 (t, J = 7.0 Hz, 2H), 3.52 (t, J = 6.8 Hz, 2H), 2.27 (m, 2H). FABMS found [M + H] +: 513.0182, 515.0192, 517.0169.

C24H18BrCIN204 requires 513.0217, 515.0196, 515.0187, 517.0167.

EXAMPLE 177 The preparation of methanesulfonate of 2- (4- (2,6-dichlorophenyl) -9-hydroxy-1,3-dioxo-3-dihydropyrrolof3.4-c1carbazol-6 (1H) -yl) -ethyl (VII. Ar = 2.6- dichlorophenyl, n = 2. mesylate) The alcohol (230) (1.0 g, 2.2 mmol) prepared as described in Example 85 was reacted according to the procedure described in Example 170 followed by the procedure described in Example 80, with the exception that the time Reaction with boron tribromide was 30 h. Chromatography on silica eluting with ethyl acetate / hexane (from 1: 1 to 4: 1) followed by crystallization from ethyl acetate / hexane gave the mesylate (231) (0.95 g, 83%) as a yellow solid , pf 255-260 ° C. 1 H NMR d [(CD 3) 2 SO] 1 1 .16 (br s, 1 H), 9.43 (br s, 1 H), 8.38 (d, J = 2.5 Hz, 1 H), 7.01 (s, 1 H), 7.63 (m, 3H), 7.51 (dd, J = 8.7, 7.3 Hz, 1 H), 7.16 (dd, J = 8.9, .2.5.Hz, 1 H), 4.85. (t, .J = 4.9 Hz, 2H ), 4.53 (t, J = 4.9 Hz, 2H), 2.88 (s, 3H). Found: C, 53.48; H, 3.22; N, 5.23. C23H16Cl2N206S requires: C, 53.18; H, 3.10; N, 5.39.

EXAMPLE 178 The preparation of 6- (3-bromopropyl) -4- (2,6-dichlorophenyl) -9- hydroxypyrrolo [3,4-c] carbazole-1.3 (2H-6H) -dione (VII: Ar = 2,6-dichlorophenyl) n = 3. bromide) (233) The alcohol (232) (0.77 g, 1.68 mmol) prepared as described in Example 86 was reacted according to the procedure described-in Example 170 followed by the procedure described in Example 80, with the exception that the reaction time with boron tribromide was 18 h. Chromatography on silica eluting with ethyl acetate / hexane (from 1: 1 to 4: 1) followed by crystallization from ethyl acetate / hexane gave the bromide (233) (0.70 g, 80%) as an orange solid. , pf 273-276 ° C. H NMR 6 [(CD3) 2 SO] 1 1.15 (br s, 1 H), 9.42 (s, 1 H), 8.38 (d, J = 2.4 Hz, 1 H), 7.87 (s, 1 H), 7.62 (m , 3H), 7.51 (dd, J = 8.9, 7.6 Hz, 1 H), 7.18 (dd, "J = 8.8, 2.4 Hz, 1 H), 4.56 (t, J = 6.9.Hz, 2H ), 3.51 (t, J = 6.7 Hz, 2H), 2.27_ (m, .2H) " Found: C, 53.44; H, 2.96; N, 5.23. C aH ^ BrC ^ Oa requires: C, 53.30; H, 2.92; N, 5.40.

Representative procedure for method 12 of scheme 3 EXAMPLE 179 The preparation of 6-f3- (dimethylamino) propyl] -9-hydroxy-4-phenylpyrrolo [3. clcarbazole-1.3 (2H.6m-dione (VIII, Ar = phenyl, n = 3. Z = NMe2) (208) To a solution of the bromide (204) prepared as described in example 173 (0.12 g, 0.27 mmol) in dimethylacetamide (4 ml) was added the amine, dimethylamine (25 equiv. Mol, 0.85 ml in this case in the form of a 40% aqueous solution). The reaction vessel was sealed and heated to 80 ° C with stirring for 18 h, before being diluted with water. Then, the resulting solution was acidified by the dropwise addition of concentrated hydrochloric acid and then the pH was adjusted to approximately pH = 9 by the addition of solid potassium carbonate. The precipitated product was collected by filtration and washed with water and diisopropyl ether before being dried or extracted with ethyl acetate. The organic layer was dried, the drying agent was removed and the solution was concentrated to dryness. Chromatography on silica eluting with methanol / dichloromethane (from 1: 9 to 1: 4) followed by trituration in ethyl acetate / hexane gave the amine (208) (52 mg, 47%) as a yellow powder, m.p. 185-189 ° C. 1 H R N d [(CD3) 2 SO] 1.05 (s, 1 H), 9.34 (s, 1 H), 8.41 (d, J = 2.4 Hz, 1 H), 7.78 (s, 1 H). 7.64 (m, 2H), 7.56 (d, J = 8.9 Hz, 1 H), 7.47 (m, 3H), 7.14 (dd, J = 8.9, 2.4 Hz, 1 H), 4.48 (t, J = 6.6 Hz , 2H), 2.16 (t, J = 6.5 Hz, 2H), 2.08 (s, 6H), 1.90 (m, 2H). Found: C, 71.98; H, 5.67; N, 10.14. C25H23N3O3. 1 / 4H20 requires: C, 71.84; H, 5.67; N, 10.05.

EXAMPLE 180 The preparation of 6- [2- (dimethylamino) ethyl] -9-hydroxy-4-phenylpyrrolo [3,4-c1carbazole-1.3 (2H.6H) -dione (VII: Ar = phenyl) n = 2. Z = NMe?) (209) The mesylate (205) prepared as described in the example 174 (70 mg, 0.16 mmol) was reacted with an aqueous solution of dimethylamine according to the procedure described in Example 179 to give the amine (209) (30 mg, 48%) as a yellow powder, m.p. 283-286 ° C. "~" "1H RN d [(CD3) 2SOj 11.05 (sa, * 1 H), 9.33 (s, 1 H), 8.41 (d, J = 2.4 Hz, 1 H), 7.77 (s, 1 H), 7.65 (m, 2H), 7.54 (d, J = 8.8 Hz, 1 H), 7.46 (m, 3H), 7.12 (d, J = 8.8, 2.4 Hz, 1 H), 4.55 (t, J = 6.5 Hz , 2H), 2.62 (t, J = 6.5 Hz, 2H), 2.19 (s, 6H) Found: C, 71.92; H, 5.16; N, 10.55. C24H21N3O3 requires: C, 72.17; H, 5.30; N, 10.52.

EXAMPLE 181 The preparation of 9-hydroxy-6- [3- (4-morpholine) propyl] -4-phenylpyrrolo [3,4-clcarbazole-1.3 (2H.6H) -dione (VIII. Ar = phenyl- n = 3. Z = 4-morpholinyl) (210 The bromide (204) (0.10 g, 0.22 mmol) prepared as described in Example 173 was reacted with morpholine according to the procedure described in Example 179 to give the amine (210) (73 mg, 72%) in the form of a yellow powder, mp 252-255 ° C. 1H RN d [(CD3) 2SO] 1 1.04 (sa, 1 H), 9.33 (s, 1 H), 8.41 (d, J = 2.5 Hz, 1 H), 7.81 (s, 1 H), 7.62 (m , 2H), 7.57 (d, J = 8.9 Hz, 1 H), 7.47 (m, 3H), 7.12 (dd, J = 8.9, 2.5 Hz, 1 H), 4.51 (t, J = 6.3 Hz, 2H) , 3.38 (t, J = 4.0 Hz, 4H), 2.18 (sa, 4H), 2.14 (t, J = 6.3 Hz, 2H), 1.93 (m, 2H). Found: C, 71.11; H, 5.46; N, 9.29. C27H25N3O4 requires: C, 7.1.19; H, 5.53; N, 9.22.

EXAMPLE 182 The preparation of 9-hydroxy-6- [2- (4-morpholinyl) ethyl] -4-phenylpyrrolo [3,4-c1carbazole-1.3 (2H.6H) -dione (VIII: Ar = phenyl- n = 2 Z = 4-morpholinyl) (211) The mesylate (205) (70 mg, 0.16 mmol) prepared as described in Example 174 was reacted with morpholine according to the procedure described in Example 179 to give the amine (211) (53 mg, 75%) in the form of a white powder, mp 260-262 ° C. 1H RN d [(CD3) 2SO] 11.04 (sa, 1 H), 9.33 (s, 1 H), 8.40 (d, J = 2.5 Hz, 1 H), 7.78 (s, 1 H), 7.64 ( m, 2H), 7.54 (d, J = 8.9 Hz, 1 H), 7.47 (m, 3H), 7.12 (dd, J = 8.9, 2.5 Hz, 1 H), 4.57 (t, J = 6.4 Hz, 2H ), 3.45 (t, J = 4.5 Hz, 4H), 2.67 (t, J = 6.4 Hz, 2H), 2.18 (ta, J = 4 Hz, 4H). Found: C, 70.55; H, 5.25; N, 9.22. C26H23N3O4 requires: C, 70.74; H, 5.25; N, 9.51.

EXAMPLE 183 The preparation of 9-hydroxy-6- [3- (1 H-imidazol-1-yl) propy-4-phenylpyrrolo [3,4-c1carbazole-1.3 (2H.6H) -dione (VIII: Ar = phenyl. n = 3. Z = 1- imidazolyl) (2121 The bromide (204) (80 mg, 0.18 mmol) prepared as described in Example 173 was reacted with imidazole according to the procedure described in Example 179 to give the amine (212) (41 mg, 53 %) in the form of a white powder, mp 309-311 ° C. 1 H NMR d [(CD3) 2 SO] 1 .06 (s, 1 H), 9.36 (s, 1 H), 8.40 (d, J = 2.3 Hz, 1 H), 7.69 (s, 1 H), 7.64 ( m, 3H), 7.47 (m, 4H), 7.22 (s, 1 H), 7.14 (dd, J = 8.8, 2.3 Hz, 1 H), 6.89 (s, 1 H), 4.44 (t, J = 7.4 Hz, 2H), 4.07 (t, J = 7.3 Hz, 2H), 2.24 (m, 2H).

Found: C, 70.31; H, 4.78; N, 12.43. C26H20N4O3. 1 / 2H20 requires: C, 70.10; H, 4.75; N, 12.57.

EXAMPLE 184 The preparation of 9-hydroxy-6- [2- (1H-imidazol-1-yl) ethyl] -4-phenylpyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (VIII. Ar = phenyl) n = 2. Z = 1-imidazolyl) The mesylate (205) (70 mg, 0.16 mmol) prepared as described in Example 174 was reacted with imidazole according to the procedure described in Example 179 to give the amine (213) (34 mg, 50%) in the form of a yellow powder, mp > 345 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.05 (br s, 1 H), 9.34 (s, 1 H), 8.39 (d, J = 2.4 Hz, 1 H), 7.59 (m, 2H), 7.45 (m, 5H), 7.27 (s, 1 H), 7.06 (dd, J = 8.8, 2.4 Hz, 1 H), 7.02 (s, 1 H), 6.75 (s, 1 H), 4.80 (t, J = 5.7 Hz , 2H), 4.41 (t, J = 5.7 Hz, 2H). : Found: C, 70.36; H, 4.38; N,. 12.68., C25H18N4O3. 1 / 4H20 requires: C, 70.33; H, 4.37; N, 13.12.

EXAMPLE 185 The preparation of 9-hydroxy-6- [3- (methylamino) propyl] -4-phenylpyrrolo [3,4-c1carbazole-1.3 (2H-6H) -dione (VIII: Ar = phenyl) n = 3. Z = NHMel (214) The bromide (204) (40 mg, 0.09 mmol) prepared as described in Example 173 was reacted with an aqueous solution of methylamine (10 equiv mol) according to the procedure described in Example 179 with the exception of that the reaction was carried out in dimethyl sulfoxide at room temperature for 3 h, to give the amine (214) (22 mg, 61%) as an orange / yellow powder, mp. 265-268 ° C. 1 H NMR 6 [(CD 3) 2 SO] 9.33 (s a, 1 H), 8.41 (d, J = 2.5 Hz, 1 H), 7.80 (s, 1 H), 7.64 (m, 2H), 7.57 (d, J = 8.8 Hz, 1 H), 7.47 (m, 3H), 7.14 (dd, J = 8.8, 2.5 Hz, 1 H), 4.51 (t, J = 6.8 Hz, 2H), 2.40 (t, J = 6.5 Hz, 2H), 2.20 (s, 3H), 1.88 (m, 2H). FABMS found [M + H] +: 400.1659. C24H22N3O3 requires 400.1661.

EXAMPLE 186 The preparation of 9-hydroxy-4-phenyl-6- [3- (1-piperazinyl) propyl] pyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (VIII; Ar = phenyl. 3. Z = 1 -piperazinyl) (215) The bromide (204) (70 mg, 0.16 mmol) prepared as described in Example 173 was reacted with piperazine according to the procedure described in Example 179 with the exception that the reaction was carried out at room temperature for 20 minutes. h, to give the amine (215) (40 mg, 55%) as a yellow powder, mp 178-183 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.0 (br s, 1 H), 9.35 (br s, 1 H), 8.40 (d, J = 2.4 Hz, 1 H), 7.78 (s, 1 H), 7.62 (m , 2H), 7.56 (d, J = 8.8 Hz, 1 H), 7.45 (m, 3H), 7.14 (dd, J = 8.8, 2.4 Hz, 1 H), 4.49 (t, J = 6.3 Hz, 2H) , 2.52 (m, 4H), 2.12 (m, 6H), 1.91 (m, 2H). Found: C, 69.31; H, 5.97; N, 11.49. C27H26N4O3. 4 / 5H20 requires: C, 69.16; H, 5.93; N, 1.94.

EXAMPLE 187 The preparation of 6- [3- (benzylamino) propyl] -9-hydroxy-4-phenylpyrrolo [3,4-clcarbazole-1.3 (2H.6H) -dione (VIII. Ar = phenyl- n = 3. Z = NHBn ) (216) The bromide (204) (75 mg, 0.17 mmol) prepared as described in Example 73 was reacted with benzylamine according to the procedure described in Example 179 with the exception that the reaction was carried out at room temperature for 20 minutes. h, to give the amine (216) (36 mg, 45%) as a yellow powder, mp 139-144 ° C. 1H NMR "d KCDafeSO] 1 1.04 (s a, 1 H), 9.33 (s a, Í_H), 8.41 (d ^ J = 2.4 Hz, 1 H), 7.80 (s, 1 H), 7.62 (m, 2 H), 7.57 (d, J = 8.8 Hz, 1 H), 7.44 (m, 3 H), 7.24-7.19 (m, 5H), 7.1 1 (dd, J = 8.8, 2.4 Hz, 1 H), 4.53 (t, J = 6.7 Hz, 2H), 3.57 (s, 2H), 2.46 (t, J = 6.4 Hz, 2H), 1.92 (m, 2H). Found: C, 74.84; H, 5.39; N, 8.80. C30H25N3O3. 1 / 4H20 requires: C, 75.06; H, 5.35; N, 8.75.

EXAMPLE 188 The preparation of 6- (3-an'linopropyl) -9-hydroxy-4-phenylpyrrolo [3,4-c] carbazole-1. 3 (2H.6H) -dione (VIII: Ar = phenyl, n = 3. Z = NHPhi 217) The bromide (204) (75 mg, 0.17 mmol) prepared as described in Example 173 was reacted with aniline according to the procedure described in Example 179 with the exception that the reaction was carried out at room temperature for 20 minutes. h, to give the aniline (217) (30 mg, 38%) as a yellow powder, mp 240 ° C (dec). 1 H RN d [(CD3) 2 SO] 1 1.04 (sa, 1 H), 9.33 (s, 1 H), 8.40 (d, J = 2.4 Hz, 1 H), 7.78 (s, 1 H), 7.59 (d , J = 8.9 Hz, 1 H), 7.48 (m, 2H), 7.42 (m, 3H), 7.10 (dd, J = 8.8, 2.4 Hz, 1 H), 7.05 (m, 2H), 6.52 (m, 3H), 5.70 (t, J = 5.3 Hz, 1 H), 4.59 (t, J = 6.8 Hz, 2H), 2.98 (t, J = 6.3 Hz, 2H), 2.07 (m, 2H). Found: C, 74.00; H, 5.22; N, 8.76. C29H23N3O2. 1 / 2H20 requires: C, 74.03; H, 5.14; N, 8.93. . _. . . . " . . .

EXAMPLE 189 The preparation of 4- (2-chloro-6-methoxyphenol) -6-. { 3- [cis-3,5-dimethyl-piperazinyl] propyl} -9-hydroxypyrrolo [3,4-c] carbazole-1.3 (2H-6H) -dione (VIII: Ar = 2-chloro-6-methoxyphenyl) n = 3. Z = 1- (cis-3,5-dimethylpiperazinyl)) (218) ) Bromide (207) (60 mg, 0. 2 mmol), prepared as described in Example 176, was reacted with cis-2,6-dimethylpiperazine according to the procedure described in Example 179 with the exception of that the reaction was carried out at room temperature for 20 h, to give the amine (218) (63 mg, 98%) as a yellow powder, mp. 199-202 ° C. H NMR d [(CD3) 2 SO] 10.99 (br s, 1 H), 9.37 (br s, 1 H). 8.36 (d, J = 2.4 Hz, 1 H), 7.75 (s, 1 H), 7.57 (d, J = 8.8 Hz, 1 H), 7.43 (t, J = 8.2 Hz, 1 H), 7.15 (m , 3H), 4.45 (t, J = 6.1 Hz, 2H), 3.67 (s, 3H), 2.49 (m, 4H), 2.1 1 (m, 2H), 1.90 (m, 2H), 1.27 (m, 2H) ), 0.79 (m, 6H). Found: C, 61.35; H, 5.68; N, 9.14. C30H31 CIN4O4. 2¼ H20 requires: C, 61.32; H, 6.09; N, 9.54.

EXAMPLE 190 The preparation of 4- (2-cyclo-6-methoxyphenyl) -9-hydroxy-6- [3- (4-morpholinyl) propinopyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (VIII: Ar = 2-chloro-6-methoxyphenyl n = 3. Z = 4-morpholinyl) (219) "" '"' ''" '~' _. ~ The bromide (207) (60 mg, 0.12 mmol), prepared as described in example 176, was reacted with morpholine according to the procedure described in example 179 with the exception that the reaction was performed at 50 °. C for 6 h, to give the amine (219) (40 mg, 66%) as a yellow powder, m.p. 169-174 ° C. 1 H NMR d [(CD3) 2 SO] 10.99 (br s, 1 H), 9.34 (br s, 1 H), 8.36 (d, J = 2.4 Hz, 1 H), 7.77 (s, 1 H), 7.58 (d, J = 8.8 Hz, 1 H), 7.44 (t, J = 8.2 Hz, 1 H), 7.18 (d, J = 8.2 Hz, 1 H), 7.12 (m, 2H), 4.47 (t, J = 6.1 Hz , 2H), 3.66 (s, 3H), 3.35 (t, J = 4.4 Hz, 4H), 2.22-2.1 1 (m, 6H), 1.91 (m.2H). Found: C, 63.09; H, 5.26; N, 7.97. C28H26CIN3O5. 3 / 4H20 requires: C, 63.04; H, 5.20; N, 7.88.

EXAMPLE 191 The preparation of 4- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) butanonitrile (VIII: Ar = 2- chlorophenyl- n = 3. Z = CN) (241) To a solution of bromide 0 (0.13 g, 0.27 mmol) prepared as described in Example 172 in dimethylsulfoxide (2 mL) was added dropwise a solution of sodium cyanide (15 mg, 0.30 mmol) in dimethyl sulfoxide (2 g). mi) for 15 minutes. After 30 minutes, the reaction was diluted with water and extracted with ethyl acetate. The organic layer was dried, the drying agent was removed and the solution was concentrated to dryness. Chromatography on silica eluting with ethyl acetate / hexane (from 1: 4 to 11), followed by crystallization from ethyl acetate / hexane gave the nitrile (241) (68 mg, 59%) as an orange powder , pf 262-266 ° C. 1 H R N d [(CD3) 2 SO] 11.08 (s a, H), 9.39 (s, 1 H), 8.39 (d, J = 2.4 Hz, 1 H), 7.83 (s, 1 H), 7.59 (m, 2H), 7.49 (m, 3H), 7.15 (dd, J = 8.8, 2.4 Hz, 1 H), 4.50 (t, J = 7.3 Hz, 2H), 2.57 (m, 2H), 2.07 (m, 2H).

FABMS found [+ H] +: 430.0927, 432.0916. C24H16CI 303 requires 430.0958, 432.0929.

EXAMPLE 192 The preparation of 4- (2-chlorophenyl) -9-hydroxy-6- [2- (phenylsulfanyl) ethylpyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (VII: Ar = 2-chlorophenyl. n = 2. Z = SPh) (242) The mesylate (229) (55 mg, 0.1 1 mmol) prepared as described in example 171 was reacted with excess thiophenol (0.10 ml) according to the procedure described in example 179, with the exception of that triethylamine (2.0 ml) was added and the reaction was heated at 1 10 ° C for 4 days. The addition of water was followed by the extraction of the compound. with ethyl acetate. The organic layer was dried, the drying agent was removed and the solution was concentrated to dryness. The . The organic layer was dried, the agent, drying was removed and the solution was concentrated to dryness followed by chromatography on silica eluting with ethyl acetate / hexane (from 1: 4 to 11) to give the carbazole (242) (16). mg, 27%) in the form of an orange powder, mp 262-264 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.04 (s a, 1 H), 9.37 (s a, 1 H), 8.34 (d, J = 2.5 Hz, 1 H), 7.58 (m, 1 H), 7.46 (m, 5H), 7.19 (m, 2H), 7.12 (m, 3H), 7.05 (m, 1 H), 4.66 (t, J = 6.4 Hz, 2H), 3.46 (t, J = 6.4 Hz, 2H).

Found: C, 63.64; H, 4.09; N, 4.98. CaaH ^ CINaOaS. 13/4? 20 requires: C, 63.39; H, 4.28; N, 5.28.

EXAMPLE 193 The preparation of the acid 2-. { [3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) propyl] amino} benzoic acid (VIII: Ar-2-chlorophenyl) n = 3. Z = 2-carboxanilino) (60) The reaction of the bromide (58) prepared as described in Example 172 with o-anthranilic acid using the procedure described in Example 179 gave the aniline (60) (88%), m.p. 261-263 ° C. 1 H NMR d [(CD3) 2 SO] 1 .05 (s, 1 H), 9.38 (s, H), 8.39 (d, J = 2.4 Hz, 1 H), 7.76 (m, 1 H), 7.75 (s) , 1 H), 7.59 (d, J = 8.7 Hz, 1 H), 7.55 (m, 1 H), 7.46 (m, 1 H), 7.40 (m, 1 H), 7.33 (m, 1 H), 7.27 (m, 1 H), 7.12 (dd, J = 8.7, 2.4 Hz, 1 H), 6.59-6.50 (m, 2H), .4.57 (t, J = 6 7 Hz, 2H), 3.22-3.10 ( m, 2H), 2.15-2.05 (m, 2H). FABMS found M +: 541.1230, 539.1234. C3oH22CIN305 requires 541.1218, 539.1248.

EXAMPLE 194 The preparation of acid 3-. { [3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1 H) -yl) propyl-amino} benzoic (HIV; Ar = 2-chlorophenyl; n = 3; Z = 3-carboxyanilino) (61) The reaction of the bromide, (58) prepared as described in Example 172 with m-anthranilic acid using the procedure described in Example 179 gave the aniline (61) (82%), m.p. 160-166 ° C (dec). 1 H NMR d [(CD 3) 2 SO] 11.04 (s, 1 H), 9.38 (s, 1 H), 8.39 (d, J = 2.4 Hz, 1 H), 7.77 (s, 1 H), 7.61 (d, J = 8.7 Hz, 1 H), 7.54 (m, 1 H), 7.45 (m, 1 H), 7.27 (m, 1 H), 7.14-7.08 (m, 4H), 6.67 (m, 1 H), 5.92 (br s, 1 H), 4.58 (m, 2H), 3.09-2.92 (m, 2H), 2.12-2.02 (m, 2H). FABMS found M +: 541.1223, 539.1237. C30H22CIN3O5 requires 541.1218, 539.1248. _; . . . _ _ _. EXAMPLE 195 The preparation of acid 4-. { [3- (4- (2-Chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) propyl] amino} benzoic (VIII: Ar-2-chlorophenyl, n = 3. Z = 4-carboxanilino) (62) The reaction of the bromide (58) prepared as described in Example 172 with p-anthranilic acid using the procedure described in Example 179 gave the aniline (62) (77%), m.p. 160-165 ° C (dec.) 1 H NMR d [(CD 3) 2 SO] 1 1.06 (br s, 1 H), 9.43 (br s, 1 H), 8.39 (d, J = 2.4 Hz, 1 H), 7.75 ( s, 1 H), 7.65-7.59 (m, 3H), 7.54 (m, 1 H), 7.45 (m, 1 H), 7.37 (m, 1 H), 7.26 (m, 1 H), 7.13 (dd) , J = 8.7, 2.4 Hz, 1 H), 6.49 (d, J = 8: 7 Hz, 2H), 4.58 (m, 2H), 3.1 1 -2.99 (m, 2H), 2.12-2.04 (m, 2H ). Found: C, 63.24; H, 4.66; N, 7.95. C30H22CIN3O5. H20 requires C, 63.55; H, 4.23; N, 7.41.

EXAMPLE 196 The preparation of 4- (2-chlorophenyl) -6-. { 3 - [(cis) -3,5-dimethylpiperazinyl] propyl > - 9-hydroxypyrrolo [3,4-c1carbazole-1.3 (2H-6H) -dione (HIV: Ar = 2-chlorophenyl, n = 3. Z = cis-3,5-dimethylpiperazinyl) (63) The reaction of the bromide (58) prepared as described in Example 172 with cis-1,3-dimethylpiperazine using the procedure described "in Example 179 gave (63) (65%), mp 165-172 ° _C, 1H NMR d [(CD3) 2 SO] 1 .04 (br s, 1 H), 9.36 (br s, 1 H), 8.38 (d, J = 2.4 Hz, 1 H), 7.80 (s, 1 H), 7.59-7.54 (m, 2H), 7.51-7.42 (m, 3H), 7.13 (dd, J = 8.7, 2.4 Hz, 1 H), 4.47 (m, 2H), 2.58-2.38 (m), 2.09 (t, J = 6.2 Hz, 2H), 1.96- 1.87 (m, 2H), 1.32-1.23 (m, 2H), 0.81 (d, J = 6.1 Hz, 3H), 0.77 (d, J = 6.1 Hz, 3H). C, 64.09, H, 5.43, N, 10.08, C29H28CIN4O3, 1.5H20 requires C, 64.14, H, 5.75, N, 10.31.

EXAMPLE 197 The preparation of 4- (2,6-dichlorophenyl) -6-. { 3 - [(cis) -3,5-dimethylpiperazinipropyl} -9-hydroxypyrrolo [3,4-c] carbazoM .3 (2H.6Hi-dione (HIV, Ar-2,6-dichlorophenyl, n = 3, Z = cis-3,5-dimethylpiperazinyl) (64) The reaction of the bromide (233) prepared as described in Example 178 with cis-1,3-dimethylpiperazine using the procedure described in Example 179 gave (64) (68%), m.p. 160-165 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.1 1 (a, 1 H), 9.39 (s at, 1 H), 8; 37 (d, J = 2.4 Hz, 1 H), 7.85 (s, 1 H), 7.62 (d, J = 8.1 Hz, 2H), 7.59 (d, J = 8.7 Hz, 1 H), 7.51 (m, 1 H), 7.16 (dd, J = 8.7, 2.4 Hz, 1 H), 4.46 (d. t, J = 5.7 Hz, 2H), 2.55-2.42 (m), 2.10 (t, J = 6.4 Hz, 2H). 1.96-1.89 (m, 2H), 1.27 (t, J = 10 Hz, 2H), 0.80 (d, J = 6.2 Hz, 6H). Found: C, 61.34; H, 5.53; N, 9.56. C 29 H 27 Cl 2 N 403. H20 requires C, 61.27; H, 5.14; N, 9.85. .

EXAMPLE 198 The following amino compounds of general structure VIII were prepared in an orderly manner by reaction of the appropriate mesylate or bromide with the appropriate amine using the procedure described in example 179: The preparation of 6- (2-aminoethyl) -9-hydroxy-4-phenylpyrrolo [3,4-c] carbazole-1.3 (2H.6HVdione (VIII; Ar = phenyl, n = 2, Z = NH2) (65) per reaction of (205) prepared as described in Example 174 with aqueous ammonia Found: M + H = 372 The preparation of 9-hydroxy-6 [2- (methylamino) ethyl] pyrrolo [3,4-cjcarbazole-1.3r2H.6HVdione (VIII, Ar = phenyl, n = 2, Z NHCH3) (66) by reaction of (205) prepared as described in Example 174 with aqueous methylamine. Found M + H = 386.

The preparation of 6- (3-aminopropyl) -9-hydroxy-4-phenylpyrrolo [3,4-cjcarbazol-1.3 (2H.6H) -dione "(Vlllj Ár" = phenyl, n = 3, Z = ÑH2) ~ (67) "by reaction of (204) prepared as described in Example 173 with aqueous ammonia Found: M + H = 386 The preparation of 9-hydroxy-4-phenyl-6- [3- (1-pyrrolidinyl) propyl] pyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (VIII, Ar = phenyl, n = 3, Z = 1-pyrrolidinyl) (68) by reaction of (204) prepared as described in Example 173 with pyrrolidine. Found: M + H = 440 The preparation of 6- [3- (dimethylamino) propyl1-9-hydroxy-4-phenylpyrrolor3.4-c1carbazole-1.3r2H.6HVdione (VIII; Ar = phenyl, n = 3, Z = N (CH2CH3) 2) (69) by reaction of (204) prepared as described in Example 173 with diethylamine. Found: + H = 442.

The preparation of 9-hydroxy-4-phenyl-6- [3- (l-piperidininpropyl] pyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (VIII; Ar = phenyl, n = 3, Z = 1-piperidinyl) (70) by reaction of (204) prepared as described in Example 173 with piperidine Found: M + H = 454.

The preparation of 9-hydroxy-6- [3- (4-methyl-1-piperazinyl) propyl] -4-phenylpyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (VIII; Ar = .phenyl, n = 3, Z = 4-methyl-1-piperazinyl) (71) by reaction of (204) prepared as described in Example 173 with I-methylpiperazine. Found: M + H = 469 The preparation of 6- [6- (dimethylamino) hexyl] -9-hydroxy-4-phenylpyrrolo [3,4-c] carbazole-1 3 (2H.6HVdione (VIII, Ar = phenyl, n 6, Z = N (CH3) 2) (72) by reaction of (206) prepared as described in example 175 with aqueous dimethylamine Found: M + H = 456.

The preparation of 9-hydroxy-6- [6- (4-methyl-1-piperazinyl) hexyl-4-phenylpyrrolo [3,4-c] carbazole-. 3 (2H 6HVdione (VIII; Ar = phenyl, n = 6, Z = 4-methy1-piperazinyl) (73) by reaction of (206) prepared as described in Example 175 with 1-methylpiperazine Found: M + H = 512.

The preparation of 6- (2-aminoethyl) -4- (2-chlorophenyl) -9-hydroxypyrrolo [3.4-c] carbazole-1.3 (2H.6H) -dione (VIII; Ar = 2-chlorophenyl, n = 2, R = NH2) (74) by reaction of (229) prepared as described in Example 171 with aqueous ammonia. Found: M + H = 404 The preparation of 4- (2-chlorophenyl) -9-hydroxy-6- [3- (dimethylamino) ethyl] pyrrolo [3,4-c] carbazole-1 .3 (2H.6H) -dione (VIII, Ar = 2- clprofenilp, n = 2, Z = .N (CH3) 2) "(7.5) by reaction of (229) prepared as described in Example 171 with aqueous dimethylamine. Found: M + H = 434.

The preparation of 4- (2-chlorophenyl) -9-hydroxy-6- [2- (1 H-imidazol-1-nitill-Pyrrolo [3,4-c] carbazole-1.3 (2H.6HVdione (VIII, Ar = 2-chlorophenyl) , n = 2, Z = 1 H-imidazol-1-yl) (76) by reaction of (229) prepared as described in Example 171 with imidazole Found: M + H = 457.

The preparation of 4- (2-chlorophenyl V9-hydroxy-6- [2- (4-morpholinyl) ethyl] pyrrolo [3,4-c] carbazole-1.3 (2H-6H) -dione (VIII, Ar = 2-chlorophenyl, n = 2, Z = 4-morpholinyl) (77) by reaction of (229) prepared as described in Example 171 with morpholine Found: M + H = 476.

The preparation of 4- (2-chlorophenyl) -9-hydroxy-6- [2- (4-methyl-1-piperazinyl) ethyl] pyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (VIII, Ar = 2-chlorophenyl, n = 2, Z = 4-methyl-1-piperazinyl) (78) by reaction of (229) prepared as described in Example 171 with 1-methylpiperazine. Found: M + H = 489.

The preparation of 6- (2-anilinoetin-4- (2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (?. "'· _ ^ G = 2-chlorophenyl, n 2, Z = anilino) (79) by reaction of (229) prepared as described in example 171 with aniline. Found: M + H = 481.

The preparation of 4- (2,6-dichlorophenyl) -9-hydroxy-6- [3- (dimethylamino] ethylpyrrolo [3,4-c] carbazole-1.3 (2H.6HVdione (VIII, Ar = 2,6-dichlorophenyl, n = 2, Z = N (CH3) 2) (80) by reaction of (231) prepared as described in example 177 with aqueous dimethylamine Found: M + H = 468.

The preparation of 4- (2,6-dichlorophenyl) -9-hydroxy-6- [2-n H-imidazol-1 -inetylPyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (VIII, Ar = 2,6-dichlorophenyl, n = 2, Z = 1H-imidazol-1-yl) (81) by reaction of (231) prepared as described in Example 77 with imidazole. Found: M + H = 491.

The preparation of 4- (2,6-dichlorophenol) -9-hydroxy-6- [2- (4-morpholin) ethyl] pyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (VIII, Ar = 2,6-dichlorophenyl, n = 2, Z = 4-morpholinyl) (82) by reaction of (231) prepared as described in example 177 with morpholine. Found: M + H = 510.

The preparation of 4- (2,6-dichlorophenin-9-hydroxy-6- [2- (4-methyl-1-piperazinyl) ethyl] pyrrolo [3,4-c] carbazole-1.3 (2H-6H) -dione (VIII, Ar 2,6-dichlorophenyl, n = 2, .Z = 4-methyl-1-piperazinyl) (83) by reaction of (231) prepared as described in example 177 with 1-methylpiperazine Found: M + H = 523.

The preparation of 6- (2-anilinoethyl) -4- (2,6-dichlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1.3 (2H.6m-dione (VIII, Ar = 2,6-dichlorophenyl, n = 2 , Z = aniline) (84) by reaction of (231) prepared as described in example 177 with aniline Found: M + H = 5 6.

The preparation of 4- (2-chlorophenin-9-hydroxy-6- [3-methylamine) propyl] pyrrolo [3,4-chlorcarbazole-1,3 (2H.6H) -dione (VIII, Ar = 2-chlorophenyl, n = 3, Z = NHMe) (85) by reaction of (58) prepared as described in Example 172 with aqueous methylamine. Found: + H = 434.

The preparation of 4- (2-dorophenyl) -6- [3- (dimethylamino) propyl] -9- hydroxypyrrolo [3,4-c] carbazole-1,3 (2H-6H) -dione (VII I; Ar 2-chlorophenyl) , n = 3, Z = N (CH3) 2) (86) by reaction of (58) prepared as described in Example 172 with aqueous dimethylamine. Found: M + H = 448.

The preparation of 4- (2-chlorophenyl) -9-hydroxy-6- [3- (1 H-imidazol-1-inpropyl] pyrrolo [3,4-c] carbazole-1 .3 (2H.6HVdione _ "_" ~~ (VII I, Ar = 2-chlorophenyl, n = 3, Z = 1 H-imidazol-1-yl) (87) 'by reaction of the bromine prepared as described in Example 172 with imidazole. + H = 471.

The preparation of 4- (2-chlorophenyl) -9-hydroxy-6- [3- (4-morpholinylpropyl] pyrrolo [3.4] carbazole-1 .3 (2H.6HVdione (VIII, Ar = 2-chlorophenyl, n = 3 , Z = 4-morpholinyl) (88) by reaction of (58) prepared as described in Example 172 with morpholine Found: M + H = 490.

The preparation of 4- (2-chlorophenyl) -9-hydroxy-6- [3- (4-methyl-1-piperazinyl) propyl-1-pyrrolo [3,4-c] carbazole-1,3 (2H.6H) -dione ( VIII, Ar 2-chlorophenyl, n = 3, Z = 4-methyl-1-piperazinyl) (89) by reaction of (58) prepared as described in Example 172 with 1-methylpiperazine. Found: M + H = 503.

The preparation of 6- (3-anilinopropyl) -4- (2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1.3 (2H.6HV-dione (VIII, Ar 2-chlorophenyl, n = 3, Z = aniline) (90) by reaction of (58) prepared as described in Example 172 with aniline Found: M + H = 495.

The preparation of 4- (2,6-dichlorophenyl) -9-hydroxy-6- [3- (methylamino) propyl] pyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (HIV, Ar = 2, 6-dicj-phenyl, n = 3, Z_NHMe) (91) by reaction of (233) prepared as described in example 178 with aqueous methylamine. Found: M + H = 468.

The preparation of 4- (2,6-dichloropheni0-6- [3- (dimethylamino) propyl] -9-hydroxypyrrolo [3,4-c1carbazole-1.3 (2H.6HVdione (VIII, Ar = 2,6-dichlorophenyl, n = 3, Z = N (CH3) 2) (92) by reaction of (233) prepared as described in Example 178 with aqueous dimethylamine Found: M + H = 482.

The preparation of 4- (2,6-dichlorophenyl) -9-hydroxy-6- [3- (1 H-imidazol-1-yl) propyl] pyrrolof3.4-c1carbazole-1 .3 (2H-6H Vdione (VIII , Ar = 2,6-dichlorophenyl, n = 3, Z = 1 H-imidazol-1-yl) (93) by reaction of (233) prepared as described in Example 178 with imidazole Found: + H = 505 The preparation of 4- (2,6-dichlorophenyl) -9-hydroxy-6- [3- (4-morpholin-propepyrrolo [3,4-c1carbazole-1.3 (2H.6H-Vdione (VIII, Ar = 2,6-dichlorophenyl, n = 3, Z = 4-morpholinyl) (94) by reaction of (233) prepared as described in Example 178 with morpholine Found: M + H = 524.

The preparation of 4- (2,6-dichlorophenyl) -9-hydroxy-6- [3- (4-methyl-1-piperazinyl) propyl] pyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione,. V ". Ar = 2,6 ~ -dichlorophene, n = 3? = 4-methyl-1-piperazinyl) (95) by reaction of (233) prepared as described in Example 178 with 1-methylpiperazine. Found: M + H = 537.

The preparation of 6- (3-anilinopropyl) -4- (2,6-dichlorophenyl) -9-hydroxypyrrolo [3,4-clcarbazole-1.3 (2H.6HVdione (VIII, Ar = 2,6-chlorophenyl, n = 3, Z = anilino ) (96) by reaction of (233) prepared as described in Example 178 with aniline Found: M + H = 530.

EXAMPLE 199 Combinatorial procedure for displacements of aniline of Br and OMs To a screw capged vial of 8 ml was added a solution of 6 (3-bromopropyl) -4- (chloro-phenyl) -9-hydroxy-6H-pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (reagent A), (0.048 g, 0.1 mmol) prepared as described in example 83 or 2- (9-hydroxy-1,3-dioxo-4-phenyl-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) methanesulfonate. ) -yl) ethyl (205) prepared as described in Example 174 (Reagent B) (See Table 2) in anhydrous dimethylacetamide (1 mL) and a solution of the appropriate aniline (0.012 g, 0.1 mmol) in dimethylacetamide. anhydrous (0.150 ml). The vial was capped and the reaction mixture was stirred for 18 hours at 10 ° C. After cooling to room temperature, the solvent was removed in vacuo. Purification was carried out by reverse phase HPLC (3% n-propanol in acetonitrile and 3% n-propanol in water as eluent, column C-18). The compounds were analyzed by mass spectral analysis.

TABLE 2 Compounds obtained combinatorially by reaction of the appropriate commercial anilines Reagent Product Analytical Data MS- APCI [M + H] + Reagent A 4- (2-Chloro-phenyl) -9-hydroxy-526.2 6- [3- (3-methoxy-phenylamino) -propyl] -6H-pyrrote [ 3,4- c] carbazole-1,3-dione Reagent A 4- (2-Chloro-phenyl) -9-hydroxy-512.3 6- [3- (4-hydroxy-phenylamino) -propyl] -6H-pyrrolo [ 3,4- c] carbazole-1,3-dione Reagent A 4- (2-Chloro-phenyl) -9-hydroxy-564.3 6- [3- (2-trifluoromethyl-phenylamino) -propyl] -6H-pyrrolo [ 3,4-c] carbazole-1,3-dione Reagent A 4- (2-Chloro-phenyl) -6- [3- (4-524.3 ethyl-phenylamino) -propyl] -9- hydroxy-6H-pyrrolo [ 3,4-c] carbazole-1,3-dione • Reagent A-6- [3- (4-Bromo-phenylamino) -. . . 576.2.,. propyl] -4- (2-chloro-phenyl) -9- hydroxy-6H-pyrrolo [3,4-c] carbazole-, 3-dione Reagent A 4- (2-chloro-phenyl) -9-hydroxy-542.3 6- [3- (3-methylsulfanyl-phenylamino) -propyl] -6H-pyrrolo [3,4-c] carbazole-1, 3-dione Reagent A 4- (2-Clo ro-f en il) -9- h id roxy- 512.3 6- [3- (3-hydroxy-phenylamino) -propyl] -6H-pyrrolo [3,4-c] carbazole-1,3-dione Reagent A 6- [3- (3-Bromo- phenylamino) - 574.3 propyl] -4- (2-chloro-phenyl) -9- hydroxy-6H-pyrrolo [3,4-c] carbazole-1,3-dione Reagent A Acid (. {3- 3- [4- (2-chloro-phenyl) -9- 554.3 hydroxy-1,3-dioxo-2,3-dihydro-1 H -pyrrolo [3,4-c] carbazol-6-yl] -propyl.} - phenyl- amino) -acetic Reagent A 4- (2-Chloro-phenyl) -9-hydroxy-6- 536.3 [3- (1 H -indazol-6-ylamino) -propyl] -6H-pyrrolo [3,4- c] ] carbazole-1, 3-dione Reagent A 3-. { 3- [4- (2-Chloro-phenyl) -9- 575.3 hydroxy-1,3-dioxo-2,3-dihydro-1 H -pyrrolo [3,4-c] carbazole-6-yl) - propylamino} - Benzenesulfonamide Reagent A 4- (2-Chloro-phenyl) -6- [3- (3-ethyl-524.3-phenylamino) -propyl] -9-hydroxy-6H-pyrrolo [3,4-c] carbazole-1, 3 - dione Reagent A 6- [3- (1, 3-Benzodioxol-5- 540.3 ylamino) -propyl] -4- (2-chloro-phenyl) -9-hydroxy-6H-pyrrolo [3,4-c] carbazole -1, 3-dione Reagent A 4- (2-Chloro-phenyl) -9-hydroxy-6- 536.3 [3- (1 H -indazolT5-ylamino) -propyl] -6H-pyrrole [3,4-c] carbazole-1, 3-dione Reagent A 4- (2-Chloro-phenyl) -9-hydroxy-6- 535.3 [3- (1 H -indol-5-ylamino) - "propyl] -6H-pyrrolo [3, 4- (c) carbazole-1,3-dione · Reagent A 4- (2-Chloro-phenyl) -6- [3- (1, 1 - 584.3 dioxo-1H-1 $ 1> 6- benzo [b ] thiophen-6-ylamino) -propyl] -9-hydroxy-6H-pyrrolo [3,4-c] carbazole-1, 3- dione Reagent A 4- (2-Chloro-phenyl) -9-hydroxy-6- 536.2 [3- (indane-5-ylamino) -propyl] -6H-pyrrolo [3,4-c] carbazole-1, 3-dione Reagent A Acid (4-. {3- [4- (2-chloro phenyl) -597.3 9-hydroxy-1,3-d-oxo-2,3-dihydro-1 H -pyrrolo [3,4-c] carbazol-6-yl] -propylamino.} benzoylamino) -acetic Reagent A 4- { 3- [4- (2-Chloro-phen il) -9- 638.4 hydroxy-1,3-dioxo-2,3-dihydro-1 H -pyrrolo [3,4-c] carbazol-6-yl] -propylamino} -N- (2- diethylamino-ethyl) -benzamide Reactive A 6- [3- (Benzothiazol-6-ylamino) -553.2 propyl] -4- (2-chloro-phenyl) -9- hydroxy-6H-pyrrolo [3,4- c] carbazole-1,3-dione Reagent A 4- (2-Chloro-phenyl) -9-hydroxy-6- 540.3. { 3 - [(2-hydroxy-ethyl) -phenylamino] -propyl} -6H-pyrrolo [3,4-c] carbazole-1,3-dione Reagent A 4- (2-Chloro-phenyl) -9-hydroxy-6- 564.2 [3- (3-trifluoromethyl-phenylamino) -propyl] -6H- pyrrolo [3,4-c] carbazole-1, 3- dione Reagent A 4- (2-Chloro-phenyl) -9-hydroxy-6- 612.3. { 3- [3- (1, 1, 2,2-tetrafluoro-ethoxy) -phenylamino] -propyl} -6H- pyrrolo [3,4-c] carbazole-1, 3-dione Reagent A Acid 3- (3- { 3- [4- (2-chloro-568.3 phenyl) -9-hydroxy-1, 3 -Dioxo-2,3-dihydro-1 H -pyrrolo [3,4-c] carbazol-6-yl] -propylamino.} - - phenyl) -propionic acid. . ... Reagent A 4- (2-Chloro-phenyl) -9-hydroxy-6- 510.3 [3- (methyl-phenyl-amino) -propyl] -6H-pyrrolo [3,4-c] carbazole-1, 3- dione Reagent B 4- (2-Chloro-phenyl) -9-hydroxy-6- 512.3 [2- (3-methoxy-phenylamino) -ethyl] -6H-pyrrolo [3,4-c] carbazole-1, 3- dione Reagent B 4- (2-Chloro-phenyl) -6- [2- (3-ethyl-510.3-phenylamino) -ethyl] -9-hydroxy-6H-pyrrolo [3,4-c] carbazole-1, 3- dione Reagent B 4- (2-Chloro-phenyl) -9-hydroxy-6- 550.3 [2- (3-trifluoromethyl-phenylamino) -ethyl] -6H-pyrrolo [3,4-c] carbazole-1, 3- dione Reagent B 4- (2-Chloro-phenyl) -9-hydroxy-6- 498.3 [2- (2-hydroxy-phenylamino) -ethyl] -6H-pyrroio [3,4-c] carbazole-1, 3- dione Reagent B 6- [2- (3-Acetyl-phenylamino) -524.3 ethyl] -4- (2-chloro-pheny] -9- hydroxy-6H-pyrroium [3, 4- c] carbazole-1,3-dione Reagent B 4- (2-Chloro-phenyl) -9-hydroxy-6- 512.3 [2- (4-methoxy-phenylamino) -ethyl] -6H-pyrrolo [3 , 4-c] carbazole-1, 3-dione Reagent B 4- (2-Chloro-phenyl) -9-hydroxy-6- 528.2 [2- (2-methylsulfanyl-phenylamino) -ethyl] -6H-pyrrolo [3 , 4-c] carbazole-1, 3-dione Reagent B 6- [2- (Bromo-phenylamino) -ethyl] -562.2 4- (2-chloro-phenyl) -9-hydroxy-6H-pyrrolo [3,4 -c] carbazole-1, 3-dione Reagent B 4- (2-Chloro-phenyl) -9-hydroxy-6,498.3 [2- (4-hydroxy-phenylamino) -ethyl) -6H-pyrrolo [3,4 -c] carbazole-1, 3-dione Reagent B 4- (2-Chloro-phenyl) -6- [2- (4-ethyl-510.3-phenylamino) -ethyl] -9-hydroxy-6H-pyrrolo [3.4rC ] carbazole-L3-dione Reagent B 6- [2- (4-Bromo-phenylamino) -562.1 ethyl] -4- (2-chloro-phenyl) -9- hydroxy-6H-pyrrolo [3,4-c] carbazole-1,3-dione Reagent B 4- (2-Chloro-phenyl) -9-hydroxy-6- 528.2 [2- (3-methylsulfanyl-phenylamino) -ethyl] -6H-pyrrolo [3,4-c] carbazole-1, 3- dione Reagent B 4- (2-Chloro-phenyl) -9-hydroxy-6- 498.3 [2- (3-hydroxy-phenylamino) -ethyl] -6H-pyrrolo [3,4- c] carbazole-1, 3- dione Reagent B 4- (2-Chloro-phenyl) -9-hydroxy-6- 512.2 [3- (2-hydroxy-phenylamino) -propyl] -6H-pyrrolo [3,4- c] carbazole-1,3-dione Reagent B 6- [2- (3-Bromo-phenylamino) -562.2 ethyl] -4- (2-chloro-phenyl) -9- hydroxy-6H-pyrrolo [3,4-c] carbazole-1,3-dione Reagent B 4-. { 2- [4- (2-Chloro-phenyl) -9- 507.3 hydroxy-1,3-dioxo-2,3-dihydro-1 H -pyrrolo [3,4-c] carbazol-6-yl] -ethylamino} -benzonitrile Reagent B Acid (3- { 2- [4- (2-chloro-phenyl) -540.3 9-hydroxy-1,3-dioxo-2,3-dihydro-1 H-pyrrolo [3,4- c] carbazol-6-yl] -ethylamino.} - phenyl) -acetic Reagent B 6- [3- (3-Acetyl-phenylamino) -538.3 propyl] -4- (2-chloro-phenyl) -9-hydroxy -6H-pyrrolo [3,4-c] carbazole-1,3-dione Reagent B 4- (2-C! Gold-phenyl) -9-hydroxy-6- 526.3 [3- (4-methoxy-phenylamino) - propyl] -6H-pyrrolo [3,4- c] carbazole-1,3-dione Reagent B 4- (2-Chloro-phenyl) -9-hydroxy-6,542.2 [3- (2-methylsulfanyl-phenylamino) - propyl] -6H- pyrrolo [3,4-c] carbazole-1, 3-dione Reagent B 6- [3- (2-Bromo-phenylamino) -576.2 ~ propyl] -4- (2-chloro-phenyl) - 9- - | · | - hydroxy-6H-pyrrolo [3,4- c] carbazole-1,3-dione EXAMPLE 200 The preparation of 4- (2-chlorophenyl) -9-hydroxy-6- [3- (methylsulfanyl) proDinDirrolof3.4-c] carbazo! -1.3 (2H.6H) -dione (VIII Ar = 2-chlorophenyl. n = 3. Z = SCH3) (130) A mixture of the bromide (58) (60.0 mg, 0.124 mmol) prepared as described in Example 173 and lithium thiomercaptide (13 mg, 0.2481 mmol) in p-dioxane (5 mL) was heated to reflux for 16 h. An additional 10 mg of LiSMe was added and heating to reflux was continued for a further 9 h. The mixture was diluted with water and extracted with ethyl acetate. The organic layer was dried, the drying agent was removed and the solution was concentrated to dryness to directly give the sulfide (130) (47.1 mg, 84%) which crystallized from ethyl acetate / petroleum ether as an orange powder, pf 218-220 ° C. "1 H NMR d [(CD3) 2 SO] 11.07 (br s, 1 H), 9.39 (br s, 1 H), 8.39 (d, J = 2.4 Hz, 1 H), 7.80 (s, 1 H), 7.61-7.56 (m, 2H), 7.53-7.43 (m, 3H), 7.15 (dd, J = 8.8, 2.4 Hz, 1 H), 4.52 (t, J = 6.9 Hz, 2H), 2.45 (t, J = 7.0 Hz , 2H), 2.01 (m, 2H), 2.00 (s, 3H) .FABMS found [M + H] +: 453.0840, 451.0859.C24H20CIN2O3S requires 453.0854, 451.0883.

EXAMPLE 201 The preparation of 4- (2-chlorophenyl) -9-hydroxy-6- [3- (phenylsulfanyl) propyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione ( VIII; Ar = 2-chlorophenyl, n = 3, Z = SPh) (131) A solution of the bromide (58) (41 mg, 0.085 mmol) prepared as described in example 172, thiophenol (9.5 μ ?, 0.093 mmol) and triethylamine (0.25 ml, 3.40 mmol) in p-dioxane (1.5 ml) it was heated to reflux for 16 h. Water was added and the mixture was extracted with ethyl acetate. The organic layer was dried, the drying agent was removed and the solution was concentrated to dryness to directly give the sulfide (131) (37.2 mg, 85%) which crystallized from ethyl acetate / petroleum ether as an orange powder, pf 229-231 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.06 (br s, 1 H), 9.37 (s, 1 H), 8.37 (d, J = 2.4 Hz, 1 H), 7.76 (s, 1 H), 7.60-7.42 (m, 5H), 7.25-7.19 (m, 4H), 7.16-7.10 (m, 2H), "." 4.57 (t, J = 6. "8 Hz, 2H) ~ 2.98 (m, 2H), 2? 1 (m ~ 2H). ~ _'_" Found: C, 67.36; H, 4.29; N, 5.36. C29H21CIN2SO3. 1 / 4H20 requires C, 67.31; H, 4.19; N, 5.41.

EXAMPLE 202 The preparation of 4- (2-chlorophenyl) -9-hydroxy-6- (3-methoxypropyl) pyrrolo [3,4-c1carbazole-1.3 (2H.6H) -dione (VIII: Ar 2-chlorophenyl) n = 3. Z = OCH3) (132) A solution of the bromide (58) (50 mg, 0.103 mmol) prepared as described in example 172 and sodium methoxide (35.2 mg, 0.65 mmol) in methanol (0.5 ml) and p-dioxane (8 ml) was heated to reflux for 3 h. The solution was acidified with 2 N HCl and extracted with ethyl acetate, the organic layer was dried, the drying agent was removed and the solution was concentrated to dryness and chromatographed on silica. Elution with ethyl acetate gave the anhydride, 4- (2-chlorophenyl) -9-hydroxy-6- (3-methoxypropyl) -1 H-furo [3,4-c] carbazole-1,3 (6H) - Diona in the form of an orange powder. 1H RN d [(CD3) 2SO] 9.57 (a, 1 H), 8.24 (d, J = 2.3 Hz, 1 H), 8.00 (s, 1 H), 7.66-7.61 (m, 2H), 7.58-7.48 (m, 3H), 7.22 (dd, J = 9.0, 2.3 Hz, 1 H), 4.56 (t, J = ¿".7 ?? ', 2H), 3.22 (t, J = 6.0 Hz, 2H), 3.13 (s, 3H), 2.02 (m, 2H) The product was added to molten ammonium acetate (10 g) at 140 ° C and the mixture was heated at this temperature for 3 h, water was added and the resulting precipitate it was filtered off, adsorbed on silica in a THF solution and chromatographed, elution with ethyl acetate / petroleum ether (1: 1) gave (132) (32 mg, 71%) as an orange powder. , mp 260-262 ° C. 1 H NMR d [(CD3) 2 SO] 11.07 (br s, 1H), 9.42 (br s, 1H), 8.39 (d, J = 2.4 Hz, 1H), 7.69 (s, 1H), 7.60-7.44 (m, 5H) , 7.15 (dd, J = 8.8, 2.4 Hz, 1H), 4.49 (t, J = 6.6 Hz, 2H), 3.22 (t, J = 6.0 Hz, 2H), 3.13 (s, 3H), 1.99 (m, 2H). FABMS found [M + H] +: 437.1088, 435.1090. C24H2oCIN204 requires 437.1082, 435.1112.

SCHEME 4 Procedures of Scheme 4 Representative procedure for method 3 of scheme 4 EXAMPLE 203 The preparation of 3- (9-methoxy-1,3-dioxo-4-phenyl-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) propanoic acid (IX; Ar = phenyl; = 2) (2431 Dess-Martin periodinane (1.91 g, 4.5 mmol) was added to a stirred solution of alcohol (202) (1.20 g, 3.0 mmol) prepared as described in Example 83 in dry tetrahydrofuran (80 mL) in a nitrogen atmosphere. After 1 hour at room temperature, a solution of saturated sodium thiosulfate and saturated sodium bicarbonate (1: 1, 1 mL) was added and the reaction mixture was stirred vigorously for 15 minutes before being extracted with ethyl acetate. The organic layer was dried, the drying agent was removed and the solution was concentrated to dryness. Then, the resulting crude aldehyde was dissolved in tert-butanol / tetrahydrofuran (9: 1, 230 ml) and 2-methyl-2-butene (12.0 mmol, 6.0 ml of a 2 M solution in tetrahydrofuran) was added. To this solution was added a solution of sodium chlorite (1.09 g, 12.0 mmol) and sodium dihydrogen phosphate (2.5 g, 18.0 mmol) in water (100 mL) containing tert-butanol (4 mL). The resulting solution was stirred at room temperature for 18 hours before being diluted with brine and extracted with ethyl acetate. The organic layer was dried, the drying agent was removed and the solution was concentrated to dryness. Chromatography on silica eluting with ethyl acetate / methanol (from 1: 0 to 9: 1), followed by crystallization from ethyl acetate / hexane, gave the acid (243) (0.86 g, 69%) as a yellow powder, pf 252-255 ° C. 1 H NMR d [(CD3) 2 SO] 12.2 (s very a, 1 H), 11 .13 (br s, 1 H), 8.55 (d, J = 2.6 Hz, 1 H), 7.89 (s, 1 H), 7.68 (m, 3H), 7.47 (m, 3H), 7.28 (dd, J = 9.0, 2.6 Hz, 1 H), 4.73 (t, J = 6.6 Hz, 2H), 3.90 (s, 3H), 2.76 ( t, J = 6.6 Hz, 2H). Found: C, 67.95; H, 4.37; N, 6.47. C24H18N2O5. 1 / 2H20 requires C, 68.08; H, 4.52; N, 6.62.

EXAMPLE 204 The preparation of 3- (4- (2,6-dichlorophenyl) -9-methoxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) propaneic acid (IX: Ar = 2,6-dichlorophenyl, n = 2) (244) Oxidation of the alcohol (232) prepared as described in Example 86 (0.50 g, 1.1 mmol) according to the procedure described in Example 203, followed by chromatography on silica eluting with methanol / dichloromethane (from 3:97). at 1: 9) and trituration in ethyl acetate / hexane gave the acid (244) (0.35 g, 66%) as a yellow powder, mp. 203-209X.

H NMR d [(CD3) 2 SO] 12.3 (s very a, 1 H), 11.19 (s at, 1 H), 8.50 (d, J = 2.6 Hz, 1 H), 7.94 (s, 1 H), 7.74 ( d, J = 9.0 Hz, 1 H), 7.62 (m, 2H), 7.51 (dd, J = 13.3, 6.1 Hz, 1 H), 7.33 (dd, J = 9.0, 2.6 Hz, 1 H), 4.71 ( t, J = 6.9 Hz, 2H), 3.91 (s, 3H), 2.75 (t, J = 6.9 Hz, 2H). Found: C, 59.74; H, 3.62; N, 5.65. C24H16Cl2N205 requires: C, 59. 63; H, 3.34; N, 5.79.

EXAMPLE 205 The preparation of 3- (4- (2-chloro-6-methoxyphenyl) -9-methoxy-1,3-dioxo-2,3-dihydropyrrolo [3-carbazol-6 (1 H) -yl) propanoic acid (IX: Ar-2) -chloro-6-methoxyphenyl n = 2) (244) Oxidation of the alcohol (105) (2.1 g, 4.5 mmol) prepared as described in Example 58 according to the procedure described in Example 203 gave the acid (245) (0.81 g, 38%) as a , yellow powder, mp 241-243 ° C. 1 H NMR d [(CD3) 2 SO] 12.5 (s very a, 1 H), 1.07 (sa, 1 H), 8.50 (d, J = 2.6 Hz, 1 H), 7.82 (s, 1 H), 7.70 (d, J = 9.0 Hz, 1 H), 7.44 (t, J = 8.3 Hz, 1 H), 7.30 (d, J = 9.0, 2.6 Hz, 1 H), 7.18 (d, J = 8.3 Hz, 1 H), 7.12 (d, J = 8.3 Hz, 1 H), 4.68 (t, J = 6.8 Hz, 2H), 3.90 (s, 3H), 3.68 (s, 3H), 2.71 (t, J = 6.8 Hz , 2H). Found: C, 62.71; H, 4.09; N, 5.62. C25H19CIN206 requires C, 62.70; H, 4.00; N, 5.85.

EXAMPLE 206 The preparation of 3- (4- (2,6-dichlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1H) -yl) propanoic acid (X: Ar-2.6- dichlorophenyl n = 2) (246) Demethylation of acid (244) (90 mg, 0.19 mmol) prepared as described in Example 204 using the procedure described in Example 80 gave phenyl (246) (63 mg, 71%) as an orange powder / yellow, pf 245-253 ° C (dec). 1 H NMR d [(CD3) 2 SO] 12.2 (s very a, 1 H), 1 1.13 (br s, 1 H), 9.40 (br s, 1 H), 8.36 (d, J = 2.5 Hz, 1 H), 7.88 (s, 1 H), 7.62 (m, 3 H), 7.50 (dd, J = 8.7, 7.3 Hz, 1 H), 7.15 (dd, J = 8.9, 2.5 Hz, 1 H), 4.66 (t, J = 6.9 Hz, 1 H), 2.73 (t, J = 6.9 Hz, 2H). Found: C, 58.98; H, 3.31; N, 5.81. C23H14CI2N205 requires: C, 58.85; H, 3.01; N, 5.97.

Representative procedure for method 14 of scheme 4 EXAMPLE 207 The preparation of N- [2- (dimethylamino) ethyl] -3- (9-methoxy-1,3-dioxo-4-phenyl-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) propanamide (XI: Ar = phenyl, n = 2, R3 = H. R4 = CH, CH2N (CHj) z) (247) To a solution of the acid (243) (100 mg, 0.24 mmol) prepared as described in Example 203 in dry tetrahydrofuran (20 mL) under a nitrogen atmosphere was added 1 drop of dimethylformamide, followed by dropwise chloride of oxalyl (84 μ ?, 0.96 mmol). The resulting solution was stirred at room temperature for 2 hours before being reduced to dryness under vacuum. To the residue was added dry benzene (20 ml) and the suspension was reduced again to dryness in vacuo before being dissolved in dry tetrahydrofuran (20 μl) and washed abundantly with nitrogen. To this solution, dimethylethylenediamine (105 ml, 0.96 mmol) was added via syringe. The reaction mixture was stirred at room temperature for 2 hours and then diluted with water, basified by the addition of solid potassium carbonate and extracted with ethyl acetate. The organic layer was dried, the drying agent was removed and the solution was concentrated to dryness. Chromatography on silica eluting with ethyl acetate / methanol / triethylamine (from 1: 0: 0 to 3: 1: traces) followed by crystallization from ethyl acetate / hexane gave the amide (247) (85 mg, 73%) in the form of a yellow powder, mp 206-21 0 ° C. 1H RN d [(CD3) 2SO] 1 1.11 (sa, 1 H), 8.54 (d, J = 2.6 Hz, 1 H), 7.81 (s, 1 H), 7.73 (t, J = 5.6 Hz, 1 H ), 7.67 (m, 3H), 7.48 (m, 3H), 7.29 (dd, J = 8.9, 2.6 Hz, 1 H), 4.73 (t, J = 6.3 Hz, 2H), 3.89 (s, 3H), 2.93 (dd, J = 6.8, 5.6 Hz, 2H), 2.59 (t, J = 6.3 Hz, 2H), 1.90 (s, 6H), 1.84 (t, J = 6.8 Hz, 2H). Found: C, 67.02; H, 5.80; N, 11.17. C28H28N4O4. H20 requires: C, 66.92; H, 6.02; N, 1 1.14.

EXAMPLE 208 The preparation of 3- (9-methoxy-1,3-dioxo-4-phenyl-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1H) -yl) propanamide (XI: Ar = phenyl- n = 2, R3 = H. R4 = H) (248) The reaction of acid (243) (100 mg, 0.24 mmol) prepared as described in Example 203 according to the procedure described in Example 207, except that a saturated solution of ammonia gas in tetrahydrofuran ( 20 ml), such as the amine, gave the amide (248) (61 mg, 62%) as a white powder, mp. 266-270 ° C. 1 H NMR d [(CD 3) 2 SO] 11.1 1 (br s, 1 H), 8.55 (d, J = 2.6 Hz, 1 H), 7.87 (s, 1 H), 7.68 (m, 3 H), 7.48 (m, 3H), 7.33 (sa, 1 H), 7.29 (dd, J = 9.0, 2.6 Hz, 1 H), 6.85 (sa, 1 H), 4.71 (t, J = 6.5 Hz, 2H), 3.90 (s, 3H), 2.60 (t, J = 6.5 Hz, 2H).

Found: C, 68.36; H, 4.70; N, 9.99. C24H19N3C. 1 / 2H20 requires: C, 68.24; H, 4.78; N, 9.94.

EXAMPLE 209 The preparation of 3- (4- (2-chlorophen-N) -9-methoxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) -N-r 2 - (dimethylamino) ethyl] propanamide (XI: Ar = 2-chlorophenyl) n = 2. R3 = H. R4 = CH2CH N (CH3) 2 (249) The reaction of the acid (16) (95 mg, 0.21 mmol) prepared as described in Example 229 according to the procedure described in Example 207, followed by trituration in diethyl ether gave the amide (249) (76 mg, 70%) in the form of a yellow powder, mp 250-252 ° C. H NMR d [(CD3) 2 SO] 1 1 .12 (br s, 1 H), 8.51 (d, J = 2.6 Hz, 1 H), 7.77 (s, 1 H), 7.76 (t partially obscured, J = 5.9 Hz, 1 H), 7.68 (d, J = 9.0 Hz, 1 H), 7.58 (m, 2H), 7.48 (m, 3H), 7.32 (dd, J = 9.0, 2.6 Hz, 1 H), 4.71 ( t, J = 6.4 Hz, 2H), 3.90 (s, 3H), 2.95 (m, 2H), 2.58 (t, J = 6.4 Hz, 2H), 1.94 (s, 6H), 1.93 (t partially obscured, J = 6.8 Hz, 2H); Found: C, 64.88; H, 5.56; N, 10.70. C28H27CIN4CU requires: C, 64.79; H, 5.24; N, 10.79.

EXAMPLE 210 The preparation of 3- (4- (2,6-dichlorophenyl) -9-methoxy-1-3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1H) -yl) propanamide (XI Ar = 2.6- dichlorophenyl, n = 2. R3 = H. R4 = H) (250) The reaction of acid (244) (0.23 g, 0.48 mmol) prepared as described in example 204 according to the procedure described in example 207, with the exception that concentrated ammonia (-30%, 20 ml) was added. ) as the amine, gave the amide (250) (0.17 g, 73%) in the form of a yellow powder, mp. 261-264 ° C. 1 H NMR d [(CD3) 2 SO] 1 1 .19 (br, 1 H), 8.50 (d, J = 2.6 Hz, 1 H), 7.87 (s, 1 H), 7.73 (d, J = 9.0 Hz, 1 H), 7.63 (m, 2H), 7.52 (dd, J = 8.8, 7.3 Hz, 1 H), 7.38 (sa, 1 H), 7.33 (dd, J = 9.0, 2.6 Hz, 1 H), 6.87 (sa, 1 H), 4.68 (t, J = 6.7 Hz, 2H), 3.91 (s, 3H), 2.57 (t, J = 6.7 Hz, 2H). Found: C, 59.55; H, Í79; ^, "8.737 C24H17CI2N3O4 requires: C, 59.75; H, 3.55; N, 8.71.

EXAMPLE 211 The preparation of 3- (4- (2,6-dichlorophenyl) -9-methoxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -ihN- 2- (dimethylamido) ethyl] propanamide (XI: Ar = 2,6-dichlorophenyl n = 2. R3 = H. R4 = CH CH2N (CH3)) (251) The reaction of the acid (244) (150 mg, 0.30 mmol) prepared as described in Example 204 according to the procedure described in Example 207, gave the amide (251) (91 mg, 55%) as a a yellow powder, mp 141-146 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.19 (s a, 1 H), 8.50 (d, J = 2.6 Hz, 1 H), 7. 82 (s, 1 H), 7.81 (t partially obscured, J = 5.6 Hz, 1 H), 7.69 (d, J = 9.0 Hz, 1 H), 7.62 (m, 2H), 7.52 (dd, J = 8.8 , 7.4 Hz, 1 H), 7.34 (dd, J = 9.0, 2.6 Hz, 1 H), 4.71 (t, J = 6.4 Hz, 2 H), 3.90 (s, 3 H), 2.95 (c, J = 6.2 Hz , 2H), 2.58 (t, J = 6.4 Hz, 2H), 2.07 (m, 2H), 2.02 (s, 6H). Found: C, 59.13; H, 4.73; N, 9.87. 028? 26? 2? 4? 4. H20 requires C, 58.85; H, 4.94; N, 9.80.

EXAMPLE 212 The preparation of 3- (4- (2-chloro-6-methoxyphenyl) -9-methoxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) -N- [ 2- (dimethylamino) ethyl] propanamide (XI, Ar = 2-chloro-6-methoxyphenyl, n = 2. R3 = H. R4 = CH2CH2N (CH3) 2) (252) The reaction of the acid (245) prepared as described in Example 205 (160 mg, 0.33 mmol) according to the procedure described in Example 207 gave the amide (252) (93 mg, 51%) as a yellow powder, pf 164-169 ° C. H NMR d [(CD3) 2 SO] 1 1.06 (br s, 1 H), 8.50 (d, J = 2.6 Hz, 1H), 7.80 (t, J = 5.6 Hz, 1 H), 7.72 (s, 1 H) , 7.66 (d, J = 9.0 Hz, 1 H), 7.45 (t, J = 8.3 Hz, 1 H), 7.30 (d, J = 9.0, 2.6 Hz, 1 H), 7.18 (d, J = 8.3 Hz , 1 H), 7.13 (d, J = 8.3 Hz, 1 H), 4.68 (t, J = 6.4 Hz, 2H), 3.90 (s, 3H), 3.68 (s, 3H), 2.98 (dd, J = 6.6, 5.6 Hz, 2H), 2.56 (t, J = 6.4 Hz, 2H), 2.05 (t, J = 6.6 ~ Hz, 2H), 1.90 (s, 6H). ~ "" * Found: C, 61.32; H, 5.28; N, 9.91. C29H29CIN4O5. H20 requires: C, 61.43; H, 5.51; N, 9.88.

EXAMPLE 213 The preparation of 3- (4- (2-chlorophenyl) -9-methoxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1H) -yl) -N- (1 H-tetrazole) 5-yl) propanamide (XI; Ar 2-chlorophenyl, n = 2. R 3 = H. R 4 = 5-tetrazolyl) (253) The reaction of acid (116) (70 mg, 0.16 mmol) prepared as described in example 229 according to the procedure described in example 207, with the exception that solid 5-aminotetrazole (27 mg, 0.31) was added. mmoles) as the amine and the reaction was heated to reflux for 2 hours before the treatment, gave the amide (253) (52 mg, 63%) as a yellow powder, mp. 232 ° C (dec). 1H RN d [(CD3) 2SO] 15.8 (s very a, 1 H), 1.90 (sa, 1 H), 11.13 (sa, 1 H), 8.52 (d, J = 2.6 Hz, 1 H), 7.84 (s, 1 H), 7.75 (d, J = 9.0 Hz, 1 H), 7.57 (d, J = 7.4 Hz, 1 H), 7.50-7.40 (m, 3H), 7.30 (dd, J = 9.0, 2.6 Hz, 1 H), 4.83 (t, J = 6.8 _ _Hz, 2H), 3.90 (s, 3H), 2.97 (t, J = 6.8 Hz, 2H). _ _ - - FABMS found [M = H] + = 516.1174, 518.1 154. C25Hi8CIN704 requires 516.1 187, 518.1 158.

EXAMPLE 214 The preparation of N- [2- (dimethylamino) ethyll-3- (9-hydroxy-1,3-dioxo-4-phenyl-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) propanamide (XIII: Ar = phenyl.

Reaction of the methyl ether (247) (70 mg, 0.14 mmol) prepared as described in Example 207 according to the procedure described in Example 81, except that the reaction mixture was diluted with water, basified by adding concentrated ammonia and extracting with ethyl acetate. The organic layer was dried, the drying agent was removed and the solution was concentrated to dryness. Chromatography on silica eluting with ethyl acetate / methanol / triethylamine (from 1: 0: 0 to 3: 1: traces). Crystallization from ethyl acetate / hexane then gave the amide (254) (35 mg, 53%) as an orange powder, m.p. 176-180 ° C. _ "- - - - | i H pMN § ~ [(CD3) 2SÓ] 1 106 (sa, 1 H)," 9.35 (s ~ a, 1 H), "8.39 (d, J = 2.5 Hz, 1 H ), 7.77 (s, 1 H), 7.74 (t, J = 5.6 Hz, 1 H), 7.66 (m, 2H), 7.53 (d, J = 8.8 Hz, 1 H), 7.48 (m, 3H), 7.12 (dd, J = 8.8, 2.5 Hz, 1 H), 4.69 (t, J = 6.4 Hz, 2H), 2.94 (m, 2H), 2.58 (t, J = 6.4 Hz, 2H), 1.91 (s, 6H), 1.87 (m, 2H) Found: C, 66.87; H, 5.83; N, 1 1.47, C27H26N404.3 / 4H20 requires: C, 67.00; H, 5.73; N, 1.57.

EXAMPLE 215 The preparation of 3- (9-hydroxy-1,3-dioxo-4-phenyl-2,3-dihydropyrrolof3.4-c] carbazole-6 (1 H) -yl) propanamide (XIII: Ar = phenyl, n = 2. Ri = H. R? = H) (255) v 3- (9-hydroxy-1,3-dioxo-4-phenyl-2,3-dihydropyrrolor3.4-c] carba2ol-6 (1H) -yl) propanoic acid (X: Ar = phenyl- n = 2) (259 The reaction of methyl ether (248) (56 mg, 0.14 mmol) prepared as described in Example 208 according to the procedure described in Example 81, followed by chromatography on silica eluting with ethyl acetate / hexane (41 ) to ethyl acetate / methanol (91) initially gave the amide (255) (11 mg, 20%) as an orange powder, mp. 284-288 ° C. H NMR d [(CD3) 2 SO] 1 1.05 (br s, 1 H), 9.33 (br s, 1 H), 8.40 (d, J = 2.5 Hz, H), 7.82 (s, 1 H), 7.67 (m, 2H), 7.56 (d, J = 8.8 Hz, 1 H), 7.47 (m, 3H), 7 34 (sa, 1 H), 7.12 (dd, J = 8.8, 2.5 Hz, 1 H), 6.86 (s) , 1 H), 4.67 (t, J = 6.5 Hz, 2H), 2.58 (t, J = 6.5 Hz, 2H). FAB S found [M + H] +: 400.1307. C23H17 3O4 requires 400. 1297. This was followed, at a lower Rf value, by the acid (256) (34 mg, 63%) in the form of an orange powder, m.p. 300-31 0 ° C (dec). 1 H NMR d [(CD3) 2 SO] 12.1 (s very a, 1 H), 1.06 (sa, 1 H), 9. 34 (sa, 1 H), 8.40 (d, J = 2.4 Hz, 1 H) , 7.84 (s, 1 H), 7.67 (m, 2H), 7.57 (d, J = 8.8 Hz, 1 H), 7.46 (m, 3H), 7.12 (dd, J = 8.8, 2.4 Hz, 1 H) , 4.69 (t, J = 6.7 Hz, 2H), 2.75 (t, J = 6.7 Hz, 2H). Found: C, 67.64; H, 4.29; N, 6.65. C23H16N2O5. 1 / 2H20 requires: C, 67.48; H, 4.19; N, 6.84.

EXAMPLE 216 The preparation of 3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1H) -yl) -N- [2- (dimethylamino) ethyl] propanamide (XIII: Ar-2-chlorophenyl) n = 2. R3 = H. R4 = CH? CH? N (CH3) 2) (257) Reaction of the methyl ether (249) (65 mg, 0.13 mmol) prepared as described in Example 209 according to the procedure described in Example 81, with the exception that the reaction mixture was diluted with water was basified by The concentrated ammonia was added and extracted with ethyl acetate. The organic layer was dried, the drying agent was removed and the solution was concentrated to dryness. Chromatography on silica eluting with ethyl acetate / methanol / ethylamine (from 1: 0: 0 to 3: 1: traces). Crystallization from ethyl acetate / hexane (257) (28 mg, 44%) then gave the amide (257) (28 mg, 44%) as an orange powder, m.p. 205-215 ° C. H NMR d [(CD3) 2 SO] 1 1.06 (br s, 1 H), 9.35 (s, 1 H), 8.37 (d, J = 2.3 Hz, 1 H), 7.81 (br s, 1 H), 7.72 (s) , 1 H), 7.57 (m, 2H), 7.48 (m, 3H), 7.14 (dd, J = 8.9, 2.3 Hz, 1 H), 4.67 (t, J = 6.4 Hz, 2H), 2.99 (m, 2H), 2.57 (t, J = 6.4 Hz, 2H), 2.03 (m, 8H). Found: C, 61.32; H, 5.49; N, 10.72. C27H25CIN4C .I Y4H2O requires: C, 61.47; H, 5.26; N, 10.62.

EXAMPLE 217 The preparation of 3- (4- (2,6-dichlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-clcarbazole-6 (1 H) -yl) propanamide (XIII: Ar = 2,6-dichlorophenyl. n = 2. R3 = H. R4 = \ (258) The reaction of methyl ether (250) (80 mg, 0.17 mmol) prepared as described in Example 210 according to the procedure described in Example 80 followed by chromatography on silica eluting with ethyl acetate and then with tetrahydrofuran and then by trituration in ethyl acetate gave the amide (258) (47 mg, 59%) as an orange powder, mp. 327-329 ° C. 1 H NMR d [(CD3) 2 SO] 1 1 .12 (br s, 1 H), 9.39 (s, 1 H), 8.36 (d, J = 2.4 Hz, 1 H), 7.82 (s, 1 H), 7.61 (m, 3H), 7.51 (dd, J = 8.8, 7.4 Hz, 1 H), 7.38 (sa, 1 H), 7.15 (dd, J = 8.9, 2.4 Hz, 1 H), 6.87 (sa, 1 H) ), 4.65 (t, J = 6.7 Hz, 2H), 2.55 (t, J = 6.7 Hz, 2H). Found: C, 57.75; H, 3.83; N, 8.50. 3 / 4H20 requires: C, 57.33; H, 3.45; N, 8.72.

EXAMPLE 218 The preparation of 3- (4- (2,6-dichlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolof3.4-clcarbazole-6 (1 H) -yl) -N-f2- (dimethylamino) ethyl] propanamide (XIII: Ar = 2,6-dichlorophenyl, n = 2. R3 = H. R4 CHZCH2N (CH3) 2) (259) The reaction of the methyl ether (251) (70 mg, 0.13 mmol) prepared as described in Example 211 according to the procedure described in Example 80, with the exception that the reaction time was 6 hours and chromatography was performed eluting with ethyl acetate / methanol / triethylamine (from 1: 0: 0 to 3: 1: traces) gave the amide (259) (31 mg, 45%) in the form of a yellow powder, mp 220-226 ° C. 1 H NMR d [(CD 3) 2 SO] 1 1.13 (br s, 1 H), 9.39 (s, 1 H), 8.36 (d, J = 2.5 Hz, 1 H), 7.84 (t, J = 5.4 Hz, 1 H ), 7.76 (s, 1 H), 7.62 (m, 2H), 7.58 (d, J = 8.9 Hz, 1 H), 7.51 (dd, J = 8.9, 7.4 Hz, 1 H), 7.16 (dd, J = 8.9, 2.5 Hz, 1 H), 4.67 (t, J = 6.5 Hz, 2H), 3.03 (m, 2H), 2.57 (t, J = 6.5 Hz, 2H), 2.16 (sa, 2H) ), 2.08 (m, 6H). Found: C, 58.09; H, 4.44; N, 9.72. C27H24CI2N4O4. H20 requires: C, 58.18; H, 4.70; N, 10.05.

EXAMPLE 219 The preparation of 3- (4. (2-chloro-6-methoxyphenyl) -9-hydroxy-1,3-dioxo-2,3-dihydro-DRLR3.4-c1carbazole-6 (1 H) -yl) -N- [ 2- (dimethylamino) ethyl] propanamide (XIII; Ar = 2-chloro-6-methoxyphenyl) n = 2. R3 = H. R4 = CH? CH, N (CH ^) (260) The reaction of the methyl ether (252) prepared as described in Example 212 (80 mg, 0.15 mmol) according to the procedure described in Example 80, with the exception that the reaction was carried out at 0 ° C for 2 hours. hours and chromatography was carried out eluting with ethyl acetate / methanol / triethylamine (from 1: 0: 0 to 3: 1: traces) gave the amide (260) (65 mg, 83%) as a yellow / orange powder , pf 200-205 ° C. 1 H NMR d [(CD 3) 2 SO] 1 1.00 (br s, 1 H), 9.34 (s, 1 H), 8.36 (d, J = 2.4 Hz, 1 H), 7.87 (br s, 1 H), 7.66 (s) , 1 H), 7.54 (d, J = 8.9 Hz, 1 H), 7.44 (t, J = 8.2 Hz, 1 H), 7.18 (dd, J = 8.2, 0.7 Hz, 1 H), 7.12 (m , 2H), 4.64 (t, J = 6.6 Hz, 2H), 3.68 (s, 3H), 3.05 (m, 2H), 2.56 (t, J = 6.6 Hz, 2H), 2.23 (s very a, 2H) , 2.15 (sa, 6H). Found: C, 58.98; H, 5.12; N, 9.59. C28H27CI N4O5. 2H20 requires: C, 58.90; H, 5.47; N, 9.81.

EXAMPLE 220 The preparation of N- [2- (dimethylamino) ethyl] -3- (9-hydroxy-4- (2-methoxyphenyl) -1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -il) propanamide (XIII, Ar = 2-methoxyphenyl, n = 2. R3 = H. R4 = CH2CH2N (CH,)) (330) To a solution of the amide (260) (40 mg, 0.07 mmol) prepared as described in example 219 in ethyl acetate / methanol (1: 1, 80 ml) was added 5% Pd-C (catalytic ). The resulting suspension was hydrogenated at 60 psi (413,685 kPa) with stirring for 4 days, adding more portions of Pd-C every 24 hours. Then, the reaction mixture was filtered through celite and concentrated under reduced pressure before being chromatographed on silica eluting with methanol / ethyl acetate / triethylamine (1: 4: traces), to give the amide (330) (6 mg , 16%) in the form of a yellow powder, mp 232-238 ° C. _ ~~~~ 1H NMR d [(CD3) 2SO] 10.95 (s a, 1 H), 9.33 (s a.'l H), 8.37 (d, J = 2.4 Hz, 1 H), 8.01 (sa, 1 H), 7.69 (s, 1 H), 7.54 (d, J = 8.9 Hz, 1 H), 7.43 (m, 1 H), 7.34 (dd, J = 7.5, 1 .8 Hz, 1 H), 7.13-7.05 (m, 3H), 4.67 (t, J = 6.2 Hz, 2H), 3.69 (s, 3H), 3.2 (m obscured, 2H), 2.60 (t, J = 6.2 Hz, 2H), 2.54-2.49 (m obscured, 8H). FABMS found [M + H] +: 501.2142. C28H28N4O5 requires 501 .2138.

EXAMPLE 221 The preparation of 3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrolo [3,4-c] carbazole-6 (1 H) -yl) N- (1 H-tetra2ol-5-yl) propanamide (XIII: Ar = 2-chlorophenyl, n = 2. R3 = H. R4 = 5-tetrazolyl) (261) The reaction of methyl ether (253) (40 mg, 0.08 mmol) prepared as described in Example 213 according to the procedure described in Example 80, except that the chromatography was performed eluting with ethyl acetate / methanol (from 1: 0 to 9: 1), gave the amide (261) (11 mg, 27%) as an orange powder, mp 283 ° C (dec). 1 H NMR d [(CD 3) 2 SO] 15.82 (br s, 1 H), 12.03 (br s, 1 H), 11.08 (s, 1 H), 9.38 (s, 1 H), 8.37 (d, J = 2.3 Hz, 1 H), 7.79 (s, 1 H), 7.62 (d, J = 8.8 Hz, 1 H), 7.56 (d, J = 7.6 Hz, 1 H), 7.49-7.38 (m, 3H), 7.13 (dd) , J = 8.8, 2.3 Hz, 1 H), 4.80 (t, J = 6.7 Hz, 2H), 2.96_ (t, J = 6.7 Hz, 2H). .1"V FABMS found M +: 501.0955, 503.0956. C24H16CIN7O4 requires 501.0952, 503.0923.

Representative procedure for method 15 of scheme 4 EXAMPLE 222 The preparation of N- [3- (4-2-chlorophenyl) -9-methoxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1H) -yl) propanoyl] methanesulfonamide (XII: Ar = 2-3-chlorophenyl, n = 2. R3 = CH) (265) To a stirred solution of the acid (16) (0.20 g, 0.45 mmol) prepared as described in Example 229, 4-dimethylaminopyridine (DMAP) (165 mg, 1.35 mmol) and methanesulfonamide (86 mg, 0.90 mmol) in dimethylformamide (10 ml) under a nitrogen atmosphere was added 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDCI HCl) (259 mg, 1.35 mmol). The resulting mixture was stirred at room temperature for 18 hours and then diluted with water, acidified by the addition of 1N hydrochloric acid and extracted with ethyl acetate. The organic phase was dried, the drying agent was removed and the solution was concentrated to dryness. Chromatography on silica eluting with ethyl acetate / hexane (41) to ethyl acetate / methanol (from 1: 9 to 9: 1) gave the acylsulfonamide (265) (151 mg, 64%) as a yellow powder, pf 293-295 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.76 (br s, 1 H), 11.14 (br s, 1 H), 8.52 (d, J = 2.6 Hz, 1 H), 7.87 (s, 1 H), 7.73 (d, J = 9.0 Hz, 1 H), 7.58 (m, 1 H), 7.53-7.46 (m, 3H), 7.32 (dd) , J = 9.0, 2.6 Hz, 1 H), 4.74 (t, J = 6.9 Hz, 2H), 3.91 (s, 3H), 3.08 (s, 3H), 2.81 (t, J = 6.9 Hz, 2H).

Found: C, 57.30; H, 3.87; N, 7.72. C25H20CIN3O6S requires: C, 57.08; H, 3.83; N, 7.99.

EXAMPLE 223 The preparation of N- [3- (4- (2-Chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) propanoyl] benzenesulfonamide (XIV) Ar = 2-chlorophenyl n = 2. R3 = Ph) (266) The reaction of the acid (16) (70 mg, 0.16 mmol) prepared as described in Example 229 with benzenesulfonamide according to the procedure described in Example 222 followed by demethylation using the procedure described in Example 80 and the chromatography on silica eluting with ethyl acetate / hexane (from 1: 1 to 31) gave the acylsulfonamide (266) (63 mg, 70%) as an orange powder, mp 291-293 ° "C. ~" "1H NMR 6 [(CD3) 2SO] 12.15 (sa, 1 H), 11.07 (s at, 1 H), 9.36 (s, 1 H), 8.35 (d, J = 2.4 Hz, 1 H), 7.81 (m, 2H), 7.76 (s, H), 7.65 (m, 1 H), 7.57-7.46 (m, 7H), 7.06 (dd, J = 8.9, 2.4 Hz, 1 H ), 4.59 (m, 2H), 2.75 (t, J = 7.1 Hz, 2H) Found: C, 60.62; H, 3.80; N, 7.20, C29H20CIN3O6S requires C, 60.68; H, 3.51; N, 7.32.

EXAMPLE 224 The preparation of N- [3- (4- (2-chloro-phenin-9-methoxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1H) -yl) propane] - 2- (dimethylamino) ethanesulfonamide (XII, Ar = 2-chlorophenyl, n = 2. R3 = CH2CH2 (CH3) 2) (267) Reaction of acid (116) (70 mg, 0.16 mmol) prepared as described in Example 229 with 2- (dimethylamino) ethanesulfonamide according to the procedure described in Example 222, except that the reaction mixture diluted with brine before extracting with ethyl acetate. The organic phase was dried, the drying agent was removed, the solution was concentrated to dryness and chromatography was carried out eluting with ethyl acetate / methanol (from 1: 0 to 4: 1), giving the acyl sulfonamide (267) (43 mg , 47%) in the form of a yellow powder, mp 208-213 ° C. "* 1 H NMR d (CD3) 2SO] 1 1 .1 1 (s a, 1 H j, 8.52 (d, J = 2.6 Hz ~ 1 H), 7. 80 (s, 1 H), 7.72 (d, J = 9.0 Hz, 1 H), 7.57 (m, 2H), 7.47 (m, 2H), 7.31 (dd, J = 9.0, 2.6 Hz, 1 H), 4.68 (m, 2H), 3.90 (s, 3H), 3.23 (m partially obscured, 2H), 2.87 (t, J = 6.9 Hz, 2H), 2.62 (t, J = 6.8 Hz, 2H), 2.43 (s) , 6H). Found: C, 59.44; H, 5.57; N, 8.52. C28H27CIN406S. 1 / 2C6H14 requires: C, 59.47; H, 5.47; N, 8.95.

EXAMPLE 225 The preparation of N- [4- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) butanoyl] methanesulfonamide (XIV: Ar = 2-chlorophenyl, n = 2. R3 = CH3) (268) The reaction of acid (262) (50 mg, 0.1 1 mmol) prepared as described in example 87 according to the procedure described in example 222 followed by demethylation using the procedure described in example 80 and chromatography on silica eluting with ethyl acetate / hexane (from 1: 1 to 3: 1) gave the acyl sulfonamide (268) (29 mg, 51%) as an orange powder, mp. 257-260 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.66 (br s, 1 H), 1.06 (sa, 1 H), 9.37 (s, 1 H), 8.38 (d, J = 2.4 Hz, 1 H), 7.79 ( s, 1 H), 7.61 -7.45 (m, 5H), 7.15 (dd, J = 8.8, 2.4 Hz, 1 H), 4.45 (t, J = 7.2 Hz, 2H), 3.10 (s, 3H), 2.32 (m, 2H), 1.97 (m, 2H). ... _ Found: C, 57.40; H, 3.94; N, 7.73. C25H20CIN3O6S requires:. . . C, 57.09; H, 3.83; N, 7.99.

EXAMPLE 226 The preparation of N-f4- (4- (2-chlorophenyl) -9-hydroxy-1,3-d-oxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) butanoyl] benzenesulfonamide ( XIV: Ar 2-chlorophenyl n = 3. R3 = Ph) (269) The reaction of acid (262) (45 mg, 0.10 mmol) prepared as described in Example 87 with benzenesulfonamide according to the procedure described in Example 222 followed by demethylation using the procedure described in Example 80 and chromatography on silica eluting with ethyl acetate / hexane (from 1: 1 to 3:19) gave the acylsulfonamide (269) (39 mg, 68%) as an orange powder, mp 224-230 ° C. 1 H NMR d [(CD 3) 2 SO] 12.09 (br s, 1 H), 1.05 (sa, 1 H), 9.36 (s, 1 H), 8.36 (d, J = 2.4 Hz, 1 H), 7.88 (m , 2H), 7.73 (s, 1 H), 7.67 (m, 1 H), 7.57 (m, 3H), 7.52-7.43 (m, 4H), 7.09 (dd, J = 8.8, 2.4 Hz, 1 H), 4.33 (t, = 7.3Hz, 2H) ,. _ 2.29 (t, J = 7.2 Hz, 2H), 1.86 (m, 2H). Found: C, 61.10; H, 3.81; N, 6.91. C30H22CI N3O6S requires: C, 61.28; H, 3.77; N, 7.15.

EXAMPLE 227 The preparation of N-r3- (4- (2-chlorophenyl-9-hydroxy-1,3-dioxo-2,3-dihydropyrrolor3,4-c1carbazol-6 (1 H) -yl) propanoyl] methanesulfonamide (XIV; Ar = 2 -chlorophenyl, n = 2. R3 = CH3) (270) The reaction of the methyl ether (265) (130 mg, 0.25 mmol) prepared according to Example 222, according to the procedure described in Example 80, with the exception that the chromatography was performed eluting with methanol / dichloromethane (from 5:95 to 1: 9), gave the acyl sulfonamide (270) (83 mg, 66%) as an orange powder, mp. 290-296 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.75 (br s, 1 H), 11.08 (br s, 1 H), 9.38 (s, 1 H), 8.38 (d, J = 2.4 Hz, 1 H), 7.80 (s) , 1 H), 7.59 (m, 2H), 7.53-7.46 (m, 3H), 7.14 (dd, J = 8.9, 2.4 Hz, 1 H), 4.69 (t, J = 6.9 Hz, 2H), 3.04 ( s, 3H), 2.76 (t, J = 6.9 Hz, 2H). ~ 7 ~ Found: C, 54.70; H, 3.81j N, 7.67. 3 / 4H20: requires: C, 54.85; H, 3.74; N, 7.99.

EXAMPLE 228 The preparation of N- [3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) propanoyl] - 2- (dimethylamino) ethanesulfonamide (XIV; Ar = 2-chlorophenyl) n = 2. R3 = CH2CH2N (CH-,),) (271) Reaction of the methyl ether (267) (35 mg, 0.06 mmol) prepared as described in Example 224 according to the procedure described in Example 81, except that the reaction mixture was diluted with saturated sodium bicarbonate and it was extracted with ethyl acetate. The organic phase was dried, the drying agent was removed and the solution was concentrated to dryness. Chromatography on silica eluting with methanol / dichloromethane (from 1: 9 to 1: 3) gave the acylsulfonamide (271) (8 mg, 23%) as an orange powder, m.p. 229-233 ° C. .... .. . . 1 H NMR d [(CD3) 2 SO] 1 1.05 (s a, 1 H), 9.37 (s a, 1 H), 8.37 (d, J = 2.5 Hz, 1 H), 7.74 (s, 1 H), 7.61 -7.52 (m, 3H), 7.50-7.43 (m, 2H), 7.14 (dd, J = 8.7, 2.5 Hz, 1 H), 4.63 (m, 2H), 3.21 (m partially obscured, 2H), 2.81 (m, 2H), 2.59 (t, J = 6.8 Hz, 2H), 2.38 (s, 6H). FABMS found [M + H] +: 569.1255, 571.1204. C27H25CIN406S requires 569.1262, 571 .1232.

EXAMPLE 229 The preparation of 3- (4- (2-chlorophenyl) -9-methoxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) propanoic acid (IX; Ar = 2 -chlorophenyl n = 2) (116) Oxidation of the alcohol (31) prepared as described in Example 40 using the procedure described in Example 203 gave acid (116) (62%) as a yellow solid, m.p. 277 ° C. 1 H NMR d [(CD 3) 2 SO] 12.61 (br s, 1 H), 1 1.12 (s, 1 H), 8.52 (d, J = 2.6 Hz, 1 H), 7.86 (s, 1 H), 7.73 (d , J = 9.0 Hz, 1 H), 7.58 (m, 1 H), 7.54-7.44 (m, 3H), 7.31 (d, J = 9.0, 2.6 Hz, 1 H), 4.71 (t, J = 6.8 Hz , 2H), 3.93 (s, 3H), 2.80 (t, J = 6.8 Hz, 2H). Found: C, 62.90; H, 3.79; N, 5.93. C24H17CIN2O5. 1 / 2H20 requires C, 62.96; H, 3.96; N, 6.12.

EXAMPLE 230 The preparation of 3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c1carbazol-6 (1 H) -yl) propanoic acid (X: Ar = 2-chlorophenyl) n = 2) (117) The demethylation of (16) prepared as described in Example 229 with pyridinium hydrochloride using the procedure described in Example 81 gave (17) (50%) as a yellow powder, m.p. 286 ° C. 1H RN d [(CD3) 2SO] 12.40 (a, 1 H), 11.06 (sa, 1 H), 9.37 (sa, 1 H), 8.37 (d, J = 2.4 Hz, 1 H), 7.81 (s, 1 H), 7.59 (d, J = 8.7 Hz, 1 H), 7.57 (m, 1 H), 7.53-7.43 (m, 3 H), 7.13 (dd, J = 8.7, 2.4 Hz, 1 H), 4.67 (t, J = 6.8 Hz, 2H), 2.74 (t, J = 6.8 Hz, 2H). Found: C, 60.00; H, 3.65; N, 5.52. C23H15CIN2O5. 1.5H20 requires C, 59.81; H, 3.92; N, 6.06.

EXAMPLE 231 The preparation of 3- (4- (2-chlorophenyl) -9-methoxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1H) - 'yl) propanamide (XI: Ar = 2-chlorophenyl, n = 2. R3 = R4 = H) (118) The reaction of the acid (17) prepared as described in Example 230 with oxalyl chloride followed by ammonia using the procedure described, in Example 207 gave the amide (118). (78%) as a yellow powder , pf 283-286 ° C. 1 H NMR d [(CD3) 2 SO] 11.12 (br s, 1 H), 8.52 (d, J = 2.6 Hz, 1 H), 7.82 (s, 1 H), 7.71 (d, J = 9.0 Hz, 1 H) , 7.58 (m, 1 H), 7.54-7.44 (m, 3H), 7.35 (a, 1 H), 7.31 (dd, J = 9.0, 2.6 Hz, 1 H), 6.86 (a, 1 H), 4.69 (t, J = 6.6 Hz, 2H), 3.90 (s, 3H), 2.58 (t, J = 6.6 Hz, 2H). Found: C, 63.52; H, 4.22; N, 9.04. C24H18CIN304. 1 / 4H20 requires C, 63.72; H, 4.12; N, 9.29.

EXAMPLE 232 The preparation of 3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) propanamide (XIII: Ar = 2- chlorophenyl n = 2. R3 = R4 = H) (119) The demethylation of (118) prepared as described in Example 231 with BBr3 using the procedure described in Example 80 gave (19) as a yellow / orange powder (77%), m.p. 319-322 ° C. 1 H NMR d [(CD3) 2 SO] 11.06 (br s, 1 H), 9.36 (br s, 1 H), 8.37 (d, J = 2.4 Hz, 1 H), 7.77 (s, 1 H), 7.60- 7.55 (m, 2H), 7.52-7.43 (m, 3H), 7.35 (a, 1 H), 7.13 (dd, J = 8.8, 2.4 Hz, H), 6.87 (a, 1 H), 4.65 (t, J = 6.7 Hz, 2H), 2.57 (t, J = 6.7 Hz, 2H). FABMS found M +: 435.0833, 433.0828. C ^ H ^ CI aO * requires 435.0800, 433.0829. . . . .... ... , _. "_ .. . EXAMPLE 233 The preparation of 3- (4- (2-chlorophenyl) -9-methoxy-1,3-dioxo-2,3-dihydropyrrolor-3,4-c1carbazole-6 (1 H) -yl) -N- [2- (4-morpholinyl ) ethyl] propanamide (XI: Ar = 2. chlorophenyl, n = 2. R3 = H. R4 = CH2CH N (CH2CH?), 0) (120) The reaction of the acid (117) prepared as described in Example 230 with oxalyl chloride followed by N- (2-aminoethyl) morpholine using the procedure described in Example 207 gave the amide (120) (73%) as of a yellow powder, mp 174-176 ° C. 1 H NMR d [(CD3) 2 SO] 11.12 (br s, 1 H), 8.51 (d, J = 2.6 Hz, 1 H), 7.77 (s, H), 7.74 (t, J = 5.6 Hz, 1 H), 7.68 (d, J = 9.0 Hz, 1 H), 7.58 (m, 1 H), 7.53-7. 44 (m, 3H), 7.31 (dd, J = 9.0, 2.6 Hz, 1 H), 4.71 (t, J = 6.3 Hz, 2H), 3.90 (s, 3H), 3.40 (t, -J = 4.6 Hz , 4H), 2.97 (m, 1 H), 2.58 (t, J = 6.3 Hz, 2H), 2.1 1 (ta, J = 4.6 Hz, 4H), 2.00 (t, J = 6.7 Hz, 2H). Found. C, 60.46; H, 5.26; N, 9.27. C30H29CIN4O5. 2H20 requires C, 60.35; H, 5.94; N, 9.38.

EXAMPLE 234 The preparation of 3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) -N- [2- (4 -morpholinyl) ethyl] propanamide (XIII: Ar = 2-chlorophenyl) n = 2. R3 = H. R4 = CH2CH2N (CH2CH2) 0) (121) The demethylation of (120) prepared as described in Example 233 with BBr3 using the procedure described in Example 80 with the exception that the reaction time was 16 h gave (121) as a yellow powder (64). %), pf 143-148 ° C (dec). 1 H NMR d [(CD3) SO] 1 1.05 (s, 1 H), 9.35 (s, 1 H), 8.36 (d, J = 2.4 Hz, 1 H), 7.74 (t, J = 5.6 Hz, 1 H ), 7.71 (s, 1 H), 7.60-7.55 (m, 2H), 7.52-7.43 (m, 3H), 7.13 (dd, J = 8.8, 2.4 Hz, 1 H), 4.67 (t, J = 6.3 Hz, 2H), 3.40 (t, J = 4.7 Hz, 4H), 2.98 (m, 2H), 2.57 (t, J = 6.3 Hz, 2H), 2.12 (t, J = 4.7 Hz, 4H), 2.02 ( t, J = 6.7 Hz, 1 H). Found: C, 62.37; H, 4.99; N, 9.82. 1 / 2H20 requires C, 62.64; H, 5.08; N, 10.08.

EXAMPLE 235 The preparation of 3- (4- (2-chlorophenyl) -9-methoxy-1,3-dioxo-2,3-dihydropyrrolor-3,4-clcarbazole-6 (1 H -in-N- ^ 2- (dirnethylamino) etin-N- methylpropanamide (XI: Ar - 2. chlorophenyl, n = 2. R3 = CH3, R4 - CH HZN (CH-,)? (122) The reaction of the acid (117) prepared as described in Example 230 with oxalyl chloride followed by?,?,? '-trimethylethylenediamine using the procedure described in Example 207 gave the amide (122) (77%) in ferma of a yellow powder, 1.46-152 ° C (dec). 1 H NMR d [(CD3) 2 SO] 1 1 .10 (a, 1 H), 8.51 (d, J = 2.6 Hz, 1 H), 7.83 (s, 0.5 H), 7.79 (s, 0.5 H), 7.72 (m, 1 H), 7.58 (m, 1 H), 7.54-7.43 (m, 3H), 7.31 (m, 1 H), 4.72 (m, 2H), 3.90 (s, 1 H), 3.25 (m , 1 H), 3.09 (m, 1 H), 2.83 (m, 2H), 2.72 (s, 1.5H), 2.71 (s, 1 .5H), 2.13 (t, J = 4.8 Hz, 1 H), 2.05 (s, 3H), 2.00 (t, J = 4.8 Hz, 1 H), 1.88 (s, 3H). Found: C, 63.42; H, 5.46; N, 10.15. C29H29CIN4O4. H20 requires C, 63.21; H, 5.67; N, 10.17.

EXAMPLE 236 The preparation of 3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolof3.4-c] carbazole-6 (1 H) -yl) -N- [2- (dimethylamino ) etin-methylpropanamide (XIII: Ar = 2-chlorophenyl, n = 2. R3 = C lr R4 = CH, CHzN (CHj.). 2 (123) The demethylation of (122) prepared as described in Example 236 with BBr3 using the procedure described in Example 80 with the exception that the reaction time was 48 h gave (123) as a yellow powder (58). %), pf 184-188 ° C. 1 H NMR d [(CD 3) 2 SO] 1 1 .06 (br s, 1 H), 9.36 (br s, 1 H), 8.37 (d, J = 2.4 Hz, 1 H), 7.78 (s, 0.5 H), 7.74 (s, 0.5H), 7.62-7.54 (m, 2H), 7.53-7.42 (m, 3H), 7.14 (dd, J = 8.8, 2.4 Hz, 1 H), 4.69 (m, 2H), 3.22 (m , 1 H), 3.09 (m, 1 H), 2.82 (m, 2H), 2.72 (s, 1.5 H), 2.71 (s, 1 .5H), 2.14 (t, J = 4.8 Hz, 1 H), 2.06 (s, 3H), 2.00 (t, J = 4.8 Hz, 1 H), 1.88 (s, 3H). Found: C, 62.23; H, 5.23; N, 10.24. C28H27CIN4O4. 1.25H20 requires C, 62.10; H, 5.49; N, 10.35.

EXAMPLE 237 The preparation of 3- (4- (2-chlorophenyl) -9-methoxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-clcarbazole-6 (1 H) -9-N- (2.2.6.6-tetramethyl-4 - piperidinyl) propanamide (X. Ar = 2-chlorophenyl n = 2. R3 = H. R4 = 2.2.6.6- tetramethyl-4-piperidinyl) (124) The reaction of the acid (117) prepared as described in Example 230 with oxalyl chloride followed by 4-amino- (2,2,6,6-tetramethyl) piperidine using the procedure described in Example 207 gave the amide ( 124) (72%) in the form of a yellow powder, mp 155-160 ° C (dec). 1 H NMR d [(CD3) 2 SO] 1 1 .12 (a, 1 H), 8.51 (d, J = 2.6 Hz, 1 H), 7.78 (s, 1 H), 7.67 (d, J = 9.0 Hz, 1 H), 7.59-7.44 (m, 6H), 7.31 (dd, J = 9.0, 2.6 Hz, 1 H), 4.71 (m, 2H), 3.90 (s, 3H), 3.82 (m, 1 H ), 2.52 (t, J = 6.2 Hz, 2H), 1 .26 (m, 1 H), 1.0 (m, 1 H), 1.03 (s, 3H), 1.02 (s, 3H), 0.91 ( s, 3H), 0.96 (s, 3H), 0.64 (t, J = 12.3 Hz. 1 H), 0.53 (t..J = 12.3.Hz, 1 H). Found: C, 64.37; H, 5.97; N, 9.20. C33H35CIN4O4. 1.5H20 requires C, 64.54; H, 6.24; N, 9.12.

EXAMPLE 238 The preparation of 3- (4- (2-chlorophenyl) -9-hydroxy-1 f3-dioxo-2,3- dihydropyrrolor3.4-c] carba2ol-6 (1 HHI) -N- (2.2.6.6-tetramethyl- 4-piperidinyl) propanamide (XIII: Ar = 2-chlorophenyl, n = 2. R3 = H. R4 = 2.2.6.6- tetramethyl-4-piperidinyl) (125) The demethylation of (124) prepared as described in Example 237 with BBr3 using the procedure described in Example 80 with the exception that the reaction time was 48 h gave (125) as a yellow powder (47 %), pf 293-299 ° C (dec). 1 H NMR d [(CD 3) 2 SO] 1 1.08 (br s, 1 H), 9.38 (br s, 1 H), 8.72 (a, 1 H), 8.37 (d, J = 2.4 Hz, 1 H), 7.83 (d , J = 7.1 Hz, 1 H), 7.75 (s, 1 H), 7.60-7.44 (m, 5H), 7.14 (dd, J = 8.8, 2.4 Hz, 1 H), 4.70 (t, J = 5.8 Hz , 2H), 3.90 (m, 1 H), 2.54 (t, J = 5.8 Hz, 2H), 1 .45-1.31 (m, 2H), 1.30 (s, 3H), 1.29 (s, 3H), 1.25 (s, 3H), 1.22 (s, .3H), 1.09-9.93 (m, 2H). Found: C, 58.67, H, 5.37, N, 8.41, C32H33CIN4O4, 1.25CH2CI2 requires C, 58.79, H, 5.27, N, 8.25.

EXAMPLE 239 The preparation of 4- (2-chlorophenyl) -6- 3- [cis-3,5-dimethylpiperazinyl-3-oxopropyl} -9-methoxypyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (XI: Ar = 2-chlorophenyl, n = 2. R3, R4 = cis-3,5-dimethylpiperazinyl) (126) Reaction of the acid (17) prepared as described in Example 230 with oxalyl chloride followed by cis-2,6-dimethylpiperazine using the procedure described in Example 207 gave the amide (126) (76%) as of a yellow powder, mp 168-173 ° C (dec). 1 H NMR d [(CD3) 2 SO] 1 1.13 (a, 1 H), 8.52 (d, J = 2.6 Hz, 1 H), 7.80 (s, 0.5H), 7.76 (s, 0.5H), 7.71 (m, 1 H), 7.58 (m, 1 H), 7.54-7.43 (m, 3H), 7.31 (dd, J = 9.0, 2.6 Hz , 1 H), 4.71 (m, 2 H), 4.17 (m, 1 H), 3.89 (s, 3 H), 2.94 (m, 1 H), 2.75 (m, 1 H), 2.23 (m, 1 H) , 2.08 (m, 1 H), 1.87 (m, 2H), 0.88-0.86 (2d, J = 5.9 Hz, 3H), 0.67 (d, J = 6.1 Hz, 3H). Found: C, 64.03; . H, 5.47; N, 9.72. C3QHÍCIÑ O4. H20 requires C, 64.00; H, 5.55; N, 9.95.

EXAMPLE 240 The preparation of 4- (2-chlorophenyl) -6- 3-r (3R.5S) -3,5-dimethyl-piperazinyl-3-oxopropyl-9-hydroxypyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (XIII: Ar-2-chlorophenyl, n = 2. R3, R4 = cis-3,5-dimethylpiperazinyl) (127) The demethylation of (126) prepared as described in Example 239 (with BBr3 using the procedure described in Example 80 with the exception that the reaction time was 48 h gave (127) as a yellow powder ( 38%), mp 220-224 ° C (dec). 1 H NMR d [(CD3) 2 SO] 11.07 (br s, 1 H), 9.36 (br s, 1 H), 8.72 (a, 1 H), 8.34 (a , 1 H), 7.72 (s, 0.5H), 7.71 (s, 0.5H), 7.60-7.54 (m, 2H), 7.52-7.43 (m, 3H), 7.13 (dd, J = 8.8, 2.4 Hz, 1 H), 4.68 (m, 3 H), 4.15, 4.12 (2 s, 2 H), 2.94 (m, 1 H), 2.72 (m, 1 H), 2.19 (m, H), 2.00 (m, 1 H ), 1.84 (m, 1 H), 0.86, 0.84 (2 d, J = 5.8 Hz, 3H), 0.64 (2 d, J = 6.1 Hz, 3H) Found: C, 63.38; H, 5, 38; N, 9.96, C29H27CIN4O4, H? 0 requires C, 63.44, H, 5.32, N, 10.20.

EXAMPLE 241 The preparation of 3- (4- (2-chlorophenyl) -9-methoxy-1,3-dioxo-2,3-dihydropyrrolof3.4-c1carbazol-6 (1 H) -yl) -Nf2- (1 H-imidazole-5) -yl) ethyl] propanamide (XI: Ar = 2-chlorophenyl) n = 2. R3 = H. R4 = (1H-imidazol-5-yl) ethyl) (128) Reaction of the acid (17) prepared as described in Example 230 with oxalyl chloride followed by histamine using the procedure described in Example 207 gave the amide (128) (81%) as a yellow powder, m.p. 144-149 ° C (dec). 1 H NMR d [(CD3) 2 SO] 11 .12 (a, 1 H), 8.52 (d, J = 2.6 Hz, 1 H), 7.91 (t, J = 5.5 Hz, 1 H), 7.76 (s, 1 H), 7.69 (d, J = 9.0 Hz, 1 H), 7.58 (m, 1 H), 7.52-7.42 (m, 4H), 7.32 (dd, J = 9.0, 2.6 Hz, 1 H), 6.56 ( s, 1 H), 4.69 (t, J = 6.4 Hz, 2H), 3.90 (s, 3H), 3.12 (m, 2H), 2.58 (t, J = 6.4 Hz, 2H), 2.39 (t, J = 7.4 Hz, 2H). . Found: C, 6J3.73; H ~ 4 9; ^ Ñ,? 1.49. C29H24CIN5O4V 1 / 2CH2Cl2 requires C, 60.62; H, 4.31; N, 1 .98.

EXAMPLE 242 The preparation of 3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolor 3,4-clcarbazole-6 (1 H) -ih-N- [2- (1 H -imidazole-5-QetiMpropanamide (XIII: Ar = 2-chlorophenyl) n = 2. R3 = H. R4 = (1 H-imidazol-5-yl) ethyl) (129) The demethylation of (128) prepared as described in Example 241 with BBr3 using the procedure described in Example 80 with the exception that the reaction time was 48 h gave (129) as a yellow powder (46 %), pf 158-162 ° C (dec). H NMR d [(CD3) 2 SO] 1 1.75 (a, 1 H), 1.05 (sa, 1 H), 9.36 (sa, 1 H), 8.37 (d, J = 2.4 Hz, 1 H), 7.91 ( t, J = 5.3 Hz, 1 H), 7.71 (s, 1 H), 7.59-7.54 (m, 2H), 7.50-7.42 (m, 4H), 7.14 (dd, J = 8.8, 2.4 Hz, 1 H ), 6.57 (a, 1 H), 4.65 (t, J = 6.5 Hz, 2H), 3.13 (m, 2H), 2.55 (t, J = 6.5 Hz, 1 H), 2.40 (t, J = 6.5 Hz , 1 HOUR). . ABMS found [M + H] +: 530.1431, 528.1440. C28H23CIN5O4 requires 530.1409, 528.1439.

Representative procedure for method 16 of scheme 5 . . EXAMPLE 243 · - | -|| ^ The preparation of .9-dihydroxy-4-phenyl-1,6-dihydropyrrolo [3,4-c] carbazole-3 (2H) -one (XV: Ar = phenyl, R10 = H) (133) and 3,9-dihydroxy-4-phenyl -3.6- dihydropyrrolor3.4-c carbazo) -1 < 2H) -one (XVI: Ar = phenyl, R 0 = H) (134? Sodium borohydride (4 portions of 0.24 g, 0.025 mol total) was added over 5 h to a solution of 9-hydroxy-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (I; Ar = phenyl) (0.50 g, 0.015 mmol) in ethanol (80 ml) and the solution was left overnight. Four more portions of sodium borohydride were added at 1 h intervals and the solution was diluted with water and extracted with ethyl acetate. The organic phase was dried, the drying agent was removed and the solution was concentrated to dryness and chromatographed on silica. The starting material (12 mg) was eluted with ethyl acetate / petroleum ether (21), followed by the compound 3-hydroxy (134) (0.07, 14%) as a cream powder, m.p. 300-310 ° C (dec). 1 H NMR d [(CD3) 2 SO] 1 .26 (br s, 1 H), 8.98 (s, 1 H), 8.83 (s, 1 H), 8.50 (d, J = 2.3 Hz, 1 H), 7.70 ( da, J = 7.0 Hz, 2H), 7.53 (s, 1 H), 7.49-7.31 (m, 4H), 6.96 (dd, J = 8.7, 2.3 Hz, 1 H), 6.25 (d J = 9.7 Hz, 1 H), 5.87 (d, J = 9.7 Hz, 1 H). Found: C, 71.77; H, 4.47; N, 8.14. C20H13 2O3. 1 / 4H20 requires C, 71.95; H, 4.08; N, 8.39. Elution with ethyl acetate gave a mixed fraction of (134) and (133) (0.014 g) followed by the pure 1-hydroxy compound (133) (0.32 g, 64%) as a white powder, m.p. 300-310 ° C (dec. 1 H NMR d [(CD3) 2 SO] 1 1.38 (br s, 1 H), 9.06 (s, 1 H), 8.55 (br s, 1 H), 7.72 (d, J = 2.2 Hz , 1 H), 7.55 (dd, J = 7.8, 2.1 Hz, 2H), 7.47-7.35 (m, * 4H), 7.32 (s, 1 H), 6.98 (dd, J = 8.6, 2.2 Hz, 1 H ), 6.38 (d, J = 10.3 Hz, 1 H), 6.20 (d, J = 10.3 Hz, 1 H) Found: C, 68.77, H, 4.66, N, 7.87, C20H13N2O3, H20 requires C, 69.15; H, 4.35; N, 8.06.

EXAMPLE 244 The preparation of 9-hydroxy-1-methoxy-4-phenyl-1,6-dihydropyrrolo [3,4-c1carbazol-3 (2m-one (XVII: Ar = phenyl, R 0-H) (135) A solution of (133) prepared as described in Example 243 (0.050 g, 0.16 mmol) and p-toluenesulfonic acid (15 mg) in methanol (5 mL) was stirred at room temperature for 30 minutes and then poured into a saturated aqueous solution of NaHCC > 3. The mixture was extracted with ethyl acetate. The organic phase was dried, the drying agent was removed and the solution was concentrated to dryness to give (135) which crystallized from ethyl acetate / petroleum ether as a white solid (0.041 g, 74%), m.p. 290-300 ° C (dec). 1 H NMR d [(CD 3) 2 SO] 11.47 (br s, 1 H), 9.15 (br s, 1 H), 8.75 (s, 1 H), 7.57-7.53 (m, 3H), 7.44-7.37 (m, 4H) , 7.36 (s, 1 H), 7.09 (dd, J = 8.7, 2.4 Hz, "1 H), 6.26 (s, 1 H), 3.25 (s, 3H). . '.. *. ~ . Found: C, 71.34; H, 4.79; N, 7.84. C2iH15N203. 1 / 2H20 requires C, 71.58; H, 4.57; N, 7.95.

EXAMPLE 245 The preparation of 9-hydroxy-4-phenyl-1,6-dihydropyrrolo [3,4-clcarbazol-3 (2m-one (XVIII: Ar = phenyl, R10 = H) (136) To a solution of (133) prepared as described in Example 243 (0.20 g, 0.605 mmol) in tetrahydrofuran (30 mL) was added p-toluenesulfonic acid (23 mg, 0.121 mmol), followed by PhSeH (1.48 ml, 4.24 mmol) and the solution was stirred at room temperature for 1 h. After diluting with water, the mixture was extracted with ethyl acetate and the extract was washed with an aqueous solution of NaHCO 3. The organic phase was dried, the drying agent was removed and the solution was concentrated to dryness and chromatographed on silica. Elution with ethyl acetate / petroleum ether (11) and then with ethyl acetate followed by ethyl acetate / methanol (95: 5) gave (136) as a white powder (0.74 g, 91% ), pf 270-280 ° C (dec). \ 1H NMR d [(Cb3j2S) '1 1741 (s a, 1 H), 9.13 (s a, 1 H), 8.27 s a,' 1 H), 7.60-7.52 (m, 2H), 7.47-7.36 (m, 4H), 7.34-7.31 (m, 1 H), 7.30 (s, 1 H), 6.99 (dd, J = 8.6, 2.2 Hz , H), 4.78 (sa, 2H). Found: C, 75.19; H, 4.88; N, 8.37. C20H14 2O2. 1 / 4H20 requires C, 75.34; H, 4.58; N, 8.78.

EXAMPLE 246 The preparation of 4- (2-chlorophenol) -1,9-dihydroxy-6 (3-hydroxypropyl) -1,6-dihydropyrrolo [3,4-clcarbazole-3 (2H) -one (XV: Ar = 2-chlorophenyl. = CH CH2CHzOH) (137? And 4- (2-chlorophenyl) -3,9-dihydroxy-6- (3-hydroxypropyl) -3,6-dihydrooirrolof3.4-clcarbazole-1 (2H) -one (XVI: Ar = 2-chlorophenyl) R10 = CH, CH2CH2OH) M38) The reduction of the alcohol (34) prepared as described in Example 243 with sodium borohydride using the procedure described in the procedure described in Example 243 of Scheme 5, followed by chromatography of the product on silica first gave compound 3- hydroxy (138) (11%) in the form of a cream-colored powder, mp 160-164 ° C (dec). 1 H NMR d [(CD3) 2 SO] 9.08 (br s, 1 H), 8.84 (s, 1 H), 8.54 (d, J = 2.5 Hz, - H), 7.62-7.36 (m, 6H) "7.03 (dd , J = 8.7, 2.5 Hz, 1 H), 5792 (a, JH), "5.81 (a, 1 H), 4.58 (t, J = 5.0 Hz, 1 H), 4.44 (t, J = 6.8 Hz, 2H), 3.38 (m, 2H), 1.88 (m, 2H) Found: C, 64.60; H, 4.82; N, 6.32, C23H19CIN2O4, 1 / 4H20 requires C, 64.64; H, 4.60; N, 6.55; of (137) (67%) in the form of a cream-colored powder, mp 240 ° C (dec). 1 H NMR d [(CD3) 2 SO] 9.18 (br, 1 H), 8.53 (br, 1 H), 7.76 (m, 1 H), 7. 50 (m, 2H), 7.43-7.35 (m, 3H), 7.40 (s, 1 H), 7.04 (dd, J = 8.7, 2.3 Hz, 1 H), 6.52 (d, J = 10.0 Hz, 0.5H ), 6.40 (d, J = 10.0 Hz, 0.5H), 6.25 (d, J = 10.0 Hz, .5H), 6.21 (d, J = 10.0 Hz, 0.5H), 4.61 (t, J = 4.7 Hz, 1 H), 4.44 (t, J = 6.8 Hz, 2H), .39 (m, 2H), 1.88 (m, 2H). Found: C, 65.17; H, 4.80; N, 6.46. C23Hi9CIN204 requires, 65.33; H, 4.53; N, 6.62.

SCHEME 6 Procedures of scheme 6 EXAMPLE 247 The preparation of methyl 2-azido-3- [4 '- (benzyloxy) -3'-methoxyphenyl] prop-2-enoate (55) A solution of 4-benzyloxy-3-methoxy-benzaldehyde (12.0 g, 49.6 mmol) and methyl azidoacetate (23 g, 0.200 mol) in methanol (50 ml) was added for 30 min to a cooled solution (ice bath). salt) of sodium methoxide which had been prepared from the addition of methanol (80 ml) to sodium (3.4 g, 0.149 mol). The reaction mixture was stirred at 0 ° C for 45 min, during which time a dense cream-colored precipitate formed, and then stored in the freezer overnight. Ice-cooled water was added and the precipitate was filtered off and dried to give methyl 2-azido-S - ^ '-. Benzyloxyj-S'-methoxyphenyl-methyl-4-enoate * (55) (12.2% ~). 73%) that was used in the next stage without purification.

EXAMPLE 248 The preparation of methyl 6- (benzyloxy) -5-methoxy-indole-2-carboxylate (56) A solution of the azidocinnamate (55) (12.2 g, 36.0 mmol) prepared as described in Example 247 in xylene (300 mL) was added dropwise to xylene at reflux temperature (100 mL) for 1.5 h, the The reaction mixture was refluxed for a further 125 min and most of the xylene was removed by distillation. The residue, after cooling to room temperature, formed a fine cream-colored precipitate of methyl 6- (benzyloxy) -5-methoxy-indole-2-carboxylate which was collected by filtration. The remaining xylene was removed by azeotropic distillation of the mother liquor with ethanol and the residue was recrystallized from ethanol to give further methyl 6- (benzyloxy) -5-methoxy-indole-2-carboxylate. The mother liquors were concentrated again and the residue was recrystallized. The 6- (benzyloxy) -5-methoxy-indole-2-carboxylic acid methyl ester (56) (total 9.9 g, 88%) was used in the next step without purification. Found: C, 69.38; H, 5.54; N, 4.55. Ci8Hi7N04 requires: C, 69.44; H, 5.50; N, 4.50.

EXAMPLE 249 - The preparation of 6- (benzyloxy) -5-methoxy-1 H-indol-2-carbaldehyde (57) To a solution of the ester (56) (1.0 g, 3.22 mmol) prepared as described in Example 248 in tetrahydrofuran (10 mL) was added dropwise a suspension of lithium aluminum hydride (0.150 g, 3.86 mmol) in tetrahydrofuran (10 mL) and the reaction mixture was stirred at room temperature for 20 min. Water (1 ml) was added dropwise and then dilute sodium hydroxide (1 ml) was added, the solution was stirred for 10 min and then filtered through Celite and concentrated. The resulting yellow oil was dissolved in chloroform (20 ml) and then manganese dioxide (2.2 g, 26.0 mmol) was added, the reaction mixture was heated at 50 ° C for 1 h and then filtered through Celite and filtered. concentrated. The residue was recrystallized from dichloromethane to give 6- (benzyloxy) -5-methoxy-1 H-indole-2-carbaldehyde (57) (0.74 g, 82%) as pale yellow needles. Found: C, 72.53; H, 5.42; N, 4.92. C17Hi5N03 requires: C, 72.58; H, 5.37; N, 4.98.

Representative procedure for method 16 of scheme 6 EXAMPLE 250 The preparation of 6- (benzyloxy) -5-methoxy-2 - [(E) -2-phenylethenyl] -1H-indole (XX: Ar = phenyl) (150) To a solution of (57) (0.60 g, 2.14 mmol) prepared as described in Example 249 and benzyltriphenylphosphonium bromide (1.0 g, 2.35 mmol) in dichloromethane (10 mL) was added dropwise a solution 17 M sodium hydroxide (1.1 ml, 18 mmol). The reaction mixture was stirred at room temperature until all the starting material was consumed (30 min) and then diluted with water and extracted with dichloromethane (2 x 40 mL). The combined extracts were dried and concentrated to give an approximately 1: 1 mixture of 6- (benzyloxy) -5-methoxy-2 - [(E) -2-phenylethenyl] -1H-indole and 6- (benzyloxy) - 5-methoxy-2 - [(Z) -2-phenylethenyl] -1 H-indole (0.75 g, 99%). Recrystallization from dichloromethane gave the E isomer (150) without contamination, m.p. 140-145 ° C (softening), 158-62 ° C (melted). 1 H NMR d [(CD3) 2 SO] 1 1.08 (s, 1 H), 7.52-7.47 (m, 4H), 7.42-7.31 (m, 5H), 7.25-7.15 (m, 2H), 7.05-7.01 (m , 2H), 6.91 (s, 1 H), 6.45 (s, 1 H), 5.12 8s, 2H), 3.78 (s, 3H). Found: C, 80.84; H, 6.11; N, 3.94. C24H21 N02 requires: C, 81.10; H, 5.96; N, 3.94.

EXAMPLE 251 The preparation of 6- (benzyloxy) -5-methoxy-1-methyl-2 - [(E) -2-phenylethenyl] -1 H- The reaction of (150) prepared as described in Example 250 with sodium hydride followed by iodomethane using the procedure described in method 3 gave (151) (100%), m.p. 142-J 4 ° .C. 1 H NMR d [(CD3) 2 SO] 7.51-7.46 (m, 4H), 7.40-7.34 (m, 6H), 7.31- 7.23 (m, 2H), 7.09-7.05 (m, 2H), 7.30 (s, 1 H), 5.21 (s, 2H), 3.93 (s, 3H), 3.70 (s, 3H). Found: C, 81.01; H, 6.31; N, 3.79. C25H23NO2 requires: C, 81.27; H, 6.27; N, 3.79.

EXAMPLE 252 The preparation of 8- (benzylloxy) -9-methoxy-6-metal-4-phenyl- .5.6.10-tetrahydropyrrolof3.4-clcarbazole-1.3 (2H.3aH) -dione (XXII: Ar = phenyl) R10 = Me) (152) The reaction of (151) prepared as described in example 251 with maleimide using the procedure described in example 69 gave the adduct (152) as a yellow solid which was used without further purification.

EXAMPLE 253 The preparation of 8- (benzyloxy) -9-methoxy-6-methyl-4-phenylpyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (XXIII: Ar = phenyl, R10 = Me) (153) - The aromatization of the crude product (152) prepared as described in example 252 with magnesium dioxide using the procedure described in example 79 gave (153) as a yellow solid (69% total from (151 )), pf 263-265 ° C. 1 H NMR d [(CD 3) 2 SO] 11.04 (br s, 1 H), 8.48 (s, 1 H), 7.73 (s, 1 H), 7.66-7.63 (m, 2H), 7.57-7.55 (m, 2H) , 7.49-7.36 (m, 7H), 5.28 (s, 2H), 3.95 (s, 3H), 3.90 (s, 3H). Found: C, 74.99; H, 4.67; N, 5.95. C 29 H 22 N 2 O 4 requires: C, 75.31; H, 4.79; N, 6.06.

Representative procedure for method 17 of scheme 6 EXAMPLE 254 The preparation of 8-Hydroxy-9-methoxy-6-methyl-4-phenylpyrrolo [3.4 cfcarbazol-1.3 (2H-6H) -dione (XXV: Ar = phenyl, R10 = Me) (154) To a solution of (153) (1.0 g, 2.16 mmol) prepared as described in Example 253 in a 1: 1 mixture of tetrahydrofuran and methanol (100 mL) was added 5% Pd / C (200 mg). and then ammonium formate (1.71 g, 22.0 mmol). The reaction mixture was stirred at room temperature for 2 h and then filtered through Celite, washing well with tetrahydrofuran. The filtrate was concentrated and then water was added; The resulting yellow precipitate was collected by filtration and dried to give (154) (0.71 g, 88%), m.p. 298-301 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.01 (s, 1 H), 9.70. (s, 1 H),. 8.46 (s, 1 H), 7. 71 (s, 1 H), 7.65-7.63 (m, 2H), 7.49-7.41 (m, 3H), 3.92 (s, 3H), 3.87 (s, 3H). Found: C, 69.85; H, 4.35; N, 7.15. C22H16N2O4. 1 / 3H20 requires: C, 69.83; H, 4.44; N, 7.40.

EXAMPLE 255 The preparation of 6- (benzyloxy) -2- [2- (2-chlorophenyl) ethenyl] -5-methoxy-1H-indole (XX: Ar = 2-chlorophenyl) (155) The reaction of the aldehyde (57) prepared as described in Example 249 with 2'-chlorobenzyltriphenylphosphonium chloride using the procedure described in the procedure described in Example 243 gave the diene (155) as a mixture of E / isomers Z (78%), green solid, mp 192-194 ° C. 1 H NMR d [(CD3) 2 SO] 11.25 (s, 1 H), 10.70 (s, minor isomer), 7.83 (dd, J = 8.0, 1.4 Hz, 1 H), 7.68-7.20 (m), 7.05 (s) , 1 H), 6.91 (s, 1 H), 6.88 (d, J = 2.9 Hz, minority isomer), 6.64 (d, J = 12.1 Hz, minority isomer), 6.51 (d, J = 1.4 Hz, 1 H ), 6.46 (d, J = 12.1 Hz, minority isomer), 5.89 (sa, minority isomer), 5.13 (s, 2H), 5.06 (s, minor isomer), 3.78 (s, 3H), 3.-71 ( s, minority isomer). Found: C, 73.92; H, 5.23; N, 3.63. C24H19CIN02 requires C, 74.13; H, 4.92; N, 3.69.

EXAMPLE 256 The preparation of 6- (benzyloxy) -2- [2- (2-chlorophenyl) ethenyl] -5-methoxy-1-methyl-1H-indole (XXI: Ar = 2-chlorophenyl, R10 = C) ( 156) The alkylation of (155) prepared as described in Example 255 with sodium hydride and iodomethane using the procedure described in method 3 gave (156) (100%) (mixture of E / Z isomers) as a yellow solid , pf 143-145 ° C. H NMR d [(CD3) 2 SO] 7.98 (dd, J = 7.9, 1.5 Hz, 1 H), 7.55-7.22 (m), 7.19 (s), 7.12 (s), 6.89 (s), 6 85 (d , J = 12.2 Hz), 6.80 (s), 6.63 (d, J = 12.2 Hz), 5.14 (s), 5.11 (s), 3.81 (s), 3.78 (s), 3.70 (s). Found: C, 74.04; H, 5.71; N, 3.49. C25H22CINO2 requires C, 74.34; H, 5.49; N, 3.47.

EXAMPLE 257 -The preparation of 8- (benzyloxy) -4- (2-chlorophenyl) -9-methoxy-6-methyl-4.5.6.10-tetrahydropyrrolo [3,4-c] carbazole-1.3 (2H.3aH) -dione ( XXII, Ar = 2-chlorophenyl, R10 = ChU) (157) Reaction of the diene (156) prepared as described in Example 256 with maleimide using the procedure described in Example 69 gave the adduct (157) (98%) as a cream powder, m.p. 174 ° C (dec), which was used without further purification.

Found: C, 68.32; H, 4.94; N, 5.51. C 29 H 24 Cl 2 O 4 1/2 H 20 requires C, 68.43; H, 4.95; N, 5.50.

EXAMPLE 258 The preparation of 8- (benzyloxy) -4- (2-chlorophenyl) -9-methoxy-6-methyl-pyrrolo [3,4-clcarbazole-1.3 (2H.6H) -dione (XXIII) (158) The aromatization of (157) prepared as described in Example 257 with manganese dioxide using the procedure described in Example 79 gave the carbazole (158) (75%) as a yellow powder, m.p. 282-285 ° C. 1 H NMR d [(CD 3) 2 SO] 1 1.05 (s, 1 H), 8.48 (s, 1 H), 7.74 (s, 1 H), 7.59-7.54 (m, 3H), 7.52-7.36 (m, 7H ), 5.30 (s, 2H), 3.96 (s, 3H), 3.91 (s, 3H). Found: C, 69.89; H, 4.44; N, 5.61. C 29 H 21 CIN 2 O 4 requires C, 70.09; H, 4.26; N, 5.64. - - | ..- -. ,. -. .

EXAMPLE 259 The preparation of 4- (2-chlorophenyl) -8,9-dihydroxy-6-methylpyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (XXIV: Ar = 2-chlorophenyl, R10 = CH2) (159 ) The reaction of (158) prepared as described in Example 258 with pyridinium hydrochloride at 220 ° C using the procedure described in Example 81 gave (159) (76%) as a yellow powder, m.p. 310-313 ° C. H NMR d [(CD3) 2 SO] 10.95 (s, 1 H), 9.57 (a, 1 H), 9.18 (a, 1 H), 8.32 (s, 1 H), 7.64 (s, 1 H), 7.56 (dd, J = 8.1, 2.2 Hz, 1 H), 7.50-7.41 (m, 4H), 7.02 (s, 1 H), 3.84 (s, 3H). Found: C, 64.11; H, 3.96; N, 6.54. C2iH13CIN204. 1 / 4CH 3 OH requires C, 63.67; H, 3.52; N, 6.98.

Representative procedure for method 18 of scheme 6 EXAMPLE 260 The preparation of 4- (2-chlorophenyl) -8-hydroxy-9-methoxy-6-methylpyrrolo [3,4- c] carbazole-1.3 (2H.6H) -dione (XXV: Ar = 2-chlorophenyl) R10 = CH ^) (160) A mixture of (158) (1.30 g, 2.62 mmol) prepared as described in Example 258. HCI conc. (40 ml) and acetic acid (65 ml) was heated at 100 ° C for 2 h. Water was added and the precipitated product was removed by filtration and dried. The solid was adsorbed on silica in a tetrahydrofuran solution and chromatographed. Elution with ethyl acetate / petroleum ether (3: 2) gave (160) (1.07 g, 85%), which crystallized from tetrahydrofuran / petroleum ether as a green solid, m.p. 280-285 ° C (dec). 1 H NMR d [(CD3) 2 SO] 1 1.0 1 (s, 1 H), 9.73 (s, 1 H), 8.44 (s, 1 H), 7.69 (s, 1 H), 7.57 (dd, J = 8.0 , 2.2 Hz, 1 H), 7.51-7.41 (m, 4H), 7.09 (s, 1 H), 3.93 (s, 3H), 3.87 (s, 3H). Found: C, 64.53; H, 3.66; N, 6.27. C22H 5CIN204. 1 / 4H20 requires C, 64.24; H, 3.80; N, 6.81.

EXAMPLE 261 The preparation of 8- (benzyloxy) -4- (2-chlorophenyl) -9-methoxy-4.5.6. 0- tetrahydropyrrolo [3,4-c] carbazole-1.3 (2H.3aH) -dione (XXII: Ar-2-chlorophenyl, R10 = H) (161) Reaction of the diene (155) prepared as described in Example 255 with maleimide using the procedure described in Example 69 gave the adduct (161) as a chestnut powder (87%) which was used without further purification. - · - EXAMPLE 262 The preparation of 8- (benzyloxy) -4- (2-chlorophenyl) -9-methoxypyrrolo [3,4- c] carbazoi-1.3 (2H.6H) -dione (XXIII: Ar = 2-chlorophenyl, R10 = H) (162) The aromatization of (161) prepared as described in Example 161 with manganese dioxide using the procedure described in Example 79 gave the carbazole (162) (93%) as an orange powder, m.p. 260-264 ° C. 1 H R N d [(CD3) 2 SO] 11.86 (s, 1 H), 11.01 (s, 1 H), 8.43 (s, 1 H), 7.58-7.34 (m, 10H). 7.26 (s, 1 H), 5.26 (s, 2H), 3.91 (s, 3H). Found: C, 69.65; H, 3.84; N, 5.61. C28Hi9CIN204 requires C, 69.64; H, 3.97; N, 5.80.

EXAMPLE 263 The preparation of 4- (2-chlorophenyl) -5-hydroxy-9-methoxypyrrolo [3,4-clcarbazole-1.3 (2H.6H) -dione (XXV: Ar = 2-chlorophenyl, R10 = H) (163) The debenzylation of (162) prepared as described in Example 262 with HCl in acetic acid using the procedure described in Example 260 gave (163) (77%) as a yellow powder, m.p. 194-196 ° C. || -. - - -1? · NMR d [(CD3) 2SO] 11.71 (s, 1 H), 10.97 (s a, 1 H), 9.68 (s a, 1 H), 8.38 (s, 1 H), 7.56 (dd, J = 8.0, 2.2 Hz, 1 H), 7.49-7.39 (m, 4H), 7.02 (s, 1 H), 3.90 (s, 3H) . Found: C, 63.38; H, 3.38; N, 6.20. C21H13CIN204. 1/4 H20 requires C, 63.49; H, 3.42; N, 7.05.

EXAMPLE 264 The preparation of 6- (benzyloxy) -2- [2- (2-chlorophenyl) ethenyl] -5-methoxy-1- (2-methoxy-ethiimh-indole (XXI: Ar = 2-chlorophenyl, R10 = CH2CH2OCHj) ( 164) Alkylation of the diene (155) prepared as described in Example 255 with sodium hydride and 1-bromo-2-methoxyethane using the procedure described in method 3 gave (164) (91%) (mixture of E / Z isomers ) in the form of an orange solid, which was used without further purification.

EXAMPLE 265 The preparation of 8- (benzyloxy) -4- (2-chlorophenyl) -9-methoxy-6- (2-methoxyethyl) -4.5.6.10c-tetrahydropyrrolo [3,4-clcarbazole-1.3 (2H. 3aH) -dione (XXII: Ar = 2-chlorophenyl, R10 = CH2CH OCH3) (165) The reaction of the diene (164) prepared as described in Example 264 with maleimide using the procedure described in Example 69 gave the adduct (165) as a tan solid (74%) which was used without further purification.

EXAMPLE 266 The preparation of 8- (benzyloxy) -4- (2-chlorophenyl) -9-methoxy-6- (2-methoxyethyl) pyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (XXIII Ar = 2-chlorophenyl, R10 = CH CH OCH2) (166) The aromatization of (165) prepared as described in Example 265 with manganese dioxide using the procedure described in Example 79 gave the carbazole (166) (89%) as an orange powder, m.p. 252-254 ° C. H NMR d [(CD3) 2 SO] 11.04 (s a, 1 H), 8.49 (s, 1 H), 7.75 (s, 1 H), 7. 59-7.35 (m, 10H), 5.29 (s, 2H), 4.66 (t, J = 5.0 Hz, 2H), 3.91 (s, 3H), 3.68 (t, J = 5.0 Hz, 2H), 3.14 (s) , 3H). Found: C, 68.72; H, 4.73; N, 5.28. C31 N25CIN2O5 requires C, 68.82; H, 4.66; N, 5.18.

Representative procedure for method 19 of scheme 6 EXAMPLE 267 The preparation of 4- (2-chlorophenyl) -8-hydroxy-9-methoxy-6- (2-methoxyethyl) pyrroium [3,4-c1carbazole-1.3 (2H.6H) -dione (XXV: Ar = 2-chlorophenyl) R10 = CH? CH2OCH2) (167) Ethanethiol (5 ml) and boron trifluoride etherate (2.5 ml) were added to a solution of benzyl ether M (155) (0.840 g, 1.55 mmol) prepared as described in example 255 in dichloromethane (100 ml) and the solution it was stirred at room temperature for 16 h. Petroleum ether (500 mL) was added and the mixture was cooled to -20 ° C for 3 h. The solid was isolated by decanting the liquid layer and partitioned between ethyl acetate and saturated aqueous NaHCO3. The organic phase was dried, the drying agent was removed and the solution was concentrated to dryness to give an oily solid which was chromatographed on silica. Elution with ethyl acetate / petroleum ether (12) gave precursors, while elution. with ethyl acetate / petroleum ether (1: 1) gave (167) (80%) which crystallized from ethyl acetate / petroleum ether as a yellow powder, m.p. 249-252X. 1 H NMR d [(CD3) 2 SO] 10.98 (a, 1 H), 9.70 (a, 1 H), 8.44 (s, 1 H), 7.70 (s, 1 H), 7.57 (dd, J = 8.0, 2.2 Hz, 1 H), 7.50-7.41 (m, 3H), 7.12 (s, 1 H), 4.56 (t, J = 5.1 Hz, 2H), 3.92 (s, 3H), 3.68 (t, J = 5.1 Hz , 2H), 3.16 (s, 3H). Found: C, 64.19; H, 4.43; N, 5.92. C 24 H 19 CIN 2 O 5 requires C, 63.93; H, 4.25; N, 6.21.

SCHEME 7 Procedures of scheme 7 EXAMPLE 268 The preparation of 4- (2-chlorophenyl) -9-hydroxy-6- (3-hydroxypropyl) - .5.6.10-tetrahydropyrrolo [3,4-c] carbazole-1.3 (2H. 3aH) -dione (XIX. = 2- chlorophenyl R10 = CH CH OH) (139) - - -. The demethylation of 4- (2-chlorophenyl) -6r (3-hydroxypropyl) -9-methoxy-4,5,6,10C-tetrahydropyrrolo [3,4-c] carbazole-1,3 ( 2H, 3aH) -dione (IV; Ar = 2-chlorophenyl, R10 = CH2CH2OH) (30) prepared by the first step of the procedure described in Example 39 with BBr3 using the procedure described in Example 80 followed by an acidic treatment gave (39) (77%) in the form of a pink powder, mp 190-196 ° C (dec). 1 H NMR d [(CD 3) 2 SO] 10.82 (br s, 1 H), 8.72 (br s, 1 H), 7.71 (dd, J = 7.7, 1.0 Hz, 1 H), 7.46 (dd, J = 8.0, 1.4 Hz , 1 H), 7.39 (m, 1 H), 7.31 (m, 1 H), 7.21 (d, J = 8.5 Hz, 1 H), 7.15 (d, J = 2.3 Hz, 1 H), 6.62 (d) , J = 8.5, 2.3 Hz, 1 H), 4.57 (t, J 4.7 Hz, 1H), 4.25 (d, J = 75 Hz, 1H), 4.11 (t, J = 6.9 Hz, 2H), 3.94 (dd) , J 7.5, 3.6 Hz, 1H), 3.53 (dt, J = 12.6, 3.7 Hz, 1H), 3.22 (m, 2H), 3.03 (dd, J = 15.6, 3.6 Hz, 1H), 1.77 (m, 2H ). Found: C, 63.57; H, 5.13; N, 6.31. C23H2iCIN204. 1 / 2H20 requires C, 63.66; H, 5.11; N, 6.45.

SCHEME 8 Procedures for scheme 8 EXAMPLE 269 The preparation of 4-methoxy-2- [2-phenylethenyl] -1H-indole (XXVI: Ar-phenyl) (141) Reaction of 4-methoxy-indole-2-carboxaldehyde with benzyltriphenylphosphonium bromide using the procedure described in Example 37 gave (141) (89%) as a fluorescent oil (mixture of E / Z isomers) which was used without additional purification.

EXAMPLE 270 The preparation of 10-methoxy-4-phenyl-4.5.6.10-tetrahydrocyclopenta [c] carbazole-1.3 (2H-3aH) -dione (XXVIII: Ar = phenyl.

Reaction of the diene (141) prepared as described in Example 269 with maleimide using the procedure described in method 4 gave the adduct (142) as a yellow solid (86%) which was used without further purification.

EXAMPLE 271 The preparation of 10-methoxy-4-phenylcyclopenta [c] carbazole-1.3 (2H-6H) dione (XXVIX: Ar = phenyl, R10 = H) 43) The aromatization of (142) prepared by the procedure described in Example 270 with DDQ using the procedure described in Example 70 gave the carbazole (143) (78%) as yellow needles, m.p. 273-276 ° C. 1 H NMR d [(CD3) 2 SO] 12.10 (s, 1 H), 10.78 (s, 1 H), 7.59 (s, 1 H), 7.57 d, J = 8.0, 1.8 Hz, 2 H), 3.99 ( s, 3H). Found: C, 73.55; H, 4.16; N, 7.93. C2iH14N203 requires C, 73.67; H, 4.12; N, 8.18.

EXAMPLE 272 - · The preparation of 10-Hydroxy-4-phenylcyclopenta [c] carbazole-1.3 (2H.6H) -dione (XXX: Ar = phenyl, R10 = H) (144) The demethylation of (143) prepared by the procedure described in Example 271 with BBr3 using the procedure described in Example 80 gave (144) as a yellow / orange solid (92%), m.p. > 300 ° C. 1 H NMR d [(CD 3) 2 SO] 12.33 (s, 1 H), 12.16 (s, 1 H), 11.65 (a, 1 H), 7.62 (s, 1 H), 7.60 (dd, J = 7.9, 1.8 Hz, 2H), 7.51-7.45 (m, 3H), 7.40 (dd, J = 7.6 Hz, 1 H), 7.03 (d, J = 7.6 Hz, 1 H), 6.63 (d, J = 7.6 Hz, 1 H) . Found: C, 72.87; H, 3.76; N, 8.44. C2oH12N203 requires C, 73.16; H, 3.68; N, 8.53.

EXAMPLE 273 The preparation of 6-methoxy-2- [2-phenylethyl] -1 H-indole (XXXI: Ar = phenyl) (146) Reaction of 6-methoxy-indole-2-carboxaldehyde (145) with benzyltriphenylphosphonium bromide using the procedure described in example 37 gave (146) (94%) as a white solid (mixture of E / Z isomers) which it was used without further purification. ÷ · - - - EXAMPLE 274 The preparation of 8-Methoxy-4-phenyl-4.5.6.10-tetrahydrocyclopenta [c] carbazole-1.3 (2H.3aH) -dione (XXXIII: Ar = phenyl, R10 = H) (147 ) Reaction of the diene (146) prepared by the procedure described in Example 273 with maleimide using the procedure described in method 4 gave the adduct, (147) as a tan solid (61%) which was used without further purification.

EXAMPLE 275 The preparation of 8-Methoxy-4-phenylcyclopenta [c] carbazole-1.3 (2H.6H) -dione (XXXIV: Ar = phenyl, R10 = H) (148) The aromatization of (147) prepared by the procedure described in Example 274 with DDQ using the procedure described in Example 70 gave the carbazole (148) (65%) as a yellow powder, m.p. 154-156 ° C. 1 H NMR d [(CD3) 2 SO] 11.87 (a, 1 H), 1.02 (a, 1 H), 8.75 (d, J = 8.8 Hz, 1 H), 7.61 (dd, J = 8.0, 1.8 Hz, 2H), 7.60 (s, 1 H), 7.49-7.40 (m, 3H), 7.10 (d, J = 2.2 Hz, 1 H), 6.94 (dd, J = 8.8, 2.2 Hz, 1 H), 3.90 ( s, 3H). Found: C, 72.49; - H, 4.14; N, 8.22. C2iH14N203. 1 / 4H20 requires C, 72.71; H, 4.21; N, 8.07.

EXAMPLE 276 The preparation of 8-Hydroxy-4-phenylcyclopenta [c] carbazole-1.3 (2H.6H) dione (XXXV: Ar = phenyl, R1Q = H) (149) The demethylation of (148) prepared by the procedure described in Example 276 with BBr3 using the procedure described in Example 80 gave (149) as a yellow powder (74%), m.p. > 330 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.75 (a, 1 H), 10.96 (a, 1 H), 10.56 (a, 1 H), 8.66 (d, J = 8.6 Hz, H), 7.60 (dd, J = 8.0, 1.8 Hz, 2H), 7.53 (s, 1 H), 7.49-7.39 (m, 3H), 6.93 (d, J = 2.1 Hz, 1 H), 6.79 (dd, J = 8.6, 2.1 Hz , 1 HOUR). Anal. found: C, 72.36; H, 3.82; N, 8.18. C2oH12N203. 1 / 4H20 requires C, 72.17; H, 3.78; N, 8.41.

EXAMPLE 277 The preparation of 2-f (E.Z) -2- (2-Chlorophenyl) ethenyl-6-methoxy-1 H-indole (XXXI: Ar = 2-chlorophenyl) (841) Reaction of 6-methoxy-indole-2-carboxaldehyde (145) with 2-chlorobenzyltriphenylphosphonium chloride using the procedure described in Example 37 gave (841) as a mixture of E / Z isomers in the form of a yellow solid ( 93%) that was used without further purification.

EXAMPLE 278 Preparation of 2 - [(EZ) -2- (2-Chlorophenyl) ethenyl] -6-methoxy-1-metal-1 H-dol (XXXH: Ar = 2-chlorophenyl, R 0 = CH 2) ( 842) The rent! of (841) with iodomethane using the procedure described in method 3 gave (842) as a yellow solid (77%) which was used without further purification.

EXAMPLE 279 The preparation of 4- (2-chlorophenyl) -8-methoxy-6-methylpyrrolo [3,4-c1carbazole-1.3 (2H.6m-dione (XXXIV: Ar = 2-chlorophenyl, R10 = CH, i 1844) The reaction of (842) prepared as described in Example 278 with maleimide using the procedure described in Method 4 Example 68 gave the adduct (XXXIII; Ar = 2-chlorophenyl, R-0 = CH3) (843) in the form of a chestnut powder that was used without further purification. Aromatization of (843) with Mn02 using the procedure described in Example 79 gave (844) as a yellow powder (total 78%), m.p. > 300 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.07 (br s, 1 H), 8.77 (d, J = 8.7 Hz, 1 H), 7.76 (s, 1 H), 7.59 (dd, J = 8.0, 2.2 Hz, 1 H), 7.52-7.43 (m, 3 H), 7.27 (m, J = 2.2 Hz, 1 H), 7.00 (d, J = 8.7, 2.2 Hz, 1 H), 3.95 (s, 3 H), 3.94 ( s, 3H). Found: C, 66.86; H, 4.04; N, 6.90; Cl, 9.26. C22H15CIN2O3. 0.2H2O requires: C, 66.99; H, 3.94; N, 7.10; Cl, 8.99.

EXAMPLE 280 The preparation of 4- (2-chlorophenyl) -8-hydroxy-6-methylpyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (XXXV: Ar = 2-chlorophenyl, R10 = CH) (845) The demethylation of (844) prepared as described in Example 279 with BBr3 using the procedure described in Example 80 gave (845) (54%) as a white solid, m.p. 304-306 ° C. 1 H NMR d [(CD3) 2 SO] 11.02 (a, 1 H), 10.08 (a, 1 H), 8.69 (d, J = 8.6 Hz, 1 H), 7.71 (s, 1 H), 7.58 (m, 1 H), 7.51-7.42 (m, 3H), 6.99 (d, J = 2.0 Hz, 1H), 6.88 (d, J = 8.6, 2.0 Hz, 1H), 3.87 (s, 3H). Found: C, 63.93; H, 3.95; N, 708; Cl, 9.12. C2 H13CIN203. H20 requires: C, 63.89; H, 3.83; N, 7.10; Cl, 8.98.

SCHEME 9 Scheme 9 procedures EXAMPLE 281 The preparation of 4- (2-chlorophenyl) -9-hydroxy-6- [2- (1 H -tetrazol-5-yl) ethyl] pyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (XXXVI: Ar = 2-chlorophenyl, n = 2) To a solution of the nitrile (238) (0.68 g, 1.63 mmol) prepared as described in example 98 in toluene / dimethylformamide (5: 1, 120 ml) was added azidotrimethyl tin (0.67 g, 3.26 mmol). The resulting solution was heated to reflux for 24 hours before a further portion of azidotrimethyl tin (0.34 g, 1.63 mmol) was added. After a further 24 hours at reflux temperature, the reaction was diluted with water and extracted with ethyl acetate. The organic phase was dried, the drying agent was removed and the solution was concentrated to dryness chromatography on silica eluting with ethyl acetate / hexane (3:11) to ethyl acetate / methanol (9: 1) followed by crystallization from ethyl acetate / hexane gave the tetrazole (272) (0.54 g, 72%) as an orange powder, mp 230-234 ° C (dec). 1 H NMR d [(CD3) 2 SO] 11.06 (g. , 1 H), 9.37 (sa, 1 H), 8.36 (d, J = 2.4 Hz, 1 H), 7.61 (s, 1 H), 7.56 (m, 1 H), 7.48 (m, 4H), 7.10 (dd, J = 8.8, 2.4 Hz, H), 4.82 (t, J = 6.9 Hz, 2H), 3.32 (t obscured, J = 6.9 Hz, 2H) Found: C, 52.69; H, 4.05; N, 15.91 C23H15CIN6O3.31 / 2H20 requires: C, 52.93; H, 4.25; N, 16.09.

EXAMPLE 282 The preparation of 4- (2-chlorophenyl) -9-hydroxy-6- [3- (1 H -tetrazol-5-yl) proprinDirrolor3.4-c1carbazole-1.3 (2H.6H-dione (XXXV: Ar = 2 -chlorophenyl, n = 3) (273) To a solution of the nitrile (241) (60 mg, 0.14 mmole) prepared as described in example 191 in toluene / dimethylformamide (5: 1, 35 ml) was added azidotrimethyltin (57 mg, 0.28 mmol). The resulting solution was heated to reflux for 72 hours before being diluted with water and extracted with ethyl acetate. The organic phase was dried, the drying agent was removed and the solution was concentrated to dryness. Chromatography on silica eluting with ethyl acetate / hexane (31) to ethyl acetate / methanol (91), followed by crystallization from tetrahydrofuran / hexane, gave tetrazole (273) (29 mg, 44%) as a orange powder, pf 269-272 ° C. - · _. - - - - - - * H NMR 6 [(CD3) 2 SO] ~ 16 (s very a, 1 H). 11.07 (s, 1H), 9.38 (s a, 1 H), 8.39 (d, J = 2.5 Hz, 1H), 7.84 (s, 1 H), 7.61 (d, J = 8.9 Hz, 1H), 7.57 (m, 1 H), 7.53-7.43 (m, 3H), 7.16 (dd, J = 8.9, 2.5 Hz, 1H), 4.59 (t, J = 7.1 Hz, 2H), 2.93 (m, 2H), 2.20 (m, 2H). Found: C, 59.71; H, 4.27; N, 16.72. C24H17CIN603. 3 / 4H20 requires: C, 59.26; H, 3.83; N, 17.27.

EXAMPLE 283 The preparation of 4- (2-chlorophenol) -9-methoxy-6-f2- (1 H-1.2.4-triazol-5-ylsulfanyl) ethyl] pyrrolo [3.4-c] carba2ol-1.3 (2H .6H) -done (XXXVII: Ar = 2- chlorophenyl R3 = 5-1 H-1.2.4-triazoMlo) (274) A solution of the mesylate (228) (0.25 g, 0.50 mmol) prepared as described in Example 170, 1 H-1, 2,4-triazole-5-thiol (76 mg, 0.75 mmol) and triethylamine (2.0 ml. ) in p-dioxane (50 ml) under a nitrogen atmosphere was heated to reflux for 48 hours before being diluted with water and extracted with ethyl acetate. The organic phase was dried, the drying agent was removed and the solution was concentrated to dryness. Chromatography on silica eluting with ethyl acetate / hexane (from 1: 1 to 1: 0) followed by crystallization from ethyl acetate / hexane gave the carbazole (274) (0.24 g, 95%) as a ^ poly. yellow ^ -f ^ ZJ - ^ ISiC. r. . · -; · - - - - ~ 1H'RMN d [(CD3) 2SO] 14.09 (sa, 1 H), 11. 13 (sa, 1 H), 8.52 (d, J = 2.6 Hz, 1 H), 8.43 (s very a, 1 H), 7.88 (s, 1 H), 7.80 (d, J = 9.0 Hz, 1 H), 7.57 (m, 1 H), 7.48 (m, 3H), 7.31 (dd, J = 9.0, 2.6 Hz, 1 H), 4.83 (t, J = 7.4 Hz, 2H), 3.91 (s, 3H), 3.52 (t, J = 7.4 Hz, 2H). Found: C, 59.29; H, 3.77; N, 13.63. C25H18CIN503S. 1 / 4H20 requires: C, 59.29; H, 3.68; N, 13.82.

EXAMPLE 284 The preparation of 4- (2-chlorophenyl) -6- [2- (1H-imidazol-2-ylsulfanyl) ethyl] -9-methoxypyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (XXXVIII: Ar = 2-chlorophenyl, R3 = 2-imidazolyl) (275) A solution of the mesylate (228) (0.30 g, 0.60 mmol) prepared as described in example 170, 2-mercaptoimidazole (0.12 g, 1.20 mmol) and triethylamine (2.0 ml) in p-dioxane (25 ml) in one The nitrogen atmosphere was heated to reflux for 24 hours, before being diluted with water to precipitate the crude product, which was collected by filtration, washed with water and dried under vacuum. Chromatography on silica with ethyl acetate / hexane (1: 1) followed by trituration in ethyl acetate gave the carbazole (275) (0.29 g, 96%) as a yellow powder, m.p. 245-247 ° C. . ^ ._ 1 H NMR d [(CD3) 2 SO] 12.24 (s.a, .1 H), 11.13 (s a, 1 H), 8.51 (d, J = 2.6 Hz, 1 H), 7.92 (s, 1 H), .75 (d, J = 9.0 Hz, 1 H), 7.58 (m, H), 7.48 (m, 3H), 7.29 (dd, J = 9.0, 2.6 Hz, 1 H), 7.00 (s very a, 2H), 4.78 (t, J = 7.5 Hz, 2H), 3.91 (s, 3H), 3.44 (t, J = 7.5 Hz, 2H). Found: C, 61.57; H, 4.14; N, 10.85. C26Hi9CIN403S. 1 / 4H20 requires: C, 61.53; H, 3.87; N, 11.03.

EXAMPLE 285 The preparation of 4- (2-chlorophenyl) -9-hydroxy-6- [2- (4H-1,2,4-triazol-3-ylsulfaninetiylpyrrolof3.4-c] carbazole-1.3 (2H.6H) -dione ( XXXVIII: Ar = 2-chlorophenyl, R3 = 5-1 H-1.2.4-triazolyl) (276) The reaction of methyl ether (274) (0.25 g, 0.50 mmol) prepared as described in Example 283 according to the procedure described in Example 80 followed by chromatography on silica eluting with ethyl acetate / tetrahydrofuran (from 1: 0 to 9: 1 to 1: 1) and trituration in methanol, gave phenyl (276) (0.22 g, 90%) as an orange powder, mp. 314-319 ° C. H NMR d [(CD3) 2 SO] 14.10 (br s, 1 H), 1.07 (sa, 1 H), 9.39 (s, 1 H), 8.42 (s very a, 1 H), 8.38 (d, J = 2.3 Hz, 1 H), 7.83 (s, 1 H), 7.68 (d, J = 8.8 Hz, 1 H), 7.57 (m, .1 H), 7.48 (m, 3H), - 7.13 (dd, J = 8.8, 2.3 Hz, 1 H) 4.79 (t, J = 7.4 ~ Hz, 2H), "3:50 (t, J = 7.4 Hz * 2H)" Found: C, 58.56; H, 3.82; N, 13.58. C24H16CIN5O3S. 2 / 5CH40 requires: C, 58.29; H, 3.53; N, 13.93.

EXAMPLE 286 The preparation of 4- (2-chlorophenyl) -9-hydroxy-6- [2- (1H-imidazol-2-ylsulfanyl) ethylpyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (XXXVIII: Ar = 2-chlorophenyl R3 = 2-imidazolyl) (277) The reaction M methyl ether (275) (130 mg, 0.24 mmol) prepared as described in example 284 according to the procedure described in example 80 , with the exception that the reaction time was 7 hours and chromatography was performed eluting with 0 ethyl acetate / hexane (from 1: 1 to 31), gave the phenyl (277) (97 mg, 83%) in form of an orange powder, mp 270-275 ° C. 1 H NMR d [(CD3) 2 SO] 12.23 (br s, 1 H), 11.07 (br s, 1 H), 9.39 (br s, 1 H), 8.37 (d, J = 2.4 Hz, 1 H), 7.86 (s, 1 H), 7.61 (d, J = 8.9 Hz, 1 H), 7.57 (m, 1 H), _ ^ 7.48 (m, 3H), 7.12 (dd, J = 8.9, 2.4 ??, · 1?) 6:98 (s very at 2H), 4.74 (t, J = 7.7 5 ??, 2H), 3.42 (t partially obscured, J = 7.7 Hz, 2H). Found: C, 60.87; H, 3.72; N, 11.00 C25H17CIN4O3S. 1 / 4H20 requires: C, 60.85; H, 3.57; N, 11.35.

EXAMPLE 287 The preparation of 4- (2-chlorophenyl) -9-hydroxy-6- [2- (1H-1,2,4-triazol-5-ylsulfinyl) ethyl-1-pyrrolof3.4-c] carbazole-1.3 (2H.6H) - dione (XXXIX: Ar = 2-chlorophenyl, m = 1. R3 = 5-1 H-1.2.4-triazolyl) (278) To a solution of the carbazole (276) (70 mg, 0.14 mmol) prepared as described in Example 285 in tetrahydrofuran (30 mL) containing glacial acetic acid (8 mL) was added 35% hydrogen peroxide (2%). my). The resulting solution was stirred at room temperature for 10 hours before being poured into solid sodium bicarbonate, diluted with water and extracted with ethyl acetate. The organic phase was dried, the drying agent was removed and the solution was concentrated to dryness. The combined organic layers were partially concentrated under reduced pressure and then adsorbed directly on silica- and chromatographed eluting with methanol / dichloromethane (5:95 to 1: 9). Grinding in diethyl ether gave the sulfoxide (279). ) (29 mg, 41%) in the form of an orange powder, mp 237-242 ° C. 1 H NMR d [(CD3) 2 SO] 14.7 (s very a, 1 H), 11.09 (s at, 1 H) , 9.41 (sa, 1 H), 8.69 (sa, 1 H), 8.38 (d, J = 2.3 Hz, 1 H), 7.79 (d, J = 9.6 Hz, 1 H), 7.60-7.46 (m, 5H ), 7.15 (dd, J = 8.8, 2.3 Hz, 1 H), 4.89 (m, 2H), 3.71 (m, 2H) Found: C, 56.85, H, 3.79, N, 13.74, C24H16CIN504S. 1 / 5C4H10O requires: C, 57.20; H, 3.48; N, 13.45.

EXAMPLE 288 The preparation of 4- (2-chlorophenyl) -9-hydroxy-6- [2- (1H-1,2,4-triazol-5-ylsulfonyl) ethylpyrrolo [3,4-c] carbazole-1.3 (2H.6H) - dione (XXXIX: Ar = 2-chlorophenyl, m = 2. R3 = 5-1H-1.2.4-triazolyl) (279) To a solution of the carbazole (276) (60 mg, 0.12 mmol) prepared as described in Example 285 in tetrahydrofuran (30 mL) containing glacial acetic acid (10 mL) was added 35% hydrogen peroxide (2%). my). The resulting solution was stirred at room temperature for 30 hours before more 35% hydrogen peroxide (2 ml) was added and the temperature was increased to 50 ° C for 18 hours. Then, the reaction was poured into solid sodium bicarbonate, diluted with water and extracted with ethyl acetate. The combined organic layers were concentrated, partially under reduced pressure and then directly adsorbed onto silica and chromatographed eluting with ethyl acetate / hexane (from 1: 1 to 1: 0). Crystallization from ethyl acetate / hexane gave the sulfone (279) (45 mg, 72%) as an orange powder, m.p. 301-304 ° C. 1 H NMR d [(CD3) 2 SO] 14.09 (s very a, 1 H), 1.07 (sa, 1 H), 9.38 (sa, 1 H), 8.60 (s, 1 H), 8.34 (d, J = 2.4 Hz, 1 H), 7.71 (s, 1 H), 7.56 (m, 2H), 7.48 (m, 3H), 7.12 (dd, J = 8.8, 2.4 Hz, 1H), 4.89 (m, 2H), 4.03 (m, 2H). Found: C, 55.12; H, 3.52; N, 12.87. C24H16CIN505S. 1 / 4C4H802 requires: C, 55.20; H, 3.34; N, 12.88.

EXAMPLE 289 The preparation of 4- (2-chlorophenyl) -9-hydroxy-6- [2- (1 H -amidazol-2-ylsulfonyl) etnipyrolo [3,4-c] carbazole-1.3 (2H.6H) - dione (XXXIX: Ar = 2-chlorophenyl, m = 2. R3 = 2-imidazolyl) (280) and 4- (2-chlorophenol) -9-hydroxy-6- [2- (1H-imidazol- 2-ylsulfinyl) ethyl] plrrolo [3,4-c] carbazole-1.3 (2H.6H) -dlone (XXXIX: Ar = 2-chlorophenyl, m = 1. R3 = 2-imidazolyl) (281) To a solution of the carbazole (277) (66 mg, 0.14 mmol) prepared as described in Example 286 in tetrahydrofuran (30 mL) containing glacial acetic acid (10 mL) was added 35% hydrogen peroxide (2%). my). The resulting solution was stirred at room temperature for 20 hours before being poured into solid sodium bicarbonate, diluted with water and extracted with ethyl acetate. The combined organic layers were concentrated partially under "reduced" pressure and then adsorbed directly on silica and chromatographed eluting with ethyl acetate / hexane (from 1: 1 to 41) to ethyl acetate / methanol (99: 1) to give a higher Rf value, sulfone (280) (36 mg, 51%) in the form of an orange powder, mp 263-265 ° C. 1 H NMR d [(CD 3) 2 SO] 11.09 (br s, 1 H), 9.44 (br s, 1 H), 8.35 (d, J = 2.4 Hz, 1 H), 7.63 (s, 1 H), 7.58 (m, 1 H), 7.52-7.45 (m, 4H), 7.19 (sa, 2H), 7.12 (dd, J = 8.8, 2.4 Hz, 1 H), 4.85 (t, J = 6.6 Hz, 2H), 3.96 (m, 2H). Found: C, 57.44; H, 3.87; N, 9.80. C25H17CIN4O5S. 1 / 2C4H802 requires: C, 57.40; H, 3.75; N, 9.92.

This was followed by a lower Rt value, the sulfoxide (281) (16 mg, 23%) in the form of an orange powder, p.f.254-259 ° C. 1H RN d [(CD3) 2SO] 13.35 (sa, 1H), 11.10 (sa, 1H), 9.42 (s, 1H), 8.39 (d, J = 2.4 Hz, 1H), 7.77 (d, J = 12.7 Hz , 1H), 7.58 (m, 2H), 7.53-7.44 (m, 3H), 7.24 (sa, 2H), 7.15 (dd, J = 8.8, 2.4 Hz, 1H), 4.85 (m, 2H), 3.69 ( m, 2H). FABMS found [M + H] +: 505.0725, 507.0666. C25H17CIN4O4S requires 505.0737.507.0708.

SCHEME 10 Procedures of scheme 10 EXAMPLE 290 The preparation of 6- (2-hydroxy-3-methoxypropyl) -9-methoxy-4-phenylpyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (XLII: Ar = phenyl, Z = OChU) (225) The alkylation of 5-methoxy-2 - [(E) -2-phenyletenyl] -1H-indole (II; Ar = phenyl) (0.20 g, 0.80 mmol) with epibromohydrin according to the procedure described in the example 38 gave the crude epoxide (XL; Ar = phenyl) which was used without further purification. The epoxide was dissolved in methanol (100 ml) to which 35% perchloric acid (10 ml) was added. The resulting solution was refluxed for 3 h before it was diluted with water and extracted with ethyl acetate. The organic phase was dried, the drying agent was removed and the solution. it -concentra -a dryness -to give him diend (XLI; Ar = phenyl, Z = OCH3). This crude material was reacted directly with maleimide (92 mg) following Method 4a, with the exception that the reaction time was 18 h. Aromatization of the crude Diels-Alder adduct using the procedure described in Example 79 gave the material which was chromatographed on silica eluting with ethyl acetate / hexane (1: 1). Crystallization from ethyl acetate / hexane gave the carbazole (225) (0.10 g, 30%) as a yellow powder, m.p. 128-136 ° C. 1 H NMR d [(CD3) 2 SO] 11 .10 (br s, 1 H), 8.55 (d, J = 2.6 Hz, 1 H), 7.81 (s, H), 7.64 (m, 3H), 7.47 (m, 3H), 7.29 (dd, J = 9.11, 2.6 Hz, 1H), 5.17 (d, J = 5.5 Hz, 1 H), 4.52 (dd, J = 4.2, 15.0 Hz, 1 H), 4.43 (dd, J = 7.1, 15.0 Hz, 1 H), 4.04 (m, 1 H), 3.90 (s, 3 H), 3.32 (m 2 H), 3.26 (s, 3 H). Found: C, 69.94; H, 5.45; N, 6.36. C25H22N2O5 requires: C, 69.76; H, 5.15; N, 6.51.

EXAMPLE 291 The preparation of 6- (2,3-dihydroxypropyl) -9-hydroxy-4-phenylpyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (XLIII: Ar = phenyl, Z = OH) (226) Demethylation of the alcohol (225) (96 mg, 0.22 mmol) prepared as described in Example 290 using the procedure described in Example 80 was followed by chromatography on silica eluting with ethyl acetate / hexane (41). Crystallization from ethyl acetate / hexane-diio-phene (226) = (28 = mg 31%) in form of a yellow / orange powder, m.p. 290: 295 ° C. H NMR d [(CD3) 2 SO] 11.04 (br s, 1 H), 9.30 (s, 1 H), 8.40 (d, J = 2.4 Hz, 1 H), 7.79 (s, 1 H), 7.63 (m, 2H), 7.55 (d, J = 8.8 Hz, 1 H), 7.47 (m, 3H), 7.11 (dd, J = 8.8, 2.4 Hz, 1 H), 5.00 (d, J = 5.4 Hz, 1 H) , 4.86 (t, J = 5.4 Hz, 1 H), 4.51 (dd, J = 3.8, 14.9 Hz, 1 H), 4.35 (dd, J = 7.5, 14.9 Hz, 1 H), 3.89 (m, 1 H ), 3.41 (m, 2H). Found: C, 67.94; H, 4.69; N, 6.50. C23H18N2O5. 1 / 4H20 requires: C, 67.89; H, 4.58; N, 6.88.

EXAMPLE 292 The preparation of 4- (2-chlorophenyl) -9-hydroxy-6- [2-hydroxy-3- (4-morpholinyl) Dropinopyrrolof3.4-c] carbazole-1.3 (2H.6H) -dione (XLIII: Ar = 2-chlorophenyl, Z = 4-morpholinyl) (282) The alkylation of the pure trans-diene (27) (0.25 g, 0.88 mmol) prepared as described in example 37 with epibromohydrin according to the procedure described in Example 38 gave the crude epoxide (XL; Ar = 2-chlorophenyl) which was used without further purification. dissolved in tetrahydrofuran (2 ml) to which morpholine (0.5 ml) was added. The resulting solution was heated at 60 ° C for 48 hours before being diluted with water and extracted with ethyl acetate. The organic phase was dried, the drying agent was removed and the solution was concentrated to dryness to give the diene (XLI; - - ^ Ar = 2-chlorophenyl-ZZ = ~ 4-morpholine). This crude material was triturated in diethyl ether / hexane and then reacted directly with maleimide (128 mg) following the procedure described in Example 68 with the exception that the reaction time was 18 h and p- was added. dioxane as co-solvent. The aromatization of the crude Diels-Alder adduct using the procedure described in Example 70 gave the carbazole (XLI I; Ar = 2- 20 chlorophenyl, Z = 4-morpholinyl) which was demethylated using the procedure described in Example 81. give the crude material which was chromatographed on silica eluting with ethyl acetate. Crystallization from diethyl ether / hexane gave the carbazole (282) (0.10 g, 22%) as a yellow powder, m.p. 275-278 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.0 (sa, 1 H), 9.34 (sa, 1 H), 8.37 (d, J = 2.4 Hz, 1 H), 7.79 (s, 1 H), 7.63 -7.56 (m, 2H), 7.47 (m, 3H), 7.12 (m, 1 H), 5.01 (t, J = 5.7 Hz, 1 H), 4.53 (m, 1 H), 4.37 (m, 1 H) ), 4.04 (sa, 1 H), 3.38 (m, 4H), 2.39-2.24 (m, 6H). Found: C, 63.90; H, 4.85; N, 8.55. C27H24CIN3O5 requires: C, 64.10; H. 4.78; N, 8.31.

EXAMPLE 293 The preparation of 4- (2-chlorophenyl) -6- [3- (cs-3,5-dimethyl-1-piperazinyl) -2-hydroxypropyl] -9-hydroxypyrrolo [3,4-c] carbazole-1.3 (2H .6H) -dione (XLIII: Ar = 2-chlorophenyl, Z = cis-3,5-dimethyl-1-piperazinyl) (283) Alkylation of the pure trans-diene (27) (0.25 g, 0.88 mmol) prepared as described in Example 37 with epibromohydrin according to the procedure described in Example 38 gave the crude epoxide (XL; Ar = 2-chlorophenyl) ) that was used without further purification. The epoxide was dissolved in tetrahydrofuran (2 ml) to which cis-2,6-dimethylpiperazine (0.50 g, 4.4 mmol) was added. The resulting solution was heated at 60 ° C for 48 hours before being diluted with water and extracted with ethyl acetate. The organic phase was dried, the drying agent was removed and the solution was concentrated to dryness to give the diene (XLI, Ar = 2-chlorophenyl, Z = cis-3,5-dimethyl-1-piperazinyl). This crude material was triturated in diethyl ether / hexane and then reacted directly with maleimide (0.13 g, 1.5 mmol) following the procedure described in Example 68 with the exception that the reaction time was 18 h and p was added. - Dioxane as co-solvent. The aromatization of the crude Diels-Alder adduct using the procedure described in Example 70 gave carbazole (XLII; Ar = 2-chlorophenyl, Z = cis-3,5-dimethyl-1-piperazinyl) which was demethylated using the procedure described in Example 81 to give the crude material which was chromatographed on silica eluting with ethyl acetate / methanol / triethylamine (4: 1: traces). Crystallization from ethyl acetate / hexane gave the carbazole (283) (65 mg, 14%) as a yellow powder, m.p. 206-210 ° C. 1 H NMR d [(CD3) 2 SO] 11.02 (br s, 1 H), 9.33 (br s, 1 H), 8.37 (d, J = 2.5 Hz, 1 H), 7.76 (d, J = 9.1 Hz, 1 H) , 7.58 (m, 2H), 7.47 (m, 3H), 7.1 i; (rn, -_ -. | - "1 H), 4.95 (sa, 1 R), 4.52 (rñ, 1 H), 4 , 34 (m, .1 H), 4.04 (m, 1 H), 2.71-2.53 (m, * 4H), 2.33 (m, 1 H), 2.20 (m, 2H), 1.46 (m, 2H), 0.81 (m, 6H) Found: C, 63.76; H, 5.30; N, 10.02, C29H29CIN4O4.3 / 4H20 requires: C, 63.73; H, 5.63; N, 10.25.

EXAMPLE 294 The preparation of 4- (2-chlorophenol) -9-hydroxy-6- [2-hydroxy-3- (meth) amino propinopyrol [3,4-clcarbazole-1.3 / 2H.6H) -done (XLIII: Ar = 2-chlorophenyl, Z = NHCHj) (284) 5 Alkylation of pure trans-diene (27) (0.25 g, 0.88 mmol) prepared as described in example 37 with epibromohydrin according to the procedure described in Example 38 gave the crude epoxide (XL; Ar = 2-chlorophenyl) which was used without further purification. The epoxide dissolved in tetrahydrofuran (2 ml) to which was added aqueous methylamine (0.5 ml, 40% solution). The resulting solution was heated at 60 ° C for 6 hours before being diluted with water and extracted with ethyl acetate. The organic phase was dried, the drying agent was removed and the solution was concentrated to dryness - z- ~ to give the "diene" (XLI, Ar-2-chlorophenyl, Z = NHCH3) This crude material is triturated in diethyl ether / hexane and then reacted directly with maleimide (0.13 g, 1.5 mmol) following the procedure described in Example 68 with the exception that the reaction time was 18 hours and p-dioxane was added. as a co-solvent. The aromatization of the crude Diels-Alder adduct using the procedure described in Example 70 gave the carbazole (XLII; Ar = 2-chlorophenyl, Z = NHCH3) which was demethylated using the procedure described in example 81 to give the crude material which was chromatographed on silica eluting with ethyl acetate / methanol / triethylamine (4: 1: traces). Crystallization from ethyl acetate / hexane gave the carbazole (284) (61 mg, 15%) as a yellow powder, m.p. 188-191 ° C. 1 H NMR d [(CD3) 2 SO] 10.9 (s very a, 1 H), 9.36 (s at, 1 H), 8.37 (d, J = 2.4 Hz, 1 H), 7.77 (s, 1 H), 7.58 ( m, 2H), 7.47 (m, 3H), 7.13 (dd, J = 8.8, 2.4 Hz, 1 H), 8.37 (d, J = 2.4 Hz, 1 H), 7.77 (s, 1 H), 7.58 ( m, 2H), 7.47 (m, 3H), 7.13 (dd, J = 8.8, 2.4 Hz, 1 H), 5.09 (sa, 1 H), 4.50 (m, 1 H), 4.34 (m, 1 H) 3.97 (m, 1 H), 2.77-2.63 (m, 2H), 2.28 (d, J = 2.1 Hz, 3H). Found: C, 62.66; H, 4.64; N, 8.69. C24H2oCIN304. 2 / 3H20 requires: C, 62.40; H, 4.66; N, 9.09.

EXAMPLE 295 The preparation of 4- (2-chlorophenyl) -6- [3- (dimethylamino) -2-hydroxypropyl] -9- hydroxypyrrolof3.4-c1carbazole-1.3 (2H.6H) -dione (XLIII: Ar = 2- Chlorophenyl Z Z. - - = N (CH,) 2) (285) Alkylation of the pure trans-diene (27) (0.25 g, 0.88 mmol) prepared as described in Example 37 with epibromohydrin according to the procedure described in Example 38 gave the crude epoxide (XL; Ar = 2-chlorophenyl) ) that was used without further purification. The epoxide was dissolved in tetrahydrofuran (2 ml) to which was added aqueous dimethylamine (0.5 ml, 40% solution). The resulting solution was heated at 60 ° C for 6 hours before being diluted with water and extracted with ethyl acetate. The organic phase was dried, the drying agent was removed and the solution was concentrated to dryness to give the diene (XLI, Ar = 2-chlorophenyl, Z = N (CH3) 2). This crude material was triturated in diethyl ether / hexane and then reacted directly with maleimide (0.13 g, 1.5 mmol) following the procedure described in example 68, with the exception that the reaction time was 18 h and added p-dioxane as co-d solvent. The aromatization of the crude Diels-Alder adduct using the procedure described in Example 70 gave the carbazole (XLII; Ar = 2-chlorophenyl, Z = N (CH3) 2) which was demethylated using the procedure described in Example 81 to give the crude material which was chromatographed on silica eluting with ethyl acetate / methanol / triethylamine (4: 1: traces). Crystallization from ethyl acetate / hexane gave the carbazole (285) (165 mg, 40%) as a yellow powder, m.p. 225-228 ° C. 1 H NMR d [(CD3) 2 SO] 11.04 (br s, 1 H), 9.34 (br s, 1 H), 8.38 (d, ^ _ J = 2.4 Hz, 1 H), 7.75 (s, 1 H), 7.57 ( m, 2H), 7.47- (mr 3H), 7.13 (dd, J = 8.8, 2A Hz, 1 H), 4.91 (sa, 1 H), 4.50 (m, 1 H), 4.34 (m, 1 H), 4.00 (m, 1 H), 2.35 (m, 1 H), 2.24 (m, 1 H), 2.17 (s, 6H). Found: C, 63.54; H, 4.60; N, 8.83. C25H22CIN304. 1 / 2H20 requires: C, 63.49; H, 4.90; H, 8.88.

SCHEME 11 Procedures of scheme 11 EXAMPLE 296 The preparation of 4- (2-chlorophenyl) -9-m9toxi-4.5.6.10c-tetrahydro-1H-furof3.4-c1carbazole-1.3 (3aH) -dione (XLIV: Ar = 2-chlorophenyl) (286) A solution of the trans-diene (27) (0.30 g, 1.06 mmol) prepared as described in Example 37 and maleic anhydride (0.16 g, 1.59 mmol) in xylene (30 mL) was heated to reflux for 18 hours, before Concentrate in vacuo and chromatograph on silica eluting with ethyl acetate / hexane (1: 2). Then, crystallization from ethyl acetate / hexane gave the anhydride (286) (0.29 g, 72%) as a pale brown powder, m.p. 189-191 ° C. ^ '1H ~ NMR d [(CD3) 2SO] 11.16 (s a, 1H), 7.69 (dd, J = 7.7, 1.4 Hz, 1 H), 7.51 (dd, J = 7.7, 1.4 Hz, 1 H), 7.43 (ddd, J = 7.7, 7.7, 1.4 Hz, 1 H), 7.36 (ddd, J = 7.7, 7.7, 1.4 Hz, 1 H), 7.25 (d, J = 8.6 Hz, 1 H), 7.15 (d, J = 2.4 Hz, 1 H), 6.77 (dd, J = 8.6, 2.4 Hz, 1 H), 4.70 (d, J = 7.7 Hz, 1 H), 4.47 (dd, J = 7.7, 3.5 Hz, 1 H), 3.78 (s, 3H), 3.71-3.66 (m, 1 H), 3.36 (dd, J = 15.9, 13.0 Hz, 1 H), 2.99 (dd, J = 15.9, 4.1 Hz, 1 H). Found: C, 65.85; H, 3.95; N, 3.70. C2iH16CIN04 requires: C, 66.06; H, 4.22; N, 3.67.

EXAMPLE 297 The preparation of 4- (2-chlorophenyl) -2- (2,4-dimethoxybenzyl) -9-methoxypyrrolo [3,4-c] carbazof-1.3 (2H-6H) -dione (XLV: Ar = 2-chlorophenyl) (287 ) To a solution of the anhydride (286) (2.80 g, 7.42 mmol) prepared as described in example 296 in glacial acetic acid (70 ml) was added 2,4-dimethoxybenzylamine (1.67 ml, 11.1 mmol). The resulting solution was refluxed for 6 h before partial concentration under reduced pressure and diluted with water to precipitate an orange solid which was collected by filtration, washed with water and dried in vacuo. Then, this crude material was dissolved in p-dioxane and flavored according to the procedure of Example 79. before chromatography on silica eluting with ethyl acetate / hexane (11). Then, crystallization from methanol gave carbazole (287) (1.46 g, 37%) as a yellow powder, m.p. 224-226 ° C. 1 H NMR d [(CD3) 2 SO] 12.02 (br s, 1 H), 8.45 (d, J = 2.6 Hz, 1H), 7.62 (s, H), 7.58 (m, 2H), 7.53-7.42 (m, 3H ), 7.25 (dd, J = 8.8, 2.6 Hz, 1 H), 6.95 (d, J = 8.4 Hz, 1 H), 6.57 (d, J = 2.3 Hz, 1 H), 6.45 (dd, J = 8.4 , 2.3 Hz, 1 H, 4.68 (s, 2H), 3.88 (s, 3H), 3.80 (s, 3H), 3.72 (s, 3H) Found: C, 68.22, H, 4.37, N, 5.29, C3oH23CIN205 requires: C, 68.38; H, 4.40; N, 5.32.

Representative procedure for method 20 of scheme 11 EXAMPLE 298 The preparation of 6-allyl-4- (2-chlorophenyl) -2- (2,4-dimethoxybenzyl) -9-methoxypyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (XLVI: Ar = 2- chlorophenyl n = 1) (288) To a solution of the carbazole (287) (150 mg, 0.28 mmol) prepared as described in Example 297 in dimethylformamide (10 mL) under a nitrogen atmosphere was added potassium carbonate (0.39 g, 2.80 mmol) and bromide. allyl (72 μ ?, 0.84 mmol). The resulting suspension was heated to 90 ° C with stirring for 3 hours before being diluted with water and extracted with ethyl acetate. The organic phase was dried, the drying agent was removed and the solution was concentrated to dryness. Chromatography on silica eluting with ethyl acetate / hexane (12) followed by crystallization from diethyl ether / hexane gave the carbazole (288) (90 mg, 57%) as a yellow powder, m.p. 171-173 ° C. 1 H NMR d [(CD3) 2 SO] 8.51 (d, J = 2.6 Hz, 1 H), 7.84 (s, 1 H), 7.67 (d, J = 8.9 Hz, 1 H), 7.58 (m, H), 7.53-7.46 (m, 3H), 7.32 (dd, J = 8.9, 2.6 Hz, 1 H), 6.97 (d, J = 8.4 Hz, 1 H), 6.57 (d, J = 2.4 Hz, 1 H), 6.45 (dd, J = 8.4, 2.4 Hz, 1 H), 5.99 (m, 1 H), 5.18 (d, J = 4.9 Hz, 2H), 5.14 (dd, J = 10.3, 1.3 Hz, 1 H), 4.99 (dd, J = 17.2, 1.3 Hz, 1 H), 4.69 (s, 2H), 3.90 (s, 3H), 3.80 (s, 3H), 3.72 (s, 3H).

Found: C, 69.97; H, 4.75; N, 5.12. C33H27CIN2O5 requires: C, 69.90; H, 4.80; N, 4.94.

EXAMPLE 299 The preparation of 6- (3-Butenyl) -4- (2-chlorophenyl) -2- (2,4-dimethoxybenzyl) -9-methoxypyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (XLVI: Ar = 2-chlorophenyl n = 2) (289) The reaction of carbazole (287) (260 mg, 0.51 mmol) prepared as described in Example 297 with 4-bromo-1-butene (155 μ ?, 1.53 mmol) according to the procedure described in example 298 gave carbazole (289) 173 mg, 58%) in the form of a yellow powder, mp 161-164 ° C. 1 H NMR d [(CD3) 2 SO] 8.50 (d, J = 2.6 Hz, 1 H), 7_.89 (s, 1 H), 7.73 - "(d, J = 9.0 Hz, 1 H), - 7.60 -7.46 (m, 4H), 7.-31 (dd, J = 9.0, 2.6 Hz, 1 H), 6! 96 (d, J = 8.5 Hz, 1 H), 6.57 (d, J = 2.3 Hz, 1 H), 6.44 (dd, J = 8.4, 2.3 Hz, 1 H), 5.84 (m, 1 H), 4.96-4.86 (m, 2H), 4.68 (s, 2H), 4.60 (t, J = 6.9 Hz, 2H), 3.89 (s, 3H), 3.80 (s, 3H), 3.72 (s, 3H), 2.54 (m partially obscured, 2H) Found: C, 70.23, H, 5.15, N, 4.91, C34H39CIN205 requires: C, 70.28; H, 5.03; N, 4.82.

Representative procedure for method 21 of scheme 1 1 EXAMPLE 300 The preparation of 4- (2-Chlorophenyl) -6- (2,3-dihydroxypropyl) -2- (2,4-dimethoxybenzyl) -9-methoxypyrrolo [3,4-c] carbazoi-1.3 (2H.6H) -dione (XLVII: Ar = 2-chlorophenyl n = 1) (290) To a solution of the carbazole (288) (80 mg, 0.14 mmol) of the procedure described in example 298 in acetone / water (4: 1, 20 ml) was added N-methylmorpholine N-oxide (33 mg, 0.28 mmol). ) and osmium tetroxide (176 μ ?, 4% solution in water, -0.028 mmol). The reaction mixture was stirred at room temperature for 18 hours before being diluted with 1N hydrochloric acid and extracted with ethyl acetate. The organic phase was dried, the drying agent was removed and the solution was concentrated to dryness, chromatography on silica eluting with ethyl acetate / hexane (2: 1) followed by crystallization from diethyl ether / hexane gave the diol ( 290) (80 mg, 94%) as a yellow powder, mp 151-156 ° C. 1 H NMR d [(CD3) 2 SO] 8.50 (d, J = 2.6 Hz, 1 H), 7.82 (s, 1 H), 7.69 (day, J = 9.0 Hz, 1 H), 7.58 (m, 1 H), 7.52-7.46 (m, 3H), 7.30 (dd, J = 9.0, 2.6 Hz, 1 H), 6.95 ( d, J = 8.4 Hz, 1 H), 6.57 (d, J = 2.4 Hz, 1 H), 6.44 (d, J = 8.4, 2.4 Hz, 1 H), 5.02 (d, J = 5.0 Hz, H) , 4.87 (sa, 1 H), 4.69 (s, 2H), 4.55 (m, 1 H), 4.38 (m, 1 H), 3.89 (m, 4H), 3.80 (s, 3H), 3.72 (s, 3H), 3.41 (m partially darkened, 2H).

Found: C, 65.32; H, 5.00; N, 4.83. C33H29CIN2O7. 1 / 4H20 requires: C, 65.45; H, 4.91; N, 4.63.

EXAMPLE 301 The preparation of 4- (2-chlorophenyl) -6- (3,4-dihydroxybutyl) -2- (2,4-dimethoxybenzyl) -9-methoxypyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione ( XLVII: Ar = 2-chlorophenyl, n = 2) (291) The reaction of carbazole (289) (100 mg, 0.17 mmol) of the procedure described in Example 299 according to the procedure described in Example 300, with the exception that the reaction time was 48 hours gave the diol (291). ) (74 mg, 71%) in the form of a yellow powder, mp 26-131 ° C. '"' '" H NMR or [(CD3) 2SO] 8.51 (d, J = 2.5 Hz, 1 H), 7.83 (s, 1 H), 7.72 (d, J = 9.0 Hz, 1 H), 7.56 ( m, 2H), 7.48 (m, 2H), 7.33 (dd, J = 9.0, 2.5 Hz, 1 H), 6.94 (d, J = 8.4 Hz, 1 H), 6.57 (d, J = 2.3 Hz, 1 H), 6.44 (dd, J = 8.4, 2.3 Hz, 1 H), 4.76 (t, J = 5.0 Hz, 1 H), 4.69 (s, 2H), 4.60-4.52 (m, 3H), 3.90 (s) , 3H), 3.80 (s, 3H), 3.72 (s, 3H), 3.45-3.20 (m partially obscured, 3H), 1.99 (m, 1 H), 1.69 (m, H). Found: C, 66.39; H, 5.02; N, 4.44. C34H31CIN2O7 requires: C, 66.39; H, 5.08; N, 4.55.

Representative procedure for method 22 of scheme 11 EXAMPLE 302 The preparation of 4- (2-chlorophenyl) -6- (2,3-dihydroxypropyl) -9-hydroxypyrrol [3,4-c1carbazole-1.3 (2H. 6H) -dione (XLVIII: Ar = 2-chlorophenyl) n = 1) (292) To a solution of the diol (290) (75 mg, 0.13 mmol) prepared as described in Example 300 in anisole (0.5 ml) was added trifluoroacetic acid (2.0 ml). The reaction vessel was sealed and heated to 90 ° C in an oil bath for 18 h before the trifluoroacetic acid was removed under reduced pressure. Then, the residue was diluted with water and extracted with diethyl ether (3 times). The combined organic extracts were washed thoroughly with 1N potassium hydroxide and then with brine before being dried over anhydrous sodium sulfate and concentrated in vacuo.Then, the aqueous layer was acidified by the addition of concentrated hydrochloric acid, extracted with diethyl ether and treated as described above. The combined crude material was triturated with diethyl ether / hexane and then dissolved in dichloromethane (20 ml) and demethylated according to the procedure described in example 80 to give, after chromatography on silica eluting with ethyl acetate / hexane (from 1: 1 to 1: 0), phenol (292) (31 mg, 57%) in the form of an orange powder, mp 305-309 ° C. 1 H NMR d [(CD3) 2 SO] 11.04 (br s, 1H), 9.33 (s, 1H), 8.38 (d, J = 2.4 Hz, 1H), 7.73 (s, 1H), 7.57 (m, 2H), 7.47 (m, 3H), 7.13 (dd, J = 8.8, 2.4 Hz, 1H), 4.99 (d, J = 5.5 Hz, 1H), 4.83 (t, J = 5.4 Hz, H), 4.50 (m, 1H) (4.32 (m, 1H), 3.87 (sa, 1H), 3.45-3.36 (m, 2H) Found: C, 63.17; H, 3.94; N, 6.18, C23H17CIN2O5 requires: C, 63.24; H, 3.92; N.6.41.

EXAMPLE 303 The preparation of 4- (2-chlorophenyl) -6- (3,4-dihydroxybutyl) -9- h -droxypyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (XLVIII: AR2-chlorophenyl. n = 2) (293) The reaction of the diol (291) (35 mg, 0.06 mmol) prepared as - "has been described in Example 301 according to the procedure described in Example 302 gave the phenol (293) (25 mg, 92%) in the form of an orange powder, mp 263-267 ° C. 1 H NMR d [(CD3) 2 SO] 11.05 (br s, 1H), 9.35 (s, 1H), 8.38 (d, J = 2.4 Hz, 1H), 7.73 (s) , 1H), 7.58 (m, 2H), 7.49 (m, 3H), 7.15 (dd, J = 8.8, 2.4 Hz, 1H), 4.73 (t, J = 4.9 Hz, 1H), 4.52 (m, 3H) 3.48-3.20 (m, 3H), 1.98 (sa, 1H), 1.67 (sa, 1H), FABMS found [M + H] +: 451.1024.453.1021, C24H19CIN2O5 requires 451.1061, 453.1031.

EXAMPLE 304 The reaction of carbazole (287) (50 mg, 0.09 mmol per reaction) prepared as described in Example 297 with iodomethane, iodoethane, 1-bromopropane, 1-bromobutane, 1-bromopentane, allyl bromide, (2-bromoethyl) ) benzene, 3-bromopropin, 1-bromo-3-methylbutane, 2-bromopropane, 2-iodo-1,1,1-trifluoroethane, 5-bromo-1-pentene, iodoacetamide, 4-bromo-1 -butene, 1-bromo-2-methylpropane and 1-bromo-4,4,4-trifluorobutane sequentially according to the procedure described in Example 298, with the exception that the reaction time was 18 hours, followed by deprotection according to the procedure described in Example 302, with the exception that ethyl acetate was used as the treatment solvent and washing with 1 N potassium hydroxide was omitted, given | respectively:, - | | - - · "" 4- (2-chlorophenyl) -9-hydroxy-6-methyl-pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = 2-chlorophenyl) , R10 = CH3) (294). Found: M + H = 377. 4- (2-chlorophenyl) -6-ethyl-9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = 2-chlorophenyl) , R10 = CH2CH3) (295). Found: M + H = 391. 4- (2-chlorophenyl) -9-hydroxy-6-propylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = 2-chlorophenyl) , R 0 = (CH 2) 2 CH 3) (296). Found: M + H = 405. 6-Butyl-4- (2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = 2-chlorophenyl) , R 0 = (CH 2) 3 CH 3) (297). Found: M + H = 419. 4- (2-chlorophenyl) -9-hydroxy-6-pentH-pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = 2-chlorophenol, R10 = (CH2) 4CH3) (298). Found: M + H = 433. 6-allyl-4- (2-chlorophenol) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H (6H) -5-dione (VI; Ar = 2-chlorophenyl, R10 = CH2CH = CH2) (299) Found: M + H = 403. 4- (2-chlorophenol) -9-hydroxy-6- (2-phenylethyl) pyrrolo [3 , 4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = 2-chlorophenyl, R10 = CH2CH2Ph) (300) Found: M + H = 467. 4- (2-chlorophenyl) - 9-hydroxy-6- (2-propynyl) pyrrolo [3,4-c] carbazole-10 1, 3 (2H, 6H) -dione (VI; Ar = 2-chlorophenyl, R10 = CH2C = CH) ( 301) Found: M + H = 401. 4- (2-chlorophenyl) -9-hydroxy-6-isopentylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = 2-chlorophenyl, R10 = CH2CH2CH (CH3) 2) (302) t "| _-, '" Found: M + H = 433. _ - 5 4- (2-chlorophenyl) -9-hydroxy-6-isopropylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = 2-chlorophenyl, R 10 = CH (CH 3) 2) (303) Found: M + H = 405. 4- (2-chlorophenyl) -9-hydroxy-6- (2,2,2-trifluoroethyl) (pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = 2-chlorophenyl) , R10 = CH2CF3) (304) Found: M + H = 445. 20 4- (2-c lorophenyl) -9-hydroxy-6- (4-pentenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = 2-chlorophenyl, R10 = (CH2) 3CH = CH2) (305). Found: M + H = 431. 2- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihiclropyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = 2-chlorophenyl, R10 = CH2CONH2) (306) Found: M + H = 420. 6- (3-butenyl) -4- (2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3 (2H, 6H) -dione (VI; Ar = 2-chlorophenyl, R10 = (CH2) 2CH = CH2) (307) Found: M + H = 417. 4- (2-chlorophenyl) -9-hydroxy- 6-isobutylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = 2-chlorophenyl, R10 = CH2CH (CH3) 2) (308) Found: M + H = 419 4- (2-chlorophenyl) -9-hydroxy-6- (4,4,4-trifluorobutyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar; = 2-chlorophenyl, R10 = (CH2) 3CF3) (309) Found: M + H = 473.

EXAMPLE 305- The reaction of carbazole (287) (50 mg, 0.09 mmol per reaction) prepared as described in Example 297 with 2-iodobutane and cyclopentyl bromide sequentially according to the procedure described in Example 298, with the exception of that the reaction time was 48 hours, followed by deprotection according to the procedure described in Example 302, with the exception that ethyl acetate was used as the treatment solvent and the washing with 1 N potassium hydroxide was omitted. , gave respectively: 6-sec-butyl-4- (2-dorophenol) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = 2 chlorophyl ether, R 10 = CH (CH 3) CH 2 CH 3) (310). Found: M + H = 419. 4- (2-chlorophenol) -6-cyclopent-9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar; = 2-chlorophenyl, R10 = cyclopentyl) (311). Found: M + H = 4321.

EXAMPLE 306 The reaction of carbazole (287) (50 mg, 0.09 mmol) prepared as described in Example 297 with 2-bromoethyl methyl ether sequentially; according to the procedure described in Example 298, with the exception that the reaction time was 18 hours, followed by the deprotection according to the procedure described in Example 302 G with the exception that acetate was used of ethyl as a treatment solvent and that washing with 1N potassium hydroxide was omitted, and of the demethylation according to the procedure described in Example 81, gave: 6- (2-chloroethyl) -4- (2-chlorophenyl) ) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = 2-chlorophenyl, R10 = CH2CH2Cl) (312). Found: M + H = 425. The reaction of carbazole (287) (50 mg, 0.09 mmol per reaction) prepared as described in Example 297 with 1-chloro-2-propanol, (S) -3-bromo- 2-methyl propanol and (R) -3-bromo-2-methylpropanol sequentially according to the procedure described in Example 298, with the exception that the reaction time was 18 hours, followed by deprotection according to with the procedure described in example 302 gave: 4- (2-chlorophenyl) -9-hydroxy-6- (2-hydroxypropyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione ( VI; Ar = 2-chlorophenyl, R10 = CH2CH (OH) CH3) (313). Found: M + H = 421. 4- (2-chlorophenyl) -9-hydroxy-6 - [(2S) -3-hydroxy-2-methylpropyl] pyrrolo [3,4-c] carbazole-1 , 3 (2H, 6H) -dione (VI; Ar = 2-chlorophenyl, R10 = CH2CH (CH3) CH2OH) (314). Found: M + H = 435. 4- (2-chlorophenyl) -9-hydroxy-6 - [(2R) -3-hydroxyl-2-methylpropyl] pyrrolo [3,4] carbazole-1,3 ( 2H, 6H) -dione (VI; Ar = 2-chlorophenyl, R10 = CH2CH (CH3) CH2OH) (315). Found: M + H = 435.

SCHEME 12 Procedures for Scheme 12 Representative procedure for method 24 of scheme 12 EXAMPLE 307 The preparation of trifluoromethanesulfonate of 4- (2-chlorophenyl) -9-methoxy-6- (2-methoxyethyl) -1,3-dioxo-1,2,3,6-tetrahydropyrrolo [3,4-c] carbazole-8 -yl (XLIX, Ar = 2-chlorophenyl, R10 = CH CH; OCHj (168) 0 Trifluoromethanesulfonic anhydride (1.30 ml, 7.77 mmol) at 0 ° C was added dropwise to a solution of phenyl (167) (0.50 g, 1.11 mmol) prepared as described in example 26 and pyridine (6.29 m). , 0.077 mol) in tetra h id rofu rano (50 ml). The solution was allowed to warm to room temperature for 1 h before dNution with 1 N HCl and extraction with 5 ethyl acetate. The extract was dried, the drying agent was removed and the solution was concentrated to dryness to give a solid that was adsorbed on silica and chromatographed. Elution with ethyl acetate / petroleum ether (11) gave the filtrate (168) (0.53 g, 82%) as a yellow powder, m.p. 229-231 ° C. 1 H NMR d [(CD3) 2 SO] 11.23 (br s, H), 8.78 (s, 1 H), 8.01 (s, 1 H), 0 7.93 (s, 1 H), 7.59 (dd, J = 8.0. Hz, 1 H), 7.54-7.44 (m, 3H), 4.73 (t, J = 4.8 Hz, 2H), 4.04 (s, 3H), 3.68 (t, J = 4.8 Hz, 2H), 3.14 (s, 3H). Found: C, 49.26; H, 2.91; N, 4.39. C25H18CIF3N2O7. 1 / 2CH2Cl2 requires C, 48.97; H, 3.06; N, 4.48.

EXAMPLE 308 The preparation of 4- (2-chlorophenyl) -9-methoxy-1,3-dioxo-1.2.3.6-tetrahydropyrrolof3.4-c] carbazol-8-yl trifluoromethanesulfonate (XLIX: Ar = 2-chlorophenyl) R10 = H ) (169) Reaction of (163) with trifluoromethanesulfonic anhydride using the procedure described in Example 307 gave triflate (169) (87%) as a yellow solid, m.p. 248-252 ° C. 1 H NMR d [(CD3) 2 SO] 12.16 (a, 1 H), 1 1.21 (a, 1 H), 8.73 (s, 1 H), 7.80 (s, 1 H), 7.71 (s, 1 H), 7.58 (d, J = 8.0, 2.2 Hz, 1 H), 7.52-7.43 (m, 3H), 4.03 (s, 3H). Found: C, 52.32; H, 2.87; N, 4.87. CaaH ^ CIFaNaSOe; THF requires C, 52.31; H, 3.38; N, 4.69. _ _ Representative procedure for method 25 of scheme 12 EXAMPLE 309 The preparation of 4- (2-chlorophenyl) -8 - [(1E) -4-hydroxy-1-butenyl] -9-methoxypyrrolof3.4-c carbazole-1.3 (2H.6H) -dione (L: Ar = 2-chlorophenyl, R10 = H. Z = CH, CH? Om (170) A solution of triflate (169) (0.20 g, 0.35 mmole) prepared as described in example 308, (3E) -4- (tributylstannyl) -3-buten-1-ol (0.19 g, 0.53 mmole) and chloride of lithium (29 mg, 0.70 mmol) in DMF (10 mL) was purged by bubbling nitrogen through the liquid for 10 min. At the end, bis (triphenylphosphine) palladium chloride (12 mg, 0.017 mmol) was added and the solution was flushed with nitrogen for a further 2 min and then heated under a nitrogen atmosphere for 3 hours. The mixture was diluted with brine, extracted with ethyl acetate and treated to give an oil which was chromatographed on silica. Elution with ethyl acetate / petroleum ether (1: 5) gave precursors, while elution with ethyl acetate / petroleum ether (1: 1) increasing to pure ethyl acetate gave (70) as a solid yellow (0.15 g, 95%), mp 271-275 ° C. 1 H NMR d [(CD 3) 2 SO] 11.86 (br s, 1 H), 11.07 (br s, 1 H), 8.45 (s, 1 H), 7.70 (s, 1 H), 7.58 (dd, J = 8.1, 2.2 Hz, 1H), 7.55 (s, 1 H), 7.51-7.41 (m, 3H), 6.87 (d, J = 16.0 Hz, 1 H), 6.44 (dt, J = 16.0, 7.1 Hz, 1 H), 4.62 (t, J = 5.3 Hz, 1 H), ~ 3.94 (s / 3H) ~; 3.58 (rñ, 2H), 2.42 (m, 2H). _. · - - · Found: C, 67.09; H, 4.36; N, 5.98. C25H19CIN2O4 requires C, 67.19; H. 4.28; N, 6.27.

Representative procedure for method 26 of scheme 12 EXAMPLE 310 The preparation of 4- (2-chlorophenyl) -8- (4-hydroxybutyl) -9-methoxypyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (Ll: Ar = 2-chlorophenyl) R10 = H. Z = CH CH OH) (171) A mixture of (170) (0.15 g, 0.33 mmol) prepared as described in Example 309 and Pt02 (20 mg) in 1: 1 tetrahydrofuran / methanol (30 mL) was stirred under an atmosphere of hydrogen gas at 40 ° C. psi (275,790 kPa) for 30 min. The catalyst was removed by filtration through Celite, washing through it with more solvent. The combined filtrates were treated and chromatographed on silica. Elution with ethyl acetate / petroleum ether (1: 1) gave (171) as an orange solid (0.20 g, 100%), m.p. 256-260 ° C (dec). 1 H NMR d [(CD3) 2 SO] 1 1.90 (a, 1 H), 11. 10 (a, 1 H), 8.34 (s, 1 H), 7.64-7.40 (m, 6H), 4.37 (a, 1 H), 3.93 (s, 3H), 3.43 (t, J = 6.3 Hz, 2H), 2.76 (t, J = 7.6 Hz, 2H), 1.66 (m, 1 H), 1.50 (m, 2H).

EXAMPLE 311 The preparation of 4- [4- (2-chlorophenyl) -9-methoxy-1,3-dioxo-1.2.3.6-tetrahydropyrrolo [3,4-c] carbazol-8-yl] butyl trifluoromethanesulfonate (LUI: Ar = 2- Chlorophenyl R10 = H. n = 4. Z = OMs) (172) Mesylation of (171) prepared as described in Example 310 with methanesulfonyl chloride and triethylamine using the procedure described in Example 170 of Scheme 3 gave the mesylate (172) as a yellow solid (98%) which was used without further purification.

Representative procedure for method 27 of scheme 12 EXAMPLE 312 _ The preparation of 4- (2-Chlorophenyl) -8- (4-iodobutyl) -9-methoxypyrrolo [3,4-c1carbazole-1.3 (2H.6H) -dione (LUI: Ar = 2-chlorophenyl) R10 = H. n = 4. Z = l) (173) A mixture of the mesylate (172) (0.12 g, 0.21 mmol) prepared as described in Example 31 1 and sodium iodide (1 g) in ethyl acetate (50 ml) was heated to reflux for 4 h. The cooled solution was washed with water and treated to give the iodide (173) which crystallized from tetrahydrofuran / petroleum ether as an orange powder (0.0 g, 85%), m.p. 142-144 ° C. 1 H NMR d [(CD 3) 2 SO] 1 1 .86 (s, 1 H), 11.05 (s, 1 H), 8.43 (s, 1 H), 7.58 (m, 1 H), 7.55 (s, 1 H), 7.52-7.43 (m, 3H), 7.42 (s, 1 H), 3.94 (s, 3H). EIMS found M + = 558.0212, 560.0178. C25H2oCIN203 requires 558.0207, 560.0178.

EXAMPLE 313 The preparation of 4- (2-chlorophenyl) -8- [4- (dimethylamino) butyl] -9-methoxypyrrolof3.4-c1carbazole-1.3 (2H.6H) -dione fLIV: Ar = 2-chlorophenyl. R10 = H: n = 4. Z = N (CH2) 2) (174) The reaction of the iodide (173) prepared as described in Example 312 with aqueous dimethylamine using the procedure described in Example 179 of Scheme 3 with the exception that the conditions of "reaction were 6 h at room temperature gave (74) ) (64%) in the form of an orange powder, mp 162-1164 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.85 (s, 1 H), 11.04 (br s, 1 H), 8.42 (s, 1 H), 7.57 (dd, J = 8.0, 2.2 Hz, 1 H), 7.55 (s, 1 H), 7.51-7.43 (m, 3H), 7.42 (s, 1 H), 3.93 (s, 3H) , 2.77 (t, J = 7.4 Hz, 2H), 2.24 (t, J = 7.3 Hz, 2H), 2.11 (s, 6H), 1.63 (m, 2H), 1.47 (m, 2H), EIMS found M + = 475.1657, 477.1650, C27H26CIN3O3 requires 475.1663, 477.1633.

EXAMPLE 314 The preparation of 4- (2-chlorophenyl) -8-f4-fdimethylamino) butyne-9-hydroxyr3.4-c] carbazole-1.3 (2H.6H) -dione (LV: Ar = 2-chlorophenyl) R10 = H. n = 4. Z = Ohúz) (175) The demethylation of (174) prepared as described in Example 313 with pyridine hydrochloride using the procedure described in Example 81 gave (176) (67%) as a yellow powder, m.p. 220-226 ° C (dec). 1 H NMR d [(CD3) 2 SO] 11.72 (s, 1 H), 10.98 (s, 1 H), 9.33 (a, 1 H), 8. 32 (s, 1 H), 7.56 (dd, J = 8.0, 2.2 Hz, 1 H), 7.49 (s, 1 H), 7.49-7.40 (m, 3H), 7.33 (s, 1H), 2.74 (t , J = 7.33 Hz, 2H), 2.54 (m, 2H), 2.34 (sa, 6H), 1.64 (m, 2H), 1.54 (m, 2H). ^. . ~ - '· FABIvlS found [M + H] +: .464.1569, 462.1578. C26H25CIN3O3 requires 464.1555, 462.1584.

EXAMPLE 315 The preparation of 4- (2-chlorophenyl) -9-methoxy-8- [4- (1-pyrrolidinyl) butyl] pyrroiof3.4-c] carbazole-1.3 (2H.6H) -dione (LIV: Ar = 2- chlorophenyl, R10 = H. n = 4. Z = 1-pyrrolodinyl) (176) The reaction of the iodide (173) prepared as described in Example 312 with pyrrolidine using the procedure described in Example 179 with the exception that the reaction conditions were 2H at room temperature gave (176) (75%) as of an orange powder, which was used without further purification, mp 173-178 ° C. 1 H NMR d [(CD3) 2 SO] 11.85 (s, 1 H), 11.04 (br s, 1 H), 8.42 (s, 1 H), 5 7.57 (dd, J = 8.0, 2.2 Hz, 1 H), 7.55 (s, 1 H), 7.51-7.43 (m, 3H), 7.42 (s, 1 H), 3.93 (s, 3H), 2.77 (t, J = 7.4 Hz, 2H), 2.24 (t, J = 7.3 Hz, 2H), 2.1 1 (s, 6H), 1.63 (m, 2H), 1.47 (m, 2H).

EXAMPLE 316 10 The preparation of 4- (2-chlorophenyl) -9-hydroxy-8- [4- (1-pyrrolidinyl) butyl] pyrroium [3,4-c] carbazole-1.3 (2H.6H) -dione (LV : Ar = 2-chlorophenyl, R10 = H. n = 4. Z = 1-pyrrolidinyl) (177) "~" "The demethylation of (173) prepared as described in Example 312 with pyridine hydrochloride using the procedure described in Example 81 gave (177) (72%). 1 H NMR d [(CD3) 2 SO] 11.70 (s, 1 H), 10.91 (s at, 1 H), 9.30 (a, 1 H), 8.31 (s, 1 H), 7.57 (dd, J = 8.0, 2.2 Hz, 1 H), 7.49 (s, 1 H), 7.49-7.40 (m, 3H), 7.32 (s, 1 H), 2.73 (t, J = 7.5 Hz, 2H), 2.44-2.36 (m, 6H) ), 1.69-1.61 (m, 6H), 1.51 (m, 20 2H). The hydrochloride salt had n m.p. from 173-178 ° C (dec). Found: C, 62.27; H, 5.22; N, 7.74. C28H26CIN3O3. HCI. H20 requires C, 62.00; H, 5.39; N, 7.75.

EXAMPLE 317 The preparation of 4- (2-chlorophenyl) -9-methoxy-6- (2-methoxyethyl) -8-vinylDirrolo [3,4-c1carbazole-1.3 (2H.6H) -dione (L: Ar = 2-chlorophenyl. R1Q = CH2CH2OCH3, Z = H) (178) The reaction of triflate (168) prepared as described in Example 307 with tetravini-stano using the procedure described in Example 309 gave the vinyl compound (178) (64%) as a yellow solid, which was used without purification additional. 1 H NMR d [(CD3) 2 SO] 1 1.11 (s, 1 H), 8.53 (s, 1 H), 7.95 (s, 1 H), 7.80 (s, 1 H), 7.58 (dd, J = 8.1, 2.2 Hz, 1 H), 7.52-7.43 (m, 3H), 7.18 (dd, J = 17.6, 11.2 Hz, H), 6.06 (dd, J = 17.6, 1.3 Hz, 1 H), 5.42 (dd, = 1.2, 1.3 Hz, 1 H), 4.71 (t, J = 5.0 Hz, 2H), 3.97 (s, 3H), 3.71 (t, J = 5.0 Hz, 2H), 3.16 (s, 3H). _ _ _r r.

EXAMPLE 318 The preparation of 4- (2-chlorophenyl) -8- (2-hydroxyethyl) -9-methoxy-6- (2-methoxyethyl) pyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (Ll: Ar = 2-chlorophenyl, R10 = H. Z = OH) (179) Hydroboration of (178) prepared as described in Example 317 with 9-BBN using the procedure described in Example 344 gave (179) (86%) as a yellow solid, m.p. 271-273 ° C.

H NMR d [(CD3) 2 SO] 1 1.08 (br s, 1 H), 8.49 (s, 1 H), 7.78 (s, 1 H), 7.60 (s, 1 H), 7.57 (dd, J = 8.0, 2.2 Hz, 1 H), 7.52-7.42 (m, 3H), 4.68 (t, J = 5.2 Hz, 1 H), 4.65 (t, J = 5.1 Hz, 2H), 3.94 (s, 3H), 3.70 ( m, 4H), 3.15 (s, 3H), 2.96 (t, J = 7.2 Hz, 2H).

EXAMPLE 319 The preparation of 4- (2-chlorophenyl) -9-hydroxy-6,8-bis (2-hydroxyethyl) pyrrolo [3,4-clcarbazole-1.3 (2H.6H) -dione (Lll: Ar = 2-chlorophenyl) R10 = CH CH2OH, Z = OH) (180) The demethylation of (179) prepared as described in Example 318 with BBr3 using the procedure described in Example 80 with the exception that the reaction conditions were 12 equiv. of reagent at 0 ° C for 67 hr (180) as a yellow solid (35), m.p. 278-280 ° C: 1 H NMR d [(CD3) 2 SO] 1 1.00 (s a, 1 H), 9.39 (a, 1 H), 8.37 (s, 1 H), 7. 72 (s, 1 H), 7.56 (dd, J = 8.0 (2.2 Hz, 1 H), 7.51 -7.42 (m, 4H), 4.82 (t, J = 5.5 Hz, 1 H), 4.72 (a, 1 H), 4.47 (t, J = 5.4 Hz, 2H), 3.76 (dt, J = 5.5, 5.4 Hz, 2H), 3.69 (t, J = 7.2 Hz, 2H), 2.93 (t, J = 7.2 Hz, 2H) .FABMS found M +: 452.0993, 450.0984, C24Hi9CIN205 requires 452.0953, 450.0982.

EXAMPLE 320 The preparation of trifluoromethanesulfonate of 9-methoxy-8-methyl-1,3-dioxo-4-phenyl-1.2.3.6-tetrahydropyrrolo [3,4-clcarbazol-8-yl (XLiX, Ar = phenyl, R10 = CH3) (185) The reaction of (154) prepared as described in Example 254 with trifluoromethanesulfonic anhydride using the procedure described in Example 307 gave 9-methoxy-6-methyl-1,3-dioxo-4-phenyl-1,2-trifluoromethanesulfonate. , 3,6-tetrahydropyrrolo [3,4-c] carbazo1-8-yl in the form of a yellow solid (85%), mp 244-246 ° C. 1 H NMR d [(CD 3) 2 SO] 11.22 (br s, 1 H), 8.76 (s, 1 H), 7.96 (s, 1 H), 7.90 (s, 1 H), 7.68-7.66 (m, 2H), 7.52-7.46 (m, 3H), 4.02 (s, 3H), 3.99 (s, 3H).

EXAMPLE 321 The preparation of 4- (2-chlorophenyl) -9-methoxy-6-methyl-1,3-dioxo-1-2.3-6-tetrahydropyrrolo [3,4-c] carbazole-8-yl trifluoromethanesulfonate (XLiX: Ar-2) -chlorophenyl, R10 = Me) (700) The reaction of (160) prepared as described in Example 260 with trifluoromethanesulfonic anhydride using the procedure described in Example 307 gave triflate (700) (89%) as a yellow solid, m.p. 251-253 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.26 (br s, 1 H), 8.80 (s, 1 H), 8.02 (s, 1 H), 7.87 (s, 1 H), 7.61-7.44 (m, 4H) . Found: C, 52.51; H, 3.14; N, 4.97. C23H14N2CIF306S. 1/4 Hexane requires: C, 52.51; H, 3.15; N, 5.00. 5 FABMS found [M + H] +: 539.0262, 541.0240.

C23H15N2CIF3O6S requires 539.0292, 541.0262.

EXAMPLE 322 The preparation of 2,8-diallyl-4- (phenyl) -9-methoxy-6-methylpyrrolo [3,4-10 clcarbazo! -1.3 (2H.6H) -dione (LVI: Ar = phenyl, R = Me) (186) and 8-allyl-4- (phenyl) -9-methoxy-6-methylpyrrolof3.4-c1carbazole-1.3 (2H.6H) -dione (LVI: Ar = phenyl, R10 = Me) (1871 The reaction of the triflate (185) prepared as described in Example 320 and allyltri-n-butyltin at 100 ° C for 1 h using the procedure described in Example 309 gave a product crude was chromatographed on silica gel (ethyl acetate / petroleum ether (1: 4)) to yield (i) the pure bis-allyl compound (186) (12%) as an orange solid, mp 188-189 ° C. 20 1 H NMR d [(CD 3) 2 SO] 8.52 (s, 1 H), 7.81 (s, 1 H), 7.66 (dd, J = 8.0, 1. 7 Hz, 2H), 7.53-7.43 (m, 4H), 6.10 (m, 1 H), 5.91 (m, 1 H), 5.21 -5.06 (m, 4H), 4.22 (d, J = 5.1 Hz, 2H ), 3.95 (s, 6H), 3.56 (d, J = 6.6 Hz, 2H).

Found C, 76.43; H, 5.59; N, 6.48. C28H24N203. 1/10 H20 requires: C, 76.73; H, 5.56; N, 6.39; followed by (i) the pure mono-allyl compound (187) (42%) m.p. 204-208 ° C. 1 H NMR d (CDCl 3) 1.08 (s, 1 H), 8.52 (s, 1 H), 7.78 (s, 1 H), 7.67- 5 7.64 (m, 2 H), 7.50 (s, 1 H), 7.49- 7.43 (m, 3H), 6.09 (ddt, J = 6.6 Hz, 1 H), 5.15- 5.07 (m, 2H), 3.94 (s, 6H), 3.56 (d, J = 6.6 Hz, 2H); Found: C, 73.75; H, 5.39; N, 6.76. C25H20 2O3. 3/2 H20 requires C, 73.51; H, 5.26; N, 6.86.

EXAMPLE 323 The preparation of 4- (phenyl) -9-methoxy-6-methyl-8-vinylpyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (L: Ar = phenyl. Z = H) (701) The reaction of the triflate, (185) prepared as described in Example 320 and tetravinyltin at 100 ° C for 1 h using the procedure described in Example 309 gave a crude product which was chromatographed on silica gel. silica (ethyl acetate / petroleum ether (1: 2)) to yield the pure 8-vinyl compound (701) (68%) as an orange solid, mp 220 ° C (dec). [(CD3) 2SO] 1 1.12 (a, 1 H), 8.57 (s, 1 H), 7.92 (s, 1 H), 7. 790 (s, 1 H), 7.69-7.64 (m, 2H), 7.52-7.43 (m, 3H), 7.20 (dd, J = 17.7, 11.2 Hz, 1 H), 6.09 (dd, J = 17.7, 1.2 Hz, 1 H), 5.42 (dd, J = 11.2, 1.2 Hz, 1 H), 4.00 (s, 3H), 3.96 (s, 3H).

Found: C, 74.45; H, 4.78; N, 6.94. C24H18N2O3. 1/4 H20 requires C, 74.50; H, 4.82; N, 7.24.

EXAMPLE 324 EXAMPLE 325 The preparation of 2-8-diallyl-4- (2-chlorophenyl) -9-methoxy-6-methylpyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (LVI: Ar = 2-chlorophenyl, R = Me) (702) and 8-allyl-4- (2-chlorophenyl) -9-methoxy-6-methylpyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (LVII: Ar = 2-chlorophenyl, R10 = Me) (703) The reaction of the triflate (700) prepared as in Example 321 and allyltri-n-butyltin at 100 ° C for 1 h using the procedure described in Example 309 gave a crude product which was chromatographed on silica gel (ethyl acetate / Petroleum ether (1: 3) to produce (i) the pure bis-allyl compound (702) (49%) as an orange solid, mp 183-185 ° C. H NMR d [(CD3) 2SO] 8.51 (s, 1 H), 7.82 (s, 1 H), 7.61-7.44 (m, 5H), 6.16-6.05 (m, 1 H), 5.95-5.85 (m, 1 H), 5.17-5.07 (m, 4H), 4.21 (day, J = 5.0 Hz, 2H), 3.96 (s, 6H), 3.57 (d, J = 6.5 Hz, 2H) Found: C, 71.53, H, 5.14, N, 6.20, C28H23, 2CE3 required: C, 71.41; H, 4.92; N, 5,954; followed by (ii) the mono-allyl compound (703) (31%) as a yellow solid, mp 269-272 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.10 (a, 1 H), 8.52 (s, 1 H), 7.77 (s, 1 H), 7.58-7.43 (m, 4H), 6.16-6.07 (m, 1 H), 5.17-5.07 (m, 2H), 3.95 (s, 6H), 3.57 (d, J = 6.5 Hz, 2H). Found: C, 69.58; H, 4.55; N, 6.46. C25H19N2CIO3 requires C, 69.69; H, 4.44; N, 6.50.

EXAMPLE 326 The preparation of 4- (2-chlorophenyl) -9-methoxy-6-methyl-8-vinylpyrrolo [3,4- c] carbazole-1.3 (2H.6H) -dione (L: Ar = 2-chlorophenyl) R10 = Me. Z = H) (704) The reaction of triflate (700) prepared as in Example 321 and tetravinyltin at 100 ° C for 1 h using the procedure described in Example 309 followed by treatment with excess ammonium acetate at 100 ° C. for 1 h more gave a crude product which was chromatographed on silica gel (ethyl acetate / petroleum ether) (12) to yield the pure 8-vinyl compound (704) (78%) as an orange solid, mp 330 ° C (dec). H NMR d [(CD3) 2 SO] 1 1.12 (a, 1 H), 8.53 (s, 1 H), 7.94 (s, 1 H), 7.78 (s, 1 H), 7.60-7.43 (m, 4H) , 7.20 (dd, J = 17.7, 11.2 Hz, 1 H), 6.10 (dd, J = 17.7, 1.2 Hz, 1 H), 5.43 (dd, J = 11.2, 1.2 Hz, 1 H), 3.99 (s, 3H), 3.97 (s, 3H). Found: C, 58.54; H, 4.08; N, 6.65. C24H17N2CIO3. CH2Cl2. 1/2 NH3 requires C, 58.84; H, 4.05; N, 6.86. FABMS found [M + H] +: 417.0982, 419.0955. C24Hi7N2CI03 requires 4 7. 006, 419.0977.

EXAMPLE 327 The preparation of 4- (2-chlorophenH) -8-f (1 E) -3-hydroxy-1-propenyl] -9-methoxy-6-methylpyrrolof3.4-c] carbazole-1.3 (2H.6H) -dione (L: Ar = 2-chlorophenyl R10 = Me. Z = CH2OH) (710) The reaction of triflate (700) prepared as in example 321 and 3-hydroxyalyltri-n-butyltin using the procedure described in example 309 at 100 ° C for 1 h gave a crude product which was chromatographed on silica gel (ethyl acetate). ethyl / petroleum ether) (1: 1) to produce (710) pure (42%) as an orange solid, mp 283-285 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.11 (s, 1 H), 8.51 (s, 1 H), 7.89 (s, 1 H), 7.76 (s, 1 H), 7.59-7.43 (m, 4H) , 7.05 (da, J = 16.0 Hz, 1 H), 6.67 (dt, J = 16.0, 5.0 Hz, 1 H), 4.94 (t, J = 5.4 Hz, 1 H), 4.22 (ta, J = 5.0 Hz , 2H), 3.99Js, 3H), 3.97 (s, 3H): '' ''. | - - | - "FAB S found M +: 446.1031, 448.1037.C24H17N2CIO3 requires 446.1033, 448.1004.

Representative procedure for method 28 of scheme 12 EXAMPLE 328 Preparation of the dealkylation of the bisalyl compound (Lvi: Ar = 2-chlorophenyl R-Me) (702) to give the monoalyl compound (LVII: Ar = 2-chlorophenyl R10 = Me) (703) The bisalyl compound (702) (72 mg, 0.153 mmol) prepared as described in Example 325 was dissolved in a mixture of acetonitrile (10 mL) and water (1 mL). To this homogeneous solution was added 5 M KOH (1 mL) and the mixture was stirred at room temperature for 64 h. Most of the acetonitrile was evaporated in vacuo and the residue was diluted with water (3 ml). After acidification with 1 N HCl at pH < 1, the acid solution was stirred at 50 ° -6 ° C (bath) for 3 h After partitioning between ethyl acetate and water, the ethyl acetate solution was evaporated and co-evaporated with toluene to give an orange solid that was treated with a large excess of ammonium acetate ground at 140-145 ° C (bath) for 3 h After cooling to room temperature and partitioning between ethyl acetate and water, the ethyl acetate solution was evaporated to give a crude product which was chromatographed on silica gel (ethyl acetate-petroleum ether) (1: 3) to give the pure monoalyl compound (703) (52 mg, 79%). Rf, pf and 1 H NMR spectrum were identical to those of the authentic sample described above.

EXAMPLE 329 The preparation of the dealkylation of the bisalyl compound (LVI: Ar = phenyl, R = Me) (186) to give the monoalyl compound (LVII: Ar = phenyl, R10 = Me) (187) Using the procedure described in Example 328, the bisalyl compound (186) prepared as described in Example 322 was converted to the monoallyl compound (187) (84%). The Rf, p.f. and the 1 H NMR spectrum were identical to those of the authentic sample described above.

EXAMPLE 330 The preparation of 8- (2,3-dihydroxypropyl) -9-methoxy-6-methyl-4-phenyl-pyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (LIX: n - 1. Ar = phenyl. - - '"'" J R10 = Me) (705) - - - The reaction of (187) prepared as in Example 328, N-methylmorpholine N-oxide and osmium tetroxide (at room temperature for 5 h) using the procedure described in Example 300 followed by chromatography on silica gel (acetate ethyl) gave (705) (81%) as an orange solid, mp 243-245 ° C. 'H NMR d [(CD3) 2 SO] 11.06 (a, 1 H), 85.1 (s, 1 H), 7.78 (s, 1 H), 7.68-7.63 (m, 2H), 7.55 (s, 1 H) , 7.50-7.42 (m, 3H), 4.58-4.52 (m, 22H), 3.95 (s, 3H), 3.93 (s, 3H), 3.40 (d, J = 5.3 Hz, 2H), 2.77 (dd, J = 13.5, 7.8 Hz, 1 H).

Found: C, 69.02; H, 5.48; N, 6.44. C25H22N2O5. 1/5 H20 requires: C, 69.18; H, 5.20; N, 6.45.

EXAMPLE 331 The preparation of 8- (1,2-dihydroxyethyl) -9-methoxy-6-methyl-4-phenyl-pyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (LIX: n = 0. Ar = phenyl R10 = Me) (706) The reaction of (701) prepared as described in Example 321, N-methylmorpholine N-oxide and osmium tetroxide (at room temperature for 5 h) using the procedure described in Example 300 followed by gel chromatography of silica (chloroform / methanol) (10: 1) gave (706) (65%) as a yellow solid, mp 242-245 ° C. 1 H NMR d [(CD 3) 2 SO] 1 1.09 (s, 1 H), 8.53 (s, 1 H), 7.81 (s, 1 H), T 7.74 (s, H), 7.68-7.64 (m, 2H) , 7.50-7.41. (m, -3H), 5.35 (d, J = 4.4 Hz, 1 H), 5.12-5.06 (m, 1 H), 4.75 (t, J = 5.3 Hz, 1 H), 3.97 (s, 3H), 3.95 (s, 3H), 3.66-3.60 (m, 1 H), 3.39-3.33 (m, 1 H). Found: C, 69.25; H, 5.14; N, 6.43. C 24 H 20 N 2 O 5 requires: C, 69.22; H, 4.84; N, 6.73.

EXAMPLE 332 The preparation of 8- (2,3-dihydroxypropyl) -9-hydroxy-6-methyl-4-phenyl-pyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (LX: n = 1. Ar = phenyl R10 = Me) (707) The reaction of (705) prepared as described in Example 330 and BBr3 (at 0 ° C for 4 h) using the procedure described in Example 80 gave the phenyl (707) (53%) as an orange solid , pf 283-285 ° C. 1 H NMR d [(CD3) 2 SO] 11.01 (a, 1 H), 9.41 (a, 1 H), 8.38 (s, 1 H), 7. 74 (s, 1 H), 7.67-7.62 (m, 2H), 7.50-7.40 (m, 4H), 3.92 (s, 3H), 3.90-3.84 (m, 1 H), 3.36 (d, J = 5.2 Hz, 2H), 2.98 (dd, J = 13.5, 5.0 Hz, 1 H), 2.74 (dd, J = 13.5. 7. 7 Hz, 1 H). FABMS found -M + = - 416.1365. C24H2oN205 requires 416.1372.

EXAMPLE 333 The preparation of 9-hydroxy-8- (2-hydroxyethyl) -6-methyl-4-phenylpyrrolo [3,4- c] carbazole-1.3 (2H.6m-dione) (Lll: Ar = phenyl: R10 = Me Z = OH) (714) The reaction of (712) prepared as described in Example 340 and BBr3 (at 0 ° C for 3 h) using the procedure described in Example 80 followed by chromatography on silica gel (chloroform / methanol) (20: 1) gave phenol (714) (31%) as a yellow solid, mp. 233-235 ° C. 1 H NMR d [(CD3) 2 SO] 11.01 (a, 1 H), 9.39 (a, 1 H), 8.39 (s, 1 H), 7.74 (s, 1 H), 7.64 (dd, J = 7.6, 1.6 Hz, 2H), 7.50-7.42 (m, 4H), 4.73 (a, 1 H), 3.92 (s, 3H), 3.70 (t, J = 7.1 Hz, 2H), 2.94 (t, J = 7.1 Hz, 2H). FABMS found + = 386.1263. C23H18 2O4 requires 386. 1267 EXAMPLE 334 The preparation of 4- (2-chlorophenyl) -9-hydroxy-8- (2-hydroxyethyl) -6-methylpyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (Lll: Ar = 2-chlorophenyl, R10 = Me, Z = OH) (715) The reaction of (713) -prepared as "has * been described in example 341 and BBr3 (at 0 ° C for 3 h) using the procedure described in example 80 followed by chromatography on silica gel (chloroform / methanol) (20: 1) gave phenyl (715) (81%) as an orange solid, mp 304-306 ° C. 1 H NMR d [(CD3) 2 SO] 11.00 (a, 1 H), 9.30 (a, 1 H), 8.37 (s, 1 H), 7.71 (s, 1 H), 7.57 (dd, J = 7.0, 2.0 Hz, 1 H), 7.52-7.42 (m, 4H), 4.74 (a, 1 H) ), 3.91 (s, 3H), 3.71 (t, J = 7.0 Hz, 2H), 2.94 (t, J = 7.0 Hz, 2H), FABMS found M +: 420.0866, 422.0875, C23H17CIN204 requires 420.0877, 4220.0847.

EXAMPLE 335 The preparation of 4- (2-chlorophenyl) -8-ethyl-9-methoxy-6-methylpyrrolof3.4-c] carbazole- (1.3 (2H.6H) -dione (Ll: Ar = 2-chlorophenyl) R10 = Me. Z = H) (708) Hydrogenation of the alkene (704) prepared as in Example 326 over Pt02 (45 min reaction time) using the procedure described in Example 310 gave the 8-ethyl derivative (708) (97%) as a solid orange, pf 262-264 ° C. H NMR d [(CD3) 2 SO] 1.08 (a, H), 8.48 (s, 1 H), 7.77 (s, 1 H), 7.60-7.42 (m, 5H), 3.95 (s, 6H), 3.90- 3.84 (m, 1 H), 2.82 (c, J = 7.5 Hz, 2H), 1.28 (t, J = 7.5 Hz, 3H). Found: C, 68.21; H, 4.38; N, 6.48. C24Hi9N2CI03. 1/10 H20 requires C, 68.52; H, 4.60; N, 6.66. "R EXAMPLE 336 The preparation of 4- (2-chlorophenyl) -8- (3-hydroxypropyl) -9-methoxy-6-methylpyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (Ll: Ar = 2- chlorophenyl, R1Q = Me, Z = CH2OH) (711) Hydrogenation of the alkene (710) prepared as described in Example 321 on Pt02 using the procedure described in method 26 followed by chromatography on silica gel (ethyl acetate / petroleum ether) (1: 1) gave the Pure 8- (3-hydroxypropyl) compound (711) (44%) as an orange solid, mp 260-263 ° C. 1 H NMR d [(CD3) 2 SO] 11.08 (s, 1 H), 8.48 (s, 1 H), 7.77 (s, 1 H), 7.59-7.43 (m, 5H), 4.50 (t, J = 5.2 Hz , 1 H), 3.95 (s, 6H), 3.49 (m, 2H), 2.83 (t, J = 7.7 Hz, 2H), 1.82 (m, 2H). FABMS found M + = 448.1194, 450.1200. C25H2 CI 2O4 requires 448.1190, 450.1160.

EXAMPLE 337 The preparation of 4- (2-chlorophenyl) -8-ethyl-9-hydroxy-6-methylpyrrolo [3,4-ctaarbazole-1.3 (2H.6m-dione: Ar = 2-chlorophenyl) R10 = Me. Z = H) (709) The reaction of (708) prepared as in Example__75-with pyridinium hydrochloride using the procedure described in Example 81 followed by chromatography on silica gel (ethyl acetate / petroleum ether) (1: 2) gave the phenyl (709) (78%) in the form of a yellow solid, mp 265-268 ° C. 1 H NMR d [(CD 3) 2 SO] 11.01 (s, 1 H), 9.39 (s, 1 H), 8.37 (s, 1 H), 7.71 (s, 1 H), 7.59-7.55 (m, 1 H) , 7.52-7.42 (m, 4H), 3.93 (s, 3H), 2.79 (c, J = 7.5 Hz, 2H), 1.27 (t, J = 7.5 Hz, 3H). EIMS found M + = 404.0925, 406.0905. C ^ H ^ CINaOa requires 404.0928, 406.0898.

EXAMPLE 338 The preparation of 8- [3- (dimethylamino) propyl] -9-hydroxy-6-methyl-4-phenylfirrolof3.4-c1carbazole-1.3 (2H.6H) -dione (LV: n = 3. Ar = phenyl R10 = Me. Z = NMe2) (720) The reaction of (717) prepared as described in Example 342 with pyridinium hydrochloride using the procedure described in Example 81 gave the phenol (720) (83%) as an orange solid, m.p. 315 ° C. 1 H NMR d [(CD3) 2 SO] 11.01 (a, 1 H), 9.79 (a, 1 H), 8.38 (s, 1 H), 7. 72 (s, 1 H), 7.64 (dd, J = 7.9, 1.4 Hz, 2H), 7.50-7.41 (m, 4H), 3.92 (s, 3H), 2.77 (t, J = 7.3 Hz, 2H), 2.25 (t, J = 7.0 Hz, 2H), 2.18 (s, 6H), 1.81 (m, 2H). FABMS found [M + H] +: 428.1972. C26H26N3O3 requires 428.1974. . - - " EXAMPLE 339 The preparation of 8- [2- (dimethylamino) ethyl] -9-hydroxy-6-methyl-4-phenylfirrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (LV: n = 2. Ar = phenyl R10 = Me. Z = Nme2) (721) The reaction of (719) prepared as described in Example 343 with pyridinium hydrochloride using the procedure described in Example 81 followed by chromatography on silica gel (chloroform / methanol) (10: 1) gave the phenyl (721) ) (97%) in the form of an orange solid, mp 278 ° C (dec). 1 H NMR d [(CD3) 2 SO] 1 1.01 (a, 2H), 8.36 (s, 1 H), 7.73 (s, 1 H), 7.64 (dd, J = 7.9, 1.4 Hz, 2H), 7.50-7.41 (m, 4H), 3.92 (s, 3H), 2.94 (t, J = 6.9 Hz, 2H), 2.64 (t, J = 6.9 Hz, 2H), 2.31 (s, 6H). FABM found [M + H] +: 414.1821. C25H24N303 requires 414. 1818 EXAMPLE 340 The preparation of 8- [2- (hydroxyethyl) -9-methoxy-6-methyl-4-phenylpyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (Ll: Ar = phenyl. Z = OH) (712) The reaction of the alkene (701) prepared as described in Example 321 with 9-BBN using the procedure described in method 29 gave, after chromatography on silica gel (chloroform / methanol) (10: 1), the compound 8- (2-hydroxyethyl) (712) (51%) as a yellow solid, mp 284-286 ° C. 1 H NMR d [(CD3) 2 SO] 1 .09 (s, 1H), 8.52 (s, 1 H), 7.79 (s, 1 H), 7.66 (da, J = 6.4 Hz, 2H), 7.56 (s) , 1 H), 7.51-7.41 (m, 3H), 4.68 (t, J = 5.2 Hz, 1 H), 3.96 (s, 3H), 3.94 (s, 3H), 3.69 (m, 2H), 2.98 ( t, J = 7.2 Hz, 2H). Found: C, 71.77; H, 5.24; N, 6.81. C 24 H 20 N 2 O 4 requires C, 71.99; H, 5.03; N, 7.00.

EXAMPLE 341 The preparation of 4- (2-chlorophenyl) -8- (2-hydroxyethyl) -9-methoxy-6-methylpyrrolof3.4-c] carbazole-1.3 (2H.6H) -dione (Ll: Ar = 2- chlorofenil R10 = Me.Z = OH) (713) The reaction of the alkene (704) prepared as in example 326 with 9-BBN using the procedure described in method 29 gave, after chromatography on silica gel ( ethyl acetate / petroleum ether) (2: 1), the compound 8- (2-hydroxyethyl) (713) (50%) in the form of a orange solid, m.p. 270-272 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.08 (s, 1 H), 8.49 (s, 1 H), 7.77 (s, 1 H), 7.59-7.55 (m, 2H), 7.53-7.43 (m, 3H ), 4.69 (t, J = 5.3 Hz, 1H), 3.94 (s, 6H), 3.69 (td, J = 7.1, 5.3 Hz, 2H), 2.98 (t, J = 7.1 Hz, 2H). - | -r - - |-- - - Found: 66:14; ? G4.69; Ñ, 6.51. C24H19N2CIO4 requires: C, 66.29; H, 4.40; N, 6.44.

EXAMPLE 342 The preparation of 8- [3- (dimethylamino) propyl] -9-methoxy-6-methyl-4-phenylpyrrolof3.4-c] carbazole-1.3 (2H.6H) -dione (LIV: n = 3. Ar = phenyl, R10 = 20 Me, Z = NMe?) (717) The reaction of (188) prepared as described in Example 344 with methanesulfonyl chloride using the procedure described in Example 170 gave the intermediate LUI (n = 3, Ar = phenyl, R = Me, Z = OS02CH3) which was reacted with dimethylamine ac. 40% (using the procedure described in example 179) at room temperature for 5 h. The conventional treatment gave a crude product which was heated to reflux in toluene in the presence of excess ammonium acetate for 23 h. After chromatography on silica gel (chloroform / methanol) (10: 1), the pure dimethylaminopropyl compound (717) (60%), m.p. 175-178 ° C. H NMR d [(CD3) 2 SO] 1 .07 (s, 1 H), 8.51 (s, 1 H), 7.78 (s, 1 H), 7.68-7.63 (m, 2H), 7.55 (s, 1 H ), 7.51-7.42 (m, 3H), 3.96 (s, 3H), 3.94 (s, 3H), 2.80 (t, J = 7.8 Hz, 2H), 2.34 (t, J = 7.8 Hz, 2H), 2.20 (s, 6H), 1.80 (m, 2H). Found: C, 69.28; H, 6.44; N, 9.05 C27H27N3O3. 3/2 H20 requires C, 69.21; H, 6.45; N, 8.97.

- ^: | - |- - EXAMPLE 343 The preparation of 8- [2- (dimethylamino) ethyl] -9-methoxy-6-methyl-4-phenylpyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (LIV: Ar = phenyl, R10 = Me, Z = Me, n = 2) (719) The reaction of (712) prepared as described in Example 340 with methanesulphonium chloride using the procedure described in Example 170 gave the intermediate LUI (Ar = phenyl, n = 2, R10 = Me, Z = OSO2CH3) which was reacted with dimethylamine ac. at 40% (using the procedure described in example 179) at room temperature for 2.5 h. The conventional treatment gave a crude product which was heated to reflux in toluene in the presence of excess ammonium acetate for 18 h. After chromatography on silica gel (chloroform / methanol) (10: 1), the pure dimethylaminoethyl compound (719) (15%), m.p. 233-236 ° C. 1 H NMR d [(CD3) 2 SO] 11.08 (s, 1 H), 8.51 (s, 1 H), 7.78 (s, 1 H), 7. 68-7.63 (m, 2H), 7.58 (s, 1 H), 7.50-7.41 (m, 3H), 3.96 (s, 3H), 3.94 (s, 3H), 2.93 (t, J = 8.0 Hz, 2H ), 2.54 (t, J = 8.0 Hz, 2H), 2.23 (s, 6H). EIMS found M + = 427.1890. C26H25N3O3 requires 427.1896.

Representative procedure for method 29 of scheme 12 EXAMPLE 344 The preparation of 8- (3-hydroxypropyl) -9-methoxy-6-methyl-4-phenylpyrrolo [3,4-c] carba2ol-1.3 (2H.6H) -dione '(LVTll: Ar = phenyl. = CH) (188) A solution of 9-borabicyclo [3.3.1] nonane (1 ml of a 0.5 M solution in tetrah id breakage, 0.49 ml) was added to a solution of (187) (65 mg, 0.16 mmol) prepared as has described in example 329 in tetrahydrofuran (5 ml). The reaction mixture was stirred at room temperature for 2 h and 20 min and then 3 M sodium acetate (1.5 ml) and 35% hydrogen peroxide (1.0 ml) were added. The mixture was stirred at room temperature for 1 h and 30 min and then diluted with brine and extracted with ethyl acetate (3 x 30 mL). The combined extracts were dried and concentrated. The residue was purified by chromatography on silica eluting with 1: 5 ethyl acetate / dichloromethane to give 8- (3-hydroxypropyl) -9-methoxy-6-methyl-4-phenylpyrrolo [3,4-c] carbazole-1. , 3 (2H, 6H) -dione (58 mg, 85%), mp 105-1 10 ° C softening, 130-134 ° C melted. 1 H NMR d [(CD3) 2 SO] 11.06 (s, 1 H), 8.51 (s, 1 H), 7.78 (s, 1 H), 7. 66-7.64 (m, 2H), 7.53 (s, H), 7.50-7.44 (m, 3H), 4.52 (t, J = 5.1 Hz, 1 H), 3.96 (s, 3H), 3.94 (s, 3H) ), 3.52-3.45 (m, 2H), 2.82 (ta, 7.8 Hz, 2H), 1.82 (dt a, J = 7.8 Hz, 2H). Found: C, 70.93; H, 5.40; N, 6.54. C25H22N2O4. 1/2 H20 requires: C, 70.91; H, 5.47; N, 6.62.

EXAMPLE 345 The preparation of 9-hydroxy-8- (3-hydroxypropyl) -6-methyl-4-phenylpyrrolo [3.4-: The demethylation of (188) prepared as described in Example 344 with BBr3 using the procedure described in Example 80 gave (189) as a yellow solid. 1 H NMR d [(CD 3) 2 SO] 11.00 (br s, 1 H), 9.46 (br s, 1 H), 8.39 (s, 1 H), 7.73 (s, 1 H), 7.46-7.63 (m, 2H), 7.49-7.42 (m, 4H), 4.50 (sa, 1 H), 3.92 (s, 3H), 3.49-3.44 (m, 2H), 2.78 (ta, J = 7.9 Hz, 2H), 1.82 (dt a, J = 7.8 Hz, 2H).

EXAMPLE 346 The preparation of 8-ethyl-9-methoxy-4-methyl-4-phenylpyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (Ll. Ar = phenyl, R10 = CH2, Z = H) (190) The reaction of triflate (185) prepared as described in Example 320 with tetraethyltin using the procedure described in Example 309 gave (190) as a yellow solid (83%), m.p. 251-253 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.07 (s, 1 H), 8.53 (s, 1 H), 7.77 (s, 1 H), 7.67-7.64 (m, 2H), 7.53 (s, 1 H) , 7.50-7.42 (m, 3H), 3.95 (s, 3H), 3.94 (s, 3H), 2.81 (c, J = 7.5 Hz, 2H), 1.27 (t, J = 7.5 Hz, 3H). Found: C, 74.48; H, 5.20; N, 7.24. C24H2oN203. 1/6 H20 requires: C, 74.40; H, 5.29; N, 7.23. r --- - - - - "=" EXAMPLE 347"". The preparation of 8-ethyl-9-hydroxy-6-methyl-4-phenylpyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (Lll: Ar = phenyl, R10 = CH, Z = H) ( 191) The demethylation of (190) prepared as described in Example 346 with BBr3 using the procedure described in Example 80 gave (191) as a yellow solid (92%), m.p. 278-283 ° C. 1 H NMR d [(CD3) 2 SO] 11.00 (br s, 1 H), 9.36 (s, 1 H), 8.40 (s, 1 H), 7.73 (s, 1 H), 7.66-7.63 (m, 2H) , 7.49-7.41 (m, 4H), 3.93 (s, 3H), 2.78 (c, J = 7.5 Hz, 2H), 1.27 (t, J = 7.5 Hz, 3H).

Found: C, 74.36; H, 5.10; N, 7.45. C23H18N2O3 requires: C,; N, 7.56. SCHEME 13 Procedures for scheme 13 EXAMPLE 348 The preparation of 4- (2-chlorophenyl) -8- (3-hydroxypropoxy) -2- (3-hydroxypropyl) -9-methoxy-6- (2-methoxyethyl) pyrrolo [3.4-c] carbazole-1.3 (2H.6H) -dione (LXV: AR2-chlorophenol.R10 = CH CH OCHj.n = 3) (181) The alkylation of (167) prepared as described in Example 267 with 3-bromopropanol using the procedure described in Example 298 gave (181) (92%) as a yellow oil which was used without further purification.

EXAMPLE 349 The preparation of'4- (2-chlorophenyl) -8- (3-hydroxypropoxy) -9-methoxy-e- (2-methoxyethyl) pyrrolo [3,4-c] carbazole-1.3 (2H.6H) - dione (LXVI: Ar = 2-chlorophenyl, R10 = CH2CH2OCH3, n = 3) (182) Treatment of (182) with the sequence of reactions indicated in the procedure described in example 328 gave (182) (58%) as an orange powder, m.p. 251-257 ° C. H NMR d [(CD3) 2 SO] 1 1.03 (br s, 1 H), 8.46 (s, 1 H), 7.74 (s, 1 H), 7.57 (dd, J = 8.0, 2.1 Hz, 1 H), 7.51 -7.42 (m, 3H), 7.36 (s, 1 H), 4.67 (t, J = 4.9 Hz, 2H), 4.61 (a, 1 H), 4.23 (t, J = 6.3 Hz, 2H), 3.90 ( s, 3H), 3.70 (t, J = 4.9 Hz, 2H), 3.64 (m, 2H), 3.16 (s, 3H), 1.98 (m, 2H). EIMS found: M +: 508.1398, 510.1358. C27H25CI 206 requires 508.1401, 510.1371.

EXAMPLE 350 The preparation of 4- (2-chlorophenyl) -9-methoxy-6- (2-methoxyethyl) -8- [3- (4-morpholinyl) propoxy] pyrrolo [3,4-c] carbazole-1.3 (2H.6H ) -dione (LXIII: Ar = 2-chlorophenyl, R10 = CH2CH2OCHj, Z = 4-morpholinalo) (183) The conversion of (182) prepared as described in Example 349 into the corresponding mesylate by reaction with methanesulfonyl chloride using the procedure described in Example 170 followed by the reaction with morpholin using the procedure described in Example -179 gave (183) (71%) in the form of a yellow powder, mp 271-275 ° C, which was immediately demethylated.

EXAMPLE 351 The preparation of 4- 2-chlorophenyl) -9-hydroxy-6- (2-hydroxyethyl) -8- [3- (4-morpholinyl) propoxy] pyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (LXIV: Ar = 2-chlorophenyl, R10 = CHgCH ^ OCH ^ .Z = 4-morpholint)) (184) The demethylation of (183) prepared as described in Example 350 with BBr3 using the procedure described in Example 80 with the exception that the reaction conditions were 0 ° C for 2H gave (184) (36%) as of a yellow solid, mp 253-255 ° C. 1 H NMR d [(CD3) 2 SO] 10.9 (s a, 1 H), 8.94 (s a, 1 H), 8.34 (s, 1 H), 7. 69 (s, 1 H), 7.56 (dd, J = 8.1, 2.2 Hz, 1 H), 7.49-7.42 (m, 3H), 7.29 (s, 1 H), 4.83 (a, 1 H), 4.49 ( t, J = 5.2 Hz, 2H), 4.18 (t, J = 6.2 Hz, 2H), 3.76 (m, 2H), 3.60 (t, J = 4.9 Hz, 4H), 2.52 (t, J = 7.1 Hz, 2H), 2.41 (m, 4H), 1.99 (m, 2H). ···. - - FABMS "found [+ H] +: 552.1732, 550.1740. C29H29CIN3O6 requires 552.1715, 550.1745.

EXAMPLE 352 The preparation of 8- (3-bromopropoxy¾-2- (3-bromopropyl) -9-methoxy-6-methyl-4-phenylpyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (LXI. = phenyl R10 = Me n = 3) (722) Alkylation of (154) prepared as described in Example 254 with, 3-dibromopropane (3.0 equiv.) Using the procedure described in Example 298 (at room temperature for 4 d) and then chromatography on silica gel ( dichloromethane / petroleum ether) (31) gave (722) (47%) in the form of an orange solid, m.p. 158-160 ° C. 1 H NMR d [(CD 3) 2 SO] 8.50 (s, 1 H), 7.76 (s, 1 H), 7.69-7.64 (m, 2 H), 7.51-7.43 (m, 3 H), 7.39 (s, 1 H) , 4.31 (t, J = 6.0 Hz, 2H), 3.98 (s, 3H), 3.92 (s, 3H), 3.77-3.71 (m, 4H), 3.59 (t, J = 6.5 Hz, 2H), 2.41- 2.34 (m, 2H), 2.23-2.15 (m, 2H). Found: C, 57.16; H, 4.58; N, 4.73. C28H26N2Br204. 1/2 hexane requires: C, 56.64; H, 5.06; N, 4.26. FABMS found M +: 612.0255, 614.0249, 616.0252.

C28H26Br2N204 requires 612.0259, 614.0239, 616.0218.

EXAMPLE 353 The preparation of 8- (3-bromopropoxy) -2 - (2-bromopropyl) -4- (2-chlorophenyl) -9-methoxy-6-methylpyrrolo [3,4-c] carbazole-1.3 (2H.6H) - dione (LXI: Ar = 2-chlorophenyl, R10 = Me, n = 3) (723) The alkylation of (160) prepared as described in Example 260 with 1,3-dibromopropane (15 equiv.) Using the procedure described in Example 298 (at room temperature for 5 d) and then chromatography on silica gel (dichloromethane / petroleum ether) (3: 1) gave (723) (65%) in the form of an orange solid, m.p. 165-167 ° C. 1 H NMR d [(CD 3) 2 SO] 8.47 (S, 1 H), 7.76 (s, 1 H), 7.60-7.57 (m, 1 H), 7.53-7.43 (m, 3H), 7.41 (s, 1 H ), 4.31 (t, J = 6.0 Hz, 2H), 3.97 (s, 3H), 3.93 (s, 3H), 3.77-3.68 (m, 4H), 3.56 (t, J = 6.5 Hz, 2H), 2.42 -2.34 (m, 2H), 2.20-2.12 (m, 2H). Found: C, 53.54; H, 4.28; N, 4.20. C28H25NCIBr204. 1/2 hexane requires: C, 53.82; H, 4.66; N, 4.05. FABMS found M +: 645.9866, 647.9868, 649.9834. C28H25N2CIBr204 requires 645.9870, 647.9849, 6479840, 649.9829, 649.9820.

EXAMPLE 354 The preparation of 4- (2-chlorophenyl) -8 - (- hydroxypropoxy) -2- (3-hydroxypropyl) -9-methoxy-6-methylpyrrolo [3,4-clcarbazole-1.3 (2H.6H) -dione (LXV : Ar = 2-chlorophenyl, R10 = Me, n = 3) (724) The alkylation of (160) prepared as described in Example 260 with 3-bromopropanol (2.2 equiv.) Using the procedure described in Example 298 (at room temperature for 31 h) and then chromatography on silica gel (chloroform) methanol) (20: 1) gave (724) (98%) as an orange solid, mp 180-183 ° C. 1 H NMR d [(CD 3) 2 SO] 8.47 (s, 1 H), 7.74 (s, 1 H), 7.60-7.57 (m, 1 H), 7.53-7.43 (m, 3 H), 7.36 (s, 1 H) , 4.60 (t, J = 5.1 Hz, 1 H), 4.50 (t, J = 5.0 Hz, 1 H), 4.25 (t, J = 6.3 Hz, 2H), 3.96 (s, 3H), 3.92 (s, 3H), 3.67-3.60 (m, 4H), 3.47-3.41 (m, H), 2.02-1.95 (m, 2H), 1.79-1.71 (m, 2H).

Found: C, 64.03; H, 5.21; N, 5.25. C28H27N2CIO6 requires C, 64.31; H, 5.20; N, 5.36.

EXAMPLE 355 The preparation of 4- (2-chlorophenyl) -8- (3-hydroxypropoxy) -9-methoxy-6-methylpyrrolor3.4-c] carbazole-1.3 (2H.6H) -dione (LXVI: Ar = 2- Chlorophenyl R10 = Me n = 3) (725) The treatment of (724) prepared as described in Example 354 with the sequence of reactions (5 M KOH / MeOH / reflux / 3 h; 1 N HCL / 100 ° C / 3 h; NH4OAc / 150 ° C / 20 min) as described in the procedure described in Example 328 gave (725) (85%) as an orange solid, mp. 285-287 ° C. . r_- =. ~ - • • -|- • H NMR'ó [(CD3) 2SOVH .02 (ai ÍH), 8.46 (s, 1 H), 7.72 (s, 1H), 7.59-7.55 (m, 1 H) , 7.51-7.42 (m, 3H), 7.34 (s, 1 H), 4.60 (t, J = 5.1 Hz, 1 H), 4.25 (t, J = 6.3 Hz, 2H), 3.95 (s, 3H), 3.91 (s, 3H), 3.67-3.61 (m, 2H), 2.02-1.95 (m, 2H). Found: C, 64.69; H, 4.60; N, 6.11. C25H21 N2CIO5 requires: C, 64.31; H, 5.20; N, 5.36.

EXAMPLE 356 The preparation 8 [3- (dimethylamino) propoxy] -2- [3- (dimethylamino) propyl] -9-methoxy-6-methyl-4-phenylpyrrolo [3,4-c] carbazole-1.3 (2H.6H) - dione (LXII: Ar = phenyl, R 0 = Me, Z = NMe2, n = 3¾ (726), The reaction of (722) prepared as described in Example 352 with excess dimethylamine, HCl in DMF in the presence of triethylamine and 4A molecular sieves at room temperature (Method 30) for 66 h gave (726) (35%) as the dihydrochloride salt, mp 278-281 ° C 10 (dec). H NMR d [(CD3) 2SO] 9.95 (a, 2H), 8.51 (s, 1 H), 7.81 (s, 1 H), 7.70-7.65 (m, 2H), 7.52-7.43 (m, 3H), 7.40 (s, 1 H), 4.28 (t, J = 6.1 Hz, 2H), 3.9 (s, 3H), 3.93 (s, 3H), 3.67 (t, J = 6.4 Hz, 2H), 3.28 (t, J = 7.6 Hz, 2H), 3 , 10 (t, _ - - J = 7: 6 Hz, 2H), ~ 2.83 (s, 6H), 2.73 (s, 6H), 2.29-2.20 (m, 2H), 2.26-1.97 (m, "2H ) 15 Found C, 59.07; H, 6.68; N, 8.44 C32H40 4CI2O4 requires: C, 58.98; H, 6.81; N, 8.60.

EXAMPLE 357 The preparation of 4- (2-chlorophenyl) -8- [3- (dimethylamino) propoxy1-2-r3- (dimethylamino) propyl] -9-methoxy-6-methylpyrrolo [3.4-c] carbazole-1.3 (2H .6H) -dione (LXH: Ar = 2-chlorophenyl, R10 = Me. Z = NMe ?. = n 3) (727) The reaction of (723) prepared as described in Example 353 with excess dimethylamine. HCl in DMF in the presence of triethylamine and 4A molecular sieves at room temperature (Method 30) for 6 d followed by chromatography on silica gel (chloroform / methanol / triethylamine) (10: 1: 0.1) gave (727) (63%) in the form of the dihydrochloride salt, mp 207-2 0 ° C. 1 H NMR d [(CD3) 2 SO] 9.89 (a, 2H), 8.48 (s, 1 H), 7.79 (s, 1 H), 6H), 2.69 (s, 67H), 2.28-2.19 (m, 2H), 2.03-1.92 (m, 2H). Found: C, 58.09; H, 6.13; N, 8.44. C32H37N4CIO4. 2.2 HCI requires: C, 58.47; H, 6.01; N, 8.52. Found: C, 59.07; H, 6.68; N, 8.44. C 32 H 40 N 4 Cl 2 O 4 requires: C, 58.98; H, 6.81; N, 8.60.

EXAMPLE 358 The preparation of 4- (2-chlorophenyl) -8- [3- (dimethylamino) propoxy] -2-f3- (dimethylamino) propyl] -9-methoxy-6-methylpyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (LXII: Ar = 2-chlorophenyl, R10 = Me. Z = NMe2. = 3) (727) On a large scale it was best prepared (727) from (160) prepared as described in Example 260 by reaction with 3-dimethylaminopropyl chloride hydrochloride (7.3 equiv.) In the presence of excess of anhydrous potassium carbonate and molecular sieves. 4A at 60-70 ° C (bath temperature) for 3 h. The yield of the crude product was 96%, which was used in the next step without further purification.

EXAMPLE 359 - The preparation of 4- (2-chlorophenyl) -8- [3- (d.methylamino) propyl] -9-rnetoxy-6-methylpyrrole [3,4-c1carbazole-1.3 (2H.6H) -dione (LXII: Ar = 2-chlorophenyl R10 = Me. Z = NMe, n = 3) (728) The treatment of (727) prepared as described in example 358 with the reaction sequence (5 M KOH / MeOH / reflux / 3 h; 1/100 ° C / 3 h HCl; NH4OAc / 170 ° C / 10 h ) as described in example 328, with the modification that after the acid treatment the reaction mixture was evaporated to dryness and fused with NH40Ac, followed by chromatography on silica (dichloromethane / MeOH = 5: 1) gave ( 728) (97%) in the form of an orange solid, mp 288-290 ° C. 1 H R N d [(CD3) 2 SO] 1 1.04 (a, 1 H), 8.46 (s, 1 H). 7.72 (s, 1 H), 7.59-7.55 (m, 1 H), 7.51-7.42 (m, 3H), 7.33 (s, 1 H), 4.21 (t, J = 6.5 Hz, 2H), 3.95 5 ( s, 3H), 3.91 (s, 3H), 2 43 (t, J = 7.0 Hz, 2H), 2.18 (s, 6H), 2.01-1.93 (m, 2H). Found: C, 68.22; H, 6.57; N, 7.43. C27H26N3CIO4. hexane requires: C, 68.58; H, 6.97; N, 7.27. FAB S found [M + H] +: 492.1689, 494.1675. C27H17N3CI04 requires 492.1690, 494.1661. EXAMPLE 360 The preparation of 4- (2-chlorophenyl) -9-methoxy-6-methyl-8- [3- (4-morpholinyl) propoxylpyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione ( LXIII: Ar = 2-γ-chlorophenyl, R10 = Me, Z = 4-morpholine, and 3) (729) The conversion of (725) prepared as described in Example 355 into the corresponding mesylate by reaction with methanesulfonyl chloride using the procedure described in Example 170 followed by the reaction with morpholine using the procedure described in Example 20 179 and treatment of the crude product with NH40Ac at 160-170 ° C for 2H gave (after a column of silica; chloroform / MeOH = 10: 1) (729) (76%) in the form of an orange powder, mp 293-295 ° C.

H NMR d [(CD3) 2 SO] 1 1.04 (a, 1 H), 8.47 (s, 1 H), 7.72 (s, 1 H), 7.59-7.55 (m, 1 H), 7.52-7.42 (m, 3H), 7.34 (s, 1 H), 4.22 (t, J = 6.4 Hz, 2H), 3.96 (s, 3H), 3.91 (s, 3H), 3.59 (ta, J = 4.6 Hz, 4H), 2.60 -2.36 (m, 6H), 2.03-1.95 (m, 2H). FABMS found [M + H] +: 534.1792, 536.1769. C29H29N3CI05 requires 534.1796, 536.1766.

EXAMPLE 361 The preparation of 4- (2-chlorophenH) -9-methoxy-6-methyl-8- [3- (1-pyrrolidinyl) propoxylpyrrolo [3 4-c] carbazole-1.3 (2H.6H) -dione (LXIII- Ar = 2-chlorophenyl, R10 = Me.7 = 1-pyrrolidinyl- n = 3) (730) The conversion of (725) prepared as described in example-355 into the corresponding mesylate with methanesulfonyl chloride using the procedure described in example 170 followed by the reaction with pyrrolidine using the procedure described in example 179 M Scheme 3 and treatment of the crude product with NH4OAc at 160-170 ° C for 4 h gave (after a silica column, chloroform / MeOH = 10: 1) (730) (78%) as an orange solid, 273- 275 ° C. H NMR d [(CD3) 2 SO] 1 1.03 (a, 1 H), 8.45 (s, 1 H), 7.73 (s, 1 H), 7. 59-7.55 (m, 1 H), 7.52-7.42 (m, 3H), 7.34 (s, 1 H), 4.22 (t, J = 6.4 Hz, 2H), 3.95 (s, 3H), 3.90 (s, 3H), 2.60 (t, J = 7.0 Hz, 2H), 2.42 (m, 4H), 2.03-1.96 (m, 2H), 1.73-1.67 (m, 4H).

Found: C, 66.40; H, 5.47; N, 7.85. C29H28 3CIO4. 1 / 2H20 requires: C, 66.09; H, 5.55; N, 7.97.

EXAMPLE 362 The preparation of 8- [3- (dimethylamino) propoxy] -9-methoxy-6-methyl-4-phenylpyrrolo [3,4-c] carba2ol-1.3 (2H.6H) -dione (LXIII: Ar = 2-phenyl) R 0 = Me. Z = NMe? N = 3) (731) The treatment of (726) prepared as described in example 356 with the sequence of reactions (5 M KOH / MeOH / reflux / 3 h; HCl 1 N / 100 ° C / 3 h; NH 4 OAc / 170 ° C / 10 h) in the procedure described in Example 328 with the modification that after the acid treatment the reaction mixture was evaporated to dryness and fused with NH 4 OAc, gave (731) (37%) -after de úñá bolümna 'de silica (dichloromethane / MeOH = 5: 1) in the form of a hygroscopic solid. 1 H NMR d [(CD 3) 2 SO] 11.04 (a, 1 H), 8.48 (s, 1 H), 7.75 (s, 1 H), 7.68-7.62 (m, 2H), 7.51-7.42 (m, 3H) , 7.33 (s, 1 H), 4.21 (t, J = 6.9 Hz, 2H), 3.97 (s, 3H), 3.90 (s, 3H), 2.43 (t, J = 7.1 Hz, 2H), 2.19 (s) , 6H), 2.01-1.93 (m, 2H). LCMS (APCI) m / z: 458.101 [M + H] +.

EXAMPLE 363 The preparation of 4- (2-chlorophenyl) -8- [3- (dimethylamino) propoxy] -9-hydroxy-6-methylpyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (LXIV) : Ar = 2-chlorophenyl Ri0 = Me. Z = NMe ?. n = 3) (732) The demethylation of (728) prepared as described in Example 359 with BBr3 using the procedure described in Example 80 with the exception that the reaction conditions were 0 ° C for 2 h gave (732) (83%) in shape of an orange solid, mp 259-262 ° C. 1 H NMR d [(CD3) 2 SO] 10.99 (s, 1 H), 9.22 (a, 1 H), 8.35 (s, 1 H), 7.70 (s, 1 H), 7.58-7.54 (m, 1 H) , 7.51-7.42 (m, 3H), 7.29 (s, 1 H), 4.22 (t, J = 6.0 Hz, 2H), 3.92 (s, 3H), 2.89 (a, 2H), 2.50 (a, 6H) . 2.13-2.03 (m, 2H). FABMS found [M + H] + 478.1532, 480.1519, C26H25N3CIO4 required-478: 1534, 480: 1504. "'_ EXAMPLE 364 The preparation of 8- [3- (dimethylamino) propoxy] -9-hydroxy-6-methyl-4-phenylpyrrolo [3,4-c] carba2ol-1.3 (2H.6H) -dione (LXIV: Ar = phenyl. = Me: Z = Me ?, n = 3) (733) The demethylation of (731) prepared as described in Example 362 with BBr3 using the procedure described in Example 80 with the exception that the reaction conditions were 0 ° C for 2H gave (733) (56%), m.p. 303-304 ° C. 1 H NMR d [(CD3) 2 SO] 11.00 (s, 1 H), 9.00 (a, 2H), 8.39 (s, 1 H), 7.73 (s, H), 7.66-7.61 (m, 2H), 7.50- 7.41 (m, 3H), 7.29 (s, 1 H), 4.26 (t, J = 5.7 Hz, 2H), 3.94 (s, 3H), 3.24 (t, J = 7.1 Hz, 2H), 2.80 (s, 6H), 2.23-2.14 (m, 2H). Found: C, 60.61; H, 5.05; N, 7.82. C26H25N3O4 requires: C, 60.48; H, 5.06; N, 8.14.

EXAMPLE 365 The preparation of 4- (2-chlorophenyl) -9-hydroxy-6-methyl-8- [3- (4-morpholinyl) propoxyprirol [3,4-c] carbazole-1.3 (2H.6H) -d ona (LXIV: Ar = 2-chlorophenyl, R10 = Me, Z = 4-morpholinyl, n = 3) (734) - The demethylation of (729) prepared as described in Example 360 with BBr3 using the procedure described in Example 80 with the exception that the reaction conditions were 0 ° C for 2H gave (734) (60% ) in the form of an orange solid, mp 235-237 ° C. 1 H NMR d [(CD3) 2 SO] 10.98 (s, 1 H), 8.97 (a, 1 H), 8.33 (s, 1 H), 7.69 (s, 1 H), 7.59-7.54 (m, 1 H) , 7.51-7.42 (m, 3H), 7.28 (s, 1 H), 4.21 (t, J = 6.1 Hz, 2H), 3.92 (s, 3H), 3.61 (a, 4H), 2.58-2.37 (m, 6H), 2.05-.95 (m, 2H). FABMS found [M + H] +: 520.1648, 522.1635. CasH NsCIOs requires 520.1639, 522.1610.

EXAMPLE 366 The preparation of 4- (2-chlorophenyl) -9-hydroxy-6-methyl-8- [3- (1-pyrrolidinyl) proDoxylpyrrolof3.4-c1carbazole-1.3 (2H.6H) -dione (LXIV: Ar = 2-chlorophenyl, R10 = Me, Z = 1-pyrrolidinyl, n = 3) (735) The demethylation of (730) prepared as described in Example 361 with BBr3 using the procedure described in Example 80 with the exception that the reaction conditions were 0 ° C for 2H gave (735) (60%) in the form of an orange solid, mp 234-236 ° C. 1 H NMR d [(CD3) 2 SO] 10.98 (a, 1 H), 9.27 (a, 1 H), 8.33 (s, 1 H), 7.68 (s, 1 H), 7.58-7.55 (m, 1 H), 7.51-7.42 (m, 3H), 7.30 (s, 1 H), 4.20 (t, J = 6.2 Hz, 2H), 3.92 (s, 3H), 2.66 (t, J = 6.8 Hz, 2H), 2.54-2.35 (m, 4H), 2.04-1.96 (m, 2H), 1.75-1.68 (m, 4H). _ _r _ - · FABMS "found- [M + H: 504.1687, - 506.1661. C28H27N3CÍO4 requires 504.1690, 506.1661.

SCHEME 14 Procedures for scheme 14 Representative procedure for method 31 of scheme 14 -rr -. = -. - EXAMPLE 367 - - - The preparation of 5-Methoxy-2 - [(E.Z) -2-phenylethenyl] -1-benzofuran (LXVIII: Ar = phenyl, R8 = H. Y1 = O) (828) To a suspension of benzyltriphenylphosphonium bromide (1.85 g, 4.26 mmol) in tetrahydrofuran (30 mL) was added a solution of lithium bis (trimethylsilyl) amide (4 mL of a solution 1 in tetrahydrofuran 3.98 mmol) and the solution turned bright orange / red. The reaction mixture was stirred at room temperature for 30 min and then a solution of 5-methoxy-1-benzofuran-2-carbaldehyde (827) (0.50 g, 2.84 mmol) in tetrahydrofuran (10 ml) was added. After 20 min, water was added and the tetrahydrofuran was removed under reduced pressure. The residue was extracted with ethyl acetate (2 x 50 mL) and the combined extracts were dried and concentrated. The residue was purified by column chromatography on silica eluting with dichloromethane to give (828) as a 1: 2 mixture of Z and E isomers, (0.63 g, 89%), m.p. 24-28 ° C. Found: C, 81.60; H, 5.61. C17H14O2 requires: C, 81.58; H, . 64 EXAMPLE 368 The preparation of 9-methoxy-4-phenyl-1H- [1] benzofuro [3.2-e] isoindol-1.3 (2H) -dione (LXX: Ar = phenyl, R8 = H. Y1 = O) (830) -. . · .. - ·. The mixed premix (828) prepared as described in Example 367 was reacted with maleimide using the procedure described in Example 69 to give the adduct (LXIX; Ar = phenyl, R8 = H, Y1 = O) (829), which was used without further purification The crude Diels-Alder adduct was aromatized with MnO2 using the procedure described in Example 79 of Scheme 2 to give dibenzofuran (830) as a yellow solid (53). %), mp 271-275 ° C. 1 H NMR d [(CD3) 2 SO] 11.41 (br s, 1 H), 8.24 (d, J = 2.7 Hz, 1 H), 7.98 (s, 1 H), 7.77 ( d, J = 9.0 Hz, 1 H), 7.67-7.65 (m, 2H), 7.51-7.45 (m, 3H), 7.30 (dd, J = 9.0, 2.7 Hz, 1 H), 3.91 (s, 3H) .

Found: C, 72.09; H, 3.84; N, 4.04. C2iH13N04. 1/3 H20 requires: C, 72.20; H, 3.94; N, 4.01.

EXAMPLE 369 The preparation of 9-hydrox4-4-phenyl-1H- [1] benzofuro [3.2-e] isoin-dol-1.3 (2H) -dione (LXX: - Ar = phenyl, R8 = H. Y1 = O ) (831) The demethylation of (830) prepared as described in Example 368 with BBr3 using the procedure described in Example 80 gave (831) as a yellow solid (100%), m.p. 288-290 ° C. 1 H NMR d [(CD3) 2 SO] 1 .37 (sa, 1 H), 9.74 (s, 1 H), 8.13 (d, J = 2.6 Hz, 1 H), 7.94 (s, 1 H), 7.66- 7.63 (m, 3H), 7.51-7.44 (m, 3H), 7.1 1 (dd, J = 8.9, 2.6 Hz, 1 H). r Found: C, 71.17; H, ¾8; Ñ, 4.07. C20HnNO 1/2 H20 requires: C, 71 .00; H, 3.58; N, 4.14.

EXAMPLE 370 The preparation of 2 - [(E.Z) -2- (2-chlorophenyl) ethenyl] -5-methoxy-1-benzofuran (LXVIII, Ar = 2-chlorophenyl, R8 H. Y1 = O) (832) The reaction of 5-methoxy-1-benzofuran-2-carbaldehyde (827) prepared as described in the example with 2-chlorobenzyltriphenylphosphonium bromide using the procedure described in the method given (832) as a 1: 2 mixture of Z isomers: E (24%), mp 90-92 ° C, which was used without further purification.

EXAMPLE 371 The preparation of 4- (2-chlorophenyl) -9-methoxy-1 H- [1] benzofuro [3.2-e] isoindol-1.3 (2H) -dione (LXX: Ar = 2-chlorophenyl) R8 = H. Y1 = O) (834) The diene mixture (832) prepared as described in Example 370 was reacted with maleimide using the procedure described in Example 69 to give the adduct (LXIX; Ar = 2-chlorophenyl, R8 = H, Y1 = O) (833) which was used without further purification. The crude Diels-Alder adduct was aromatized with Mn02 using the procedure described in Example 79 of Scheme 2 to give dibenzofuran (834) as a solid, yellow (49%) r pf- 246-248 ° c7 '- - "?? NMR [(CD3) 2SO] 1 .46 (sa, 1 H), 8.22 (d, J = 2.7 Hz, 1 H), 7.99 (s, 1 H), 7.80 (d, J = 9.0 Hz, 1 H), 7.61-7.58 (m, 1 H), 7.53-7.44 (m, 3H), 7.33 (dd, J = 9.0, 2.7 Hz, 1 H), 3.92 (s, 3H) Found: C , 66.53; H, 3.41; N, 3.54, C2iH12CIN04 requires: C, 66.77; H, 3.20; N, 3.71.

EXAMPLE 372 The preparation of 4- (2-chlorophenyl) -9-hydroxy-1 H- [1] benzofurof3.2- elisoindol-1.3 (2H) -dione (LXXI: Ar = 2-chlorophenyl) R8 = H. Y1 = O) (835) The demethylation of (834) prepared as described in Example 371 with BBr3 using the procedure described in Example 80 gave (835) as a yellow solid (89%), m.p. 140-145 ° C. 1 H NMR d [(CD3) 2 SO] 11.39 (br s, 1 H), 9.78 (s, 1 H), 8.12 (d, J = 2.6 Hz, 1 H), 7.93 (s, 1 H), 7.66 (d, J = 8.9 Hz, 1 H), 7.60-7.58 (m, 1 H), 7.52-7.43 (m, 3H), 7.13 (dd, J = 8.9, 2.6 Hz, 1 H). EIMS found M +: 363.0294, 365.0269. C2oH10CIN04 requires: 363.0298, 365.0289.

|-- - ---- - --- 'EXAMPLE 373- - - - - - - The preparation of 2 - [(EZ) -2- (2-chlorophenyl) ethenyl] -5-methoxy-1-benzothiophene (LXVIII: Ar = 2-chlorophenol, R8 = H. Y1 = S) (837) The reaction of 5-methoxy-1-benzothiophene-2-carbaldehyde (836) with 2-chlorobenzyltriphenylphosphonium chloride using the procedure described in Example 37 gave the diene (837) as a mixture of E / Z (63%) . 1 H NMR d (CDCl 3) minority isomer: 7.6 (d, 1 H), 7.4 (m, 5 H), 7.15 (s, 1 H), 7.05 (s, 1 H), 6.9 (d, 1 H), 6.75 ( m, 2H), 3.85 (s, 3H), major isomer: 7.75 (d, J = 9 Hz, 1 H), 7.55 (m, 2H), 7.25-7.4 (m, 3H), 7.18 (m, 2H) , 7.05 (s, 1 H), 6.95 (m, 2H).

EXAMPLE 374 The preparation of 4- (2-chlorophenyl) -9-methoxy-1 H- [1] benzothie-no [3.2-e] isoindol-1.3 (2H) -dione (LXX: Ar = 2-chlorophenyl) R8 = H. Y1 = S) (839) The reaction of (837) prepared as described in example 373 with maleimide using the procedure described in method 4 with the exception that the reaction time was 6 days gave the adduct (LXIX; Ar = 2-chlorophenyl, R8 = H, Y1 = S) (838) which was used without further purification. Aromatization of (838) with DDQ using the procedure described in Example 70 of Scheme 2 with the exception that the solvent was chloroform and the reaction conditions were 5 days' at 40 ° C gave (839) in the form of a yellow solid (44%). 1 H NMR d [(CD3) 2 SO] 1 1.46 (S, 1 H), 9.37 (d, J = 2.5 Hz, 1 H), 8.38 (s, 1 H), 8.2 (d, J = 9 Hz, 1 H ), 7.62 (m, 2H), 7.48 (m, 3H), 7.31 (dd, J = 2.5, 9.0 Hz, 1 H), 3.94 (s, 3H).

EXAMPLE 375 The preparation of 4- (2-chlorophenyl) -9-hydroxy-1 H- [1] l-benzoth-e [3-e] isoindol-1.3 (2 H) -dione (LXXI: Ar = 2-chlorophenyl. R8 = H. Y1 = S) (840) The demethylation of (839) prepared as described in Example 374 with BBr3 using the procedure described in Example 80 with the exception that the reaction time was 48 hours gave (840) (65%) as a solid yellow, mp 31 1-313 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.42 (S, 1 H), 9.85 (s, 1 H), 9.17 (d, J = 2.5 Hz, 1 H), 8.32 (s, 1 H), 7.9 (d , J = 9 Hz, 1 H), 7.62 (m, 2H), 7.5 (m, 3H), 7.17 (dd, J = 2.5, 9 Hz, 1H), MH + 346. Found: C, 68.75; H, 3.43; N, 3.89; S, 9.35. C20H11NO3S. 0.2 H20 requires: C, 68.83; H, 3.29; N, 4.01; S, 9.19. z _:. . . ^ EXAMPLE 376 The preparation of 6- (benzyloxy) -2 - [(EZ) -2- (chlorophenyl) ethenyl] -5-methoxy-1-benzofuran (LXVili: R8 = OCH Ph. Y1 = O. Ar = 2- chlorophenyl) (601) The reaction of 6- (benzyloxy) -5-methoxy-1-benzofuran-2-carbaldehyde (LXVIII; Y1 = O, R8 = OCH2Ph) with 2-chlorobenzyltri-phenylphosphonium chloride using the procedure described in method 2 with a time reaction time of 4 hours gave (601) as a pale yellow solid (83%), mp 130-135 ° C. 1 H NMR d [(CD3) 2 SO] 7.88 (d, J = 6.4 Hz, 1 H), 7.51-7.31 (m, 12H), 7.18 (s, 1 H), 6.93 (s, 1 H), 5.17 (s) , 2H), 3.78 (s, 3H). EIMS found: M + = 390.1021. C24H19CIN03 requires 390. 1023. 5 EXAMPLE 377 The preparation of 8- (benzyloxy) -4- (2-chlorophenyl) -9-methoxy-1H- [1] benzofuro [3.2-e1isoindole-1.3 (2H) -done (LXX: R8 = OCH2Ph, Y1 = O. Ar = 2-chlorophenyl) (603) 0 Compound (602) (LXIX, R8 = OCH2Ph, Y1 = O; Ar = 2-chlorophenyl) was prepared from (601) using the procedure described in method 4a using xylene as solvent to give a brown solid. The crude Diels-Alder adduct was flavored with 5 Mn02 using the procedure described in Example 79 to give (603) as a bright yellow solid (24%), m.p. 296-300 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.38 (s, 1 H), 8.17 (s, 1 H), 7.94 (s, 1 H), 7.67 (s, 1 H), 7.58-7.36 (m, 13H) , 5.28 (s, 2H), 3.93 (s, 3H). EIMS found: M + = 483.0871. C28Hi8CIN05 requires 0 483.0873.

SCHEME 15 EXAMPLE 378 The preparation of 4- (2-chlorophenyl) -8-hydroxy-9-methoxy-H- [1] benzofuro [3.2-e] isoindol-1.3 H) -dione (LXXII.Ar = 2-chlorophenyl) (604 ) Removal of the benzyl ether group from (603) prepared as described in Example 377 using the procedure described in Example 260 gave (604) as a yellow solid (86%), m.p. 294-298 ° C.

H NMR d [(CD3) 2 SO] 11.34 (s, 1H), 10.40 (s, 1H), 8.12 (s, 1H), 7.87 (s, 1H), 7.59-7.30 (m, 4H), 7.23 (s, 1H), 3.96 (s, 3H). EIMS found: M + = 393.0400. C2iH12CIN05 requires 393. 0404.

EXAMPLE 379 The preparation of trifluoromethanesulfonate of 4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydro-1H- [l] benzofuro [3.2-e] isoindol-8-yl (LXXIII: Ar = 2- chlorophenyl) (605) Compound (605) was prepared from (604) using the procedure described in Example 307 as a pale brown solid (88%), p.f.237-240 ° C. r. ^ ----- "1H RMÑ'ó [~ (CD3) 2SO] 11.55 (s, 1H), 8.47 (sr1H), 8.29 (s ~ Í'H), 8.11 (s, 1H), 7.62-7.45 ( m, 4H), 4.07 (s, 3H) .FABMS found: [M + H] + = 525.9958, 527.9940. C22H 2CIF3NS07 requires 525.9975, 527.9946.

EXAMPLE 380 The preparation of 4- (2-chlorophenyl) -8-et! L-9-methoxy-1H-ri] benzo-furof3.2- elisoindol-1.3 (2H) -dione (LXXV: Z = H. Ar = 2-chlorophenyl) (606) Compound 606 was prepared from (605) prepared as described in Example 379 using the procedure described in Example 309 and tetraethyltin as stannane, in the form of a yellow solid (87%), m.p. 252-257 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.45-1 1.15 (a, 1 H), 8.16 (s, 1 H), 7.91 (s, 1 H), 7.60-7.56 (m, 1 H), 7.54 (s) , 1 H), 7.52-7.41 (m, 3H), 4.23 (s, 3H), 3.92 (m, 2H), 2.16-2.09 (m, 3H). The S found: M + = 405.0766. C23Hi6CIN04 requires 405. 0768.

EXAMPLE 381 The preparation of 4- (2-chlorophenyl) -8-ethyl-9-hydroxy-1 H- [1] ben2ofuro [3.2- thesoindol-1.3 (2H) -dione (LXXVIH: n = 2. Z = H. Ar = 2-chlorophenyl) (607) The demethylation of (606) prepared as described in Example 380 by the procedure described in Example 80 gave (607) as a yellow solid (32%), m.p. 265-268 ° C. 1 H NMR d [(CD 3) 2 SO] 8.13 (s, 1 H), 7.68 (s, 1 H), 7.57-7.52 (m, 3 H), 7.44-7.31 (m, 4 H), 2.85 (c, J = 7.6 Hz , 2H), 1.35 (t, J = 7.6 Hz, 3H).

EIMS found: M + = 391.0612. C22H14CIN04 requires 391. 061 1.

EXAMPLE 382 The preparation of 4- (2-chlorophenyl) -8 - [(1 E) -4-hydroxy-1-butenyl] -9-methoxy-1 H- [1] benzofuro [3.2-e] isoindol-1.3 ( 2H) -dione (LXXIV: Z = CH? CHzOH, Ar = 2-chlorophenyl) (608) Compound 608 was prepared from the triflate, (605) prepared as described in example 379 using the procedure described in example 309 and (3E) -4- (tributylstannyl) -3-buten-1-ol as the stannane in the form of a yellow solid (84%), mp 247-250 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.43 (s, 1 H), 8.23 (s, 1 H), 7.92 Js. / IH), - • 7.86 (s, 1 H) 7.58"(d, J = 6.5? G?), 7.48-7.42 (m, 3H), 6.85 (d, J = 16.0 Hz, 1 H), 6.53 (m, 1 H), 4.35 (a, 1 H), 3.97 (s, 3H), 3.57 (t, J = 6.6 Hz, 2H), 2.41 (m, 2H), EIMS found: M + = 447.0886, C25H18CINC > 5 requires 447. 0873 EXAMPLE 383 The preparation of 4- (2-chloropheni) -8- (4-hydroxybutyl) -9-methoxy-1H- [1] benzofuro [3.2-e1-solindole-1.3 (2H) -dione (LXXV: Z = CH2CH2OH, Ar = 2- chlorophenyl) (609) Hydrogenation of (608) prepared as described in Example 382 using the procedure described in Example 310 gave (609) as a yellow solid (96%), m.p. 1 58-162 ° C. 1 H NMR d [(CD 3) 2 SO] 11.40 (s, 1 H), 8.29 (s, 1 H), 7.71 (s, 1 H), 7.60 (s, 1 H), 7.56-7.39 (m, 4H), 4.36 (a, 1 H), 3.95 (s, 3H), 3.39 (m, 2H), 2.75 (t, J = 7.6 Hz, 2H), 1.65 (m, 2H), 1.51 (m, 2H). FAB S found: [+ H] +: 450.1083, 452.1078. C25H21CINO5 requires C, 450.1 108, 452.1079. _ EXAMPLE 384 The preparation of 4- (2-chlorophenyl) -9-hydroxy-8- (4-hydroxybutyl) -1H- f11benzofuro [3.2-e] isoindol-1.3 (2H) -dione (LXXVHI: n = 4. Z = OH, Ar = 2-chlorophenyl) (610) The demethylation of (609) prepared as described in Example 383 using the procedure described in Example 80 gave (610) as a yellow solid (38%), m.p. 256-259 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.40 (a, 1 H), 9.80 (s, 1 H), 8.13 (s, 1 H), 7.90 (s, 1 H), 7.60-7.56 (m, 1 H ), 7.54 (s, 1 H), 7.52-7.42 (m, 3H), 4.38 (s, 1 H), 3.44 (m, 2H), 2.72 (t, J = 7.4 Hz, 2H), 1.66 (m, 2H), 1.50 (m, 2H). FABMS found: [M + H] +: 436.0942, 483.0922. C24H19CIN05 requires 436.0952, 438.0915.

EXAMPLE 385 The preparation of 8- (3-bromopropoxy) -2- (3-bromopropyl) -4- (2-chlorophenyl) -9-methoxy-1 H-rilbenzofuro [3.2-e] isoindol-1.3 (2H) -d8one (LXXIX: Ar = 2-chlorophenyl, n = 3) (331) The reaction of phenol (604) (245 mg, 0.62 mmol) prepared as described in example 378 with 1,3-dibromopropane (excess, 3.07 ml) according to the procedure described in example 298, with the exception that the reaction was performed in refluxing acetone (80 ml) gave the dibromide (331) (300 mg, 76%) as a yellow powder, mp. 180-187 ° C. H NMR d [(CD3) 2 SO] 8.16 (s, 1 H), 7.96 (s, 1 H), 7.60 (m, 2H), 7. 53-7.44 (m, 3H), 4.26 (t, J = 6.0 Hz, 2H), 3.95 (s, 3H), 3.72 (t, J = 6.4 Hz, 4H), 3. 57 (t, J = 6.6 Hz, 2H), 2.35 (m, 2H), 2.17 (m, 2H). Found: C, 51.25; H, 3.52; N, 2.37. C27H22Br2CIN05 requires: C, 5 .01; H, 3.49; N, 2.20.

EXAMPLE 386 The preparation of 4- (2-chlorophenyl) -8- [3- (dimethylamino) propoxy] -9-methoxy-1 H- [1] benzofuror3.2] isoindol-1.3 (2H) -dione (LXXXI : Ar = 2-chlorophenyl n = 3. Z = N (CH,) 2) (332) The reaction of dibromide (331) (100 mg, 0.16 mmol) prepared as described in Example 385 with an aqueous solution of dimethylamine (40%, 5.0 ml) according to the procedure described in example 179, with the exception of that the reaction was carried out in tetrahydrofuran (50 ml) at room temperature for 30 hours, gave the crude diamine (LXXX; Ar = 2-chlorophenyl, n = 3, Z = N (CH3) 2) which was used without further purification in the form of a solution in tetrahydrofuran, To this solution was added 5N potassium hydroxide (2.5 ml) and then it was added. The procedure indicated in Example 328 followed with the exception that the treatment with HCl was carried out for 24 hours and the chromatography was carried out eluting with methanol / dichloromethane / concentrated ammonia (5: 85: traces). Trituration in ethyl acetate gave the amine (332) (64 mg, 84%) as a yellow powder, m.p. 251-253 ° C. H NMR d [(CD3) 2 SO] 1 1.37 (br s, 1 H), 8.15 (s, 1 H), 7.93 (s, 1 H), 7.59 (m, 1 H), 7.55 (s, 1 H), 7.52-7.43 (m, 3H), 4.18 (t, J = 6.4 Hz, 2H), 3.93 (s, 3H), -2.5 (m obscured, 2H), 2.23 (sa, 6H), 1.96 (m, 2H) . Found: C, 65.03; H, 4.79; N, 6.00. C26H23CIN2O5 requires: C, 65.21; H. 4.84; N, 5.85.

EXAMPLE 387 The preparation of 4- (2-chlorophenyl) -9-methoxy-8- [3- (1-pyrrolidinyl) propoxy] -1 H-fnbenzofurof3.2-e1soindol-1.3 (2H) -dione (LXXXI: Ar = 2-chlorophenyl, n = 3. Z = 1-pyrrolidinyl) (333) The reaction of dibromide (331) (110 mg, 0.17 mmol) prepared as described in Example 385 with pyrrolidine (361 μ ?, 4.33 mmol) according to the procedure described in Example 179, except that the The reaction was carried out in tetrahydrofuran (50 ml) at room temperature for 3 days, gave the crude diamine (LXXX; Ar = 2-chlorophenyl, n = 3, Z = 1-pyrrolidinyl), which was used without further purification in the form of a solution in tetrahydrofuran. To this solution was added 5 N potassium hydroxide (2.5 ml) and then the indicated procedure was followed in Example 328 with the exception that the treatment with HCl was done for 24 hours and the chromatography was carried out by eluting with methanol / dichloromethane / concentrated ammonia (15: 85: traces). Crystallization from ethyl acetate / hexane gave the amine (333) (51 mg, 59%) as a yellow powder, m.p. 252-255 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.35 (br s, 1 H), 8.15 (s, 1 H), 7.91 (s, 1 H), 7.58 (m, 1 H), 7.54 (s, 1 H ), 7.52-7.43 (m, 3H), 4.19 (t, J = 6.4 Hz, 2H), 3.93 (s, 3H), 2.57 (t, J = 7.1 Hz, 2H), 2.46 (m, 4H), 1.97 (m, 2H), 1.69 (m, 4H). Found: C, 66.46; H, 5.15; N, 5.43. C 28 H 25 Cl 2 O 5 requires C, 66.60; H, 4.99; N, 5.55.

EXAMPLE 388 The preparation of 4- (2-chlorophenol-8- [3- (dimethylammon) propoxy-1-hydroxy-1H- [11-benzofurof3.2-e] isoindol-1.3 (2H) -dione (LXXXII: AR2-chlorophenyl, n = 3, Z = N (CH3) 2) (334) The demethylation of the amine (332) (70 mg, 0.15 mmol) prepared as described in Example 386 according to the procedure described in Example 80, with the exception that the reaction was carried out at 0 ° C for 18 hours. hours and chromatography was performed eluting with methanol / dichloromethane / triethylamine (15:85: traces), gave the amine (334) (48 mg, 71%) as a yellow powder, which was converted to the hydrochloride salt, mp 255-258 ° C. 1 H NMR d [(CD3) 2 SO] 11.34 (br s, 1 H), 9.96 (br s, 1 H), 9.44 (br, - 1 H), 8. 10 (s.'IH), 7? 9Í (s > 1_H), 7.58 (m, 1 H), 7.51-7.43 (m, 4H), 4.23 (t, J = 5.9 Hz, 2H), -3.3 (m obscured, 2H), 2.81 (s, 6H), 2.21 (m, 2H). Found: C, 58.86; H, 4.68; N, 5.35. C25H21CIN2O5. HCI.1 / 2H20 requires: C, 58.84; H, 4.54; N, 5.49.

EXAMPLE 389 The preparation of 4- (2-chlorophenyl) -9-hydrox! -8- [3- (1-pyrrolidinyl) propoxy] -1 H-rilbenzofurof3.2-eisoisole-1,3 (2H) -dione (LXXXII : Ar = 2-chlorophenyl n = 3. Z = 1 -pyrrolidinyl) (335) The demethylation of the amine (333) (50 mg, 0.10 mmol) prepared as described in Example 387 according to the procedure described in Example 80, with the exception that the reaction was carried out at 0 ° C for 6 hours and the chromatography was performed eluting with methanol / dichloromethane / triethylamine (15:85: trace), gave the amine (335) (mg,%) as a yellow powder, which was converted to the hydrochloride salt, mp. 302-304 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.34 (S, 1 H), 9.99 (a, 1 H), 9.47 (a, 1 H), -_- - 8: 10 (s, 1 H), 7.90 (s, 1 H), 7.58 (m, 1 H), 7.51 (s, 1 H), 7: 52-7.42 (m, 3H j, 4.24 (t, J = 5.7 Hz, 2H), 3.6 (a, 2H), 3.03 (a, 2H), 2.22 (m, 2H), 2.08-1.81 (m, 6H) Found: C, 61.18; H, 4.56; N, 5.16. C ^ HaaCINaOs. HCI requires C, 61.49; H, 4.59; N, 5.31.

SCHEME 16 Procedures of scheme 16 EXAMPLE 390 The preparation of trifluoromethanesulfonate of 4- (2-chlorophenyl) -6-methyl-1,3-dioxo-1.2.3.6-tetrahydropyrrolo [3,4-c1carbazol-8-yl (LXXXIII: Ar = 2-chlorophenyl, R10 = CH2) ( 316) The reaction of phenol (845) (0.25 g, 0.66 mmol) prepared as described in example 280 according to the procedure described in example 307 gave triflate (316) (323 mg, 96%) in the form of a pale yellow solid, mp 230-233 ° C. 1 H NMR d [(CD3) 2 SO] 11.26 (br s, 1 H), 9.04 (d, J = 8.7 Hz, 1 H), 8.03 (d, J = 2.3 Hz, 1 H), 7.94 (s, 1 H) , 7.59 (m, 1 H), 7.50 (m, 4H), 4.04 (s, 3H). . "| ~ 'Found:. ^, _ 51.98; H, 2.29; N, - 5.41. - 22H2CIF3Ñ2SO5 requires C, 5.93; H, 2.38; N, 5.51.

EXAMPLE 391 The preparation of 4- (2-chlorophenii) -6-methyl-8-vinylpyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (LXXXIV: Ar = 2-chlorophenyl, R10 = CH,) ( 317) The reaction of] triflate (316) (0.32 g, 0.63 mmol) prepared as described in Example 390 with tetravinyltin (172 μ ?, 0.94 mmol) according to the procedure described in Example 309 gave the alkene ( 137) (193 g, 79%) as a pale yellow solid, mp 276-282 ° C. H NMR d [(CD3) 2 SO] 1 1.13 (br s, 1 H), 8.86 (d, J = 8.2 Hz, 1 H), 7.84 (m, 2H), 7.60-7.46 (m, 5H), 6.98 (dd) , J = 17.6, 10.9 Hz, 1 H), 6.09 (d, J = 17.6 Hz, 1 H), 5.42 (d, J = 10.9 Hz, 1 H), 4.00 (s, 3H). Found: C, 69.64; H, 4.03; N, 6.88. C23H15CIN202. 1 / 2H20 requires: C, 69.79; H, 4.07; N, 7.08.

EXAMPLE 392 The preparation of 4- (2-chlorophenyl) -8- (2-hydroxyethyl) -6-methylpyrrolo [3,4- c] carbazole-1.3 (2H.6H) -dione (LXXXV: Ar = 2-chlorophenyl. CH3) (318) The reaction of alkene (317) (60 mg, 0.16 mmol) prepared, -as described in Example 391 according to the procedure described in Example 344 gave the alcohol (318) (36 mg, 57%) in the form of a pale yellow solid, mp 289-292 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.10 (br s, 1 H), 8.81 (d, J = 8.1 Hz, 1 H), 7.82 (s, 1 H), 7.58 (m, 2H), 7.49 (m, 3H), 7.27 (d, J = 8.1 Hz, 1 H), 4.73 (t, J = 5.2 Hz, 1 H), 3.97 (s, 3H), 3.75 (m, 2H), 2.99 (t, J = 7.0 Hz, 2H). Found: C, 67.47; H, 4.37; N, 6.51. C23Hi7CIN203. 1 / 4H20 requires: C, 67.49; H, 4.31; N, 6.84.

EXAMPLE 393 The preparation of 4- (2-chlorophenyl) -8- (1,2-dihydroxyethyl) -6-methylpyrrolo [3. c] carbazoM3 (2H.6H) -done (LXXXVI: Ar = 2-chlorophenyl, R10 = CHZ) The reaction of the alkene (317) (50 mg, 0.13 mmol) prepared as described in Example 391 according to the procedure described in Example 300 gave the diol (319) (40 mg, 74%) in the form of a pale yellow solid, mp 252-255 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.1 1 (br s, 1 H), 8.84 (d, J = 8.2 Hz, 1 H), 7.84 (s, 1 H), 7.71 (sa, 1 H), 7.58 ( m, 1 H), 7.49 (m, 3H), 7.39 (day, J = 8.2 Hz, 1 H), 5.46 (d, J = 4.2 Hz, 1 H), 4.79 (m, 2H), 3.98 (s, 3H), 3.57 (m, 2H). Found: C, 65.72; H, 4.50; N, 6.32. C23H17CIN204 requires: C, 65.64; H, 4.07; N, 6.66. _. _ _ ^ EXAMPLE 394 The preparation of 4- (2-chlorophenyl) -8- (hydroxymethyl) -6-methylpyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (LXXXVII: Ar = 2-chlorophenyl) R10 = CH * ) (320) Ozone was bubbled through a solution of alkene (317) (60 mg, 0.16 mmol) prepared as described in Example 391 in methanol / dichloromethane (1 1: 1, 40 ml) at -78 ° C for 10 minutes , during which time the solution turned from yellow to yellow / green. The excess ozone was purged from the solution by bubbling nitrogen through it for 2 minutes and then a solution of sodium borohydride (180 mg, 4.76 mmol) in methanol (20 mL) was added. The resulting solution was allowed to warm to room temperature for 20 minutes and then diluted with water and the extraction was carried out with ethyl acetate, the organic phase was dried, the drying agent was removed and the solution was concentrated to dryness. Chromatography on silica eluting with ethyl acetate / hexane (3: 1 to 1: 0), followed by crystallization from ethyl acetate / hexane, gave the alcohol (320) (39 mg, 62%) as a pale yellow solid, mp 291-294 ° C. 1 H NMR d [(CD3) 2 SO] 11.11 (br s, 1 H), 8.85 (d, J = 8.1 Hz, 1 H), 7.84 (s, 1 H), 7.70 (br s, 1 H), 7.58 (m, 1 H), 7.49 (m, 3H), 7.35 (day, J = 8.1 Hz, 1 H), 5.42 (t, J = 5.6 Hz, 1 H), 4.77 (ci, J = 5.6 Hz, 2H), 3.98 (s, 3H). Found: C, 67.74; H, 4.11; N, 7.13. C22H 5CIN203 requires: C, 67.61; H, 3.87; N, 7.117. - ,, = _ .-.

EXAMPLE 395 The preparation of 4- (2-chlorophenyl) -8- (3-hydroxypropoxy) -2- (3-hydroxypropyl) -6-methylpyrrolof3.4-c] carbazole-1.3 (2H.6H) -dione ( LXXXVIII: Ar = 2-chlorophenyl, R10 = CHi) (321) The reaction of phenol (845) (0.53 g, 1.41 mmol) prepared as described in example 280 with 3-bromopropan-1-ol (280 μ ?, 3.10 mmol) according to the procedure described in example 298 gave the diol (321) (0.29 g, 42%) in the form of a yellow powder, mp 36-140 ° C. 1 H NMR d [(CD3) 2 SO] 8.77 (d, J = 8.7 Hz, 1 H), 7.76 (s, 1 H), 7.58 (m, 1 H), 7.49 (m, 3 H), 7.28 (d, J = 2.0 Hz, 1 H), 7.00 (dd, J 8.7, 2.0 Hz, 1 H), 4.61 (t, J = 5.1 Hz, 1 H), 4.49 (t, J = 5.0 Hz, 1 H), 4.24 ( t, J 6.3 Hz, 2H), 3.94 (s, 3H), 3.63 (m, 4H), 3.43 (m, 2H), 1.96 (m, 2H), 1.75 (m, 2H). Found: C, 64.91; H, 5.13; N, 5.63. C27H25CIN2O4 1 / 4H20 requires C, 65.19; H, 5.17; N, 5.63.

EXAMPLE 396 The preparation of 4- (2-chlorophenyl) -8- (3-hydroxypropoxy) -6-methylpyrrolo [3,4- c1carbazole-1.3 (2H.6H) -dione (LXXXIX; Ar-2-chlorophenyl) R1Q = CH- ,) (322) The reaction of the diol (321) (270 mg, 0.55 mmol) prepared as described in Example 395 according to the procedure described in Example 328, except that ethanol was used in place of acetonitrile and the HCI treatment was carried out for 18 hrs, gave the crude material which was dissolved in methanol / dichloromethane (4: 1, 80 ml), to which 1 M potassium carbonate (2.0 ml) was added (to hydrolyze a small amount of the acetate present as shown in the analysis by tic). The resulting solution was stirred at room temperature for 2 hours before being diluted with water and extracted with ethyl acetate, the organic phase was dried, the drying agent was removed and the solution was concentrated to dryness. Chromatography on silica eluting with ethyl acetate / hexane (21), followed by crystallization from ethyl acetate / hexane, gave the alcohol (322) (136 mg, 57%) as a yellow solid, m.p. 274-276 ° C. H NMR d [(CD3) 2 SO] 1 1.06 (br s, 1 H), 8.75 (d, J = 8.7 Hz, 1 H), 7.75 (s, 1 H), 7.57 (m, 1 H), 7.48 (m , 3H), 7.27 (d, J = 2.1 Hz, 1 H), 7.00 (dd, J = 8.7, 2.1 Hz, 1 H), 4.61 (t, J = 4.9 Hz, 1 H), 4.24 (t, J = 6.3 Hz, 2H), 3.94 (s, 3H), 3.63 (m, 2H), 1.96 (s, 2H). Found: C, 66.01; H, 4.41; H, 6.41. C24Hi9CIN204 requires: C, 66.29; H, 4.40; N, 6.44.

EXAMPLE 397 The preparation of 4- (2-chlorophenyl) -8- (3-iodopropoxy) -6-methylpyrrolo [3,4- c] carbazole-1.3 (2H.6H) -dione (XC: Ar = 2-chlorophenyl) R10 = CH2) (323) The reaction of the alcohol (322) (82 mg, 0.19 mmol) prepared as described in Example 396 according to the procedure described in Example 170 followed by the use of the procedure described in Method 27 gave after chromatography on silica eluting with ethyl acetate / hexane (21), iodide (323) (92 mg, 89%) as a yellow solid, mp 264-266 ° C. 1 H NMR d [(CD3) 2SO ] 11.07 (sa, 1 H), 8.77 (d, J = 8.7 Hz, 1 H), 7. 76 (s, 1 H), 7.58 (m, 1 H), 7.47 (m, 3H), 7.31 (d, J = 2.1 Hz, 1 H), 7.02 (dd, J = 8.7, 2.1 Hz, 1 H) , 4.23 (t, J = 6.0 Hz, 2H), 3.95 (s, 3H), 3.46 (t, J = 6.7 Hz, 2H), 2.30 (m, 2H).

Found: C, 53.30; H, 3.27; N, 5.08. C24H18CIN2O4. requires: C, 52.91; H, 3.33; N, 5.14.

EXAMPLE 398 The preparation of 4- (2-chlorophenyl) -8- [3- (dimethylamino) propoxy] -6-methylpyrrolof3.4-c] carbazole-1.3 (2H.6H) -dione (XCI: Ar = 2-chlorophenyl) R10 = CH ,. Z = N (CH,)) (324) The reaction of iodide (323) (50 mg, 0.09 mmol) prepared as described in example 397 with dimethylamine according to: the procedure described in example 179, with the exception that the reaction was carried out at room temperature during 2 hours and the chromatography was carried out on alumina (grade ll-III) eluting with ethyl acetate / methane (1: 0 a = 9: 1) dio1a ~ amine "(324) as a yellow powder, which crystallized in the form of the hydrochloride salt (43 mg, 96%) in methanol / diethyl ether / hexane, mp 262-265 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.08 (br.s, 1 H), 10.0 (br. 1 H), 8.78 (d, J = 8.7 Hz, 1 H), 7.78 (s, 1 H), 7.58 (m, 1 H), 7.48 (m, 3 H), 7.29 (d, J = 2.1 Hz, 1 H), 7.02 (dd, J = 8.7, 2.1 Hz, 1 H), 4.26 (t, J = 6.0 Hz, 2H), 3.96 (s, 3H), 3.28 (m partially obscured, 2H), 2.82 (s, 6H), 2.22 (m, 2H) Found: C, 59.62; H, 5.01; N, 8.02, C-26H24CIN3O3, HCI 1.5H20 requires: C, 59.43; H, 5.37; N, 8.00.

EXAMPLE 399 The preparation of 4- (2-chlorophenyl) -6-methyl-8- [3- (methylamino) propropoxypyrrolof3.4-c] carba2ol-1.3 (2H: 6H) -dione (XCL Ar = 2-chlorophenyl, R10 = CH2, Z = NHCH¾) (325) The reaction of iodide (323) (17 mg, 0.03 mmol) prepared as described in Example 397 with an aqueous solution of methylamine (40%, 54 pl) according to the procedure described in example 179, with the exception that the reaction was carried out at room temperature in tetrahydrofuran for 20 hours, gave the amine (325) (6 mg, 43%) as a yellow powder, mp. 269-271 ° C. HRN d [(CD3) 2 SO] 8.75 (d, J = 8.7 Hz, 1 H), 7.76 (s, 1 H), 7.57 (m, 1 H), 7.47 (m, 3H), 7.27 (d, J = 2.1 Hz, 1 H), 8.99 (dd, _J = 8.7 ^ 2.1 Hz, 1 H), 4.22 (t7 J = 6.4¾? 2H), "3.94" (s, 3H), 2.67 (t, J = 6.7 ?? - 2H), 2.32 (s, 3H), 1.94"(m, 2H) .FABMS found: [M + H] + = 448.1447. 450.1428.C25H22CIN3O3 requires 448.1428, 450.1398.

EXAMPLE 400 The preparation of 4- (2-chlorophenyl) -8- [3- (cis-3,5-dimethyl-1-piperazinyl) propoxy] -6-methylpyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (XCI: Ar = 2-chlorophenyl, R10 = CHj, Z-cs-3,5-dimethyl-1-piperazinyl) (326) The reaction of iodide (323) (17 mg, 0.03 mmol) prepared as described in Example 397 with cis-2,6-dimethylpiperazine (71 mg, 0.62 mmol) according to the procedure described in Example 179, with the exception that the reaction was carried out at room temperature in tetrahydrofuran for 20 hours and the chromatography was carried out on alumina (grade ll-III) eluting with ethyl acetate / methanol (from 1: 0 to 9: 1), gave the amine (326) (15 mg, 91%) in the form of a yellow powder, mp 225-227 ° C. H NMR d [(CD3) 2 SO] 1 1.06 (br s, 1 H), 8.75 (d, J = 8.7 Hz, 1 H), 7.76"(IH)," 7.57 fm, ÍH), 7.47 (m, 3H), 7.25- (d, J = 2.1 Hz, 1 H), 8! 99 (dd; J = 8.7, 2.1 Hz, 1 H), 4.19 (t, J = 6.3 Hz, 2H), 3.94 (s, 3H), 2.73 (m, 4H), 2.44 (t, J = 7.1 Hz, 2H), 1.96 (m, 2H), 1.46 (t, J = 10.6 Hz, 2H), 0.92 (d, J = 6.2 Hz, 6H). FABMS found: [M + H] + = 531.2166, 533.2162. C30H31CIN4O3 requires 531.2163, 533.2133.

EXAMPLE 401 The preparation of 8- (allyloxy) -4- (2-chlorophenH) -6-methylpyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (XCIII: Ar = 2-chlorophenyl) R10 = CH ^ (327) The reaction of phenyl (845) (250 mg, 0.66 mmol) prepared as described in Example 280 with allyl bromide according to the procedure described in Example 298 gave the bis-allyl derivative (XCII; Ar = 2 chlorophenyl, R = CH 3), which was used without further purification. Reaction of the crude material according to the procedure described in Example 328 gave the alkene (327) (216 mg, 79%) as a yellow powder, m.p. 253-256 ° C. 1 H NMR d [(CD3) 2 SO] 1 .07 (sa, IH), 8.77 (d, J = 8.7 Hz, 1H), 7.76 (s, 1 H), 7.57 (m, 1 H), 7.47 (m, 3H). 7.30 (d, J = 2 Hz, 1 H), 7.03 (dd,: J = 8.7, 2.2 Hz, H), 6.20-6.1 1 (m, 1 H), 5.51 (m, 1 H), 5.33 (m, 1 H), 4.77 (m, 2H), 3.92 (s, 3H). Found: C, 69.42; H, 4.27; N, 6.50. C 24 H 17 CIN 2 O 3 requires: C, 69.15; H. 4.11; N, 6.72.

EXAMPLE 402 The preparation of 4- (2-chlorophenyl) -8- (2-hydroxyethoxy) -6-methylpyrrolof3.4-c] carbazole-1.3 (2H.6H) -dione (XCIV: Ar = 2-chlorophenyl) FU = CH3) (328) Ozone was bubbled through a solution of alkene (327) (50 mg, 0.12 mmol) prepared as described in Example 401 in methanol / dichloromethane (1: 1, 40 ml) at -78 ° C for 10 minutes, du which time the solution turned yellow to yellow / green. The excess ozone was purged from the solution by bubbling nitrogen through it for 2 minutes and then a solution of sodium borohydride (136 mg, 3.60 mmol) in methanol (20 mL) was added. The resulting solution was allowed to warm to room temperature for 45 min and then diluted with water and extracted with ethyl acetate, the organic phase was dried, the drying agent was removed and the solution concentrated to dryness. Chromatography on silica eluting with ethyl acetate / hexane (from 1: 1 to 3: 1), followed by trituration in diethyl ether, gave the alcohol (328) (11 mg, 22%) as a yellow solid, mp 309-312 ° C. 1 H NMR d [(CD3) 2SO] 11.06 (br s, 1 H), 8.77 (d, J = 8.7 Hz, 1 H), 7.75 (m, 1 H), 7.57 (m, 1 H), 7.47 (m, 3H), 7.28 (d, J = 2.0 Hz, 1 H), 7.01 (dd, J = 8.7, 2.0 Hz, 1 H), 4.94 (t, J = 5.4 Hz, 1 H) , 4.19 (t, J 5.1 Hz, 2H), 3.95 (s, 3H), 3.81 (m, 2H) .FABMS found [M + H] +: 421.09932, 423.0912. CsaH ^ CINaO * requires 421.0955, 423.0926.

EXAMPLE 403 The preparation of 4- (2-chlorophenyl) -8- (2,3-dihydroxypropoxy) -6-methylpyrrolor-3,4-clcarbazole-1.3 (2H.6H) -dione (XCV: Ar = 2-chlorophenite. .) (329) The reaction of the aiquene (327) (30 mg, 0.07 mmol) prepared as described in Example 401 according to the procedure described in Example 300 gave the diol (329) (19 mg, 60%) as a solid yellow, mp 287-290 ° C. 1 H NMR d [(CD3) 2 SO] 1 1 .06 (s, 1 H), 8.77 (d, J = 8.7 Hz, 1 H), 7.76 (s, 1 H), 7.57 (m, 1 H), 7.47 (m, 3H), 7.27 (d, J = 2.2 Hz, 1 H), 7.00 (dd, J = 8.7, 2.2 Hz, 1 H), 5.04 (d, J = 5.1 Hz, 1 H), 4.73 (t , J = 5.6 Hz, 1 H), 4.20 (dd, J = 8.8, 4.5 Hz, 1 H), 4.07 (dd, J = 9.9, 6.1 Hz, 1 H), 3.95 (s, 3H), 3.89 (m , 2H), 3.52 (t, J = 5.6 Hz,.-2). 'FABMS found [M + H] +: 451.1052, 453.1039. C24H19CIN2O5 requires 451.1061, 453.1031.

SCHEME 17 Procedures for scheme 17 Representative procedure for method 32 of scheme 17 EXAMPLE 404 The preparation of 1- (5-methoxy-1H-indol-2-yl) ethanone (XCV1, R2 = CH2) (800) To a solution of 5-methoxy-1 H-indole-2-carbaldehyde (1) (2.0 g, 1.0 mmol) in tetrahydrofuran (30 ml) at 0 ° C was added dropwise a solution of methylmagnesium bromide. (11 mL of a 3M solution in ether, 34.0 mmol). The cooling bath was removed and the reaction mixture was allowed to warm to room temperature for 50 min. Saturated ammonium chloride was added and then the tetrahydrofuran was removed under reduced pressure.

The residue was extracted with ethyl acetate (2 x 60 mL) and the combined extracts were washed, dried and concentrated. The crude alcohol was dissolved in chloroform (40 ml), manganese dioxide (15 mg, 0.171 mmol) was added and the reaction mixture was heated to reflux for 40 min. The mixture was filtered through Celite and then concentrated to give an off-white solid. The solid was purified by recrystallization from dichloromethane to give (800) (1.80 g, 83%), m.p. 170-172 ° C. H NMR d [(CD3) 2 SO] 11.58 (br s, 1 H), 7.34 (d, J = 9.0 Hz, 1 H), 7.23 (s, 1 H), 7.12 (d, J = 2.4 Hz, 1 H) , 6.94 (dd, J = 9.0, 2.4 Hz, 1 H), 3.77 (s, 3H), 2.52 (s, 3H). Found: C, 69.77; H, 5.95; N, 7.54. CnHnN02 requires: C, 69.83; H, 5.86; N, 7.40.

Representative procedure for method 33 of scheme 17 EXAMPLE 405 The preparation of methyl 2 - [(E.Z) -1-methyl-2-phenylethenyl] -1H-indole-5-methyl ether (XCVII: R = CHj.R1 = phenyl) (801) To a suspension of benzyltriphenylphosphonium bromide (3.4 g, 7.9 mmol) in tetrahydrofuran (30 mL) was added a solution of LDA (4.9 mL of a 1.5M solution in cidohexane, 7.4 mmol). The red / orange reaction mixture was stirred for 10 min and then a solution of the ketone (1.0 g, 5.3 mmol) in tetrahydrofuran (15 mL) was added. The mixture was heated to reflux overnight and then water was added and the solvent was removed under reduced pressure. The organic material was extracted with ethyl acetate (3 x 50 mL). The combined extracts were dried and concentrated. The residue was purified by column chromatography on silica eluting with dichloromethane to give methyl (801) (0.26 g, 19%) as a mixture of E and Z isomers, which was used without further purification.

EXAMPLE 406 The preparation of 9-methoxy-5-methyl-4-phenylpyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (XCIX: R2 = CH3, R ± = phenyl) (803) The reaction of (801) prepared as described in - ^ T (0 405 cmmaleimide at 180 ° C for 40 min using the procedure described in Example 69 gave the adduct (XCVIII; R2 = CH3, R1 = phenyl) (802), which was used without further purification The crude Diels-Alder adduct was aromatized with Mn02 using the procedure described in Example 79 of Scheme 2 to give (803) (69%).

EXAMPLE 407 The preparation of 9-hydroxy-5-methyl-4-phenylpyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (C: R2 = CH-? R1 = phenyloi (804) The demethylation of (803) prepared as described in Example 406 with BBr3 using the procedure described in Example 69 gave (804) (90%), m.p. 270-280 ° C. 1 H NMR d [(CD3) 2 SO] 11.60 (s, 1 H), 10.82 (s, 1 H), 9.22 (s, 1 H), 8.31 (d, J = 2.0 Hz, 1 H), 7.47-7.42. (m, 4H), 7.36-7.23 (m, 2H), 7.06 (dd, J = 8.7, 2.0 Hz, 1 H), 2.32 (s, 3H). EIMS found M +: 342.1005. C21 H14 2O3 requires: 342.1004.

EXAMPLE 408 The preparation of (5-methoxy-1 HHndol-2-yl) (phenyl) methanone- (XCVI: -R2 = ~~ phenyl) (805) Reaction of 5-methoxy-1 H-indole-2-carbaldehyde with phenylmagnesium bromide using the procedure described in Example 404 gave (805) (91%), m.p. 159-161 ° C. 1 H NMR d [(CD3) 2 SO] 11 .86 (s, 1 H), 7.94-7.91 (m, 2H), 7.71-7.66 (m, 1 H), 7.61-7.57 (m, 2H), 7.42 (d , J = 8.9 Hz, 1 H), 7.16 (d, J = 2.4 Hz, 1 H), 7.03 (s, 1 H), 6.99 (dd, J = 8.9, 2.4 Hz, 1 H), 3.77 (s, 3H).

Found: C, 76.28; H, 5.21; N, 5.42. C 6Hi3N02 requires: C, 76.48; H, 5.21; N, 5.57.

EXAMPLE 409 The preparation of 2 - [(E) -1,2-diphenylethenyl] -5-methoxy-H-indole [XCVII: R1 = R2 = phenyl] (806) Freshly washed magnesium filings (0.29 g, 12 mmol) and a crystal of iodine in ether (20 ml) were added with benzyl chloride (1.4 ml, 12 mmol) at a rate such as to maintain the reaction mixture at room temperature. reflux, After the addition of the benzyl chloride was complete, the reaction mixture was refluxed for a further 3 h and then added to a solution of the ketone (1.0 g, 3.98 mmol) in tetrahydrofuran (20 ml). . The reaction mixture was stirred at RT temperature for 1 hr and then 2 M hydrochloric acid (2 ml) was added. The mixture was filtered and then the solvent was removed under reduced pressure. The crude oily yellow alcohol was dissolved in ethanol / tetrahydrofuran / 2M HCl (2: 2: 1) and stirred at room temperature for 15 min, water was added and the organic solvents were removed under reduced pressure. The organic material was extracted with ethyl acetate (3 x 50 mL) and the combined extracts were dried and concentrated. The residue was purified by recrystallization from dichloromethane (0.95 g, 73%), m.p. 144-147 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.24 (s, 1 H), 7.49-7.42 (m, 3H), 7.29-7.26 (m, 4H), 7.17-7.08 (m, 3H), 6.97-6.95 (m , 2H), 6.92 (d, J = 2.4 Hz, 1 H), 6.75 (dd, J = 8.7, 2.4 Hz, 1 H), 5.81 (s, 1 H), 3.70 (s, 3H). Found: C, 84.30; H, 5.85; N, 4.36. C23H19NO 1/10 H20 requires: C, 84.43; H, 5.91; N, 4.28.

EXAMPLE 410 The preparation of 9-methoxy-4-5-diphenylpyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (XCIX, R1 = R2 = phenyl) (808) The reaction of (806) prepared as described in Example 409 with maleimide at 180 ° C using the procedure described in Example 69 gave the adduct (XCVIII; R1 = R2 = phenyl) (807), which was used without purification additional. The crude Diels-Alder adduct was aromatized with "MnÓ2 using the procedure described" in Example 79 of Scheme 2 to give (808) (77%). 1 H NMR d [(CD3) 2 SO] 1 1.08 (s, 1 H), 1.02 (sa, 1 H), 8.52 (d, J = 2.6 Hz, 1 H), 7.50 (d, J = 8.9 Hz, 1 H), 7.36-7.28 (m, 3H), 7.21-7.11 (m, 8H), 3.89 (s, 3H).

EXAMPLE 411 The preparation of 9-hydroxy-4,5-diphenylpyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (C: R1 | R2 = phenyl) (809) The demethylation of (807) prepared as described in Example 410 with BBr3 using the procedure described in Example 80 gave (809) as a yellow powder (87%), m.p. > 300 ° C. 1 H NMR d [(CD3) 2 SO] 10.96 (s, 1 H), 10.94 (s, 1 H), 9.23 (s, 1 H), 8.37 (d, J = 2.4 Hz, 1 H), 7.39 (d, J = 8.7 Hz, 1 H), 7.35-7.29 (m, 3H), 7.22-7.10 (m, 7H), 7.03 (dd, J = 8.7, 2.4 Hz, 1 H). Found: C, 77.16; H, 4.00; N, 6.83. C26Hi6N203 requires: C, 77.22; H, 3.99; N, 6.93.

EXAMPLE 412 ~ - · .. '- - "" "The preparation of 5-methoxy-2 - [(1 E) -1-phenyl-1-propenyl] -1 H-indole (XCVII: R2 = phenyl. CH¾) (810) The reaction of (805) prepared as described in Example 408 with ethyltriphenylphosphonium bromide using the procedure described in Example 405 gave (810) (72%), m.p. 128-130 ° C. 1 H NMR d [(CD3) 2 SO] 10.97 (s, 1 H), 7.47-7.39 (m, 3H), 7.28-7.19 (m, 3H), 6.88 (d, J = 2.4 Hz, 1 H), 6.69 ( dd, J = 8.7, 2.4 Hz, 1 H), 6.38 (c, J = 6.9 Hz, 1 H, 5.69 (s, 1 H), 3.69 (s, 3H), 1.67 (d, J = 6.9 Hz, 3H ).

Found: C, 81.78; H, 6.26; N, 5.33. C 8H17NO requires: C, 82.10; H, 6.51; N, 5.32.

EXAMPLE 413 The preparation of 9-methoxy-4-methyl-8-phenylpyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (XCVIII: R2 = phenyl, R1 = CH3) (812) The reaction of (810) prepared as described in Example 412 with maleimide at 180 ° C using the procedure described in Example 69 gave the adduct (XCIV; R2 0 phenyl, R1 = CH3) (81 1), which used without further purification. The crude Diels-Alder adduct was aromatized with Mn02 using the procedure described in Example 79 of Scheme 2 to give (812) (74%), m.p. 284-286 ° C. 1H RN d [(CD3) 2SO] 11.06 (sa, 1 H), 10.93 (s, 1 H), 8.43"(d," "'J = 6 Hz, 1 H) 7.64-7.54 (m, 3H) , 7.45-7.42 (m, "3H), 7.14 (dd, J = 8.9, 2.6 Hz, 1 H), 3.32 (s, 3H), 2.48 (s, 3H). Found: C, 73.13; H, 4.32; N, 7.72. C22H16N203. 1/3 H20 requires: C, 72.92; H, 4.64; N, 7.73.

EXAMPLE 414 The preparation of 9-hydroxy-4-methyl-5-phenylpyrrolof3.4-clcarbazole-1.3 (2H.6H) -dione (C: R2 = phenyl, R = CH,) The demethylation of (812) prepared as described in Example 413 with BBr3 using the procedure described in Example 80 gave (813) (85%), m.p. > 300 ° C. 1 H NMR d [(CD3) 2SO] 11.01 (s, 1 H), 10.79 (s, 1 H), 9.17 (s, 1 H), 8.28 (d, J = 2.4 Hz, 1 H), 7.34-7.60 (m, 2H), 7.57-7.52 (m, 1 H), 7.43-7.41 (m, 10 2H), 7.34 (d, J = 8.7 Hz, 1 H), 6.98 (dd, J = 8.7, 2.4 Hz, 1 H), 2.26 (s, 3H). EIMS found M +: 342.1003. C2iH14 203 requires: 342.1004.

EXAMPLE 415 The preparation of 5-methoxy-2-vinyl-1H-indole (XCVII: R1 = R2 = H) (814) "15" "- · The reaction of 5-methoxy-1 H-indole-2-carbaldehyde with methyltriphenylphosphonium bromide using the procedure described in method 33 gave (814) (87%), mp 80-81 ° C. NMR d [(CD3) 2 SO] 11.09 (s, 1 H), 7.21 (d, J = 8.7 Hz, 1H), 6.97 20 (d, J = 2.3 Hz, 1 H), 6.75-6.66 (m, 2H) , 6.37 (s, 1 H), 5.76 (d, J = 17.3 Hz, 1 H), 5.21 (d, J = 11.6 Hz, H), 3.73 (s, 3H) Found: C, 73.34; H, 6.24; N, 8.11.C, HuNO requires: C, 76.28; H, 6.40; N, 8.09.

EXAMPLE 416 The preparation of 9-methoxypyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (XCIX: R1 = R2 = H) (816) The reaction of (814) prepared as described in Example 415 with maleimide at 180 ° C using the procedure described in Example 69 gave the adduct (XCVIII; R = R '= H) (814) which was used without purification additional. The crude Diels-Alder adduct was aromatized with Mn02 using the procedure described in Example 79 to give (815) (76%), m.p. 260-270 ° C. 1 H NMR d [(CD3) 2 SO] 1.91 (s, 1 H), 11. 10 (s, 1 H), 8.38 (d, J = 2.6 Hz, 1 H), 7.81 (d, J = 8.2 Hz, 1 H), 7.76 (d, J = 8.2 Hz, 1 H), 7.54 (d, J = 8.8 Hz, 1 H), 7.22 (d, J = 8.8, 2.6 Hz, 1 H), 3.88 (s, 3H) . Found: C, 65.44; H, 3.96; N, 10.30. C15H10N2O3. 1/2 H20 requires: C, 65.45; H, 4.03; N, 10.18. ....., · - - ~ - - "r" "_ EXAMPLE 417 The preparation of 9-hydroxypyrid > or [3,4-c] carbazole-1.3 (2HT6H) -dione (C: R1 = R2 = H) (817) The demethylation of (816) prepared as described in Example 416 with BBr3 using the procedure described in Example 80 gave (817) (79%), m.p. 335-345 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.77 (s, 1 H), 11.04 (s, 1 H), 9.23 (s, 1 H), 8.24 (d, J = 2.3 Hz, 1 H), 7.75 (2 d, J = 8.2 Hz, 2H), 7.43 (d, J = 8.7 Hz, 1 H), 7.05. dd, J = 8.7. 2.3 Hz, 1 H). Found: C, 64.44; H, 3.45; N, 10.41. Ci4HeN203. 1/2 H20 requires: C, 64.37; H, 3.47; N, 10.72.

EXAMPLE 418 The preparation of methyl 2- (1-phenylvinyl) -1H-indol-5-yl ether (XCVII: R2 = phenyl, R1 = H) f818) The reaction of (805) prepared as described in Example 408 with methyltriphenylphosphonium bromide using the procedure described in Example 405 gave (818) (95%), m.p. 119-121 ° C. H NMR d [(CD3) 2 SO] .1 1.13 (s, 1 H), 7: 47-7: 39 (m, 5H), 7.26 ~ (d, _J = 8.8 Hz, 1 H), 6.97 (d, J = 2: 4 Hz, 1 H), * 6.76 (dd, J = 8.8, 2.4 Hz, 1 H), 6.12 (s, 1 H), 5.77 (s, 1 H), 5.30 (s, 1 H) 3.72 (s, 3H). Found: C, 81.83; H, 6.22; N, 5.59. C17H15NO requires: C, 81.90; H, 6.06; N, 5.62.

EXAMPLE 419 The preparation of 9-methoxy-5-phenylpyrrolo [3.4-c] carba2ol-1.3 (2H.6H) -dione (XCIX: R2 = phenyl, R1 = H) (820) The reaction of (818) prepared as described in example 418 with maleimide at 180 ° C using the procedure described in example 69 gave the adduct (XCVIII; R = phenyl, R '= H) (819) which was used without additional purification. The crude Diels-Alder adduct was aromatized with Mn02 using the procedure described in Example 79 to give (820) (73%), m.p. 281-285 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.63 (br s, 1 H), 1 1.15 (br s, 1 H), 8.45 (d, J = 2.5 Hz, 1 H), 7.78-7.76 (m, 2H), 7.68 (s, H), 7.65-7.62 (m, 2H), 7.57-7.53 (m, 2H), 7.22 (dd, J = 8.8, 2.5 Hz, 1 H), 3.89 (s, 3H). requires: EXAMPLE = O 420 The preparation of 9-hydrox8-5-phenylpyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (C: R2 = phenyl, R = H) (821) The demethylation of 820 prepared as described in Example 419 with BBr3 using the procedure described in Example 80 gave (821) (89%), m.p. 335-345 ° C.

H NMR d [(CD3) 2 SO] 11.50 (s, 1H), 11.10 (s, 1H), 9.26 (d, J = 2.4 Hz, H), 8.30 (d, J = 2.4 Hz, 1H), 7.77-7.75 (m, 2H), 7.65-7.61 (m, 3H), 7.56-7.52 (m, 1H), 7.46 (d, J = 8.7 Hz, 1H), 7.06 (dd, J = 8.7.2.4 Hz, 1H). Found: C, 72.71; H, 3.55; N, 8.16. C2oH12N203 requires: C, 73.16; H, 3.68; N, 8.53.

EXAMPLE 421 The preparation of 1- (5-methoxy-1H-indol-2-yl) -1-propanone (XCV1: R2 = CH2CH3) (822) Reaction of 5-methoxy-1H-indole-2-carbaldehyde with ethylmagnesium bromide using the procedure described in Example 404 gave (822) (82%), m.p.170-171.5 ° C. 1 H NMR d [(CD3) 2Sg] 1.56 (s, 1H) r-7.34 (d "J = 9.T ?????), 7.22 (d, J = 1.7 Hz, 1H), 7.1 (d, J = 2.4 Hz, 1H), 6.93 (d, J = 9.1, 2.4 Hz, 1H), 3.77 (s, 3H), 2.96 (c, J = 7.3 Hz, 2H), 1.13 (t, J = 7.3 Hz, 1H ), 6.93 (d, J = 9.12.4 Hz, 1H), 3.77 (s, 3H), 2.96 (c, J = 7.3 Hz, 2H), 1.13 (t, J = 7.3 Hz, 3H) Found: C 71.15, H, 6.45, N, 7.07, Ci2Hi3N02 requires: C, 70.92, H, 6.45, N, 6.89.

EXAMPLE 422 The preparation of 2 - [(E.Z) -1-ethyl-2-phenylethen-5-methoxy-1H-indole tXCVII: R2 = CH? CH. R1 = phenyl) (823) The reaction of (822) prepared as described in Example 421 with benzyltriphenylphosphonium bromide using the procedure described in Example 404 gave (823) (38%), m.p. 95-97 ° C. Found: C, 82.28; H, 6.98; N, 5.07. C 9H19NO requires: C, 82.28; H, 6.90; N, 5.05.

EXAMPLE 423 The preparation of 5-ethyl-9-methoxy-4-phenylpyrrolo [3,4-c] carbazole-1.3 (2H.6H) - The reaction was prepared as described in example 422 with maleimide at 180 ° C using the procedure described in example 69 gave the adduct (XCVIII; R = CH2CH3, R '= phenyl) (824) , which was used without further purification. The crude Diels-Alder adduct was aromatized with Mn02 using the procedure described in Example 79 to give (825) (68%), m.p. 301-303 ° C. 1 H NMR d [(CD3) 2 SO] 11.78 (s, 1 H), 10.87 (s, 1 H), 8.47 (d, J = 2.6 Hz, 1 H), 7.56 (d, J = 8.8 Hz, 1 H) , 7.48-7.41 (m, 3H), 7.32-7.30 (m, 2H), 7.23 (dd, J = 8.8, 2.6 Hz, 1 H), 3.89 (s, 3H), 2.76 (c, J = 7.4 Hz, 2H), 1.07 (t, J = 7.4 Hz, 3H).

EXAMPLE 424 The preparation of 5-ethyl-9-hydroxy-4-phenylamino [3,4-c] carbazole-1.3 (2H.6H) -dione (C: R2 = CH2CH3, R1 = phenyl) (826) The demethylation of (825) prepared as described in Example 423 with BBr3 using the procedure described in Example 80 gave (826) (97%), m.p. 190-96 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.63 (s, 1 H), 10.81 (s, 1 H), 9.21 (s, 1 H), 8.31 (d, J = 2.4 Hz, 1 H), 7.48-7.40 (m, 4H), 7.31-7.29 (m, 2H), 7.06 (dd, J = 8.7, 2.4 Hz, 1 H), 2.74 (c, J = 7.4 Hz, 2H), 1.06 (t, J = 7.4 Hz , 3H). Found: C, 72.43; . H, 4:54; N, 7.54. C22H 6N2O3. 1/2 H20 -requires: C, 72.32; ~ H, 4.69; N, 7.67.

SCHEME 18 Procedures for scheme 18 EXAMPLE 425 - The preparation of 5- (benzyloxy) -2 - [(E.Z) -2- (2-methoxyphenyl) ethenyl] -1H-indole (Cl: Ar = 2-methoxyphenyl) (847) Reaction of 5- (benzyloxy) -1H-indole-2-carbaldehyde (846) with 2-methoxybenzyltriphenylphosphonium bromide using the procedure described in Example 37 gave (847) as a cream colored solid ( E / Z isomer mixture) (89%) which was used without further purification.

HRN d [(CD3) 2SO] (major isomer) 1 1.26 (s, 1 H), 7.62 (d, J = 6.8 Hz, 1 H), 7.48 (m), 7.41-7.15 (m), 7.08-7.02 ( m). 6.97 (m, 1 H), 6.81 (dd, J = 8.7, 2.4 Hz, H), 6.45 (s, 1H), 5.08 (s, 2H), 3.87 (s, 3H).

EXAMPLE 426 The preparation of 5- (benzyloxy) -2 - [(EZ) -2- (2-methoxyphenyl) ethenyl] -1- [2- (4-morpholinyl) etin-1 H-indole (Cll: Ar = 2 -methoxyphenyl, R10 = ?? 2 ?? 2? (?? 2) 2?) (848) Alkylation of (847) prepared as described in Example 425 with 4- (2-chloroethyl) morpholine using the procedure described in method 3 gave (848) (87%) as a pale yellow solid, which was used without further purification.

"'". - ~ EXAMPLE 427 The preparation of 9- (benzyloxy (-4- (2-methoxyphenyl) -6- [2- (4-morpholinyl) ethyl] pyrrolor3.4-cTcarbazol-1.3 (2H.6H ^ -dione (CIV: Ar = 2-methoxyphenyl, R10 = CH? CH, N (CH2) 2Q) (850) The reaction of (848) prepared as described in example 426 with maleimide using the procedure described in method 4a gave the adduct (Clll; Ar = 2-methoxyphenyl, R10 = CH2CH2N (CH2) 20) (849), which it was used without further purification. Aromatization of (849) with Mn02 using the procedure described in Example 79 gave (850) (36%) as a yellow solid, m.p. 170-172 ° C.

EXAMPLE 428 The preparation of 9-hydroxy-4- (2-methoxyphenyl) -6- [2- (4-morphol-8-nyl) etn-pyrrolo [3,4-c] carbazoM.3 (2H.6H) -dione ( VI: Ar = 2-methoxyphenyl, R10 = CH CHZN (CH2) 20) (851) Removal of the benzyl ether group from (850) prepared as described in Example 427 by hydrogenolysis using the procedure described in Example 254 gave (851) (66%) as a yellow powder, m.p. 262-264 ° C. 1 H NMR d [(CD3) 2S01 10.92 (br s, 1H), 9.31 (br, 1H), 8.37 (d, J = 2.5 Hz, 1 H), 7.69 (s, 1 H), 7.54 (d, J = 8.8 Hz, 1H), 7.42 (m.'lH), 7.33 (dd, J = 7.4, 1.7 Hz, 1H), 7.12-7.08 (m, 2H), 7.05 (m, 1 H), 4.54 (t, J = 6.3 Hz, 2H), 3.68 (s, 3H), 3.45 (t, J = 4.4 Hz, 4H), 2.65 (t, J = 6.3 Hz, 2H), 2.41 (ta, 4H). Found EIMS M +: 471.1789. C27H25N3O5 requires 471.1794.

EXAMPLE 429 The preparation of 5- (benzyloxy) -2-. { (E) -2- [2- (2-methoxyetho-xpfenilletenyl] -1 H- indole (Cl: Ar ± 2- (2-methoxyethoxy) phenyl) (852) Reaction of 5- (benzyloxy) -1H-indole-2-carbaldehyde (846) with 2- (2-methoxyethoxy) benzyltriphenylphosphonium bromide using the procedure described in Example 37 gave (847) as a solid colored cream (mixture of E / Z isomers) (86%), which was used without further purification.

EXAMPLE 430 The preparation of 9- (benzyloxy) -4- [2- (2-methoxyethoxy) phenyl] pyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (CIV: Ar = 2- (2-methoxyethoxy )phenyl. "'described in method 4a gave the adduct (Clll; Ar = 2- (2-methoxyethoxy) phenol, Rio = H) (853), which was used without further purification. Aromatization of (853) with nÜ2 using the procedure described in Example 79 gave (854) (46%) as an orange solid, mp 157-159 ° C, which was used without further purification.

EXAMPLE 431 The preparation of 9-hydroxy-4- [2- (2-methoxyethoxy) phenyl] pyrrolo [3,4-c1carbazole-1.3 (2H.6H) -dione (VI: Ar = 2- (2-methoxyethoxy) phenyl) R10 = H) (855) Removal of the benzylic ether group from (854) prepared as described in Example 430 by hydrogenolysis using the procedure described in Example 254 gave (855) (53%) as a yellow powder, m.p. 275-279 ° C. 1 H NMR d [(CD3) 2 SO] 1 .71 (br s, 1 H), 10.89 (br s, 1 H), 9.22 (br s, 1 H), 8.31 (d, J 2.2 Hz, 1 H), 7.51 (s) , 1 H), 7.43 (d, J 8.5 Hz, 1 H), 7.39 (m, 1 H), 7.34 (dd, J 7.5 Hz, 1 H), 1.7 Hz, 1 H), 7.10 (d, J 7.7 Hz, 1 H), 7.05 (m, 2H), 4.04 (m, 2H), 3.45 (t, J = 4.7 Hz, 2H), 3.10 (s, 3H). EIMS found Mt: 402.1213. C ^ HVeNzOs requires 402.1215: EXAMPLE 432 Preparation of 2-methoxy-4-nitrobenzyl) (tri-phenyl) phosphonium bromide (582) Bromination of (2-methoxy-4-nitrophenyl) methanol with 30% HBr in acetic acid, followed by the reaction of the crude bromide with triphenylphosphine, using the procedure described in Example 12, with the exception that the conditions for displacement were 3 days at 20 ° C followed by 1 day at 55 ° C, gave the phosphonium salt (582) (84%) as a yellow solid, mp (CH2Cl2 / benzene) 194-196 ° C. 1 H NMR (CDCl 3) d 7.83-7.63 (m, 17H), 7.45 (s a, 1 H), 5.52 (d, J = 15.0 Hz, 2H). Found: C, 61.10; H, 4.73; N, 3.05. C26H23Br 03P requires C, 61 .43; H, 4.56; N, 2.76.

EXAMPLE 433 The preparation of 5- (benzyloxy) -2 - [(E) -2- (2-methoxy-4-nitrophenyl) ethenyl] -1H-indole (583) (Cl: Ar = 2-methoxy-4-nitrophenyl) ) The aldehyde (846) was reacted with (2-methoxy-4-nitrobenzyl) (triphenyl) phosphono (582) bromide prepared as described in example 432 using the procedure. described in method 2, with the exception that the LDA and the aldehyde were added (sequentially) at 0 ° C, the ratio of LDA: aldehyde was 1.5: 1 and the reaction time was 5 h, to give (after the crystallization in CH2Cl2 / pentane) the diene (583) in the form of an orange solid (the pure E-isomer) (63%), mp 156-159 ° C. 1 H NMR (CDCl 3) d 8.23 (sa, 1 H), 7.87 (dd, J = 8.5, 2.1 Hz, 1 H), 7.76 (d, J = 2.2 Hz, 1 H), 7.68 (d, J = 8.6 Hz , 1 H), 7.48 (d, J = 7.3 Hz, 2H), 7.39 (t, J 7.3 Hz, 2H), 7.32 (t, J 7.2 Hz, 1 H), 7.28 (d, J = 17.1 Hz, 1 H), 7.26 (d, J 8.7 Hz, 1 H), 7.20 (d, J 16.7 Hz, 1 H), 7.12 (d, J = 2.4 Hz, H), 6.97 (dd, J 8.7, 2.5 Hz, 1 H), 6.63 (sa, 1 H), 5.11 (s, 2H), 4.01 (s, 3H).

Found: C, 71.69; H, 4.94; N, 7.11. C 24 H 20 N 2 O 4 requires C, 71.99; H, 5.03; N, 7.00.

EXAMPLE 434 The preparation of 9- (benzyloxy) -4- (2-methoxy-4-nitrophenyl) -4.5.6.10-tetrahydropyrrole3.4-c1carbazole-1.3 (2H.6H) -dione (584) (CIH. RQ = H. Ar = 2-methoxy-4-nitrophenyl) and 9-benzyloxy-4- (2-methoxy-4-nitrophenyl) pyrrolo [3,4- c1carbazole-1.3 (2H.6H) -dione (585) (CIV R10 = H. Ar = 2-methoxy-4-nitrophenyl) A foil-coated mixture of pure Diene E (583) (185 mg, 0.463 mmol prepared as described in Example 433 and maleimide (260 mg, 2.68 mmol) in dry toluene (3 mL) was stirred in a vial. Hermetically sealed at reflux temperature for 22 h (Method-4a)! The resulting dense suspension was transferred to a flask using dioxane (7 mL) and then treated with manganese dioxide (900 mg, 10.4 mmol), stirring at room temperature. reflux temperature for 24 h (according to the procedure described in example 79), to give (after the treatment) a mixture which was adsorbed on silica gel and chromatographed Elution with 0-0.25% MeOH / CH2Cl2 gave precursors and then elution with 0.25-33% MeOH / CH 2 Cl 2 gave (after crystallization in THF / CH 2 Cl 2 / pentane) the crude product (585) (64 mg) .The latter was further purified by chromatography on silica gel (eluting with 20% EtOAc / petroleum ether) to give (after crystallization from THF / CH2Cl2 / pentane) the pure material (585) (58 mg, 25%) as a yellow solid, m.p. 301-303 ° C. 1 H NMR d [(CD 3) 2 SO] 11.97 (br s, 1 H), 11.08 (br s, 1 H), 8.54 (d, J = 2.5 Hz, 1 H), 7.94 (dd, J = 8.3, 2.2 Hz, 1 H ), 7.88 (d, J = 2.2 Hz, 1 H), 7.64 (d, J = 8.2 Hz, 1 H), 7.63 (s, 1 H), 7.58 (d, J = 8.8 Hz, 1 H), 7.56 (da, J = 7.1 Hz, 2H), 7.42 (t, J = 7 4 Hz, 2H), 7.35 (t, J = 7.4 Hz, 1 H), 7.32 (dd, J = 8.9, 2.7 Hz, 1 H ), 5.23 (s, 2H), 3.83 (s, 3H). Found: C, 68.14; H, 3.89; N, 8.41. C28Hi9N306 requires C, 68.15; H, 3.88; N, 8.52. Additional elution with 1% MeOH / CH 2 Cl 2 gave (after crystallization in eOH / CH 2 Cl 2 / petroleum ether) the recovered adduct (584) (72 mg, 31%) as a pale yellow solid (which was directly aromatized with 5 equiv of DDQ using the procedure described in example 70 to give more product with a yield of 79%).; "~" 71H NMR 5 [(CD3) 2SO] 10.96 (sa, 1 H), 10.86 (sa, 1 H), 7.90 (d, J 8.5, 2.3 Hz, 1 H), 7.78 (d, J = 2.2 Hz , 1 H), 7.72 (d, J = 8.6 Hz, 1 H), 7.50 (d, J 7.1 Hz, 2H), 7.40 (t, J = 7.3 Hz, 2H), 7.34 (d, J = 2.4 Hz, 1 H), 7.33 (t, J = 7.4 Hz, 1 H), 7.21 (d, J = 8.7 Hz, 1 H), 6.80 (dd, J = 8.7, 2.5 Hz, 1 H), 5.09 (s, 2H) ), 4.27 (d, J = 7.6 Hz, 1 H), 3.98 (dd, J = 7.6, 3.6 Hz, 1 H), 3.97 (s, 3H), 3.54 (dt, J = 12.9, 3.8 Hz, 1 H ), 3.24 (dd a, J = 15.7, 13.5 Hz, 1 H), 2.89 (dd, J = 15.4, 3.6 Hz, 1 H). FABMS found: M + = 497.1601. C28H23N3O6 requires 497. 1587 EXAMPLE 435 The preparation of 9-hydroxy-4- (2-methoxy-4-nitrophenyl) pyrrolof3.4-c1carbazole-1.3 (2H.6H) -dione (VI.R1Q = H. Ar = 2-methoxy-4-nitrophenyl) ) A suspension of the benzyl ether (585) (55 mg, 0.112 mmol) prepared as described in example 434 in glacial AcOH (1.2 m) was treated with concentrated HCl (6.7 ml of 36%), stirring at 100 ° C. for 50 min (using the procedure described in Example 260 of Scheme 18). The cooled solution was slowly added to ice / NaHCC > Water (150 ml) was added and then extracted with EtOAc (5 x 100 ml). The extracts were washed with water, then adsorbed on silica gel and chromatographed. Elution with 0-1% MeOH / CH 2 Cl 2 gave precursors and then elution with 1.5% MeOH / 2 2 dio 2 gave (after crystallization in THF / CH 2 Cl 2 / pentane) phenyl (586) (86% ) -in: orange solid-form, pf-242-244 ° C: '' "1H NMR d [(CD3) 2SO] 11.84 (br, 1 H), 11.02 (br, 1 H), 9.28 ( sa, 1 H), 8.31 (d, J = 2.4 Hz, 1 H), 7.93 (dd, J = 8.2, 2.1 Hz, 1 H), 7.87 (d, J = 2.1 Hz, 1 H), 7.63 (d , J = 8.2 Hz, 1 H), 7.58 (s, 1 H), 7.45 (d, J = 8.7 Hz, 1 H), 7.08 (dd, J = 8.7, 2.4 Hz, 1 H), 3.83 (s, 3H) Found: C, 62.55; H, 3.22; N, 10.13, C21H13N306 requires C, 62. 53; H, 3.25; N, 10.42.

EXAMPLE 436 The preparation of 4- (4-amino-2-methoxyphenyl) -9-hydroxypyrrolo [3,4- cJcarbazol-1.3 (2H.6H) -dione (587) (VI: R10 = H. Ar = 4-amino -2- methoxyphenyl) A mixture of the nitro derivative (586) (31 mg, 0.0769 mmol) prepared as described in example 435 and freshly prepared (wet) nickel boride (242 mg) in eOH (2.4 ml) and 1 M HCl (0.6 ml) ) was stirred at reflux temperature for 1 h. Six drops of HCl conc. and then the mixture was stirred at reflux temperature for a further 1 h. Concentrated aqueous ammonia and aqueous NaHCO3 (100 mL) were added and the mixture was extracted with EtOAc (8 x 100 mL). The extracts were concentrated, adsorbed on silica gel and chromatographed. Elution with 0-2% MeOH / CH2Cl2 gave precursors after elution with MeOH ~ 2-3% / CH2Cl2- dio (after crystallization in MeOH / THF / CH2Cl2 / pentane) the amine (587) (77% ) in the form of a yellow-orange solid, mp 308-316 ° C. 1 H NMR d [(CD3) 2 SO] 11.57 (br s, 1 H), 10.79 (br s, 1 H), 9.17 (br s, 1 H), 8.29 (d, J = 2.4 Hz, 1 H), 7.43 (s, 1 H), 7.39 (d, J = 8.7 Hz, 1 H), 7.02 (dd, J = 8.7, 2.5 Hz, 1 H), 6.95 (d, J = 7.9 Hz, 1 H), 6.30 (d, J) = 2.0 Hz, 1 H), 6.22 (dd, J = 8.0, 1.9 Hz, 1 H), 5.26 (sa, 2H), 3.59 (s, 3H). Found: C, 67.65; H, 4.06; N, 11.01. C2iH15N304 requires C, 67.56; H. 4.05; N, 11 .25.

SCHEME 19 Scheme procedures 19 EXAMPLE 437 The preparation of methyl 7-bromo-5-methoxy-1-benzofuran-2-carboxylate (856) To a solution containing 3-bromo-2-hydroxy-5-methoxy-benzaldehyde (94.7 g, 0.410 mol) and dimethyl bromomalonate (103 g, 0.492 mol) in toluene (1.2 g) was added potassium carbonate in the mixture. freshly prepared powder (85 g, 0.615 mol) and tetra-n-butylammonium bromide (13.2 g, 0.041 mol). The reaction was heated to reflux in a Dean-Stark trap for 48 h. The reaction was concentrated and the residue was dissolved with dichloromethane (-0.5 I) and filtered through Celite, washing with dichloromethane (-0.5 I). The filtrate was washed with ~ 1 L of 1 M sodium hydroxide and water (2 x 1 L), then the organic phase was passed through a 400 g layer of silica gel washing with dichloromethane (-1 L). ) and the filtrate was concentrated to give the desired benzofuran (64 g, 56%) as an orange solid, mp 107-1 1 ° C. 1 H NMR d (CDCl 3) 7.50 (s, 1 H), 7.23 (d , 1H), 7.03 (d, 1 H), 3.98 (s, 3H), 3.82 (s, 3H).

EXAMPLE 438 The preparation of 7-bromo-2-hydroxymethyl-5-methoxybenzofuran and 7-bromo-5-methoxybenzofuran-2-carbaldehyde (858) A solution containing the aster (857) (69 g, 242 mmol) prepared as described in Example 856 in anhydrous tetrahydrofuran (2.5 I) was cooled to -78 ° C. A 1 M solution of lithium aluminum hydride in tetrahydrofuran (242 mL, 242 mmol) was added over a period of 30 min. The reaction was stirred at -78 ° C for 1.25 h and carefully quenched with 50 ml of water. The mixture was poured into 1 L of a 1 M solution cooled with ice of hydrochloric acid and extracted with ethyl acetate (4 x 500 mL). The combined organic phases were dried (Na2SO4) and concentrated in vacuo to give 67 g of an orange solid. This residue was adsorbed on 20 g of silica gel and added to a column of silica gel (1 '~ kg, ~ 70-230 mesh) and eluted with 1: 9, 1: 4 and 1: 3. of ethyl acetate-heptanes.

This gave first 25 g (41%) of the final aldehyde (858) as a pale yellow solid, m.p. 119-121 ° C. H R N 6 (CDCl 3) 9.90 (s, 1 H), 7.55 (s, 1 H), 7.38 (d, 1 H), 7.10 (s, 1 H), 3.85 (s, 3 H). Found: C, 47.06; H, 2.66; Br, 31.41. Ci0H7BrO3 requires C, 47.09; H, 2.77; N, 31.33; followed by 20 g (33%) of the expected alcohol, H NMR d (CDCl 3) 7.08 (m, 1 H), 6.9 (m, 1 H), 6.68 (s, 1 H), 4.78 (s, 2 H), 3.85 (s, 3H).

EXAMPLE 439 The preparation of 7-bromo-5-methoxybenzofuran-2-carbaldehyde (858) To a solution of the above isolated alcohol (560 mg, 2.18 mmol) prepared as described in Example 858, tetrahydrofuran (20 mL) and ether (60 mL) was added manganese dioxide (1.9 g, 21.8 mmol). The reaction was stirred for 2 days and filtered through Celite. The filtrate was concentrated in vacuo and chromatographed on silica to give 200 mg (-50%) of the desired aldehyde (858) (spectrum as shown above).

Representative procedure for method 34 of scheme 19 EXAMPLE 440 ~ "" "The preparation of 7-bromo-2-f (E) -2- (2-chlorophenyl) ethenyl] -5-methoxy-1-benzofuran (CV: Ar = 2-chlorophenyl) (859) To a solution of diethyl 2-chlorobenzylphosphonate (4.91 g, 0.018 mol) and 7-bromo-5-methoxybenzofuran-2-carbaldehyde (1.27 g, 0.016 mol) in tetrahydrofuran (80 ml) was added sodium hydride (sodium dispersion). 60% in mineral oil, 0.74 g, 0.0185 moles). After 5 min, the reaction mixture was heated at 60 ° C for 1 h. The reaction mixture was cooled to room temperature, water (10 ml) was carefully added and the tetrahydrofuran was removed. Water (50 ml) was added and the mixture was extracted with ethyl acetate (3 x 100 ml). The combined ethyl acetate extracts were washed with brine (50 ml), dried over magnesium sulfate, filtered and concentrated to dryness. Trituration with diethyl ether (20 mL) gave the solid material which was then washed with diethyl ether (20 mL). The mother liquors were concentrated and triturated with diethyl ether (10 ml), collecting the solid. The combined solids gave (859) (4.89 g, 84%). 1 H NMR d (CDC½) 7.70 (d, J = 16 Hz, 1 H), 7.65 (dd, J = 7.7, 1.5 Hz, 1 H), 7.4 (dd, J = 6.0, 1 Hz, 1 H), 7.23 (m, 2H), 7.05 (d, J = 2.3 Hz, 1 H), 6.94 (d, J = 16 Hz, 1 H), 6.92 (d, J = 2.3 Hz, 1 H), 6.72 (s, 1 H), 3.82 (s, 3H); MH +: 364.9, 362.9 MH ": 362.9, 360.9.

EXAMPLE 441 The preparation of 7-bromo-4- (2-chlorophenyl) -9-methoxy-3a.4.5.10-tetranidro-1 Hf11benzofuror3.2-e1soindol-1.3 (2H) -dione (CVI: Ar = 2 - chlorophenyl) (860) A solution of 859 (4.89 g, 0.0185 mol) prepared as described in example 441, maleimide (1.44 g, 0.02 mol) and tin chloride (11) (2.8 g, 0.02 mol) in xylenes (40 ml) was heated at 150 ° C overnight. After the addition of more maleimide (1.44 g, 0.02 mol) and tin chloride (11) (1.44 g, 0.01 mol), the reaction was heated again at 150 ° C overnight. The solid that formed was collected and washed with xylenes (20 ml) before being dissolved in ethyl acetate (200 ml). Water (50 ml) was added and the mixture was filtered through a pad of celite. The resulting layers were separated, the organic phase was washed with brine (50 ml), dried over magnesium sulfate, filtered and concentrated to dryness. The product (860) (6.1 g, 71%) was used without further purification. 1 H NMR d (CDCl 3) 7.60 (d, J = 6.5 Hz, 1 H), 7.40 (m, 2 H), 7.25 (m, 1 H), 7.1 (m, 2 H), 4.36 (dd, J = 7.3, 1 Hz, 1 H), 4.0 (m, 1 H), 3.86 (s, 3 H), 3.81 (m, 1 H), 3.45 (m, 1 H), 3.10 (dd, J = 4.7, 17 Hz, 1 H ); H + = 462,460.

EXAMPLE 442 The preparation of 7-bromo-4- (2-chlorophenyl) -9-methoxy-1H- [1] benzofuro [3-2- e] isoindol-1.3 (2H) -dione (CVII: Ar = 2-chlorofertil ) (861) Argonatorization of (860) = prepared "as described in Example 442 with n02 using the procedure described in Example 79 gave dibenzofuran (861) as a yellow solid (67%). 1H NMR d [(CD3 ) 2SO] 8.22 (d, J = 2.6 Hz, 1 H), 8.14 (s, 1 H), 7.62 (m, 2H), 7.48 (m, 3H), 3.98 (s, 3H). ?? ': 458.457 , 456,454.

EXAMPLE 443 The preparation of 7-bromo-4- (2-chlorophenyl) -9-hydroxy-1 H- [1] benzofuro [3.2-elisoindole-1.3 (2m-dione fCVIII: Ar = 2-chlorophenylol (8621 The demethylation of (861) prepared as in Example 442 with BBr3 using the procedure described in Example 80 gave (862) (98%) that was used without further purification. 1 H NMR d [(CD3) 2 SO] 8.04 (d, J = 2.3 Hz, 1 H), 7.91 (s, 1 H), 7.56 (d, J = 8 Hz, 1 H), 7.45 (m, 3H), 7.2 (d, J = 2.5 Hz, 1H). H ": 443.9, 441.9, 439.9.

EXAMPLE 444 The preparation of 4- (2-chlorophenyl) -9-hydroxy-7-vinyl-1 H- [1] benzofuro [3.2- e] isoindol-1.3 (2H) -dione (CIX: Ar = 2-chlorophenyl) Z = H) (863) The reaction of (862) prepared as described in Example 443 with tributylvinyltin using the procedure described in Example 309 gave (863) (79%). 1 H NMR d [(CD3) 2SO] 9.80 (s, 1H), 8.04 (d, J = 2.7 Hz, 1 H), 7.91 (s, 1 H), 7.56 (d, J = 8 Hz, 1H), 7.45 (m, 3H), 7.2 (d, J 2.5 Hz, 1 H), 6.96 (dd, 20 J = 18.11 Hz, 1 H), 6.2 5 (d, J = 18 Hz, 1 H), 5.52 (d, J 1 1 Hz, 1 H). = 390,388.

EXAMPLE 445 The preparation of 4- (2-chlorophenyl) -7-ethyl-9-hydroxy-1 H- [1] benzo-furo [3.2-elisoindole-1.3 (2H) -dione (CX: Ar = 2-chlorophenyl. Z = H) (864) A solution of (863) (0.054 g, 0.167 mmol) prepared as described in example 444 in a mixture of methanol: tetrahydrofuran (1: 1, 4 ml) was hydrogenated over Raney nickel (100 mg) and hydrogen The product was purified by column chromatography using a gradient of 0-100% ethyl acetate in dichloromethane to give (864) (0.032 g, 59%). 1 H NMR d [(CD3) 2 SO] 9.65 (S, 1 H), 7 92 (m, 1 H), 7.56 (d, J = 3.0 Hz, 1 H), 7.43 (m, 3H), 6.96 (d, J = 2.5 Hz, 1 H), 2.90 (c, 2H), 1.5 (t, 3H). MH ": 392,390.

EXAMPLE 446 'The preparation of 4- (2-chlorophenyl) -7- (1,2-dihydroxyethyl) -9-hydroxy-1 H- [1] benzofuro [3.2-e] isoindol-1.3 (2H) -dione (CXI: Ar = 2-chlorophenyl, Z = H) (865) The reaction of (863) prepared as described in Example 444 with Os04 using the procedure described in Example 300 gave (865) (35%). 1 H NMR d [(CD 3) 2 SO] 9.68 (s, 1 H), 7 96 (d, J = 2.5 Hz, 1 H), 7.9 (s, 1 H), 7.55 (d, J = 7.8 Hz, 1 H ), 7.45 (m, 3H), 7.17 (d, J = 2.5 Hz, 1 H), 5.55 (d, J = 4.6 Hz, 1 H), 5.06 (m, 1 H), 4.87 (t, J = 5.7) Hz, 1 H), 3.65 (m, 1 H), 3.55 (m, 1 H). MH ": 424,422.

SCHEME 20 EXAMPLE 447 The preparation of 1,3-dioxo-4-phenyl-1,2,3,6-tetrahydropyrrolo [3,4- c] carbazol-9-yl-dibenzyl phosphate (CXII: Ar = phenyl) (336) To a solution of 9-hydroxy-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (I; Ar = phenyl) (0.50 g, 1.52 mmole) in pyridine ( 30 ml) in a nitrogen atmosphere was added dropwise phosphorus oxychloride (140 μ ?, 1.52 mmoles). After 40 minutes of stirring at room temperature, an additional portion of phosphorus oxychloride (40 μ?) Was added and after another 20 minutes, benzyl alcohol (0.66 ml, 6.38 mmol) was added. After 3 hours, the reaction mixture was diluted with 1N hydrochloric acid and extracted with ethyl acetate, the organic phase was dried, the drying agent was removed and the solution was concentrated to dryness, before chromatography on silica eluting with methanol / dichloromethane (3:97) to give dibenzyl phosphate (336) (284 mg, 32%) as a yellow powder, mp 193-194 ° C. H NMR d [(CD3) 2 SO] 12.12 (br s, 1 H), 11. 15 (br s, 1 H), 8.81 (br, 1 H), 7.69 (s, 1 H), 7.63 (m, 3H), 7.48-7.34 (m, 14H), 5.22 (d, JH-F = 8.3 HZ, 4H).

Found: C, 69.65; H, 4.37; N, 4.88; P, 5.26. C34H25N2O6P requires: C, 69.38; H, 4.28; N, 4.76; P, 5.26.

EXAMPLE 448: - · The preparation of 1,3-dioxo-4-phenyl-1,2,3,6-tetrahydropyrrolo [3,4-clcarbazol-9-yl] dihydrogenphosphate (CXIII: Ar = phenyl) (337) A solution of dibenzyl phosphate (336) (100 mg, 0.17 mmol) prepared as described in Example 447 in methanol / tetrahydrofuran (3: 1, 70 ml) was hydrogenated at 60 psi (413,685 kPa) on Pd-C (5%, catalytic) with stirring for 3 hours. Then, the reaction mixture was filtered through celite and concentrated in vacuo. Trituration in ethyl acetate / hexane gave the phosphate (337) (49 mg, 71%) as a yellow solid, m.p. 285-299 ° C. H NMR d [(CD3) 2 SO] 12.01 (sa, 1 H), 1.09 (sa, 1 H), 8.66 (sa, 1 H), 7.63 (m, 3H), 7.57 (da, J = 8.6 Hz, 1 H), 7.50-7.44 (m, 4H). Found: C, 55.19; H, 3.29; N, 6.34; P, 6.84. C20H13N2O6P. 1 ½ H20 requires: C, 55.18; H, 3.71; N, 6.43; P, 7.12.

EXAMPLE 449 The preparation of 6-acetyl-4- (2-chlorophenyl) -9-methoxypyrrolo [3,4-c] carbazole 1.3 (2H.6H) -dione (CXIV: Ar = 2-chlorophenyl) (338) To a solution of the carbazole (33) (45 mg, 0.12 mmol) prepared as described in Example 79 in acetic anhydride (4.0 ml) was added 35% perchloric acid - (2 drops); The resulting solution was stirred at room temperature for 30 minutes before being poured into ice water, basified by the addition of solid potassium bicarbonate and extracted with ethyl acetate.The organic phase was dried, the drying agent was removed and The solution was concentrated to dryness, chromatography on silica eluting with ethyl acetate / hexane (2: 3), followed by trituration in ethyl acetate gave acetamide (338) (40 mg, 80%) as a solid. pale yellow, mp 277-280 ° C.

H NMR d [(CD3) 2 SO] 11.46 (br s, 1 H), 8.74 (d, J = 2.8 Hz, 1 H), 8.53 (s, 1 H), 8.17 (d, J = 9.2 Hz, 1 H) , 7.60 (m, 1 H), 7.54-7.47 (m, 3H), 7.32 (dd, J = 9.2, 2.8 Hz, 1 H), 3.93 (s, 3H), 2.91 (s, 3H). Found: C, 65.50; H, 3.49; N, 6.61. C ^ H ^ CINaC ^. 1 / 4H20 requires: C, 65.26; H, 3.69; N, 6.62.

EXAMPLE 450 The preparation of 6-acetyl-4- (2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione tCXV: Ar = 2-chlorophenyl) (339) The demethylation of acetamide (338) (/ 35 mg, 0.08 mmol) prepared as described in Example 449 according to the procedure described in Example 80, with the exception that the reaction time was 24 hours and -chromatography "was carried out eluting with ethyl acetate / hexane (from 1: 2 to ~ 2: 1), gave the phenol (339) (22 mg, 65%) as a pale yellow powder, mp 258-261 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.41 (br s, 1 H), 9.80 (br s, 1 H), 8.59 (d, J = 2.6 Hz, 1 H), 8.53 (s, 1 H), 8.07 (d, J = 9.1 Hz, 1 H), 7.59 (m, 1 H), 7.53-7.46 (m, 3H), 7.15 (dd, J = 9.1, 2.6 Hz, 1 H), 2.89 (s, 3H) Found: C, 65.03; H, 3.14; N, 6.68, C22H13CIN2O4 requires: C, 65.28; H, 3.24; N, 6.92.

SCHEME 21 Procedures for scheme 21 EXAMPLE 451 The preparation of ethyl (2E) -2 - [(4-nitrophenyl) hydrazone] propanoate (901) A mixture of para-nitroaniline (900) (10.0 g, 72.0 mmol), ice (72 g) and 15% hydrochloric acid (72 ml) was treated with a solution of sodium nitrite (5.4 g, 78.0 mmol) in water ( 5 mi) at a speed such that the temperature does not exceed 7 ° C. The reaction mixture was stirred for a further 5 min and then filtered through Celite to give a pale yellow / brown solution which was added rapidly to a suspension of ethyl acetate (59.0 g, 0.72 mol), ethanol (72 ml). Ethyl 2-methylacetoacetate (11.4 ml, 80.0 mmol) and ice (72 g). The resulting red mixture was stirred for 2.5 h then extracted with dichloromethane (3 x 100 mL). The combined extracts were dried and concentrated to give a red oil (18 g). The red oil was dissolved in ethanol (40 ml), concentrated hydrochloric acid (15 ml) was added and an orange / yellow fine precipitate formed instantaneously. The reaction mixture was refluxed for 15 min and then poured into ice. The orange / yellow precipitate was collected by filtration and dried to give ethyl (2E) -2 - [(4-nitrophenyl) hydrazono] propanoate (901) (15.2 g, 84%). 1 H NMR d [(CD 3) 2 SO] 10.50 (s, 1 H), 8.20 (m, 2 H), 7.40 (m, 2 H), 4.23 (c, J = 7.2 Hz, 2 H), 2.13 (s, 3 H), 1.29 (t, J = 7 Hz, 3H).

EXAMPLE 452 Ethyl 5-Nitro-1H-indolo-2-carboxylate (902) (2E) -2 - [(4-nitrophenol) ethyl] propanoate (901) (10.6 g, 42 mmol) prepared as described in Example 451 in polyphosphoric acid (70 g) was heated to 1 10 ° C until no starting material remained as indicated by tic analysis (40 min). Ice (500 g) was added with vigorous stirring and a dense brown precipitate formed which was filtered off and dried to give ethyl 5-nitro-1 H-indole-2-carboxylate (902) (6.04 g, 61% ). This material was used in the next step without purification. _. - 1 H NMR d [(CD3) 2 SO] 12.59 (aJ H), 8.73 (d, J = 2.4 Hz, 1 H), 8.13 (dd, J = 9.2, 2.4 Hz, 1 H), 7.61 (d, J = 9.12 Hz, 1 H), 7.44 (s, 1 H), 4.38 (c, J = 7.0 Hz, 2H), 1.36 (t, J = 7.0 Hz, 3H).

EXAMPLE 453 The preparation of (5-nitro-1 H-indol-2-yl) methanol (903) To a solution of ethyl 5-nitro-1 H-indole-2-carboxylate (9.8 g, 42.0 mmol) in methanol (300 mL) was added a 2 M potassium hydroxide solution (31 mL, 63.0 mmol). The reaction mixture was refluxed for 2 h and then the hot solution was filtered, poured on ice and acidified. The resulting fine pale brown precipitate was collected by filtration and dried. The crude acid was dissolved in tetrahydrofuran (250 ml) and stirred with 1, 1'-carbonyl diimidazole (10.2 g, 63.0 mmol) with gentle heating for 2 h. Water was added and then solid sodium borohydride (7.9 g, 0.21 mol) was added portionwise over 30 min, the reaction mixture was stirred for a further 40 min and then quenched with 1 M hydrochloric acid. The tetrahydrofuran was removed under reduced pressure. and the residue was dissolved in ethyl acetate, washed, dried and concentrated to give (5-nitro-1 H-indol-2-yl) methanol (903). This material was used in the next step without purification.

EXAMPLE 454 The preparation of 5-nitro-1H-indoi-2-carbaldehyde (904) - - A solution of crude (5-nitro-1 H-indol-2-yl) methanol (3.60 g, 18.7 mmol) in chloroform (200 mL) was heated at 50 ° C with manganese dioxide (20 g, 0.23 mol) during 3 h. Then, the reaction mixture was filtered through Celite and concentrated to give 5-nitro-1 H-indole-2-carbaldehyde (904) (2.04 g, 57% in two steps). 1 H NMR d [(CD3) 2 SO] 12.64 (a, 1 H), 9.96 (s, 1 H), 8.83 (d, J = 2.3 Hz, 1 H), 8.18 (dd, J = 9.0 Hz, 2.3 Hz, 1H), 7.69 (d, J = 0.7 Hz, H), 7.62 (d, J = 9 Hz, 1 H).

EXAMPLE 455 The preparation of 2- [2- (2-chlorophenyl) ethenyl] -5-nitro-1 H-indole (CXVI: Ar = 2-chlorophenyl) (905) The reaction of the aldehyde (904) prepared as described in Example 454 with 2-chlorobenzyltriphenylphosphonium chloride using the procedure described in Example 37 (at room temperature) gave the diene (905) as a mixture of E / isomers Z in the form of a yellow solid (95%). Crystallization from aqueous methanol produced the pure E-isomer in the form of yellow needles (80%), m.p. 230-232 ° C. 1 H NMR d [(CD3) 2 SO] 12.28 (br s, 1 H), 8.55 (d, J = 2.3 Hz, 1?), 8.03 (dd, J = 9.1, 2.3 Hz, 1 H), 7.91 (dd, J = 7.8, 1.5 Hz, 1 H), 7.32-7.61 (m, 6H), 6.92 (s, 1 H). _. . · - - - _ Ex contract: -C, 64.59; H, 5.68; N, 9.49. C éHi CIN202 requires C, 64.33; H, 5.68; N, 9.49.

EXAMPLE 456 The preparation of methyl 2- [2- (5-nitro-1 H -indol-2-yl) ethenyl] phenyl ether (CXVI: Ar = 2-methoxyphenyl) (906) The reaction of the aldehyde (904) prepared as described in Example 454 with 2-methoxybenzyltriphenylphosphonium bromide using the procedure described in Example 37 gave the diene (905) as a mixture of E / Z isomers in the form of a yellow solid (95%) that was used without further purification.

EXAMPLE 457 The preparation of methyl 2- [2- (1-methyl-5-nitro-1 H -indol-2-yl) ethenyl] phenyl ether (CXII, Ar = 2-methoxyphenyl, R10 = Me) (907) Alkylation of the diene (906) prepared as described in Example 456 with methyl iodide using the procedure described in method 3 gave the corresponding diene (908) (94%) as a yellow solid (a mixture of isomers E / Z), which was used without further purification.

EXAMPLE 458 The preparation of 2- [2- (2-chlorophenyl) ethenyl] -1-methyl-5-nitro-1H-indole (CXVII: ... Ar = 2-chlorophenyl, R10 = Me) (908) Alkylation of the diene (905) prepared as described in Example 455 with methyl iodide using the procedure described in Example 38 gave the corresponding diene (908) (99%) as a yellow solid. A sample was crystallized from methanol in the form of orange needles, m.p. 161-163 ° C. 1 H NMR d [(CD3) 2 SO] 8.53 (d, J = 2.3 Hz, 1 H), 8.05 (dd, J = 7.7, 1.6 Hz, 1 H), 8.02 (dd, J = 9.1, 2.3 Hz, 1 H ), 7.67 (d, J = 9.1 Hz, 1 H), 7.46-7.64 (m, 3H), 7.43 (dt, J = 7.7, 1.6 Hz, 1 H), 7.36 (dt, J = 7.7, 1.6 Hz, 1 H), 7.22 (s, 1 H), 3.95 (s, 3H). Found: C, 65.55; H, 4.19; N, 8.90. Ci7H13CIN202 requires C, 65.28; H, 4.19; N, 8.96.

EXAMPLE 459 The preparation of 4- (2-methoxyphenyl) -6-methyl-9-nitro-4,5,6.10-tetrahydropyrrolo [3,4-c] carbazole-1.3 (2H.3aH) -dione (CXVIII: Ar = 2 - methoxyphenyl, R1Q = Me) (909) Reaction of the diene (907) prepared as described in Example 457 with maleimide using the procedure described in Example 68 gave the adduct (909) (84%) as a glassy solid which was flavored immediately "~~ "" "~ -.

EXAMPLE 460 The preparation of 4- (2-chlorophenyl) -6-methyl-9-nitro-4.5.6.10-tetrahydropyrrolo [3,4-c] carbazole-1.3 (2H.3aH) -dione (CXVIII: Ar = 2-chlorophenyl) R10 = Me) (910) Reaction of the diene (908) prepared as described in Example 458 with maleimide using the procedure described in Example 68 gave the adduct (910) (88%) as a dark vitreous solid which flavored immediately.

EXAMPLE 461 The preparation of 4- (2-chlorophenyl) -9-nitro-4.5.6.10c-tetrahydropyrrolo [3,4-c1carbazole-1.3 (2H.3aH) -dione (CXVIII: Ar = 2-chlorophenyl R10 = H) Reaction of the diene (905) prepared as described in Example 455 with maleimide using the procedure described in Example 68 gave the adduct (917) (74%) as a dark solid which was immediately flavored.

EXAMPLE 462 The preparation of 4- (2-methoxyphenyl) -6-m-ethoxy-1-carbazole-1.3f2H.6m-dione (CXIX: Ar = 2-methoxyphenite, R 0 = Me) f911l The aromatization of the adduct (909) prepared as described in Example 459 with manganese dioxide using the procedure described in Example 79 with the exception that the reaction time was 4 h gave the nitrocarbazole (911) (50%) ) in the form of a brown solid, mp 320-330X (desc). 1 H NMR d [(CD3) 2 SO] 1 1.24 (s, 1 H), 9.76 (d, J = 2 Hz, 1 H), 8.50 (dd, J = 9.1 1, 2.2 Hz, 1 H), 7.93 (s) , 1 H), 7.91 (d, J = 9.1 Hz, 1 H), 7.46 (t, J = 7.3 Hz, 1 H), 7.38 (d, J = 7.3 Hz, 1 H), 7.13 (d, J = 7.3 Hz, 1 H), 7.08 (t, J = 7.3 Hz, 1 H), 4.05 (s, 3H), 3.70 (s, 3H). Found: C, 65.76; H, 3.83; N, 9.30. C22H15N3O5 requires: C, 65.83; H, 3.77; N, 10.47.

EXAMPLE 463 The preparation of 4- (2-chlorophenol) -6-methyl-9-nitropyrrolor3,4-c1carbazole-1.3 (2H.6Hi-dione IXIX: Ar = 2-chlorophenyl, R10 = Me (912) The aromatization of the adduct (910) prepared as described in Example 460 with manganese dioxide using the procedure described in Example 79 with the exception that the reaction time was 4 h gave nitrocarbazole (912) (78%) ) in the form of an orange solid, p! f. > 320 ° C. "- - * - -" "" - = - - - 1 H NMR d [(CD3) 2 SO] 11.35 (s, 1 H), 9.68 (d, J = 2.3 Hz, 1 H), 8.46 (dd, J = 9.1, 2.3 Hz, 1 H), 8.0 (s, 1 H), 7.88 (d, J = 9.1 Hz, 1 H, 7.47-7.62 (m, 4H), 4.04 (s, 3H). Found: C, 58.90, H, 3.28, N, 10.30, C2iH12CIN304, H20 requires: C, 59.57, H, 3.30, N, 9.93.

EXAMPLE 464 The preparation of 4-f2-chlorophenol) -9-n -tropyrrolof3.4-c1carbazole-1.3 (2H.6H) -dione IXIX: Ar = 2-chlorophenyl, R10 = H) (918) The aromatization of the adduct (917) prepared as described in Example 463 with manganese dioxide using the procedure described in Example 79 with the exception that the reaction time was 4 h gave nitrocarbazole (918) (84%) as a yellow solid, m.p. 253-258 ° C. 1H RN d [(CD3) 2SO] 12.78 (s, 1 H), 11.33 (s, 1 H), 9.74 (d, J = 2.5 Hz, 1 H), 8.45 (dd, J = 9.1, 2.5 Hz, 1 H), 7.80 (d, J = 9.1, 1 H), 7.77 (s, 1 H), 7.60 (dd, J = 7.2, 1.5 Hz, 1 H), 7.45-7.54 (m, 3H). Found: C, 62.39; H, 3.03; N, 10.10. C20H10CIN3O4. 1/6 hexane requires: C, 62.22; H, 3.04; N, 10.37.

Representative procedure for method 34 of scheme 21 EXAMPLE 465 The preparation of 9-amino-4-f-2-chlorophenyl) -6-methylpyrrolor-3,4-c1carbazole-1.3 (2H.6H) -dione (CXX: Ar = 2-chlorophenyl, R10 = Me) (914) The nitrocarbazole (912) (0.055 g, 0.14 mmol) prepared as described in Example 463 was suspended in a mixture of ethanokawa (4: 1, 20 ml) and heated to reflux temperature. After 15 min, iron powder (0.076 g, 1.4 mmol) was added, followed by acetic acid (0.041 g, 0.70 mmol). The red solution was refluxed for 1 hour, turning dark. The cooled solution was filtered through Celite, washing with ethyl acetate (2 x 100 mL). The solvent was evaporated under reduced pressure, leaving a brown residue, which was dissolved in ethyl acetate (200 ml). The solution was washed with saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride and then dried and treated to give the amine (914) as a red solid, m.p. 208-216 ° C. 1 H NMR d [(CD3) 2 SO] 11.00 (s, H), 8.15 (d, J = 2.2 Hz, 1 H), 7.68 (s, 1 H), 7.56 (dd, J = 7.0, 1.9 Hz, 1 H ), 7.43-7.49 (m, 4H), 7.02 (dd, J = 8.7, 2.2 Hz, 1 H), 5.03 (s, 2H, is exchanged with D20), 3.88 (s, 3H). Found: C, 64.48; H, 3.82; N, 10.32. C21 H14CIN3O2. H20 requires: C, 64.12; H, 4.07; N, 10.68.

EXAMPLE 466 The preparation of 9-amino-4- (2-methoxyphenyl) -6-methylpyrrolor3,4-c1carbazole-1.3 (2H-6Hl-dione (CXX: Ar = 2-methoxyphenyl, R1Q = Me) (913) The nitrocarbazole (911) prepared as described in Example 462 was reduced with iron powder using the procedure described in Example 34, to give the amine (913) as a brown solid (74%), m.p. 188-192 ° C. 1 H NMR d [(CD3) 2 SO] 10.87 (s, 1 H), 8.14 (d, J = 1.7 Hz, 1 H), 7.61 (s, 1 H), 7.40-7.42 (m, 2H), 7.33 (dd) , J = 7.3, 1.6 Hz, 1 H), 6.98-7.10 (m, 3H), 5.00 (s broad, 2H, interchanged with D20), 3.86 (s, 3H), 3.68 (s, 3H). Found: C, 69.61; H, 4.66; N, 9.32. C22H17N3O3. 1 / 2C4H80 requires: C, 69.40; H, 506; N, 10.12.

EXAMPLE 467 The preparation of 9-amino-4- (2-chlorophenyl) pyrrolof3.4-c1carbazole-1.3 (2H.6H -dione (CXX, Ar = 2-chlorophenyl, R10 = H) (919) The nitrocarbazole (918) prepared as described in Example 464 was reduced with iron powder using the procedure described in Example 465 with a reaction time of 45 min and the product was precipitated in THFférér: petroleum to give the amine "(919) in the form" of a brown solid (91%), mp 216-222X. 1 H NMR d [(CD3) 2 SO] 1 1.66 (s, 1 H), 10.96 (s, 1 H), 8.09 (d, J = 2.3 Hz, 1 H), 7.57 (dd, J = 8.1, 1.8 Hz, H), 7.40-7.50 (m, 4H), 7.35 (d, J = 8.6 Hz, 1 H), 6.95 (dd, J = 8.6, 2.3 Hz, 1 H), 4.95 (sa, 2H). EIMS found: M + = 361.0611, 363.0587. C20H12CIN3O2 requires 361 .0818, 363.0589.

Representative procedure for method 35 of scheme 21 EXAMPLE 468 The preparation of N- [4- (2-methoxyphenyl) -6-methyl-1,3-dioxo-1.2.3.6-tetrahydropyrrolo [3,4-c] carbazol-9-yl] acetamide (CXXI: Ar = 2-methoxyphenyl, R10 ¾ Me, R4, "Me") (916) Acetic acid (1 mL) and acetic anhydride (1 mL) were mixed under a nitrogen atmosphere at 0 ° C and the solution was stirred at 0 ° C for 1 hour. A solution of the amine (913) (0.06 g, 0.16 mmol) prepared as described in Example 466 in dry dichloromethane was added and the mixture was allowed to warm to room temperature for 2 h and then the solvent was evaporated under reduced pressure. The resulting yellow solid was purified by chromatography on silica gel eluting with petroleum ether: ethyl acetate (100: 0 to 0: 100). Then, the product (916) was precipitated from tetrahydrofuran with petroleum ether in the form of a yellow powder (0.044 g, -67%), m.p. 300-304 ° C. 1 H NMR d [(CD3) 2 SO] 10.98 (s, 1 H), 10.12 (s, 1 H), 8.99 (d, J = 2.0 Hz, 1 H), 7.97 (dd, J = 8.8, 2.0 Hz, 1 H), 7.74 (s, 1 H), 7.66 (d, J = 8.8 Hz, 1 H), 7.43 (dt, J = 7.4, 1.7 Hz, 1 H), 7.34 (dd, J = 7.4, 1 .7 Hz, 1 H), 7.12 (d, J = 8.1 Hz, 1 H), 7.05 (t, J = 8.1 Hz, 1 H), 3.95 (s, 3H), 3.68 (s, 3H), 2.10 (s, 3H). Found: C, 66.10; H, 4.60; N, 9.44. C24H 9N304. H20 requires: C, 66.82; H, 4.41; N, 9.74.

EXAMPLE 469 The preparation of 4- (2-chlorophenyl) -6-methyl-1,3-dioxo-1.2.3.6-tetrahydropyrrolo [3,4-c] carbazol-9-ylformamide (CXXI: Ar = 2-chlorophenyl) R10 = Me R4 = H) (920) The amine (914) prepared as described in Example 465 and formic acid were reacted using the procedure described in method 35 with a reaction time of 16 h to give formamide (920) (92%) in the form of a yellow powder, mp 345-348 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.16 (s, 0.5H), 1 1.12 (s, 1 H), 10.36 (m, 1.5H), 9.08 (d, J = 2.0 Hz, 1 H), 8.72 ( m, 0.5H), 8.32 (d, J = 1.8 Hz, 1 H), 7.99 (dd, J = 8.8, 2.0 Hz, 1 H), 7.85 (s, 0.5H), 7.83 (s, 1 H ), 7.70-7.73 (m, 1.5H), 7.46-7.60 (m, 7H), 3.98 (s, 1.5H), 3.98 (s, 3H). FABMS found: [M + H] + = 404.0790, 406.0779. C22H15CIN303 requires 404.0802, 4060.0772.

EXAMPLE 470 The preparation of 4- (2-chlorophenyl) -1,3-dioxo-1,2,3,6-tetrahydropyrrolo [3,4- c] carbazol-9-lformamide (CXXI: Ar = 2-chlorophenyl) R 0 = H. R 4 = H ) (921) The amine (919) prepared as described in Example 467 and formic acid was reacted using the procedure described in Example 468 with a reaction time of 4 h to give formamide (921) (54%) as a a yellow powder, mp 293-297 ° C. 1 H R N d [(CD3) 2 SO] 12.11 (s, 0.5H); 12.08 (s, 1 H), 1 1.12 (s, 0.5H), 1 1.08 (s, 1 H), 10.34 (s, 1 H), 10.30 (s, 0.5H), 9.03 (d, J = 1. 9 Hz, 1 H), 8.69 (m, 0.5 H), 8.31 (d, = 1 .8 Hz, 1 .5 H), 7.92 (dd, J = 8.8, 1 .9 Hz, 1 H), 7.42-7.65 (m, 9.5H). Found: C, 64.78; H, 3.53; N, 9.96. C2iH12CIN303. ¾THF requires: C, 64.86; H (3.44; N, 10.32.

EXAMPLE 471 The preparation of N- [4- (2-chlorophenyl) -6-methyl-1,3-dioxo-1 -2.3.6- tetrahydropyrrolo [3,4-c] carbazol-9-yl] acetamide (CXXI: Ar = 2- Chlorophenyl, R10 = Me, R4 = Me) (923) The amine (914) prepared as described in the example 465 and acetic acid were reacted using the procedure described in Example 468 with a reaction time of 14 h to give acetamide (923) (85%) as a yellow powder, m.p. 338-340 ° C. 1 H NMR d [(CD3) 2 SO] 1 1 .10 (sa, exchange with D20, 1 H), 10.14 (s, exchange with D20, 1 H), 9.01 (d, J = 2.0 Hz, 1 H) , 7.99 (dd, J = 8.9, 2.0 Hz, H), 7.82 (s, 1 H), 7.68 (d, J = 8.9 Hz, 1 H), 7.57 (dd, J = 7.2, 1 .9 Hz, 1 H), 7.44-7.53 (m, 3H), 3.93 (s, 3H), 2. 0 (s, 3H).

Found: C, 64.44; H, 4.08; N, 8.98. C23H16CIN3O3. I / 2CH 3 COOH requires C, 64.43; H, 4.03, N, 9.39.

EXAMPLE 472 The preparation of N- [4- (2-chlorophenyl) -1.3-dioxo-1.2.3.6-tetrahydropyrrolo [3,4-c] carbazol-9-yl] acetamide (CXXI: Ar = 2-chlorophenyl) R10 = H. R4 = Me) (926) The amine (919) prepared as described in Example 467 and acetic acid were reacted using the procedure described in Example 468 with a reaction time of 4 h to give acetamide (926) (43%) as a a yellow powder, mp 240-245 ° C. 1 H NMR d [(CD 3) 2 SO] 12.04 (br s, 1 H), 11.07 (br s, 1 H), 10.10 (s, 1 H), 8.95 ~ (d, J = 2.1 HzJ.H), 7.90 (dd, J = 8.8, .2.1 Hz, 1H), 7.58 (m, 2H), 7.42-7.51 (m, 4H), 2.10 (s, 3H). FABMS found: [M + H] + = 404.0787, 406.0776. C22H15CLN3O3 requires 404.0802, 406.0772.

Representative procedure for method 36 of scheme 21 EXAMPLE 473 The preparation of N- [4- (2-chlorophenyl) -6-methyl-1,3-dioxo-1.2.3.6-tetrahydropyrrolo [3,4-c] carbazol-9-yl] -3- (1-piperidinyl) propanamide ( CXXI: Ar = 2-chlorophenyl, R10 = Me, R4 = 3- (1-piperidinyl) propyl) (925) 3-Piperidinylpropanoic acid (0.036 g, 0.23 mmol) and 1 - [3- (dimethylamino) propyl] -3-ethylcarbodiimide hydrochloride (0.044 g, 0.23 mmol) in dry dimethylformamide (2 mL) at 0 ° C were combined in a nitrogen atmosphere and left stirring for 1 h. A solution of the amine (914) (0.085 g, 0.23 mmol) in dry dimethylformamide (3 mL) was added to the reaction mixture. The solution was allowed to warm to room temperature for 16 h. The solvent was removed under reduced pressure and the residue was adsorbed on silica. Purification by column chromatography with luyendb with ethyl acetate: methanol: triphenylphosphine (from 100: 0: 0 to 75: 24: 1) yielded (925) as a yellow solid (0.036 g, 30%), m.p. 241 -246 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.12 (s, 1 H), 10.46 (s, 1 H), 9.92 (broad s, 1 H), 9.09 (d, J = 2.0 Hz, 1 H), 7.98 ( dd, J = 8.9, 2.0 Hz, 1 H), 7.83 (s, 1 H), 7.71 (d, J = 8.9 Hz, 1 H), 7.45-7.60 (m, 4H), 3.98 (s, 3H), 3.38 (m, 2H), 3.10 (m, 2H), 2.95 (m, 2H), 1.80 (m, 4H), 1.42 (m, 2H). FABMS found: [M + H] +: 515.1842, 517.1833. C29H28CIN403 requires 515.1850, 517.1820.

EXAMPLE 474 The preparation of N- [4- (2-chlorophenyl) -6-methyl-1,3-dioxo- 1.2.3.e-tetrahydro-tetrahydro [3,4-c] carbazole-9-yl] -4 hydrochloride - (dimethylamino) butanarnide (CXXI: Ar = 2-chlorophenyl, R 0 = Me, R 4 = 4-dimethylaminobutyl) (928) The amine (914) prepared as described in Example 465 was reacted with EDCI and 4-dimethylaminobutyric acid hydrochloride using the procedure described in Example 473 to give the amide (928) (44%) as a powder orange, pf 3311-333 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.11 (s, 1 H), 10.25 (s, 1 H), 9.82 (s a, 1 H), 9.07 (d, J = 2.0 Hz, 1 H), 7.98 (dd, J = 9.0, 2.0 Hz, 1 H), 7.83 (s, 1 H), 7.70 (d, J = 9.0 Hz, 1 H), 7.58 (d. m, 1 H), 7.44-7.52 (m, 3H), 3.97 (s, 3H), 2.99-3.1 1 (m, 4H), 2.77 (s, 6H), 2.00 (m, 2H). "FABMS found: [M + H] +: 489.1689, 491.1681, C27H26CIN4O3 -requires 489.1693, 491.1664.

Representative procedure for method 37 of scheme 21 EXAMPLE 475 The preparation of 4- (2-chlorophenyl) -6-methyl-9- (methylamino) pyrrolo [3,4- c carbazole-1.3 (2H.6H) -dione (CXXII: Ar = chlorophenyl) R10 = Me. R4 = H) (922) Borane-Methyl sulfide complex (0.074 mL, 0.78 mmol) and trimethyl borate (0.089 mL, 0.78 mmol) were added at 0 ° C under a nitrogen atmosphere to a solution of the amine (920) (0.105 g, 0.26). mmoles) prepared as described in Example 469 in dry tetrahydrofuran (10 mL). After stirring at 0 ° C for 30 min, the solution was allowed to warm to room temperature for 16 h. Methanol (200 ml) was added and the reaction mixture was stirred for 12 h. The solvent was removed under reduced pressure and the yellow residue was purified by column chromatography on silica, eluted with petroleum ether: ethyl acetate (from 100: 0 to 0: 100) to give (922) as a solid red (0.053 g, 45%), mp 293-296 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.01 (br s, 1 H), 8.10 (d, J = 2.3 Hz, 1 H), 7.69 (s, 1 H), 7.57 (dd, J = 7.11, 2.0 Hz, 1 H, 7.42-7.52 (m, 4H), 7.02 (dd, J = 8.8, 2.3 Hz, 1 H), 5.61 (c, J = 5.2 Hz, 1 H), 3.90 (s, 3H), 2.81 (d , J = 5.2 Hz, 3H) EIMS found: M + = 389.0929, 391.0905. C22H16CIN302 requires 389.0931, 391.0902.

EXAMPLE 476 The preparation of 4- (2-chlorophenyl) -9- (ethylamino) -6-methylpyrrolo [3,4- c] carbazole-1.3 (2H-6H) -dione (CXXll: Ar = chlorophenyl) R10 = Me. R4 = Me) (924) The amide (923) prepared as described in Example 471 was reduced with borane-methyl sulfide complex using the procedure described in method 37 to give the amine (924) as a red powder, m.p. 232-236 ° C. 1 H NMR d [(CD3) 2 SO] 11.00 (s, exchanged with D20, 1 H), 8. 13 (d, J = 2.2 Hz, 1 H), 7.69 (s, 1 H), 7.57 (dd, J = 7.0, 2.0 Hz, 1 H), 7.42-7.51 (m, 4H), 7.05 (dd, J = 8.8, 2.2 Hz, 1 H), 5.51 (t, J = 5.4 Hz, interchanged with D20, 1 H), 3.15 (m, 2H), 1.27 (t, J = 7.1 Hz, 3H). 'EÍMS "found V M + = 403,1080, .405.1061 C23H18CI 3O2 requires 403.1087, 405.1058.

EXAMPLE 477 The preparation of 4- (2-chlorophenyl) -9- (methylamino) pyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (CXXll: Ar = chlorophenyl, R10 = H. R4 = H) ( 9271 The amide (921) (0.051 g, 0.13 mmol) prepared as described in Example 470 was reacted with borane-methyl sulfide complex using the procedure described in method 37 to give the amine (927) (0.021 g) , 43%) in the form of an orange powder; p.f. 182-84 ° C. 1 H NMR d [(CD3) 2 SO] 1 1.69 (broad s, 1 H), 10.97 (broad s, 1 H), 8.05 (d, J = 2.1 Hz, 1 H), 7.40-7.57 (m, 5H), 6.97 (dd, J = 8.7, 2.4 Hz, 1 H), 5.55 (c, J = 4.9 Hz, 1 H), 2.80 (d, J = 5.2 Hz, 3H). EIMS found: M + = 375.0768, 377.0749. C2iH14CIN302 requires 375.0774, 377.0745.

Representative procedure for method 38 of scheme 21 EXAMPLE 478 The preparation of 9- (dimethylamino) -4- (2-methoxyphenyl) -6-methylpyrrolo [3,4- c] carba2ol-1.3 (2H.6H) -dione (CXXIII: Ar = methoxyphenyl) R10 = Me. R3 = H) (915) _ .. .... - The amine (913) (0.049 g, 0.13 mmol) prepared as described in Example 466 was suspended in methanol (15 mL) and stirred at 0 ° C. Formaldehyde (0.01 ml, 37% aqueous solution, 0.13 mmol) was added portionwise followed immediately by sodium cyanoborohydride (0.022 g, 3.5 mmol) and the mixture was stirred at room temperature for 14 h. The solvent was removed under reduced pressure and the residue was dissolved in ethyl acetate (100 ml). The solution was washed with water (2 x 100 mL) and saturated aqueous sodium chloride (2 x 100 mL), then dried over anhydrous sodium sulfate and the solvent was evaporated. The residue was chromatographed on silica, eluting with petroleum ether: diethyl ether (from 100: 0 to 0: 100) to give (915) as a red solid (0.017 g, 33%), m.p. 246-251 ° C. H NMR d [(CD3) 2 SO] 10.92 (s, 1 H), 8.39 (d, J = 2.5 Hz, 1 H), 7.67 (s, 1 H), 7.58 (d, J = 9.0 Hz, 1 H) , 7.41 (dt, J = 7.4, 1.7 Hz, 1 H), 7.37 (dd, J = 7.4, 1.7 Hz, 1 H), 7.25 (dd, J = 9.0, 2.5 Hz, 1H), 7.10 (d, J = 7.4 Hz, 1 H), 7.04 (t, J = 7.4 Hz, 1 H), 3.91 (s, 3H), 3.68 (s, 3H), 2.99 (s, 6H). EIMS found M +: 399.1580. C24H2iN303 requires 399.1583.

Scheme procedures 22 EXAMPLE 479 The preparation of 4- (2-chlorophenyl) -1,3-dioxo-1,2,3,6-tetrahydropyrrolo [3,4-c] carbazol-9-yl trifluoromethanesulfonate (CXXIV: Ar-2-chlorophenyl) (615) Compound (615) was prepared from (9) (I; (Ar = 2-chlorophenyl) prepared as described in Example 8 using the procedure described in Example 307 to give a yellow oil. [(CD3) 2SO] 11 .83 (s, 1 H), 1.03 (s, 1 H), 8.28 (s, 1 H), 8.32 (s, H), 7.6-7.4 (m, 5H), 7.07 (s, H), EIMS found: M + = 493.9946, C2iH10CIF3N2SO5 required 493. 9951 '' "" _ ~ EXAMPLE 480 5 The preparation of 4- (2-chlorophenyl) -9-vinylpyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (CXXV: Ar = 2-chlorophenyl) (616) Compound (616) was prepared from (615) prepared as described in Example 479 (using the procedure described in Example 309, with tetraethyltin like stannane to give a yellow oil. 1 H NMR d [(CD3) 2 SO] 11.71 (s, 1 H), 11.48 (a, 1 H), 8.23 (s, 1 H), 8.78 (s, 1 H), 7.99 (s, 1 H), 7.62 -7.43 (m, 5H), 7.2-7.1 (m, 1 H), 6.10 (d, J = 17.6 Hz, 1 H), 5.46 (d, J = 1 1.3 Hz, 1 H). EIMS found: M + = 372.0661. C22H13CI 2O2 requires 372.0666.

EXAMPLE 481 The preparation of 4- (2-chlorophenyl) -9- (1,2-dihydroxyethyl) pyrrolo [3,4-c] carbazole-1.3 (2H.6H) -dione (CXXVI: Ar = 2-chlorophenyl) (617) The diol (617) was prepared from (616) prepared as described in Example 480 using the procedure described in Example 300 to give a yellow solid, m.p. 265-268 ° C. 1 H NMR d [(CD3) 2 SO] 12.06 (a, 1 H), 11.08 (a, 1 H), 8.87 (s, 1 H), 7.60-7.40 (m, 7H), 5.32 (d, J = 3.8 Hz , 1 H), 4.74 (m, 2H), 3.55 (m, 2H). EIMS found: M + = 406.0718. C22H15CIN2O4 requires 406. 0720 EXAMPLE 482 The preparation of 4- (2-chlorophenyl) -9- (2-hydroxyethyl) pyrrolo [3,4-clcarbazole-1.3 (2H.6H) -dione CXXVM: Ar = 2-chlorophenyl) (618) Compound (618) was prepared from (616) prepared as described in Example 480 using the procedure described in Example 344 to give a yellow solid, m.p. 253-257 ° C. 1H RN d [(CD3) 2SO] 12.03 (a, 1 H), 1.08 (a, 1 H), 8.73 (s, 1 H), 7.60-7.40 (m, 6H), 4.69 (t, J = 5.2 Hz, 1 H), 3.71 (m, 2H), 2.93 (t, J = 7.2 Hz, 2H). EIMS found: M +: 390.0769. C25Hi5CIN203 requires 390.0771.

EXAMPLE 483 Other new control point inhibitors Next, other control point inhibitors of the present invention are presented which can be prepared by processes known in the art, processes described hereinabove, or a combination of said processes. A person skilled in the art will understand how each compound is prepared by reference to the description of this document.

COMPOSITE NAME p.f. (Grades C) APCI (pos) Mass Found 4- (4-Amino-2-methoxy-phenyl) -9- 308-316 hydroxy-6H-pyrrolo [3,4-c] carbazole-1,3-dione N- [4- (2-Chloro-phenyl) ) -1, 3-dioxo-240-245 1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazol-9-N] -acetamide N- [4- (2-Chloro-phenyl ) -6-methyl-1, 3-488/450 dioxo-1, 2,3,6-tetrahydro-pyrrol [3,4-c] carbazol-9-yl] -4-dimethylamino-butyramide 4- (2-Chloro-phenyl) -9-methylamino-6H-182-184 pyrrolo [3,4-c] carbazole-1,3-dione 9-Hydroxy-4- (2-methoxy-4-nitro-phenyl) ) - 242-244 6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -9-hydroxy-8- (4-191-193 morpholin-4-) il-butyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; hydrochloride salt 4- (2-Chloro-phenyl) -8- [3- (3,5-dimethyl-252-254 pperazin-1-yl) -propoxy] -9-hydroxy-6-methyl-6H -pyrrolo [3,4-c [carbazole-1,3-dione 4- (2-chloro-phenyl) -9-hydroxy-8- (3- 285-288 hydroxhpropoxy) -6-methyl-6H- - ~ - "; pyrrolo [3,4-c] carbazolr1, 3-dione 4- (2-chloro-phenyl) -8- (4-hydroxy-221-223-butoxy) -6-methyl-6H-pyrrolo [3,4- c] carbazole-1,3-dione 4- (2-chloro-phenyl) -8- (3,4-dihydroxy-240-234-butoxy) -6-methyl-6H-pyrrolo [3,4-c] carbazole- 1,3-dione 4- (2-Chloro-phenyl) -6-methyl-8- (4- 204-208 methylamino-butoxy) -6 H -pyrrolo [3,4-c] carbazole-1,3-dione 4 - (2-Chloro-phenyl) -1,3-dioxo-1, 2,3,6- 293-296 tetrahydro-pyrrolo [3,4-c] carbazole-9-yl-ester of acetic acid 4- (2 -Chloro-phenyl) -9-hydroxy-8- (4- 212-214 methylamino-butyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione 2- (9-Hydroxy) 1,3-d-oxo-1, 2,3,6- 330-334 tetrahydro-pyrrolo [3,4-c] carbazol-4- l) -benzamide 4- (2-chloro-phenyl) -6- methyl-8-piperidin- 444.1 / 446.1 3-α-6H-pyrrolo [3,4-c] carbazole-1,3-dione 8- (3-Amino-pyrrolidine-1-carbonyl) - 473/475 4- (2-chloro-phenyl) l) -6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; salt hydrochloride 4- (2-Chloro-phenyl) -9-pyridin-2-yl-6H-295-297 pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-Chloro-phe L) -9-pyridn-4-u-6H-266-296 pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -8- (3-dimethylamino-243-245 propoxy) -9-hydroxy-6- (2-h idroxy-ethyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2- Chloro-phenyl) -6-methyl-9-pyridin-2-257-259-yl-6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -9-hydroxy -6- (2- 244-247 hydroxy-ethyl) -8- (3-pyrrolidin-1-yl-propoxy) -6H-pyrrolo [3,4-c] carbazole-1,3-dione N- [4- (2-Chloro-phenyl) -1,3-dioxo-300-310 1, 2,3,6-tetrahydro-pyrrolo [3,4- ^ - c] carbazol: 9-yl] -3-piperidin- 1-yl-propionamide 4- (2-Chloro-phenyl) -9-hydroxy-6-methyl-255-258 8- (3-methylamino-propoxy) -6H- (dec.) Pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -8- (4-hydroxy-but-1-280-283 enyl) -6-methyl-6H-pyrrolo [3, 4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -8- (4-hydroxy-butyl) -269-272 6-methyl-6H-pyrrolo [3,4-c] carbazole -1, 3-dione 4- (2-Chloro-phenyl) -8- (3-dimethylamino-180-183-propoxy) -9-hydroxy-6- (3-hydroxy-propyl) -6H-pyrrolo [3,4 -c] carbazole-1,3-dione 6- (3-Bromo-propyl) -4- (2-chloro-phenyl) -296-300 8- (3-dimethylamino-propoxy) -9- (dec. ) hydroxy-6-Hyrrolo [3,4-c] carbazole-, 3-dione-4- (2-chloro-phenyl) -8- (4-dimethyl-3-28-233-hydroxy-butoxy) - 6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; hydrochloride salt 4- (2-Chloro-phenyl) -8-hydroxy-6- (3- 283-288 hydroxy-propyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2 -Chloro-phenyl) -8- (4-dimethylamino-258-262 butyl) -6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) - 6-methyl-8- (4- 231-234 pyrrolidin-1-yl-butyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -6- methyl-8- (4- 232-236 methylamino-butyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -9-hydroxy-6- (3 - 252-254 hydroxy-propyl) -8- (3-pyrrolidin-1-yl-propoxy) -6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-Cioro-phenyl) ) -8 - [# - (3,5-dimethyl-210-215 piperazin-1-yl) -prppox] -9-hydroxy-6- (dec.) - - - '(3: hydroxypropyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -9-hydroxy-8- (4- 287-289 hydroxy-butyl) -6-methyl- 6H-pyrrolo [3,4-c] carbazole-1,3-dione 8-. { 3- [Bis- (2-hydroxy-ethyl) -amino] -129-132-propoxy} -4- (2-chloro-phenyl) -9-hydroxy-6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -9-hydroxy- 6- (3- 186-191 hydroxy-propyl) -8- [3- (4-methyl- (dec.) Piperazin-1-yl) -propoxy] -6H-pyrrolo [3,4-c] carbazole-1 , 3-dione 4- (2-Chloro-phenyl) -6- (3-hydroxy-268-272 propyl) -9-nitro-6H-pyrrolo] 3,4-c] carbazole-1,3-dione 9- Amino-4- (2-chloro-phenyl) -6- (3- 230 (dec.) H -droxy-propyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione Acid 3- [ 4- (2-Chloro-phenyl) -9-nitro-256-258 1, 3-dioxo-2,3-dihydro-1 H-pyrrolo [3,4-c] carbazol-6-yl] -propionic 4 - (2-Chloro-phenyl) -9-hydroxy-8- (4- 225-227-hydroxy-butoxy) -6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione - (2-Chloro-phenyl) -6- (3-hydroxy-255-257-propyl) -8-methoxy-6H-pyrrolo [3,4-c] carbazole-1,3-dione-4- ( 2-Clo ro-phen I) -9-fl uoro-8-methoxy-347-351 6-methy1-6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2- Chloro-phenyl) -9-fluoro-8-hydroxy-305-310 6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -8- ( 3-dimethylamino-208-211 propoxy) -6- (3-hydroxy-propyl) -6H-pir rolo [3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -6- (3-hydroxy-208-210-propyl) -8- (3-pyrrolidin-1-yl-propoxy) ) -6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-Gloro-pheny!) -9-fluoro-8- (3- ~ 31-31 hydroxy-propoxy) -6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -9-fluoro-6-methyl-8- 317-321 (3-methylamino-propoxy) -6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -9-hydroxy-6-methyl-257-260 8- (4 -morpholin-4-yl-butyl) -6H-pyrrolo [3,4-c] carbazole-, 3-dione 4- (2-chloro-phenyl) -9-fluoro-6-methyl-8-270- 273 (3-pyrrolidin-1-yl-propoxy) -6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -9-hydroxy-6- (2- 177-183 hydroxyethyl) -8- [3- (4-methyl-piperazin- (dec.) 1 -yl) -propoxy] -6H-pyrrolo [3,4-c] carbazole-1,3-dione 4 - (2-Chloro-phenyl) -8- (3-diethyl-165-167-propoxy) -9-hydroxy-6- (2-hydroxy-ethyl) - (dec.) 6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -8- (3-d-methylamino- 272-275 propoxy) -9-fluoro-6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione N- [4- (2-chloro-phenyl) -6- (3-hydroxy-193-196 propyl) -1-methylene-3-oxo-1, 2,3,6-tetrahydro -pyrrolo [3,4-c] carbazol-9-yl] -formamide 4- (2-chloro-phenyl) -6-methyl-8-pyridin-4,438.1-6H-pyrrolo [3,4- c] carbazole-1,3-dione 4- (2-chloro-phenyl) -9-hydroxyl-6- (3- 504/506 hydroxy-propyl) -8-piperidin-4-yl-6H-pyrrolo [3,4-c] carbazole-1,3-dione 8- (3- (R) - Amino-pyrrolidine-1- 473.1 carboniI) -4- (2-chloro-phenyl) -6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; hydrochloride salt 8- (3- (S) -Amino-pyrrolidine-1- 473.1 carbonyl) -4- (2-chloro-phenyl) -6-methyl-6H-pyrrolo [3,4-c] carbazole-1, 3 -diona; hydrochloride salt 4- (2-Chloro-phenyl) -6-methyl-8-piperidin-444.1 4- | i-6H-pyrrolo [3,4-c] carbazole-1, 3-. -dione '4- (2; Chloro-phenyl) -6-methyl-8- 473/475 (piperazine-1 -carbonyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; salt hydrochloride 4- (2-Chloro-phenyl) -8- (4-dimethylamino-246-250-butyl) -9-hydroxy-6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-Chloro-phenyl) -9-hydroxy-6-methyl-250-254 8- (4-pyrrolidin-1-yl-butyl) -6H-pyrrolo [3,4-c] carbazole-1, 3 -dione 4- (2-Chloro-phenyl) -9-hydroxy-6-methyl-254 (dec.) 8- (4-methylamino-butyl) -6H-pyrrolo [3,4-c] carbazole-, 3-dione [4- (2-Chloro-phenyl) -6-methyl-1,3-dioxo-300 (dec.), 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole-9- il] -urea 4- (2-Chloro-phenyl) -9-hydroxy-8- (3- 264-266 hydroxy-2-methyl-propoxy) -6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -8- (4-dimethylamino-224-226-butoxy) -9-hydroxy-6-methyl-6H-pyrrolo [3,4- c] carbazole-1,3-dione 4- (2-chloro-phenyl) -6- (3-methoxy-502.2 propyl) -8-p -peridin-3-yl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; hydrochloride salt 4- (2-Chloro-phenyl) -6- (3-hydroxy-208-214 propyl) -8- (3-methylamino-propoxy) -6H-pyrrolo [3,4-c] carbazole-1 , 3-dione 9-Bromo-4- (2-chloro-phenyl) -6- (3- 190-196 hydroxy-propyl) -8- (3-methylamino-propoxy) -6H-pyrrolo [3,4-c ] carbazole-1, 3-dione 4- [4- (2- (221-224) chloro-phenyl) -6-methyl-1,3-dioxo-1, 2,3,6-tetrahydic acid tert-butyl ester dro-pyrrolo [3,4, -c] carbazol-8-methylmethyl-piperidine-1-carboxylic acid 4- (2-chloro-phenyl) -6-methyl-8-piperidin-265-270 4-ylmethyl -6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -6- (3-methoxy-502.1 iS,,: propyl) -8-piper Din-4-yl-6H - "-" "". · -pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -6- (3-methoxy-488.2-propyl) -8-piperidin-3-yl-6H-pyrrolo [3,4-c] carbazole-1,3-dione hydrochloride salt; hydrochloride salt 4- (2-Chloro-phenyl) -6- (3-hydroxy-488.1 propyl) -8-p-peridin-4-yl-6H-pyrrolo [3,4-c] carbazole-1, 3 -diona; hydrochloride salt 4- (2-Chloro-phenyl) -6-methyl-8-487 / 489 (perhydro-1,4-diazepine-1-carbonyl) -6H-pyrrolo [3,4-c] carbazole-1,3 -diona; salt hydrochloride 4- (2-Chloro-phenyl) -9-hydroxy-6-methyl-247-250 8- [4- (4-methyl-piperazin-1-yl) -butyl] -6H-pyrrolo [3,4 -c] carbazole-1,3-dione 4- (2-chloro-phenyl) -6-methyl-8-pyrrolidin-428/430 3-yl-6H-pyrrolo [3,4-c] carbazole-1, 3-dione; trifluoroacetic acid salt 4- (2-Chloro-phenyl) -6-methyl-1, 3- 403/405 NB acid. dioxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-apcl (neg.) c] carbazole-8-carboxylic acid N-t4- (2-chloro-phenyl) -7-methoxy-6-313- 317 methyl-1,3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazol-9-yl] -formamide 4- (2-chloro-phenyl) -7-hydroxy- 6-methyl- > 300 9-nitro-6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -9-hydroxy-6-methyl-232-235 8- [2- ( 1-methyl-pyrrolidin-2-yl) -ethoxy] -6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -9-hydroxy-6-methyl-210 -212 8- [4- (4-Methyl-piperazin-1-yl) -butoxy] -6H-pyrrolo [3, 4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -9-hydroxy-6-methyl-212 8- (4-morpholin-4-yl-butoxy) -6H-pyrrolo [3 , 4-c] carbazole-1,3-dione N- [4- (2-chloro-phenyl) -6- (2-hydroxy-273-275 eyl) -1, 3-dioxo-1, 2,3, 6-tetrahydro-pyrrolo [3,4-c] carbazol-9-yl] -formamide 4- (2-Fluoro-6-methoxy-phenyl) -9- 377 -hydroxy: 6H-pyrrolo [3,4-c] carbazole - - - | · 1, 3-dione N- [4- (2-Chloro-phenyl) -6- (3-hydroxy-492/494 propyl) -8-methoxy-1,3-dioxo-1, 2, 3,6-tetrahydro-pyrrolo [3,4-c] carbazole-9-ii] -formamide N- [4- (2-chloro-phenyl) -6- (3-hydroxy-478/480 propyl) - 8-methoxy-1,3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazol-9-yl] -formamide N- [4- (2-chloro-phenyl) -8 -hydroxy-6- (3-464/466 hydroxy-propyl) -1, 3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazol-9-yl] -formamide 6-Butyl-6- (2-chloro-phenyl) -9-hydroxy-8-22-225 (3-pyrrolidin-1-yl) -propoxy) -6H-pyrrolo [3,4-c] carbazole- 1,3-dione 8- (3- (S) -Amno-pyrrolidine-1 - 517 carbonyl) -4- (2-chloro-phenyl) -6- (3-hydroxy-propyl) -6H-pyrrolo [ 3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -6- methyl-8-pyrrolidin-430/432 2-yl-6H-pyrrolo [3,4-c] carbazole-1,3-dione 8- (4-Amino-butyl) -4- (2-chloro) -phenyl) - 432/434 6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione [3- [9-Amino-4- (2-chloro-phenyl) -1, 3 > 350 dioxo-2,3-dihydro-1 H -pyrrolo [3,4-c] carbazol-6-yl] -propionyl] -amide of 2-dimethylamino-ethanesulfonic acid. { 3- [4- (2-Chloro-phenyl) -9-formylamino- > 370 1- (2-Chloro-phenyl) 2,3-dioxo-2,3-dihydro-1 H-arnolo [3,4-c] carbazol-6-yl] -propionylj-amide of 2-dimethylamino-ethanesulfonic acid -9-hydroxy-6-methyl-242-244 8- (2-methyl-3-pyrrolidin-1-yl-propoxy) -6H-pyrrolo [3,4-c] carbazole-1,3-dione 4 - (2-Chloro-phenyl) -9-hydroxy-8- (3- 290-293 hydroxy-2,2-dimethyl-propoxy) -6-methyl- .. .. 6H-pyrrolo [3,4 -c] carbazole-1,3-dione _ '' 4- (2-chloro-phenyl) -9-methoxy-6- 435/437-methylene-1,3-dioxo-1, 2,3 acid 6-tetrahydro-pyrrolo [3,4-c] ca rbazol-8-carboxylic acid 4- (2-chloro-phenyl) -9- 434/436-methoxy-6-methyl-1,3-dioxo- acid amide 1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole-8-carboxylic (2-pyrrolidin-1-yl-ethyl) -amide of 531/533 4- (2- chloro-phenyl) -9-methoxy-6-methyl-1,3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole-8-carboxylic acid 4- (2-chloro- phenyl) -9-hydroxy-6- 419/421 methyl-1,3-dioxo-1, 2,3,6-tetrahydro- (APCI neg.) pyrrolo [3,4-c] carbazole-8-carboxylic acid 4- (2-chloro-phenyl) -9- 420/422 hydroxy-6-methyl-1,3-dioxo-1 acid amide, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole-8-carboxylic acid (2-Pyrrolidin-1-ethyl-ethyl) -amide of 517/519 4- (2-chloro- phenyl) -9-hydroxy-6-methyl-1,3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole-8-carboxylic acid N- [4- (2-Chloro- phenyl) -7-hydroxy-6- > 350 Methyl-1, 3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazol-9-yl] -formamide Methyl ester of 4- (2-chloro-449.1 phenyl) - 6- (2-hydroxy-ethyl) -1,3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole-8-carboxylic acid (2-pyrrolidin-1-ethyl-ethyl) -amide 501/503 4- (2-chloro-phenyl) -6-methyl-1,3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole-8 -carboxylic 3- [4- (2-Chloro-phenyl) -8- (3- 235-237 dimethylamino-propoxy) -9-hydroxy- (dec.) 1,3-dioxo-2,3-dihydro-1 H -pyrrolo [3,4-c] carbazol-67-yl] -propionamide 4- (2-Chloro-phenyl) -8- [3- (ethyl-propyl-520/522 amino) -propylsulfanyl] -9-hydroxy- 6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione 9-Hydroxy-6-methyl-4-phenyl-8- (3- 248-250 pyrr-lidin-1-yl-propoxy) -6H- -pyrrolo [3,4-c] carbazole-1,3-dione 9-Amino-4- (2-chloro-phenyl) -6-methyl-7- > 350 vinyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -8- (3-530.2 (R) dimethylamino-pyrrolidine-1-carbonyl) -6- (2-hydroxy-ethyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione N- [4- (2-chloro-phenyl) -6-methyl-1, 3- 248-254 dioxo -7-vinyl-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazol-9-yl] -formamide N- [4- (2-chloro-phenyl) -7- (1, 2 -dihydroxy-> 340 ethyl) -6-methyl-, 3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazol-9-yl] -formamide N- [4- ( 2-Chloro-phenyl] -9-hydroxy-6-310-315 methyl-1,3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole-8-carbonyl ] -methanesulfonamide [4- (2-Chloro-phenyl) -9-hydroxy-6-methyl-285-293, 1,3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole-8-carbonyl] -amido of 2-dimethylamino-ethanesulfonic acid Dimethylamide of 4- (2-chloro-448/450 phenyl) -9-hydroxy-6-methyl-1,3-dioxo-1, 2,3 , 6-tetrahydro-pyrrolo [3,4-c] carbazole-8-carboxylic acid 4- (2-chloro-phenyl) -9-hydroxy-8- (3-178-184 morpholin-4-yl-propoxy) - 6H- Pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -9-hydroxy-6-m ethyl- 242-244 8- (2-pyrrolidin-1-yl-ethoxy) -6H-pyrrolo [3,4-c] carbazole-1,3-dione 8- (3-Amino-propoxy) -4- (2 -chloro- 293-296 phenyl) -9-hydroxy-6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; salt hydrochloride 4- (2-chloro-phenyl) -9-hydroxy-6-methyl-245-248 8- (2-methyl-3-pyrrolidin-1-yl-propoxy) -6H-pyrrolo [3,4-c ] carbazole-1,3-dione (2-diethylamino-ethyl) -amide of the acid 503/505 4- (2-chloro-phenyl) -6-methyl-1,3-dioxo-1, 2,3,6-tetrahydro - [3,4-c] carbazole-8-carboxylic acid [3- (4-Methyl-piperazin-1-yl) -propyl] - 544/546 4- (2-chloro-phenyl) - amide 6-Methyl-1,3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole-8-carboxylic acid (3-diethylamino-2-hydroxy-propyl) - 533 / 535 4- (2-Chloro-phenyl) -6-methyl-1,3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole-8-carboxylic acid amide (3 Pyrrolidin-1-yl-propyl) -amide of 515/517 4- (2-chloro-phenyl) -6-methyl-1,3-d-oxo-1, 2,3,6-tetrahydro-pyrrolo [ 3,4-c] carbazole-8-carboxylic acid 4- (2-chloro-phenyl) -8- (3- (S) -531.2 dimethylamino-pyrrolidine-1-carbonyl) -6- (2-hydroxy-ethyl) ) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; salt of trifluoroacetic acid (2-pyrrolidin-1-yl-ethyl) -amide of 531.3 4- (2-chloro-phenyl) -6- (2-hydroxy-ethyl) -1,3-dioxo-1 acid , 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole-8-carboxylic acid 4- (2-chloro-phenyl) -6- 432.1 (2-hydroxy-ethyl) -1 acid, 3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole-8-carboxylic acid 4- (2-chloro-phenyl) -8- (3-dimethylamino-155-160 propoxy ) -9-hydroxy-6H-pyrrolo [3,4- (dec.) C] carbazole-1,3-dione 4- (2-chloro-phenyl) -9-hydroxy-8- [3- (4- 238) -244 methyl-piperazin-1-yl) -propoxy] -6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -9-hydroxy-8- (3 - 170-175 pyrrolidin-1-yl-propoxy) -6H- (dec.) Pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -9-hydroxy-6- methyl- 292-294 8- (2-morpholin-4-yl-ethoxy) -6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-chlorophenyl) -9-hydroxy -6-rnetil-. 272-274 -8- [2- (4-R-ethyl-piperazin-1-yl) -ethoxy] - - - 6 H - pyrrolo [3,4-c] carbazole-1,3-dione N- [4- (2 Chloro-phenyl) -8-methoxy-6- 338-342 methyl-1,3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazol-9-yl] -formamide 4 - (2-Chloro-phenyl) -9-hydroxy-8- (3- 235-239 hydroxy-propoxy) -6H-pyrrolo [3,4-c] carbazole-1,3-dione (2-Dimethylamino-ethyl) ) -methyl-amide 505/507 of 4- (2-chloro-phenyl) -9-hydroxy-6-methyl-1,3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [3,4] c] carbazole-8-carboxylic acid (1-Ethyl-pyrrolidin-2-ylmethyl) -amide of 531/533 4- (2-chloro-phenyl) -9-hydroxy-6-methyl-1,3-dioxo acid -1,3,3,6-tetrahydro-pyrrolo [3,4-c] carbazole-8-carboxylic acid (3-diethylamino-propyl) -amide of 533/535 4- (2-chloro-phenyl) - 9-hydroxy-6-methyl-1,3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole-8-carboxylic acid 4- (2-chloro-phenyl) - 9-hydroxy-6-methyl-445/445 8- (1 H-tetrazol-5-yl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione [2- (1-Methyl) 531/533 4- (2-Chloro-phenyl) -9-hydroxy-6-methyl-1,3-d -oxo acid-pyrrolidin-2-yl) -ethyl] -amide -1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole-8-carboxylic acid 4- (2-chloro-phenyl) -9-hydroxy-6- (2- 538/540 hyd roxy-ethyl) -8-. { 3 - [(2-h id roxi-eti I) -methyl-amino] -propoxy} -6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -9-hydroxy-8-. { 3 - [(2- 508/510 hydroxy-ethyl) -methyl-amino] -propoxy} -6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -9-hydroxy-6- (2- 548/550 hydroxy-ethyl) ) -8- (3-piperidin-1-yl-propoxy) -6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -9-hydroxy-6 -methyl- 518/520 8- (3-piperidin-1-yl-propoxy) -6H-pyrrolo [3,4-c] carbazole-1,3-dione 8- [3- (Benzyl-methyl-ammon ) -propoxy] - 584/586 4- (2-chloro-phenyl) -9-hydroxy-6- (2-hydroxy-ethyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione 8 - [3- (Benzyl-methyl-amino) -propoxy] -554/556 4- (2-chloro-phenyl) -9-hydroxy-6-methyl-6H-pyrrolo [3,4-c] carbazole-1, 3-dione 4- (2-Chloro-phenyl) -9-hydroxy-6- (2-626/628 hydroxy-ethyl) -8- [3- (4-pyridin-2-yl-piperazin-1-yl) -propoxy] -6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -9-hydroxy-6-methyl-596/598 8- [3- (4- pyridin-2-yl-piperazin-1-yl) -propoxy] -6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-phenyl-phenyl) -8- (3- dipentylamino- 620/622 prop¾xi) -9-hydroxy-6- (2-hydroxy-ethyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -8 - (3-dipentylamino- 590/592 propoxy) -9-hydroxy-6-methy l-6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -8-. { 3 - [(2- 565/567 dimethylamino-ethyl) -methyl-amino] -propoxy} -9-h-d roxy-6- (2-h idroxy-ethyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -8- . { 3 - [(2-535/537 dimethylamino-ethyl) -methyl-amino] -propoxy} -9-hydroxy-6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -9-hydroxy-6- (2- 550/552 hydroxy) ethyl) -8- [3- (3-hydroxy-pyrrolidin-1-yl) -propoxy] -6H-pyrrolo] 3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) - 9-hydroxy-8- [3- (3- 520/522 hydroxy-pyrrolidin-1-yl) -propoxy] -6-methyl-6H-pyrrolo [3,4-c] carbazole -1, 3-dione 4- (2-Chloro-phenyl) -8- [3- (cyclohexyl-576/579 methyl-amino) -propoxy] -9-hydroxy-6- (2-hydroxy-ethyl) -6H -pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -8- [3- (cyclohexyl- 546/548 methyl-amino) -propoxy] -9-hydroxy-6 -methyl-6H-pyrrolp [3,4-c] carbazpJ-1, 3 -dione 4- (2-chloro-phenyl) -9-hydroxy-6- (2- 562/564 hydroxy-ethyl) -8 - [3- (2-methyl-piperidin-1-yl) -propoxy] -6H-pyrrolo [3, 4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -9-hydroxy-6-methyl-532/534 8- [3- (2-methylpperidin-1 -yl) -propoxy] -6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -9-hydroxy-6- (2- 578/580 hydroxy-ethyl) -8- [3- (2-hydroxymethyl-piperidin-1-yl) -propoxy] -6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -9- hydroxy-8- [3- (2- 548/550 hydroxymethyl-piperidin-1-yl) -propoxyl] -6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2 -Chloro-phenyl) -9-hydroxy-6- (2- 585/587 hydroxy-ethyl) -8- [3- (methyl-pyridin-3-ylmethyl-amine) -propoxy-6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -9-hydroxy-6-methyl-555/557 8- [3- (methyl-pyridine -3-ylmethyl-amino) -propoxy-6H-pyrrolo 4- (2-Chloro-phenyl) -9-hydroxyl-6- (2- 564/566 hydroxy-ethyl) -8- [ 3- (2-hydroxymethyl-pyrrolidin-1-yl) -propoxy] -6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -9-hydroxy-8 - [3- (2- 534/536 hydroxymethyl-pyrrolidin-1-yl) -propoxy] -6-methy1-6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-Chloro-phenyl) -8- [3- (etl-methyl-522/524 a m.no) -propoxy] -9-hydroxy-6- (2-hydroxy-ethyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) - 8- [3- (et.l-met.l- 492/464 amino) -propoxy] -9-hydroxyl-6-methyl-6H-pyrrolo [3,4-c] carbazole-1, 3-dione 4- (2-Chloro-phenyl) -8- (3- 564/566 dipropylamino-propoxy) -9-hydroxy-6- (2-hydroxy-ethyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -8- (3- - "": 534/536 dipropylamino-propoxy) -9-hydroxy-6-methyl-6H-pyrrolo [3,4- c] carbazole-1,3-dione 4- (2-chloro-phenyl) -8- (3-diethylamino-506/508 propoxy) -9-hydroxy-6-methyl-6H-pyrrolo [3,4-c] carbazol-1, 3-dione 8-. { 3- [Bis- (3-methyl-butyl) -amino] -590/592 propoxy} -4- (2-chloro-phenyl) -9-hydroxy-6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -8- [ 3- (2,6-dimethyl-576/578 piperidin-1-yl) -propoxy-9-hydroxy-6- (2-hydroxy-ethyl) -6H-pyrrolo [3,4-c] carbazole -1, 3-dione 4- (2-Chloro-phenyl) -8- [3- (2,6-dimethyl-546/548 piperidin-1-yl) -propoxyl-9-hydroxy-6-methyl-6H -pyrrolo [3,4-c] carbazole-1,3-dione 9-Hydroxy-6- (2-hydroxy-ethyl) -4-phenyl-8-500.2 (3-pyrrolidin-1-yl-propoxy) -6H -pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -8- (3- 644/646 d, cyclohexylamino-propoxy) -9-hydroxy-6- ( 2-hydroxy-ethyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; trifluoro-acetic acid salt 4- (2-Chloro-phenyl) -8- (3- 564/566 diisopropylamino-propoxy) -9-hydroxy-6- (2-hydroxy-ethyl) -6H-pyrrolo [ 3,4-c] carbazole-1,3-dione; salt of trifluoro-acetic acid 9-Amino-4- (2-chloro-phenyl) -6-methyl-8-285-288 (3-pyrrolidin-1-yl-propoxy) -1, 2,3,6-tetrahydro -pyrrolo [3,4-c] carbazole-1,3-dione N- [4- (2-chloro-phenyl) -6-methyl-1, 3- 262-264 dioxo-8- (3-pyrrolidin-1) -yl-propoxy) -1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazol-9-yl] -formamide (2-pyrrolidin-1-ethyl-ethyl) -amide of 553/555 acid 4- (2-chloro-phenyl) -9-hydroxy-6-methyl-1,3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole-8-sulphonic 4- (2-Chloro-phenyl) -8: (3-, .. r 532/534 cyclohexylamino-propoxy) -9-hydroxy-6-methyl-6H-pyrrolo [3,4-c] carbazole-1, 3-dione 4- (2-Chloro-phenyl) -9-hydroxy-6-methyl-305-312 8- (3-pyrrolidin-1-yl-propane-1- (dec.) Sulfinyl) -6H-pyrrolo [ 3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -9-hydroxy-6-methyl-252-258 8- (3-pyrrolidin-1-yl-propane-1 - ( dec.) sulfonyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -9-h id roxi-6- (2- 198-203 h) droxy-ethyl) -8- (4-pyrrolidin-1-yl-butyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) - 9-h idroxy-6- (2- 269-272 hydroxy-ethyl) -8- (4-morpholin-4-yl-butyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-Chloro-phenyl) -9-hydroxy-6- (2-196-201 hydroxy-ethyl) -8- [4- (4-methyl-piperazin-1-yl) -butyl] -6H- pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -8- [3- (ethyl-propyl-238-240 amino) -butoxy] -9-hydroxy-6- methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione 4- (2-chloro-phenyl) -9-hydroxy-6-methyl-225-227 8- (1-methyl) -3-pyrrolidin-1-yl-propoxy) -6H-pyrrolo [3,4-c] carbazole-1,3-dione 9-Amino-4- (2-chloro-phenyl) -8- ( 4- 224-227 hydroxy-butyl) -6-methyl-pyrrolo [3,4-c] carbazole-1,3-dione N- [4- (2-chloro-phenyl) -6-methyl- 1, 3-252-257 dioxo-8- (4-pyrrolidin-1-yl-butyl) -1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole-1,3-dione N- [4- (2-Chloro-phenyl) -6-methyl-8- [4- (4- 270-273 methyl-piperazin-1-yl) -butyl] -1,3-dioxo-1, 2,3, 6-tetrahydro-pyrroio [3,4-c] carbazole-1,3-dione N- [4- (2-chloro-phenyl) -6-methyl-8- (4- 205-209 morpholin-4-yl- butyl) -1, 3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole-1,3-dione 9-Ami no-4- (2-chloro -fen il) -7- (4- 202-208: hydroxy-butyl) -6-methyl-6H-pyrrolo [3,4- 'cJcarbazoM, 3-dione · N- [4- (2-chloro-phenyl) -7- (4-hydroxy-230-243-butyl) -6-methyl-1,3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazol-9-yl] -formamide N- [4- (2-Chloro-phenyl) -6-methyl-7- (4-256-260 morpholin-4-yl-butyl) -1, 3-dioxo-1, 2,3,6-tetrahydro- pyrrolo [3,4-c] carbazol-9-yl] -formamide N- [4- (2-Chloro-phenyl) -6-methyl-7- [4- (4- 205-209 methyl-piperazine-1 - il) -butyl] -1,3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole-1,3-dione N- [4- (2-chloro-phenyl) - 7- (4-257-259 dimethylamino-butyl) -6-methyl-1,3-d-oxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole-, 3- dione N- [4- (2-Chloro-phenyl) -6-methyl-1, 3- 238-240 dioxo-7- (4-pyrrolidin-1-yl-butyl) -1, 2,3,6 -tetrahydro-pyrrolo [3,4-c] carbazol-9-yl] -formamide 9-Amino-4- (2-chloro-phenyl) -6-methyl-7- 158-162 (4-morpholin-4) -l-butyl) -6H-pyrrolo [3,4- (dec.) C] carbazole-1,3-dione 9-Amino-4- (2-chloro-phenyl) -6-methyl- 7- 162-166 [4- (4-methyl-piperazin-1-yl) -butyl] -6H- (dec.) Pyrrolo [3,4-c] ca rbazol-13-dione 9-Amino-4- (2-chloro-phenyl) -7- (4-21-1-2-di-methylamino-butyl) -6-methyl-6H-pyrrolo [3,4-c] ] carbazole-1,3-dione 9-Amino-4- (2-chloro-phenyl) -6-methyl-7- 204-206 (4-pyrrolidin-1-yl-butyl) -6H-pyrrolo [3 , 4-c] carbazole-1,3-dione EXAMPLE 484 Wee1 inhibition filter binding assay (OY) to test Wee1 inhibition activity ~ "This assay provides a measure of the inhibitory capacity ~ of the test compounds against the isolated Wee1 kinase." The Wee1 kinase assay measures the tyrosine enzyme-mediated phosphorylation in a synthetic peptide substrate in the presence of the compounds to be tested. The assay was performed in 96-well filter microtiter plates (Millipore No. MADP NOB10) The compounds were dissolved and diluted in DMSO To the test wells were added 10 pl of 3 x EDB buffer (150 mM Tris, pH 8.0, 30 mM NaCl, 30 mM MgCl 2, 3 mM DTT), 18 μl of water and 2 μl of drug dilution were thoroughly mixed in. To the wells were also added 10 μl of enzyme-substrate mixture. The Wee1 enzyme concentration (human Wee1 kinase aa215-647, Onyx Pharmaceuticals, expressed and purified in a baculovirus protein expression system) was 0.01 μ? / Μ? And the substrate concentration (Poly Ornithiner Thyrosine (4: 1 ), Sigma Chemical Co.) was 0.6 g / l in 1 X EDB buffer. The plates were thoroughly mixed for 5 minutes at room temperature. The reaction was started by adding 10 μ? of 1 X EDB buffer containing ATP 47.5 μ? (Sigma) and 0.026 pCi / μ? from? -32 P-ATP (ICN Biomedicals, Inc.). The plates were mixed at room temperature for 20 minutes. The reaction was stopped by adding 50 μ? of 20% TCA cooled with ice with 0.1 M tetrasodium pyrophosphate. Plates were incubated on ice or refrigerated at 4 ° C for 1 hour. The liquid reaction mixture was removed in a vacuum manifold and the precipitated phosphorylated substrate was rinsed 5 times with 200 μ? of 10% TCA cooled with ice with tetrasodium pyrophosphate 0.1. "To the substrate stained to the membrane seje added 25 μ? Of liquid scintillation cocktail ~ and the plate was read in a Microbeta plate reader (Perkin-Elmer). The activity of the compounds was calculated in comparison with control determinations. Not inhibited in each trial The data shown in Table 3 show activities (IC50) of Wee1 less than 0.1 μ? reaching up to 1.65 μ? However, Compound X with the highest activity on Wee1 of this table is a compound Representative of U.S. Patent No. 4,912,107 Compound X is not included within the scope of this invention structurally or as a checkpoint override of the present invention In this assay, the activity of Compound X against Wee1 kinase it is less potent than the upper limit for the preferred compounds.The data in Table 3 show that the modification of the core structure leads to unexpected power in inhibiting the kinase Wee1 and at a selectivity of at least 10-fold with respect to the inhibition of the PKC enzyme. The compounds of the present invention are considered suitable for use in an animal to treat cell proliferation diseases alone or in combination with one or more other antineoplastic modalities if the Wee1 activity has an IC50 value of less than 1 μ? in the test described above. Preferably, the compounds have an IC50 less than 0.5 μ? and even more preferably an IC50 less than 0.1 μ ?.

- TABLE 3 Activity of Wee1, Chk1 v PKC WEE10Y CHK1A PCK CIsoMM) ClSOIm) Clso (μ?) Compound X 1.65 0.297 3.6 Compound of Example 94 0.263 0.056 1.8 Compound of Example 80 0.006 0.167 1.49 Compound of Example 68 0.011 0.435 0.48 Compound of Example 369 0.428 > 10 > 4 Compound of Example 230 0.009 4.46 1.5 EXAMPLE 485 Chk1 Enzyme Inhibition Assay To determine the inhibitory activity of the compounds of the present invention against Chk1, the following assay was performed to measure the inhibition of the isolated Chk1 enzyme. The assay was carried out in 96 well plates of round bottom polypropylene (Costar). The compounds were tested in serial dilutions starting with a high concentration of 50 μ? followed by up to nine 3-fold dilutions. The compounds were dissolved and diluted in DMSO. 2 μ? of drug on the bottom of the test plates, then diluted with 58 μ? of Chk1 buffer (20 mM Tris, pH 8.0, 50 mM NaCl, 10% glycerol, 10 mM MgCl2, 5 mM dithiothreitol) and mixed at room temperature for 1 minute. 20 μ? of buffer containing 250 ng / well of enzyme Chk1 (Onyx Pharmaceuticals) and 1 μg / well of substrate GST-Cdc25 (Onyx). The contents of the wells were mixed for 1 minute and incubated at room temperature for 10 minutes. 20 μ? of buffer containing ATP 20 μ? and 0.4 μ ?? of ATP [v- ^ PJ -.- The contents were mixed for 1 minute and incubated at 30 ° C for 30 minutes. The reaction was stopped by adding 50 μ? of 120 mM EDTA to each well, except for the control wells that already contained EDTA. 140 μ? from the contents of the wells to the wells of 96-well white plates coated with glutathione Reacti-Bind (Pierce). The contents were mixed for 1 minute and incubated at room temperature for 1 hour. All wells were rinsed three times with 300 μ? of PBS each time and air dried. They put 200 μ? of MicroScint 20 (Packard) in the wells. The plates were hermetically sealed with an adhesive lid and counted in a Top Count Microplate scintillation counter (Packard). The activity of the compounds was calculated in comparison with the control determinations without inhibition in each assay. The data shown in table 4 show activities (IC50) of Chk1 less than 0.002 μ? that reached 0.297 μ ?. However, Compound X with the highest Chk1 activity in this table is a representative compound of U.S. Patent No. 4,912,107. Compound X is not included within the scope of this invention structurally or as a checkpoint override of the present invention. The activity of Compound X against the Chk1 kinase in this assay is less potent than the upper limit for the preferred compounds. The data in Table 4 demonstrate that the modification of the core structure leads to an unexpected potency in the inhibition of the Chk1 kinase and a selectivity of at least 10 times with respect to the inhibition of the PKC aienzyme: "" - " The compounds of the present invention are considered suitable for use in an animal for treating cell proliferation diseases in conjunction with another antineoplastic modality if the Chk1 activity has an IC50 less than 0.275 μ in the assay described above. have an IC 50 less than 0.2 μ? and even more preferably an IC 50 less than 0.1 μ ?..

TABLE 4 Activity of Wee1, Chk1 v PKG WEE10Y CH 1A PCK Clso (μ?) Clso (μ?). CIso ÍMM) Compound X 1.65 0.297 3.6 Compound of Example 198 0.193 0.013 0.132 Compound of Example 214 0.295 0.002 0.171 Some of the compounds of the present invention are dual inhibitors, being selective to inhibit both Wee1 activity and Chk1 activity. These compounds may be equal in efficacy to compounds that selectively inhibit Wee1 or Chk1 although the activity against any of the enzymes is greater than that desired for the individual inhibitors. Preferably, the dual inhibitors have an IC50 less than 1 μ ?, more preferably less than 500 nM and even more preferably less than 100? "" ~ "'" TABLE 5 Dual inhibitors WEE10Y CHK1A EXAMPLE 486 Myt-1 inhibition scintillation proximity assay for assaying the inhibition activity of Myt-1 This assay provides a measure of the inhibitory activity of the test compounds against the isolated Myt-1 kinase. The assay was performed on 96-well Wallac SPA (Scintillation Proximity Assay) plates. The compounds were tested at 50 μ? followed by up to nine 3-fold dilutions (ie, 50, 16.67, 5.56, 1.85, 0.617, etc.). The drugs were dissolved and diluted in DMSO. 2 μ? of drug on the lower surface of the wells of the SPA plates. To each well was added 30 μ? of buffer F (50 mM Tris, pH 8.0, 100 mM NaCl, 0.1% Tween 20, 1 mM MgCl 2, 100 μM DTT) containing cold ATP "27 ~ pM ~ and then 9 μm of. MF buffer with Myt-1 enzyme (MW = 54.6 kDa) at a concentration of 177.8. The plates were mixed at room temperature for 1 minute and then incubated at room temperature for 5-15 minutes. MHKB buffer (50 mM Tris, pH 8.0, 1 mM MgCl2, 100 μM DTT, 0.1 mM Na3V04) with Cdc2 / B (MW = 84.5 kDa) 88.9, and mixed at room temperature for 1 minute. centrifuged up to 2400 RPM and incubated for 30 minutes at 30 ° C. 30 μ? of MHKB buffer containing peptide substrate of 1 μ? biotinylated histone H1 (Amersham) (stock: 1 mM) and 10 μ ?? / was added. μ? of ATP [? -33?] The plates were mixed at room temperature for 1 minute, centrifuged until 2400 RPM, and incubated for 30 minutes at 30 ° C. The reaction was stopped with 200 μ? of buffer of stop, 5 mM EDTA and 0.1% Triton X-100 (from a 10X stock solution of EDTA at 50 mM and 1.0% Triton X-100 diluted with PBS) with streptavidin SPA beads (Amersham) at a concentration of at least 20 pg / ml and ATP 50 μ ?. The plates were hermetically sealed with an adhesive lid, mixed by inverting them 10 times and incubated for 10 minutes at room temperature. The plates were centrifuged at 2400 RPM for 15 minutes at room temperature and counted in a Wallac Microbeta Trilux counter. The activity of the compounds was calculated in comparison with control determinations without inhibition in each assay. In this assay, none of the compounds of the present invention had an IC 50 value for activity on Myt-1 less than 10 μ. As the phosphorylation of the "thr ~ 14 in cdc2 (catajizada by the kinase Myt-1) -also is an event that establishes a point of control, a compound that inhibits both the Wee1 kinase and the Myt-1 kinase can be a null of control points due to its dual inhibitory activity.Therefore, the lack of inhibition of Myt-1 rules out the conttion of Myt-1 to the abolition of control points.The absence of significant inhibitory activity of Myt-1 The compounds of the present invention demonstrate the selectivity of these compounds as inhibitors of Wee1 kinase and Chk1 kinase.

EXAMPLE 487 Quinase C protein assay (PKC) The PCK assay provides a measure of the inhibitory activity of test compounds against PKC contained in a rat brain preparation. The enzyme was prepared from a rat brain preparation (Promega) of 0.5 pg diluted with 1.6 ml of 10 m Hepes buffer pH 7.5. The reaction buffer comprised 150 mM Hepes buffer, 4 mM CaCl2, 15 mM MgCl2, 3 mM EDTA, and 3.75 mM EGTA at pH 7.5. The histone substrate was obtained by dissolving the histone H1 (Sigma) in water at 1.5 mg / ml. Phosphatidylserine / diolein liposomes were obtained by mixing 75 μ? of phosphatidyl serine at a concentration of 10 mg / ml (Sigma) in CHCl3 with 60 μ? of - - diolein "at 2.5 mg / ml in CHCI3 (Sigma) in a glass vial evaporating-CHCI3 in an atmosphere of N2.The film was suspended in 1 ml of water and sonicated 6 times for 15 seconds with a probe Microtip at room temperature To perform the assay, 50 μ? Of buffer, 20 μ? Of histone, 20 μ? Of liposomes and inhibitor or solvent control were added to the wells of a 96-well filter plate (Millipore) with enough water, if necessary, to constitute the final volume of 110 μ? 20 μ? of enzyme preparation solution was added and incubated for 10 minutes at room temperature This was continued by the addition of 20 μ? of 32 P ATP (ATP 75 μ? In water, ATP labeled at 25 pCi / ml), and the mixture was incubated for 15 minutes at room temperature The reaction was terminated by the addition of 50 μ? Of 40% trichloroacetic acid (w / v) The filters were washed by vacuum filtration with 5 x 125 μl of trichloroacetic acid a l 10% (w / v) cooled with ice The filters were placed in scintillation fluid and counted to determine the precipitated labeled phosphate incorporated in the substrate. The percent inhibition was calculated in comparison with the non-inhibited controls.

EXAMPLE 488 Histone H1 Cdc2 kinase assay in 96 wells, based on cells for the cancellation of the G2 checkpoint _--- | | - ---- - - -This cell assay is a measure of the effect of test compounds on the activity of the Cdc2 / cyclin B complex on one of its physiological substrates, histone H1. HT-29, 20,000 cells per well (NUNCLON ™ catalog number 163320, 96-well plate) were cultured in 171 μ? of medium [Eagle Medium Modified by Dulbecco with 4500 mg / L of glucose (DME with high glucose content), penicillin and 1% streptomycin, 2% L-glutamate and 10% FBS]. The plate was incubated at 37 ° C for 24 hours. To each well was added 9 μ? of a solution of adriamycin 5 μ? (final concentration 250 nM) and incubated at 37 ° C for an additional 16 hours. Then 20 μ? of nocodazole at 500 ng / ml per well followed immediately by the addition of 5 μ? of test compound. The plate was incubated at 37 ° C for 4 hours. The plate was removed from the incubator and centrifuged in a Beckman GS-6R centrifuge for 10 minutes, at 800 rpm, at 4 ° C. The medium was removed and the plate was surface dried with blotting paper. 100 μ? of PBS to each well. The plate was centrifuged as indicated above. The PBS was removed from the plate and the surface of the plate dried. Then 20 μ? Were added to each well. of lysis buffer (50 mM Hepes pH 7.5, 250 mM NaCl, 0.1% NP 40, 10 mM β-glycerophosphate, 1 mM NaF, 1 mM EDTA, 1 mM Pefabloc, 1 mM DTT, 0.1 mM sodium orthovanadate, Aprotinin a 10 pg / ml and Leupeptin 20 μ) followed by agitation at medium speed at 4 ° C for 45 minutes. After lysis, 30 μ? of assay buffer kinase (50 mM Hepes, 22 mM MgCl2, 1 mM DTT, "histone HI a? 66G7 ng / μ ?, ATP 83 μ ?, 0.033 μ? '/ μ? of [? -33?]? The plate was incubated in a plate heater at 32 ° C for 25 minutes.The reaction of the kinase was stopped by adding 80 μl of 100 mM EDTA pH 7.8 to each well.The lysate was collected on a Wallac P filter. -30 (Wallac 1450-523, fiberglass filter with negatively charged P30 active groups, size 90 x 120 mm) using 75 mM H3PO4 for 10 seconds, followed by a 10 second aspiration step. 75 mM H3PO4 bath and stirred gently for 10 minutes at room temperature, and then placed inside the fold of a single sheet of paper tower, and subjected to high power microwave for 2 to 3 minutes, or until The filter was dried The filter was placed in a sample bag (Wallac 1450-432), 5 ml of non-aqueous scintillation fluid was added to the sample bag and the lsa was hermetically sealed. The samples were read in a MicroBeta Wallac 1450 liquid scintillation counter. The data shown in Table 6 demonstrate the cellular effect of a Wee1 and / or Chk1 inhibitor on a physiological substrate of cdc2 / cyclin B, said complex being itself same substrate of the Wee1 kinase.

TABLE 6 History Kinase Assay EXAMPLE 489 Procedure for clonogenic assays in HT-29 + adriamycin cells This cell assay is a measure of the toxicity of the test compounds in the absence and presence of DNA lesions induced by a conventional chemotherapeutic agent.

HT-29 cells were cultured in Dulbecco's Modified Eagle Medium with a high glucose content, supplemented with 1 mM sodium pyruvate, 2 mM L-glutamine, 16 mM HEPES, 8 mM MOPS and 10% fetal bovine serum. The cells were incubated at 37 ° C in an atmosphere with 5% C02 and 100% relative humidity. Two or three T-75 tissue culture flasks were seeded at approximately 50% confluence in 30 ml of medium and incubated for approximately 24 hours. To the flasks were added adriamycin (ADR) (dissolved at 5 mM in distilled water (dh ^ O)) at a final concentration of 1 μ? or 500 nM. One flask did not receive ADR. The cells were allowed to incubate with the ADR for 1 hour. Then, all the flasks were washed twice with 20 ml of medium and allowed to incubate for an additional 16 hours in 30 ml of medium. E | agar <; je resérvá (Seaplaque GTG Agarose at 3.2%. (BioWhittaker · Molecular Aplications)) was suspended in distilled water and sterilized in an autoclave for 20 minutes. The agar melted before use in a microwave. The bottom agar was a 1: 4 dilution of the stock agar in medium with enough fetal bovine serum added to bring the solution to 10%. In each well of 6-well tissue culture plates, one microliter was placed and the plates allowed to solidify. The cloning agar (a 1: 8 dilution of stock agar in medium with 10% fetal bovine serum added) was prepared and maintained at 40 ° C until use.

The cells were trypsinized using Trypsin-EDTA and their concentration was adjusted to 75,000 cells per microliter with medium. One hundred microliters of each cell suspension was placed in 15 ml sterile plastic centrifuge tubes. Twenty-five microliters of each test compound was added to the appropriate tubes, followed by the addition of 5 ml of hot cloning agar. The tubes were mixed well and 2 ml of the agar / cell suspension was added to duplicate wells of the 6-well plates that had been coated with agar above. The plates were shaken and placed in the refrigerator for 5 minutes. After the plates returned to room temperature, they were incubated for 10 to 14 days until the colonies were visible. The colonies were stained with INT (p-Yodonitrotetrazolium violet) (dissolved in dH20 at 1 mg / ml and sterilized with a filter). To each well was added 1 ml of INT and the plates were incubated ~ -during night at 37 ° C, 5% C02 and 100%. of relative humidity. The colonies were counted using a Hamamatsu video imaging system and ImageQuant software.

TABLE 7 Data of the clonogenic assay % of Colonies% of Control Colonies without Control with Lesions in the DNA lesions DNA Compound of Example 366 38% 2.8% (250 nM) EXAMPLE 490 Procedures for the Western blot determination of phosphotyrosine 15 in Cdc-2 and change of mobility of Myt-1 These Western blot assays measure the phosphorylation state of the physiological substrate of Wee1: tyrosine 15 of the Cdc2 kinase. This is achieved by means of a phospho-specific antibody whose signal is normalized by comparison with the total amount of Cdc2 detected in the samples. The change of the Myt-1 protein to a lower mobility in a Western blot is used as a measure of the progression to the M phase of the cell cycle. A. Procedure for detecting phosphotyrosine 15, change of Myt-1 and total Cdc-2 of cultured HT-29 cells in response to potential checkpoint overriders ± Adriamycin and / or Nocodazole. HT-29 cells were cultured in Dulbecco's Modified Eagle Medium with high glucose content, supplemented with 1 mM sodium pyruvate, 2 mM L-glutamine, 16 mM HEPES, 8 mM MOPS and 10% fetal bovine serum. The cells were incubated at 37 ° C in 5% C02 and 100% relative humidity. Cells were cultured and treated in 6-well tissue culture plates. The cells were seeded in 3 ml of medium at a concentration of 200,000 per ml. Once seeded, the cells were allowed to bind for 24 hours. All treatments were performed in duplicate wells. The wells that were treated with adriamycin (ADR) were exposed to ADR 1 μ? for 1 hour. The ADR was dissolved in sterile distilled water. After incubation for 1 hour, the cells were washed twice with 2 ml of medium and then incubated in 3 ml of medium for 16 hours. After incubation for 16 hours, the cells were treated with various concentrations of Nocodazole + (NOC) at 50 ng / ml. The knockers were dissolved in dimethylsulfoxide (DMSO) at a concentration of 10 mM and diluted with growth medium before being added to the cells and the NOC was dissolved at 1 mg / ml in DSO and diluted with growth medium before the administration to the cells. The cells were incubated for 6 hours with the nullifier and NOC. Duplicate wells .se. they scraped on ice -and they -combined in a 15-ml centrifuge tube. The wells were rinsed with Dulbecco's phosphate-buffered saline (DPBS) without calcium and magnesium and the rinses were combined with the scraped cells. The cells were centrifuged at 200 X g at 4 ° C for 5 minutes. The supernatant was discarded and the pellets were resuspended in 100 μ? of DPBS. The cell suspension was then transferred to 1.5 ml eppendorf centrifuge tubes and centrifuged at 4 ° C for 4 minutes at 4000 rpm. After removing the supernatant, the pellet was frozen on dry ice and stored at -80 ° C.

The sediments were thawed on ice before lysis. Lysis buffer, ELB (2.5 mM HEPES (7.5), 150 mM NaCl, 25 μM NaF and 0.5% NP40) supplemented with 1 mM AEBSF, 1 mM sodium orthovanadate and 1 mM dithiothreitol, and inhibitor cocktail tablets were used. of complete protease (Roche Biochemicals). The tablets were dissolved in 2 ml of distilled water and diluted 1: 25 in the lysis buffer. The sediments were suspended in 100 μ? of complete lysis buffer and incubated on ice for 30 minutes. After lysis, the suspension was centrifuged at 14,000 rpm for 15 minutes at 4 ° C. The supernatant fluid was collected and the protein concentration was determined using the Pierce BCA protein assay kit following the manufacturers' instructions. The protein concentration was adjusted to 3 mg / ml with DPBS. The samples were then diluted 1: 1 with Invitrogen 2 X tris-glycine sample buffer supplemented "with" 50 μg / ml 2-mercaptoethanol. they were boiled-for-3 minutes and stored in the frozen state at -20 ° C. Thirty micrograms of protein per lane were processed in 12 x 12%, 1.5 mm, 10-well, 10-well, polyacrylamide and tris-glycine gels, using Novex process buffer and Invitrogen (see Blue Plus 2 molecular weight standards). The gels were processed at 100 volts for 30 minutes and then at 125 volts for 1.5 hours. The proteins were transferred to pore nitrocellulose membranes of 0.45 μm using Novex transfer buffer and the Novex X-Cell II transfer module. The nitrocellulose membranes were blocked overnight at room temperature. The blocking buffer was 5 mM Tris (8.0), 150 mM NaCl, 0.1% Tween 20, 1 mM NaF, 10 mM glycerol phosphate, 100 μM sodium orthovanadate. and 3% bovine serum albumin. After blocking, the gels were cut with a razor blade and the upper portion treated with anti-Myt-1 antibody diluted 1: 5000 with blocking buffer. The lower portion of the gel was treated with biotinylated antiphosphotyrosine 15, also diluted 1: 5000 in blocking buffer. The membranes were incubated for 2 hours at room temperature with constant agitation. The antibody solutions were removed and the membranes were washed 3 times for 20 minutes each with TNT buffer. The TNT buffer consisted of 50 mM Tris (8.0), 150 mM NaCl and 0.1% Tween 20. Then secondary antibody was added in blocking buffer. HRP neutravidin was used at 1: 40,000 for the biotinylated phosphotyrosine stains 15 and "BioRad goat anti-rabbit antibody was used at 1: 10,000 for the - - · - Stain of Myt-1 Stains remained on the secondary antibody for 1 hour at room temperature followed by three 20 minute washes with TNT buffer.The protein bands were detected using the ECL detection kit from Amersham Pharmacia and a Kodak Bio Max film following the manufacturer's instructions.Posphotyrosine membranes 15 discovered using the kit Chemicon International Re-Blot following the manufacturer's instructions. The spots were then washed twice with TNT buffer and once with blocking buffer for 20 minutes each time. It was diluted anti Cdc-2 (cdkl: Labvision Corporation) at 150 μ? per 50 ml of blocking buffer and incubated with the spots for 2 hours at room temperature followed by three 20 minute wash in TNT buffer. The secondary antibody was goat anti-mouse HRP from BioRad and was diluted 1: 10,000 in blocking buffer before incubation for 1 hour with the spots at room temperature. Three washes of 20 minutes preceded the detection of ECL. B. Procedure to detect MPM_2 in cultivated HT-29 cells +/- potential inhibitors of control points, adriamycin and nocodazole. This assay uses polyclonal antibody to quantify specific M-phase histological markers in the determination of a mitotic index (fraction of cells found in mitosis). HT-29 cells were cultured in Eagle's Medium Modified by: Dülbécco with high gjucose content, supplemented with pyruvate, 1 mM sodium, 2 mM L-glutamine, 16 mM HEPES, 8 mM MOPS, and 10% fetal bovine serum. They were incubated at 37 ° C in an atmosphere of 5% C02 and 100% relative humidity. The cells were seeded in tissue culture plates from 96 wells to 100 μ? per well at a concentration of 40,000 for me. The cells were allowed to attach and begin to grow for 24 hours. 100 μ? of adriamycin (ADR) at a concentration of 2 μ? (final = 1 μ?) to the test cells and the cells were incubated for one hour as indicated above. After incubation, the plates were washed twice with growth medium. The medium was replaced by 100 μ? of new medium and incubated for 16 more hours. Two-fold serial dilutions of potential cancellers were added to the assay wells. To the rows that received nocodazole (NOC) were added 2 μ? from NOC to 2.5 pg / ml. Then, the plates were incubated for a further 6 hours. After incubation, the plates were centrifuged for 5 minutes at 4 ° C to 200 g. To each well was added directly 100 pl of Carnoy's fixative, 3 parts of methanol for one part of acetic acid, and left at room temperature for 15 minutes. The medium / fixative mixture was removed by suction and replaced with ethanol: acetic acid cooled with ice in a ratio of 20: 1. The plates were stored at 4 ° C until they were stained. The fixed cells were stained with respect to MPM-2 using the rhodamine detection kit Upstate Biotechnology MPM-2 following the manufacturer's instructions. In short, the cells. sextavaron with Dulbecco's phosphate buffered saline (DPBS) with calcium and magnesium followed by incubation with blocking buffer consisting of 8% bovine serum albumin (BSA) for a minimum of 1 hour. The cells were then washed with PBS once and treated overnight at 4 ° C with primary antibody at 5 pg / ml (100 μl per well) diluted with DPBS with 1% BSA. The cells were then washed twice for 15 minutes each with DPBS and then incubated with a 1: 1000 dilution of goat anti-mouse IgG conjugated to rhodamine in DPBS with 1% BSA for 1 hour. The secondary antibody was washed in three 30 minute washes with DPBS.

The cells were then stained with contrast dye using the Molecular Probes Mycoflour kit to stain the nuclei following the instructions for the kit. The stained cells were visualized by fluorescence microscopy using fluorescence filters suitable for detecting rhodamine and DAPI stains. The images were captured using a Spot digital camera and the images were analyzed using ImageQuant to quantify the total nuclei and to count the positive MPM-2 cells.

TABLE 8 MPM-2 assay (Values are% of cells in M phase) + Medium + ADR + NOC + ADR + NOC Control 8.4 7.0 26.4 25.9 Compound of Example 363 26.4 18.9 37.2 86.2 to 312.5 Nm _ - ---- EXAMPLE 491 Procedure for the in vivo assay of Wee1 inhibitors. Wee1 / Chk1 or Chk1 in combination with adriamycin and cisplatin These experiments measured the in vivo modulation of Py15 on Cdc2 in tumor and evaluated the therapeutic effect of the Wee1, Wee1 / Chk1 or Chk1 inhibitors of the present invention together with a conventional agent. The therapeutic effect is measured by an increase in the duration of life of the treated animals.

EXPERIMENTS IN VIVO In vivo methods The initial in vivo experiments demonstrate the biochemical and physiological evidence of the inhibition of Wee1, Wee1 / Chk1 or Chk1 by examining downstream target modulation (ie, the phosphorylation state of Cdc2 tyrosine 15) and the effects of the cell cycle on murine leukemia tumor cells L1210. The L1210 line was chosen because of its lack of p53 function, the pronounced accumulation of G2 in response to DNA lesions, the ease of spreading in mice, and the rapid cycle time. In CD2F1 mice weighing 25 to 26 grams, 105 or 5 x 10 5 L12 0 cells were intraperitoneally (ip) inoculated and distributed randomly in treatment groups of 3 mice each. On day 4, 5 - ~ or 6 after tumor implantation, the mice were treated with a single injection of DNA lesion agent (cisplatin, 8 or 6 mg / kg iv), one or more injections of the Example 80 (20 mg / kg ip, se or iv) or the two agents. Injections of the compound of Example 80 were spaced from 3 to 8 hours and initiated simultaneously with the DNA lesion agent or after a delay of 8 or 16 hours. The control animals received only 0.2 ml of iv saline. The DNA lesion agents were dissolved in saline and the compound of Example 80 was dissolved in 1 of 2 vehicles: (1) 10% cremaphor, 10% ethanol and 80% H20 or (2) 5% dimethylacetamide. , 25% propylene glycol and 70% polyvinylpyrrolidine (30% w / v in H20). The mice were sacrificed at various time points ranging from 8 to 40 hours after starting treatment and the tumor cells were harvested in phosphate buffered saline containing 1 mM sodium orthovanadate and 5 mM EDTA. The L1210 cells were counted in a Coulter counter and for each group an aliquot of 2.5 x 10 7 cells was centrifuged and frozen in the pellet form and an aliquot of 2.5 x 10 6 was frozen in Vindelov1 citrate buffer at -80 ° C. The larger pellets were homogenized for 30 seconds with a sonicator in cold lysis buffer (RIPA) containing 25 mM Tris (base) pH 7.4, 350 mM sodium chloride, 1% nonidet P40, 5 mM EDTA (tetrasodium), 0.5% sodium deoxycholate, 0.1% sodium dodecyl sulfate, 1 mM AEBSF, 1 mM sodium fluoride, 0.5 mM sodium orthovanadate, 5 pg / ml aprotinin, 20 μl leptospray, 10 μM β-glycerophosphate and DTT 1-mM in H20.- The '- - - - 5 lysates were diluted 1: 10 with a mixture of 4 parts of RIPA and 5 parts of sample buffer of Novex 2X electrophoresis which, when diluted to a working concentration contained 2% sodium dodecyl sulfate, 0.0025% bromophenol blue, 10% glycerol and 60 mM dithiothreitol in H20 The samples were heated at 98 ° C for 5 minutes, 1 mm mm minigels were loaded from 15 wells of polyacrylamide 4-20% Novex Tris-glycine duplicates with 15 μ? / Well and processed at 200 V (constant) for 45 minutes. eines were transferred to nitrocellulose membranes in Novex transfer buffer at 25 V (constant) for 2 hours. One of the membranes was labeled for the total Cdc2 protein with MS-1 10P antibodies from LabVision at 1: 200, followed by goat anti-mouse IgG 172-1011 from BioRad-HRP at 1: 10,000. The other membrane was labeled for photyrosine 15 of Cdc2 (Ptyr15) with biotinylated rabbit polyclonal antibodies supplied by Onyx Pharmaceuticals at 1: 5000 followed by Pierce-HRP neutravidin 31001 at 1: 20,000 (50 ng / ml). The antibodies were detected with Amersham ECL reagents. The images of the spots were captured on a Kodak Bio ax MR film and formed into a Molecular Dynamics Personal Densitometer SI. The densitometry was performed with Molecular Dynamics Image QuaNT software. The densitometric values for the Pd15 of Cdc2 were normalized for the total Cdc2 protein (divided by the values for the total Cdc2 to obtain a ratio of total pho: Cdc2) and divided by the ratio of the control samples to obtain the percentage of the control phorylation values for each tumor sample. The smallest sediments were stained to determine the DNA content by the Vindelov method (Vindel v LL, Christensen IJ and Nissen NI.A detergent-trypsin method for the preparation of nuclei for flow cytometric DNA analysis.; 3: 323-327). The fluorescence was analyzed by propidium iodide in a Beckman-Coulter Elite flow cytometer. The distributions of cell cycles were estimated by the widened trapezoidal model of BagweII (BagweII, CB Theoretical aspects of flow cytometry data analysis, in; KD Bauer, RE Duque, S. Shankey, (eds.), Clinical Flow Cytometry: Principles and Application, pp. 41-61, Baltimore; Williams & Wilkins, 1993) as done by the Verity Software House ModFit LT program. Subsequent in vivo experiments were designed to determine whether the addition of a Wee1, Wee1 / Chk1 or Chk1 inhibitor to conventional chemotherapy with agents that cause DNA damage results in a beneficial therapeutic effect. In CD2F1 mice weighing 24 to 26 g, 104 L1210 ip cells were inoculated and the mice were randomized into treatment groups of 6 mice each. On days 3, 7 and 11 after implantation, the mice were treated with a single iv injection of 1 of 3 dosage levels of an agent that produces DNA lesions (cisplatin or doxorubicin) alone or in combination with two ip injections of 1 of 2 dosage levels of the compound of Example 80. Control mice received appropriate vehicle in place of active agents. The dosage levels were based on the. average body weights of the group. The mortality data were collected over a period of three weeks and the average survival times of each group were calculated. The efficacy data (% T / C) are presented as the average life duration of the treated animals divided by the average life span of the control animals x 100. Then the maximum% T / C value was compared of the combination groups with the maximum% T / C value of those treated with agents that produce DNA lesions. As shown in Table 9, the only groups that produced a measure of therapeutic benefit were associated with the addition of a Wee1 inhibitor, Wee1 / Chk1 or Chk1 of the present invention.

TABLE 9 Distribution of the cell cycle of L1210 cells Cell cycle distribution of L1210 cells treated in vivo with cisplatin at a concentration of 6 mg / kg and with the compound of Example 80 at 20 mg / kg. The cells were examined 24 hours after the administration of the drug and the compound. The values are percentages of the cells examined. All compositions and / or methods described and claimed in the present invention can be manufactured and performed without undue experimentation in light of the present disclosure. Although the compositions and methods of this invention have been described in terms of preferred embodiments, it will be apparent to those skilled in the art that variations can be applied to the compositions and / or methods and in the steps or in the step sequences of the methods for prepare these compounds.

Claims

NOVELTY OF THE INVENTION
CLAIMS wherein each dashed line represents an optional link; R1 is hydrogen, halogen, C8 alkyl, NR5R6 or an aryl or heteroaryl ring optionally substituted with up to five, substituents selected from halogen, alkyl, haloalkyl, hydroxyl, nitro, cyano, C (0) R3, OR3, S (0) MR3, NR3R4, OC (0) R3, NR3 (CO) OR4, CH2NR3R4, CH2OR3, COOR3, CONR3R4, NR3COR4, S02NR3R4, CONHS02R3, NR3S (0) mR4, NHCONR3R4, NR3CONHR4; or a cycloalkyl or cycloalkenyl ring optionally substituted with up to five substituents selected from halogen, alkyl, haloalkyl, hydroxyl, nitro, cyano, C (0) R3, OR3, S (0) mR3, NR3R4, OC (0) R3, NR3 ( CO) OR4, CH2NR3R4, CH2OR3, COOR3, CONR3R4, NR3COR4, S02NR3R4, CONHS02R3, NR3S (0) mR4, NHCONR3R4, NR3CONHR4; or a heterocyclic ring optionally substituted with up to five substituents selected from halogen, alkyl, haloalkyl, hydroxyl, nitro, cyano, C (0) R3, OR3, S (0) mR3, NR3R4, OC (0) R3, NR3 (CO) OR4, CH2NR3R4, CH2OR3, COOR3, CONR3R4, NR3COR4, S02NR3R4, CONHS02R3, NR3S (0) mR4, NHCONR3R4, NR3CONHR4; m is 0-2; X is hydrogen or halogen; Y1 is O, S (0) m or NR10, R9 is hydrogen, hydroxyl, halogen, NR3C (0) R4, NHCONR3R4, (C = NR3) NHR4, NH (C = NR3) NHR4, NH (C = NH) NR3R4, NH (C = 0) OR3, NR5R6, (CR5R6) rZ; r is 0-6; R2, R7, R8 and R10 in each case are independently selected from ((CR5R6) nT) to (C11R2) b) -Z, where the sum of n, a and b is in each case less than 10; T may be absent or, when present, in each case 3 is independently selected from O, CONR3, CONHS02, S (0) m, NR3, NR30, OS (0) m, S (0) mO, NR3S (0) 2 or S (0) 2NR3; n is independently in each case 0-6; a is independently in each case 0-6; b is independently in each case 0-6; Z is selected from hydrogen, halogen, alkyl, haloalkyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, heteroaryl, cyano, nitro, hydroxy,. < C (0) R3, CONHSO2R3, OR3, S (0) MR3 OSO2R3, NR3R4, C02R3, 'CONR3R4, NR3COR4, S02NR3R4, OPO (OR3) (OR4), CH = CR3R4, CCR3, (C = NR3) NHR4, NH (C = NR3) NHR4, NH (C = NH) NR3R4, where the alkyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl or heteroaryl group may be substituted with up to four groups independently selected from halogen, alkyl, hydroxyl, nitro, cyano, OR3 , S (0) MR3, NR3R4, OC (0) R3, NR3 (CO) OR4, C (0) R3, COOR3, CONR3R4, NR3COR4, S02NR3R4, CONHSO2R3, NR3S (0) mR4, CH2NR3R4, CH2OR3, NHCONR3R4, NR3CONHR4; R5, R6, R11 and R12 are independently selected in each case from hydrogen, hydroxyl, alkyl, haloalkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclic, halogen, cyano, nitro, CH2NR3R4, CH2OR3, C (0) R3, OR3, S (0) mR3, NR3R4, COOR3, CONR3R4, S02NR3R4, NHCONR3R4, NR3CONHR4; wherein the alkyl, cycloalkyl, cycloalkenyl, heterocyclic, aryl or heteroaryl group can be substituted with up to four groups independently selected from halogen, alkyl, hydroxyl, nitro, cyano, OR3, S (0) mR3, NR3R4, OC (0) R3, NR3 (CO) OR4, C (0) R3, COOR3, CONR3R4, NR3COR4, S02NR3R4, CONHS02R3, NR3S (0) mR4, NHCONR3R4, NR3CONHR4; R5 and R6 or R11 and R12 together with the carbon atom to which they are attached can form a carbonyl group; or together with the carbon or heteroatom to which they are attached can form a cycloalkyl or heterocyclic group, wherein said carbonyl, cycloalkyl or heterocyclic group can be substituted with up to four groups independently selected from halogen, hydroxyl, nitro, cyano, alkyl, haloalkyl, halogen , alkyl, nitro, cyano, OR3, S (0) MR3, NR3R4, OC (0) R3, NR3 (CO) OR4, C (0) R3, COOR3, CONR3R4, NR3COR4, S02NR3R4, CONHS02R3, NR3S (0) mR4 , NHC0NR3R4, NR3CONHR4; R3 and R4 are independently selected from hydrogen, alkyl, haloalkyl or a substituted or unsubstituted carbocyclic group selected from cycloalkyl, cycloalkenyl, heterocyclic, aryl and heteroaryl, wherein said alkyl, or a substituted group may be substituted with up to 4 groups selected from halogen , hydroxyl, nitro, cyano, alkyl, haloalkyl, alkyloxy, carboxy, COOH, CONH2, NHCOCH3, N (CH3) 2, NHCH3, thiomethyl, thioethyl, SOCH3, S02CH3; R3 and R together with the carbon atom or heteroatom to which they are attached can form a cycloalkyl or heterocyclyl group with up to four groups independently selected from halogen, hydroxyl, nitro, cyano, alkyl, haloalkyl, alkyloxy, formyl, carboxy, acetyl, CH2NH2 , CH2OH, COOH, CONH2, NHCOCH3, N (CH3) 2, thiomethyl, thioethyl, SOCH3, S02CH3, alkoxycarbonyl, alkylcarbonyl, alkynylamino, aminoalkyl, aminoalkylcarbonyl, amino, mono- or dialkylamino, or R3 and R4 together with the nitrogen to which they are joined can form a heterocyclic ring containing 3-8 members, up to four of which are optionally carbonyl groups or heteroatoms independently selected from oxygen, sulfur, S (O), S (0) 2 and nitrogen, where the carbocyclic group is unsubstituted or substituted with up to four groups independently selected from halogen, hydroxy, hydroxyalkyl, alkyl, haloalkyl, alkoxy, alkoxycarbonyl, alkylcarbonyl, alkynylam ino, aminoalkyl, aminoalkylcarbonyl, amino, mono- or dialkylamino. 2. The compound according to claim 1, further characterized in that R1 is selected from an unsubstituted aryl ring or an aryl ring substituted with up to 3 substituents selected from the group consisting of halogen, haloalkyl, alkoxy, hydroxyl, nitro or NR3R4 .
3. The compound according to claim 1, further characterized in that R9 is selected from a group hydrogen, hydroxyl, halogen or NHCHO.
4. - The compound according to claim 1, further characterized in that Y1 is oxygen.
5. The compound according to claim 1, further characterized in that Y1 is sulfur.
6. The compound according to claim 1, further characterized in that Y1 is NR10.
7. The compound according to claim 1, further characterized in that R9 is NR5R6 or OH, R1 is aryl and Y1 is NR10.
8. The compound according to claim 1, further characterized in that R9 is hydroxyl, Y1 is NR10 and the bond represented by dashed line (C-0) is absent.
9. The compound according to claim 3, further characterized in that R9 is hydroxyl and R8 is not hydrogen.
10. The compound according to claim 1, further characterized in that R8 is not hydrogen and R9 is hydrogen.
11. The compound according to claim 1, further characterized in that R9 is hydrogen and R8 is ((CR5R6) nT) a (CR11R12) b) -Z; where T may be absent or O and Z are NR3R4.
12. The compound according to claim 1, further characterized in that R9 is selected from halogen or hydroxyl and R8 is ((CR5R6) nT) a (CR11R12) b) Z where T and Z are absent.
13. The compound according to claim 1, further characterized in that R9 is selected from NR5R6 and OH, R7 is (CR5R6) nT) a (CR1R2) b) Z, and Y is selected from O and NR0.
14. - The compounds: 2- (4- (2,6-dichlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl methanesulfonate )ethyl; 2- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) ethyl methanesulfonate; 3- (4- (2,6-Dichlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) -N- [2 - (dimethylamino) ethyl] propanamide; 3- (4- (2-chloro-6-methoxyphenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) -N- [2- (dimethylamino) ethyl] propanamide; 3- (4- (2-chlorophenyl) -9-Hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) -N- (1 H-) tetrazol-5-yl) propanamide; 3- (4- (2-chlorophenyl) -9-Hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) -N- [2- ( 1H-imidazol-5-yl) ethyl] propanamide (129); 3- (4- (2-chlorophenyl) -9-hydroxy-1,3-d-oxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) -N- [2 - (4-morpholinyl) ethyl] propanamide (121); 3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) -N- [2- (dimethylamino) ethyl] propanamide; 3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) -propanonitrile; 3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1H) -yl) propanoic acid; 3- (9-Hydroxy-1,3-dioxo-4-pheny1,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) propanamide; 3- (9-Hydroxy-1,3-dioxo-4-phenyl-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) propanoic acid; 4- (2,3-Dichlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione (18) 4- (2-chloro-5-hydroxyphenyl) -9- hydroxy-pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2,6-Dibromophenyl) -9- hydroxy-pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2,6-Dichloro-3-hydroxy-phenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2,6-Dichloro-4-hydroxyphenyl) -9-hydroxy-pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2,6-Dichlorophenyl) -9-hydroxy-6- (2-hydroxyethyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2,6-Dichlorophenyl) -9- hydroxy-6- (3-hydroxypropyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -d ona; 4- (2,6-Dichlorophenol) -9-hydroxy-6- [3- (1 H -amidazol-1-yl) propyl] pyrrolo [3,4-c] carbazole- 1, 3- (2H, 6H) -dione; 4- (2,6-Dichlorophenyl) -9-hydroxy-pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2,6-D-methoxy-phenyl) -9-hydroxypyrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Bromophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chloro-3-hydroxyphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chloro-4-hydroxyphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chloro-6-hydroxyphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-Chloro-6-methoxyphenyl) -9-hydroxy-6- (2-hydroxyethyl) pyrro! Or [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chloro-6-methoxyphenyl) -9-hydroxy-6- (3-hydroxypropyl) pyrrolo [3-c] carbazole-1, 3 - - - - - - - -. 2H, 6H) -dione; - 4 ^ (2-chloro-6-methoxyphenyl) -9-hydroxy-6- [3- (4-morpholinyl) propyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -d Ona; 4- (2-chloro-6-methoxy-phenyl) -9-hydroxy-pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -6- (2,3-dihydroxypropyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -6- (2-hydroxyethyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenol) -6- (3,4-dihydroxybutyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -6-etl-9-Hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-chlorophenol) -9-hydroxy-6- (2-hydroxypropyl) pyrrolo [3,4-c] carbazol-1, 3- (2H, 6H) -dione (313); 4- (2-chlorophenyl) -9-hydroxy-6- (3-methoxypropyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione (132); 4- (2-chlorophenyl) -9-Hydroxy-6 - [(2R) -3-Hydroxy-2-methylpropyl] pyrrolo [3,4-c] carbazole-, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -9-hydroxy-6 - [(2S) -3-hydroxy-2-methylpropyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione (314 ); 4- (2-chlorophenyl) -9-hydroxy-6- [2- (1 H-1, 2,4-triazol-5-ylsulfinyl) ethyl] pyrrolo [3,4-c] carbazole-1, 3- ( 2H, 6H) -dione; 4- (2-chlorophenyl) -9-hydroxy-6- [2- (1 H-1, 2,4-triazol-5-ylsulfonyl) ethyl] pyrrolo [3,4-c] carbazole-1, 3- ( 2H, 6H) -dione; 4- (2-chlorophenyl) -9-hydroxy-6- [2- (1 H-imidazol-2-ylsulfanyl) ethyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -9-hydroxy-6- [2- (1 H -imidazol-2-ylsulfinyl) ethyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -9-hydroxy-6- [2- (1 H -imidazol-2-ylsulfonyl) ethyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -9-hydroxy-6- [2- (1 H -tetrazol-5-yl) ethyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -9-hydroxy-6- [2- (4H-1, 2,4-triazol-3-ylsulfanyl) ethyl] pyrrolo [3,4-c] carbazole-1, 3- (2H , 6H) -dione; 4- (2-chlorophenyl) -9-hydroxy-6- [2-hydroxy-3- (4- - - rox - r rox T met am not prop p rro or -c car azo -, ^ 6 H) -dione ( 284); 4- (2-chlorophenyl) -9-hydroxy-6- [3- (1 H-imidazol-1-yl) propyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -9-hydroxy-6- [3- (1 H -tetrazol-5-yl) propyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) - diona; 4- (2-chlorophenyl) -9-hydroxy-6- [3- (methylsulfanyl) propyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -9-hydroxy-6-isopropylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -9-hydroxy-6-methylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chlorophenyl) -9-Hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (3-Amino-2-cyanophenyl) -9- hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (3-Amhnophenol) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (3-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) butanonitrile (241); 4- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1 H) -yl) butanoic acid; 4- (4-Amino-2-bromophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (4-Amino-2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 6- (2-chloroethyl) -4- (2-chlorophenol) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 6- (3-Bromopropyl) -4- (2,6-dichlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione (233); 6- (3-Bromopropyl) -4- (2-chloro-6-methoxyphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 6- (3-Bromopropyl) -4- (2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 6-Acetyl-4- (2-chlorophenyl) -9-Hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 6-Butyl-4- (2-chlorophenyl) -9-Hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 9-Hydroxy-4- (2-hydroxyphenyl) pyrrolo [3,4-c] carbazole-, 3- (2H H) -done; , 9-Hydroxk4- - = - (2-iodophenyl) pyrro! Or [3,4-cc] carbazole-1,3 (2Hr-6H) -dione; 9-Hydroxy-4- (2-methoxyphenyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 9-Hydroxy-4- (2-nitrophenyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 9-Hydroxy-4- (3-thienyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 9-Hydroxy-4- (4-hydroxyphenyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 9-Hydroxy-4- [2- (methylsulfanyl) phenyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 9-Hydroxy-6- (2-hydroxyethyl) -4- (2-methoxyphenyl) pyrrolo [3) 4-c] carbazole-1, 3- (2H, 6H) -dione; 9-Hydroxy-6- (2-hydroxyethyl) -4-phenylpyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 9-Hydroxy-6- (3-hydroxypropyl) -4- (2-methoxyphenyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione (107); 9-Methoxy-4- (2-methoxy-5-nitrophenyl) -4,5,6,10c-tetrahydropyrrolo [3,4-c] carbazole-1, 3- (2H, 3aH) -d Ona; 3- (4- (2-chlorophenol) -9-Hydroxy-1,3-d -oxo-2,3-dihydrochloride [3,4-c] carbazole-6 ( 1 H) -yl) methyl propanoate (264); N- [3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) propanoyl] -2 - (dimethylamino) ethanesulfonamide; N- [3- (4- (2-chlorophenol) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) propanoyl] benzenesulfonamide; N- [3- (4- (2-chlorophenyl) -9-hydroxy-1,3-d-oxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -l ) propanoyl] methanesulfonamide; N- [4- (4- (2-chlorophenol) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) - l) butanoyl] benzenesulfonamide; N- [4- (4- (2-chlorophenyl) -9-hydroxyl-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -l) butanoyl] methanesulfonamide; 2- (9-Hydroxy-1,3-d-oxo-1, 2,3,6-tetrahydropyrrolo [3,4-c] carbazol-4-yl) benzonitrile; 3- (9-Hydroxy-1,3-dioxo-1, 2,3,6-tetrahydro-arolo [3,4-c] carbazol-4-yl) benzonyl ether; 4- (2,3-Dichlorophenol) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione (18); 4- (2-chloro-5-hydroxyphenyl) -9 ^ hydro ^^ 6H) -dione; 4- (2,6-D-bromo-phenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2,6-D-chloro-3-hydroxyphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2,6-D-chloro-4-hydroxyphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2,6-Dichlorophenol) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2,6-4- (2,6-Dimethylene) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; Dimethoxyphenyl ) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Acetyl-phenyl) -9-Hydroxy-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-aminophenyl) -9-hydroxypyrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Bromo-4-nitrophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-Bromophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chloro-3-hydroxyphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chloro-4-hydroxyphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chloro-4-nitrophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chloro-6-hydroxyphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-chloro-6-methoxyphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-Ethoxy-phenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (2-Ethylphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1 > 3 (2H, 6H) -dione; 4- (3-Amino-2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (3-Aminophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (3-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (4-Amino-2-bromophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (3-Amino-2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (4-Aminophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- (4-chlorophenyl) -9-hydroxy-pyrio [3,4-c] carbazole-1, 3- (2H, 6H) -dione;. 4- (5-Amho-2-methoxyphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 4- [1,1-Biphenyl] -2-yl-9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4-Furan-2-yl-9-hydroxy-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 9-Hydroxy-4- (2-hydroxyphenyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 9-Hydroxy-4- (2-iodophenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 9-Hydroxy-4- (2-methoxyphenyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 9-Hydroxy-4- (2-methylsulfanyl-phenol) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 9-Hydroxy-4- (2-nitrophenyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 9-Hydroxy-4- (2-thienyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 9-Hydroxy-4- (2-trifluoromethylene) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 9-Hydroxy-4- (3-hydroxy-4-methoxyphenyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 9-Hydroxy-4- (3-Hydroxymethyl-phenyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 9-Hydroxy-4- (3-Hydroxy-phenyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 9-Hydroxy-4- (3-hydroxyphenyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 9-Hydroxy-4- (3-nitrophenyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 9-Hydroxy-4- (3-thienyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 9-Hydroxy-4- (3-trifluoromethoxy-phenyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 9-Hydroxy-4- (4-hydroxylmethenyl) pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 9-Hydroxy-4- (4-hydroxy-phenyl) -pyrrolo [3,4-c] carbazole-, 3- (2H, 6H) -dione; 9-Hydroxy-4- (4-trifluoromethoxy-phenyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 9-Hydroxy-4- [2- (hydroxymethyl) phenyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 9-Hydroxy-4- [2- (methylsulfanyl) phenyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 9-Hydroxy-4- [2- (methylsuifinyl) phenyl] pyrrolo [3,4-c] carbazole-1, 3- (2H, 6H) -dione; 9-Hydroxy-4-m-tolyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 9-Hydroxy-4-o-tolyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-chlorophenyl) -7- (1,2-dihjdroxetij) -9-hydroxy-1 H- [1] benzofuro [3,2-e] isoindol-1, 3- (2H) -dione; 4- (2-chlorophenyl) -7-ethyl-9-hydroxy-1 H- [1] benzofuro [3,2-e] isoindol-1, 3- (2H) -dione; 4- (2-chlorophenyl) -8- [3- (dimethylamino) propoxy] -9-hydroxy-1 H- [1] benzofuro [3,2-e] isoindol-1,3 (2H) -dione; and 4- (2-chlorophenyl) -8-ethyl-9-hydroxy-1 H- [1] benzofuro [3,2-e] isoindol-1, 3- (2H) -dione; 4- (2-chlorophenyl) -9-hydroxy-1 H- [1] benzofuro [3,2-e] isoindol-1, 3- (2H) -dione; 4- (2-chlorophenyl) -9-hydroxy-8- (4-hydroxybutyl) -1 H- [1] benzofuro [3,2-e] isoindol-1, 3- (2H) -dione; 9-Hydroxy-4-phenyl-1 H- [1] benzofuro [3,2-e] isoindol-1, 3- (2H) -dione; 4- (2-chlorophenyl) -9-hydroxy-6-propylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 1,3-dioxo-4-phenyl-1, 2,3,6-tetrahydropyrrolo [3,4-c] carbazole-9-No dihydrogen phosphate; 2- (4- (2-Chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) acetamide; Acid 2-. { [3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1 H) -yl) propyl] amino} benzoic; 3- (4- (2,6-Dichlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) propanoic acid; 3- (4- (2-Chlorophenyl) -9- (formylamino) -1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) -N- [2 - (dimethylamino) ethyl] propanamide; 3- (4- (2-Chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) -N- (2,2 , 6,6-tetramethyl-4-piperidinyl); 3- (4- (2-Chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) -N- [2- ( 1 H-imidazol-5-yl) ethyl] propanamide; 3- (4- (2-Chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) -N- [2- ( dimethylamino) ethyl] -N-methylpropanamide; 3- (9-Amino-4- (2-chlorophenyl) -1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) -N- [2- ( dimethylamino) ethyl] propanamide; 3,9-Dihydroxy-4-phenyl-3,6-dihydropyrrolo [3,4-c] carbázol-1 (2H) -one; 3- [4- (2-Chlorophene |) -9-nitro-1,3-dioxo-2,3-dihydro-1 H -pyrrolo [3,4-c] carbazol-6-yl] -propionic acid; Acid 3-. { [3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -yl) propyl] amino } benzoic; 4- (2,6-dichlorophenyl) -6- [3- (dimethylamino) propyl] -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2,6-Diciorophenyl) -6-. { 3 - [(cis) -3,5-dimethylpiperazinyl] propyl} -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2,6-Dichlorophenyl) -8- [3- (dimethylamino) propoxy] -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2,6-Dichlorophenol) -8- [4- (dimethylamino) butyl] -9-hydroxy-6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) - diona; 4- (2,6-Dichlorophenol) -9-hydroxy-6- [2- (4-methyl-1-piperazinyl) ethyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H ) -diona; 4- (2,6-Dichlorophenol) -9-hydroxy-6- [2- (4-morpholinyl) etl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2,6-Dichlorophenyl) -9-hydroxy-6- [3- (1 H -amidazol-1-yl) propyl] pyrrolo [3,4-c] carbazole-1, 3 (2H, 6H) -dione; 4- (2,6-Dichlorophenyl) -9-hydroxy-6- [3- (4-methyl-1-piperazinyl) propyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -diona; 4- (2,6-Dichlorophenyl) -9-hydroxy-6- [3- (4-morpholinyl) propyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -done; 4- (2,6-Dichlorophenol) -9-hydroxy-6- [3- (dimethylammon) ethyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2,6-Dichlorophenyl) -9-hydroxy-6- [3- (methylamino) propyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2,6-Dichlorophenol) -9-hydroxy-6-methyl-8- [3- (methylamine) propoxy] pyrrolo [3,4-c] carbazole-1,3 (2H , 6H) -dione; 4- (2,6-Dichlorophenyl) -9-hydroxy-8- [4- (methylamino) butyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Bromophenyl) -8- [3- (dimethylamino) propoxy] -9-hydroxy-6-rnethylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Bromophenyl) -8- [3- (dimethylamino) propoxy] -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Bromophenyl) -8- [4- ^ dimethylamine monobutyl J-g-hydroxypyrrolotS ^ -cJcarb 4- (2- ~ Bromophenyl) -9-hydroxy-6-methyl-8- [3- (methylamino) propoxy] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Bromophenyl) -9-hydroxy-8- [3- (methylamino) propoxy] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Bromophenyl) -9-hydroxy-8- [4- (methylamino) butyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chloro-3-hydroxy-phenyl) -8- [4- (methylamino) butyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chloro-3-hydroxyphenyl) -9-fIuoro-6- (3-hydroxypropyl) -8- [4- (methylamino) buti] pyrrolo [3,4- c] carbazole-1, 3 (2H, 6H) -dione; 4- (2-Chloro-3-hydroxyphenyl) -9-fluoro-8- [3- (methylamino) propoxy] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chloro-3-hydroxyphenyl) -9-fluoro-8- [4- (methylamino) butyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chloro-6-methoxyphenyl) -6-. { 3- [cis-3,5-dimethylpiperazinyl] propyl} -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chloro-6-methoxyphenyl) -8- [3- (dimethylamino) propoxy] -9-hydroxy-6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chloro-6-methoxyphenyl) -8- [3- (dimethylamino) propoxy] -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chloro-6-methoxyphenyl) -8- [4- (dimethylamino) butii] -9-hydroxy-6-methylpyrrolo [3,4-c] carbazole-1,3 (2HH6H) -dione; 4- (2-Chloro-6-methoxyphenyl) -8- [4- (dimethylamino) butyl] -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chloro-6-methoxyphenyl) -9-hydroxy-6- [2- (4-morpholinyl) ethyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chloro-6-methoxyphenyl) -9-hydroxy-6-methyl-8- [3- (methylamino) propoxy] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chloro-6-methoxyphenyl) -9-hydroxy-8- [3- (methylamino) propoxy] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-chloro-6-methoxyphenyl) -9-hydroxy-8- [4- (methylamino) butyl] pyrrolo [3,4-c] c ^, 3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -1,9-dihydroxy-6- (3-hydroxypropyl) -1,6-dihydropyrrolo [3,4- c] carbazol-3 (2H) -one; 4- (2-Chlorophenyl) -3,9-dihydroxy-6- (3-hydroxypropyl) -3,6-dihydropyrrolo [3,4-c] carbazole-1 (2H) -one; 4- (2-chlorophenyl) -6- (3-hydroxypropyl) -1,3-dioxo-1, 2,3,6-tetrahydropyrrolo [3,4-c] carbazol-9-ylformamide; 4- (2-Chloro-phenyl) -6- (3-hydroxy-propyl) -8- (3-pyrrolidin-1-yl-propoxy) -6H-pyrrolo [3,4-c] carbazole-1, 3- diona; 4- (2-Chlorophenyl) -6- (3-hydroxypropyl) -8- [3- (methylamino) propoxy] pyrrolo [3,4- c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -6- (3-hydroxy-propyl) -8-methoxy-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chlorophenyl) -6- (3-hydroxy-propyl) -8-piperidin-3-yl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chlorophenyl) -6- (3-hydroxypropyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -6- [3- (cis-3,5-d-methyl-1-piperazinyl) -2-hydroxypropyl] -9-hydroxypyrrolo [3,4-c] carbazole-1, 3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -6- [3- (dimethylamino) -2-hydroxypropyl] -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -6- [3- (dimethylamino) propyl] -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -6-. { 3 - [(cis) -3,5-dimethylpiperazyl] lpropyl} -9-hydroxy-pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -6-. { 3- [cis-3,5-dimethylpiperazinyl] -3-oxopropyl} -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-chlorophenyl) -6-cyclopentyl-9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chloro-phenyl) -6-methyl-8- (4-methylamino-butyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -6-methyl-8- (4-pyrrolidin-1-yl-butyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chlorophenyl) -6-methyl-8 - [(1 E) -4- (methylamino) -l-butenyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -6-methyl-8- [3- (methylamino) propoxy] -1,3-dioxo-1, 2,3,6-tetrahydropyrrolo [3,4-] carbazbl-9 -formamide; 4- (2-Chlorophenyl) l-8- [3- (methylamino) propoxy] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-chlorophenyl) ) -6-methyl-8- [4- (methylamino) butoxy] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-chlorophenyl) -6-methyl-8 - [4- (methylamino) butyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-chloro-phenyl) -6-methyl-8-piperidin-3- iI-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-chloro-phenyl) -6-methyl-8-piperidin-4-yl-6H-pyrrolo [3,4- c] carbazole-1,3-dione; 4- (2-chloro-phenyl) -6-methyl-8-piperidin-4-yl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chlorophenyl) -6-methyl-9- { [3- (1-piperidinyl) propyl] amino} pyrrolo [3,4- c] carbazole-1,3 (2H, 6H) - diona; 4- (2-Chlorophenyl) -6-methyl-9-. { [4- (methylamino) butyl] amino) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-chlorophenyl) -8- (1, 2-dihydroxyethyl) -6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -8- (2,3-dihydroxypropoxy) -6-methylpyrrolo [3,4-c] carbazole-1, 3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -8- (2-hydroxyethoxy) -6-methylpyrrolo [3,4- c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -8- (2-hydroxyethyl) -6-methylpyrrolo [3,4- c] carbazole-1,3 (2H, 6H) -dione; 4- (2-chlorophenyl) -8- (3,4-dihydroxybutoxy) -6-methylpyrrolo [3,4-c] ca rbazol-1,3 (2H, 6H) -dione; 4- (2-Chloro-phenyl) -8- (3-diethylamino-propoxy) -9-hydroxy-6- (2-hydroxyethyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2- (chloro-phenyl) -8- (3-dimethylamino-propoxy) -6- (3-hydroxy-propyl) -6H-pyrrolo [3,4- c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -8- (3-dimethylamino-propoxy) -9-fluoro-6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -8- (3-dimethylamino-propoxy) -9-hydroxy-6- (3-hydroxypropyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-chlorophenyl) -8- (3-hydroxypropoxy) -6- [3- (methylamino) propyl] pyrrolo [3,4-c] carbazole-1, 3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -8- (3-hydroxypropoxy) -6-methylpyrrolo [3,4- | -| c] carbazole-1,3 (2H-6H) -dione; "4- (2-Chlorophenyl) -8- (3-hydroxy-propoxy) -9-methoxy-6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chloro-phenyl) ) -8- (4-dimethylamino-3-hydroxy-butoxy) -6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-chloro-phenyl) -8- (4-dimethylamino-butyl) -6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chlorophenyl) -8- (4-hydroxybutoxy) -6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -8- (4-hydroxybutyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chloro-phenyl) -8- (4-hydroxy-piperidin-3-yl) -6- (3-hydroxy-propyl) -2-aza-cyclopenta [c] fluorene-1,3-dione; 4- (2-Chloro-phenyl) -8- (4-hydroxy-piperidin-3-yl) -6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chlorophenyl) -8- (hydroxymethyl) -6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -8 - [(1 E) -4- (dimethylamino) -l-butenyl] -6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-chlorophenyl) -8 - [(1 E) -4- (methylamino) -1-butenyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -5-dione; 4- (2-Chlorophenyl) -8 - [(1 E) -4-hydroxy-1-butenyl] -6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -8 - [(1 E) -4-hydroxy-1-butenyl] pyrrolo [3,4- c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -8- [3- (cis-3,5-dimethyl-1-piperazinyl) propoxy] -6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) - diona; 4- (2- Chlorophenyl) -8- [3- (dimethylamino) propoxy] -6-methyl-1,3-dioxo-1, 2,3,6-tetrahydropyrrolo [3,4-c] carbazol-9-ylformamide; 4- (2-Chlorophenyl) -8- [3- (dimethylamino) propoxy] -6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2- Chlorophenyl) -8- [3- (dimethylamino) propoxy] -9-hydroxy-6- (2-hydroxyethyl) pyrrolo [3,4- c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -8- [3- (dimethylamino) propoxy] -9-hydroxy-6- (3-hydroxypropyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -8- [3- (dimethylamino) propoxy] -9-hydroxy-6-methylpyrrolo [3,4-c] carbazole-1, 3 (2H, 6H) -dione; = _ '* ~ ¾- (2-Chlorophenol) -8- [3- (dimethma hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-chlorophenyl) -8- [3- (dimethylamino) propoxy] -9-methoxy-6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-chlorophenyl) -8- [ 3- (methylamino) propoxy] -6- [3- (methylamino) propyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-chlorophenyl) -8- [ 3-hydroxy-4- (1-pyrrolidinyl) butoxy] -6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-chlorophenyl) -8- [3- hydroxy-4- (methylamino) butoxy] -6-methylpyrrolo [3,4- c] carbazole-1,3 (2H, 6H) -dione; 4- (2-chlorophenyl) -8- [4- (dimethylamino) - 3- hydroxybutoxy] -6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -8- [4- (dimethylamine) butanoyl] -9-hydroxyl-6-methy1rrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-chlorophenyl) -8- [4- (dimethyl Lamno) butyl] -6-methy1pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-chlorophenyl) -8- [4- (dimethylamino) butyl] -9-hydroxy-6- (2-hydroxyethyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-chlorophenyl) - 8- [4- (dimethylamino) butyl] -9-hydroxy-6- (3-hydroxypropyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -8- [4- (dimethylamino) butyl] -9-hydroxy-6- (3-hydroxypropyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -8- [4- (dimethylamino) butyl] -9-hydroxy-6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -8- [4- (dimethylamino) butyl] -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -8- [4- (methylamino) but N] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -8-. { [3- (dimethylamino) propyl] sulfinyl} -9-hydroxy-6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; and 4- (2-Chlorophenyl) -8-. { 3 - [(3,5-dimethylpiperazinyl] propoxy) -9-hydroxy-6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -8-ethyl-9-hydroxy-6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4 = (2-chloro-pentyl) -8-hydroxy-6- (3-hydroxyl-propyl) -6H-pyrrolq [3,4-c] c ^ 1,3-dione; 4- (2-Chlorophenyl) -8-hydroxy-6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -9- (hydroxymethyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -9- (trifluoromethyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -9- [1-hydroxy-2- (1-piperidinyl) ethyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -9- [1-hydroxy-2- (4-morpholinyl) ethyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -9- [1-hydroxy-2- (methylamino) ethyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -9- [2- (dimethylamino) -1-hydroxyethyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -9-. { [3- (1-piperidinyl) propyl] amino) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2- Chlorophenol) -9-. { [4- (dimethylammon) butyl] amino} -6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -9-fIuoro-6- (3-hydroxypropyl) -8- [4- ((methylamino) butyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) - diona; 4- (2-Chloro-phenyl) -9-fluoro-6-methyl-8- (3-methylamino-propoxy) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -9-fluoro-6-methyl-8- (3-pyrrolidin-1-N-propoxy) -6H-pyrrolo [3,4- c] carbazole-1,3-dione; 4- (2-Chlorophenyl) -9-fluoro-6-methyl-8- [3- (methylamino) propoxylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -9-10-fluoro-6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -9-fluoro-8- (3-hydroxypropoxy) -6- [3- (methylamino) propyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chloro-phenyl) -9-fluoro-8- (3-hydroxy-propoxy) -6-methyl-6H-pyrrolo [3,4- c] carbazole-1,3-dione; 4- (2-Chlorophenyl) -9-fluoro-8- (3-hydroxypropoxy) -6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -9-fluoro-8- (4-hydroxybutoxy) -6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chlorophenyl) - - 9-fluoro-8- [3- (methylamino) prop0xy] -6- [3- (methylamino) propyl] pyrrz ^^ c] carbazole-1,3 (2H, 6H) - diona; 4- (2-Chloro-phenyl) -9-fluoro-8-hydroxy-6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -9-fluoro-8-methoxy-6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chlorophenyl) -9-fluoropyrrolo [3,4-c] carbazole-1, 3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -9-hydroxy-6- (2,2,2-tnfluoroethyl) pyrrolo [3,4- c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chloro-phenyl) -9-hydroxy-6- (2-hydroxy-ethyl) -8- [3- (4-methyl-piperazin-1-yl) -propoxyl-6H-pyrrolo [3,4-c] ] carbazole-1,3-dione; 4- (2-Chlorophenyl) -9-hydroxy-6- (2-hydroxyethyl) -8- [3- (4-morpholinyl) propoxy] pyrrolo [3,4- c] carbazole-1,3 (2H, 6H) -diona; 4- (2-Chlorophenyl) -9-hydroxy-6- (2-hydroxyethyl) -8- [3- (methylamine) propoxy] pyrrolo [3,4-c] carbazole- 1, 3 (2H, 6H) -dione; 4- (2-Chlorophenol) -9-hydroxy-6- (2-hydroxyethyl) -8- [4- (methylamino) butyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -diona; 4- (2-Chlorophenol) -9-hydroxy-6- (2-phenylethyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -9-hydroxy-6- (2-propynyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -9-hydroxy-6- (3-hydroxypropyl) -4,5,6,10c-tetrahydropyrrolo [3,4-c] carbazole-1,3 (2H, 3aH) -dione; 4- (2-Chloro-phenyl) -9-hydroxy-6- (3-hydroxy-propyl) -8- (3-pyrrolidin-1-yl-propoxy) -6H-pyrrolo [3,4-c] ] carbazole-1,3-dione; 4- (2-Chlorophenyl) -9-hydroxy-6- (3-hydroxypropyl) -8- [3- (1-pyrrolidinyl) propoxy] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chloro-phenyl) -9-hydroxy-6- (3-hydroxy-propyl) -8- [3- (4-methylpi-c] carbazole-1,3-dione; Chlorophenol) -9-hydroxy-6- (3-hydroxypropyl) -8- [3- (methylamino) propoxy] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) - dione; 4- (2-chloro-phenyl) -9-hydroxy-6- (3-hydroxy-propyl) -8-piperidin-4-yl-6H-pyrrolo [3,4-c] carbazole- 1,3-dione; 4- (2-Chlorophenyl) -9-hydroxy-6- (4,4,4-trifluorobutyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; "-: '4 :-( 2-Clorophene) -9 ^ hydroxy-6 ^ 4-pentenyl) pyrro c] carbazole-1,3 (2H, 6H) -dione; 4- (2-chlorophenyl) -9 -hydroxy-6,8-bis (2-hydroxyethyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-chlorophenyl) -9-hydroxy- 6- [2- (1 H-imidazol-1-yl) ethyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-chlorophenyl) -9-hydroxy- 6- [2- (4-methyl-1-piperazinyl) ethyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-chlorophenyl) -9-hydroxy-6 - [2- (4-morpholinyl) ethyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-chlorophenyl) -9-hydroxy-6- [2 - (phenylsulfanyl) ethyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-chlorophenyl) -9- hdr oxy-6- [3- (4-meth1l-1-piperazinyl) propyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -9-hydroxy-6- [3- (4-morpholonyl) propyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -9-hydroxy-6- [3- (dimethylammono) ethyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -9-hydroxy-6- [3- (methylamino) propyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -9- hydroxy-6-isobutyl-pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -9- hydroxy-6-isopentyl-pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chloro-phenyl) -9- hydroxy-6-methyl-8- (4-morpholin-4-yl-butyl) -6H-pyrrolo [3,4-c] carbazole-1, 3-dione; 4- (2-Chlorophenyl) -9-hydroxy-6-methyl-8- [3- (1-pyrrolidinyl) propoxy] pyrrolo [3,4-c] carbazole-10 1.3 (2H, 6H )-Mrs; 4- (2-Chlorophene!) - 9-hydroxy-6-methyl-8- [3- (4-morpholinyl) propoxy] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -9-hydroxy-6-methyl-8- [3- (methylamino) propoxy] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chlorophenol) -9-hydroxy-6-methyl-8- [4- (methylamino) butanoyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -9-hydroxy-6-methyl-8- [4- (methylamino) butylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H )-Mrs; 4- (2-Chlorophenol) -9- -: hydroxy-6-methyl-8-. { [3- (methylamihdo) propyl] suifonyl) pyrrolo ^^ 1,3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -9-hydroxy-6-pentyl-pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chloro-phenyl) -9-hydroxy-7- (1-hydroxy-2-methylene-ethyl) -6-oxa-2-aza-cyclopenta [c] -fluorene- 1,3-dione; 4- (2-Chloro-phenyl) -9-hydroxy-7- (1-20-hydroxy-2-morpholin-4-yl-ethyl) -6-oxa-2-aza-cyclopenta [c] Fluorene-1, 3-dione; 4- (2-chloro-phenyl) -9-hydroxy-7- (1-hydroxy-2-piperazin-1-yl-ethyl) -6-oxa-2-aza-cyclopenta [c] fluorene- 1,3-dione; 4- (2-Chloro-phenyl) -9-hydroxy-7- [1-hydroxy-2- (2-methoxy-ethoxy) -etl] -6-oxa-2-aza-cyclopenta [c ] fluorene-1,3-dione; 4- (2-Chlorophenyl) -9-hydroxy-8- (2-hydroxyethyl) -6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-chloro-phenyl) -9-hydroxy-8- (4-hydroxy-butoxy) -6-methyl-6H-pyrrolo [3,4-c] carbazole-1, 3-dione; 4- (2-Chloro-phenyl) -9-hydroxy-8- (4-hydroxy-butyl) -6-methyl-6H-pyrrolo [3,4- c] carbazole-1,3-dione; 4- (2-Chlorophenyl) -9-hydroxy-8- [3-5 (methylamino) propoxy] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -done; 4- (2-Chlorophenyl) -9- hydroxy-8- [4- (1-pyrrolidinyl) butyl) -1 H- [1] benzofuro [3,2-e] isoindol-1,3 (2H) -diona; 4- (2-Chlorophenol) -9-hydroxy-8- [4- (1-pyrrolidinyl) butyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Chlorophenyl) -9-hydroxyl-8- [4- (methylamino) butyl] -6-propylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -Mrs; 4- (2-Chlorophenyl) -9-hydroxy-8- [4-0 (methylamino) butyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (2-Methoxyphenyl) -6-methyl-1,3-dioxo-1, 2,3,6-tetrahydropyrrolo [3,4-c] carbazole-9-lformamide; 4- (2-Methoxyphenyl) -6-methylene-9- (methylamino) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (3-Amino-2-chlorophenol) -9-fluoro-6- (3-hydroxypropyl) -8- [4- (methylamino) butyl] pyrrolo [3,4-c] carbazole-1, 3 (2H, 6 H) -done; 4- (3-Amino-2-5-chlorophenyl) -9-fluoro-8- [3- (methylamine) propoxy] pyrrolo [3,4-c] carbazole-1J3 (2H > 6H ) -_ .... diona; ^ 4- (3-methyl-2-c] orophenyl) -9-fluoro-8r [4-r (methylamino) butyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (5-Amino-2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- (5-Amino-2-methoxyphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 4- Acid. { [3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -l) propyl] amino} benzoic; 6- (2-Aminoethyl) -4- (2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 6- (2-Anilinoetyl) -4- (2,6-dichlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2HH6H) -dione; 6- (2-Anilinoethyl) -4- (2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 6- (3-Aminopropyl) -9-hydroxy-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 6- (3-Anilinopropyl) -4- (2,6-dichlorophenyl) -9-hydroxypyrrolo [3,4- c] carbazole-1,3 (2H, 6H) -dione; 6- (3-Anilinopropyl) -4- (2-chlorophenyl) -9- hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 6- (3-Anilinopropyl) -9-hydroxy-4-5-phenyl-pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 6- (3-Bromo-propyl) -4- (2-chloro-phenyl) -8- (3-dimethylamino-propoxy) -9-hydroxy-6H-pyrrolo [3,4-c] carbazole-1, 3- diona; 6- (3-Butenyl) -4- (2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 6- [3- (Benzylamino) propyl-9-hydroxy-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 6- [3- (Diethylamino) propyl] -9-hydroxy-4-phenylpyrrolo [3,4-c] carbazole-1, 3 (2H, 6H) -dione; 6- [6- (Dimethylamino) hexyl] -9-hydroxy-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 6-Allyl-4- (2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 6-Benzyl-4- (2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 6-Butyl-4- (2,6-dichlorophenyl) -8- [3- (dimethylamino) propoxyl-9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 6- 15-Butyl-4- (2,6-dichlorophenyl) -8- [4- (dimethylN-butyl) butyl] -9-hydroxypyrrolo [3,4- - - c] carbazok1, 3 (2M, 6H) -dioria; ~ 'e-Butyl-4- (2,6-dichlorophenyl) -9-hydroxy-8- [3- (methylamino) propoxy] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H ) -diona; 6-Butyl-4- (2,6-dichlorophenyl) -9-hydroxy-8- [4- (methylamino) butyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 6-Butyl-4- (2-chloro-6-methoxyphenyl) -8- [3- (dimethylamino) propoxy] -9- 20 hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 6-Butyl-4- (2-chloro-6-methoxyphenyl) -8- [4- (dimethylamino) butyl] -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 6-Butyl-4- (2-chloro-6-methoxyphenyl) -9-hydroxy-8- [3- (methylamino) propoxy] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 6-Butyl-4- (2-chlorophenyl) -8- [3- (di-methyl-amino) -propoxy] -9-hydroxy-pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) - diona; 6-Butyl-4- (2-chlorophenyl) -8- [4- (dimethylamine) butyl] -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) - diona; 6-Butyl-4- (2-chlorophenyl) -9-hydroxy-8- [3- (methylamino) propoxy] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 6- Butyl-4- (2-chlorophenyl) -9-hydroxy-8- [4- (1-pyrrolidinyl) butyl] pyrrolo [3,4-c] carbazole-, 3 (2H, 6H) -dione; 6-sec-Butyl-4- (2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 7- (2-Amino-1-hydroxy-ethyl) -4- (2-chlorophenyl) -6-oxa-2-aza-cyclopenta [c] fluorene-1,3-dione; 7- (2-Amino-1-hydroxy-ethyl) -4- (2-chlorophenyl) -9- hydroxy-6-oxa-2-aza- [Cl-fidoren-1,3-dione; 8- (1-Aminomethyl-2-hydroxy-ethyl) -4- (2-c-orophenyl) -6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 8- (2,3-Dihydroxypropyl) -9- hydroxyl-6-methyl-4-phenylfronium [3,4-c] carbazole-1,3 (2H, 6H) -dione; 8- (4-Aminobutyl) -4- (2-chlorophenyl) -9-hydroxy-1 H- [l] benzofuro [3,2-e] isoindol-1,3 (2H) -dione; 8- (4-Aminobutyl) -4- (2-chlorophenyl) -9-hydroxy-6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) - diona; 8- (4-Aminobutyl) -4- (2-chlorophenol) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 8- [2- (D-methylamino) etl] -9-hydroxy-6-methyl-4-phenyl-pyrrolo [3,4-, r-c] carbazole-1, 3 (2H; 6H )-Mrs; ~ 8- [3- ^ methylamino) propoxyll-9-hydroxyw6-methyl-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 8- [3- (Dimethylamino) propyl] -9-hydroxy-6-methyl-4-phenylfrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 8-. { 3- [Bis- (2-hydroxy-ethyl) -amino] -propoxy} -4- (2-chlorophenyl) -9-hydroxy-6-methyl-6H-pyrrolo [3,4- c] carbazole-1,3-dione; 8-Ethyl-9-hydroxy-6-methyl-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 8-Hydroxy-4-phenylcyclopenta [c] carbazole-1,3 (2H, 6H) -dione; 9- (2-Amino-1-hydroxyethyl) -4- (2-chlorophenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 9-Amino-4- (2-chlorophenyl) -6- (3-hydroxy-propyl) -6H-pyrrolo [3,4-c] carbazole-1, 3-dione; 9-Amino-4- (2-chlorophenyl) -6- (3-hydroxypropyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 9-Hydroxy-4- (2-hydroxy-phenyl) -6- (3-hydroxypropyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 9-Hydroxy-4- (2-methoxyphenyl) -6- [2- (4-morpholinyl) ethyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) - diona; 9-Hydroxy-4,5-diphenyl-pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 9-Hydroxy-4-phenyl-6- [3- (1-p-piperazinyl) propyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 9-Hydroxy-4-phenyl-6- [3- (1-piperidinyl) propyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 9-Hydroxy-4-phenyl-6- [3- (1-pyrrolidinyl) propyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -done; 9-Hydroxy-5-methyl-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 9-Hydroxy-6- (3-hydroxypropyl) -4-phenolyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 9-Hydroxy-6- (6-hydroxyhexyl) -4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 9-Hydroxy-6- [2- (1 H -methazol-1-yl) ethyl] -4-phenol-pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -diona; 9-Hydroxy-6- [2- (4-morpholinyl) ethyl] -4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 9-Hydroxy-6- [2- (methylamino) ethyl] -4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 9-Hydroxy-6- [3- (1 H-imidazol-1-yl) propyl] -4-phenyl-pyroolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 9-Hydroxy-6- [3- (4-methyl-1-piperazinyl) pro] 1,3 (2H, 6H) -dione; 9-Hydroxy-6- [3- (4-morpholinyl) propyl] -4-phenol-pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 9-Hydroxy-6- [3- (methylamino) propyl] -4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 9-Hydroxy-6- [6- (4-methyl-1-p¡perazinyl) hexyl] -4-phenypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 9-Hydroxy-6-methyl-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H) 6H) -dione; 9-Hydroxy-8- (2-hydroxyethyl) -6-methyl-4-phenypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; 9-Hydroxy-8- (3-hydroxypropyl) -6-methyl-4-phenylfrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione; N- [2- (Dimethylamine) etl] -3- (9-hydroxy-1,3-dioxo-4-phenyl-2,3-dydrohydrolo [3,4- c] carbazole-6 (1 H) -N) propanamide; N- [2- (Dimethylamino) ethyl] -3- (9-hydroxy-4- (2-methoxyphenyl) -1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1 H) -l) propanamide; N- [4- (2-Chlorophenyl) -6- (3-hydroxy-propyl) -1,3-d-oxo-1, 2,3,6-tetrahydro-pyrrolo [3,4- 5 c] carbazole-9-yl] -formamide; and 6- (2-Aminoethyl) -9-hydroxy-4-phenylfrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione.
15. The compounds: 4- (4-Amino-2-methoxy-phenyl) -9-hydroxy-6H-pyrrolo [3,4-c] carbazole-1,3-dione; N- [4- (2-Chloro-phenyl) -1,3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazol-9-yl] -acetamide; N- [4- (2-Chloro-phenyl) -6-methyl-l, l, 3-dioxo-l, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazol-9-yl] -4 -dimethylamino-butyramide; 4- (2-Chloro-phenyl) -9-methylamino-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 9-Hydroxy-4- (2-methoxy-4-nitro-phenyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-chloro-phenyl) -9-hydroxy-8- (4-morpholin-4-yl-butyl) -6H-pyrrolo [3,4-c] carbazole-1, 3-dione; hydrochloride salt; 4- (2-Chloro-phenyl) -8- [3- (3,5-dimethyl-piperazin-1-yl) -15-propoxy] -9-hydroxy-6-methyl-6H-pyrrolo [3,4-c] ] carbazole-1,3-dione; 4- (2-Chloro-phenyl) - - r 9-hydroxy-8- (3-hydroxy-propoxy) -6-methyl-6H-pyrrole [3,4-c] carb 4- (2-chloro- phenyl) -8- (4-hydroxy-butoxy) -6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -8- (3,4-dihydroxy-butoxy) -6-methyl-6H-pyrrolo [3,4-c] carbazole-1, 3-dione; 4- (2-Chloro-phenyl) -6-methyl-8- (4-methylamino-butoxy) -6H-pyrrolo [3,4-20 c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -1,3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole-9-yl ester of acetic acid; 4- (2-Chloro-phenyl) -9-hydroxy-8- (4-methylamino-butyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 2- (9-Hydroxy-1,3-dioxo-1,2- (3,6-tetrahydro-pyrrolo [3,4-c] carbazol-4-yl) -benzamide; 4- (2-chloro-phenyl) - 6- methyl-8-piperidn-3-yl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 8- (3-amino-pyrrolidin-1-carbonyl) ) -4- (2-chloro-phenyl) -6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; hydrochloride salt; 4- (2-chloro-phenyl) -9 -pyridin-2-yl-6 H -pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-chloro-phenyl) -9-pyridin-4-yl-6H-pyrrolo [3, 4-c] carbazole-1,3-dione; 4- (2-chloro-phenyl) -8- (3-dimethylamino-propoxy) -9-hydroxy-6- (2-hydroxy-ethyl) -6H-pyrrolo c ] carbazole-1,3-dione; 4- (2-chloro-phenyl) -6-methyl-9-pyridin-2-yl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; - (2-Chloro-phenyl) -9-hydroxy-6- (2-hydroxy-ethyl) -8- (3-pyrrolidin-1-yl-propoxy) -6H-pyrrolo [3,4-c] carbazole -1, 3-dione; N- [4- (2-Chloro-phenyl) -1,3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole-9-yl] -3-piperidin-1-yl-propionamide; 4- (2-chloro-phenyl) -9-hydroxy-6-methyl-8- (3-methylamino-propoxy) -6H-pyrrolo [3,4-c] carbazole -1, 3-dione; 4- (2-Chloro-phenyl) -8- (4-hydroxy-but-1-enyl) -6-methyl-6 H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -8- (4-hydroxy-butyl) -6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -8- (3-dimethylamino-propoxy) -9-hydroxy-6- (3-hydroxy-propyl) -6H-pyrrolo [3,4-c] carbazole-1, 3- diona; 6- (3-Bromo-propyl) -4- (2-chloro-phenyl) -8- (3-d-methylammon-propoxy) -9-hydroxy-6H-pyrrolo [3,4-c] carbazole- 1-3-dione; -4- (2-Chloro-feriyl) -8- (4-dimethylamino-3-hydroxy-butoxy) -6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; hydrochloride salt; 4- (2-Chloro-phenyl) -8-hydroxy-6- (3-hydroxy-propyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -8- (4A-dimethylamino-butyl) -6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -6-methyl-8- (4-pyrrolidin-1-yl-butyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -6-methyl-8- (4-methylamino-butyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -9-hydroxy-6- (3-hydroxy-propyl) -8- (3-pyrrolidin-1-yl-propoxy) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -8- [3- (3,5-dimethyl-piperazin-1-yl) -propoxy] -9-hydroxy-6- (3-hydroxy-propyl) - 6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -9-hydroxy-8- (4-hydroxy-butyl) -6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 8-3- [Bis- (2-hydroxy-ethyl) -amino] -propoxy} -4- (2-Chloro-phenyl) -9-hydroxy-6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -9- hydroxy-6- (3-hydroxy-propyl) -8- [3- (4-methyl-piperazin-1-yl) -propoxy] -6H- pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -6- (3-hydroxy-propyl) -9-nitro-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 9-Amino-4- (2-chloro-phenyl) -6- (3-hydroxy-propyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 3- [4- (2-Chloro-phenyl) -9-nitro-1,3-d-oxo-2,3-dihydro-1 H -pyrrolo [3,4-c] carbazol-6-yl] - acid propionic; 4- (2-Chloro-phenyl) -9- hydroxy-8- (4-hydroxy-butoxy) -6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-chloro-phenyl) -6- (3-hydroxy-propyl) -8-methoxy-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -9-fluoro-8-methoxy-6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -9-fluoro-8-hydroxy-6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -8- (3-dimethylamino-propoxy) -6- (3-hydroxy-propyl) -6H-pyrrolo [3,4- c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -6- (3-hydroxy-propyl) -8- (3-pyrrolidin-1-yl-- - propoxyJ-eH-pyrrolop ^ -chlorcarbazole-1. ^ Ione ";" 4 - (2-Chloro-phenyl) -9; fluoro-8 - (3-hydroxy-propoxy) -6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; -Chloro-phenyl) -9- fluoro-6-methyl-8- (3-methylamino-propoxy) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-chloro phenyl) -9-hydroxy-6-methyl-8- (4-morpholin-4-yl-butyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; Chloro-phenyl) -9-fluoro-6-methyl-8- (3-pyrrolidin-1-yl-propoxy) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; - (2-Chloro-phenyl) -9-hydroxy-6- (2-hydroxy-ethyl) -8- [3- (4-methyl-piperazin-1-yl) -propoxy] -6H-pyrrolo [ 3,4-c] carbazole-1, 3-dione; 4- (2-chloro-phenyl) -8- (3-diethylamino-propoxy) -9-hydroxy-6- (2-hydroxy-ethyl) - 6H- pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-chloro-phenyl) -8- (3-dimethylamino-propoxy) -9-fluoro-6-methyl-6H-pyrrolo [ 3,4-c] carbazole-1,3-dione; N- [4- (2-chloro-phenyl) -6- (3-hydroxy-propyl) -1-methylene-3-oxo-1, 2,3 , 6-tetrahydropyrrolo [3,4-c] carbazol-9-yl] -formamide; 4- (2-Chloro-phenyl) -6-me til-8-pyridin-4-yl-6 H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -9-hydroxy-6- (3-hydroxy-propyl) -8-piperidin-4-yl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 8- (3- (R) -Amino-pyrrolidine-1 -carbonyl) -4- (2-chloro-phenyl) -6-methyl-6H-pyrrolo [3,4-c] carbazole-1, 3- Mrs; Hydrochloride salt; 8- (3- (S) Amino-pyrrolidine-1-carbonyl) -4- (2-chloro-phenyl) -6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; hydrochloride salt; 4- (2-Chloro-phenyl) -6-methyl-8-piperidin-4-yl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -6-methyl-8- (piperazine-1-carbonyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; hydrochloride salt; 4- (2-Chloro-phenyl) -8- (4-dimethylammon-butN) -9-hydroxy-6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -9-hydroxy-6-methyl-8- (4-pyrrolidin-1-yl-butyl) -6H-pyrrolo [3,4-c] carbazole- 1,3-dione; 4- (2-Chloro-phenyl) -9-hydroxy-6-methyl-8- (4-methylamino-butyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; [4- (2-Chloro-phenyl) -6-methyl-1,3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [3; 4-c] carbazol-9-yl-urea; "" 4- (2-Chloro-phenyl) -9-hydroxy-8- (3-hydroxy-2-methyl-propoxy) -6-methyl-6H-pyrrolo [3,4-c] carbazole-1, 3-dione; 4- (2-Chloro-phenyl) -8- (4-dimethylamino-butoxy) -9-hydroxy-6-methyl-6H-pyrrolo [3,4-c] carbazole-1-dione; 4- (2-Chloro-phenyl) -6- (3-methoxy-propyl) -8-piperidin-3-yl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; hydrochloride salt; 4- (2-Chloro-phenyl) -6- (3-hydroxy-propyl) -8- (3-methylamino-propoxy) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 9-Bromo-4- (2-chloro-phenyl) -6- (3-hydroxy-propyl) -8- (3-methylamino-propoxy) -6H-pyrrolo [3,4-c] carbazole-1, 3- diona; 4- [4- (2-Chloro-phenyl) -6-methyl-1,3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] tert-butyl ester ] carbazole-8-methyl] -piperidine-1-carboxylic acid; 4- (2-Chloro-phenyl) -6-methyl-8-piperidin-4-ylmethyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -6- (3-methoxy-propyl) -8-piperidin-4-yl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; hydrochloride salt; 4- (2-Chloro-phenyl) -6- (3-hydroxy-propyl) -8-piperidin-3-yl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; hydrochloride salt; 4- (2-Chloro-phenyl) -6- (3-hydroxy-propyl) -8-p -peridin-4-yl-6H-pyrrolo [3,4-c] carbazole-1, 3 -diona; hydrochloride salt; 4- (2-Chloro-phenyl) -6-methyl-8- (perhydro-1,4-diazepine-1-carbonyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; hydrochloride salt; 4- (2-Chloro-phenyl) -9-hydroxy-6-methyl-8- [4- (4-methyl-p-piperazin-1-yl) -butyl] -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -9-hydroxy-6-methyl-8- (4-pyrrolidin-1-yl-butoxy) -6H-pyrrolo [3,4-c] carbazole-1, 3- diona; 4- (2-Chloro-phenyl) -8- [4- (3,5-dimethyl-piperazin-1-yl) -butoxy] -9-hydroxy-6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -6-methyl-1,3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [2-dimethylamino-ethyl) -methyl amide [3,4-c] Carbazole-8-carboxylic acid; compound with trifluoroacetic acid; 8 - ((S) -3-Amino-pyrrolidine-1-carbonyl) -4- (2-chloro-phenyl) -6- (2-hydroxy-ethyl) -6H ^ irrolo [3,4-c] carbazl -1, 3-dioná; hydrobromide salt; 4- (2-Chloro-phenyl) -6- (2-hydroxy-ethyl) -8-piperidin-4-yl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; hydrobromide salt; 9-Amino-4- (2-chloro-phenyl) -6- (2-hydroxy-ethyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -9-hydroxy-6-methyl-8- [3- (4-methyl-piperazin-1-yl) -propoxy] -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 3- [9-Amino-4- (2-chloro-phenyl) -1,3-d-oxo-2,3-dihydro-1 H -pyrrolo [3,4-c] carbazol-6-yl] -N - (2-dimethylamino-ethyl) -propionamide; 3- [4- (2-Chloro-phenyl) -9-formylamino-1,3-dioxo-2,3-dihydro-1 H -pyrrolo [3,4-c] carbazol-6-yl] -N - (2-d-methylamino-ethyl) -propionamide; 9-Amino-4- (2-chloro-phenyl) -7-methoxy-6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 3- [4- (2-Chloro-phenyl) -9-hydroxy-1,3-dioxo-8- (3-pyrrolidin-1-yl-propoxy) -2,3-dihydro-1 H-pyrrolo [3,4-c] carbazol-6-yl] -propionamide; 4- (2-Chloro-phenyl) -6-methyl-8-pyrrolidin-3-yl-6H-pyrro! Or [3,4-c] carbazole-1,3-dione; trifluoroacetic acid salt; 4- (2-Chloro-phenyl) -6-methyl-1,3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole-8-carboxylic acid; N- [4- (2-Chloro-phenyl] -7-methoxy-6-methyl-1,3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole -9-yl] -formamide; 4- (2-Chloro-phenyl) -7-hydroxy-6-methyl-9-nitro-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -9-hydroxy-6-methyl-8- [2- (1-methyl-pyrrolidin-2-yl) -ethoxy] -6H-pyrrolo [3,4-c] ] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -9-hydroxy-6-methyl-8- [4- (4-methyl-piperazin-1-yl) -butoxy] -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -9-hydroxy-6-methyl-8- (4-morpholin-4-yl-butoxy) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; N- [4- (2-Chloro-phenyl) -6- (2-hydroxy-ethyl) -1, 3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole-9 -yl] -formamide; 4- (2-Fluoro-6-methoxy-phenyl) -9-hydroxy-6H-pyrrolo [3,4-c] carbazole-1,3-dione; N- [4- (2-Chloro-phenyl) -6- (3-hydroxy-propyl) -8-methoxy-1,3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] ] carbazol-9-yl] -acetamide; - N- [4- (2-Chloro-phenyl) -6- (3-hydroxy-propy) 8-methoxy-1 ^, 2,3,6-, tetrahydro-pyrrolo [3,4-c] carbazole- 9-yl] -formamide; N- [4- (2-Chloro-phenyl) -8-hydroxy-6- (3-hydroxy-propyl) -1, 3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] ] carbazol-9-yl] -formamide; 6-Butyl-4- (2-chloro-phenyl) -9-hydroxy-8- (3-pyrrolidin-1-H-propoxy) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 8- (3- (S) -Amino-pyrrolidine-1-carbonyl) -4- (2-chloro-phenyl) -6- (3-hydroxy-propyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -6-methyl-8-pyrrolidin-2-yl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 8- (4-Amino-butyl) -4- (2-chloro-phenyl) -6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; . { 3- [9-Amino-4- (2-chloro-phenyl) -1,3-dioxo-2,3-dihydro-1 H -pyrrolo [3,4-c] carbazol-6-yl] -propionyl} 2-dimethylamino-ethanesulfonic acid amide; . { 3- [4- (2-Chloro-phenyl) -9-formylamino-1,3-dioxo-2,3-dihydro-1 H -pyrroio [3,4-c] carbazol-6-yl] -propionyl} 2-dimethylamino-ethanesulfonic acid amide; 4- (2-Chloro-phenyl) -9-hydroxy-6-methyl-8- (2-methyl-3-pyrrolidin-1-H-propoxy) -6H-pyrrolo [3,4-c] carbazole- 1,3-dione; 4- (2-Chloro-phenyl) -9-hydroxy-8- (3-hydroxy-2,2-dimethyl-propoxy) -6-methyl-6H-pyrrolo [3,4-c] carbazole-1, 3- diona; 4- (2-Chloro-phenyl) -9-methoxy-6-methyl-1,3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole-8-carboxylic acid; 4- (2-Chloro-phenyl) -9-methoxy-6-methyl-1,3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole-8-carboxylic acid amide; 4- (2-Chloro-phenyl) -9-methoxy-6-methyl-1,3-dioxo-1, 2,3,6-tetrahydro- (2-pyrrolidin-1-yl-ethyl) -amide. pyrrolo [3,4-c] carbazole-8-carboxylic acid; 4- (2-chloro-phenyl) -9-hydroxy-6-methyl-1,3-d-oxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole acid -8-carboxylic acid; 4- (2-Chloro-phenyl) -9-hydroxy-6-methyl-1,3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole-8-carboxylic acid amide; 4- (2-Chloro-phenyl) -9-hydroxy-6-methyl-1,3-dioxo-1, 2,3,6-etrahdrone (2-pyrrolidin-2-yl-ethyl) -amide -pyrrolo [3,4-c] carbaz l-8-carboxylic; N- [4- (2-Chloro-pheny] -7-hydroxy-6-methyl-1,3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole- 9-yl] -formamide; 4- (2-Chloro-phenyl) -6- (2-hydroxy-ethyl) -1,3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole- methyl ester 8-carboxylic; 4- (2-Chloro-phenyl) -6-methyl-1,3-dioxo-1, 2,3,6-tetrahydro-pyrroloic acid (2-pyrrolidin-1-yl-ethyl) -amide [3,4 -c] carbazole-8-carboxylic acid; 3- [4- (2-Chloro-phenyl) -8- (3-dimethylamino-propoxy) -9-hydroxy-1,3-dioxo-2,3-dihydro-1 H-pyrrolo [3, 4-c] carbazol-6-yl] -propionamide; 4- (2-Chloro-phenyl) -8- [3- (ethyl-propyl-amino) -propylsulfanyl] -9-hydroxy-6-methyl-6H-pyrrolo [3,4-c] carbazole-1, 3- diona; 9-Hydroxy-6-methyl-4-phenyl-8- (3-pyrrolidol-1-yl-propoxy) -6H-pyrrolo [3,4-c] carbazole-1,3-d Ona; 9-Amino-4- (2-chloro-pheny1) -6-methyl-7-v1n1l-6H-pyrrolo [3,4-c] carbazole-1,3-di ona; 4- (2-Chloro-phenyl) -8- (3- (R) dimethylamino-pyrrolidine-1-carbonyl) -6- (2-hydroxy-ethyl) -6H-pyrrolo [3,4-c] ] carbazole-1,3-dione; N- [4- (2-Chloro-phenyl) -6-methyl-1,3-dioxo-7-vinyl-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole-9 -yl] -formamide; N- [4- (2-Chloro-phenyl] -7- (1,2-d-hydroxy-ethyl) -6-methyl-1,3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazol-9-yl] -formamide; N- [4- (2-Chloro-phenyl) -9-hydroxy-6-methyl-1,3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole-8-carbonyl ] -metanesuifonamide; [4- (2-Chloro-phenyl) -9-hydroxy-6-methyl-1,3-d-oxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole-8 -carbonyl] -2-dimethylamino-ethanesulfonic acid amide; Dimethylamide of 4- (2-chloro-phenyl) -9-hydroxy-6-methyl-1,3-d-oxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] ] carbazole-8-carboxylic acid; 4- (2-Chloro-phenyl) -9-hydroxy-8- (3-morpholin-4-yl-propoxy) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -9-hydroxy-6-methyl-8- (2-pyrrolidin-1-yl-ethoxy) -6H-pyrrolo [3,4-c] carbazole-1, 3- diona; 8- (3-Amino-propoxy) -4- (2-chloro-phenyl) -9-hydroxy-6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; hydrochloride; 4- (2-Chloro-phenyl) -9-hydroxy-6-methyl-8- (2-methyl-3-pyrrolidin-1-yl-propoxy) -6H-pyrrolo [3,4-c] carbazole -, 3-dione; 4- (2-Chloro-phenyl) -6-methyl-1,3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole (2-Diethylamino-ethyl) -amide -8-carboxylic acid; [3- (2-Chloro-phenyl) -6-methyl-1,3-dioxo-1, 2,3,6-tetrahydro [3- (4-methyl-piperazin-1-yl) -propyl] -amide] -pyrrolo [3,4-c] carbazole-8-carboxylic acid; 4- (2-Chloro-phenyl) -6-methyl-1,3-dioxo-1, 2,3,6-tetrahydro-pyrrolo acid (3-diethylamino-2-hydroxy-propyl) -amide [3,4 -c] carbazole-8-carboxylic acid; 4- (2-Chloro-phenyl) -6-methyl-1,3-dioxo-1, 2,3,6-tetrahydro-pyrrolo acid (3-pyrrolidin-1-yl-propyl) -amide [3,4 -c] carbazole-8-carboxylic acid; 4- (2-Chloro-phenyl) -8- (3- (S) -dimethylamino-pyrrolidine-1-carbonyl) -6- (2-hydroxy-ethyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; Trifluoroacetic acid salt; 4- (2-Chloro-phenyl) -6- (2-hydroxy-ethyl) -1,3-dioxo-1, 2,3,6- (2-pyrrolidin-1-yl-ethyl) -amide. tetrahydro-pyrrolo [3,4-c] carbazole-8-carboxylic acid; 4- (2-Chloro-phenyl) -6- (2-hydroxy-ethyl) -1,3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole acid amide -8- carboxylic acid; 4- (2-Chloro-phenyl) -8- (3-dimethylamino-propoxy) -9-hydroxy-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -9-hydroxy-8- [3- (4-methyl-piperazin-1-yl) -propoxy] -6H-pyrrolo [3,4-c] carbazole-1, 3-dione; 4- (2-Chloro-phenyl) -9-10-hydroxy-8- (3-pyrrolidin-1-yl-propoxy) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-chloro-phenyl) -9-hydroxy-6-methyl-8- (2-morpholin-4-yl-ethoxy) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -9-hydroxy-6-methyl-8- [2- (4-methyl-piperazin-1-yl) -ethoxy] -6H-pyrrolo [3,4-c] carbazole- 1,3-dione; N- [4- (2-Chloro-phenyl) -8-methoxy-6-methyl-1, 3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole-9-yl ] -formamide; 4- (2-Chloro-phenyl) -15-9-hydroxy-8- (3-hydroxy-propoxy) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; (2- (dimethylamino-ethyl) -methyl-amide "del1 4- (2-chloro-phenyl) -9-hydroxy-6-methyl-1, 3- d -oxo-1, 2,3,6- tetrahydro-pyrrolo [3,4-c] carbazole-8-carboxylic acid 4- (2-chloro-phenyl) -9-hydroxy-6-methyl (1- Ethyl-pyrrolidin-2-ylmethyl) -amide -1,3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole-8-carboxylic acid (3-diethylamino-propyl) -amide of 4- (2-chloro- phenyl) -9-hydroxy-6-methyl-1,3-d-oxo-1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole-8-carboxylic acid; 4- (2-chloro- phenyl) -9-hydroxy-6-methyl-8- (1H-tetrazol-5-yl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; [2- (1-ethyl-pyrrolidine 2- (2-Chloro-phenyl) -9-hydroxy-6-methyl-1,3-dioxo-1, 2,3,6-tetrahydro-pyrrolo acid [2-yl] -ethyl] -amide. 3,4- c] carbazole-8-carboxylic acid 4- (2-chloro-phenyl) -9-hydroxy-6- (2-hydroxy-ethyl) -8- { 3 - [( 2-hydroxy-ethyl) -methyl-amino] -propoxy-phenyl} -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-chloro-phenyl) - 9-hydroxy-8- { 3 - [(2-hydroxy-ethyl) -met-1-amino] -propoxy.] -6-methyl-6H-pyrrolo [3,4-c] carbazole- 1, 3-dione; 4- ( 2-Chloro-phenyl] -9-hydroxy-6- (2-hydroxy-ethyl) -8- (3-pipen'din-H-propoxy) -6H-pyrrolo [3,4-c ] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -9-hydroxy-6-methyl-8- (3-pperidin-1-yl-propoxy) -6H-pyrrolo [3,4-c] carbazole- 1,3-dione; 8- [3- (Benzyl-methyl-amine) -propoxy] -4- (2-chloro-phenyl) -9-hydroxy-6- (2-hydroxy-ethyl) -6H -pyrrolo [3,4-c] carbazole-1,3-dione; 8- [3- (Benzyl-methyl-amino) -propoxyl-4- (2-chloro-phenyl) -9-hydroxy-6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -9-hydroxy-6- (2-hydroxy-ethyl) -8- [3- (4-pyridin-2-yl-p-piperazin-1- L) -propoxy] -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -9-hydroxy-6-methyl-8- [3- (4-pyridin-2-yl-piperazin-1-yl) -propox ] -6 H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -8- (3-dipentylamino-propoxy) -9-hydroxy-6- (2-hydroxy-ethyl) -6H-pyrrolo [3,4-c] carbazole-1, 3-dione; 4- (2-Chloro-phenyl) -3- (3-d-pentylamino-propoxy-9-hydroxy-6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 2-Chloro-phenyl) -8- { 3 - [(2-dimethylamino-ethyl) -methyl-amino] -propoxy] -9-hydroxy-pyrrolo [3,4-c] carbazole- 1,3-dione; 4- (2-Chloro-phenyl) -8- { 3 - [(2-dimethylamino-ethyl) -methyl-amino] -propoxy.] -9-hydroxy-6-methyl- 6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-chloro-phenyl) -9-hydroxy-6- (2-hydroxy-ethyl) -8- [3- ( 3-hydroxy-pyrrolidin-1-yl) -propoxy] -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-chloro-phenyl) -9-hydroxy-8 - [3- (3-hydroxy-pyrrolidin-1-yl) -propoxy] -6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-chloro- phenyl) -8- [3- (cyclohexyl-methyl-amino) -propoxy] -9-hydroxy-6- (2-hydroxy-ethyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -8- [3- (cyclohexyl-methyl-amino) -propoxy] -9-hydroxy-6-methyl-6H-pyrrolo [3,4-c] carbazole-1, 3- d, 4- (2-chloro-phenyl) -9-hydroxy-6- (2-hydroxy-ethyl) -8- [3- (2-methyl-piperidin-1- il) -propox!] -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-chloro-phenyl) -9-hid Roxy-6-methyl-8- [3- (2-methyl-piperidin-1-yl) -propoxyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -9-hydroxy-6-5 (2-hydroxy-ethyl) -8- [3- (2-hydroxymethyl-piperidin-1-yl) -propoxy] -6H-pyrrolo [3 , 4- c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -9-hydroxy-8- [3- (2-hydroxymethyl-piperidin-1-yl) -propoxy] -6-methyl-6H-pyrrolo [3,4- c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -9- hydroxy-6- (2-hydroxy-ethyl) -8- [3- (methy1-pyridin-3-ylmethyl-amino) -propoxy ] -6H- pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -9-hydroxy-6-methyl-8- [3- (methyl-0-pyridin-3-ylmethyl-amino) -propoxy] -6H-pyrrolo [3,4-c] carbazole -1, 3-dione; 4- (2-Chloro-phenyl) -9-hydroxy-6- (2-hydroxy-ethyl) -8- [3- (2-hydroxymethyl-pyrrolidin-1-yl) -propoxy-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -9-hydroxy-8- [3- (2-hydroxymethyl-pyrrolidin-1-yl) -propoxy] -6-methyl-6H-pyrrolo [3,4-c] carbazole- 1,3-dione; 4- (2-Chloro-phenyl) -8- [3- (ethyl-methyl-amino) -propoxy] -9-hydroxy-6- (2-hydroxy-ethyl) -6H-pyrrolo [3,4-5 c] ] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -8- [3- (ethyl-methyl-amino) -propoxy] -9-hydroxy-6-methyl-6H-pyrrolo [3; 4-c] carbazole-f, 3-diode '"' 4- (2-Chloro-phenyl) -8- (3-dipropylamino-propoxy) -9-hydroxy-6- (2-hydroxy-ethyl) -6H-pyrrolo [3,4-c] ] carbazole-1, 3-dione; 4- (2-chloro-phenyl) -8- (3-dipropylamine-propoxy) -9-hydroxy-6-methyl-6H-pyrrolo [3,4-c] ] carbazol-1, 3-dione; 4- (2-Chloro-phenyl) -8- (3-diethylamino-propoxy) -9-0-hydroxy-6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; 8-. { 3- [Bis- (3-methyl-butyl) -amino] -propoxy) -4- (2-chloro-phenyl) -9-hydroxy-6-methyl-6H-pyrrolo [3,4-c] carbazole -1, 3- diona; 4- (2-Chloro-phenyl) -8- [3- (2,6-dimethyl-p -peridin-1-yl) -propoxy] -9-hydroxy-6- (2-hydroxy-ethyl) -6H- pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -8- [3- (2,6-d-methyl-piperidin-1-yl) -propoxy] -9-hydroxy-6-methyl-6H-p Rrolo [3,4-c] carbazol-1, 3-dione; 9-Hydroxy-6- (2-hydroxy-ethyl) -4-phenyl-8- (3-pyrrolidin-1-H-propoxy) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -8- (3-dicyclohexylamino-propoxy) -9-hydroxy-6- (2-hydroxy-ethyl) -6H-pyrrolo [3,4-c] carbazole-1, 3- diona; salt of trifluoroacetic acid; 4- (2-Chloro-phenyl) -8- (3-disopropylamino-propoxy) -9-hydroxy-6- (2-hydroxy-ethyl) -6H-pyrrolo [3,4-c] carbazole -1, 3-dione; trifluoroacetic acid salt; 9-Amino-4- (2-chloro-phenyl) -6-methyl-8- (3-pyrrolidin-1-yl-propoxy) -6H-pyrrolo [3,4-c] carbazole-1, 3-dione; N- [4- (2-Chloro-pheny] -6-methyl-1,3-dioxo-8- (3-pyrrolidin-1-yl-propoxy) -1, 2,3,6-tetrahydro-pyrrolo [3,4-c] carbazol-9-yl] -formamide; 4- (2-Chloro-phenyl) -9-hydroxy-6-methyl-1, 3-dioxo-1, 2,3,6-tetrahydro- (2-pyrrolidin-1-ethyl-ethyl) -amide pyrrolo [3,4-c] carbazole-8-sulfonyl; 4- (2-Chloro-phenyl) -8- (3-cydohexylamino-propoxy) -9-hydroxy-6-methyl-6H-pyrrolo [3,4-c] carbazo1-1, 3-dione; 4- (2-Chloro-phenyl) -9-hydroxy-6-methyl-8- (3-pyrrolidin-1-yl-propane-1-sulfinyl) -6 H -pyrrolo [3,4-c] carbazole-1 , 3-dione; 4- (2-Chloro-phenyl) -9-hydroxy-6-methyl-8- (3-pyrrolidin-1H-propane-1-sulfonyl) -6H-pyrrolo [3,4-c] carbazole-1 , 3-dione; 4- (2 - -. _ Chloro-phenyl) -9-hydroxy-6- (2-hydroxy-ethyl) -8- (4-pyrrolidin-1-yl-butyl) - ^ c] carbazole-1, 3 -diona; 4- (2-Chloro-phenyl) -9-hydroxy-6- (2-hydroxyethyl) -8- (4-morpholin-4-yl-butyl) -6H-pyrrolo [3,4- c] carbazole-1,3-dione; 4- (2-Chloro-phenyl) -9-hydroxy-6- (2-hydroxy-ethyl) -8- [4- (4-methyl-p-piperazin-1-yl) -butyl] -6H-pyrrolo [ 3,4-c] carbazol-1, 3- 20 dione; 4- (2-Chloro-phenyl) -8- [3- (etl-propyl-amino) -butoxy] -9-hydroxy-6-methyl-6H-pyrrolo [3,4-c] carbazole-1, 3-dione; 4- (2-Chloro-phenyl) -9-hydroxy-6-methyl-8- (1-methyl-3-pyrrolidin-1H-propoxy) -6H-pyrrolo [3,4-c] carbazole-1, 3-dione; 9-Amino-4- (2-chloro-phenyl) -8- (4-hydroxy-butyl) -6-methyl-pyrrolo [3,4-c] carbazole-1,3-dione; N- [4- (2-Chloro-phenyl) -6-methylene-1,3-dioxo-8- (4-pyrrolidin-1-yl-butyl) -1, 2,3,6-tetrahydro -pyrrolo [3,4-c] carbazol-9-yl] -formamide; N-. { 4- (2-Chloro-phenyl) -6-methyl-8- [4- (4-methyl-piperazin-1-yl) -butyl] -1,3-dioxo-1, 2,3,6- tetrahydro-pyrrolo [3,4-c] carbazole-9-yl} -fornriam¡da; N- [4- (2-Chloro-phenyl) -6-methyl-8- (4-morpholin-4-yl-butyl) -1, 3-d -oxo-1, 2,3 , 6-tetrahydro-pyrrolo [3,4-c] carbazol-9-yl] -formamide; 9-Amino-4- (2-chloro-phenyl) -7- (4-hydroxy-butyl) -6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; N- [4- (2-Chloro-pheny!) - 7- (4-hydroxy-butyl) -6-methylene-1,3-dioxo-1, 2,3,6-tetrahydro Rrolo [3,4-c] carbazol-9-yl] -formamide; N- [4- (2-Chloro-phenyl) -6-methyl-7- (4-morpholin-4-yl-butyl) -1, 3-dioxo-1, 2,3,6-tetrahydro -pyrrolo [3,4-c] carbazol-9-yl] -formamide; N-. { 4- (2-Chloro-phenyl) -6-methyl-7- [4- (4-methyl-piperazin-1-yl) -butl] -1,3-d -oxo-1, 2,3, 6-tetrahydro-pyrrolo [3,4-c] carbazol-9-yl} -formed; N- [4- (2-Chloro-phenyl] -7- (4-dimethylamino-butyl) -6-methyl-1,3-dioxo-1, 2,3,6-tetrahydro-pyrrolo [3 , 4-c] carbazol-9-yl] -formamide; N- [4- (2-Chloro-phenyl) -6-methyl-1,3-dioxo-7- (4-pyrrolidin-1-yl-butyl) -1, 2,3,6-tetrahydro - pyrrolo [3,4-c] carbazol-9-yl] formamide; 9-Amino-4- (2-chloro-phenyl) -6-methyl-7- (4-morpholin-4-yl-butyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; 9-Amino-4- (2-chloro-phe!) R6-meti-7- [4- (4-meti-piperazin-1r-1) -butl] -6Hzp Rrolo [3,4-c] carbazole-1, 4-dione; 9-Amino-4- (2-chloro-phenyl) -7- (4-dimethylamino-butyl) -6-methyl-6H-pyrrolo [3 c] carbazole-1,3-dione; and 9-Amino-4- (2-chloro-phenyl) -6-methyl-7- (4-pyrrolidin-1-yl-butyl) -6H-pyrrolo [3,4-c] carbazole-1 , 3-dione.