JP2006504632A - Inhibitors of checkpoint kinases (Wee1 and Chk1) - Google Patents

Abstract

The present invention relates to pyrrolocarbazole derivatives of formula (I). In the formula, R ¹ , R ² , r ⁷ , R ⁸ , R ⁹ , X and Y are as defined in the present specification. Said derivative specifically inhibits one or both of the checkpoint kinases Wee1 and Chk1.

Description

  The present invention relates to small chemical molecules that specifically inhibit one or both of the checkpoint kinases Wee1 and Chk1.

Several intracellular signaling pathways are required to properly organize the steps necessary for cells to progress through the cell cycle in order. Many of these pathways utilize protein kinases to transmit critical signals at the appropriate time and intracellular location. Cell cycle kinases are natural enzymes involved in the regulation of the cell cycle that are generally divided into four parts: G ₁ (gap ₁ ), S (DNA synthesis), G ₂ (gap 2) and M (mitosis). It is. Some of these kinases are responsible for inhibiting the normal progression of cells through cell division, while other kinases usually promote cell progression through the cell cycle leading to cell division. It is effective for. Increased or transient abnormal activation of these kinases has been found to cause tumors and other proliferative disorders.

One type of related protein kinase is the tyrosine-specific kinase Wee1, which has another kinase complex called Cdc2 / cyclin B as its substrate. Wee1 kinase is a regulatory kinase with Cdc2 / cyclin B as its substrate, and when Wee1 is active, it phosphorylates a specific tyrosine (Tyr15) on Cdc2 to inactivate the Cdc2 / cyclin B complex. It is, thereby resulting in a pause or checkpoint in G ₂ and M transition phases of the cell cycle. Cdc2 / kinase activity of cyclin B from cells G ₂ phase of the cell division cycle, M (or, mitosis) two daughter cells by division of the parent cell are formed absolutely necessary to proceed to phase is there. Under normal circumstances, as the cells progress fart cell cycle, Cdc2 / cyclin B complex is built through S Late and G ₂ phases. Usually, Wee1 is active, therefore, to phosphorylate Cdc2 / cyclin B complex to _{G 2} year period. The G ₂ end stage, all the necessary components for cells enter M phase are combined. Wee1 activity is then reduced and phosphatase removes the inhibitory phosphorylation of Tyr15 in Cdc2 / cyclin B, activating this complex. The cell enters the M phase and the replicating DNA divides to form daughter cells. When Wee1 is inhibited, the inhibitory phosphorylation of Cdc2 / cyclin B at Tyr15 does not occur and cells enter mitosis potentially inappropriately early.

  In addition to regulating the transition of cells between different phases of the normal cell cycle, cell cycle transition is regulated in response to DNA damage. This presumably gives the cell an opportunity to repair potentially genotoxic DNA damage before replication using the damaged DNA template occurs, or to permanently escape from the cell cycle and die.

  Another kinase of interest is called Chk1 and is involved in this signaling pathway that depends on DNA damage by phosphorylating a phosphatase called Cdc25C. Cdc25C is active in itself and coexists with Cdc2 / cyclin B in the nucleus to dephosphorylate Tyr15 and activate the Cdc2 / cyclin B complex. Cdc25C phosphorylation mediated by Chk1 is transported out of the nucleus when Cdc25C can no longer be dephosphorylated and therefore can no longer activate Cdc2 / cyclin B. Thus, if Chk1 is active (in response to DNA damage), its activity is required to proceed to M phase by maintaining phosphorylation that inactivates Tyr15 on Cdc2 / cyclin B ) Contributes indirectly to inactivate Cdc2 / cyclin B. Conversely, when Chk1 is inhibited, Cdc2 / cyclin B is dephosphorylated by the nuclear phosphatase Cdc25C (which is not phosphorylated by Chk1 and therefore not transported to the cytoplasm), resulting in activation of Cdc2 / cyclin B. The cells transition to mitosis.

  When Wee1 or Chk1 or both kinases are inhibited in the presence of conventional DNA-targeted chemotherapeutic agents or radiation-damaged DNA, cells are inappropriate using the cellular regulatory pathway And there is a possibility of proceeding to M period early. Since such cells enter M phase in the presence of potentially catastrophic damaged DNA, they are unlikely to survive and further divide (Alan J. Kraker and Robert N. Booher, “New Cell Cycle). Targets ", Ann. Rep. Med. Chem., 1999; 34: 247-256).

  Small molecule inhibitors of Wee1 kinase are described in WO0119825 and Cancer Res. (2001), 61 (22), 8211-8217. Small molecule inhibitors of Chk1 kinase are also described in WO0016781, Cancer Res. (2000), 60 (3), 566-572.

  Although pyrrolocarbazole derivatives are known to have inhibitory activity against protein kinase c and antitumor activity (US Pat. No. 4,912,107), compared to the compounds of the present invention, US Pat. , 107 have extremely low checkpoint kinase inhibitory activity (abrogator activity). It is also known that pyrrolocarbazole derivatives stimulate platelet production (WO 96/28447) and promote platelet formation (WO 9809967). EP 0 695 755 discloses another pyrrolocarbazole derivative having protein kinase c activity. US Pat. No. 5,166,204 discloses anti-tumor isoindole derivatives having a linking group or lower alkylene group attached to the 2- and 3-positions or the 3- and 4-positions of the carbazole skeleton. . US Pat. No. 5,728,709 discloses pyrrolocarbazole derivatives that stimulate platelet production. WO 01/85686 also discloses pyrrolocarbazole derivatives.

  However, no type of pyrrolocarbazole that inhibits Wee1 or Chk1 kinase has been reported. Furthermore, no type of pyrrolocarbazole that inhibits both Wee1 and Chk1 kinases has been reported.

  The claimed compounds have the general structure of Formula I.

式中、各破線は、結合を表わしてもよく、
Ｒ^１は、水素、ハロゲン、Ｃ_１〜Ｃ_８アルキル、ＮＲ^５Ｒ^６、または
ハロゲン、アルキル、ハロアルキル、ヒドロキシル、ニトロ、シアノ、Ｃ（Ｏ）Ｒ^３、ＯＲ^３、Ｓ（Ｏ）_ｍＲ^３、ＮＲ^３Ｒ^４、ＯＣ（Ｏ）Ｒ^３、ＮＲ^３（ＣＯ）ＯＲ^４、ＣＨ_２ＮＲ^３Ｒ^４、ＣＨ_２ＯＲ^３、ＣＯＯＲ^３、ＣＯＮＲ^３Ｒ^４、ＮＲ^３ＣＯＲ^４、ＳＯ_２ＮＲ^３Ｒ^４、ＣＯＮＨＳＯ_２Ｒ^３、ＮＲ^３Ｓ（Ｏ）_ｍＲ^４、ＮＨＣＯＮＲ^３Ｒ^４、ＮＲ^３ＣＯＮＨＲ^４から選択される最高５個の置換基で置換されていてもよいアリール環もしくはヘテロアリール環、または
ハロゲン、アルキル、ハロアルキル、ヒドロキシル、ニトロ、シアノ、Ｃ（Ｏ）Ｒ^３、ＯＲ^３、Ｓ（Ｏ）_ｍＲ^３、ＮＲ^３Ｒ^４、ＯＣ（Ｏ）Ｒ^３、ＮＲ^３（ＣＯ）ＯＲ^４、ＣＨ_２ＮＲ^３Ｒ^４、ＣＨ_２ＯＲ^３、ＣＯＯＲ^３、ＣＯＮＲ^３Ｒ^４、ＮＲ^３ＣＯＲ^４、ＳＯ_２ＮＲ^３Ｒ^４、ＣＯＮＨＳＯ_２Ｒ^３、ＮＲ^３Ｓ（Ｏ）_ｍＲ^４、ＮＨＣＯＮＲ^３Ｒ^４、ＮＲ^３ＣＯＮＨＲ^４から選択される最高５個の置換基で置換されていてもよいシクロアルキル環もしくはシクロアルケニル環、または
ハロゲン、アルキル、ハロアルキル、ヒドロキシル、ニトロ、シアノ、Ｃ（Ｏ）Ｒ^３、ＯＲ^３、Ｓ（Ｏ）_ｍＲ^３、ＮＲ^３Ｒ^４、ＯＣ（Ｏ）Ｒ^３、ＮＲ^３（ＣＯ）ＯＲ^４、ＣＨ_２ＮＲ^３Ｒ^４、ＣＨ_２ＯＲ^３、ＣＯＯＲ^３、ＣＯＮＲ^３Ｒ^４、ＮＲ^３ＣＯＲ^４、ＳＯ_２ＮＲ^３Ｒ^４、ＣＯＮＨＳＯ_２Ｒ^３、ＮＲ^３Ｓ（Ｏ）_ｍＲ^４、ＮＨＣＯＮＲ^３Ｒ^４、ＮＲ^３ＣＯＮＨＲ^４から選択される最高５個の置換基で置換されていてもよい複素環であり、
ｍは０〜２であり、
Ｘは水素またはハロゲンであり、
Ｙ^１はＯ、Ｓ（Ｏ）ｍまたはＮＲ^１０であり、
Ｒ^９は、水素、ヒドロキシル、ハロゲン、ＮＲ^３Ｃ（Ｏ）Ｒ^４、ＮＨＣＯＮＲ^３Ｒ^４、（Ｃ＝ＮＲ^３）ＮＨＲ^４、ＮＨ（Ｃ＝ＮＲ^３）ＮＨＲ^４、ＮＨ（Ｃ＝ＮＨ）ＮＲ^３Ｒ^４、ＮＨ（Ｃ＝Ｏ）ＯＲ^３、ＮＲ^５Ｒ^６、（ＣＲ^５Ｒ^６）_ｒ−Ｚであり、
ｒは０〜６であり、
Ｒ^２、Ｒ^７、Ｒ^８およびＲ^１０は、各場合において（（ＣＲ^５Ｒ^６）_ｎＴ）_ａ（ＣＲ^１１Ｒ^１２）_ｂ）−Ｚから独立に選択され、ｎ、ａおよびｂの合計は各場合において１０未満であり、
Ｔは存在しなくてもよく、存在するときには、各場合においてＯ、ＣＯＮＲ^３、ＣＯＮＨＳＯ_２、Ｓ（Ｏ）_ｍ、ＮＲ^３、ＮＲ^３Ｏ、ＯＳ（Ｏ）_ｍ、Ｓ（Ｏ）_ｍＯ、ＮＲ^３Ｓ（Ｏ）_２またはＳ（Ｏ）_２ＮＲ^３から独立に選択され、
ｎは、各場合において独立に０〜６であり、
ａは、各場合において独立に０〜６であり、
ｂは、各場合において独立に０〜６であり、
Ｚは、水素、ハロゲン、アルキル、ハロアルキル、シクロアルキル、シクロアルケニル、ヘテロシクリル（ｈｅｔｅｒｏｃｙｃｌｙｌ）、アリール、ヘテロアリール、シアノ、ニトロ、ヒドロキシ、Ｃ（Ｏ）Ｒ^３、ＣＯＮＨＳＯ_２Ｒ^３、ＯＲ^３、Ｓ（Ｏ）ｍＲ^３、ＯＳＯ_２Ｒ^３、ＮＲ^３Ｒ^４、ＣＯ_２Ｒ^３、ＣＯＮＲ^３Ｒ^４、ＮＲ^３ＣＯＲ^４、ＳＯ_２ＮＲ^３Ｒ^４、ＯＰＯ（ＯＲ^３）（ＯＲ^４）、ＣＨ＝ＣＲ^３Ｒ^４、ＣＣＲ^３、（Ｃ＝ＮＲ^３）ＮＨＲ^４、ＮＨ（Ｃ＝ＮＲ^３）ＮＨＲ^４、ＮＨ（Ｃ＝ＮＨ）ＮＲ^３Ｒ^４から選択され、前記アルキル、シクロアルキル、シクロアルケニル、ヘテロシクリル、アリールまたはヘテロアリール基は、ハロゲン、アルキル、ヒドロキシル、ニトロ、シアノ、ＯＲ^３、Ｓ（Ｏ）_ｍＲ^３、ＮＲ^３Ｒ^４、ＯＣ（Ｏ）Ｒ^３、ＮＲ^３（ＣＯ）ＯＲ^４、Ｃ（Ｏ）Ｒ^３、ＣＯＯＲ^３、ＣＯＮＲ^３Ｒ^４、ＮＲ^３ＣＯＲ^４、ＳＯ_２ＮＲ^３Ｒ^４、ＣＯＮＨＳＯ_２Ｒ^３、ＮＲ^３Ｓ（Ｏ）_ｍＲ^４、ＣＨ_２ＮＲ^３Ｒ^４、ＣＨ_２ＯＲ^３ＮＨＣＯＮＲ^３Ｒ^４、ＮＲ^３ＣＯＮＨＲ^４から独立に選択される最高４個の基で置換されていてもよく、
Ｒ^５、Ｒ^６、Ｒ^１１およびＲ^１２は、各場合において、水素、ヒドロキシル、アルキル、ハロアルキル、シクロアルキル、シクロアルケニル、アリール、ヘテロアリール、ヘテロシクリル、ハロゲン、シアノ、ニトロ、ＣＨ_２ＮＲ^３Ｒ^４、ＣＨ_２ＯＲ^３、Ｃ（Ｏ）Ｒ^３、ＯＲ^３、Ｓ（Ｏ）_ｍＲ^３、ＮＲ^３Ｒ^４、ＣＯＯＲ^３、ＣＯＮＲ^３Ｒ^４、ＳＯ_２ＮＲ^３Ｒ^４、ＮＨＣＯＮＲ^３Ｒ^４、ＮＲ^３ＣＯＮＨＲ^４から独立に選択され、
前記アルキル、ハロアルキル、シクロアルキル、シクロアルケニル、ヘテロシクリル、アリールまたはヘテロアリール基は、ハロゲン、アルキル、ヒドロキシル、ニトロ、シアノ、ＯＲ^３、Ｓ（Ｏ）_ｍＲ^３、ＮＲ^３Ｒ^４、ＯＣ（Ｏ）Ｒ^３、ＮＲ^３（ＣＯ）ＯＲ^４、Ｃ（Ｏ）Ｒ^３、ＣＯＯＲ^３、ＣＯＮＲ^３Ｒ^４、ＮＲ^３ＣＯＲ^４、ＳＯ_２ＮＲ^３Ｒ^４、ＣＯＮＨＳＯ_２Ｒ^３、ＮＲ^３Ｓ（Ｏ）_ｍＲ^４、ＮＨＣＯＮＲ^３Ｒ^４、ＮＲ^３ＣＯＮＨＲ^４から独立に選択される最高４個の基で置換されていてもよく、
Ｒ^５とＲ^６またはＲ^１１とＲ^１２は、これらが結合している炭素原子とともにカルボニル基を形成することができ、あるいはこれらが結合している炭素またはヘテラトムとともにシクロアルキル基またはヘテロシクリル基を形成することができ、前記カルボニル基、シクロアルキル基またはヘテロシクリル基は、ハロゲン、ヒドロキシル、ニトロ、シアノ、アルキル、ハロアルキル、ハロゲン、アルキル、ニトロ、シアノ、ＯＲ^３、Ｓ（Ｏ）_ｍＲ^３、ＮＲ^３Ｒ^４、ＯＣ（Ｏ）Ｒ^３、ＮＲ^３（ＣＯ）ＯＲ^４、Ｃ（Ｏ）Ｒ^３、ＣＯＯＲ^３、ＣＯＮＲ^３Ｒ^４、ＮＲ^３ＣＯＲ^４、ＳＯ_２ＮＲ^３Ｒ^４、ＣＯＮＨＳＯ_２Ｒ^３、ＮＲ^３Ｓ（Ｏ）_ｍＲ^４、ＮＨＣＯＮＲ^３Ｒ^４、ＮＲ^３ＣＯＮＨＲ^４から独立に選択される最高４個の基で置換されていてもよく、
Ｒ^３、Ｒ^４は、水素、アルキル、ハロアルキル、またはシクロアルキル、シクロアルケニル、ヘテロシクリル、アリールおよびヘテロアリールから選択される置換もしくは非置換炭素環式基から独立に選択され、前記アルキルまたは置換炭素環式基は、ハロゲン、ヒドロキシル、ニトロ、シアノ、アルキル、ハロアルキル、アルキルオキシ、カルボキシ、ＣＯＯＨ、ＣＯＮＨ_２、ＮＨＣＯＣＨ_３、Ｎ（ＣＨ_３）_２、ＮＨＣＨ_３、チオメチル、チオエチル、ＳＯＣＨ_３、ＳＯ_２ＣＨ_３から選択される最高４個の基で置換されていてもよく、
Ｒ^３とＲ^４は、これらが結合している炭素原子またはヘテロ原子とともに、ハロゲン、ヒドロキシル、ニトロ、シアノ、アルキル、ハロアルキル、アルキルオキシ、ホルミル、カルボキシ、アセチル、ＣＨ_２ＮＨ_２、ＣＨ_２ＯＨ、ＣＯＯＨ、ＣＯＮＨ_２、ＮＨＣＯＣＨ_３、Ｎ（ＣＨ_３）_２、チオメチル、チオエチル、ＳＯＣＨ_３、ＳＯ_２ＣＨ_３、アルコキシカルボニル、アルキルカルボニル、アルキニルアミノ、アミノアルキル、アミノアルキルカルボニル、アミノ、モノもしくはジアルキルアミノから独立に選択される最高４個の基で置換されたシクロアルキル基またはヘテロシクリル基を形成することができ、あるいは
Ｒ^３とＲ^４は、これらが結合している窒素とともに、３〜８個の員子を含む複素環を形成することができ、その員子のうち最高４個は、カルボニル基でも、酸素、硫黄、Ｓ（Ｏ）、Ｓ（Ｏ）_２および窒素から独立に選択されるヘテロ原子でもよく、前記炭素環式基は、置換されていないか、あるいはハロゲン、ヒドロキシ、ヒドロキシアルキル、アルキル、ハロアルキル、アルコキシ、アルコキシカルボニル、アルキルカルボニル、アルキニルアミノ、アミノアルキル、アミノアルキルカルボニル、アミノ、モノもしくはジアルキルアミノから独立に選択される最高４個の基で置換されている。

Where each dashed line may represent a bond,
R ¹ is hydrogen, halogen, C ₁ -C ₈ alkyl, NR ⁵ R ⁶ , or halogen, alkyl, haloalkyl, hydroxyl, nitro, cyano, C (O) R ³ , OR ³ , S (O) _m R ³ , NR ³ R ⁴ , OC (O) R ³ , NR ³ (CO) OR ⁴ , CH ₂ NR ³ R ⁴ , CH ₂ OR ³ , COOR ³ , CONR ³ R ⁴ , NR ³ COR ⁴ , SO ₂ NR ³ An aryl or heteroaryl ring optionally substituted with up to 5 substituents selected from R ⁴ , CONHSO ₂ R ³ , NR ³ S (O) _m R ⁴ , NHCONR ³ R ⁴ , NR ³ CONHR ⁴ Or halogen, alkyl, haloalkyl, hydroxyl, nitro, cyano, C (O) R ³ , OR ³ , S (O) _m R ³ , NR ³ R ⁴ , OC (O) R ³ , NR ³ (CO) OR ⁴ , CH ₂ NR ³ R ⁴ , CH ₂ OR ³ , COOR ³ , CONR ³ R ⁴ , NR ³ COR ⁴ , SO ₂ NR ³ R ⁴ , CONHSO ₂ R ³ , NR ³ S ( _{^{O) m R 4, NHCONR 3}} R 4, NR 3 CONHR up to five may be substituted with a substituent cycloalkyl ring or cycloalkenyl ring selected from ^4, or halogen, alkyl, haloalkyl, hydroxyl, nitro , Cyano, C (O) R ³ , OR ³ , S (O) _m R ³ , NR ³ R ⁴ , OC (O) R ³ , NR ³ (CO) OR ⁴ , CH ₂ NR ³ R ⁴ , CH ₂ ^{OR 3, COOR 3, CONR 3} R 4, NR 3 COR 4, SO 2 NR 3 R 4, CONHSO 2 R 3, NR 3 S (O) m R 4, NHCON A ³ R ^{4, NR 3} CONHR ⁴ up to five heterocyclic ring which may be substituted with a substituent selected from,
m is 0-2,
X is hydrogen or halogen;
Y ¹ is O, S (O) m or NR ¹⁰ ;
R ⁹ is hydrogen, hydroxyl, ^{halogen, NR 3 C (O) R} 4, NHCONR 3 R 4, (C = NR 3) NHR 4, NH (C = NR 3) NHR 4, NH (C = NH) NR ^{3 R 4, NH (C =} O) OR 3, NR 5 R 6, a _{^{(CR 5 R 6) r -Z}} ,
r is 0-6,
R ² , R ⁷ , R ⁸ and R ¹⁰ are in each case independently selected from ((CR ⁵ R ⁶ ) _n T) _a (CR ¹¹ R ¹² ) _b ) -Z, the sum of n, a and b Is less than 10 in each case,
T may not be present, and when present, in each case O, CONR ³ , CONHSO ₂ , S (O) _m , NR ³ , NR ³ O, OS (O) _m , S (O) _m O, Independently selected from NR ³ S (O) ₂ or S (O) ₂ NR ³ ;
n is independently 0 to 6 in each case;
a is independently 0 to 6 in each case;
b is independently 0 to 6 in each case;
Z is hydrogen, halogen, alkyl, haloalkyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, heteroaryl, cyano, nitro, hydroxy, C (O) R ³ , CONHSO ₂ R ³ , OR ³ , S ( _{^{O) mR 3, OSO 2 R}} 3, NR 3 R 4, CO 2 R 3, CONR 3 R 4, NR 3 COR 4, SO 2 NR 3 R 4, OPO (OR 3) (OR 4), CH = CR ³ R ^{4, CCR 3,} is selected from ^{(C = NR 3) NHR 4} , NH (C = NR 3) NHR 4, NH (C = NH) NR 3 R 4, said alkyl, cycloalkyl, cycloalkenyl, heterocyclyl , aryl or heteroaryl group, halogen, alkyl, hydroxyl, nitro, cyano, oR ^{3 _{S (O) m R 3,}} NR 3 R 4, OC (O) R 3, NR 3 (CO) OR 4, C (O) R 3, COOR 3, CONR 3 R 4, NR 3 COR 4, SO 2 Up to ^four independently selected from NR ³ R ⁴ , CONHSO ₂ R ³ , NR ³ S (O) _m R ⁴ , CH ₂ NR ³ R ⁴ , CH ₂ OR ³ NHCONR ³ R ⁴ , NR ³ CONHR ⁴ Optionally substituted with a group
R ⁵ , R ⁶ , R ¹¹ and R ¹² are in each case hydrogen, hydroxyl, alkyl, haloalkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, halogen, cyano, nitro, CH ₂ NR ³ R ⁴ , CH ₂ OR ³ , C (O) R ³ , OR ³ , S (O) _m R ³ , NR ³ R ⁴ , COOR ³ , CONR ³ R ⁴ , SO ₂ NR ³ R ⁴ , NHCONR ³ R ⁴ , NR ³ independently selected from ⁴ CONHR ⁴ ;
The alkyl, haloalkyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl or heteroaryl group is halogen, alkyl, hydroxyl, nitro, cyano, OR ³ , S (O) _m R ³ , NR ³ R ⁴ , OC (O) R ³ , NR ³ (CO) OR ⁴ , C (O) R ³ , COOR ³ , CONR ³ R ⁴ , NR ³ COR ⁴ , SO ₂ NR ³ R ⁴ , CONHSO ₂ R ³ , NR ³ S (O) _m Optionally substituted with up to 4 groups independently selected from R ⁴ , NHCONR ³ R ⁴ , NR ³ CONHR ⁴ ;
R ⁵ and R ⁶ or R ¹¹ and R ¹² can form a carbonyl group with the carbon atom to which they are bonded, or can form a cycloalkyl group or a heterocyclyl group with the carbon or heteratom to which they are bonded. The carbonyl group, cycloalkyl group or heterocyclyl group can be halogen, hydroxyl, nitro, cyano, alkyl, haloalkyl, halogen, alkyl, nitro, cyano, OR ³ , S (O) _m R ³ , NR ³ R ⁴ , OC (O) R ³ , NR ³ (CO) OR ⁴ , C (O) R ³ , COOR ³ , CONR ³ R ⁴ , NR ³ COR ⁴ , SO ₂ NR ³ R ⁴ , CONHSO ₂ R ³ , Independently selected from NR ³ S (O) _m R ⁴ , NHCONR ³ R ⁴ , and NR ³ CONHR ⁴ May be substituted with up to 4 groups,
R ³ , R ⁴ are independently selected from hydrogen, alkyl, haloalkyl, or a substituted or unsubstituted carbocyclic group selected from cycloalkyl, cycloalkenyl, heterocyclyl, aryl and heteroaryl, wherein the alkyl or substituted carbocycle Shikimoto is halogen, hydroxyl, nitro, cyano, alkyl, haloalkyl, alkyloxy, _{carboxy, COOH, CONH 2, NHCOCH 3} , N (CH 3) 2, NHCH 3, thiomethyl, _thioethyl, SOCH _{3, SO} 2 CH 3 May be substituted with up to 4 groups selected from
R ³ and R ⁴ together with the carbon atom or hetero atom to which they are attached, halogen, hydroxyl, nitro, cyano, alkyl, haloalkyl, alkyloxy, formyl, carboxy, acetyl, CH ₂ NH ₂ , CH ₂ OH, _{COOH, CONH 2, NHCOCH 3,} N (CH 3) 2, thiomethyl, _{thioethyl, SOCH 3, SO 2 CH 3} , alkoxycarbonyl, alkylcarbonyl, alkynyl, aminoalkyl, aminoalkylcarbonyl, amino, mono or dialkylamino Can form a cycloalkyl or heterocyclyl group substituted with up to four independently selected groups, or R ³ and R ⁴ together with the nitrogen to which they are attached, 3-8 members To form a heterocycle containing children And up to four of its members may be carbonyl groups or heteroatoms independently selected from oxygen, sulfur, S (O), S (O) ₂ and nitrogen, wherein the carbocyclic group is Up to 4 unsubstituted or independently selected from halogen, hydroxy, hydroxyalkyl, alkyl, haloalkyl, alkoxy, alkoxycarbonyl, alkylcarbonyl, alkynylamino, aminoalkyl, aminoalkylcarbonyl, amino, mono or dialkylamino Substituted with 1 group.

  Unless otherwise stated, throughout this specification and claims, the words “include”, “include”, etc. have a comprehensive meaning contrary to the exclusive or exhaustive meaning, ie, “include” But should not be construed as being limited thereto.

  The compounds of the present invention have the general structure of Formula I.

式中、各破線は、結合を表わしてもよく、
Ｒ^１は、水素、ハロゲン、Ｃ_１〜Ｃ_８アルキル、ＮＲ^５Ｒ^６、または
ハロゲン、アルキル、ハロアルキル、ヒドロキシル、ニトロ、シアノ、ＣＯＲ^３、ＯＲ^３、Ｓ（Ｏ）_ｍＲ^３、ＮＲ^３Ｒ^４、ＯＣ（Ｏ）Ｒ^３、ＮＲ^３（ＣＯ）ＯＲ^４、ＣＨ_２ＮＲ^３Ｒ^４、ＣＨ_２ＯＲ^３、ＣＯＯＲ^３、ＣＯＮＲ^３Ｒ^４、ＮＲ^３ＣＯＲ^４、ＳＯ_２ＮＲ^３Ｒ^４、ＣＯＮＨＳＯ_２Ｒ^３、ＮＲ^３Ｓ（Ｏ）_ｍＲ^４、ＮＨＣＯＮＲ^３Ｒ^４、ＮＲ^３ＣＯＮＨＲ^４から選択される最高５個の置換基で置換されていてもよいアリール環もしくはヘテロアリール環、または
ハロゲン、アルキル、ハロアルキル、ヒドロキシル、ニトロ、シアノ、Ｃ（Ｏ）Ｒ^３、ＯＲ^３、Ｓ（Ｏ）_ｍＲ^３、ＮＲ^３Ｒ^４、ＯＣ（Ｏ）Ｒ^３、ＮＲ^３（ＣＯ）ＯＲ^４、ＣＨ_２ＮＲ^３Ｒ^４、ＣＨ_２ＯＲ^３、ＣＯＯＲ^３、ＣＯＮＲ^３Ｒ^４、ＮＲ^３ＣＯＲ^４、ＳＯ_２ＮＲ^３Ｒ^４、ＣＯＮＨＳＯ_２Ｒ^３、ＮＲ^３Ｓ（Ｏ）_ｍＲ^４、ＮＨＣＯＮＲ^３Ｒ^４、ＮＲ^３ＣＯＮＨＲ^４から選択される最高５個の置換基で置換されていてもよいシクロアルキル環もしくはシクロアルケニル環、または
ハロゲン、アルキル、ハロアルキル、ヒドロキシル、ニトロ、シアノ、Ｃ（Ｏ）Ｒ^３、ＯＲ^３、Ｓ（Ｏ）_ｍＲ^３、ＮＲ^３Ｒ^４、ＯＣ（Ｏ）Ｒ^３、ＮＲ^３（ＣＯ）ＯＲ^４、ＣＨ_２ＮＲ^３Ｒ^４、ＣＨ_２ＯＲ^３、ＣＯＯＲ^３、ＣＯＮＲ^３Ｒ^４、ＮＲ^３ＣＯＲ^４、ＳＯ_２ＮＲ^３Ｒ^４、ＣＯＮＨＳＯ_２Ｒ^３、ＮＲ^３Ｓ（Ｏ）_ｍＲ^４、ＮＨＣＯＮＲ^３Ｒ^４、ＮＲ^３ＣＯＮＨＲ^４から選択される最高５個の置換基で置換されていてもよい複素環であり、
ｍは０〜２であり、
Ｘは水素またはハロゲンであり、
Ｙ^１はＯ、Ｓ（Ｏ）ｍまたはＮＲ^１０であり、
Ｒ^９は、水素、ヒドロキシル、ハロゲン、ＮＲ^３Ｃ（Ｏ）Ｒ^４、ＮＨＣＯＮＲ^３Ｒ^４、（Ｃ＝ＮＲ^３）ＮＨＲ^４、ＮＨ（Ｃ＝ＮＲ^３）ＮＨＲ^４、ＮＨ（Ｃ＝ＮＨ）ＮＲ^３Ｒ^４、ＮＨ（Ｃ＝Ｏ）ＯＲ^３、ＮＲ^５Ｒ^６、（ＣＲ^５Ｒ^６）_ｒ−Ｚであり、
ｒは０〜６であり、
Ｒ^２、Ｒ^７、Ｒ^８およびＲ^１０は、各場合において（（ＣＲ^５Ｒ^６）_ｎＴ）_ａ（ＣＲ^１１Ｒ^１２）_ｂ）−Ｚから独立に選択され、ｎ、ａおよびｂの合計は各場合において１０未満であり、
Ｔは存在しなくてもよく、存在するときには、各場合においてＯ、ＣＯＮＲ^３、ＣＯＮＨＳＯ_２、Ｓ（Ｏ）_ｍ、ＮＲ^３、ＮＲ^３−Ｏ、Ｏ−Ｓ（Ｏ）_ｍ、Ｓ（Ｏ）_ｍ−Ｏ、ＮＲ^３−Ｓ（Ｏ）_２またはＳ（Ｏ）_２−ＮＲ^３から独立に選択され、
ｎは、各場合において独立に０〜６であり、
ａは、各場合において独立に０〜６であり、
ｂは、各場合において独立に０〜６であり、
Ｚは、水素、ハロゲン、アルキル、ハロアルキル、シクロアルキル、シクロアルケニル、ヘテロシクリル、アリール、ヘテロアリール、シアノ、ニトロ、ヒドロキシ、ＣＯＲ^３、ＣＯＮＨＳＯ_２Ｒ^３、ＯＲ^３、Ｓ（Ｏ）ｍＲ^３、ＯＳＯ_２Ｒ^３、ＮＲ^３Ｒ^４、ＣＯ_２Ｒ^３、ＣＯＮＲ^３Ｒ^４、ＮＲ^３ＣＯＲ^４、ＳＯ_２ＮＲ^３Ｒ^４、ＯＰＯ（ＯＲ^３）（ＯＲ^４）、ＣＨ＝ＣＲ^３Ｒ^４、ＣＣＲ^３、（Ｃ＝ＮＲ^３）ＮＨＲ^４、ＮＨ（Ｃ＝ＮＲ^３）ＮＨＲ^４、ＮＨ（Ｃ＝ＮＨ）ＮＲ^３Ｒ^４から選択され、前記アルキル、シクロアルキル、シクロアルケニル、ヘテロシクリル、アリールまたはヘテロアリール基は、ハロゲン、アルキル、ヒドロキシル、ニトロ、シアノ、ＯＲ^３、Ｓ（Ｏ）_ｍＲ^３、ＮＲ^３Ｒ^４、ＯＣ（Ｏ）Ｒ^３、ＮＲ^３（ＣＯ）ＯＲ^４、Ｃ（Ｏ）Ｒ^３、ＣＯＯＲ^３、ＣＯＮＲ^３Ｒ^４、ＮＲ^３ＣＯＲ^４、ＳＯ_２ＮＲ^３Ｒ^４、ＣＯＮＨＳＯ_２Ｒ^３、ＮＲ^３Ｓ（Ｏ）_ｍＲ^４、ＣＨ_２ＮＲ^３Ｒ^４、ＣＨ_２ＯＲ^３ＮＨＣＯＮＲ^３Ｒ^４、ＮＲ^３ＣＯＮＨＲ^４から独立に選択される最高４個の基で置換されていてもよく、
Ｒ^５、Ｒ^６、Ｒ^１１およびＲ^１２は、各場合において、水素、ヒドロキシル、アルキル、ハロアルキル、シクロアルキル、シクロアルケニル、アリール、ヘテロアリール、ヘテロシクリル、ハロゲン、シアノ、ニトロ、ＣＨ_２ＮＲ^３Ｒ^４、ＣＨ_２ＯＲ^３、Ｃ（Ｏ）Ｒ^３、ＯＲ^３、Ｓ（Ｏ）_ｍＲ^３、ＮＲ^３Ｒ^４、ＣＯＯＲ^３、ＣＯＮＲ^３Ｒ^４、ＳＯ_２ＮＲ^３Ｒ^４、ＮＨＣＯＮＲ^３Ｒ^４、ＮＲ^３ＣＯＮＨＲ^４から独立に選択され、
前記アルキル、ハロアルキル、シクロアルキル、シクロアルケニル、ヘテロシクリル、アリールまたはヘテロアリール基は、ハロゲン、アルキル、ヒドロキシル、ニトロ、シアノ、ＯＲ^３、Ｓ（Ｏ）_ｍＲ^３、ＮＲ^３Ｒ^４、ＯＣ（Ｏ）Ｒ^３、ＮＲ^３（ＣＯ）ＯＲ^４、Ｃ（Ｏ）Ｒ^３、ＣＯＯＲ^３、ＣＯＮＲ^３Ｒ^４、ＮＲ^３ＣＯＲ^４、ＳＯ_２ＮＲ^３Ｒ^４、ＣＯＮＨＳＯ_２Ｒ^３、ＮＲ^３Ｓ（Ｏ）_ｍＲ^４、ＮＨＣＯＮＲ^３Ｒ^４、ＮＲ^３ＣＯＮＨＲ^４から独立に選択される最高４個の基で置換されていてもよく、
Ｒ^５とＲ^６またはＲ^１１とＲ^１２は、これらが結合している炭素原子とともにカルボニル基を形成することができ、あるいはこれらが結合している炭素またはヘテラトムとともにシクロアルキル基またはヘテロシクリル基を形成することができ、前記カルボニル基、シクロアルキル基またはヘテロシクリル基は、ハロゲン、ヒドロキシル、ニトロ、シアノ、アルキル、ハロアルキル、ハロゲン、アルキル、ニトロ、シアノ、ＯＲ^３、Ｓ（Ｏ）_ｍＲ^３、ＮＲ^３Ｒ^４、ＯＣ（Ｏ）Ｒ^３、ＮＲ^３（ＣＯ）ＯＲ^４、Ｃ（Ｏ）Ｒ^３、ＣＯＯＲ^３、ＣＯＮＲ^３Ｒ^４、ＮＲ^３ＣＯＲ^４、ＳＯ_２ＮＲ^３Ｒ^４、ＣＯＮＨＳＯ_２Ｒ^３、ＮＲ^３Ｓ（Ｏ）_ｍＲ^４、ＮＨＣＯＮＲ^３Ｒ^４、ＮＲ^３ＣＯＮＨＲ^４から独立に選択される最高４個の基で置換されていてもよく、
Ｒ^３、Ｒ^４は、水素、アルキル、ハロアルキル、またはシクロアルキル、シクロアルケニル、ヘテロシクリル、アリールおよびヘテロアリールから選択される置換もしくは非置換炭素環式基から独立に選択され、前記アルキルまたは置換炭素環式基は、ハロゲン、ヒドロキシル、ニトロ、シアノ、アルキル、ハロアルキル、アルキルオキシ、カルボキシ、ＣＯＯＨ、ＣＯＮＨ_２、ＮＨＣＯＣＨ_３、Ｎ（ＣＨ_３）_２、ＮＨＣＨ_３、チオメチル、チオエチル、ＳＯＣＨ_３、ＳＯ_２ＣＨ_３から選択される最高４個の基で置換されていてもよく、
Ｒ^３とＲ^４は、これらが結合している炭素原子またはヘテロ原子とともに、ハロゲン、ヒドロキシル、ニトロ、シアノ、アルキル、ハロアルキル、アルキルオキシ、ホルミル、カルボキシ、アセチル、ＣＨ_２ＮＨ_２、ＣＨ_２ＯＨ、ＣＯＯＨ、ＣＯＮＨ_２、ＮＨＣＯＣＨ_３、Ｎ（ＣＨ_３）_２、チオメチル、チオエチル、ＳＯＣＨ_３、ＳＯ_２ＣＨ_３、アルコキシカルボニル、アルキルカルボニル、アルキニルアミノ、アミノアルキル、アミノアルキルカルボニル、アミノ、モノもしくはジアルキルアミノから独立に選択される最高４個の基で置換されたシクロアルキル基またはヘテロシクリル基を形成することができ、あるいは
Ｒ^３とＲ^４は、これらが結合している窒素とともに、３〜８個の員子を含む複素環を形成することができ、その員子のうち最高４個は、カルボニル基でも、酸素、硫黄、Ｓ（Ｏ）、Ｓ（Ｏ）_２および窒素から独立に選択されるヘテロ原子でもよく、前記炭素環式基は、置換されていないか、あるいはハロゲン、ヒドロキシ、ヒドロキシアルキル、アルキル、ハロアルキル、アルコキシ、アルコキシカルボニル、アルキルカルボニル、アルキニルアミノ、アミノアルキル、アミノアルキルカルボニル、アミノ、モノもしくはジアルキルアミノから独立に選択される最高４個の基で置換されている。

Where each dashed line may represent a bond,
R ¹ is hydrogen, halogen, C ₁ -C ₈ alkyl, NR ⁵ R ⁶ , or halogen, alkyl, haloalkyl, hydroxyl, nitro, cyano, COR ³ , OR ³ , S (O) _m R ³ , NR ³ R ⁴ , OC (O) R ³ , NR ³ (CO) OR ⁴ , CH ₂ NR ³ R ⁴ , CH ₂ OR ³ , COOR ³ , CONR ³ R ⁴ , NR ³ COR ⁴ , SO ₂ NR ³ R ⁴ , CONHSO _An aryl or heteroaryl ring optionally substituted with up to 5 substituents selected from ₂ R ³ , NR ³ S (O) _m R ⁴ , NHCONR ³ R ⁴ , NR ³ CONHR ⁴ , or halogen; Alkyl, haloalkyl, hydroxyl, nitro, cyano, C (O) R ³ , OR ³ , S (O) _m R ³ , NR ³ R ⁴ , OC (O) R ³ , N R ³ (CO) OR ⁴ , CH ₂ NR ³ R ⁴ , CH ₂ OR ³ , COOR ³ , CONR ³ R ⁴ , NR ³ COR ⁴ , SO ₂ NR ³ R ⁴ , CONHSO ₂ R ³ , NR ³ S (O ) A cycloalkyl or cycloalkenyl ring optionally substituted with up to 5 substituents selected from _m R ⁴ , NHCONR ³ R ⁴ , NR ³ CONHR ⁴ , or halogen, alkyl, haloalkyl, hydroxyl, nitro, Cyano, C (O) R ³ , OR ³ , S (O) _m R ³ , NR ³ R ⁴ , OC (O) R ³ , NR ³ (CO) OR ⁴ , CH ₂ NR ³ R ⁴ , CH ₂ OR ³ , COOR ³ , CONR ³ R ⁴ , NR ³ COR ⁴ , SO ₂ NR ³ R ⁴ , CONHSO ₂ R ³ , NR ³ S (O) _m R ⁴ , NHCONR ³ A heterocyclic ring optionally substituted with up to 5 substituents selected from R ⁴ and NR ³ CONHR ⁴ ;
m is 0-2,
X is hydrogen or halogen;
Y ¹ is O, S (O) m or NR ¹⁰ ;
R ⁹ is hydrogen, hydroxyl, ^{halogen, NR 3 C (O) R} 4, NHCONR 3 R 4, (C = NR 3) NHR 4, NH (C = NR 3) NHR 4, NH (C = NH) NR ^{3 R 4, NH (C =} O) OR 3, NR 5 R 6, a _{^{(CR 5 R 6) r -Z}} ,
r is 0-6,
R ² , R ⁷ , R ⁸ and R ¹⁰ are in each case independently selected from ((CR ⁵ R ⁶ ) _n T) _a (CR ¹¹ R ¹² ) _b ) -Z, the sum of n, a and b Is less than 10 in each case,
T may not be present, and when present, in each case O, CONR ³ , CONHSO ₂ , S (O) _m , NR ³ , NR ³ —O, OS—S (O) _m , S (O) _m ^-O, is selected from NR 3 -S _{(O) 2} or _{S (O)} 2 -NR ³ independently,
n is independently 0 to 6 in each case;
a is independently 0 to 6 in each case;
b is independently 0 to 6 in each case;
Z is hydrogen, halogen, alkyl, haloalkyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, heteroaryl, cyano, nitro, hydroxy, COR ³ , CONHSO ₂ R ³ , OR ³ , S (O) mR ³ , OSO ₂ R ³ , NR ³ R ⁴ , CO ₂ R ³ , CONR ³ R ⁴ , NR ³ COR ⁴ , SO ₂ NR ³ R ⁴ , OPO (OR ³ ) (OR ⁴ ), CH = CR ³ R ⁴ , CCR ³ , ^{(C = NR 3) NHR 4} , NH (C = NR 3) is selected from NHR 4, NH (C = NH ) NR 3 R 4, said alkyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl or heteroaryl group , Halogen, alkyl, hydroxyl, nitro, cyano, OR ³ , S (O) _m R ³ , NR ³ R ⁴ , OC (O) R ³ , NR ³ (CO) OR ⁴ , C (O) R ³ , COOR ³ , CONR ³ R ⁴ , NR ³ COR ⁴ , SO ₂ NR ³ R ⁴ , CONHSO ₂ R ³ , NR ³ Optionally substituted with up to 4 groups independently selected from S (O) _m R ⁴ , CH ₂ NR ³ R ⁴ , CH ₂ OR ³ NHCONR ³ R ⁴ , NR ³ CONHR ⁴ ;
R ⁵ , R ⁶ , R ¹¹ and R ¹² are in each case hydrogen, hydroxyl, alkyl, haloalkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, halogen, cyano, nitro, CH ₂ NR ³ R ⁴ , CH ₂ OR ³ , C (O) R ³ , OR ³ , S (O) _m R ³ , NR ³ R ⁴ , COOR ³ , CONR ³ R ⁴ , SO ₂ NR ³ R ⁴ , NHCONR ³ R ⁴ , NR ³ independently selected from ⁴ CONHR ⁴ ;
The alkyl, haloalkyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl or heteroaryl group is halogen, alkyl, hydroxyl, nitro, cyano, OR ³ , S (O) _m R ³ , NR ³ R ⁴ , OC (O) R ³ , NR ³ (CO) OR ⁴ , C (O) R ³ , COOR ³ , CONR ³ R ⁴ , NR ³ COR ⁴ , SO ₂ NR ³ R ⁴ , CONHSO ₂ R ³ , NR ³ S (O) _m Optionally substituted with up to 4 groups independently selected from R ⁴ , NHCONR ³ R ⁴ , NR ³ CONHR ⁴ ;
R ⁵ and R ⁶ or R ¹¹ and R ¹² can form a carbonyl group with the carbon atom to which they are bonded, or can form a cycloalkyl group or a heterocyclyl group with the carbon or heteratom to which they are bonded. The carbonyl group, cycloalkyl group or heterocyclyl group can be halogen, hydroxyl, nitro, cyano, alkyl, haloalkyl, halogen, alkyl, nitro, cyano, OR ³ , S (O) _m R ³ , NR ³ R ⁴ , OC (O) R ³ , NR ³ (CO) OR ⁴ , C (O) R ³ , COOR ³ , CONR ³ R ⁴ , NR ³ COR ⁴ , SO ₂ NR ³ R ⁴ , CONHSO ₂ R ³ , Independently selected from NR ³ S (O) _m R ⁴ , NHCONR ³ R ⁴ , and NR ³ CONHR ⁴ May be substituted with up to 4 groups,
R ³ , R ⁴ are independently selected from hydrogen, alkyl, haloalkyl, or a substituted or unsubstituted carbocyclic group selected from cycloalkyl, cycloalkenyl, heterocyclyl, aryl and heteroaryl, wherein the alkyl or substituted carbocycle Shikimoto is halogen, hydroxyl, nitro, cyano, alkyl, haloalkyl, alkyloxy, _{carboxy, COOH, CONH 2, NHCOCH 3} , N (CH 3) 2, NHCH 3, thiomethyl, _thioethyl, SOCH _{3, SO} 2 CH 3 May be substituted with up to 4 groups selected from
R ³ and R ⁴ together with the carbon atom or hetero atom to which they are attached, halogen, hydroxyl, nitro, cyano, alkyl, haloalkyl, alkyloxy, formyl, carboxy, acetyl, CH ₂ NH ₂ , CH ₂ OH, _{COOH, CONH 2, NHCOCH 3,} N (CH 3) 2, thiomethyl, _{thioethyl, SOCH 3, SO 2 CH 3} , alkoxycarbonyl, alkylcarbonyl, alkynyl, aminoalkyl, aminoalkylcarbonyl, amino, mono or dialkylamino Can form a cycloalkyl or heterocyclyl group substituted with up to four independently selected groups, or R ³ and R ⁴ together with the nitrogen to which they are attached, 3-8 members To form a heterocycle containing children And up to four of its members may be carbonyl groups or heteroatoms independently selected from oxygen, sulfur, S (O), S (O) ₂ and nitrogen, wherein the carbocyclic group is Up to 4 unsubstituted or independently selected from halogen, hydroxy, hydroxyalkyl, alkyl, haloalkyl, alkoxy, alkoxycarbonyl, alkylcarbonyl, alkynylamino, aminoalkyl, aminoalkylcarbonyl, amino, mono or dialkylamino Substituted with 1 group.

In one preferred embodiment of the invention, the compound of formula I is
4- (2-chlorophenyl) -6- (3-hydroxypropyl) -9-methoxypyrrolo [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- (2-hydroxyphenyl) -6- (3-hydroxypropyl) pyrrolo [3,4-c] carbazole-1,3 (211,611) -dione;
4- (2-chloro-6-methoxyphenyl) -9-hydroxy-6- [2- (4-morpholinyl) 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-hydroxyhexyl) -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;
3-{[3- (4- (2-Chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) propyl] amino )benzoic acid;
2-{[3- (4- (2-Chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) propyl] amino )benzoic acid;
4-([3- (4- (2-Chlorophenyl) -9-hydroxy-1,3-dioxo-2; 3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) propyl] amino )benzoic acid;
4- (2-Chlorophenyl) -6- (3-[(cis) -3,5-dimethylpiperazinyl] 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-piperazinyl) 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] carbazole-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-chlorophenyl) -9-hydroxy-6- [2- (1H-imidazol-1-yl) 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- (4-methyl-1-piperazinyl) ethyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
6- (2-anilinoethyl) -4- (2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2,6-dichlorophenyl) -9-hydroxy-6- [3- (dimethylamino) ethyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2,6-dichlorophenyl) -9-hydroxy-6- [2- (4-morpholinyl) ethyl] pyrrolo [3,4-c] carbazole-1,3 (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) -dione ;
6- (2-aminoethyl) -4- (2,6-dichlorophenyl) -9-hydroxypyrrolo [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) -6- [3- (dimethylamino) propyl] -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2-chlorophenyl) -9-hydroxy-6- [3- (4-morpholinyl) propyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2-chlorophenyl) -9-hydroxy-6- [3- (4-methyl-1-piperazinyl) propyl] pyrrolo [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;
4- (2,6-dichlorophenyl) -9-hydroxy-6- [3- (methylamino) propyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2,6-dichlorophenyl) -6- [3- (dimethylamino) propyl] -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2,6-dichlorophenyl) -9-hydroxy-6- [3- (1H-imidazol-1-yl) propyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione ;
4- (2,6-dichlorophenyl) -9-hydroxy-6- [3- (4-morpholinyl) 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) -dione ;
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-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
9-hydroxy-6- [2- (4-morpholinyl) ethyl] -4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
9-hydroxy-6- [3- (1H-imidazol-1-yl) propyl] -4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
9-hydroxy-6- [2- (1H-imidazol-1-yl) ethyl] -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-piperidinyl) 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-anilinopropyl) -9-hydroxy-4-phenylpyrrolo [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-chlorophenyl) -9-hydroxy-6- [2- (phenylsulfanyl) ethyl] 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] carbazol-6 (1H) -yl) -N- [2- ( Dimethylamino) ethyl] -N-methylpropanamide;
3- (4- (2-Chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -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-piperidinyl);
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] carbazol-6 (1H) -yl) -N- [2- ( 1H-imidazol-5-yl) ethyl] propanamide (XIII; Ar = 2-chlorophenyl, n = 2, R ³ = H, R ⁴ = (1H-imidazol-5-yl) ethyl);
3- (4- (2,6-dichlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) propanoic acid;
N- [2- (dimethylamino) ethyl] -3- (9-hydroxy-1,3-dioxo-4-phenyl-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl ) Propanamide;
N- [2- (dimethylamino) ethyl] -3- (9-hydroxy-4- (2-methoxyphenyl) -1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1H) -yl) propanamide;
3,9-dihydroxy-4-phenyl-3,6-dihydropyrrolo [3,4-c] carbazol-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-1 (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-isopentylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2-chlorophenyl) -9-hydroxy-6- (2,2,2-trifluoroethyl) 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] carbazol-6 (1H) yl) acetamide;
6- (3-butenyl) -4- (2-chlorophenyl) -9-hydroxypyrrolo [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-chlorophenyl) -9-hydroxy-6- (4,4,4-trifluorobutyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
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- (dimethylamino) 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) -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-hydroxyethyl) -8- [3- (4morpholinyl) propoxy] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -Dione;
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-dihydroxypropyl) -9-hydroxy-6-methyl-4-phenylpyrrolo [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;
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-diphenylpyrrolo [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) -dione;
8- (3- (dimethylamino) propoxy] -9-hydroxy-6-methyl-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2-chlorophenyl) -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- (1-pyrrolidinyl) propoxy] pyrrolo [3,4-c] carbazole-1,3 (2H, W-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- (cis-3,5-dimethyl-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 [3,4-c] carbazol-9-yl dihydrogen phosphate;
4- (2-chlorophenyl) -8- (3-dimethylamino-propoxy) -9-hydroxy-6- (3-hydroxy-propyl) 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-dione;
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-chlorophenyl) -8- (4-dimethylamino-butyl) -6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione;
4- (2-chlorophenyl) -6-methyl-8- (4-pyrrolidin-1-yl-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-yl-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-hydroxy-ethyl) -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- (2-chloro-phenyl) -9-nitro-1,3-dioxo-2,3-dihydro-1H-pyrrolo [3,4-c] carbazol-6-yl] -propionic acid;
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-propoxy) -6H-pyrrolo [3,4-c] carbazole-1,3- 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-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;
4- (2-chloro-phenyl) -9-fluoro-6-methyl-8- (3-pyrrolidin-1-yl-propoxy) -6H-pyrrolo [3,4-c] carbazole-1,3-dione;
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- 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) -1,3-dioxo-1,2,3,6-tetrahydropyrrolo [3,4-c] carbazole-9- Yl] -formamide;
4- (2-chloro-phenyl) -9-hydroxy-6- (3-hydroxy-propyl) -8-piperidin-4-yl-6H-pyrrolo [3,4-c] carbazol-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-hydroxy-ethyl) -4- (2-chlorophenyl) -9-hydroxy-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- Dione;
4- (2-Chloro-phenyl) -9-hydroxy-7- (1-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- (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-piperidin-3-yl-6H-pyrrolo [3,4-c] carbazole-1,3-dione;
4- (2-Chlorophenyl) -8- (4-hydroxy-piperidin-3-yl) -6- (3-hydroxy-propyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione
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- (dimethylamino) propoxy] -9-hydroxy-6- (2hydroxyethyl) 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)- Dione;
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- (2hydroxyethyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H)- Dione;
4- (2-Chlorophenyl) -8- [4- (dimethylamino) butyl] -9-hydroxy-6- (3hydroxypropyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H)- Dione;
4- (2-Chlorophenyl) -8- [4- (dimethylamino) butyl] -9-hydroxy-6- (3hydroxypropyl) 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-Chlorophenyl) -8- [3- (dimethylamino) propoxy] -9-hydroxy-6- (3hydroxypropyl) pyrrolo [3,4-c] carbazole-1,3 (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-chlorophenyl) -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-chlorophenyl) -8- [4- (dimethylamino) butyl] -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-1,3 (2H, 6H ) -Dione;
6-butyl-4- (2-chlorophenyl) -8- [4- (dimethylamino) butyl] -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2-chlorophenyl) -9-hydroxy-8- [4- (methylamino) butyl] -6-propylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
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) -8- [3- (dimethylamino) propoxy] -9-hydroxypyrrolo [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-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) -dione;
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-hydroxypyrrolo [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- (2,6-dichlorophenyl) -8- [3- (dimethylamino) propoxy] -9-hydroxypyrrolo [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) -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) -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- (2,6-dichlorophenyl) -9-hydroxy-6-methyl-8- [3- (methylamino) propoxy) pyrrolo [3,4-c] 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) -dione;
4- (2-bromophenyl) -8- [3- (dimethylamino) propoxy] -9-hydroxy-6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2,6-dichlorophenyl) -8- [4- (dimethylamino) butyl] -9-hydroxy-6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
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-methoxyphenyl) -8- [3- (dimethylamino) propoxy] -9-hydroxy-6-methylpyrrolo [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-methoxyphenyl) -8- [4- (dimethylamino) butyl] -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -Dione;
6-butyl-4- (2,6-dichlorophenyl) -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] -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
6-butyl-4- (2,6-dichlorophenyl) -9-hydroxy-8- [3- (methylamino) propoxy) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
6-butyl-4- (2,6-dichlorophenyl) -9-hydroxy-8- [4- (methylamino) butyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2-chlorophenyl) -9-hydroxy-8- [4- (1-pyrrolidinyl) butyl) -1H- [1] benzofuro [3,2-e] isoindole-1,3 (2H) -dione;
8- (4-aminobutyl) -4- (2-chlorophenyl) -9-hydroxy-1H- [1] benzofuro [3,2-e] isoindole-1,3 (2H) -dione;
8- (4-aminobutyl) -4- (2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
8- (4-aminobutyl) -4- (2-chlorophenyl) -9-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;
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- (dimethylamino) -1-hydroxyethyl] 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) -8- (4-hydroxybutoxy) -6-methylpyrrolo [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] 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-[(1E) -4- (dimethylamino) -1-butenyl] -6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2-Chlorophenyl) -6-methyl-8-[(1E) -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;
44- (2-chlorophenyl) -8- [4- (dimethylamino) butyl] -6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2-chlorophenyl) -8-[(1E) -4-hydroxy-1-butenyl] -6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2-chlorophenyl) -8-[(1E) -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-[(1E) -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) -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-hydroxypropoxy) -6- [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] carbazole-1,3 (2H, 6H)- Dione;
4- (2-Chlorophenyl) -9-fluoro-6- (3-hydroxypropyl) -8- [4 (methylamino) butyl] pyrrolo [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-6-methyl-8- [3- (methylamino) propoxy] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2-chlorophenyl) -9-fluoro-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-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-3-hydroxyphenyl) -9-fluoro-6- (3-hydroxypropyl) -8- [4 (methylamino) butyl] pyrrolo [3,4-c] carbazole-1,3 ( 2H, 6H) -dione;
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-amino-2-chlorophenyl) -9-fluoro-8- [4- (methylamino) butyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (3-amino-2-chlorophenyl) -9-fluoro-8- [3- (methylamino) propoxy] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2-chlorophenyl) -9-fluoro-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] carbazol-6 (1H) -yl) -N- [ 2- (dimethylamino) ethyl] propanamide;
3- (9-Amino-4- (2-chlorophenyl) -1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) yl) -N- [2- (dimethyl Amino) ethyl] propanamide;
4- (2-chlorophenyl) -6-methyl-9-{[3- (1-piperidinyl) propyl) amino) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2-chlorophenyl) -9-fluoropyrrolo [3,4-c] carbazole-1,3 (2H, 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] carbazole-1,3 (2H, 6H) -dione;
4- (2-chlorophenyl) -6-methyl-9-1 [4- (methylamino) butyl] amino) 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-methoxyphenyl) -6-methyl-1,3-dioxo-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-chlorophenyl) -8- [4- (dimethylamino) butanoyl] -9-hydroxy-6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2-Chlorophenyl) -8- [3- (dimethylamino) propoxy] -6-methyl-1,3-dioxo-1,2,3,6 tetrahydropyrrolo [3,4-c] carbazole-9- Ilformamide;
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) -9-hydroxy-6-methyl-8-{[3 (methylamino) propyl] sulfonyl} pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione
Selected from the group consisting of

In another preferred embodiment of the invention, R ^{1 in} the compounds of formula I is aryl.

In one preferred embodiment, R ¹ is 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 NR ³ R ^4. Selected compounds of formula I.

In a more preferred embodiment is a compound of formula I wherein R ¹ is an aryl ring substituted with up to two halogen groups or alkoxy groups.

Another preferred embodiment of the invention comprises a compound of formula I, wherein R ¹ is selected from Me and I.

In one preferred embodiment of the invention, R ^{9 in} the compound of formula I is a hydrogen, hydroxyl, halogen or NHCHO group.

In another embodiment, at least one of X, R ⁷ , R ⁸ and R ⁹ is a compound of formula I that is not hydrogen. In another embodiment, when 3 of X, R ⁷ , R ⁸ and R ⁹ are hydrogen and R ¹ is lower alkyl, R ² must be hydrogen.

In a more preferred embodiment of the invention R ^{9 in} the compounds of formula I is a hydroxyl group.

In a more preferred embodiment of the invention R ^{9 in} the compounds of formula I is a fluorine group.

In a more preferred embodiment of the present invention,
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, 6R) -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-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2,6-dichlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2,3-dichlorophenyl) -9-hydroxypyrrolo [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) -dione;
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-hydroxyphenyl) -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-hydroxyphenyl) -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;
9-hydroxy-4- (2-hydroxyphenyl) 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] carbazol-4-yl) 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- (methylsulfinyl) phenyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2-ethoxyphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
9-hydroxy-4-(. 3-nitrophenyl) 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) -dione;
4- (2-chloro-4-nitrophenyl) -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′-biphenyl] -2-yl-9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (4-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
9-hydroxy-4- (4-hydroxymethylphenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
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-yl-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; and 4- (2-acetyl-phenyl) -9-hydroxy-6H-pyrrolo Compounds of formula I wherein R ⁹ is hydroxyl and R ¹ is aryl, such as, but not limited to, [3,4-c] carbazole-1,3-dione.

In yet another preferred embodiment of the present invention,
4- (2-chlorophenyl) -7- (1,2-dihydroxyethyl) -9-hydroxy-1H- [1] benzofuro [3,2-e] isoindole-1,3 (2H) -dione;
4- (2-chlorophenyl) -9-hydroxy-1H- [1] benzofuro [3,2-e] isoindole-1,3 (2H) -dione;
4- (2-chlorophenyl) -8-ethyl-9-hydroxy-1H- [1] benzofuro [3,2-e] isoindole-1,3 (2H) -dione;
4- (2-chlorophenyl) -7-ethyl-9-hydroxy-1H- [1] benzofuro [3,2-e] isoindole-1,3 (2H) -dione;
9-hydroxy-4-phenyl-1H- [1] benzofuro [3,2-e] isoindole-1,3 (2H) -dione;
4- (2-chlorophenyl) -8- [3- (dimethylamino) propoxy] -9-hydroxy-1H- [1] benzofuro [3,2-e] isoindole-1,3 (2H) -dione; and Y ( ¹ ) such as 4- (2-chlorophenyl) -9-hydroxy-8- (4-hydroxybutyl) -1H- [1] benzofuro [3,2-e] isoindole-1,3 (2H) -dione Compounds of Formula I that are oxygen, but are not limited to these.

In another preferred embodiment of the present invention,
Compounds of formula I wherein Y ¹ is sulfur, such as 4- (2-chlorophenyl) -9-hydroxy-1H- [1] benzothieno [3,2-e] isoindole-1,3 (2H) -dione However, it is not limited to these.

In another preferred embodiment of the invention are compounds of formula I, wherein R ⁹ is hydroxyl and Y ¹ is NR ¹⁰ .

In another preferred embodiment of the present invention,
9-amino-4- (2-methoxyphenyl) -6-methylpyrrolo [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;
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-c] carbazol-9-yl] -3- (1-piperidinyl) propanamide Compounds of formula I wherein R ⁹ is NR ⁵ R ⁶ , R ¹ is aryl and Y ¹ is NR ¹⁰ such as, but not limited to, compounds.

In another preferred embodiment of the invention are compounds of formula I, wherein R ⁹ is hydroxyl and Y ¹ is NR ¹⁰ .

In another preferred embodiment of the invention are compounds of formula I, wherein R ⁹ is hydroxyl, Y ¹ is NR ¹⁰ and T may be absent, O, CONR ³ or CONHSO ₂ . Examples of such compounds are shown below.
9-methoxy-4- (2-methoxy-5-nitrophenyl) -4,5,6,10c-tetrahydropyrrolo [3,4-c] carbazole-1,3 (2H, 3aH) -dione;
N- [3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) propanoyl] benzenesulfone An amide;
4- (2,6-dichlorophenyl) -9-hydroxy-6- (3-hydroxypropyl) 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;
3- (4- (2-Chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol- (1H) -yl) -N- (1H-tetrazole- 5-yl) propanamide;
4- (2-Chlorophenyl) -9-hydroxy-6- [2- (1H-1,2,4-triazol-5-ylsulfinyl) ethyl] pyrrolo [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;
3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) propanoic acid;
N- [3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -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] carbazol-6 (1H) -yl) propanoyl] methanesulfone An amide;
4 '-(4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) butanoic acid;
N- [4- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) butanoyl] methanesulfone An amide;
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] carbazol-6 (1H) -yl) -N- [2 -(Dimethylamino) ethyl] propanamide;
3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) propanenitrile;
4- (2-chlorophenyl) -9-hydroxy-6- [3- (1H-tetrazol-5-yl) propyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2-Chlorophenyl))-9-hydroxy-6- [2- (1H-imidazol-2-ylsulfanyl) ethyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione ;
N- [4- (4- (2-Chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) butanoyl] benzenesulfone An amide;
4- (2-Chlorophenyl) -9-hydroxy-6- [2- (1H-1,2,4-triazol-5-ylsulfonyl) ethyl] pyrrolo [3,4-c] carbazole-1,3 (2H , 6H) -dione;
4- (2-chlorophenyl) -9-hydroxy-6- [2- (1H-imidazol-2-ylsulfinyl) ethyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2-chlorophenyl) -9-hydroxy-6- [2- (1H-tetrazol-5-yl) 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] carbazol-6 (1H) yl) propanamide;
4- (2-chlorophenyl) -9-hydroxy-6- [2- (1H-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] carbazol-6 (1H) 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] carbazol-6 (1H) -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-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) -N- [2- ( 1H-imidazol-5-yl) ethyl] propanamide;
9-hydroxy-6- (3-hydroxypropyl) -4- (2-methoxyphenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
Methyl 3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) propanoate;
3- (4- (2-Chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) -N- [2- ( 4-morpholinyl) ethyl] propanamide;
4- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c, carbazol-6 (1H) -yl] butanenitrile;
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] carbazol-6 (1H) -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] carbazol-6 (1H) -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] carbazol-6 (1H) -yl) ethyl methanesulfonate;
4- (2-chloro-6-methoxyphenyl) -9-hydroxy-6- (3-hydroxypropyl) 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;
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-1-pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4). - (2-chlorophenyl) -6-ethyl-9-hydroxy-pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) - dione (VI; Ar = _{2-chlorophenyl, R-CH} 2 CH 3) ;
4- (2-chlorophenyl) -9-hydroxy-6-isopropylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2-chlorophenyl) -9-hydroxy-6- [3- (1H-imidazol-1-yl) propyl] pyrrolo [3,4-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) -dione;
6- (2-chloroethyl) -4- (2-chlorophenyl) -9-hydroxypyrrolo [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-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-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- (1H-imidazol-1-yl) propyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione And 6-butyl-4- (2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione.

In a more preferred embodiment of the invention are compounds of formula I, wherein R ⁹ is hydroxyl, Y ¹ is NR ¹⁰ and the bond (C—O) indicated by the dashed line is absent.

In a particularly preferred embodiment of the invention are compounds of formula I, wherein R ⁹ is hydroxyl and R ⁸ is not hydrogen.

In another preferred embodiment of the invention are compounds of formula I, wherein R ⁹ is hydroxyl, Y ¹ is NR ¹⁰ and R ¹ is aryl.

Another particularly preferred embodiment of the present invention is a compound of formula I wherein R ⁸ is not hydrogen and R ⁹ is hydrogen.

Another particularly preferred embodiment of the present invention is a compound of formula I wherein R ⁸ is not hydrogen, R ⁹ is hydrogen and Y ¹ is NR ¹⁰ .

Another particularly preferred embodiment of the present invention is that R ⁹ is hydrogen, R ⁸ is ((CR ⁵ R ⁶ ) _n T) _a (CR ¹¹ R ¹² ) _b ) -Z, and T is present. Including compounds of formula I wherein O may be present and Z is NR ³ R ⁴ .

Another particularly preferred embodiment of the present invention is that R ⁹ is selected from halogen or hydroxyl, R ⁸ is ((CR ⁵ R ⁶ ) _n T) _a (CR ¹¹ R ¹² ) _b ) Z, where T is Including compounds of formula I that are absent and Z is hydrogen.

  The following are definitions of terms used in this specification. The initial definition given to a group or term herein applies to that group or term throughout the present specification, unless otherwise stated, or as part of another group.

  When stereoisomers or enantiomers are present, all possible combinations are claimed.

  The terms “halogen” and “halo” mean fluorine, chlorine, bromine and iodine.

  The term “unsaturated ring” includes partially unsaturated rings and aromatic rings.

  The term “alkyl” in the present invention means a linear or branched hydrocarbon group having 1 to 8 carbon atoms, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl. , Isobutyl, tert-butyl, n-pentyl, isopentyl, n-hexyl and the like. The term “aryl” refers to a single ring (eg, phenyl), multiple rings (eg, biphenyl), or multiple condensed rings (eg, 1,2,3,4-at least one aromatic). Means an aromatic carbocyclic group having tetrahydronaphthyl, naphthyl, anthryl or phenanthryl).

  The term “heteroaryl” refers to an aromatic “heterocycle”, “heterocyclic”, “heterocyclyl” or “heterocyclo” group containing at least one heteroatom as defined below.

Aryl or heteroaryl ring, NH _(C 1 ~C ₆ alkyl), _{N (C} 1 ~C _{6 alkyl) 2,} thio _C 1 -C _{6 alkyl,} C 1 -C ₆ alkoxy, hydroxy, carboxy, _{C 1} -C ₆ alkoxycarbonyl, halo, with up to 5 substituents selected from nitrile and cycloalkyl may be substituted.

  “Alkoxy” means, for example, methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, sec-butoxy, tert-butoxy, pentoxy, 2-pentyloxy, isopentoxy, neopentoxy, hexoxy, 2-hexoxy, 3-hexoxy, A straight or branched alkoxy group having 1 to 10 carbon atoms, such as 3-methylpentoxy.

  “Alkynyl” means straight chain and branched hydrocarbon groups having 2 to 8 carbon atoms and one triple bond, including ethynyl, 3-butyn-1-yl, propynyl, 2-butyne-1 -Yl, 3-pentyn-1-yl and the like.

  The terms “cycloalkyl” and “cycloalkenyl” mean cyclic hydrocarbon groups of 3 to 8 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl and the like.

  “Acyl” means an alkyl, aryl, cycloalkyl, heterocycle, heterocycle, heterocyclyl or heterocyclo group attached through a carbonyl group, ie, R—C (O) —. Typical acyl groups are acetyl, benzoyl and the like having 1 to 10 carbon atoms, preferably 1 to 6 carbon atoms.

  The term “haloalkyl” refers to an alkyl group substituted with 1 to 6 halogen atoms, including trifluoromethyl, trichloromethyl, tribromomethyl, trifluoroethyl, trifluoropropyl, trifluorobutyl, pentafluoroethyl. Etc. are included.

The alkyl, alkenyl, alkoxy and alkynyl groups are preferably NH (C ₁ -C ₆ alkyl), N (C ₁ -C ₆ alkyl) ₂ , phenyl, substituted phenyl, thio C ₁ -C ₆ alkyl, C ₁ -C ₆ alkoxy, hydroxy, _carboxy, C 1 -C ₆ alkoxycarbonyl, halo, nitrile, cycloalkyl, 5- or 6-membered carbocyclic or nitrogen, one or two are selected from substituted nitrogen, oxygen and sulfur, It may be substituted with 1 to 3 groups selected from 5-membered or 6-membered heterocycle having a heteroatom. “Substituted nitrogen” means a nitrogen having C ₁ -C ₆ alkyl or (CH ₂ ) _p Ph (p is 1, 2 or 3). Perhalo and polyhalo substitutions are also included.

  The term “heteroatom” means an oxygen, nitrogen, sulfur or phosphorous atom.

  The term “heterocycle”, “heterocyclic”, “heterocyclyl” or “heterocyclo” refers to an aromatic (heteroaryl) or non-aromatic cyclic group, eg a 4 to 7 membered monocyclic, 7 membered Means fully saturated or unsaturated having at least one heteroatom in a ring containing at least one carbon atom, including from 1 to 11 membered bicyclic or 10 to 15 membered tricyclic systems. Each ring of the heterocyclic group containing a heteroatom can contain 1, 2, 3 or 4 heteroatoms selected from nitrogen, oxygen and / or sulfur atoms, where the nitrogen and sulfur heteroatoms are It may be oxidized and the nitrogen heteroatom may be quaternary. The heterocyclic group may be attached to any heteroatom or carbon atom of the ring or ring system.

Monocyclic heterocyclic groups include piperidine, 2,6-dimethylpiperazine, piperazine, n-methylpiperazine, pyrrolidinyl, pyrrolyl, pyrazolyl, oxetanyl, pyrazolinyl, imidazolyl, imidazolinyl, S (O) -imidazole, S (O ) ₂ -Imidazoleoxazolyl, oxazolidinyl, isoxazolinyl, isoxazolyl, thiazolyl, thiadiazolyl, thiazolidinyl, isothiazolyl, isothiazolidinyl, morpholine and dimethylmorpholine, 2-thiophene, thiophene, 1-imidazole, 2-imidazole, furyl, tetrahydro Furyl, thienyl, oxadiazolyl, piperidinyl, piperazinyl, 2-oxopiperazinyl, 2-oxopiperidinyl, 2-oxopyrrolodinyl inyl), 2-oxoazepinyl, 2-azepinyl, 4-piperidonyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, tetrahydropyranyl, morpholinyl, thiamorpholinylsulfoxide, thiamorpholinylsulfoxide Examples include, but are not limited to sulfone, 1,3-dioxolane and tetrahydro-1,1-dioxothianyl, tetrazole, SO-triazole, SO ₂ -triazole.

  Bicyclic heterocyclic groups include indolyl, benzothiazolyl, benzoxazolyl, benzodioxolyl, benzothienyl, quinuclidinyl, quinolinyl, tetrahydroisoquinolinyl, isoquinolinyl, benzimidazolyl, benzopyranyl, indolizinyl, benzophalyl, chromonyl ( chloroylyl, coumalinyl, benzopyranyl, cinnolinyl, quinoxalinyl, indazolyl, pyrrolopyridyl (such as furo [2,3-c] pyridinyl, furo [3,2-b] pyridinyl or furo [2,3-b1pyridinyl) Including, but not limited to, furopyridinyl, dihydroisoindolyl, dihydroquinazolinyl (such as 3,4-dihydro-4-oxo-quinazolinyl), tetrahydroquinolinyl, and the like. No. Tricyclic heterocyclic groups include, but are not limited to, carbazolyl, benzindolyl, phenanthrolinyl, acridinyl, phenanthridinyl, xanthenyl and the like.

  The term “cancer” refers to the following cancers: breast cancer, ovarian cancer, cervical cancer, prostate cancer, testicular cancer, esophageal cancer, stomach cancer, skin cancer, lung cancer, bone cancer, colon cancer, pancreatic cancer, thyroid cancer, biliary tract Cancer, buccal oral and pharyngeal (oral) cancer, lip cancer, tongue cancer, mouth cancer, pharyngeal cancer, small intestine cancer, colorectal cancer, colon cancer, rectal cancer, brain tumor and central nervous system cancer, glioblastoma , Neuroblastoma, keratoacanthoma, epidermoid carcinoma, large cell carcinoma, adenocarcinoma, adenoma, follicular adenocarcinoma, undifferentiated cancer, papillary carcinoma, seminoma, melanoma, sarcoma, bladder cancer, liver cancer, kidney cancer Including, but not limited to, bone marrow disorders, lymphoid disorders, Hodgkin's disease, hairy cell cancer and leukemia.

  As used herein, the term “pharmaceutically acceptable salts, esters, amides, and prodrugs” refers to excessive toxicity, irritation, allergic response, etc., within reasonable medical judgment, within reasonable medical judgment. Carboxylic acid salts, amino acid addition salts, esters, amides and prodrugs of the compounds of the present invention that are suitable for use in contact with the patient's tissue Means a compound of the invention in the form of a ionic ion. The term “salt” refers to the relatively non-toxic inorganic and organic 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 compound, or the salt formed by reacting the purified compound in the free base form separately with a suitable organic or inorganic acid. Can be prepared by isolating. Typical salts include hydrobromide, hydrochloride, sulfate, hydrogen sulfate, nitrate, acetate, oxalate, valerate, oleate, palmitate, stearic acid, laurate , Borate, benzoate, lactate, phosphate, tosylate, citrate, maleate, fumarate, succinate, tartrate, naphthylate mesylate, glucoheptonate, lactobionic acid Salts and lauryl sulfonates. These include cations based on alkali and alkaline earth metals such as sodium, lithium, potassium, calcium, magnesium, as well as ammonium, tetramethylammonium, tetraethylammonium, methylamine, dimethylamine, trimethylamine, triethylamine, ethylamine, etc. Non-toxic ammonium, quaternary ammonium and amine cations are also included, but are not limited to these. (See, for example, Berge SM et al., “Pharmaceutical Salts,” J. Pharm. Sci., 1977; 66: 1-19, incorporated herein by reference.)

  The compounds of formula I are further pharmaceutically acceptable including salts, including but not limited to salts, acid addition and / or base salts of compounds of formula I, solvates and N-oxides. A formulation can also be formed. The present invention also provides a pharmaceutical formulation comprising a compound of formula I and a pharmaceutically acceptable carrier, diluent or excipient thereof. All of these forms are within the scope of the present invention.

  Pharmaceutically acceptable acid addition salts of the compounds of formula I include salts derived from inorganic acids such as hydrochloric acid, nitric acid, phosphoric acid, sulfur, hydrobromic acid, hydroiodic acid, phosphorus, and aliphatic mono And salts derived from organic acids such as dicarboxylic acids, phenyl-substituted alkane carboxylic acids, hydroxyalkane carboxylic acids, alkanedioic acids, aromatic acids, aliphatic sulfonic acids, aromatic sulfonic acids, and the like. Therefore, such salts include sulfate, pyrosulfate, hydrogen sulfate, sulfite, bisulfite, nitrate, phosphate, monohydrogen phosphate, dihydrogen phosphate, metaphosphate, pyrolin Acid, chloride, bromide, iodide, acetate, propionate, caprylate, isobutyrate, oxalate, malonate, succinate, suberate, sebacate, fumarate, maleate Acid, mandelate, benzoate, chlorobenzoate, methylbenzoate, dinitrobenzoate, phthalate, benzenesulfonate, toluenesulfonate, phenylacetate, citrate, lactate , Maleate, tartrate and methanesulfonate. Also contemplated are salts of amino acids such as alginate, gluconate, galacturonate. For example, Berge et al., “Pharmaceutical Salts” of Pharmaceutical Science, 1977; 66: 1-19.

  Acid addition salts of basic compounds are prepared by contacting the free form base with a sufficient amount of the desired acid to produce the salt by conventional methods. The free base can be regenerated by contacting the salt with a base and isolating the free base by conventional methods. The free base is somewhat different from the respective salt in certain physical properties, such as solubility in polar solvents, but otherwise the salt is equivalent to the respective free base in the present invention.

  Pharmaceutically acceptable base addition salts are formed with metals or amines, such as alkali metal hydroxides, alkaline earth metal hydroxides, or organic amines. Examples of metals used as cations are sodium, potassium, magnesium, calcium and the like. Examples of suitable amines are N, N'-dibenzylethylenediamine, chloroprocaine, choline, diethanolamine, ethylenediamine, N-methylglucamine and procaine, see, for example, Berge et al., Supra, 1977.

  Base addition salts of acidic compounds are prepared by contacting the free acid with a sufficient amount of the desired base to produce the salt by conventional methods. The free form of the acid can be regenerated by contacting the salt with an acid and isolating the free acid by conventional methods. The free form acid is somewhat different from the respective salt in certain physical properties such as solubility in polar solvents, but otherwise the salt is equivalent to the respective free acid in the present invention.

Pharmaceutically acceptable non-toxic esters of the compounds of the present invention include C ₁ -C ₆ alkyl esters in which the alkyl group is straight or branched. Acceptable esters, such as C ₅ -C ₇ cycloalkyl esters as well as benzyl, although this only not limited arylalkyl esters are also included. C ₁ -C ₄ alkyl esters are preferred. Esters of the compounds of the present invention can be prepared using the conventional method “March's Advanced Organic Chemistry, 5th Edition”, ^M.M. B. Smith & J.M. And can be prepared according to March, John Wiley & Sons, 2001.

Examples of non-toxic amides of the pharmaceutically acceptable compounds of the present invention include ammonia, primary C ₁ -C ₆ alkylamines and secondary C ₁ -C ₆ dialkylamines in which the alkyl group is straight or branched. Is an amide derived from In the case of secondary amines, the amines can also be in the form of 5-membered or 6-membered heterocycles containing one nitrogen atom. Amides derived from ammonia, C ₁ -C ₃ alkyl primary amines and C ₁ -C ₂ dialkyl secondary amines are preferred. Amides of the compounds of the present invention are described in “March's Advanced Organic Chemistry, 5th Edition”, ^M.M. B. Smith & J.M. It can be prepared according to conventional methods such as March, John Wiley & Sons, 2001.

  The term “prodrug” refers to a compound that is rapidly transformed in vivo to yield the parent compound of the above formula, for example by hydrolysis in blood. T.A. Higuchi and V. Stella, “Pro-drugs as Novel Delivery Systems”, Vol. C. S. Symposium Series, and Bioreversible Carriers in Drug Design, Edward B. A detailed discussion can be found in Roche, American Pharmaceutical Association and Pergamon Press, 1987. Both of these are hereby incorporated by reference.

The present invention relates to isotopes that are identical to compounds of formula I, except that one or more atoms are replaced by atoms having an atomic mass or mass number different from the naturally occurring atomic mass or mass number. Also includes a labeled compound. Examples of isotopes that can be incorporated into the compounds of the present invention are ² H, ³ H, ¹³ C, ¹¹ C, ¹⁴ C, ¹⁵ N, ¹⁸ O, ¹⁷ O, ³¹ P, ³² P, ³⁵ S, ¹⁸ F. , ³⁶ Cl and the like, respectively, isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine and chlorine. Also within the scope of the invention are compounds of the invention, prodrugs thereof, and pharmaceutically acceptable salts of the compounds or salts of the prodrugs that contain the isotope and / or other isotopes of other atoms. Certain isotopically-labeled compounds of the present invention, for example those of the present invention incorporating radioactive isotopes such as ³ H, ¹⁴ C, are useful in drug and / or substrate tissue distribution assays. Tritium, ie, ³ H and carbon-14, ie, ¹⁴ C-labeled isotopes are particularly preferred because they are easy to prepare and detect. Also, replacement with deuterium, i.e., heavier isotopes such as ² H, may have certain therapeutic benefits resulting from increased metabolic stability, such as increased in vivo half-life, or dosage requirements. May result in a decrease and may therefore be preferred in certain circumstances. The isotope-labeled compounds of formula I and their prodrugs of the present invention are generally readily accessible to unisotopically labeled reagents by performing the following schemes and / or procedures shown in the Examples and Preparations It is prepared by substituting with an isotope labeling reagent.

  The compounds of formula I and their pharmaceutically acceptable salts can be administered to mammals by oral, parenteral (subcutaneous, intravenous, intramuscular, intrasternal, infusion techniques, etc.), rectal, intranasal or topical routes. it can. In general, these compounds are most desirably administered at about 10 to about 10,000 mg / day in single or divided doses (ie, 1 to 4 doses / day), although the species to be treated, body weight and Variations will necessarily occur depending on the condition and the particular route of administration chosen. However, dosage levels in the range of about 0.15 mg to about 150 mg / kg body weight / day are most desirably used. Nevertheless, variations can occur depending on the species of animal to be treated and its individual response to the medicament, as well as the type of pharmaceutical formulation selected and the duration and interval at which such administration is performed. Dosage levels below the lower limit of the range may be adequate enough, or higher doses may be used without causing any harmful side effects. However, such high dose levels are initially divided into several smaller doses throughout the day.

  The compounds of the invention can be administered by any of the above routes, alone or in combination with a pharmaceutically acceptable carrier or diluent, and such administration is performed in a single dose or multiple doses. be able to. In particular, the novel therapeutic agents of the present invention can be administered in a wide variety of different dosage forms: tablets, capsules, electuary, lozenges, hard candy, powders, sprays, emulsions, ointments. (Salves), suppositories, jellies, gels, pastes, lotions, ointments, aqueous suspensions, injections, elixirs, syrups, etc. It can be combined with an active carrier. Such carriers include solid diluents or fillers, sterile aqueous media, various non-toxic organic solvents, and the like. Furthermore, the oral pharmaceutical composition can be appropriately sweetened and / or flavored. In general, the therapeutically effective compounds of the present invention are present in such dosage forms at a concentration of from about 5.0% to about 70% by weight.

  For oral administration, tablets containing various excipients such as microcrystalline cellulose, sodium citrate, calcium carbonate, dicalcium phosphate, glycine, starch (and preferably corn, potato or tapioca starch), It can be used with various disintegrants such as alginic acid, certain complex silicates, granulating binders such as polyvinylpyrrolidone, sucrose, gelatin and gum arabic. Also, lubricants such as magnesium stearate, sodium lauryl sulfate, and talc are often very useful for tableting. Similar types of solid compositions can also be used as fillers in gelatin capsules. Preferred materials in this context include lactose, lactose, high molecular weight polyethylene glycols and the like. When aqueous suspensions and / or elixirs are desired for oral administration, the active ingredient may be combined with diluents such as water, ethanol, propylene glycol, glycerin, various combinations thereof, various sweeteners or flavoring agents, It can be combined with colorants or pigments and, if desired, emulsifiers and / or suspending agents.

  For parenteral administration, solutions of the compounds of the invention in sesame or peanut oil or aqueous propylene glycol can be used. These aqueous solutions should be appropriately buffered (preferably at a pH of about 3 to about 8) as necessary, and the dilutions should first be made isotonic. These aqueous solutions are suitable for intravenous injection purposes. These oily solutions are suitable for intra-articular, intramuscular and subcutaneous injection. All these solutions are readily prepared under aseptic conditions by standard pharmaceutical techniques well known to those skilled in the art.

  The compounds of the present invention can also be administered locally when treating a proliferative cell condition in the skin. This can be done with emulsions, jellies, gels, pastes, patches, ointments and the like according to standard pharmaceutical practice.

The activity of the compounds of the present invention is determined by whether they act as check point inhibitors. Checkpoint inhibitors inhibit kinases involved in the regulation of G ₂ / M checkpoints and reverse the checkpoint under action. Wee1 or Chk1 are examples of such kinases. Utilizing damaged DNA, such as, but not limited to, conventional DNA to cells containing intact DNA for cells with chemotherapeutic agents or DNA damaged by radiation Using the pathway, the cells are advanced to the M phase at an inappropriate early stage. Since such cells enter the M phase in the presence of potentially catastrophic damaged DNA, they are unlikely to survive and divide further. In the case of intact cells without detectable DNA damage, treatment of these cells with the checkpoint inhibitors of the present invention may cause early M phase progression due to similar cytotoxic effects. (Alan J. Kraker and Robert N. Booher, “New Cell Cycle Targets”, Ann. Rep. Med. Chem., 1999; 34: 247-256).

  Activity is measured in the assays described in Examples 483 (Wee1) and 484 (Chk1) and 486 (PKC) and has at least 1/10 the activity of the Wee1 assay in the PKC assay, or the Chk1 assay in the PKC assay. The checkpoint inhibitor of the present invention can be identified by selecting a compound having at least 1/5 of the activity.

The invention is illustrated by the following examples. However, it should be understood that the invention is not limited to the specific details of these examples. The melting point is not corrected. Proton nuclear magnetic resonance spectrum ( ¹ H NMR) and ¹³ C nuclear magnetic resonance spectrum were measured for deuterated chloroform (CDCl ₃ ) or CD ₃ OD or CD ₃ SOCD ₃ solution, and the peak position was tetramethylsilane (TMS). It is expressed in parts per million (ppm) on the low magnetic field side. The peak shape is expressed as follows: s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet; b, broad.

  The compounds of the present invention can exist in unsolvated forms as well as solvated forms, including hydrated forms. In general, solvated forms, including hydrated forms, are equivalent to unsolvated forms and are encompassed 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 include cancers (eg, leukemias and skin cancers such as lung cancer, breast cancer, prostate cancer, and melanoma), as well as psoriasis, HSV, HIV, restenosis and atherosclerosis It is useful for treating other proliferative diseases, not limited to, in combination with other conventional therapies. In order to treat cancer using a compound of the present invention, an effective amount of a compound of the present invention is administered to a patient in need of such treatment, such as a patient with cancer or other cell proliferative disorder.

  The compounds of the present invention may also include other clinical therapeutic agents and physical therapy means such as, but not limited to, X-ray irradiation, phototherapy, gemcitabine, paclitaxel, docetaxel, cisplatin, carboplatin, etoposide, adriamycin, topotecan, CPT -11, as a conventional chemotherapeutic agent such as capecitabine, or ionizing radiation alkylating agents, antimetabolites, antibodies, DNA intercalators, or other such anti-proliferative agents that ultimately cause DNA damage When combined, it is useful for the treatment of cancer. When new antineoplastic agents or physical therapy measures are discovered, the combination of Wee1 inhibitors and / or Chk1 inhibitors with these other therapeutic agents or physical therapy measures is contemplated.

  Although the in vivo studies described herein teach administering a compound of formula I at the same time as, or subsequent to, administration of a conventional agent, the compounds of the present invention can be compared to conventional chemotherapeutic agents. It is also contemplated that it can be administered before.

  The following examples illustrate specific embodiments of the invention and do not in any way limit the specification, including the claims. Those skilled in the art will appreciate that numerous changes and modifications can be made to the preferred embodiments of the invention, and such changes and modifications can be made without departing from the spirit of the invention. Accordingly, all such equivalent variations are intended to be within the true spirit and scope of the present invention.

  The chemical synthesis scheme shown below illustrates the best mode for preparing the compounds of the present invention. This patent describes several synthetic transformations known to those skilled in the art. In each case, it is known to the person skilled in the art and is described in the literature, for example Advanced Organic Chemistry 5th edition, author: Jerry March, m. b. Smith & J.M. March, John Wiley & Sons 2001; Comprehensive Organic Transformation, Author: Richard C. The desired product can also be obtained by alternative conditions as described in Larock, The Journal of Organic Chemistry, American Chemical Society publications and references cited therein.

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

  Scheme 1-Preparation of Substituted 4-Arylpyrrolo [3,4-c] carbazole

Example 1 Preparation of benzyl (2E) -3- (5-methoxy-1H-indol-2-yl) -2-propenoate (2) Benzyl (triphenylphosphoroanilidene) acetate (49.2 g, 0 .120 mol) was added to a stirred solution of 5-methoxy-1H-indole-2-carbaldehyde (1) (20.0 g, 0.114 mol) in CH ₂ Cl ₂ (500 mL) and the solution was at room temperature for 4 h. Stir. The solvent was removed under reduced pressure and the residue was slurried with methanol (200 mL) to crystallize the product. The mixture was filtered, washed several times with cold methanol, dried, and pale yellow plate-like benzyl (2E) -3- (5-methoxy-1H-indol-2-yl)-having a melting point of 155-157 ° C. 30.46 g of 2-propenoate (2) was obtained with a yield of 87%. ¹ H NMR δ (CDCl ₃ ) 8.28 (s, 1H), 7.69 (d, J = 16.1 Hz, 1H), 7.43-7.32 (m, 5H), 7.23 (d , J = 9.1 Hz, 1H), 7.03 (d, J = 2.3 Hz, 1H), 6.92 (dd, J = 9.1, 2.3 Hz, 1H), 6.74 (d, J = 1.8 Hz, 1H), 6.24 (d, J = 16.1 Hz, 1H), 5.26 (s, 2H), 3.84 (s, 3H). Found: C, 74.45; H, 5.62; N, 4.58. Calculated C of _{C 19 H 17 NO 3, 74.25} ; H, 5.57; N, 4.56.

Example 2 Benzyl 9-methoxy-1,3-dioxo-1,2,3,3a, 4,5,6,10c-octahydropyrrolo [3,4-c] carbazole-4-carboxylate (3 Maleimide (4.82 g, 0.050 mol) was prepared from benzyl (2E) -3- (5-methoxy-1H-indol-2-yl) -2-propenoate (12. 71 g, 0.041 mol) in THF (150 mL) was added in a 250 mL flat bottom flask and the mixture was stirred until homogeneous. The THF was removed under reduced pressure and the residue was dried under high vacuum for 30 minutes. The flask was immersed in an oil bath at 175 ° C. and the mixture was stirred at this temperature for 3 hours. The solid melt was cooled to room temperature and ethyl acetate (100 mL) was added. The solid mass was partially broken with a spatula and the mixture was stirred vigorously overnight to give a creamy precipitate product (3). Filtration, washing with diethyl ether, benzyl 9-methoxy-1,3-dioxo-1,2,3,3a, 4,5,6,10c-octahydropyrrolo [3,4] -C] Carbazole-4-carboxylate (13.76 g, 83%) was obtained. ¹ H NMR δ [(CD ₃ ) ₂ SO] 10.98 (br s, 1 H), 10.87 (s, 1 H), 7.45 to 7.32 (m, 5 H), 7.20 (d, J = 2.4 Hz, 1H), 7.17 (d, J = 8.7.Hz, 1H), 6.69 (dd, J = 8.7, 2.4 Hz, 1H), 5.21 (s) , 1H), 4.22 (br d, J = 7.8 Hz, 1H), 4.14 (dd, J = 7.8, 4.2 Hz, 1H), 3.75 (s, 3H), 3. 19-3.13 (m, 1H), 3.00 (dd, J = 16.5, 4.8 Hz, 1H), 2.79-2.70 (m, 1H).

Example 3 Preparation of benzyl 9-methoxy-1,3-dioxo-1,2,3,6-tetrahydropyrrolo [3,4-c] carbazole-4-carboxylate (4) Activated manganese dioxide (69 g ) Was prepared as in Example 2 benzyl 9-methoxy-1,3-dioxo-1,2,3,3a, 4,5,6,10c-octahydropyrrolo [3,4-c] carbazole- 4-carboxylate (13.76 g, 0.034 mol) in p-dioxane (300 mL) was added and the mixture was refluxed for 0.5-2 hours with vigorous stirring. The mixture was filtered hot through a plug of celite and washed thoroughly with a MeOH / p-dioxane (1: 1) mixture until the wash became colorless. The combined washings and filtrate are concentrated to dryness, the residue is triturated several times with diethyl ether, and a yellow / orange powder of benzyl 9-methoxy-1,3-dioxo-1,2,3,6 having a melting point of 245 ° C. -Tetrahydropyrrolo [3,4-c] carbazole-4-carboxylate (4) (12.47 g, 91.5%) was obtained. A small sample was recrystallized from EtOAc to give an orange cubic benzyl 9-methoxy-1,3-dioxo-1,2,3,6-tetrahydropyrrolo [3,4-c] carbazole of melting point 289-292 ° C. -4-carboxylate was obtained. ¹ H NMR δ [(CD ₃ ) ₂ SO] 12.11 (br s, 1 H), 11.27 (br s, 1 H), 8.45 (d, J = 2.6 Hz, 1 H), 7.98 (S, 1H), 7.59 (d, J = 8.9 Hz, 1H), 7.55 to 7.51 (m, 2H), 7.44 to 7.34 (m, 3H), 7.27 (Dd, J = 8.9, 2.6 Hz, 1H), 5.41 (s, 2H), 3.88 (s, 3H). Found: C, 68.99; H, 4.09; 6.91. Calculated C of _{C 23 H 16 N 2 O 5} , 69.00; H, 4.03; N, 6.99.

Example 4 Preparation of 9-methoxy-1,3-dioxo-1,2,3,6-tetrahydropyrrolo [3,4-c] carbazole-4-carboxylic acid (5) 5% Pd-C (0 Benzyl 9-methoxy-1,3-dioxo-1,2,3,6-tetrahydropyrrolo [3,4-c] carbazole-4-carboxylate prepared as in Example 3 (.50 g) 2.00 g) in DMF / MeOH (4: 1) (50 mL) was hydrogenated at 410 kPa (60 psi) for 2 hours (Parr apparatus). The solution was filtered through a plug of celite, washed 6 times with pure DMF and then with MeOH (several cycles). The combined filtrate and washings were concentrated to dryness under reduced pressure and the residue was slurried with diethyl ether to give a greenish solid 9-methoxy-1,3-dioxo-1,2,3,6-tetrahydropyrrolo [ 3,4-c] carbazole-4-carboxylic acid (5) was obtained. This reaction is repeated 5 times on this scale and the products are mixed to give 9-methoxy-1,3-dioxo-1,2,3,6-tetrahydropyrrolo [3,4-c] carbazole-4-carboxylic acid (8.1 g, 84%) was obtained. A portion of the product was adsorbed onto silica and then purified by chromatography on silica eluting with EtOAc. The product is triturated with diethyl ether and converted to an orange solid 9-methoxy-1,3-dioxo-1,2,3,6-tetrahydropyrrolo [3,4-c] carbazole-4-ethyl with a melting point> 300 ° C. Carboxylic acid was obtained. ¹ H NMR δ [(CD ₃ ) ₂ SO] 12.15 (s, 1H), 8.42 (d, J = 2.5 Hz, 1H), 7.97 (s, 1H), 7.57 (d , J = 8.8 Hz, 1H0, 7.25 (dd, J = 8.8, 2.5 Hz, 1H), 3.82 (s, 3H), 3.40 (br, 2H). _{, 58.69; H, 3.55; N} , 8.40.C 16 H 10 N 2 O 5 .H 2 O calculated C, 58.54; H, 3.68; N, 8.53.

Example 5 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 prepared. 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 _was added to Et 3 N (1.17 mL, of anhydrous t- butanol (300 mL) solution of 8.38 mmol), the mixture was refluxed for 16 hours under a nitrogen atmosphere. The solution was concentrated under reduced pressure and the residue was partitioned between EtOAc and saturated aqueous NaHCO ₃ . The two layers were filtered through celite to remove insoluble material and further washed with EtOAc. The organic phase was dehydrated, the dehydrating agent was removed, and the solution was concentrated to dryness to give a yellow solid. This material was dissolved in CH ₂ Cl ₂ / trifluoroacetic acid (1: 1) (200 mL) and the solution was kept at room temperature for 1 hour. After concentration in vacuo, the residue was partitioned between EtOAc and saturated aqueous NaHCO ₃ . The EtOAc solution was dehydrated, the dehydrating agent was removed, and the solution was concentrated to dryness to give an orange solid. This was adsorbed onto silica and chromatographed. Elution with ethyl acetate / petroleum ether (1: 1) followed by ethyl acetate and then methanol / ethyl acetate (1: 9) yields 4-amino-9-methoxypyrrolo as an orange powder with a melting point of 342-345 ° C. 3,4-c] carbazole-1,3 (2H, 6H) -dione (6) (2.16 g, 93%) was obtained. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.18 (s, 1 H), 10.78 (br s, 1 H), 8.18 (d, J = 2.5 Hz, 1 H), 7.29 ( d, J = 8.7 Hz, 1H), 7.01 (dd, J = 8.7, 2.5 Hz, 1H), 6.83 (s, 1H), 6.28 (brs, 2H), 3 .82 (s, 3H). Found: C, 63.05; H, 3.99; N, 14.05. _{C 15 H 11 N 3 O 3} . Calculated for _1/2 H2O C, 63.04; H, 4.06; N, 14.7.

Example 6 Preparation of 4-iodo-9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (7) Concentrated H ₂ SO ₄ (10 mL) was prepared in Example 5. To 4-amino-9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (0.50 g, 1.78 mmol) prepared and powdered as follows at room temperature, The mixture was stirred for 5 minutes and then cooled in an ice bath. Ice water slurry (about 40 mL) was added all at once with vigorous stirring and the mixture was stirred for an additional 15 minutes to give a tan precipitate. When the internal temperature reached 3 ° C., a solution of NaNO ₂ (0.18 g, 2.65 mmol) in cold water (1 mL) was added dropwise over 30 seconds and the mixture was stirred for an additional 3 minutes. Powdered urea (74 mg, 1.23 mmol) was added and the mixture was stirred for an additional 3 minutes. Finally, a suspension of KI (1.46 g, 8.79 mmol) and CuI (1.46 g, 7.66 mmol) in cold water (10 mL) was added and the mixture was stirred vigorously for 5 minutes, then gradually And kept at this temperature for 1 hour. Ethyl acetate was added and the biphasic mixture was filtered through a plug of celite and further washed with EtOAc. The mixed organic portion was washed with 0.5N aqueous sodium sulfite solution, dehydrated, the dehydrating agent was removed, and the solution was concentrated to dryness to give an oil. This oil was chromatographed on silica. Elution with EtOAc, followed by crystallization of the product from THF / petroleum ether gave 4-iodo-9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H as a yellow powder, mp 322-325 ° C. , 6H) -dione (7) (0.32 g, 46%). ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.89 (s, 1 H), 11.29 (s, 1 H), 8.40 (d, J = 2.6 Hz, 1 H), 8.18 (s , 1H), 7.54 (d, J = 8.9 Hz, 1H), 7.24 (dd, J = 8.9, 2.6 Hz, 1H), 3.87 (s, 3H). Found: C, 45.49; H, 2.36; N, 6.92. _{C 15 H 9 IN 2 O 3} . 1 / 4H ₂ O Calculated C, 45.42; H, 2.41; N, 7.06.

Example 7 Preparation of 9-hydroxy-4-iodopyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (8) Prepared and powdered 4-iodo as in Example 6 -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (0.50 g, 1.27 mmol) was added to a freshly prepared anhydrous pyridine hydrochloride melt into a CaCl ₂ dry tube. At 200 ° C. and the mixture was stirred at this temperature for 15 minutes. Water was added and the mixture was extracted with EtOAc. The EtOAc extract was dehydrated, the dehydrating agent was removed, and the solution was concentrated to dryness to give a solid. This solid was chromatographed on silica. Eluting with EtOAc, 9-hydroxy-4-iodopyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (8) (0.43 g, 89) as an orange powder of melting point> 350 ° C. %). ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.76 (br s, 1 H), 11.24 (br s, 1 H), 9.29 (br s, 1 H), 8.27 (d, J = 2.4 Hz, 1H), 8.13 (s, 1H), 7.44 (d, J = 8.7 Hz, 1H), 7.08 (dd, J = 8.7, 2.4 Hz, 1H). Found: C, 44.90; H, 1.79; N, 7.14. Calculated for _{C 14 H 7 IN 2 O 3} C, 44.47; H, 1.87; N, 7.40.

Example 8 Preparation of 4- (2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (9) (I, Ar = 2-chlorophenyl) 9-hydroxy-4-iodopyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (41.8 mg, 0.110 mmol), 2-chlorobenzeneboronic acid (4) prepared as in Example 7. A mixture of 52 mg, 0.332 mmol) p-dioxane (3 mL) and 2N Na ₂ CO ₃ (0.5 mL) was purged with nitrogen. Pd (dppf) Cl ₂ (35 mg, 0.011 mmol) was added and the mixture was refluxed for 4 h under N ₂ and then partitioned between EtOAc and water. The organic layer was dehydrated, the dehydrating agent was removed, 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 solid carbazole (50). This was crystallized from EtOAc / petroleum ether to give 4- (2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) as a yellow powder with a melting point of 215-220 ° C. -Dione (9) (I, Ar = 2-chlorophenyl) (33.1 mg, 83%) was obtained. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.83 (br s, 1 H), 11.01 (br s, 1 H), 9.27 (br s, 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), 1H). Found: C, 65.72; H, 3.50; N, 6.97. _{C 20 H 11 ClN 2 O 3} . Calculated 1/4 EtOAc C, 65.54; H, 3.40; N, 7.28.

Example 9 9-Hydroxy-4- (3-hydroxy-4-methoxyphenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (10) (I, Ar = 3 -Hydroxy-4-methoxyphenyl) 9-hydroxy-4-iodopyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione, prepared as in Example 7, was prepared in Example 8. 9-hydroxy-4- (3-hydroxy-4-methoxyphenyl) pyrrolo [3,4-c] carbazole-1 having a melting point of 265 ° C. is reacted with 3-hydroxy-4-methoxybenzeneboronic acid by the procedure described. , 3 (2H, 6H) -dione (10) (I, Ar = 3-hydroxy-4-methoxyphenyl) (51%). ¹ H NMR δ [(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, 1H), 7.57 (s, 1H), 7.41 (d, J = 8.7 Hz, 1H), 7.22 (d, J = 2.0 Hz, 1H) ), 7.06 to 6.99 (m, 2H), 6.85 (d, J = 8.1 Hz, 1H), 3.81 (s, 3H). Calculated value of EIMS M ⁺ : 374.0900. Calcd 374.0903 for _{C 21 H 14 N 2 O 5} .

Example 10 Preparation of 9-hydroxy-4- (3-thienyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (12) (I, Ar = 3-thienyl) 9-Hydroxy-4-iodopyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione, prepared as in Example 7, was combined with 3-thienylboronic acid by the procedure described in Example 8. 9-hydroxy-4- (3-thienyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (12) (I, Ar = 3-thienyl) having a melting point of 247 ° C. ) Was obtained in a yield of 74%. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.73 (br s, 1 H), 11.05 (br s, 1 H), 9.24 (s, 1 H), 9.15 (s, 1 H), 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, 1H). Found: C, 61.05; H, 2.96; N, 7.60. _{C 18 H 10 N 2 SO 3} . Of H ₂ O Calcd C, 61.36; H, 3.43; N, 7.95.

Example 11 4- (3-Aminophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (15) (I, Ar = 3-aminophenyl) Preparation of 9-Hydroxy-4-iodopyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione prepared as in Example 7 was prepared according to the procedure described in Example 8 using 3-aminobenzene. Reaction with boronic acid yields 4- (3-aminophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (15) (I), mp 279-284 ° C. , Ar = 3-aminophenyl) was obtained in a yield of 62%. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.70 (s, 1H), 10.96 (s, 1H), 9.22 (s, 1H), 8.33 (d, J = 2.4 Hz) , 1H), 7.50 (s, 1H), 7.42 (d, J = 8.7 Hz, 1H), 7.10 to 7.03 (m, 2H), 6.77 to 6.74 (m , 1H), 6.72 to 6.68 (m, 1H), 6.61 (dd, J = 8.1, 2.3 Hz), 1H), 5.11 (brs, 2H). Calculated: C, 69.41; H, 4.12; N, 10.73. C ₂₀ H ₁₃ N ₃ Calculated _{O 3 C, 69.96; H,} 3.82; N, 12.24.

Example 12 4- (4-Aminophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (16) (I, Ar = 4-aminophenyl) Preparation of 9-Hydroxy-4-iodopyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione, prepared as in Example 7, was prepared according to the procedure described in Example 8 to 4- (4 , 4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenylamine to give 4- (4-aminophenyl) -9-hydroxypyrrolo [3] having a melting point of 256-258 ° C. , 4-c] carbazole-1,3 (2H, 6H) -dione (16) (I, Ar = 4-aminophenyl) was obtained in a yield of 57%. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.60 (s, 1 H), 10.92 (s, 1 H), 9.19 (s, 1 H), 8.31 (d, J = 2.3 Hz) , 1H), 7.48 (s, 1H), 7.39 (d, J = 8.6 Hz, 1H), 7.30 (d, J = 8.4 Hz, 2H), 7.02 (dd, J = 8.6, 2.3 Hz, 1H), 6.62 (d, J = 8.4 Hz, 2H), 5.29 (brs, 2H). Found: C, 68.09; H, 4.34; N, 11.03. _{C 20 H 13 N 3 O 3} . Calculated for _1/2 H2O C, 68.17; H, 4.00; N, 11.92.

Example 13 4- (2,6-Dimethylphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (17) (I, Ar = 2,6 -Dimethylphenyl) 9-hydroxy-4-iodopyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione prepared as in Example 7 was prepared by the procedure described in Example 8. 4- (2,6-dimethylphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) having a melting point of 230-238 ° C. by reacting with 2,6-dimethylbenzeneboronic acid ) -Dione (17) (I, Ar = 2,6-dimethylphenyl) was obtained in 62% yield. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.72 (s, 1 H), 10.95 (s, 1 H), 9.25 (s, 1 H), 8.32 (d, J = 2.3 Hz) , 1H), 7.44 (d, J = 8.7 Hz, 1H), 7.35 (s, 1H), 7.20 (t, J = 7.5 Hz, 1H), 7.12 (d, J = 7.5 Hz, 2H), 7.06 ((dd, J = 8.7, 2.3 Hz, 1H), 1.93 (s, 6H). Calculated value of EIMS M ⁺ : 356.1159. C ₂₂ Calculated value for H ₁₆ N ₂ O ₃ 356.1161.

Example 14 4- (2,3-Dichlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (18) (I, Ar = 2,3- Preparation of 9-hydroxy-4-iodopyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione, prepared as in Example 7, was prepared according to the procedure described in Example 8. 4- (2,3-dichlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione having a melting point of 233 to 235 ° C. by reacting with 3-dichlorobenzeneboronic acid (18) (I, Ar = 2,3-dichlorophenyl) was obtained in a yield of 27%. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.87 (br, 1H), 11.05 (br, 1H), 9.29 (br, 1H), 8.31 (d, J = 2.5 Hz , 1H), 7.74-7.70 (m, 1H), 7.55 (s, 1H), 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. _{C 20 H 10 Cl 2 N 2} O 3. Calculated for _1/2 H2O C, 59.13; H, 2.73; N, 6.89.

Example 15 4- (2,6-dimethoxyphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (19) (I, Ar = 2,6 -Dimethoxyphenyl) 9-hydroxy-4-iodopyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione prepared as in Example 7 was prepared by the procedure described in Example 8. 4- (2,6-dimethoxyphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) having a melting point of 275-277 ° C. by reacting with 2,6-dimethoxybenzeneboronic acid ) -Dione (19) (I, Ar = 2,6-dimethoxyphenyl) was obtained in 43% yield. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.62 (br s, 1 H), 10.83 (br s, 1 H), 9.21 (br s, 1 H), 8.29 (d, J = 2.4 Hz, 1H), 7.42 (s, 1H), 7.41 (d, J = 8.4 Hz, 1H), 7.35 (t, J = 8.4 Hz, 1H), 7.04 ( dd, J = 8.4, 2.4 Hz, 1H), 6.75 (d, J = 8.4 Hz, 2H), 3.63 (s, 6H). Found: C, 66.31; H, 4.50, N, 6.70. _{C 22 H 16 N 2 O 5} . Calculated for _1/2 H2O C, 66.49; H, 4.31; N, 7.04.

Example 16 9-Hydroxy-4- (2-methoxyphenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (20) (I, Ar = 2-methoxyphenyl) Preparation of 9-Hydroxy-4-iodopyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione, prepared as in Example 7, was prepared according to the procedure described in Example 8 using 2-methoxybenzene. 9-hydroxy-4- (2-methoxyphenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (20) (I, Ar), reacted with boronic acid, mp 216 ° C. = 2-methoxyphenyl) was obtained in a yield of 75%. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.70 (s, 1H), 10.90 (s, 1H), 9.23 (s, 1H), 8.31 (d, J = 2.4 Hz) , 1H), 7.50 (s, 1H), 7.43 (d, J = 8.0 Hz, 1H), 7.43-7.38 (m, 1H), 7.31 (dd, J = 8 0.0, 2.4 Hz, 1H), 7.11 to 7.01 (m, 3H), 3.68 (s, 3H). Found: C, 69.21; H, 3.80; N, 7.58. _{C 21 H 14 N 2 O 4} . 1 / 4H ₂ O Calculated C, 69.51; H, 4.03; N, 7.72.

Example 17 9-Hydroxy-4- (4-hydroxymethylphenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (21) (I, Ar = 4-hydroxymethyl Preparation of 9-hydroxy-4-iodopyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione prepared as in Example 7 according to the procedure described in Example 8. 9-hydroxy-4- (4-hydroxymethylphenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (mp) 266-271 ° C., reacted with hydroxymethylbenzeneboronic acid 21) (I, Ar = 4-hydroxymethylphenyl) was obtained in a yield of 34%. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.74 (br s, 1 H), 11.00 (br s, 1 H), 9.25 (br s, 1 H), 8.34 (d, J = 2.4 Hz, 1H), 7.56 (d, J = 8.3 Hz, 2H), 7.56 (s, 1H), 7.43 (d, J = 8.7 Hz, 1H), 7.40 ( d, J = 8.3 Hz, 1H), 7.06 (dd, J = 8.7, 2.4 Hz, 1H), 5.27 (t, J = 5.7 Hz, 1H), 4.59 (d , J = 5.7 Hz, 2H). Found: C, 69.74; H, 4.04; N, 7.57. _{C 21 H 14 N 2 O 4} . 1 / 4H ₂ O Calculated C, 69.51; H, 4.02; N, 7.72.

Example 18 9-Hydroxy-4- (2-trifluoromethylphenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (22) (I, Ar = 2-tri Preparation of 9-hydroxy-4-iodopyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione, prepared as in Example 7, was prepared by the procedure described in Example 8. 9-hydroxy-4- (2-trifluoromethylphenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H)-having a melting point of 210 ° C. by reacting with 2-trifluoromethylbenzeneboronic acid Dione (22) (I, Ar = 2-trifluoromethylphenyl) was obtained in a yield of 47%. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.81 (br s, 1 H), 11.01 (br s, 1 H), 9.30 (br s, 1 H), 8.31 (d, J = 2.4 Hz, 1 H), 7.86 (br d, J = 7.2 Hz, 1 H), 7.75-7.64 (m, 2 H), 7.51 (s, 1 H), 7.49 (br d, J = 7.6 Hz, 1H), 7.46 (d, J = 8.7 Hz, 1H), 7.09 (dd, J = 8.7, 2.4 Hz, 1H). Calculated value of EIMS M ⁺ : 396.0721. Calc'd for C ₂₁ H ₁₁ F ₃ N ₂ O ₃ 3966.0722.

Example 19 9-Hydroxy-4- (4-hydroxy-3-methoxyphenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (23) (I, Ar = 4 -Hydroxy-3-methoxyphenyl) 9-hydroxy-4-iodopyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione, prepared as in Example 7, was prepared in Example 8. Reaction with 2-methoxy-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenol by the described procedure yields 9-hydroxy-, mp 290-295 ° C. 4- (4-hydroxy-3-methoxyphenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (23) (I, Ar = 4-hydroxy-3-methoxyphenyl). Yield Obtained at a rate of 58%. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.67 (br s, 1 H), 10.97 (br s, 1 H), 9.22 (br s, 1 H), 9.15 (s, 1 H) , 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). Calculated FABMS, [M + H] ⁺ : 375.0973. Calcd 375.0981 for _{C 21 H 15 N 2 O 5} .

Example 20 4- (2-Ethylphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (501) (I; Ar = 2-ethylphenyl) Preparation of 9-Hydroxy-4-iodopyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione prepared as in Example 7 was prepared by the procedure described in Example 8 with 2-ethylbenzeneboron. React with acid to give 4- (2-ethylphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H at melting point (MeOH / CH ₂ Cl ₂ / hexane) 273-275 ° C. , 6H) -dione (501) (1; Ar = 2-ethylphenyl) was obtained in a yield of 69%. ¹ H NMR [(CD ₃ ) ₂ SO] δ 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, 1 H), 7.36 (td, J = 7.2, 1.5 Hz, 1 H), 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.H). 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. Calculated C of _{C 22 H 16 N 2 O 3} , 74.15; H, 4.53; N, 7.86.

Example 21 9-Hydroxy-4- [2- (hydroxymethyl) phenyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (503) (I; Ar = 2 Preparation of (Hydroxymethyl) phenyl) 9-Hydroxy-4-iodopyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione prepared as in Example 7 was described in Example 8. 9-Hydroxy-4- [2- (hydroxymethyl) with a melting point (THF / CH ₂ Cl ₂ / Hexane) 270-280 ° C. reacted with 2- (hydroxymethyl) benzeneboronic acid cyclic monoester by the procedure Phenyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (503) (I; Ar = 2- (hydroxymethyl) phenyl) was obtained in a yield of 57%. ¹ H NMR [(CD ₃ ) ₂ SO] δ 11.76 (br s, 1 H), 10.96 (br s, 1 H), 9.25 (br s, 1 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, 1H), 7.31 (td, J = 7.4, 0.9 Hz, 1H), 7.23 (dd, J = 7.5, 1.0 Hz, 1H) ), 7.06 (dd, J = 8.7, 2.5 Hz, 1H), 5.00 (t, J = 5.4 Hz, 1H), 4.33 (dd, J = 13.6, 5.. 2 Hz, 1 H), 4.24 (dd, J = 13.5, 5.3 Hz, 1 H). Found: C, 68.41; H, 4.29; N, 7.59. _{C 21 H 14 N 2 O 4} . 1/2 H ₂ O Calculated C, 68.66; H, 4.12; N, 7.63.

Example 22 4- (2-Ethoxyphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (504) (I; Ar = 2-ethoxyphenyl) Preparation of 9-Hydroxy-4-iodopyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione, prepared as in Example 7, was prepared according to the procedure described in Example 8 with 2-ethoxybenzene. Reacting with boronic acid, 4- (2-ethoxyphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (melting point (THF / CH ₂ Cl ₂ / hexane) 190-193 ° C. 2H, 6H) -dione (504) (I; Ar = 2-ethoxyphenyl) was obtained in a yield of 74%. ¹ H NMR [(CD ₃ ) ₂ SO] δ 11.71 (br s, 1 H), 10.91 (br s, 1 H), 9.23 (s, 1 H), 8.31 (d, J = 2. 4 Hz, 1 H), 7.51 (s, 1 H), 7.43 (d, J = 8.7 Hz, 1 H), 7.38 (td, J = 7.8, 1.7 Hz, 1 H), 7. 33 (dd, J = 7.5, 1.7 Hz, 1H), 7.07 (br d, 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 (q, J = 6.7 Hz, 2H), 1.11 (t, J = 6.9 Hz, 3H) . Found: C, 70.63; H, 4.74; N, 6.88. _{C 22 H 16 N 2 O 4} . 1/4 calculated for THF C, 70.76; H, 4.65; N, 7.18.

Example 23 Preparation of 9-hydroxy-4- (2-thienyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (505) (I; Ar = 2-thienyl) 9-Hydroxy-4-iodopyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione, prepared as in Example 7, was combined with 2-thiopheneboronic acid by the procedure described in Example 8. 9-hydroxy-4- (2-thienyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) with a melting point (THF / CH ₂ Cl ₂ / hexane) 179-184 ° C. -Dione (505) (I; Ar = 2-thienyl) was obtained with a yield of 69%. ¹ H NMR [(CD ₃ ) ₂ SO] δ 11.75 (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, 1H), 7.20 (dd, J = 5.1, 3.6 Hz, 1H), 7.07 (dd, J = 8.7, 2.H). 5Hz, 1H). Found: C, 62.38; H, 3.11; N, 7.74. _{C 18 H 10 N 2 O 3} S. 3/4 H ₂ O Calculated C, 62.15; H, 3.33; N, 8.05.

Example 24 3- (9-Hydroxy-1,3-dioxo-1,2,3,6-tetrahydropyrrolo [3,4-c] carbazol-4-yl) benzaldehyde (507) (I; Ar = Preparation of 3-formylphenyl) 9-Hydroxy-4-iodopyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione prepared as in Example 7 was prepared according to the procedure described in Example 8. To 3- (9-hydroxy-1,3-dioxo-1,2,3,6-) having a melting point (THF / CH ₂ Cl ₂ / hexane) of 280-286 ° C. Tetrahydropyrrolo [3,4-c] carbazol-4-yl) benzaldehyde (507) (I; Ar = 3-formylphenyl) was obtained in a yield of 69%. ¹ H NMR [(CD ₃ ) ₂ SO] δ 11.82 (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, 1H), 8.14 (t, J = 1.4 Hz, 1H), 7.97 (m, 2H), 7.70 (t, J = 7.7 Hz) , 2H), 7.65 (s, 1H), 7.46 (d, J = 8.7 Hz, 1H), 7.08 (dd, J = 8.7, 2.5 Hz, 1H). Calculated value of FABMS [M + H] ⁺ : 357.0857. Calcd 357.0875 for _{C 21 H 13 N 2 O 4} .

Example 25 9-Hydroxy-4- [2- (methylsulfanyl) phenyl] pyrrolo [3,4-c] carbazole-1.3 (2H, 6H) -dione (508) (I; Ar = 2 Preparation of (methylsulfanyl) phenyl) 9-Hydroxy-4-iodopyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione prepared as in Example 7 was described in Example 8. by procedures was reacted with 2- (methylthio) benzene boronic acid, mp (MeOH / _{CH 2} Cl 2 / hexane) 208-216 ° C. of 9-hydroxy-4- [2- (methylsulfanyl) phenyl] pyrrolo [3 , 4-c] carbazole-1,3 (2H, 6H) -dione (508) (I; Ar = 2- (methylsulfanyl) phenyl) was obtained in a yield of 72%. ¹ H NMR [(CD ₃ ) ₂ SO] δ 11.76 (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 (br.d, J = 7.5 Hz, 1H), 7.27 (dd, J = 7.8, 2.2 Hz, 1H), 7.24 (td, J = 7.3, 1.3 Hz) , 1H), 7.07 (dd, J = 8.7, 2.5 Hz, 1H), 2.32 (s, 3H). Found: C, 66.55; H, 3.88; N, 7.38. _{C 21 H 14 N 2 O 3} S. 1/4 H ₂ O Calculated C, 66.57; H, 3.86; N, 7.39.

Example 26 4- (9-Hydroxy-1,3-dioxo-1,2,3,6-tetrahydropyrrolo [3,4-c] carbazol-4-yl) benzaldehyde (509) (I; Ar = Preparation of 4-formylphenyl) 9-Hydroxy-4-iodopyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione prepared as in Example 7 was prepared according to the procedure described in Example 8. With 4-formylbenzeneboronic acid to give 4- (9-hydroxy-1,3-dioxo-1,2,3,6-tetrahydro) of melting point (THF / CH ₂ Cl ₂ / pentane) 276-280 ° C. Pyrrolo [3,4-c] carbazol-4-yl) benzaldehyde (509) (I; Ar = 4-formylphenyl) was obtained in a yield of 52%. ¹ H NMR [(CD ₃ ) ₂ SO] δ 11.84 (br s, 1 H), 11.07 (br s, 1 H), 10.11 (s, 1 H), 9.28 (br s, 1 H), 8.34 (d, J = 2.3 Hz, 1H), 8.00 (d, J = 8.2 Hz, 2H), 7.85 (d, J = 8.1 Hz, 2H), 7.65 (s) , 1H), 7.46 (d, J = 8.7 Hz, 1H), 7.08 (dd, J = 8.7, 2.4 Hz, 1H). Found: C, 68.43; H, 4.16; N, 7.26. _{C 21 H 12 N 2 O 4} . 3/4 H ₂ O Calculated C, 68.20; H, 3.68; N, 757. Calculated value of FABMS [M + H] ⁺ : 357.0841. Calcd 357.0875 for _{C 21 H 13 N 2 O 4} .

Example 27 9-Hydroxy-4- [2- (methylsulfinyl) phenyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (510) (I; Ar = 2 Preparation of (methylsulfinyl) phenyl 9-Hydroxy-4- [2- (methylsulfanyl) phenyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione prepared according to Example 25 (508) ) (34.5 mg, 0.092 mmol) and 2-phenylsulfonyl-3-phenyloxaziridine (Davis reagent) (26.5 mg, 0.102 mmol) in THF (10 mL) at 20 ° C. for 2.5 hours. stirred, then .0~3% MeOH / _{CH 2} Cl 2 was subjected to silica gel chromatography adsorbed directly onto silica gel, then 3 % Eluted with MeOH / _{CH 2} Cl 2, (after crystallization from _THF / CH 2 _Cl 2 / pentane) as a melting point 321 to 323 ° C. a yellow solid 9-hydroxy-4- [2- (methylsulfinyl) phenyl ] pyrrolo [3,4-c] carbazole -1,3 (2H, 6H) - dione ^{(510). (I; Ar} = 2- ( methylsulfinyl) phenyl) was obtained in 86% yield 1 H NMR [ (CD ₃ ) ₂ SO] δ 11.86, 11.85 (2br s, 1H), 11.09 (br s, 1H), 9.30 (br s, 1H), 8.32 (d, J = 2 .4 Hz, 1H), 8.04, 7.97 (2d, J = 7.6 Hz, 1H), 7.74 (t, J = 7.6 Hz, 1H), 7.65, 7.62 (2t, J = 7.4 Hz, 1H), 7.62, 7.54 (2 s, 1 ), 7.47 (d, J = 9.1 Hz, 1H), 7.44 (d, J = 8.4 Hz, 1H), 7.09 (dd, J = 8.7, 2.5 Hz, 1H) 2.43, 2.31 (2s, 3H) Measured values: C, 64.60; H, 3.88; N, 6.87.Calculated value of C ₂₁ H ₁₄ N ₂ O ₄ S C, 64 .61; H, 3.61; N, 7.18.

Example 28 9-Hydroxy-4- (4-hydroxyphenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (24) (I, Ar = 4-hydroxyphenyl) The 9-hydroxy-4- (4-methoxyphenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione prepared as described in Example 34 was prepared in Example 80. 9-hydroxy-4- (4-hydroxyphenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H), mp 230 ° C., reacted with BBr ₃ using the procedure of Scheme 2 described -Dione (24) (I, Ar = 4-hydroxyphenyl) was obtained in 92% yield. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.67 (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, 1H), 7.51 (s, 1H), 7.43 (d, J = 8.7 Hz, 1H), 7.41 (d, J = 8.6 Hz, 2H) ), 7.04 (dd, J = 8.7, 2.4 Hz, 1H), 6.84 (d, J = 8.6 Hz, 2H). Calculated value of FABMS [M + H] ⁺ : 345.0875. Calcd 345.0875 for _{C 20 H 13 N 2 O 4} .

Example 29 9-Hydroxy-4- (3-hydroxyphenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (25) (I, Ar = 3-hydroxyphenyl) Preparation of 9-hydroxy-4- (3-methoxyphenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (prepared as described in Example 35) 80 reaction with BBr ₃ using the procedure described in Scheme 2 to give 9-hydroxy-4- (3-hydroxyphenyl) pyrrolo [3,4-c] carbazole- 1,3 (2H, 6H) -dione (25) (I, Ar = 3-hydroxyphenyl) was obtained in 88% yield. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.73 (br s, 1 H), 11.00 (br s, 1 H), 9.48 (br s, 1 H), 9.24 (s, 1 H) 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, 1 H), 7.05 (dd, J = 8.7, 2.4 Hz, 1 H), 7.01 to 6.96 (m, 2 H), 6.82 (dd, J = 8) .2, 2.1 Hz, 1H). Calculated value of FABMS [M + H] ⁺ : 345.0865: Calculated value of C ₂₀ H ₁₃ N ₂ O ₄ 345.0875.

Example 30 4- (2-Chloro-6-hydroxyphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-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, prepared as in Example 33) 6H) -dione is reacted with BBr ₃ using the procedure of Scheme 2 described in Example 80 to give 4- (2-chloro-6-hydroxyphenyl) -9-hydroxypyrrolo [mp 228-235 ° C. 3,4-c] carbazole-1,3 (2H, 6H) -dione (26) (I, Ar = 2-chloro-6-hydroxyphenyl) was obtained in a yield of 70%. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.73 (s, 1 H), 10.94 (s, 1 H), 9.75 (br s, 1 H), 9.25 (s, 1 H), 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) .1Hz, 1H). Calculated value of FABMS [M + H] ⁺ : 381.0461, 379.0479. Calculated 381.0456,379.0486 of _{C 20 H 12 ClN 2 O 4} .

  An array format by reacting the compounds described in Examples 31-35 with an appropriately substituted arylboronic acid using the procedure described in Example 8 with iodide (8) prepared as described in Example 7. It was prepared with.

Example 31 4- (3-Chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (I; Ar = by reaction with 3-chlorobenzeneboronic acid 3-Chlorophenyl) (866). Found [M + H] ⁺ : 363.

Example 32 4- (4-Chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (I; Ar = by reaction with 4-chlorobenzeneboronic acid 4-Chlorophenyl) (867). Found [M + H] ⁺ : 363.

Example 33 4- (2-Chloro-6-methoxyphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H by reaction with 2-chloro-6-methoxybenzeneboronic acid , 6H) -dione (I; Ar = 2-chloro-6-methoxyphenyl) (868). Found [M + H] ⁺ : 393.

Example 34 9-Hydroxy-4- (4-methoxyphenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (I;) by reaction with 4-methoxybenzeneboronic acid Preparation of Ar = 4-methoxyphenyl) (870). Actual value [M + H] ⁺ : 359

Example 35 9-Hydroxy-4- (3-methoxyphenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (I;) by reaction with 4-methoxybenzeneboronic acid Preparation of Ar = 4-methoxyphenyl). Actual value [M + H] ⁺ : 359

Example 36 A series using multiple parallel synthesis techniques from 9-hydroxy-4-iodopyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione prepared as in Example 7. Preparation of compounds of Combichem procedure 1
A solution of 9-hydroxy-4-iodo-6H-pyrrolo [3,4-c] carbazole-1,3-dione (0.1 mmol) in dioxane (1 ml) prepared as in Example 7 in an 8 ml screw mouth vial. , Reagent 1 (see table) (0.1 mmol) in 1: 1 dioxane / 2.5M K ₂ CO ₃ (1 ml), and [1,1′bis (diphenylphosphino) ferrocene] -dichloropalladium (II) Complex and dichloromethane (0.003 g, 0.0037 mmol) were added. The vial was capped and the reaction mixture was shaken at 90 ° C. for 4 hours. After cooling to room temperature, the solution was removed under reduced pressure. Purification was carried out using reverse phase HPLC (3% eluent of 3% n-propanol in acetonitrile and 3% n-propanol in water; C-18 column). The product was characterized by mass spectral analysis (see Table 1).

Combichem procedure 2
Into an 8 ml screw-mouth vial, 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). Solution, 1: 1 anhydrous toluene / dimethylformamide (1 ml) solution of reagent 1 (see table), and 0.05 M palladium (II) diacetate and 0.2 M o-dicyclohexylphosphinobiphenyl in anhydrous toluene (20 μl), And 40 mg of K ₃ PO ₄ .2H ₂ O was added under N ₂ . The vial was capped and the reaction mixture was shaken at 100 ° C. for 20 hours. After cooling to room temperature, the solution was removed under reduced pressure. Purification was carried out using reverse phase HPLC (3% eluent of 3% n-propanol in acetonitrile and 3% n-propanol in water; C-18 column). The product was characterized by mass spectral analysis (see Table 1).

  Scheme 2 procedure

  Representative Procedure for Method 2 of Scheme 2

Example 37 Preparation of 2- [2- (2-chlorophenyl) ethenyl] -5-methoxy-1H-indole (II; Ar = 2-chlorophenyl) (27) Lithium diisopropylamide (34.4 mL of 1.5N solution) , 0.052 mol) was added dropwise under nitrogen to a suspension of benzyl (triphenyl) phosphonium chloride (20.17 g, 0.048 mol) in anhydrous THF (200 mL) and the solution was stirred at room temperature for 15 minutes. 5-Methoxy-1H-indole-2-carbaldehyde (1) (6.99 g, 0.040 mol) in THF (30 mL) was added and stirring was continued for 15 minutes at room temperature, then the reaction mixture was refluxed for 6 hours. And heated. The cooled solution was diluted with water and extracted with EtOAc, the organic phase was dried, the dehydrating agent was removed, and the solution was concentrated to dryness to give an oil. The oil was adsorbed onto silica and chromatographed on silica. Elution with ethyl acetate / petroleum ether (1: 1) gave 2- [2- (2-chlorophenyl) ethenyl] -5-methoxy-1H-indole (27) as a mixture of E / Z isomers in 9 .76 g, 87%. A small sample was crystallized from methanol to give the pure E-isomer, mp 135-137 ° C. ¹ H NMR δ (CDCl ₃ ) 11.39 (s, 1H), 7.86 (dd, J = 7.8, 1.5 Hz, 1H), 7.49 (dd, J = 8.0, 1. 2 Hz, 1H), 7.43 (d, J = 16.4 Hz, 1H), 7.37 (m, 1H), 7.31 to 7.23 (m, 3H), 7.01 (d, J = 2.4 Hz, 1H), 6.77 (dd, J = 8.7, 2.4 Hz, 1H), 6.56 (s, 1H), 3.75 (s, 3H). Found: C, 72.01; H, 5.03; N, 4.98. C ₁₇ H ₁₄ ClNO Calculated C, 71.96; H, 4.79; N, 4.94.

  Representative Procedure for Method 3 of Scheme 2

Example 38 1- (3-{[tert-Butyl (dimethyl) silyl] oxy} propyl) -2- [2- (2-chlorophenyl) ethenyl] -5-methoxy-1H-indole (III: Ar = Preparation of 2-chlorophenyl, R ¹⁰ = CH ₂ CH ₂ CH ₂ OSiMe ₂ t-Bu) (28) Sodium hydride (1.05 g 50% dispersion in mineral oil, 0.022 mol) was prepared according to Example 37. 2- [2- (2-Chlorophenyl) ethenyl] -5-methoxy-1H-indole (4.13 g, 0.014 mol) in DMF (30 mL) was added and the solution was stirred at room temperature for 5 minutes. 3-Bromopropyl tert-butyl (dimethyl) silyl ether (4.04 g, 0.016 mol) was added and stirring continued for 2 hours. The solution was diluted with water and extracted with EtOAc. It is washed thoroughly with brine, the organic phase is dehydrated, the dehydrating agent is removed, the solution is concentrated to dryness and the oily solid 1- (3-{[tert-butyl (dimethyl) silyl] Oxy} propyl) -2- [2- (2-chlorophenyl) ethenyl] -5-methoxy-1H-indole (28) (4.98 g) was obtained (as a mixture of E / Z isomers). This was used without further purification.

Example 39 6- (3-{[tert-Butyl (dimethyl) silyl] oxy} propyl) -4- (2-chlorophenyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 ( 2H, 6H) - dione (V; Ar = 2- ^{_{chlorophenyl, R 10 = CH 2 CH 2}} CH 2 OSiMe 2 t-Bu) ( prepared by Preparative example 38 of 29) 1- (3 - {[ tert- Butyl (dimethyl) silyl] oxy} propyl) -2- [2- (2-chlorophenyl) ethenyl] -5-methoxy-1H-indole is prepared by the procedure described in Example 68 except that the reaction time is 16 hours. Reacted with maleimide. The resulting product was reacted with MnO ₂ by the procedure described in Example 81 except that the reaction time was 8 hours. After chromatography on silica, the product is triturated with diethyl ether to give 6- (3-{[tert-butyl (dimethyl) silyl] oxy} propyl) -4- as a yellow solid with a melting point of 199-201 ° C. 4.87 g of (2-chlorophenyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (29) was obtained in a yield of 61%. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.12 (br, 1H), 8.52 (d, J = 2.6 Hz, 1H), 7.75 (s, 1H), 7.66 (d , J = 8.9 Hz, 1H), 7.57 (dd, J = 8.3 Hz, 1H), 7.5 to 7.4 (m, 3H), 7.30 (dd, J = 8.9, 2.6 Hz, 1H), 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. C ₃₀ H ₃₂ ClSiN ₂ Calculated _{O 4 C, 65.74; H,} 5.88; N, 5.11.

Example 40 4- (2-Chlorophenyl) -6- (3-hydroxypropyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (V; Ar = Preparation of 2-chlorophenyl, R ¹⁰ = CH ₂ CH ₂ CH ₂ OH) (31) 3N HCl (50 mL) was prepared according to Example 39. 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) in 1: 1 THF / methanol ( (200 mL) was added to the solution. After stirring at room temperature for 2 hours, most of the solvent was removed under reduced pressure, 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. The product was filtered off and triturated several times with diethyl ether. The solid was crystallized from THF / petroleum ether to give 4- (2-chlorophenyl) -6- (3-hydroxypropyl) -9-methoxypyrrolo [3,4-c] carbazole as a yellow powder with a melting point of 228-230 ° C. -1,3 (2H, 6H) - dione (V; Ar = 2- _{^{chlorophenyl, R 10 = CH 2 CH 2}} CH 2 OH) and (31) 3.77 g was obtained in 88% yield. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.12 (br s, 1 H), 8.52 (d, J = 2.5 Hz, 1 H), 7.80 (s, 1 H), 7.70 ( d, J = 8.9 Hz, 1H), 7.58 (dd, J = 8.1, 2.2 Hz, 1H), 7.53 to 7.42 (m, 3H), 7.31 (dd, J = 8.9, 2.5 Hz, 1H), 4.63 (br, 1H), 4.53 (t, J = 6.9 Hz, 2H), 3.91 (s, 3H), 3.40 (m , 2H), 1.91 (m, 2H). Found: C, 66.00; H, 4.23; N, 6.55. C ₂₄ H ₁₉ ClN ₂ Calculated _{O 4 C, 66.29; H,} 4.40; N, 6.44.

Example 41 2- {2- [2- (2-chlorophenyl) ethenyl] -5-methoxy-1H-indol-1-yl} ethanol (III; Ar = 2-chlorophenyl, R ¹⁰ = CH ₂ CH ₂ Preparation of OH) (44) 2- [2- (2-Chlorophenyl) ethenyl] -5-methoxy-1H-indole (27) prepared according to Example 37 was converted to 2-bromoethyltetrahydro-2H-pyran-2-yl. Alkylation with ether by the procedure described in Example 38 and reaction of the crude product with 2N HCl in methanol gave 2- {2- [2- (2-chlorophenyl) ethenyl] -5-methoxy- 1H- indol-1-yl} ethanol (III; Ar = 2- _{^{chlorophenyl, R 10 = CH 2 CH 2}} OH) (44) yield 86% It was obtained as a mixture of E / Z isomers. This was used without further purification.

Example 42 4- (2-Chlorophenyl) -6- (2-hydroxyethyl) -9-methoxy-4,5,6,10c-tetrahydropyrrolo [3,4-c] carbazole-1,3 (2H , 3aH) -dione (IV; Ar = 2-chlorophenyl, R ¹⁰ = CH ₂ CH ₂ OH) (45) 2- {2- [2- (2-chlorophenyl) ethenyl]-prepared according to Example 41 5-Methoxy-1H-indol-1-yl} ethanol (III; Ar = 2-chlorophenyl, R ¹⁰ = CH ₂ CH ₂ OH) (44) was reacted with maleimide according to the procedure described in Example 68 to give an oil Solid 4- (2-chlorophenyl) -6- (2-hydroxyethyl) -9-methoxy-4,5,6,10c-tetrahydropyrrolo [3,4-c] carbazole -1,3 (2H, 3aH) - dione; the (IV Ar = _{^{2-chlorophenyl, R 10 = CH 2 CH 2}} OH) (45) was obtained in 79% yield. This was used without further purification.

Example 43 4- (2-Chlorophenyl) -6- (2-hydroxyethyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (V; Ar = ^{_{2-chlorophenyl, R 10 = CH 2 CH 2}} OH) (46) was prepared by Preparative example 42 4- (2-chlorophenyl) -6- (2-hydroxyethyl) -9-methoxy -4,5,6 , 10c-tetrahydropyrrolo [3,4-c] carbazole-1,3 (2H, 3aH) -dione (IV; Ar = 2-chlorophenyl, R ¹⁰ = CH ₂ CH ₂ OH) (45) except a 18 hour reacted with MnO ₂ by the procedure described in example 79, as a yellow powder having a melting point of two hundred fifty-five to two hundred fifty-seven ° C. 4-(2-chlorophenyl) -6- (2-hydroxyethyl ) -9-methoxy-pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) - dione (V; Ar = ^{_{2-chlorophenyl, R 10 = CH 2 CH 2}} OH) and (46) yield 72 %. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.10 (br s, 1H), 8.52 (d, J = 2.6 Hz, 1H), 7.80 (s, 1H), 7.71 ( d, J = 9.0 Hz, 1H), 7.59-7.56 (m, 1H), 7.52-7.43 (m, 4H), 7.29 (dd, J = 9.0, 2) 2.6 Hz, 1H), 4.84 (t, J = 5.0 Hz, 1H), 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. Calculated _{C 23 H 17 ClN 2 O 4} C, 65.64; H, 4.07; N, 6.66.

Example 44 4- (2-Chlorophenyl) -6- (2-hydroxyethyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = Preparation of 2-chlorophenyl, R ¹⁰ = CH ₂ CH ₂ OH) (47) 4- (2-Chlorophenyl) -6- (2-hydroxyethyl) -9-methoxypyrrolo [3,4-prepared according to Example 43 c] Carbazole-1,3 (2H, 6H) -dione (V; Ar = 2-chlorophenyl, R ¹⁰ = CH ₂ CH ₂ OH) (46) and BBr ₃ using the procedure described in Example 80. React to 4- (2-chlorophenyl) -6- (2-hydroxyethyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (yellow / orange powder having a melting point of 265 ° C. H, 6H) - dione (VI; Ar = 2- ^{chlorophenyl,} to give the _{R 10 = CH 2 CH 2 OH} ) (47) in 87% yield. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.04 (br s, 1 H), 9.33 (br s, 1 H), 8.38 (d, J = 2.4 Hz, 1 H), 7.75 (S, 1H), 7.60 to 7.56 (m, 2H), 7.52 to 7.43 (m, 4H), 7.12 (dd, J = 8.8, 2.4 Hz, 1H) 4.83 (t, J = 5.5 Hz, 1H), 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. _{C 22 H 15 ClN 2 O 4} . Calculated for _1/2 H2O C, 63.54; H, 3.87; N, 6.73.

Example 45 Preparation of 5-methoxy-2- [2- (2-methoxy-5-nitrophenyl) ethenyl] -1H-indole (II; Ar = 2-methoxy-5-nitrophenyl) (35) -Methoxy-1H-indole-2-carbaldehyde (1) was reacted with 2-methoxy-5-nitrobenzyltriphenylphosphonium chloride by the procedure described in Example 37 to give an orange solid (E / Z isomer). Of 2-methoxy-2- [2- (2-methoxy-5-nitrophenyl) ethenyl] -1H-indole (II; Ar = 2-methoxy-5-nitrophenyl) (35) in a yield of 76 %. This was used without further purification.

Example 46 Preparation of 5-methoxy-2- [2- (3,5-dinitrophenyl) ethenyl] -1H-indole (II; Ar = 3,5-dinitrophenyl) (40) Indole-2-carbaldehyde (1) was reacted with 3,5-dinitrobenzyltriphenylphosphonium bromide by the procedure described in Example 37 to give 5 of an orange solid (mixture of E / Z isomers). -Methoxy-2- [2- (3,5-dinitrophenyl) ethenyl] -1H-indole (II; Ar = 3,5-dinitrophenyl) (40) was obtained in a yield of 26%. This was used without further purification.

Example 47 4- (3,5-dinitrophenyl) -9-methoxy-4,5,6,10c-tetrahydropyrrolo [3,4-c] carbazole-1,3 (2H, 3aH) -dione ( IV; Preparation of Ar = 3,5-dinitrophenyl, R ¹⁰ = H) (41) 5-Methoxy-2- [2- (3,5-dinitrophenyl) ethenyl] prepared as described in Example 46 1H-indole (II; Ar = 3,5-dinitrophenyl) (40) is reacted with maleimide by the procedure described in Example 69 to give 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, R ¹⁰ = H) (41 It was obtained in 89% yield. This was used without further purification.

Example 48 4- (3,5-dinitrophenyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (V; Ar = 3,5-dinitrophenyl) , R ¹⁰ = H) (42) Preparation of 4- (3,5-dinitrophenyl) -9-methoxy-4,5,6,10c-tetrahydropyrrolo [3,4] prepared as described in Example 47. -C] carbazole-1,3 (2H, 3aH) -dione (IV; Ar = 3,5-dinitrophenyl, R = H) (41) is reacted with DDQ by the procedure described in Example 70; 4- (3,5-dinitrophenyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (V; Ar = 3,5-dinitro as a reddish solid ^phenyl, R 10 = H) (42 It was obtained in 42% yield. This was used without further purification.

Example 49 4- (3,5-dinitrophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (V; Ar = 3,5-dinitrophenyl) , R ¹⁰ = H) Preparation of (43) 4- (3,5-dinitrophenyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H) prepared as described in Example 48 , 6H) -dione (V; Ar = 3,5-dinitrophenyl, R ¹⁰ = H) (42) was reacted with pyridinium hydrochloride by the procedure described in Example 81 to give an orange color with a melting point> 330 ° C. 4- (3,5-dinitrophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (V; Ar = 3,5-dinitrophenyl, R ¹⁰ as a powder = H) (43) Obtained in 57% yield. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.94 (br s, 1 H), 11.18 (br s, 1 H), 9.32 (br s, 1 H), 8.91 (s, 3 H) 8.35 (d, J = 2.3 Hz, 1H), 7.83 (s, 1H), 7.49 (d, J = 8.7 Hz, 1H), 7.11 (dd, J = 8. 7, 2.3 Hz, 1 H).

Example 50 Preparation of 5-methoxy-2- [2- (2-methoxyphenyl) ethenyl] -1H-indole (II; Ar = 2-methoxyphenyl) (97) 5-methoxy-1H-indole-2 Carbaldehyde (1) was reacted with 2-methoxybenzyltriphenylphosphonium chloride by the procedure described in Example 37 to give 5-methoxy-2- [2- (2-Methoxyphenyl) ethenyl] -1H-indole (II; Ar = 2-methoxyphenyl) (97) was obtained in a yield of 98%. This was used without further purification.

Example 51 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 2 OSiMe 2 t-Bu) prepared 5-methoxy-2- [2- (2-methoxyphenyl like of example 50 (98)) ethenyl ] -1H-indole (II; Ar = 2-methoxyphenyl) (97) was reacted with 3-bromopropyl tert-butyl (dimethyl) silyl ether by the procedure described in Example 38 to give 1- (3- {[Tert-Butyl (dimethyl) silyl] oxy} propyl) -5-methoxy-2- [2- (2-methoxyphenyl) ethenyl] -1H-India Le; the (III Ar = ^{_{2-methoxyphenyl, R 10 = CH 2 CH 2}} CH 2 OSiMe 2 t-Bu) (98) was obtained in 97% yield. It was used without further purification.

Example 52 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; R 10 = CH 2 CH 2}} CH 2 OSiMe 2 t-Bu) (99) preparation example 51 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 2 OSiMe 2 t-Bu) (98), is reacted with a maleimide by the procedure described in example 68 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; R 10 = CH 2 CH 2}} CH 2 OSiMe 2 t-Bu) (99) yield 89% Got in. This was used without further purification.

Example 53 6- (3-Hydroxypropyl) -9-methoxy-4- (2-methoxyphenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (V; Ar = ^{_{2-methoxyphenyl, R 10 = CH 2 CH 2}} CH 2 OH) preparation of (100).
6- (3-{[tert-Butyl (dimethyl) silyl] oxy} propyl) -9-methoxy-4- (2-methoxyphenyl) -4,5,6,10c prepared as described in Example 52. - tetrahydropyrrolo [3,4-c] carbazole -1,3 (2H, 3aH) - dione ^(IV;; Ar = 2- methoxyphenyl _{R 10 = CH 2 CH 2 CH} 2 OSiMe 2 t-Bu), performed React with DDQ by the procedure described in Example 70, react with 2N HCl in THF / methanol to give 6- (3-hydroxypropyl) -9-methoxy-4- ( 2-methoxyphenyl) pyrrolo [3,4-c] carbazole -1,3 (2H, 6H) - dione (V; Ar = 2-methoxyphenyl, R = _CH 2 _CH CH ₂ OH) (100) was obtained in 72% yield. ¹ H NMR δ [(CD ₃ ) 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, 1H), 7.45-7.40 (m, 1H), 7.36 (dd, J = 7.4, 1.7 Hz, 1H), 7.29 (dd, J = 8 .9, 2.7 Hz, 1H), 7.11 (d, J = 8.1 Hz, 1H), 7.06 (dd, J = 7.2, 7.2 Hz, 1H), 4.63 (t, J = 4.8 Hz, 1H), 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. C ₂₅ H ₂₂ Calculated _{N 2 O 5 C, 69.76;} H, 5.15; N, 6.51.

Example 54 9-Hydroxy-4- (2-hydroxyphenyl) -6- (3-hydroxypropyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = ^{_{2-hydroxyphenyl, R 10 = CH 2 CH 2}} CH 2 OH) preparation of (101).
6- (3-hydroxypropyl) -9-methoxy-4- (2-methoxyphenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H)-prepared as described in Example 53 Dione (V; Ar = 2-methoxyphenyl, R ¹⁰ = CH ₂ CH ₂ CH ₂ OH) (100) was reacted with BBr ₃ using the procedure described in Example 80 to give a melting point of 306-309 ° C. As an orange powder, 9-hydroxy-4- (2-hydroxyphenyl) -6- (3-hydroxypropyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = ^{_{2-hydroxyphenyl, R 10 = CH 2 CH 2}} CH 2 OH) and (101) was obtained in 82% yield. ¹ H NMR δ [(CD ₃ ) ₂ SO] 10.90 (br, 1H), 9.40 (br, 1H), 8.38 (d, J = 2.4 Hz, 1H), 7.67 (s , 1H), 7.56 (d, J = 8.8 Hz, 1H), 7.30 to 7.23 (m, 2H), 7.13 (dd, J = 8.8, 2.4 Hz, 1H) 6.94 to 6.88 (m, 2H), 4.78 (br, 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. _{C 23 H 18 N 2 O 5} . Calculated for _1/2 H2O C, 67.14; H, 4.65; N, 6.80.

Example 55 Preparation of 2- [2- (2-Chloro-6-methoxyphenyl) ethenyl] -5-methoxy-1H-indole (II; Ar = 2-chloro-6-methoxyphenyl) (102) -Methoxy-1H-indole-2-carbaldehyde (1) was reacted with 2-chloro-6-methoxybenzyltriphenylphosphonium bromide by the procedure described in Example 37 to give a yellow solid (E / Z isomer). 2- [2- (2-chloro-6-methoxyphenyl) ethenyl] -5-methoxy-1H-indole (II; Ar = 2-chloro-6-methoxyphenyl) (102) in a yield of 92 %. This was used without further purification.

Example 56 1- (3-{[tert-Butyl (dimethyl) silyl] oxy} propyl) -2- [2- (2-chloro-6-methoxyphenyl) ethenyl] -5-methoxy-1H-indole Preparation of (III; Ar = 2-chloro-6-methoxyphenyl, R ¹⁰ = CH ₂ CH ₂ CH ₂ OSiMe ₂ t-Bu) (103) 2- [2- (prepared as described in Example 55 2-Chloro-6-methoxyphenyl) ethenyl] -5-methoxy-1H-indole (II; Ar = 2-chloro-6-methoxyphenyl) (102) was prepared according to the procedure described in Example 38. Reaction with tert-butyl (dimethyl) silyl ether yields 1- (3-{[tert-butyl (dimethyl) silyl] oxy} propyl) -2- [2- ( - chloro-6-methoxyphenyl) ethenyl] -5-methoxy -1H- indole (III; Ar = 2- _{^{chloro-6-methoxyphenyl, R 10 = CH 2 CH 2}} CH 2 OSiMe 2 t-Bu) (103) Was obtained in a yield of 91%. This was used without further purification.

Example 57 6- (3-{[tert-Butyl (dimethyl) silyl] oxy} propyl) -4- (2-chloro-6-methoxyphenyl) -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 2}} CH 2 OSiMe 2 t-Bu) Preparation of (104).
1- (3-{[tert-Butyl (dimethyl) silyl] oxy} propyl) -2- [2- (2-chloro-6-methoxyphenyl) ethenyl] -5-prepared as described in Example 56. Methoxy-1H-indole (III; Ar = 2-chloro-6-methoxyphenyl, R ¹⁰ = CH ₂ CH ₂ CH ₂ OSiMe ₂ t-Bu) (103) was reacted with maleimide by the procedure described in Example 68. 6- (3-{[tert-butyl (dimethyl) silyl] oxy} propyl) -4- (2-chloro-6-methoxyphenyl) -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 2 CH 2 OSiMe 2 t} -Bu) and (104) was obtained in 77% yield. This was used without further purification.

Example 58 4- (2-Chloro-6-methoxyphenyl) -6- (3-hydroxypropyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione preparation of; (Ar = ^{_{2-chloro-6-methoxyphenyl, R 10 = CH 2 CH 2}} CH 2 OH V) (105).
6- (3-{[tert-butyl (dimethyl) silyl] oxy} propyl) -4- (2-chloro-6-methoxyphenyl) -9-methoxy-4,5 prepared as described in Example 57. , 6,10C- tetrahydropyrrolo [3,4-c] carbazole -1,3 (2H, 3aH) - dione (IV; Ar = 2- ^{_{chloro-6-methoxyphenyl, R 10 = CH 2 CH 2}} CH 2 OSiMe ₂ t-Bu) (104) is reacted with DDQ according to the procedure described in Example 70 and then with 2N HCl in THF / methanol to give 4- (2 -Chloro-6-methoxyphenyl) -6- (3-hydroxypropyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dio The; (V Ar = 2- ^{_{chloro-6-methoxyphenyl, R 10 = CH 2 CH 2}} CH 2 OH) (105) was obtained in 76% yield. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.05 (br, 1H), 8.51 (d, J = 2.6 Hz, 1H), 7.75 (s, 1H), 7.69 (d , J = 8.9 Hz, 1H), 7.44 (dd, J = 8.2, 8.2 Hz, 1H), 7.31 (dd, J = 8.9, 2.6 Hz, 1H), 7. 18 (d, J = 8.2 Hz, 1H), 7.13 (d, J-8.2 Hz, 1H), 4.63 (t, J = 4.9 Hz, 1H), 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 Calculated _{N 2 O 5 C, 69.76;} H, 5.15; N, 6.51.

Example 59 4- (2-Chloro-6-methoxyphenyl) -9-hydroxy-6- (3-hydroxypropyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione preparation of; (Ar = ^{_{2-chloro-6-methoxyphenyl, R 10 = CH 2 CH 2}} CH 2 OH VI) (106).
4- (2-Chloro-6-methoxyphenyl) -6- (3-hydroxypropyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H) prepared as described in Example 58. , 6H) -dione (V; Ar = 2-chloro-6-methoxyphenyl, R ¹⁰ = CH ₂ CH ₂ CH ₂ OH) (105) with BBr ₃ using the procedure described in Example 80 for 90 minutes. React to 4- (2-chloro-6-methoxyphenyl) -9-hydroxy-6- (3-hydroxypropyl) pyrrolo [3,4-c] carbazole-1 as an orange powder with a melting point of 270-273 ° C. , 3 (2H, 6H) - dione; was obtained (VI Ar = = 2- ^{_{chloro-6-methoxyphenyl, R 10 CH 2 CH 2 CH}} 2 OH) (106) in 64% yield. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.01 (br s, 1 H), 9.35 (br s, 1 H), 8.37 (d, J = 2.4 Hz, 1 H), 7.70 (S, 1H), 7.58 (d, J = 8.7 Hz, 1H), 7.44 (dd, J = 8.3, 8.3 Hz, 1H), 7.20 to 7.11 (m, 3H), 4.61 (br t, 1H), 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. C ₂₄ H ₁₉ Calculated _{ClN 2 O 5 C, 63.93;} H, 4.25; N, 6.21.

Example 60 9-Hydroxy-6- (3-hydroxypropyl) -4- (2-methoxyphenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = ^{2-methoxyphenyl,} preparation of _{R 10 = CH 2 CH 2 CH} 2 OH) (107).
4- (2-Chloro-6-methoxyphenyl) -9-hydroxy-6- (3-hydroxypropyl) pyrrolo [3,4-c] carbazole-1,3 (2H) prepared as described in Example 59. , 6H) - dione (VI; Ar = 2- _{^{chloro-6-methoxyphenyl, R 10 = CH 2 CH 2}} CH 2 OH) (106) (0.20g, 0.44mmol), potassium acetate (0.20 g) And a solution of 5% Pd / C in ethyl acetate (25 ml) and methanol 1: 1 (25 mL) were reacted at 410 kPa (60 psi) for 7 hours under a hydrogen atmosphere. The catalyst was removed by filtration, and the filtrate was concentrated to dryness. The residue was partitioned between ethyl acetate and water, the organic solution was dehydrated, the dehydrating agent was removed, the solution was concentrated to dryness and chromatographed on silica. Elution with ethyl acetate / petroleum ether (2: 1) to give 9-hydroxy-6- (3-hydroxypropyl) -4- (2- Methoxyphenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = 2-methoxyphenyl, R ¹⁰ = CH ₂ CH ₂ CH ₂ OH) (107) in yield Obtained at 51%. ¹ H NMR δ [(CD ₃ ) 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, 1H), 7.55 (d, J = 8.8 Hz, 1H), 7.42 (m, 1H), 7.35 (dd, J = 7.5, 1.7 Hz, 1H), 7 .13 to 7.08 (m, 2H), 7.05 (dd, J = 7.2, 7.2 Hz, 1H), 4.62 (t, J = 4.8 Hz, 1H), 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 Calculated _{N 2 O 5 C, 69.22;} H, 4.84; N, 6.73.

Example 61 2- {2- [2- (2-chloro-6-methoxyphenyl) ethenyl] -5-methoxy-1H-indol-1-yl} ethanol (III; Ar = 2-chloro-6- Preparation of Methoxyphenyl, R ¹⁰ = CH ₂ CH ₂ OH) (109) 2- [2- (2-Chloro-6-methoxyphenyl) ethenyl] -5-methoxy-1H prepared as described in Example 55 Indole (II; Ar = 2-chloro-6-methoxyphenyl) (102) was reacted with 2-bromoethyltetrahydro-2H-pyran-2-yl ether by the procedure described in Example 38 and then the crude The product is reacted with 2N HCl in methanol to give 2- {2- [2- (2-chloro-6-methoxyphenyl) ethenyl] -5-methoxy-1H-yne. Lumpur-1-yl} ethanol; as a mixture of (III Ar = _{^{2-chloro-6-methoxyphenyl, R 10 = CH 2 CH 2}} OH) and (109) E / Z isomers in 91% yield . This was used without further purification.

Example 62 4- (2-Chloro-6-methoxyphenyl) -6- (2-hydroxyethyl) -9-methoxy-4,5,6,10c-tetrahydropyrrolo [3,4-c] carbazole- 1,3 (2H, 3aH) - dione; preparation of (IV Ar = ^{_{2-chloro-6-methoxyphenyl, R 10 = CH 2 CH 2}} OH) (110).
2- {2- [2- (2-Chloro-6-methoxyphenyl) ethenyl] -5-methoxy-1H-indol-1-yl} ethanol (III; Ar = 2) prepared as described in Example 61 - _{chloro-6-methoxyphenyl, R = CH 2 CH 2 OH} ) and (109), is reacted with a maleimide by the procedure described in example 68, the creamy powder 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-methoxy ^phenyl, _{R 10 = CH 2 CH 2 OH} ) (110) was obtained in 72% yield. This was used without further purification.

Example 63 4- (2-Chloro-6-methoxyphenyl) -6- (2-hydroxyethyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione Preparation of (V; Ar = 2-chloro-6-methoxyphenyl, R ¹⁰ = CH ₂ CH ₂ OH) (111) 4- (2-chloro-6-methoxyphenyl) prepared as described in Example 62 -6- (2-hydroxyethyl) -9-methoxy-4,5,6,10c-tetrahydropyrrolo [3,4-c] carbazole-1,3 (2H, 3aH) -dione (IV; Ar = 2 chloro-6-methoxy ^phenyl, _{R 10 = CH 2 CH 2 OH} ) (110), with the exception the reaction time is 8 hours to react with MnO ₂ by the procedure described in example 79, melting point two hundred sixty-four to two hundred and sixty-eight ° C. of / 4- (2-chloro-6-methoxyphenyl) -6- (2-hydroxyethyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione as orange powder (V; Ar = 2-chloro-6-methoxyphenyl, R ¹⁰ = CH ₂ CH ₂ OH) (111) was obtained in a yield of 75%. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.04 (br s, 1 H), 8.50 (d, J = 2.6 Hz, 1 H), 7.75 (s, 1 H), 7.69 ( d, J = 9.0 Hz, 1H), 7.44 (dd, J = 8.3, 8.3 Hz, 1H), 7.28 (dd, J = 9.0, 2.6 Hz, 1H), 7 .18 (d, J = 8.3 Hz, 1H), 7.13 (d, J = 8.3 Hz, 1H), 4.83 (t, J = 5.5 Hz, 1H), 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. C ₂₄ H ₁₉ Calculated _{ClN 2 O 5 C, 63.93;} H, 4.25; N, 6.21.

Example 64 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) (112) prepared 4- (2-chloro-6-methoxyphenyl) as described in Preparative example 63 -6- (2-hydroxyethyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (V; Ar = 2-chloro-6-methoxyphenyl, R = CH the ₂ CH ₂ OH) (111), except the reaction conditions are 2 hours at 0 ℃ reacted with BBr ₃ using the procedure described in example 80, melting point two hundred and seventy-five to two hundred and seventy-eight ° C. as a yellow powder (56% ) As 4- (2- Olo-6-methoxyphenyl) -9-hydroxy-6- (2-hydroxyethyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar-2-chloro-6) - give ^{_{methoxyphenyl, R 10 = CH 2 CH 2}} OH) and (112) in 56% yield. ¹ H NMR δ [(CD ₃ ) 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, 1H), 7.57 (d, J = 8.7 Hz, 1H), 7.43 (dd, J = 8.3, 8.3 Hz, 1H), 7.17 (d, J = 7. 9 Hz, 1H), 7.14 to 7.09 (m, 2H), 4.81 (t, J = 5.5 Hz, 1H), 4.46 (t, J = 5.3 Hz, 2H), 3. 74 (dt, J = 5.5, 5.3 Hz, 2H), 3.66 (s, 3H). Calculated value of FABMS [M + H] ⁺ : 439.0882, 437.08989. Calculated 439.0875,437.0904 of _{C 23 H 18 ClN 2 O 5} .

Example 65 9-Hydroxy-6- (2-hydroxyethyl) -4- (2-methoxyphenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = ^{_{2-methoxyphenyl, R 10 = CH 2 CH 2}} OH) (113) prepared 4- (2-chloro-6-methoxyphenyl, as described in example 64) -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) (112 ) Is reacted with hydrogen gas using a Pd / C catalyst according to the procedure of Example 60 to give 9-hydroxy-6- (2-hydroxyethyl) -4- (2- Me Toxiphenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = 2-methoxyphenyl, R ¹⁰ = CH ₂ CH ₂ OH) (113) in a yield of 77% I got it. ¹ H NMR δ [(CD ₃ ) 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, 1H), 7.55 (d, J = 8.8 Hz, 1H), 7.42 (m, 1H), 7.33 (dd, J = 8.8, 2.4 Hz, 1H), 7 .12-7.02 (m, 3H), 4.84 (t, J = 5.5 Hz, 1H), 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. _{C 23 H 18 N 2 O 5} . Calculated for _1/2 H2O C, 67.15; H, 4.65; N, 6.81.

Example 66 2- (4- (2-Chloro-6-methoxyphenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1H) -Il) Preparation of ethyl methanesulfonate (VII; Ar = 2-chloro-6-methoxyphenyl, n = 2, mesylate) (114).
4- (2-Chloro-6-methoxyphenyl) -6- (2-hydroxyethyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H) prepared as described in Example 63. , 6H) -dione (V; Ar = 2-chloro-6-methoxyphenyl, R ¹⁰ = CH ₂ CH ₂ OH) (111) was reacted with methanesulfonyl chloride and then described in Scheme 3 of Example 170 The procedure was used to react with BBr ₃ to give 2- (4- (2-chloro-6-methoxyphenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4] as a yellow solid. -C] carbazol-6 (1H) -yl) ethyl methanesulfonate (VII; Ar = 2-chloro-6-methoxyphenyl, n = 2, mesylate) (114) was obtained. This was used without further purification.

Example 67 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) (115).
2- (4- (2-Chloro-6-methoxyphenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole prepared as described in Example 66 -6 (1H) -yl) ethyl methanesulfonate (VII; Ar = 2-chloro-6-methoxyphenyl, n = 2, mesylate) (114) is reacted with morpholine by the procedure described in Scheme 3 of Example 179. 4- (2-chloro-6-methoxyphenyl) -9-hydroxy-6- [2- (4-morpholinyl) ethyl] pyrrolo [3,4-c] carbazole-1 as a yellow powder with a melting point of 185 ° C. , 3 (2H, 6H) -dione (VIII; Ar = 2-chloro-6-methoxyphenyl, n = 2, Z = 4-morpholinyl) (115) was obtained in 81% yield. ¹ H NMR δ [(CD ₃ ) ₂ SO] 10.99 (br s, 1 H), 9.34 (br s, 1 H), 8.37 (d, J = 2.4 Hz, 1 H), 7.69 (S, 1H), 7.57 (d, J = 8.8 Hz, 1H), 7.44 (dd, J = 8.3, 8.3 Hz, 1H), 7.17 (d, J = 8. 3 Hz, 1H), 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. _{C 27 H 24 ClN 3 O5.1 /} 4H 2 O Calculated C, 63.53; H, 4.84; N, 8.23.

  Representative Procedure for Method 4 of Scheme 2

Example 68 4- (2-Chlorophenyl) -9-methoxy-4,5,6,10c-tetrahydropyrrolo [3,4-c] carbazole-1,3 (2H, 3aH) -dione (N; Ar = 2-Chlorophenyl, R ¹⁰ = H) (32) Preparation 2- [2- (2-Chlorophenyl) ethenyl] -5-methoxy-1H-indole (II; Ar = 2-chlorophenyl) prepared according to Example 37 A toluene (25 mL) solution of (27) (1.5 g, 5.29 mmol), maleimide (0.61 g, 6.34 mmol) and SnCl ₂ (0.20 g, 1.05 mmol) was refluxed for 6 hours. After dilution with ethyl acetate, the solution is washed with water, the organic phase is dehydrated, the dehydrating agent is removed, the solution is concentrated to dryness and a yellow solid (as a mixture of diastereomers) 4- (2-Chlorophenyl) -9-methoxy-4,5,6,10c-tetrahydropyrrolo [3,4-c] carbazole-1,3 (2H, 3aH) -dione (IV; Ar = 2-chlorophenyl, R ¹⁰ = H) (32) was obtained in a yield of 1.98 g, 98%. This was used without further purification.

  Representative Procedure for Method 5 of Scheme 2

Example 69 9-Methoxy-4- (2-methoxy-5-nitrophenyl) -4,5,6,10c-tetrahydropyrrolo [3,4-c] carbazole-1,3 (2H, 3aH)- Preparation of dione (IV; Ar = 2-methoxy-5-nitrophenyl, R ¹⁰ = H) (185) 5-methoxy-2- [2- (2-methoxy-5) prepared as described in Example 45. -Nitrophenyl) ethenyl] -1H-indole (II; Ar = 2-methoxy-5-nitrophenyl) (0.437 g, 1.35 mmol) 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 a 180 ° C. oil bath and the resulting melt was held at this temperature for 4 hours. 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] as a tan powder. Carbazole-1,3 (2H, 3aH) -dione (IV; Ar = 2-methoxy-5-nitrophenyl, R ¹⁰ = H) (185) was obtained in a yield of 0.51 g and 90%. This was used in the next step without further purification.

  Representative Procedure for Method 6 of Scheme 2

Example 70 9-Methoxy-4- (2-methoxy-5-nitrophenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (V; Ar = 2-methoxy- Preparation of 5-nitrophenyl, R ¹⁰ = H) (36) 9-methoxy-4- (2-methoxy-5-nitrophenyl) -4,5,6,10c-tetrahydropyrrolo [3] prepared according to Example 69 , 4-c] carbazole-1,3 (2H, 3aH) -dione (IV; Ar = 2-methoxy-5-nitrophenyl, R ¹⁰ = H) (185) (0.51 g, 1.21 mmol) and DDQ A solution of (0.82 g, 3.63 mmol) in dioxane (30 mL) was refluxed for 2 hours. After dilution with water, the solution was extracted with dichloromethane. The organic extract was washed with saturated aqueous NaHCO ₃ (3 ×). The organic phase was dehydrated, the dehydrating agent was removed, and the solution was concentrated to dryness to give a solid. This was chromatographed on silica. Elution with ethyl acetate / petroleum ether (3: 7) followed by ethyl acetate / petroleum ether (1: 1) gave a solid. This solid was 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) was obtained in a yield of 0.42 g, 82%. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.95 (br s, 1H), 11.06 (br s, 1H), 8.46 (d, J = 2.6 Hz, 1H), 8.37 (Dd, J = 9.2, 3.0 Hz, 1H), 8.22 (d, J = 3.0 Hz, 1H), 7.69 (s, 1H), 7.57 (d, J = 8. 8 Hz, 1H), 7.36 (d, J = 9.2 Hz, 1H), 7.24 (dd, J = 8.8, 2.6 Hz, 1H), 3.89 (s, 3H), 3. 85 (s, 3H). Found: C, 63.90; H, 3.79; N, 9.52. Calculated C of _{C 22 H 15 N 3 O 6} , 63.61; H, 3.62; N, 10.07.

Example 71 9-Hydroxy-4- (2-hydroxy-5-nitrophenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = 2-hydroxy- Preparation of 5-nitrophenyl, R ¹⁰ = H) (37) 9-methoxy-4- (2-methoxy-5-nitrophenyl) pyrrolo [3,4-c] carbazole-1,3 prepared according to Example 70 (2H, 6H) -dione (V; Ar = 2-methoxy-5-nitrophenyl, R = H) (36) was reacted using the procedure described in Example 81 by reaction at 210 ° C. for 30 minutes. 9-hydroxy-4- (2-hydroxy-5-nitrophenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI) as a yellow / orange powder with a melting point> 330 ° C. Ar ^{2-hydroxy-5-nitrophenyl,} R 10 = H) (37) was obtained in 82% yield. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.78 (s, 1 H), 10.99 (s, 1 H), 9.26 (s, 1 H), 8.32 (d, J = 2.4 Hz) , 1H), 8.21 to 8.16 (m, 2H), 7.63 (s, 1H), 7.45 (d, J = 8.7 Hz, 1H), 7.08 (m, 2H).

Example 72 9-Hydroxy-4- (2-methoxy-5-nitrophenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = 2-methoxy- Preparation of 5-nitrophenyl, R ¹⁰ = H) (38) 9-methoxy-4- (2-methoxy-5-nitrophenyl) pyrrolo [3,4-c] carbazole-1,3 prepared according to Example 70 (2H, 6H) -dione (V; Ar = 2-methoxy-5-nitrophenyl, R ¹⁰ = H) (36) was reacted using the procedure described in Example 80 to give a melting point of 265-273 ° C. 9-Hydroxy-4- (2-methoxy-5-nitrophenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = 2-methoxy-5-) as a yellow powder Nitrophenyl, ¹⁰ = H) (38) was obtained in 76% yield. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.86 (br, 1H), 11.01 (br, 1H), 8.38 (dd, J = 9.3, 2.8 Hz, 1H), 8 .31 (d, J = 2.4 Hz, 1H), 8.20 (d, J = 2.8 Hz, 1H), 7.65 (s, lh), 7.48 (d, J = 8.7 Hz, 1H), 7.36 (d, J = 9.3 Hz, 1H), 7.10 (dd, J = 8.7, 2.4 Hz, 1H), 3.84 (s, 3H). Calculated value of EIMS M ⁺ : 403.0794. Calcd 403.0804 for _{C 21 H 13 N 3 O 6} .

Example 73 4- (5-Amino-2-methoxyphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = 5-amino- Preparation of 2-methoxyphenyl, R ¹⁰ = H) (39) 9-Hydroxy-4- (2-methoxy-5-nitrophenyl) pyrrolo [3,4-c] carbazole-1,3 prepared according to Example 72 To a solution of (2H, 6H) -dione (VI; Ar = 2-methoxy-5-nitrophenyl, R ¹⁰ = H) (38) (64 mg, 0.159 mmol) in methanol (10 mL) and THF (1 mL), 2N HCl (1 mL) was added. Freshly prepared nickel boride (about 0.50 g) was added and the mixture was warmed at 60 ° C. After 1 hour, HCl (1 mL) and Ni ₂ B (ca. 0.50 g) were added and the reaction mixture was maintained at 60 ° C. for a total of 4 hours. The solvent was removed under reduced pressure and the residue was partitioned between ethyl acetate and 2N HCl. The aqueous layer was basified with concentrated ammonia solution and extracted with ethyl acetate. The organic phase was dehydrated, the dehydrating agent was removed, and the solvent was concentrated to dryness to give a solid. Crystallization of this solid from THF / petroleum ether gave 4- (5-amino-2-methoxyphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 as a yellow powder with a melting point of 246-250 ° C. (2H, 6H) -dione (VI; Ar = 5-amino-2-methoxyphenyl, R ¹⁰ = H) (39) was obtained in 49.7 mg, 84% yield ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.67 (s, 1H), 10.87 (s, 1H), 9.21 (s, 1H), 8.30) d, J = 2.4 Hz, 1H), 7.44 ( s, 1H), 7.42 (d, J = 8.7 Hz, 1H), 7.05 (dd, J = 8.6, 2.5 Hz, 1H), 6.80 (d, J = 8.7 Hz) , 1H), 6.61 (dd, J = 8.6, 2.7 Hz, 1H), 6.55 (d, J = 2). 8Hz, 1H), 4.68 (br, 2H), 3.53 (s, 3H). Calculated value of FABMS [M + H] ⁺ : 373.10.56. Calcd 373.1062 for _{C 21 H 15 N 3 O 4} .

Example 74 2-[(E) -2- (2-bromo-4-nitrophenyl) ethenyl] -5-methoxy-1H-indole (II, Ar = 2-bromo-4-nitrophenyl) (49 5-methoxy-1H-indole-2-carbaldehyde (1) was reacted with 2-bromo-4-nitrobenzyltriphenylphosphonium bromide by the procedure described in Example 37 to give a red solid diene. The yield of 2-[(E) -2- (2-bromo-4-nitrophenyl) ethenyl] -5-methoxy-1H-indole (II, Ar = 2-bromo-4-nitrophenyl) (49) was 98. %. This was used without further purification.

Example 75 4- (2-Bromo-4-nitrophenyl) -9-methoxy-4,5,6,10c-tetrahydropyrrolo [3,4-c] carbazole-1,3 (2H, 3aH)- Preparation of dione (IV: Ar = 2, bromo-4-nitrophenyl, R ¹⁰ = H) (50) 2-[(E) -2- (2-bromo-4) prepared as described in Example 74 -Nitrophenyl) ethenyl] -5-methoxy-1H-indole (II, Ar = 2-bromo-4-nitrophenyl) (49) was reacted with maleimide using the procedure described in Example 69 to give a melting point. 4- (2-Bromo-4-nitrophenyl) -9-methoxy-4,5,6,10c-tetrahydropyrrolo [3,4-c] carbazole-1,3 (2H, 3aH as a tan powder at 272 ° C. ) -Dione (IV Ar = 2, ^{bromo-4-nitrophenyl,} R 10 = H) (50) was obtained in 54% yield. This was used without further purification.

Example 76 4- (2-Bromo-4-nitrophenyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (V; Ar = 2-bromo- ^{4-nitrophenyl,} R 10 = H) preparation of (51).
4- (2-Bromo-4-nitrophenyl) -9-methoxy-4,5,6,10c-tetrahydropyrrolo [3,4-c] carbazole-1,3 (prepared as described in Example 75 2H, 3aH) -dione (IV; Ar = 2, bromo-4-nitrophenyl, R ¹⁰ = H) (50) is reacted with DDQ using the procedure described in Example 70, mp 288-292 4- (2-bromo-4-nitrophenyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (V; Ar = 2-bromo- 4-nitrophenyl, R ¹⁰ = H) (51) was obtained in 67% yield. ¹ H NMR δ [(CD ₃ ) ₂ SO] 12.07 (br, 1H), 11.18 (br, 1H), 8.56 (d, J = 2.3 Hz, 1H), 8.46 (d , J = 2.6.Hz, 1H), 8.33 (dd, J = 8.5, 2.6 Hz, 1H), 7.80 (d, J = 8.5 Hz, 1H), 7.63 ( s, 1H), 7.59 (d, J = 8.8 Hz, 1H), 7.27 (dd, J = 8.8, 2.3 Hz, 1H), 3.90 (s, 3H). Found: C, 54.06; H, 2.59; N, 8.72. Calculated C of _{C 21 H 12 BrN 3 O 5} , 54.10; H, 2.59; N, 9.01.

Example 77 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) preparation of (52).
4- (2-Bromo-4-nitrophenyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (V; Ar) prepared as described in Example 76 = 2-bromo-4-nitrophenyl, R ¹⁰ = H) (51) was reacted with pyridinium hydrochloride using the procedure described in the procedure described in Example 81 to give a yellow powder with a melting point> 330 ° C. 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) was obtained in 92% yield. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.94 (s, 1 H), 11.13 (s, 1 H), 9.32 (br s, 1 H), 8.55 (d, J = 2. 3 Hz, 1 H), 8.34 (d, J = 2.4 Hz, 1 H), 8.31 (m, 2 H), 7.79 (d, J = 8.5 Hz, 1 H), 7.58 (s, 1H), 7.48 (d, J = 8.7 Hz, 1H), 7.11 (dd, J = 8.7, 2.4 Hz, 1H).

Example 78 4- (4-Amino-2-bromophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = 4-amino- ^{2-bromophenyl,} R 10 = H) preparation of (53).
Freshly prepared nickel boride (5.00 g, 0.039 mol) was added to 4- (2-bromo-4-nitrophenyl) -9-hydroxypyrrolo [3,4-prepared as described in Example 77. c] Carbazole-1,3 (2H, 6H) -dione (VI; Ar = 2-bromo-4-nitrophenyl, R ¹⁰ = H) (52) (0.50 g, 1.10 mmol) in methanol (80 mL) To the solution and 2N HCl (5.0 mL) was added portionwise at 60 ° C. After 2 hours, the mixture was cooled, diluted with water, basified with concentrated aqueous ammonia and extracted with ethyl acetate. This extract was processed to give a solid. This was chromatographed on silica. Eluting with ethyl acetate, 4- (4-amino-2-bromophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = 4- Amino-2-bromophenyl, R ¹⁰ = H) (53) was obtained in a yield of 0.47 g, 97%. It crystallized from ethyl acetate / petroleum ether as a yellow powder with a melting point of 324-326 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.71 (brs, 1H), 10.93 (brs, 1H), 9.23 (brs, 1H), 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 to 7.03 (m, 2 H), 6.89 (d, J = 2.1 Hz, 1H), 6.61 (dd, J = 8.6, 2.4 Hz, 1H), 5.48 (brs, 2H). Found: C, 56.79; H, 3.26; N, 8.77. _{C 20 H 12 BrN 3 O 3} . Calculated 1/2 EtOAc C, 56.67; H, 3.46; N, 9.01.

  Representative Procedure for Method 7 of Scheme 2

Example 79 4- (2-Chlorophenyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (V; Ar = 2-chlorophenyl, R ¹⁰ = H) Preparation of (33) Manganese dioxide (12.0 g) was prepared as described in Example 68. 4- (2-Chlorophenyl) -9-methoxy-4,5,6,10c-tetrahydropyrrolo [3,4 -c] carbazole -1,3 (2H, 3aH) - dione; was added (IV Ar = ^{2-chlorophenyl, R 10 = H) (32} ) (2.1g, 5.51mmol) in dioxane (100 mL) solution of The mixture was refluxed for 16 hours with stirring. The mixture was filtered hot through a plug of celite and washed with more dioxane and then 10% methanol / dioxane. The combined filtrate and washings were concentrated to dryness and the residue was adsorbed on silica and chromatographed. Eluting with ethyl acetate / petroleum ether (3: 7) to give 4- (2-chlorophenyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (V; Ar = 2-chlorophenyl, R ¹⁰ = H) (33) was obtained in a yield of 1.66 g, 79%. This crystallized from THF / petroleum ether as a yellow powder with a melting point of 170-175 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.96 (br s, 1H), 11.08 (br s, 1H), 8.46 (d, J = 2.6 Hz, 1H), 7.60 -7.55 (m, 3H), 7.51-7.42 (m, 3H), 7.24 (dd, J = 8.9, 2.6 Hz, 1H), 3.89 (s, 3H) . Found: C, 65.64; H, 3.63; N, 7.12. _{C 21 H 13 ClN 2 O 3} . Calculated for _1/2 H2O C, 65.37; H, 3.66; N, 7.26.

  Representative Procedure for Method 8 of Scheme 2

Example 80 4- (2-Chlorophenyl) -9-hydroxy-6- (3-hydroxypropyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = Preparation of 2-chlorophenyl, R ¹⁰ = CH ₂ CH ₂ CH ₂ OH) (34) A solution of 1N BBr ₃ in CH ₂ Cl ₂ (11.5 mL, 0.011 mol) was prepared as described in Example 40. 4- (2-chlorophenyl) -6- (3-hydroxypropyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (V; Ar = 2-chlorophenyl, R _{^{10 = CH 2 CH 2 CH 2}} OH) (31) (1.00g, was added under nitrogen to a _CH 2 Cl ₂ solution of the 2.30 mmol), and stirred the reaction mixture at room temperature for 3 hours. Saturated aqueous NaHCO ₃ was added and the solution was diluted with water and extracted with ethyl acetate. The organic phase was dehydrated, the dehydrating agent was removed, the solution was concentrated to dryness, adsorbed on silica and 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, R 10 CH 2 CH 2 CH}} 2 OH) (34) yield 0.90 g, was obtained in 93%. This crystallized from THF / petroleum ether as a yellow / orange powder with a melting point of 291-294 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.05 (br s, 1 H), 9.36 (s, 1 H), 8.38 (d, J = 2.5 Hz, 1 H), 7.74 ( s, 1H), 7.59-7.54 (m, 2H), 7.52-7.42 (m, 3H), 7.14 (dd, J = 8.7, 2.5 Hz, 1H), 4.62 (br t, 1H), 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. _{C 23 H 17 ClN 2 O 4} . 1 / 4H ₂ O Calculated C, 64.94; H, 4.15; N, 6.58.

  Representative Procedure for Method 9 of Scheme 2

(Example 81) 4- (2-chlorophenyl) -9-hydroxy-pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) - dione (VI; Ar = ^{2-chlorophenyl, R} 10 = H) Preparation of (9) 4- (2-Chlorophenyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (V; Ar) prepared as described in Example 79 = 2-chlorophenyl, R ¹⁰ = H) (33) (0.512 g, 1.36 mmol) was added to the pyridinium hydrochloride melt at 200 ° C. and the mixture was stirred at this temperature for 20 minutes. Water was added and the resulting precipitate was filtered off, washed thoroughly with water, adsorbed on silica and chromatographed. Eluting with ethyl acetate / petroleum ether (1: 1), 4- (2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H), mp 215-220 ° C - dione (VI; Ar = ^{2-chlorophenyl,} R 10 = H) and (9) yield 0.42 g, was obtained in 85%. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.83 (br s, 1 H), 11.01 (br s, 1 H), 9.27 (br s, 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), 1H). Found: C, 65.72; H, 3.50; N, 6.97. _{C 20 H 11 ClN 2 O 3} . Calculated _{1/4 CH 3 COOCH 2 CH 3 C} , 65.54; H, 3.40; N, 7.28.

Example 82 6- (2-Hydroxyethyl) -9-methoxy-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (V; Ar = phenyl, R ¹⁰ _{= (CH 2) 2 OH)} (201) preparation of 5-methoxy -2 - [(E, Z) -2- phenylethenyl]-1H-indole (II; Ar = phenyl) (1.93g, 7. 74 mmol was reacted with 2- (2-bromoethoxy) tetrahydro-2H-pyran using the procedure described in Example 38. This material was reacted with maleimide (0.79 g) using the procedure described in Method 4. The product obtained was reacted directly using the procedure described in Example 70 to give the crude material, which was then dissolved in methanol (100 mL) and p-toluenesulfonic acid ( 30mg The solution was warmed for 3 hours to 50 ° C. The solution was then diluted with water and extracted with ethyl acetate, the organic phase was dehydrated, the dehydrating agent was removed, and the solution was concentrated to dryness. Adsorbed on silica and chromatographed, eluting with ethyl acetate / hexane (1: 2 → 1: 1) to give 6- (2-hydroxyethyl) -9- as a yellow powder with a melting point of 262-264 ° C. Methoxy-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (V; Ar = phenyl, R ¹⁰ = (CH ₂ ) ₂ OH) (201) in a yield of 0. 51 g, 17% ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.09 (br s, 1 H), 8.56 (d, J = 2.6 Hz, 1 H), 7.83 (s , 1H), 7.66 (m, 3H), 7.47 (m, 3H), .28 (dd, J = 9.0, 2.6 Hz, 1H), 4.86 (t, J = 5.5 Hz, 1H), 4.55 (t, J = 5.3 Hz, 2H), 3. 90 (s, 3H), 3.78 (m, 2H) Found:. C, 71.47; H, 4.77; N, calculated _{7.32.C 23 H 18 N 2 O 4} : C 71.49; H, 4.70; N, 7.25.

Example 83 6- (3-Hydroxypropyl) -9-methoxy-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (V; Ar = phenyl, R ¹⁰ _{= (CH 2) 3 OH)} (202) preparation of 5-methoxy -2 - [(E, Z) -2- phenylethenyl]-1H-indole (II; Ar = phenyl) (6.85g, 27. 5 mmol) was reacted with 3-bromopropyl tert-butyl (dimethyl) silyl ether 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 crude Diels-Alder adduct was aromatized by the procedure described in Example 79 to give a crude material. This was then dissolved in methanol (300 mL) and 1N hydrochloric acid (50 mL) was added. The solution was stirred at room temperature for 3 hours, diluted with water and extracted with ethyl acetate. The organic layer was dehydrated, the dehydrating agent was removed, and the solution was concentrated to dryness. The residue was adsorbed on silica, chromatographed, eluting with dichloromethane then ethyl acetate / dichloromethane (7: 3). Trituration with diethyl ether gave alcohol (202) as a yellow powder (2.55 g, 23%) with a melting point of 241 ° -243 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.10 (br s, 1 H), 8.56 (d, J = 2.6 Hz, 1 H), 7.82 (s, 1 H), 7.67 ( m, 3H), 7.47 (m, 3H), 7.30 (dd, J = 9.0, 2.6 Hz, 1H), 4.66 (t, J = 4.9 Hz, 1H), 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. Calculated _{C 24 H 26 N 2 O 4} : C, 71.99; H, 5.03; N, 6.99.

Example 84 6- (6-Hydroxyhexyl) -9-methoxy-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (V; Ar = phenyl, R ¹⁰ _{= (CH 2) 6 OH)} (203) preparation of 5-methoxy -2 - [(E, Z) -2- phenylethenyl]-1H-indole (II; Ar = phenyl) (0.30g, 0. 71 mmol)) was alkylated with 6-bromohexyl-tert-butyl (dimethyl) silyl ether by the procedure described in Example 38 to give the crude material. This was reacted directly with maleimide (0.14 g) according to Method 4a.

The crude Diels-Alder adduct was aromatized by the procedure described in Example 79 to give a crude material. This was then dissolved in methanol (100 mL) and 1N hydrochloric acid (15 mL) was added. The solution was stirred at room temperature for 2 hours, diluted with water and extracted with ethyl acetate. The organic layer was dehydrated, the dehydrating agent was removed, and the solution was concentrated to dryness. Chromatography on silica, eluting with dichloromethane and then ethyl acetate / hexane (4: 1) and triturated with diethyl ether gave alcohol (203) as a yellow powder with a melting point of 170-173 ° C. (0. 31 g, 98%). ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.10 (br s, 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, 1H), 4.50 (t, J = 7.0 Hz, 2H), 4. 28 (t, J = 5.1 Hz, 1H), 3.90 (s, 3H), 3.32 (t, J = 6.4 Hz, 2H), 1.76 (m, 2H), 1.36 to 1.26 (m, 6H). Found: C, 73.57; H, 6.17; N, 6.39. Calculated for _{C 27 H 26 N 2 O 4} : C, 73.28; H, 5.92; N, 6.33.

Example 85 4- (2,6-dichlorophenyl) -6- (2-hydroxyethyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (V; Preparation of Ar = 2,6-dichlorophenyl, R ¹⁰ = (CH ₂ ) ₂ OH) (230) Pure trans-diene (512) prepared as described in Example 103 (3.0 g, 10.6 mmol) Was alkylated with 2- (2-bromoethoxy) tetrahydro-2H-pyran by the procedure described in Example 38 to give the crude material. This was dissolved in methanol / tetrahydrofuran (4: 1, 250 mL), 2N hydrochloric acid (20 mL) was added, and the solution was stirred 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. It 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 chromatographed Diels-Alder adduct was aromatized using the procedure described in Example 70 to give the material. This material was then ground from methanol to give alcohol (230) as a yellow powder with a melting point of 229-231 ° C. (2.14 g, 44%). ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.17 (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, 1H), 7.62 (m, 2H), 7.51 (dd, J = 8.9, 7.4 Hz, 1H), 7.31 (dd, J = 9.0) , 2.6 Hz, 1H), 4.83 (t, J = 5.3 Hz, 1H), 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. Calculated _{C 23 H 16 Cl 2 N 2} O 4: C, 60.66; H, 3.54; N, 6.15.

Example 86 4- (2,6-dichlorophenyl) -6- (3-hydroxypropyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (V; Preparation of Ar = 2,6-dichlorophenyl, R ¹⁰ = (CH ₂ ) ₃ OH) (232) The diene (512) (3.0 g, 9.43 mmol) prepared as described in Example 103 was The crude material was obtained by alkylation with 3-bromopropyl tert-butyl (dimethyl) silyl ether by the procedure described in 38. This was dissolved in methanol / dichloromethane (3: 1, 300 mL) and 1N hydrochloric acid (60 mL) was added. The solution was stirred at room temperature for 2 hours, diluted with saturated sodium bicarbonate and concentrated in vacuo to precipitate the crude product. This was collected by filtration and dried in vacuo. This solid was reacted with maleimide (1.20 g) according to the procedure described in Example 68. The crude Diels-Alder adduct was aromatized using the procedure described in Example 70 to give a material. This material was then chromatographed on silica eluting with methanol / dichloromethane (2: 98 → 5: 95) to give alcohol (232) (2.4 g, 54%) as a yellow powder with a melting point of 254-256 ° C. Got. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.18 (br s, 1H), 8.51 (d, J = 2.6 Hz, 1H), 7.86 (s, 1H), 7.72 ( d, J = 9.0 Hz, 1H), 7.63 (m, 2H), 7.51 (dd, J = 8.8, 7.4 Hz, 1H), 7.34 (dd, J = 9.0) , 2.6 Hz, 1H), 4.62 (t, J = 5.0 Hz, 1H), 4.54 (t, J = 6.9 Hz, 2H), 3.91 (s, 3H), 3.42 (M, 2H), 1.90 (m, 2H). Calculated for FABMS M ⁺ = 468.630, 470.0628, 472.0626. Calculated 468.0644,470.0614,472.0585 of _{C 24 H 18 Cl 2 N 2} O 4.

Example 87 4- (4- (2-Chlorophenyl) -9-methoxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) butanoic acid Preparation of (V; Ar = 2-chlorophenyl, R ¹⁰ = (CH ₂ ) ₃ COOH) (262) The diene (27) (0.40 g, 1.41 mmol), prepared as described in Example 37, was run. Alkylation with ethyl bromobutyrate by the procedure described in Example 38 gave the crude material. This was reacted with maleimide (0.27 g) according to the procedure described in Example 68. Using the procedure described in Example 70, the Diels-Alder adduct was aromatized to give a crude material. This was then dissolved in methanol (100 mL) and 2N potassium hydroxide (2 mL) was added. The solution was stirred at room temperature for 2 hours, diluted with water and acidified by adding 1N hydrochloric acid to precipitate a yellow solid product. This was collected by filtration, washed with water and dried in vacuo. Chromatography on silica eluting with ethyl acetate and triturated with diethyl ether / hexanes afforded acid (262) as a yellow powder with a melting point of 251-254 ° C. (0.10 g, 16%). ¹ H NMR δ [(CD ₃ ) ₂ SO] 12.12 (br s, 1 H), 11.12 (br s, 1 H), 8.53 (d, J = 2.6 Hz, 1 H), 7.85 (S, 1H), 7.72 (d, J = 9.0 Hz, 1H), 7.58 (m, 1H), 7.53 to 7.45 (m, 3H), 7.32 (dd, J = 9.0, 2.6 Hz, 1H), 4.50 (t, J = 7.3 Hz, 2H), 3.91 (s, 3H), 2.30 (m, 2H), 1.97 (m , 2H). Calculated value of FABMS [M + H] ⁺ : 463.1025, 465.1034. Calculated 463.1061,465.1031 of _{C 25 H 19 ClN 2 O 5} .

Example 88 4- (4- (2-Chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) butanoic acid Preparation of (VI; Ar = 2-chlorophenyl, R ¹⁰ = (CH ₂ ) ₃ COOH) (263) Acid (262) prepared as described in Example 87 (32 mg, 0.07 mmol) was prepared in Example 80. To give phenol (263) (6 mg, 19%) as an orange powder with a melting point of 274-277 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 12 (v br s, 1 H), 11.06 (br s, 1 H), 9.38 (br s, 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 to 7.43 (m, 3 H) ), 7.14 (dd, J = 8.9, 2.4 Hz, 1H), 4.45 (t, J = 7.5 Hz, 2H), 2.27 (m, 2H), 1.95 (m) , 2H). Calculated value of FABMS [M + H] ⁺ : 449.0874, 451.0879. Calculated 449.0904,451.0875 of _{C 24 H 17 ClN 2 O 5} .

Example 89 9-Hydroxy-6- (2-hydroxyethyl) -4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = phenyl, R ¹⁰ = Preparation of (CH ₂ ) ₂ OH) (220) Alcohol (201) (135 mg, 0.35 mmol) prepared as described in Example 82 was demethylated using the procedure described in Example 81. The alcohol (220) (90 mg, 69%) was obtained as an orange powder having a melting point of 298-301 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.04 (br s, 1 H), 9.31 (br s, 1 H), 8.40 (d, J = 2.5 Hz, 1 H), 7.79 (S, 1H), 7.64 (m, 2H), 7.55 (d, J = 8.8 Hz, 1H), 7.47 (m, 3H), 7.10 (dd, J = 8.8) , 2.5 Hz, 1H), 4.85 (t, J = 5.3 Hz, 1H), 4.51 (t, J = 5.4 Hz, 2H), 3.77 (m, 2H). Found: C, 68.88; H, 4.43; N, 6.76. _{C 22 H 16 N 2 O 4} . 3 / 4H ₂ O Calculated: C, 68.48; H, 4.57 ; N, 7.26.

Example 90 9-Hydroxy-6- (3-hydroxypropyl) -4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = phenyl, R ¹⁰ _{= (CH 2) 3 OH)} (221 alcohol, prepared as described in example 83) (202) and (60 mg, 0.15 mmol), and demethylation using the procedure described in example 80 The alcohol (221) (45 mg, 78%) was obtained as an orange powder with a melting point of 274-276 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.05 (br s, 1H), 9.33 (s, 1H), 8.41 (d, J = 2.4 Hz, 1H), 7.77 ( s, 1H), 7.64 (m, 2H), 7.56 (d, J = 8.8 Hz, 1H), 7.46 (m, 3H), 7.12 (dd, J = 8.8, 2.4 Hz, 1H), 4.64 (t, J = 4.9 Hz, 1H), 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. Calculated _{C 23 H 18 N 2 O 4} : C, 71.49; H, 4.70; N, 7.25.

Example 91 9-Hydroxy-6- (6-hydroxyhexyl) -4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = phenyl, R ¹⁰ _{= (CH 2) 6 OH)} ( alcohol, prepared as described in example 84 of 222) (203) (55mg, 0.12mmol), was demethylated using the procedure described in example 80 The alcohol (222) (12 mg, 23%) was obtained as an orange powder with a melting point of 132-140 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.04 (br s, 1H), 9.33 (s, 1H), 8.41 (d, J = 2.5 Hz, 1H), 7.77 ( s, 1H), 7.64 (m, 2H), 7.54 (d, J = 8.8 Hz, 1H), 7.46 (m, 3H), 7.12 (dd, J = 8.8, 2.5 Hz, 1H), 4.46 (t, J = 7.1 Hz, 2H), 4.29 (t, J = 5.1 Hz, 1H), 3.31 (m, 2H), 1.75 ( m, 2H), 1.36 to 1.26 (m, 6H). Calculated for FABMS M ⁺ : 428.1730. Calcd 428.1736 for _{C 26 H 24 N 2 O 4} .

(Example 92) 9-methoxy-6-methyl-4-phenyl-pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) - dione (V; Ar = ^phenyl, R 10 = _CH 3) ( 223) Pure trans 5-methoxy-2-[(E) -2-phenylethenyl] -1H-indole (II; Ar = phenyl) (0.20 g, 0.80 mmol) was prepared in Example 38. Alkylation with methyl iodide by the procedure described gave the crude material. This was reacted with maleimide (92 mg) according to Method 4a except that the reaction time was 24 hours. The crude Diels-Alder adduct was aromatized by the procedure described in Example 79 to give a crude material. This was chromatographed on silica eluting with ethyl acetate / dichloromethane (1: 3). Trituration from methanol gave carbazole (223) (0.20 g, 70%) as a yellow powder with a melting point of 286-291 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.11 (br s, 1 H), 8.53 (d, J = 2.6 Hz, 1 H), 7.80 (s, 1 H), 7.66 ( m, 3H), 7.47 (m, 3H), 7.30 (dd, J = 9.0, 2.6 Hz, 1H), 3.96 (s, 3H), 3.90 (s, 3H) . Found: C, 74.29; H, 4.67; N, 7.86. Calculated for _{C 22 H 16 N 2 O 3} : C, 74.15; H, 4.53; N, 7.86.

(Example 93) 9-hydroxy-6-methyl-4-phenyl-pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) - dione (VI; Ar = ^phenyl, R 10 = _CH 3) ( The alcohol (223) prepared as described in Example 92 (180 mg, 0.51 mmol) was demethylated using the procedure described in Example 81 and chromatographed on silica to give acetic acid. Elute with ethyl / dichloromethane (1: 2). Trituration from dichloromethane / hexane gave alcohol (224) (155 mg, 90%) as an orange powder with a melting point of 297-300 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.05 (br s, 1 H), 9.34 (s, 1 H), 8.39 (d, J = 2.5 Hz, 1 H), 7.76 ( s, 1H), 7.65 (m, 2H), 7.54 (d, J = 8.8 Hz, 1H), 7.46 (m, 3H), 7.13 (dd, J = 8.8, 2.5 Hz, 1H), 3.93 (s, 3H). Found: C, 69.96; H, 4.58; N, 7.70. _{C 21 H 14 N 2 O 3} . Of H ₂ O Calculated: C, 69.99; H, 4.48 ; N, 7.77.

Example 94 4- (2,6-dichlorophenyl) -9-hydroxy-6- (2-hydroxyethyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Preparation of Ar = 2,6-dichlorophenyl, R ¹⁰ = (CH ₂ ) ₂ OH) (234) Alcohol (230) (0.10 g, 0.22 mmol) prepared as described in Example 85 was Demethylation using the procedure described in 80 gave phenol (234) (49 mg, 50%) as an orange / yellow powder with a melting point of 254-257 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.10 (br s, 1H), 9.35 (s, 1H), 8.36 (d, J = 2.4 Hz, 1H), 7.80 ( s, 1H), 7.61 (m, 3H), 7.50 (dd, J = 8.7, 7.3 Hz, 1H), 7.13 (dd, J = 8.8, 2.4 Hz, 1H) ), 4.82 (t, J = 5.5 Hz, 1H), 4.49 (t, J = 5.2 Hz, 2H), 3.75 (m, 2H). Found: C, 58.76; H, 3.34; N, 6.25. _{C 22 H 14 Cl 2 N 2} O4.1 / 2H 2 O Calculated: C, 58.67; H, 3.36 ; N, 6.22.

Example 95 4- (2,6-dichlorophenyl) -9-hydroxy-6- (3-hydroxypropyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Preparation of Ar = 2,6-dichlorophenyl, R ¹⁰ = (CH ₂ ) ₃ OH) (235) Alcohol (232) (0.36 g, 0.77 mmol) prepared as described in Example 86 was Demethylation using the procedure described in 80 gave phenol (235) (0.32 g, 92%) as an orange / yellow powder with a melting point of 215-218 ° C. ¹ H NMR δ [(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, 1H), 7.61 (m, 3H), 7.51 (dd, J = 8.7, 7.2 Hz, 1H), 7.16 (dd, J = 8.8, 2.5 Hz, 1H) ) 4.61 (t, J = 5.0 Hz, 1H), 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. Calculated _{C 23 H 16 Cl 2 N 2} O 4: C, 60.66; H, 3.54; N, 6.15.

Example 96 3- {2-[(E) -2- (2-chlorophenyl) ethenyl] -5-methoxy-1H-indol-1-yl} propanenitrile (III; Ar = 2-chlorophenyl, R ¹⁰ = CH ₂ CH ₂ CN) (236) Preparation To a solution of trans-diene (27) (1.5 g, 5.25 mmol) prepared in Example 37 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 nitrogen for 18 hours, diluted with water and extracted with ethyl acetate. The organic layer was dehydrated, the dehydrating agent was removed, and the solution was concentrated to dryness. Chromatography on silica, eluting with ethyl acetate / hexane (1: 1), then triturated from methanol to give diene (236) (1.36 g, 77%) as an off-white solid, mp 136-138 ° C Got. ¹ H NMR δ [(CD ₃ ) ₂ SO] 8.05 (dd, J = 7.0, 1.5 Hz, 1H), 7.50 (m, 4H), 7.41 (m, 1H), 7 .33 (m, 1H), 7.04 (d, J = 2.4 Hz, 1H), 6.90 (s, 1H), 6.81 (dd, J = 9.0, 2.4 Hz, 1H) 4.68 (t, J = 6.6 Hz, 2H), 3.77 (s, 3H), 2.93 (t, J = 6.6 Hz, 2H). Found: C, 71.32; H, 5.14; N, 8.51. C ₂₀ H ₁₇ ClN ₂ O Calculated: C, 71.31; H, 5.09 ; N, 8.31.

Example 97 3- (4- (2-Chlorophenyl) -9-methoxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) propanenitrile Preparation of (V; Ar = 2-chlorophenyl, R ¹⁰ = CH ₂ CH ₂ CN) (237) The diene (236) (1.30 g, 3.86 mmol) prepared as described in Example 96 was Reaction with maleimide (0.49 g) according to the procedure described in 68 followed by aromatization by the procedure described in Example 70 gave the crude material. This was chromatographed on silica, eluting with ethyl acetate / hexane (1: 1). Trituration from methanol gave nitrile (237) (1.33 g, 80%) as a yellow powder with a melting point of 287-288 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.16 (br s, 1H), 8.53 (d, J = 2.6 Hz, 1H), 8.02 (s, 1H), 7.83 ( d, J = 9.0 Hz, 1H), 7.59 (m, 1H), 7.49 (m, 3H), 7.33 (dd, J = 9.0, 2.6 Hz, 1H), 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. _{C 24 H 16 ClN 3 O 3} . 3 / 4H ₂ O Calculated: C, 65.01; H, 3.98 ; N, 9.47.

Example 98 3- (4- (2-Chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) propanenitrile Preparation of (VI; Ar = 2-chlorophenyl, R ¹⁰ = CH ₂ CH ₂ CN) (238) Nitrile (237) (0.15 g, 0.35 mmol) prepared as described in Example 97 was Demethylated using the procedure described in 80, then triturated from methanol to give phenol (238) (0.13 g, 89%) as an orange / yellow powder with a melting point of 332-336 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.10 (br s, 1 H), 9.42 (br s, 1 H), 8.39 (d, J = 2.4 Hz, 1 H), 7.96 (S, 1H), 7.69 (d, J = 8.8 Hz, 1H), 7.58 (m, 1H), 7.48 (m, 3H), 7.15 (dd, J = 8.8) , 2.4. Hz, 1H), 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. Calculated _{C 23 H 14 ClN 3 O 3} : C, 66.43; H, 3.39; N, 10.10.

Example 99 6-Benzyl-4- (2-chlorophenyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (V; Ar = 2-chlorophenyl, R ¹⁰ = CH ₂ Ph) (239) Preparation of pure trans-diene (27) (0.20 g, 0.70 mmol) prepared as described in Example 37 was brominated by the procedure described in Example 38. Alkylation with benzyl gave the crude material. This was reacted directly with maleimide (103 mg) according to the procedure described in Example 68 except that the reaction time was 24 hours. The crude Diels-Alder adduct was aromatized using the procedure described in Example 70 to give a crude material. This was chromatographed on silica eluting with ethyl acetate / hexane (1: 2). Trituration from ethyl acetate / hexane gave carbazole (239) (0.15 g, 46%) as a yellow powder with a melting point of 234-237 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.15 (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, 1H), 7.56 (m, 1H), 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. Calculated for _{C 28 H 19 ClN 2 O 3} : C, 72.02; H, 4.10; N, 6.00.

Example 100 6-Benzyl-4- (2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = 2-chlorophenyl, R ¹⁰ = CH ₂ Ph) (240) Preparation Carbazole (239) (0.10 g, 0.21 mmol) prepared as described in Example 99 was demethylated using the procedure described in Example 80, It was then chromatographed on silica, eluting with ethyl acetate / hexane (1: 2). Trituration from ethyl acetate / hexane gave carbazole (240) (87 mg, 91%) as an orange / yellow powder with a melting point of 269-271 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.09 (br s, 1 H), 9.40 (s, 1 H), 8.40 (d, J = 2.5 Hz, 1 H), 7.86 ( s, 1H), 7.56 (m, 2H), 7.45 (m, 3H), 7.25 (m, 3H), 7.16 (m, 2H), 7.11 (dd, J = 8 .9, 2.5 Hz, 1H), 5.75 (s, 2H). Found: C, 72.06; H, 4.18; N, 6.20. Calculated for _{C 27 H 17 ClN 2 O 3} : C, 71.60; H; 3.78; N, 6.18.

Example 101 Methyl 3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) propanoate Preparation of (VI, Ar = 2-chlorophenyl, R ¹⁰ = (CH ₂ ) ₂ COOCH ₃ ) (264) Gaseous hydrochloric acid was prepared as described in Example 230 Acid (117) (35 mg, 0.08 mmol ) Through a stirred solution of methanol (10 mL) for 30 seconds. The resulting solution was stirred at room temperature for 30 minutes, diluted with water and extracted with ethyl acetate. The organic layer was dehydrated, the dehydrating agent was removed, and the solution was concentrated to dryness. Chromatography on silica, eluting with ethyl acetate / hexane (1: 1) and then crystallized from ethyl acetate / hexane to give ester (264) (25 mg as an orange powder, mp 218-220 ° C. 70%). ¹ H NMR δ [(CD ₃ ) 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, 1H), 7.57 (m, 2H), 7.51 to 7.44 (m, 3H), 7.14 (dd, J = 8.8, 2.5 Hz, 1H), 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. _{C 24 H 17 ClN 2 O 5} . 3 / 4H ₂ O Calculated: C, 62.34; H, 4.03 ; N, 6.06.

  Exemplary Procedure for Method 10a of Scheme 2

Example 102 Preparation of (2,6-dichlorobenzyl) (triphenyl) phosphonium bromide (511) 2,6-dichlorotoluene (20.1 g, 0.125 mol), N-bromosuccinimide (24.6 g, 0.138 mol) and 2,2′-azobisisobutyronitrile (0.41 g, 2.50 mmol) in anhydrous benzene (300 mL) were continuously irradiated with a 100 W lamp and refluxed under N ₂ The mixture was stirred for 6 hours. The resulting reaction mixture was concentrated in vacuo (to 50 mL), cooled, filtered and washed with anhydrous benzene. The filtrate (containing crude benzyl bromide) was treated directly with triphenylphosphine (49.3 g, 0.188 mol) and stirred at reflux for 17 hours. After cooling, the precipitate was collected by filtration, washed thoroughly with anhydrous benzene and then pentane, and dried under reduced pressure at 50 ° C. to give a creamy powder (62.1 g, 99% ) To obtain a phosphonium salt (511). ¹ H NMR (CDCl ₃ ) δ 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. C ₂₅ H ₂₀ BrCl ₂ P Calculated C, 59.79; H, 4.01.

Example 103 Preparation of 2-[(E) -2- (2,6-dichlorophenyl) ethenyl] -5-methoxy-1H-indole (512) (II, Ar = 2,6-dichlorophenyl) LDA and aldehyde Was added at 0 ° C. (continuously), the LDA: aldehyde ratio was 1.37: 1, and the reaction time was 5 hours, followed by the procedure described in Example 37 to give 5-methoxy-1H-indole. 2-carbaldehyde (1) was reacted with (2,6-dichlorobenzyl) (triphenyl) phosphonium bromide (511) prepared as described in Example 102 to give (CH ₂ Cl ₂ / to The diene (512) (97%) was obtained as a yellow solid (pure E isomer) mp 144-147 ° C. (after crystallization from xane). ¹ H NMR (CDCl ₃ ) δ 8.20 (br s, 1H), 7.36 (d, J = 8.1 Hz, 1H), 7.27 (m, 1H), 7.25 (d, J = 16 .8 Hz, 11H), 7.11 (t, J = 8.0 Hz, 1H), 7.03 (d, J = 2.4 Hz, 1H), 6.93 (d, J = 16.8 Hz, 1H) 6.88 (dd, J = 8.7, 2.5 Hz, 1H), 6.61 (d, J = 1.8 Hz, 1H), 3.86 (s, 3H). Found: C, 64.04; H, 4.13; N, 4.39. Calculated for _{C 17 H 13 Cl 2 NO C} , 64.17; H, 4.12; N, 4.40.

Example 104 4- (2,6-dichlorophenyl) -9-methoxy-4,5,6,10c-tetrahydropyrrolo [3,4-c] carbazole-1,3 (2H, 3aH) -dione (513 ) Preparation of (IV, R ¹⁰ = H, Ar = 2,6-dichlorophenyl) Pure E diene (512), prepared as described in Example 103, was prepared in a diene: maleimide: SnCl ₂ ratio of 1: 4: React with maleimide in a sealed vial covered with foil by the procedure described in Example 68 except that the reaction time is 3 hours except that the reaction time is 3 hours to obtain a crude solid containing the adduct (513). It was. This was used without further purification.

(Example 105) 4- (2,6-dichlorophenyl) -9-methoxy-pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) - dione ^{(514) (V, R 10} = H, Ar = 2,6-dichlorophenyl) The crude adduct (513) prepared as described in Example 104 was prepared in Example 70 except that the solvent was 1: 1 toluene / dioxane and the reaction time was 48 hours. Aromatization with DDQ (5 eq) using the procedure described to give the product (514) as a yellow crystalline solid, mp 299-301 ° C. (after crystallization from MeOH / CH ₂ Cl ₂ / hexane) (78%) was obtained. ¹ H NMR [(CD ₃ ) ₂ SO] δ 12.02 (br s, 1 H), 11.15 (br s, 1 H), 8.45 (d, J = 2.6 Hz, 1 H), 7.61 ( d, J = 7.7 Hz, 2H), 7.61 (s, 1H), 7.59 (d, J = 8.9 Hz, 1H), 7.50 (dd, J = 8.8, 7.4 Hz) , 1H), 7.26 (dd, J = 8.9, 2.7 Hz, 1H), 3.90 (s, 3H). Found: C, 61.26; H, 2.92; N, 6.65. C ₂₁ H ₁₂ Calculated _{Cl 2 N 2 O 3 C,} 61.33; H, 2.94; N, 6.81.

Example 106 4- (2,6-dichlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (515) (VI, R ¹⁰ = H, Ar = 2,6-dichlorophenyl) The methyl ether (514) prepared as described in Example 105 was demethylated with BBr ₃ by the procedure described in Example 80 to give (MeOH / CH ₂ Cl ₂ / After crystallization from hexane) phenol (515) (98%) was obtained as an orange solid with a melting point of 205-215 ° C. ¹ H NMR [(CD ₃ ) ₂ SO] δ 11.89 (br s, 1 H), 11.08 (br s, 1 H), 9.32 (br s, 1 H), 8.30 (d, J = 2) .4 Hz, 1H), 7.61 (d, J = 7.9 Hz, 2H), 7.55 (s, 1H), 7.50 (dd, J = 8.7, 7.4 Hz, 1H), 7 .47 (d, J = 8.7 Hz, 1H), 7.10 (dd, J = 8.7, 2.4 Hz, 1H). Found: C, 58.98; H, 2.99; N, 6.68. _{C 20 H 10 Cl 2 N 2} O 3. Calculated for _1/2 H2O C, 59.13; H, 2.73; N, 6.90.

Example 107 (2,6-Dibromobenzyl) (triphenyl) phosphonium bromide (516)
Bromination of 2,6-dibromotoluene using NBS / AIBN followed by reaction of the crude bromide with triphenylphosphine according to the procedure described in Example 102 except that the reaction time for bromination was 3 hours. Phosphonium salt (516) (95%) was obtained as a cream powder having a melting point (CH ₂ Cl ₂ / benzene) of 241 to 243 ° C. ¹ H NMR (CDCl ₃ ) δ 7.78 (m, 9H), 7.64 (m, 6H), 7.40 (br d, J = 7.9 Hz, 2H), 6.99 (td, J = 8) 0.0, 2.5 Hz, 1H), 5.58 (d, J = 14.1 Hz, 2H). Found: C, 47.06; H, 3.37. C ₂₅ H ₂₀ Br ₃ P. 3 / _4CH 2 of Cl ₂ Calculated C, 47.23; H, 3.31.

Example 108 Preparation of 2-[(E) -2- (2,6-dibromophenyl) ethenyl] -5-methoxy-1H-indole (517) (II, Ar = 2,6-dibromophenyl) 5 -Methoxy-1H-indole-2-carbaldehyde (1) was prepared according to the procedure described in Example 37, except that the LDA: aldehyde ratio was 1.37: 1 and the reaction time was 5 hours. Reacting with (2,6-dibromobenzyl) (triphenyl) phosphonium bromide (516) prepared as described and having a melting point of 140-141 ° C. (after crystallization from CH ₂ Cl ₂ / hexane) Diene (517) (80%) was obtained as a yellow solid (pure E isomer). ¹ H NMR (CDCl ₃ ) δ 8.20 (br s, 1H), 7.60 (d, J = 8.1 Hz, 1H), 7.27 (d, J = 8.2 Hz, 1H), 7.05 (Br s, 1H), 7.03 (d, J = 16.7 Hz, 1H), 6.96 (t, J = 8.0 Hz, 1H), 6.88 (dd, 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, 3 H). Found: C, 50.37; H, 3.24; N, 3.37. Calculated for _{C 17 H 13 Br 2 NO C} , 50.16; H, 3.22; N, 3.44.

Example 109 4- (2,6-dibromophenyl) -9-methoxy-4,5,6,10c-tetrahydropyrrolo [3,4-c] carbazole-1,3 (2H, 3aH) -dione ( 518) Preparation of (IV, R ¹⁰ = H, Ar = 2,6-dibromophenyl) Pure E diene (517), prepared as described in Example 108, was prepared with a diene: maleimide: SnCl ₂ ratio of 1: 5: Reacted with maleimide in a sealed vial covered with foil according to the procedure described in Example 68 except that the reaction time was 3.5 hours except 0.075 and the reaction time was 3.5 hours. ) This was used without further purification.

Example 110 4- (2,6-Dibromophenyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (519) (V, R ¹⁰ = H, Ar = 2,6-dibromophenyl) Preparation of the crude adduct (518) prepared as described in Example 109, except that the solvent was 1: 1 toluene / dioxane and the reaction time was 24 hours. 70. Aromatization with DDQ (5 equivalents) using the procedure described in No. 70 to produce the product as an orange crystalline solid with a melting point of 329-331 ° C. (after crystallization from MeOH / CH ₂ Cl ₂ / hexane) (519) (68%) was obtained. ¹ H NMR [(CD ₃ ) ₂ SO] δ 12.02 (br s, 1 H), 11.13 (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, 1H), 7.54 (s, 1H), 7.33 (t, J = 8.0 Hz, 1H), 7.26 (dd, J = 8.8, 2.6 Hz, 1H), 3.90 (s, 3H). Found: C, 50.29; H, 2.32; N, 5.69. C ₂₁ H ₁₂ Br ₂ Calculated _{N 2 O 3 C, 50.43;} H, 2.42; N, 5.60.

Example 111 4- (2,6-dibromophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (520) (VI, R ¹⁰ = H, Ar = 2,6 the prepared ether as described in example 110 of dibromophenyl) (519), the BBr ₃ by the procedure described in example 80 except the reaction time was 1.5 hours Was used to demethylate (after crystallization from MeOH / CH ₂ Cl ₂ / EtOAc / hexane) to give phenol (520) (98%) as a yellow-orange solid, mp 180-190 ° C. ¹ H NMR [(CD ₃ ) ₂ SO] δ 11.90 (br s, 1 H), 11.08 (br s, 1 H), 9.35 (br s, 1 H), 8.30 (d, J = 2) .3 Hz, 1 H), 7.80 (d, J = 8.1 Hz, 2 H), 7.49 (s, 1 H), 7.48 (d, J = 8.9 Hz, 1 H), 7.33 (t , J = 8.1 Hz, 1H), 7.11 (dd, J = 8.7, 2.5 Hz, 1H). Found: C, 49.13; H, 2.29; N, 6.05. _{C 20 H 10 Br 2 N 2} O 3 Calculated 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) (2,6-dichloro-4-methoxyphenyl) methanol (3.00 g, 14.5 mmol) ) In 30% HBr acetic acid (45 mL) was stirred at 20 ° C. for 3 h, then poured onto ice water (120 mL) and extracted with pentane (6 × 100 mL). The extract was washed with water (3 × 200 mL) and back extracted with pentane (100 mL). Removal of the solvent gave the crude bromide as white crystals. This was immediately redissolved in benzene (80 mL), treated with triphenylphosphine (5.70 g, 21.7 mmol) and stirred at reflux for 15 hours. After cooling, the precipitate was collected by filtration, washed thoroughly with anhydrous benzene and then pentane, dried in vacuo at 50 ° C., and phosphonium salt as a white solid with a melting point (CH ₂ Cl ₂ / benzene) 188-190 ° C. (521) (7.75 g, 100%) was obtained. ¹ H NMR (CDCl ₃ ) δ 7.83 to 7.60 (m, 15H), 6.74 (s, 2H), 5.37 (d, J = 13.5 Hz, 2H), 3.76 (s, 3H). Found: C, 58.40; H, 4.35. C ₂₆ H ₂₂ BrCl ₂ OP Calculated C, 58.67; H, 4.17.

Example 113 2-[(E) -2- (2,6-dichloro-4-methoxyphenyl) ethenyl] -5-methoxy-1H-indole (522) (II, Ar = 2,6-dichloro- Preparation of 4-methoxyphenyl) According to the procedure described in Example 37 except that the aldehyde was added at 0 ° C., the LDA: aldehyde ratio was 1.37: 1 and the reaction time was 5 hours. 1H-indole-2-carbaldehyde (1) is reacted with (2,6-dichloro-4-methoxybenzyl) (triphenyl) phosphonium bromide (521) prepared as described in Example 112, The diene (522) (70%) was obtained as a creamy solid (pure E isomer) with a melting point of 128-129 ° C. (after crystallization from CH ₂ Cl ₂ / hexane). ¹ H NMR (CDCl ₃ ) δ 8.17 (br s, 1H), 7.25 (d, J = 8.7 Hz, 1H), 7.17 (d, J = 16.8 Hz, 1H), 7.04 (D, J = 2.4 Hz, 1H), 6.93 (s, 2H), 6.88 (d, J = 16.8 Hz, 1H), 6.86 (dd, J = 8.7, 2.H). 5 Hz, 1 H), 6.57 (br d, J = 1.7 Hz, 1 H), 3.85 (s, 3 H), 3.82 (s, 3 H). Found: C, 62.01; H, 4.23; N, 4.21. C ₁₈ H ₁₅ Calculated _{Cl 2 NO 2 C, 62.09;} H, 4.34; N, 4.02.

Example 114 4- (2,6-dichloro-4-methoxyphenyl) -9-methoxy-4,5,6,10c-tetrahydropyrrolo [3,4-c] carbazole-1,3 (2H, 3aH ) Preparation of dione (523) (IV, R ¹⁰ = H, Ar = 2,6-dichloro-4-methoxyphenyl) The pure E diene (522) prepared as described in Example 113 was converted to Addition by reacting with maleimide in a sealed vial covered with foil according to the procedure described in Example 68 except that the maleimide: SnCl ₂ ratio is 1: 6: 0.05 and the reaction time is 1.5 hours. A crude solid (523) containing body was obtained. This was used without further purification.

Example 115 4- (2,6-dichloro-4-methoxyphenyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (524) (V, R ¹⁰ = H, Ar = 2,6-dichloro-4-methoxyphenyl) The crude adduct (523) prepared as described in Example 114 was prepared using a 1: 1 toluene / dioxane solvent and a reaction time. Aromatized with DDQ (6 equivalents) using the procedure described in Example 70 except after 24 hours, and after crystallization from MeOH / CH ₂ Cl ₂ / hexanes, mp 272-274 ° C. The product (524) (74%) was obtained as a yellow-orange crystalline solid. ¹ H NMR [(CD ₃ ) ₂ SO] δ 11.98 (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, 1H), 7.57 (s, 1H), 7.26 (dd, J = 8.8, 2.6 Hz, 1H), 7.23 (s, 2H), 3. 89 (2s, 2x3H). Found: C, 56.89; H, 3.18; N, 5.94. _{C 22 H 14 Cl 2 N 2} O 4. 5 / 4H ₂ O Calculated C, 56.97; H, 3.59; N, 6.04.

Example 116 4- (2,6-dichloro-4-hydroxyphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (525) (VI, R ¹⁰ = H, Ar = 2,6-dichloro-4-hydroxyphenyl) Methyl ether (524) prepared as described in Example 115 was reacted for 4 hours with 10 equivalents of BBr ₃ and then additional Crystallized from (MeOH / CH ₂ Cl ₂ / hexane) by demethylating twice with BBr ₃ (bis-demethylate) according to the procedure described in Example 80 except 10 equivalents of BBr ₃ for an additional 9 hours. Phenol (525) (95%) was obtained as a yellow-orange solid with a melting point of 300-308 ° C. ¹ H NMR [(CD ₃ ) ₂ SO] δ 11.82 (br s, 1 H), 11.03 (br s, 1 H), 10.47 (br s, 1 H), 9.28 (br s, 1 H) 8.29 (d, J = 2.4 Hz, 1H), 7.50 (s, 1H), 7.46 (d, J = 8.7 Hz, 1H), 7.08 (dd, J = 8. 7, 2.5 Hz, 1H), 6.96 (s, 2H). Found: C, 56.28; H, 2.94; N, 6.16. _{C 20 H 10 Cl 2 N 2} O 4. 3 / 4H ₂ O Calculated C, 56.29; H, 2.72; N, 6.56.

Example 117 Preparation of (2,6-dichloro-3-methoxybenzyl) (triphenyl) phosphonium (526) bromide According to the procedure described in Example 112 except that the reaction time for the substitution was 36 hours ( 2,6-dichloro-3-methoxyphenyl) methanol was brominated with 30% HBr acetic acid solution, then the crude bromide was reacted with triphenylphosphine to give a white melting point (CH ₂ Cl ₂ / benzene) 242-244 ° C. The phosphonium salt (526) (97%) was obtained as a solid. ¹ H NMR (CDCl ₃ ) δ 7.83 to 7.60 (m, 15H), 7.15 (dd, J = 9.1, 0.8 Hz, 1H), 6.88 (dd, J = 9.0) , 2.4 Hz, 1H), 5.41 (d, J = 14.3 Hz, 2H), 3.84 (s, 3H). Found: C, 58.68; H, 4.16. C ₂₆ H ₂₂ BrCl ₂ OP Calculated C, 58.67; H, 4.17.

Example 118 2-[(E) -2- (2,6-dichloro-3-methoxyphenyl) ethenyl] -5-methoxy-1H-indole (527) (II, Ar = 2,6-dichloro- Preparation of 3-methoxyphenyl) According to the procedure described in Example 37 except that aldehyde was added at 0 ° C., the LDA: aldehyde ratio was 1.55: 1 and the reaction time was 5 hours. Indole-2-carbaldehyde (1) is reacted with (2,6-dichloro-3-methoxybenzyl) (triphenyl) phosphonium bromide (526) prepared as described in Example 117, and ( The diene (527) (76%) was obtained as a creamy solid (pure E isomer) with a melting point of 138-140 ° C. after crystallization from CH ₂ Cl ₂ / hexane. ¹ H NMR (CDCl ₃ ) δ 8.21 (br s, 1H), 7.32 (d, J = 8.9 Hz, 1H), 7.26 (d, J = 8.7 Hz, 1H), 7.22 (D, J = 16.8 Hz, 1H), 7.04 (d, J = 2.4 Hz, 1H), 6.92 (d, J = 16.8 Hz, 1H), 6.87 (dd, J = 8.8, 2.5 Hz, 1H), 6.80 (d, J = 8.9 Hz, 1H), 6.61 (d, J = 1.7 Hz, 1H), 3.92 (s, 3H), 3.85 (s, 3H). Found: C, 61.92; H, 4.52; N, 3.91. C ₁₈ H ₁₅ Calculated _{Cl 2 NO 2 C, 62.09;} H, 4.34; N, 4.02.

Example 119 4- (2,6-dichloro-3-methoxyphenyl) -9-methoxy-4,5,6,10c-tetrahydropyrrolo [3,4-c] carbazole-1,3 (2H, 3aH Preparation of) -dione (528) (IV, R ¹⁰ = H, Ar = 2,6-dichloro-3-methoxyphenyl) Pure E diene (527), prepared as described in Example 118, was prepared as: Addition by reacting with maleimide in a sealed vial covered with foil according to the procedure described in Example 68 except that the maleimide: SnCl ₂ ratio is 1: 5: 0.03 and the reaction time is 2.5 hours. A crude solid (528) containing body was obtained. This was used without further purification.

Example 120 4- (2,6-Dichloro-3-methoxyphenyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (529) (V, R ¹⁰ = H, Ar = 2,6-dichloro-3-methoxyphenyl) The crude adduct (528), prepared as described in Example 119, was prepared using a 1: 1 toluene / dioxane solvent and a reaction time. Aromatic with DDQ (5 equivalents) using the procedure described in Example 70 except for 24 hours and (after crystallizing from CH ₂ Cl ₂ / hexane) an orange color with a melting point of 240-242 ° C. The product (529) (70%) was obtained as a crystalline solid. ¹ H NMR [(CD ₃ ) ₂ SO] δ 12.00 (br s, 1 H), 11.13 (br s, 1 H), 8.45 (d, J = 2.6 Hz, 1 H), 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, 1H), 7.26 (dd, J = 9.0, 2.4 Hz, 1H), 3.94 (s, 3H), 3.90 (s, 3H). Found: C, 60.11; H, 3.16; N, 6.30. Calculated for _{C 22 H 14 Cl 2 N 2} O 4 C, 59.88; H, 3.20; N, 6.35.

Example 121 4- (2,6-dichloro-3-hydroxyphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (530) (VI, R ¹⁰ = H, Ar = 2,6 dichloro-3 prepared ether as described in example 120 of hydroxyphenyl) (529), except the reaction time was 10 equivalents BBr ₃ in 6 hours Phenol as an orange crystalline solid with a melting point of 313-318 ° C. (after crystallization from MeOH / CH ₂ Cl ₂ / hexane) by demethylation twice with BBr ₃ by the procedure described in Example 80. (530) (91%) was obtained. ¹ H NMR [(CD ₃ ) ₂ SO] δ 11.84 (br s, 1 H), 11.05 (br s, 1 H), 10.56 (br s, 1 H), 9.29 (br s, 1 H) 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. _{C 20 H 10 Cl 2 N 2} O 4. Calculated for 1/2 MeOH C, 57.36; H, 2.82; N, 6.53.

Example 122 Preparation of 2-[(E) -2- (2-bromophenyl) ethenyl] -5-methoxy-1H-indole (531) (II, Ar = 2-bromophenyl) The aldehyde at 0 ° C. And 5-methoxy-1H-indole-2-carbaldehyde (1) was odorized according to the procedure described in Example 37 except that the LDA: aldehyde ratio was 1.46: 1 and the reaction time was 5 hours. Diene as a yellow solid (pure E isomer) with a melting point of 120-123 ° C. (after crystallization from CH ₂ Cl ₂ / hexane) by reaction with (2-bromobenzyl) (triphenyl) phosphonium 531) (88%). ¹ H NMR (CDCl ₃ ) δ 8.21 (br s, 1H), 7.66 (dd, J = 7.9, 1.5 Hz, 1H), 7.59 (dd, J = 8.1, 1.. 0 Hz, 1H), 7.32 (br t, J = 7.1 Hz, 1H), 7.27 (d, J = 8.3 Hz, 1H), 7.22 (d, J = 16.4 Hz, 1H) 7.12 (td, J = 7.6, 1.5 Hz, 1H), 7.05 (d, J = 16.4 Hz, 1H), 7.04 (d, J = 2.4 Hz, 1H), 6.88 (dd, J = 8.8, 2.4 Hz, 1H), 6.59 (d, J = 1.7 Hz, 1H), 3.86 (s, 3H). Found: C, 61.97; H, 4.30; N, 4.17. C ₁₇ H ₁₄ BrNO Calculated C, 62.21; H, 4.30; N, 4.27.

  Representative procedure for combining method 4a and method 6 of Scheme 2

Example 123 4- (2-Bromophenyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (532) (V, R ¹⁰ = H, Ar = Preparation of 2-bromophenyl) Anhydrous toluene (1.48 g, 15.2 mmol) in a mixture of pure E diene (531) (1.00 g, 3.05 mmol) and maleimide (1.48 g, prepared as described in Example 122). 10 mL) solution was covered with foil and stirred for 24 hours at reflux in a sealed vial. The resulting thick suspension was further transferred to a flask with toluene (30 mL) and dioxane (40 mL), then treated with DDQ (3.49 g, 15.4 mmol) and stirred at reflux for 24 hours. The resulting mixture was treated with saturated aqueous NaHCO ₃ (250 mL) and the product was extracted with 15% MeOH / CH ₂ Cl ₂ . These extracts were washed with aqueous NaHCO ₃ and water. Aqueous NaHCO ₃ and water were extracted several times with 15% MeOH / CH ₂ Cl ₂ and then the combined extract was concentrated to dryness. The residue was adsorbed on silica gel and chromatographed. _{0~0.75% MeOH / CH 2 Cl 2} , then eluted with _{0.75% MeOH / CH 2 Cl 2} , to give the crude product (532). This was crystal purified from MeOH / CH ₂ Cl ₂ / hexane as an orange crystalline solid (1.23 g, 96%) with a melting point of 273-275 ° C. ¹ H NMR [(CD ₃ ) ₂ SO] δ 11.96 (br s, 1 H), 11.08 (br s, 1 H), 8.46 (d, J = 2.6 Hz, 1 H), 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. C ₂₁ H ₁₃ BrN ₂ O ₃ Calculated C, 59.88; H, 3.11; N, 6.65.

Example 124 4- (2-Bromophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (533) (VI, R ¹⁰ = H, Ar = Preparation of 2-bromophenyl) Methyl ether (532) prepared as described in Example 123 was demethylated using BBr ₃ by the procedure described in Example 80 except that the reaction time was 4 hours. . Crystallization from MeOH / CH ₂ Cl ₂ / hexane afforded phenol (533) as a yellow-orange solid, mp 244-246 ° C., in 89% yield. ¹ H NMR [(CD ₃ ) ₂ SO] δ 11.83 (br s, 1 H), 11.01 (br s, 1 H), 9.29 (br s, 1 H), 8.31 (d, J = 2) .4 Hz, 1 H), 7.73 (br d, J = 7.9 Hz, 1 H), 7.47 (m, 4 H), 7.38 (m, 1 H), 7.08 (dd, J = 8. 7, 2.5 Hz, 1 H). Found: C, 57.82; H, 2.90; N, 6.72. _{C 20 H 11 BrN 2 O 3} . Calculated for _1/2 H2O C, 57.71; H, 2.91; N, 6.73.

Example 125 4- [1,1′-biphenyl] -2-yl-9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (534) (V, R ¹⁰ = H, Ar = 2-biphenyl) Bromo derivative (532) (85.5 mg, 0.203 mmol), [1,1′-bis (diphenylphosphino) ferrocene, prepared as described in Example 123 ] dichloropalladium _{(II), CH 2 Cl 2} (85mg, 0.104mmol) and tetraphenyl tin 4 at 130 ° C. in a sealed vial in anhydrous DMF (2.5 mL) solution of a mixture of (0.451,1.06mmol) Stir for days. The resulting mixture was added to aqueous NaHCO ₃ (100 mL) and then extracted with 2: 1 CH ₂ Cl ₂ / EtOAc (5 × 80 mL). The extract was washed with water. The water was extracted with 2: 1 CH ₂ Cl ₂ / EtOAc, 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%). This was mixed with material from a similar reaction, to purified by preparative reverse-phase C-18HPLC _(CH 3 CN / aqueous _HCO 2 NH ₄ buffer for 65 to 99% gradient, with PH3.45) The pure product (534) (21% total) was obtained as a yellow solid (after crystallization from MeOH / CH ₂ Cl ₂ / hexane), mp 220-223 ° C. ¹ H NMR [(CD ₃ ) ₂ SO] δ 11.76 (br s, 1 H), 10.87 (br s, 1 H), 8.39 (d, J = 2.6 Hz, 1 H), 7.50 ( m, 5H), 7.38 (s, 1H), 7.20 (dd, J = 8.9, 2.6 Hz, 1H), 7.10 (m, 5H), 3.86 (s, 3H) . Found: C, 77.37; H, 4.21; N, 6.88. Calculated C of _{C 27 H 18 N 2 O 3} , 77.50; H, 4.34; N, 6.69.

Example 126 4- [1,1′-biphenyl] -2-yl-9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (535) (VI, R ¹⁰ = H, Ar = 2-biphenyl) Methyl ether (534), prepared as described in Example 125, was prepared using BBr ₃ according to the procedure described in Example 80 except that the reaction time was 4 hours. Demethylation afforded phenol (535) (98%) as a yellow solid with a melting point of 198-203 ° C. (after crystallization from MeOH / CH ₂ Cl ₂ / hexane). ¹ H NMR [(CD ₃ ) ₂ SO] δ 11.61 (br s, 1 H), 10.82 (br s, 1 H), 9.22 (br s, 1 H), 8.24 (d, J = 2) .4 Hz, 1 H), 7.52 (m, 1 H), 7.45 (m, 3 H), 7.37 (d, J = 8.7 Hz, 1 H), 7.31 (s, 1 H), 7. 11 (m, 5H), 7.03 (dd, J = 8.7, 2.5 Hz, 1H). Found: C, 76.38; H, 3.94; N, 6.99. _{C 26 H 16 N 2 O 3} . 1 / 4H ₂ O Calculated C, 76.37; H, 4.07; N, 6.85.

Example 127 Preparation of 5-methoxy-2-[(E) -2- (2-nitrophenyl) ethenyl] -1H-indole (536) (II, Ar = 2-nitrophenyl) 5-methoxy-1H Indole-2-carbaldehyde (1) was prepared according to the procedure described in Example 37 except that the LDA: aldehyde ratio was 1.37: 1 and the reaction time was 5 hours. phenyl) is reacted with a phosphonium, _(CH 2 after Cl ₂ / to from hexane crystallized) red mp 136-138 ° C. - diene as orange crystals (pure E isomer) (536) (47% ) ¹ H NMR (CDCl ₃ ) δ 8.25 (br s, 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). Found: C, 69.44; H, 4.49; N, 9.70. Calculated C of _{C 17 H 14 N 2 O 3} , 69.38; H, 4.79; N, 9.52.

Example 128 9-Methoxy-4- (2-nitrophenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (537) (V, R ¹⁰ = H, Ar = Preparation of 2-nitrophenyl) Pure E diene (536), prepared as described in Example 127, was subjected to a sequential reaction with maleimide and then DDQ according to the representative procedure described in Example 123 above, ( After crystallization from MeOH / EtOAc / CH ₂ Cl ₂ / hexane) the product (537) (97%) was obtained as a yellow-orange solid with a melting point of 294-298 ° C. ¹ H NMR [(CD ₃ ) ₂ SO] δ 12.01 (br s, 1 H), 11.10 (br s, 1 H), 8.44 (d, J = 2.5 Hz, 1 H), 8.21 ( dd, J = 8.1, 1.0 Hz, 1H), 7.86 (td, J = 7.5, 1.4 Hz, 1H), 7.74 (td, J = 7.8, 1.3 Hz, 1H), 7.67 (s, 1H), 7.65 (dd, J = 7.6, 1.4 Hz, 1H), 7.59 (d, J = 8.9 Hz, 1H), 7.25 ( dd, J = 8.7, 2.6 Hz, 1H), 3.90 (s, 3H). Found: C, 64.99; H, 3.42; N, 10.79. Calculated C of _{C 21 H 13 N 3 O 5} , 65.12; H, 3.38; N, 10.85.

Example 129 9-Hydroxy-4- (2-nitrophenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (538) (VI, R ¹⁰ = H, Ar = Preparation of 2-nitrophenyl) Methyl ether (537), prepared as described in Example 128, has a reaction time of 5 eq. BBr ₃ for 5 hours and then an additional 5 eq. BBr ₃ for an additional 21 hours. Except for demethylation with BBr ₃ according to the procedure described in Example 80 and (after crystallization from MeOH / CH ₂ Cl ₂ / hexane) phenol as an orange solid (mp. 322-330 ° C.) 538) (53%). ¹ H NMR [(CD ₃ ) ₂ SO] δ 11.88 (br s, 1 H), 11.05 (br s, 1 H), 9.29 (br s, 1 H), 8.30 (d, J = 2) .4 Hz, 1H), 8.20 (dd, J = 8.2, 1.1 Hz, 1H), 7.85 (td, J = 7.5, 1.2 Hz, 1H), 7.73 (td, J = 7.9, 1.4 Hz, 1H), 7.63 (dd, J = 7.6, 1.4 Hz, 1H), 7.61 (s, 1H), 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. _{C 20 H 11 N 3 O 5} . Calculated for 1/2 MeOH C, 63.24; H, 3.37; N, 10.79.

Example 130 4- (2-Aminophenyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (539) (V, R ¹⁰ = H, Ar = Preparation of 2-nitrophenyl) The nitro derivative (537) (71 mg, 0.183 mmol) prepared as described in Example 128, containing 10% Pd-C (71 mg) moistened with 2: 1 THF / The MeOH (45 mL) solution was hydrogenated at 410 kPa (60 psi) for 7 hours. The solution was filtered through celite, the celite and catalyst were washed thoroughly with MeOH and THF, and then the filtrate was concentrated to dryness. The residue was crystallized from MeOH / CH ₂ Cl ₂ / hexane to give amine (539) (67 mg, 97%) as a yellow solid with melting point> 320 ° C. ¹ H NMR [(CD ₃ ) ₂ SO] δ 11.80 (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, 1H), 7.51 (s, 1H), 7.21 (dd, J = 8.8, 2.6 Hz, 1H), 7.08 (td, J = 7, 7 , 1.5 Hz, 1H), 7.01 (dd, J = 7.6, 1.5 Hz, 1H), 6.73 (dd, J = 8.1, 0.6 Hz, 1H), 6.61 ( td, J = 7.4, 0.9 Hz, 1H), 4.70 (s, 2H), 3.89 (s, 3H). Found: C, 67.22; H, 4.50; N, 11.03. _{C 21 H 15 N 3 O 3} . Of H ₂ O Calcd C, 67.19; H, 4.56; N, 11.19.

Example 131 4- (2-Aminophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (540) (VI, R ¹⁰ = H, Ar = Preparation of 2-nitrophenyl) Nitro derivative (538) (81 mg, 0.217 mmol) prepared as described in Example 129 containing 2% THF / wet 10% Pd-C (81 mg). The MeOH (60 mL) solution was hydrogenated at 410 kPa (60 psi) for 12 hours. The solution was filtered through celite, the celite and catalyst were washed thoroughly with MeOH and THF, and then the filtrate was concentrated to dryness. The residue was crystallized from MeOH / CH ₂ Cl ₂ / hexanes to give amine (540) (60 mg, 81%) as a brown solid with a melting point> 330 ° C. ¹ H NMR [(CD ₃ ) ₂ SO] δ 11.67 (br s, 1 H), 10.88 (br s, 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, 1H), 7.00 (dd, J = 7.6, 1.4 Hz, 1H), 6.72 (brd, J = 8.1 Hz, 1H) ), 6.60 (td, J = 7.4, 0.9 Hz, 1H), 4.69 (s, 2H). Found: C, 66.35; H, 4.06; N, 11.76. _{C 20 H 13 N 3 O 3} . Of H ₂ O Calcd C, 66.48; H, 4.18; N, 11.63.

Example 132 4- (2-Hydroxyphenyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (541) (V, R ¹⁰ = H, Ar = 2-Hydroxyphenyl) A solution of amine (539) (129 mg, 0.361 mmol) in 90% H ₂ SO ₄ (7.5 mL) prepared as described in Example 130 was cooled to −10 ° C. and iced water Dilute with (20 mL). After stirring at −10 ° C. for 10 minutes, the resulting suspension was treated dropwise with a cold water (2 × 1 mL) solution of NaNO ₂ (38 mg, 0.551 mmol) and stirred at −10 to −5 ° C. for 30 minutes. did. A solution of urea (13 mg, 0.216 mmol) in cold water (2 × 0.75 mL) was added to the mixture and stirred at −5 ° C. for 5 minutes. Finally, a cold water (2 × 2.5 mL) suspension of KI (400 mg, 2.41 mmol) and CuI (402 mg, 2.11 mmol) was added, then the cooling bath was removed and the mixture was stirred for 10 minutes, Subsequently, it stirred at 60-65 degreeC for 2 hours. Aqueous sodium metabisulfite (5%, 100 mL) was added, then the pH was adjusted to pH = 3 with NaHCO ₃ and the mixture was extracted with EtOAc (5 × 100 mL). The extract was 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. Elute with 0-0.5% MeOH / CH ₂ Cl ₂ then 0.5% MeOH / CH ₂ Cl ₂ to obtain the crude iodide mixture (543, 544) (24 mg, see experiment below for analytical data). Obtained. Elution with 1% MeOH / CH ₂ Cl ₂ to give phenol (541) (31 mg, 24%) as a light yellow solid (after crystallization from THF / CH ₂ Cl ₂ / pentane) mp 264-267 ° C. Obtained. ¹ H NMR [(CD ₃ ) ₂ SO] δ 11.82 (br s, 1 H), 10.95 (br s, 1 H), 9.41 (br s, 1 H), 8.47 (d, J = 2) .6 Hz, 1H), 7.56 (s, 1H), 7.54 (d, J = 8.9 Hz, 1H), 7.25 (dd, J = 7.4, 1.6 Hz, 1H), 7 .23 (td, J = 7.9, 1.7 Hz, 1H), 7.22 (dd, J = 8.7, 2.6 Hz, 1H), 6.91 (brd, J = 7.5 Hz, 1H), 6.87 (td, J = 7.4, 0.9 Hz, 1H), 3.89 (s, 3H). Found: C, 70.40; H, 4.06; N, 7.95. Calculated _{C 21 H 14 N 2 O 4} C, 70.39; H, 3.94; N, 7.82.

Example 133 9-Hydroxy-4- (2-hydroxyphenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (542) (VI, R ¹⁰ = H, Ar = Preparation of 2-hydroxyphenyl) Methyl ether (541) prepared as described in Example 132 was demethylated using BBr ₃ by the procedure described in Example 80 except that the reaction time was 4 hours. Phenol (542) (73%) was obtained as a yellow-orange solid with a melting point of 291-296 ° C. (after crystallization from MeOH / THF / CH ₂ Cl ₂ / hexane). ¹ H NMR [(CD ₃ ) ₂ SO] δ. 11.67 (br s, 1H), 10.88 (br s, 1 H), 9.37 (br s, 1 H), 9.22 (br s, 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, 1H), 7.05 (dd, J = 8.7, 2.5 Hz, 1H), 6.91 (brd, J = 8.0 Hz, 1H) ), 6.86 (td, J = 7.4, 0.9 Hz, 1H). Found: C, 66.61; H, 3.67; N, 7.70. _{C 20 H 12 N 2 O 4} . Of H ₂ O Calcd C, 66.30; H, 3.89; N, 7.73.

(Example 134) 4- (2-iodophenyl) -9-methoxy-pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) - dione ^{(543) (V, R 10} = H, Ar = Preparation of 2-iodophenyl) A solution of amine (539) (46 mg, 0.129 mmol) prepared as described in Example 130 in 90% H ₂ SO ₄ (2.5 mL) was cooled to −5 ° C. and iced water (2.5 mL) and then warmed to 7 ° C. The resulting suspension was treated dropwise with a solution of NaNO ₂ (13.6 mg, 0.197 mmol) in cold water (2 × 0.5 mL) and stirred at 7 ° C. for 8 minutes. A solution of urea (5 mg, 0.083 mmol) in cold water (2 × 0.4 mL) was added to the mixture and stirred at 7 ° C. for 4 minutes. Finally, a cold water (2 × 1 mL) suspension of KI (140 mg, 0.843 mmol) and CuI (140 mg, 0.735 mmol) is added, then the cooling bath is removed and the mixture is stirred for 10 minutes, then 60 Stir at ~ 65 ° C for 2 hours. Aqueous sodium metabisulfite (0.5%, 100 mL) was added and then the mixture was extracted with 20% THF / EtOAc (5 × 100 mL). The extract was 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. _{0~0.5% MeOH / CH 2 Cl 2} , then obtain eluted with 0.5% MeOH / _{CH 2} Cl 2 to the crude product (22 mg). This was further purified by silica gel chromatography (eluting with 1% EtOH / CHCl ₃ ) to give the major crude iodide (543) (18 mg, 30%). This was mixed with the material from a similar reaction, chromatographed again (eluting with 20% EtOAc / petroleum ether), and MeOH / THF / CH ₂ Cl ₂ as yellow-orange crystals, mp 311-315 ° C. Crystallized from / hexane. ¹ H NMR [(CD ₃ ) ₂ SO] δ 11.95 (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, 1H), 7.58 (d, J = 8.8 Hz, 1H), 7.50 (td, J = 7.6, 0.9 Hz, 1H), 7 .48 (s, 1H), 7.44 (dd, J = 7.6, 1.8 Hz, 1H), 7.25 (dd, J = 8.9, 2.7 Hz, 1H), 7.19 ( td, J = 7.6, 1.8 Hz, 1H), 3.89 (s, 3H). Found: C, 53.87; H, 2.76; N, 5.98. Calculated _{C 21 H 13 IN 2 O 3} C, 53.87; H, 2.80; N, 5.98. Calculated for FABMS [M + H] ⁺ : 469.0046. Calcd 469.0049 for _{C 21 H 14 IN 2 O 3} .

Example 135 9-Hydroxy-4- (2-iodophenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (545) (VI, R ¹⁰ = H, Ar = Preparation of 2-iodophenyl) Methyl ether (543) prepared as described in Example 134 was demethylated with BBr ₃ by the procedure described in Example 80 to give (MeOH / CH ₂ Cl ₂ / After crystallization from hexane) phenol (545) (88%) was obtained as a yellow-orange solid with a melting point of 217-223 ° C. ¹ H NMR [(CD ₃ ) ₂ SO] δ 11.82 (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 (br d, J = 7.8 Hz, 1 H), 7.49 (br t, J = 7.7 Hz, 1 H), 7.46 (d, J = 8.9 Hz, 1H), 7.42 (s, 1H), 7.42 (dd, J = 7.4, 1.7 Hz, 1H), 7.19 (td, J = 7.6, 1.7 Hz, 1H), 7.08 (dd, J = 8.7, 2.5 Hz, 1H). Found: C, 52.93; H, 2.55; N, 6.07. C ₂₀ H ₁₁ Calculated _{IN 2 O 3 C, 52.89;} H, 2.44; N, 6.17. Calculated value of FABMS [M + H] ⁺ : 454.9889. Calcd 454.9893 for _{C 20 H 12 IN 2 O 3} .

Example 136 Preparation of (2-Cyanobenzyl) (triphenyl) phosphonium bromide (547) o-Tolunitrile was converted to NBS / N by the procedure described in Example 102 except that the reaction time for bromination was 2 hours. Bromination with AIBN, then the crude bromide was reacted with triphenylphosphine (1.2 eq) to give the phosphonium salt (547) as a light brown powder of melting point (CH ₂ Cl ₂ / benzene) 237-241 ° C. (70%) was obtained. ¹ H NMR (CDCl ₃ ) δ 7.90 (dd, J = 7.8, 2.3 Hz, 1H), 7.85 to 7.63 (m, 15H), 7.52 (br t, J = 7. 7 Hz, 1 H), 7.44 (br d, 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. C ₂₆ H ₂₁ BrNP Calculated C, 68.13; H, 4.62; N, 3.06.

Example 137 Preparation of 2-[(E) -2- (5-methoxy-1H-indol-2-yl) ethenyl] benzonitrile (548) (II, Ar = 2-cyanophenyl) LDA and aldehyde (Consecutively) at 0 ° C., the LDA: aldehyde ratio is 1.55: 1, and the reaction time is 5 hours, followed by the procedure described in Example 37 to 5-methoxy-1H-indole- 2-Carbaldehyde (1) is reacted with (2-cyanobenzyl) (triphenyl) phosphonium bromide (547) prepared as described in Example 136 to produce crystals from (CH ₂ Cl ₂ / hexane). Diene (548) (60%) was obtained as a yellow solid (pure E isomer) with a melting point of 192-196 ° C. ¹ H NMR (CDCl ₃ ) δ 8.40 (br s, 1H), 7.79 (d, J = 8.1 Hz, 1H), 7.66 (dd, J = 8.1, 0.9 Hz, 1H) 7.58 (td, J = 7.9, 1.3 Hz, 1H), 7.32 (td, J = 8.0, 0.9 Hz, 1H), 7.29 (d, J = 8.5 Hz) , 1H), 7.28 (d, J = 16.9 Hz, 1H), 7.18 (d, J = 16.4 Hz, 1H), 7.04 (d, J = 2.4 Hz, 1H), 6 .91 (dd, J = 8.9, 2.4 Hz, 1H), 6.64 (d, J = 1.8 Hz, 1H), 3.86 (s, 3H). Found: C, 79.05; H, 5.16; N, 10.31. C ₁₈ H ₁₄ N ₂ O Calculated C, 78.81; H, 5.14; N, 10.21.

Example 138 2- (9-methoxy-1,3-dioxo-1,2,3,6-tetrahydropyrrolo [3,4-c] carbazol-4-yl) benzonitrile (549) (V, R ¹⁰ = H, Ar = 2-cyanophenyl) E diene (548), prepared as described in Example 137, except that the diluted product solution is filtered to obtain the bulk of the poorly soluble end product. Subjected to a sequential reaction with maleimide followed by DDQ by the procedure described in the representative Example 123 above, then washed thoroughly with aqueous NaHCO ₃ , 15% MeOH / CH ₂ Cl ₂ and water. The reminder was obtained by extracting the aqueous phase with ethyl acetate. The organic layer was dehydrated, the dehydrating agent was removed, and the solution was concentrated to dryness. Crystallization from THF / CH ₂ Cl ₂ / hexane gave the product (549) (96%) as a yellow solid, mp 348-350 ° C. ¹ H NMR [(CD ₃ ) ₂ SO] δ 12.06 (br s, 1H), 11.19 (br s, 1H), 8.48 (d, J = 2.6 Hz, 1H), 7.96 ( dd, J = 7.7, 1.0 Hz, 1H), 7.82 (td, J = 7.7, 1.4 Hz, 1H), 7.71 (brd, J = 7.4 Hz, 1H), 7.71 (s, 1H), 7.66 (td, J = 7.6, 1.1 Hz, 1H), 7.60 (d, J = 8.9 Hz, 1H), 7.27 (dd, J = 8.8, 2.6 Hz, 1H), 3.90 (s, 3H). Calculated value of EIMS M ⁺ : 367.0956. Calcd 367.0957 for _{C 22 H 13 N 3 O 3} .

Example 139 2- (9-Hydroxy-1,3-dioxo-1,2,3,6-tetrahydropyrrolo [3,4-c] carbazol-4-yl) benzonitrile (550) (VI, R ¹⁰ = H, Ar = 2-cyanophenyl) Methyl ether (549), prepared as described in Example 138, was further added with a reaction time of 5 eq. BBr ₃ for 5 hours and then with an additional 5 eq. BBr ₃ As a yellow solid with a melting point of 199-204 ° C. (after crystallizing from THF / CH ₂ Cl ₂ / hexane) and demethylating with BBr ₃ by the procedure described in Example 80 except for 4 hours Phenol (550) (83%) was obtained. ¹ H NMR [(CD ₃ ) ₂ SO] δ 11.93 (br s, 1 H), 11.13 (br s, 1 H), 9.31 (br s, 1 H), 8.34 (d, J = 2 .4 Hz, 1 H), 7.96 (dd, J = 7.6, 0.9 Hz, 1 H), 7.82 (td, J = 7.7, 1.4 Hz, 1 H), 7.70 (br d , 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. _{C 21 H 11 N 3 O 3} . 1 / 4H ₂ O Calculated C, 70.49; H, 3.24; N, 11.74.

Example 140 Preparation of 5-methoxy-2-[(E) -2- (3-nitrophenyl) ethenyl] -1H-indole (551) (II, Ar = 3-nitrophenyl) LDA and aldehyde 0 C. 5-methoxy-1H-indole-2-carbamate according to the procedure described in Example 37, except that it was added continuously at 0.degree. C., the LDA: aldehyde ratio was 1.5: 1 and the reaction time was 5 hours. Rudehydr (1) is reacted with (3-nitrobenzyl) (triphenyl) phosphonium bromide (after crystallizing from MeOH / CH ₂ Cl ₂ / hexane) orange with a melting point of 178-182 ° C. Diene (551) (51%) was obtained as a red solid (pure E isomer). ¹ H NMR [(CD ₃ ) ₂ SO] δ 11.27 (br s, 1H), 8.34 (t, J = 1.9 Hz, 1H), 8.09 (dd, J = 8.1, 1. 8 Hz, 1H), 7.99 (d, J = 7.9 Hz, 1H), 7.67 (t, J = 8.0 Hz, 1H), 7.47 (d, J = 16.5 Hz, 1H), 7.26 (d, J = 8.6 Hz, 1H), 7.25 (d, J = 16.6 Hz, 1H), 7.03 (d, J = 2.4 Hz, 1H), 6.77 (dd , J = 8.8, 2.5 Hz, 1H), 6.61 (d, J = 1.6 Hz, 1H), 3.76 (s, 3H). Found: C, 69.36; H, 4.77; N, 9.78. Calculated C of _{C 17 H 14 N 2 O 3} , 69.38; H, 4.79; N, 9.52.

Example 141 9-Methoxy-4- (3-nitrophenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (552) (V, R ¹⁰ = H, Ar = Preparation of 3-nitrophenyl) Pure E prepared as described in Example 140 by the procedure described in Example 123 above, except that the diluted product solution was filtered to obtain a poorly soluble end product. The diene (551) was subjected to sequential reaction with maleimide and then DDQ, then washed thoroughly with aqueous NaHCO ₃ , 15% MeOH / CH ₂ Cl ₂ and water, followed by crystallization from MeOH / THF, melting point> The product (552) (81%) was obtained as a brown solid at 340 ° C. ¹ H NMR [(CD ₃ ) ₂ SO] δ 11.99 (br s, 1 H), 11.18 (br s, 1 H), 8.50 (d, J = 2.5 Hz, 1 H), 8.48 ( t, J = 1.9 Hz, 1H), 8.31 (dd, J = 8.1, 1.7 Hz, 1H), 8.11 (brd, J = 7.8 Hz, 1H), 7.78 ( t, J = 8.0 Hz, 1H), 7.75 (s, 1H), 7.58 (d, J = 8.8 Hz, 1H), 7.25 (dd, J = 8.8, 2.6 Hz) , 1H), 3.90 (s, 3H). Found: C, 62.17; H, 3.52; N, 10.33. _{C 21 H 13 N 3 O 5} . Of H ₂ O Calcd C, 62.22; H, 3.73; N, 10.37.

Example 142 9-Hydroxy-4- (3-nitrophenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (553) (VI, R ¹⁰ = H, Ar = Preparation of 3-Nitrophenyl) Methyl ether (552) prepared as described in Example 142 was demethylated with pyridinium hydrochloride by the procedure described in Example 81 to give crystals from (THF / hexane). After conversion, phenol (553) (74%) was obtained as an orange-brown solid with a melting point of 300-310 ° C. ¹ H NMR [(CD ₃ ) ₂ SO] δ 11.86 (br s, 1 H), 11.11 (br s, 1 H), 9.29 (br s, 1 H), 8.46 (t, j = 1) .9 Hz, 1H), 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). Calculated for FABMS M ⁺ : 373.0692. Calcd 373.0699 for _{C 20 H 11 N 3 O 5} .

Example 143 Preparation of (2-chloro-3-nitrobenzyl) (triphenyl) phosphonium bromide (554) Brominated reaction time was 2 hours, carried out except that the substitution reaction was carried out at 70 ° C. for 1 day Using the procedure described in Example 102, 2-chloro-3-nitrotoluene was brominated with NBS / AIBN, followed by reaction of the crude bromide with triphenylphosphine, mp (CH ₂ Cl ₂ / benzene) The phosphonium salt (554) (44%) was obtained as a light brown solid at 224-228 ° C. ¹ H NMR (CDCl ₃ ) δ 8.09 (br d, J = 8.3 Hz, 1H), 7.86-7.63 (m, 16H), 7.34 (t, J = 8.1 Hz, 1H) 5.95 (d, J = 14.6 Hz, 2H). Found: C, 58.68; H, 4.12; N, 2.79. C ₂₅ H ₂₀ BrClNO ₂ P Calculated C, 58.56; H, 3.93; N, 2.73.

Example 144 2-[(E) -2- (2-Chloro-3-nitrophenyl) ethenyl] -5-methoxy-1H-indole (555) (II, Ar = 2-chloro-3-nitrophenyl ) Preparation of LDA and aldehyde (successively) at 0 ° C., the LDA: aldehyde ratio is 1.5: 1 and the reaction time is 5 hours by the procedure described in Example 37. -Methoxy-1H-indole-2-carbaldehyde (1) was reacted with (2-chloro-3-nitrobenzyl) (triphenyl) phosphonium bromide (554) prepared as described in Example 143. The diene (555) (50%) was obtained as an orange crystalline solid (pure E isomer), mp 131-133 ° C. (after crystallization from CH ₂ Cl ₂ / pentane). ¹ H NMR (CDCl ₃ ) δ 8.24 (br s, 1H), 7.86 (dd, J = 8.0, 1.4 Hz, 1H), 7.63 (dd, J = 7.9, 1. 4 Hz, 1H), 7.40 (t, J = 8.0 Hz, 1H), 7.28 (d, J = 8.5 Hz, 1H), 7.25 (d, J = 15.8 Hz, 1H), 7.15 (d, J = 16.4 Hz, 1H), 7.05 (d, J = 2.4 Hz, 1H), 6.91 (dd, J = 8.9, 2.4 Hz, 1H), 6 .65 (d, J = 1.7 Hz, 1H), 3.86 (s, 3H). Found: C; 61.97; H, 3.92; N, 8.50. Calculated C of _{C 17 H 13 ClN 2 O 3} , 62.11; H, 3.99; N, 8.52.

Example 145 4- (2-Chloro-3-nitrophenyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (556) (V, R ¹⁰ = Preparation of H, Ar = 2-chloro-3-nitrophenyl) Pure E diene (555) prepared as described in Example 144 was reacted with maleimide followed by DDQ by the procedure described in Example 123. To give the product (556) (93%) as a yellow-brown solid (after crystallization from THF / pentane) mp 315-320 ° C. ¹ H NMR [(CD ₃ ) ₂ SO] δ 12.07 (br s, 1 H), 11.16 (br s, 1 H), 8.46 (d, J = 2.6 Hz, 1 H), 8.11 ( dd, J = 8.1, 1.5 Hz, 1H), 7.82 (dd, J = 7.7, I.6 Hz, 1H), 7.69 (t, J = 7.9 Hz, 1H), 7 .69 (s, 1H), 7.59 (d, J = 8.9 Hz, 1H), 7.26 (dd, J = 8.8, 2.6 Hz, 1H), 3.90 (s, 3H) . Found: C, 60.47; H, 3.17; N, 9.78. _{C 21 H 12 ClN 3 O 5} . Calculated for 1/4 THF C, 60.08; H, 3.21; N, 9.55.

Example 146 4- (2-Chloro-3-nitrophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (557) (VI, R ¹⁰ = H, Ar = 2-chloromethyl-3-methyl ether, prepared as described in Preparative example 145-nitrophenyl) (556), except the reaction time was 5 hours at 10 equiv BBr ₃ in example 80 Demethylation with BBr ₃ according to the procedure described gave phenol (557) (84%) as a yellow solid with a melting point of 304-308 ° C. (after crystallization from THF / CH ₂ Cl ₂ / pentane). . ¹ H NMR [(CD ₃ ) ₂ SO] δ 11.92 (br s, 1 H), 11.11 (br s, 1 H), 9.30 (s, 1 H), 8.31 (d, J = 2. 4 Hz, 1 H), 8.11 (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. C ₂₀ H ₁₀ ClN ₃ Calculated _{O 5 C, 58.91; H,} 2.47; N, 10.30.

Example 147 4- (3-Amino-2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (558) (VI, R ¹⁰ = H , Ar = 3-amino-2-chlorophenyl) of the nitro derivative (557) (66 mg, 0.162 mmol) prepared as described in Example 146, freshly prepared (wet) nickel boride (202 mg) A mixture of MeOH (4.8 mL) solution and 1M HCl (1.2 mL) was stirred at reflux for 100 minutes. Concentrated aqueous ammonia and aqueous NaHCO ₃ (100 mL) were added and the mixture was extracted with EtOAc (8 × 100 mL). The extract was concentrated, adsorbed on silica gel and chromatographed. Elution with 0-1% MeOH / CH ₂ Cl ₂ followed by 1.5% MeOH / CH ₂ Cl ₂ and THF (after crystallization from THF / CH ₂ Cl ₂ / pentane) mp 348-352 ° C. Of amine (558) (83%) as a yellow-orange solid. ¹ H NMR [(CD ₃ ) ₂ SO] δ 11.76 (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, 1H), 6.86 (dd, J = 8.1, 1.5 Hz, 1H), 6.60 (dd, J = 7.4, 1.3 Hz, 1H) ), 5.39 (s, 2H). Found: C, 63.79; H, 3.47; N, 10.37. _{C 20 H 12 ClN 3 O 3} . Calculated for 1/2 THF C, 63.85; H, 3.90; N, 10.15.

(Example 148) Preparation of (2-chloro-4-nitrobenzyl) (triphenyl) phosphonium bromide (559) The reaction time of bromination was 24 hours, and the substitution reaction was carried out at 20 ° C for 7 days. Using the procedure described in Example 102, 2-chloro-4-nitrotoluene was brominated using NBS / AIBN, followed by reaction of the crude bromide with triphenylphosphine, mp (benzene) 70-75 ° C. Of the crude phosphonium salt (559) (34%) as a light brown solid. ¹ H NMR [(CD ₃ ) ₂ SO] δ 8.21 (d, J = 2.5 Hz, 1H), 8.13 (dd, J = 8.7, 2.5 Hz, 1H), 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, 1H), 5.33 ( d, J = 15.7 Hz, 2H). Calculated for FABMS M ⁺ = 432.0916, 434.0904. Calculated for _{C 25 H 20 ClNO 2 P 432.0921,434.0891} .

Example 149 2-[(E) -2- (2-chloro-4-nitrophenyl) ethenyl] -5-methoxy-1H-indole (560) (II, Ar = 2-chloro-4-nitrophenyl) ) Preparation of LDA and aldehyde at 0 ° C. (sequentially), the LDA: aldehyde ratio is 1.5: 1, and the reaction time is 5 hours, according to the procedure described in Example 37. -Methoxy-1H-indole-2-carbaldehyde (1) was reacted with (2-chloro-4-nitrobenzyl) (triphenyl) phosphonium bromide (559) prepared as described in Example 148. The diene (560) (46%) was obtained as a dark red-brown solid (pure E isomer), mp 239-241 ° C. (after crystallization from CH ₂ Cl ₂ / hexane). ¹ H NMR [(CD ₃ ) ₂ SO] δ 11.57 (br s, 1H), 8.32 (d, J = 2.0 Hz, 1H), 8.18 (dd, J = 8.8, 2. 1 Hz, 1H), 8.15 (d, J = 8.9 Hz, 1H), 7.59 (d, J = 16.3 Hz, 1H), 7.47 (d, J = 16.3 Hz, 1H), 7.29 (d, J = 8.9 Hz, 1H), 7.05 (d, J = 2.4 Hz, 1H), 6.82 (dd, J = 8.7, 2.5 Hz, 1H), 6 .70 (s, 1H), 3.76 (s, 3H). Found: C, 62.14; H, 3.91; N, 8.52. C17H ₁₃ ClN ₂ O ₃ Calculated C, 62.11; H, 3.99; N, 8.52.

Example 150 4- (2-Chloro-4-nitrophenyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (561) (V, R ¹⁰ = H, Ar = 2-chloro-4-nitrophenyl) Pure E diene (560) prepared as described in Example 149 was reacted with maleimide followed by DDQ by the procedure described in Example 123. To give the product (561) (98%) as an orange solid with a melting point of 279-282 ° C. (after crystallization from THF / hexane). ¹ H NMR [(CD ₃ ) ₂ SO] δ 12.06 (br s, 1 H), 11.20 (br s, 1 H), 8.46 (d, J = 2.6 Hz, 1 H), 8.43 ( d, J = 2.2 Hz, 1H), 8.29 (dd, J = 8.4, 2.4 Hz, 1H), 7.83 (d, J = 8.4 Hz, 1H), 7.66 (s) , 1H), 7.59 (d, J = 8.9 Hz, 1H), 7.27 (dd, J = 8.8, 2.6 Hz, 1H), 3.90 (s, 3H). Found: C, 59.83; H, 3.61; N, 9.57. _{C 21 H 12 ClN 3 O 5} . Calculated for 1/4 THF C, 60.08; H, 3.21; N, 9.55.

Example 151 4- (2-Chloro-4-nitrophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (562) (VI, R ¹⁰ = H, Ar = 2-chloro-4-nitrophenyl) Methyl ether prepared as described in Example 150 (561) was reacted with 5 eq BBr ₃ for 5 hours, then an additional 5 eq. Besides being an additional 5 hours at BBr ₃ is demethylated using BBr ₃ by the procedure described in example 80, (after crystallization from _THF / CH 2 _Cl 2 / pentane) of melting point 301 to 305 ° C. Phenol (562) (85%) was obtained as a red-orange solid. ¹ H NMR [(CD ₃ ) ₂ SO] δ 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, 1H), 7.61 (s, 1H), 7.48 (d, J = 8.7 Hz, 1H), 7.10 (dd, J = 8.7, 2.5 Hz, 1H). Found: C, 58.81; H, 2.35; N, 10.05. C ₂₀ H ₁₂ ClN ₃ Calculated _{O 5 C, 58.91; H,} 2.47; N, 10.30.

Example 152 4- (4-Amino-2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (563) (VI, R ¹⁰ = H , Ar = 4-amino-2-chlorophenyl) of the nitro derivative (562) (90 mg, 0.221 mmol) prepared as described in Example 151, freshly prepared (wet) nickel boride (277 mg). A mixture of MeOH (7.2 mL) and 1M HCl (1.8 mL) was stirred at reflux for 1 hour. Concentrated aqueous ammonia and aqueous NaHCO ₃ (120 mL) were added and the mixture was extracted with EtOAc (6 × 80 mL). The extract was concentrated, adsorbed on silica gel and chromatographed. Elution with 0-2% MeOH / CH ₂ Cl ₂ followed by THF (after crystallization from THF / CH ₂ Cl ₂ / pentane) amine (563) as an orange solid with a melting point of 293-303 ° C. (100%) was obtained. ¹ H NMR [(CD ₃ ) ₂ SO] δ 11.70 (br s, 1 H), 10.92 (br s, 1 H), 9.23 (br s, 1 H), 8.30 (d, J = 2) .4 Hz, 1H), 7.44 (s, 1H), 7.43 (d, J = 8.7 Hz, 1H), 7.09 (d, J = 8.2 Hz, 1H), 7.05 (dd , J = 8.7, 2.5 Hz, 1H), 6.71 (d, J = 2.2 Hz, 1H), 6.58 (dd, J = 8.1, 2.2 Hz, 1H), 5. 51 (s, 2H). Found: C, 60.42; H, 3.64; N, 10.05. _{C 20 H 12 ClN 3 O 3} . 5 / 4H ₂ O Calculated C, 60.01; H, 3.65; N, 10.50.

Example 153 Preparation of (2-chloro-5-nitrobenzyl) (triphenyl) phosphonium bromide (564) Using the procedure described in Example 112, (2-chloro-5-nitrophenyl) methanol was Bromination with 30% HBr acetic acid solution followed by reaction of the crude bromide with triphenylphosphine to give the phosphonium salt (564) (63%) as a white solid of melting point (CH ₂ Cl ₂ / benzene) 239-243 ° C. Obtained. ¹ H NMR (CDCl ₃ ) δ 8.22 (br s, 1 H), 8.07 (br d, J = 8.7 Hz, 1 H), 7.87-7.65 (m, 15 H), 7.41 ( d, J = 8.9 Hz, 1H), 5.80 (d, J = 14.8 Hz, 2H). Found: C, 58.56; H, 3.93; N, 2.73. C ₂₅ H ₂₀ BrClNO ₂ P Calculated C, 58.47; H, 3.98; N, 2.66.

Example 154 2-[(E) -2- (2-chloro-5-nitrophenyl) ethenyl] -5-methoxy-1H-indole (565) (II, Ar = 2-chloro-5-nitrophenyl) ) According to the procedure described in Example 37 except that LDA and aldehyde were added continuously at 0 ° C., the LDA: aldehyde ratio was 1.5: 1 and the reaction time was 5 hours. 1H-indole-2-carbaldehyde (1) is reacted with (2-chloro-5-nitrobenzyl) (triphenyl) phosphonium bromide (564) prepared as described in Example 153 to give ( The diene (565) (57%) was obtained as an orange solid (pure E isomer) with a melting point of 191-193 ° C. after crystallization from CH ₂ Cl ₂ / pentane. ¹ H NMR (CDCl ₃ ) δ 8.54 (d, J = 2.6 Hz, 1H), 8.25 (br s, 1H), 8.02 (dd, J = 8.8, 2.6 Hz, 1H) 7.56 (d, J = 8.9 Hz, 1H), 7.28 (d, J = 8.7 Hz, 1H), 7.26 (d, J = 16.4 Hz, 1H), 7.20 ( d, J = 16.5 Hz, 1H), 7.06 (d, J = 2.4 Hz, 1H), 6.91 (dd, J = 8.8, 2.5 Hz, 1H), 6.70 (br s, 1H), 3.86 (s, 3H). Found: C, 61.44; H, 3.92; N, 8.55. _{C 17 H 13 ClN 2 O 3} . 1 / 4H ₂ O Calculated C, 61.27; H, 4.08; N, 8.41.

Example 155 4- (2-Chloro-5-nitrophenyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (566) (V, R ¹⁰ = H, Ar = 2-chloro-5-nitrophenyl) Pure E diene (565) prepared as described in Example 154 was prepared by maleimide and then DDQ by the procedure described in the representative Example 123 above. To give the product (566) (95%) as a yellow-orange solid with a melting point of 285-287 ° C. (after crystallization from THF / CH ₂ Cl ₂ / pentane). ¹ H NMR [(CD ₃ ) ₂ SO] δ 12.06 (br s, 1 H), 11.16 (br s, 1 H), 8.46 (d, J = 2.6 Hz, 1 H), 8.36 ( d, J = 2.8 Hz, 1H), 8.33 (dd, J = 8.7, 2.7 Hz, 1H), 7.91 (d, J = 8.7 Hz, 1H), 7.71 (s) , 1H), 7.60 (d, J = 8.9 Hz, 1H), 7.27 (dd, J = 8.9, 2.6 Hz, 1H), 3.90 (s, 3H). Found: C, 57.34; H, 2.68; N, 9.38. _{C 21 H 12 ClN 3 O 5} . 1 / Calculated _{4CH 2 Cl 2 C, 57.61;} H, 2.84; N, 9.48.

Example 156 4- (2-Chloro-5-nitrophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (567) (VI, R ¹⁰ = Preparation of H, Ar = 2-chloro-5-nitrophenyl) Methyl ether (566) prepared as described in Example 155 was reacted with 6 equivalents of BBr ₃ for a reaction time of 6 hours and then an additional 10 equivalents. Besides being an additional 4 hours at BBr ₃ is demethylated using BBr ₃ by the procedure described in example 80, (after crystallization from _THF / CH 2 _Cl 2 / pentane) mp 268 ° C. yellow - Phenol (567) (88%) was obtained as an orange solid. ¹ H NMR [(CD ₃ ) ₂ SO) δ 11.94 (br s, 1 H), 11.11 (br s, 1 H), 9.31 (br s, 1 H), 8.35 (d, J = 2 .6 Hz, 1H), 8.32 (dd, J = 8.6, 2.9 Hz, 1H), 8.32 (d, J = 2.4 Hz, 1H), 7.91 (d, J = 8. 7 Hz, 1H), 7.66 (s, 1H), 7.48 (d, J = 8.7 Hz, 1H), 7.10 (dd, J = 8.7, 2.5 Hz, 1H). Found: C, 58.31; H, 2.45; N, 9.98. _{C 20 H 10 ClN 3 O 5} . 1 / 4H ₂ O Calculated C, 58.27; H, 2.57; N, 10.19.

Example 157 4- (5-Amino-2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (568) (VI, R ¹⁰ = H , Ar = 5-amino-2-chlorophenyl) The nitro derivative (567) (70 mg, 0.172 mmol) prepared as described in Example 156, and freshly prepared (wet) nickel boride (266 mg) A mixture of MeOH (5.6 mL) and 1M HCl (1.4 mL) was stirred at reflux for 3 hours. Concentrated aqueous ammonia and aqueous NaHCO ₃ (100 mL) were added and the mixture was extracted with EtOAc (5 × 70 mL). The extract was washed with water, concentrated, adsorbed on silica gel and chromatographed. Elution with 0-2% MeOH / CH ₂ Cl ₂ then 3% MeOH / CH ₂ Cl ₂ (after crystallizing from THF / CH ₂ Cl ₂ / pentane) Amine (568) (97%) was obtained as a solid. ¹ H NMR [(CD ₃ ) ₂ SO] δ 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, 1H), 6.62 (dd, J = 8.2, 2.8 Hz, 1H), 6.60 (d, J = 2.3 Hz, 1H), 5. 29 (s, 2H). Found: C, 63.09; H, 3.17; N, 10.91. _{C 20 H 12 ClN 3 O 3} . 1 / 4H ₂ O Calculated C, 62.84; H, 3.30; N, 10.99.

Example 158 Preparation of (2-chloro-3-methoxybenzyl) (triphenyl) phosphonium bromide (569) Using the procedure described in Example 102 except that the bromination reaction time was 5 hours. 2-Chloro-1-methoxy-3-methylbenzene brominated with NBS / AIBN, followed by reaction of the crude bromide with triphenylphosphine to give a mixture of phosphonium salts containing (569) (20%) Was obtained as a light brown solid. This was used without further purification. A small amount of pure salt (569) was obtained as white needles with a melting point (CH ₂ Cl ₂ / benzene) 228-231 ° C. by crystallization of the mother liquor. ¹ H NMR (CDCl ₃ ) δ 7.81 to 7.60 (m, 15 H), 7.17 (dt, 1 = 7.8, 2.0 Hz, 1 H), 7.11 (t, J = 8.0 Hz) , 1H), 6.87 (dt, J = 8.2, 1.8 Hz, 1H), 5.65 (d, J = 14.4 Hz, 2H), 3.81 (s, 3H). Found: C, 62.88; H, 4.64. C ₂₆ H ₂₃ BrClOP Calculated C, 62.73; H, 4.66.

Example 159 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-1H-indol-2-yl) ethenyl] phenol (571) (II, Ar = 2-chloro-3-hydroxyphenyl) LDA and aldehyde were added continuously at 0 ° C., the LDA: aldehyde ratio was 1.5: 1, and the reaction time was 5 hours, followed by the procedure described in Example 37 to give 5-methoxy-1H— Indole-2-carbaldehyde (1) was prepared from the very crude (2-chloro-3-methoxybenzyl) (triphenyl) phosphonium bromide (569) prepared as described in Example 158. The reaction gave a crude mixture of dienes. This was chromatographed on silica gel. Elution with 0-50% CH ₂ Cl ₂ / petroleum ether, followed by elution with 60% CH ₂ Cl ₂ / petroleum ether (after crystallization from CH ₂ Cl ₂ / pentane), mp 179-183 ° C. The main product diene (570) (31%) was obtained as a pale yellow solid (pure E isomer). ¹ H NMR (CDCl ₃ ) δ 8.22 (br s, 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. C ₁₈ H ₁₆ ClNO ₂ Calculated C, 68.90; H, 5.14; N, 4.46. In addition, the column was eluted with 60% CH ₂ Cl ₂ / petroleum ether and CH ₂ Cl ₂ (after crystallizing from CH ₂ Cl ₂ / pentane) a light yellow solid (pure 172 ° -175 ° C.) A small amount of product diene (571) (25%) was obtained as E isomer). ¹ H NMR (CDCl ₃ ) δ 8.20 (br s, 1H), 7.27 (m, 1H), 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) , 1H), 5.65 (s, 1H), 3.86 (s, 3H). Found: C, 67.23; H, 4.72; N, 4.72. C ₁₇ H ₁₄ ClNO ₂ . 1 / 4H ₂ O Calculated C, 67.11; H, 4.80; N, 4.60.

Example 160 4- (2-Chloro-3-hydroxyphenyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (572) (V, R ¹⁰ = Preparation of H, Ar = 2-chloro-3-hydroxyphenyl) A mixture of pure E diene (571) (110 mg, 0.367 mmol) and maleimide (180 mg, 1.85 mmol) prepared as described in Example 159. An anhydrous toluene (2 mL) solution was covered with foil and stirred for 24 hours at reflux in a sealed vial (Method 4a). The resulting thick suspension was added to water and extracted with ethyl acetate, then transferred to a flask with dioxane (5 mL) and then manganese dioxide (738 mg, as described, for example, in the procedure of Example 79). It was treated with 8.49 mmol), and stirred for 22 hours at reflux under _{N 2.} The organic phase was dehydrated, the dehydrating agent was removed, and the solvent was concentrated to dryness. Chromatography and crystallization from THF / CH ₂ Cl ₂ / pentane. Product (572) (34%) as an orange-brown solid, mp 280-290 ° C. ¹ H NMR [(CD ₃ ) ₂ SO] δ 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, 1H), 7.57 (d, J = 8.8 Hz, 1H), 7.52 (s, 1H), 7.24 (dd, J = 8.9, 2.6 Hz, 1H), 7 .21 (t, J = 7.8 Hz, 1H), 7.05 (dd, J = 8.2, 1.5 Hz, 1H), 6.88 (dd, J = 7.5, 1.4 Hz, 1H) ) 3.89 (s, 3H). Found: C, 64.09; H, 3.48; N, 7.25. C ₂₁ H ₁₃ ClN ₂ Calculated _{O 4 C, 64.21; H,} 3.34; N, 7.13.

Example 161 4- (2-Chloro-3-hydroxyphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (573) (VI, R ¹⁰ = H, Ar = 2-chloro-3-hydroxyphenyl) The methyl ether (572) prepared as described in Example 160 was demethylated with BBr ₃ by the procedure described in Example 80, and Phenol (573) (91%) was obtained as a yellow-orange solid with a melting point of 197-203 ° C. (after crystallization from THF / CH ₂ Cl ₂ / pentane). ¹ H NMR [(CD ₃ ) ₂ SO] δ 11.78 (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, 1H), 7.47 (s, 1H), 7.45 (d, J = 8.7 Hz, 1H), 7.20 (t, J = 7.8 Hz) , 1H), 7.07 (dd, J = 8.7, 2.5 Hz, 1H), 7.04 (dd, J = 8.3, 1.5 Hz, 1H), 6.87 (dd, J = 7.5, 1.4 Hz, 1 H). Found: C, 62.06; H, 3.29; N, 7.36. _{C 20 H 11 ClN 2 O 4} . Calculated for _1/2 H2O C, 61.95; H, 3.12; N, 7.22.

(Example 162) Preparation of (2-chloro-4-methoxybenzyl) (triphenyl) phosphonium bromide (574) Brominated reaction time was 4 hours, and substitution reaction time was 28 hours. Using the procedure described in Example 112, (2-chloro-4-methoxyphenyl) methanol was brominated with 30% HBr acetic acid solution, followed by reaction of the crude bromide with triphenylphosphine to give a melting point (CH ₂ Cl ₂ / Benzene) The phosphonium salt (574) (100%) was obtained as a white solid at 223 to 226 ° C. ¹ H NMR (CDCl ₃ ) δ 7.82 to 7.61 (m, 15H), 7.53 (dd, J = 8.4, 2.7 Hz, 1H), 6.72 (d, J = 2.8 Hz) , 1H), 6.70 (dd, J = 8.9, 2.5 Hz, 1H), 5.57 (d, J = 13.6 Hz, 2H), 3.74 (s, 3H). Found: C, 63.05; H, 4.74. C ₂₆ H ₂₃ BrClOP Calculated C, 62.73; H, 4.66.

Example 163 2-[(E) -2- (2-chloro-4-methoxyphenyl) ethenyl] -5-methoxy-1H-indole (575) (II, Ar = 2-chloro-4-methoxyphenyl) ) According to the procedure described in Example 37 except that LDA and aldehyde were added continuously at 0 ° C., the LDA: aldehyde ratio was 1.5: 1 and the reaction time was 5 hours. 1H-indole-2-carbaldehyde (1) is reacted with (2-chloro-4-methoxybenzyl) (triphenyl) phosphonium bromide (574) prepared as described in Example 162, and ( Diene (575) (64%) was obtained as a pale yellow solid (pure E isomer) mp 129-132 ° C. after crystallization from CH ₂ Cl ₂ / pentane. ¹ H NMR (CDCl ₃ ) δ 8.17 (br s, 1H), 7.60 (d, J = 8.8 Hz, 1H), 7.25 (d, J = 8.3 Hz, 1H), 7.19 (D, J = 16.5 Hz, 1H), 7.03 (d, J = 2.4 Hz, 1H), 6.96 (d, J = 17.3 Hz, 1H), 6.94 (d, J = 2.4 Hz, 1H), 6.86 (dd, J = 8.7, 2.6 Hz, 1H), 6.85 (dd, J = 8.7, 2.8 Hz, 1H), 6.54 (d , J = 1.7 Hz, 1H), 3.85 (s, 3H), 3.83 (s, 3H). Found: C, 69.05; H, 5.41; N, 4.68. C ₁₈ H ₁₆ ClNO ₂ Calculated C, 68.90; H, 5.14; N, 4.46.

Example 164 4- (2-Chloro-4-methoxyphenyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (576) (V, R ¹⁰ = H, Ar = 2-chloro-4-methoxyphenyl) Pure E diene (575), prepared as described in Example 163, was prepared by maleimide and then DDQ by the procedure described in representative Example 123 above. To give the product (576) (86%) as a yellow-orange solid with a melting point of 284-286 ° C. (after crystallization from THF / pentane). ¹ H NMR [(CD ₃ ) ₂ SO) δ 11.93 (br s, 1 H), 11.06 (br s, 1 H), 8.46 (d, J = 2.6 Hz, 1 H), 7.56 ( d, J = 8.9 Hz, 1H), 7.54 (s, 1H), 7.41 (d, J = 8.5 Hz, 1H), 7.24 (dd, J = 8.9, 2.6 Hz) , 1H), 7.15 (d, J = 2.6 Hz, 1H), 7.01 (dd, J = 8.5, 2.6 Hz, 1H), 3.89 (s, 3H), 3.86 (S, 3H). Found: C, 65.30; H, 4.79; N, 5.82. _{C 22 H 15 ClN 2 O 4} . Calculated THF C, 65.20; H, 4.84; N, 5.85.

Example 165 4- (2-chloro-4-hydroxyphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (577) (VI, R ¹⁰ = H, Ar = 2-chloro-4 prepared ether as described in example 164 hydroxyphenyl) (576), except the reaction time was 5 hours at 10 equiv BBr ₃ in example 80 the described and twice demethylated using BBr ₃ by the procedure, _(THF / CH 2 after _Cl 2 / pentane crystallized) melting point 330-340 ° C. yellow - phenol (577) as an orange solid (90 %). ¹ H NMR [(CD ₃ ) ₂ SO] δ 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, 1H), 7.47 (s, 1H), 7.44 (d, J = 8.7 Hz, 1H), 7.27 (d, J = 8.4 Hz) , 1H), 7.06 (dd, J = 8.7, 2.5 Hz, 1H), 6.93 (d, J = 2.5 Hz, 1H), 6.82 (dd, J = 8.3). 2.4 Hz, 1H). Found: C, 62.63; H, 3.44; N, 7.10. _{C 20 H 11 ClN 2 O 4} . 1 / 4H ₂ O Calculated C, 62.68; H, 3.02; N, 7.31.

Example 166 Preparation of (2-chloro-5-methoxybenzyl) (triphenyl) phosphonium bromide (578) Using the procedure described in Example 102, except that the reaction time for bromination was 4 hours. 1-Chloro-4-methoxy-2-methylbenzene is brominated using NBS / AIBN, and the crude bromide is subsequently reacted with triphenylphosphine to give a melting point (CH ₂ Cl ₂ / benzene) 189-190.5. The phosphonium salt (578) (76%) was obtained as a light brown solid at ° C. ¹ H NMR (CDCl ₃ ) δ 7.82 to 7.61 (m, 15H), 7.21 (t, J = 2.8 Hz, 1H), 7.04 (dd, J = 8.8, 0.8 Hz) , 1H), 6.76 (d, J = 8.9, 2.7 Hz, 1H), 5.59 (d, J = 14.4 Hz, 2H), 3.58 (s, 3H). Found: C, 62.75; H, 4.70. C ₂₆ H ₂₃ BrClOP Calculated C, 62.73; H, 4.66.

Example 167 2-[(E) -2- (2-chloro-5-methoxyphenyl) ethenyl] -5-methoxy-1H-indole (579) (II, Ar = 2-chloro-5-methoxyphenyl) ) Preparation of LDA and aldehyde at 0 ° C. (sequentially), the LDA: aldehyde ratio is 1.5: 1, and the reaction time is 5 hours, according to the procedure described in Example 37. -Methoxy-1H-indole-2-carbaldehyde (1) was reacted with (2-chloro-5-methoxybenzyl) (triphenyl) phosphonium bromide (578) prepared as described in Example 166. The diene (579) (85%) was obtained as a pale yellow solid (pure E isomer) with a melting point of 119-121 ° C. (after crystallization from CH ₂ Cl ₂ / hexane). ¹ H NMR (CDCl ₃ ) δ 8.22 (br s, 1H), 7.29 (d, J = 8.9 Hz, 1H), 7.26 (br d, J = 8.7 Hz, 1H), 7. 22 (d, J = 16.5 Hz, 1H), 7.18 (d, J = 3.0 Hz, 1H), 7.06 (d, J = 16.7 Hz, 1H), 7.04 (br s, 1H), 6.88 (dd, J = 8.7, 2.5 Hz, 1H), 6.77 (dd, J = 8.8, 3.0 Hz, 1H), 6.59 (d, J = 1) .8 Hz, 1H), 3.86 (s, 3H), 3.85 (s, 3H). Found: C, 68.70; H, 5.11; N, 4.37. C _l8 H ₁₆ ClNO ₂ Calculated C, 68.90; H, 5.14; N, 4.46.

Example 168 4- (2-Chloro-5-methoxyphenyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (580) (V, R ¹⁰ = H, Ar = 2-chloro-5-methoxyphenyl) Pure E diene (579), prepared as described in Example 167, was prepared by maleimide and then DDQ by the procedure described in the representative Example 123 above. To give the product (580) (84%) as a light orange solid with a melting point of 284-286 ° C. (after crystallization from MeOH / CH ₂ Cl ₂ / hexane). ¹ H NMR [(CD ₃ ) ₂ SO] δ 11.96 (br s, 1 H), 11.08 (br s, 1 H), 8.46 (d, J = 2.6 Hz, 1 H), 7.58 ( s.1H), 7.57 (m, 1H), 7.46 (d, J = 8.7 Hz, 1H), 7.25 (dd, J = 8.8, 2.6 Hz, 1H), 7. 07 (d, J = 2.9 Hz, 1H), 7.04 (dd, J = 8.7, 3.1 Hz, 1H), 3.89 (s, 3H), 3.80 (s, 3H). Found: C, 62.50; H, 3.77; N, 6.54. _{C 22 H 15 ClN 2 O 4} . Of H ₂ O Calcd C, 62.20; H, 4.03; N, 6.59.

Example 169 4- (2-Chloro-5-hydroxyphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (581) (VI, R ¹⁰ = H, Ar = 2-chloromethyl-5-methyl ether, prepared as described in Preparative example 168 hydroxyphenyl) (580), except the reaction time was 10 equivalents BBr ₃ in 6.5 hours example Demethylated twice with BBr ₃ according to the procedure described in 80 and (after crystallization from MeOH / CH ₂ Cl ₂ / hexane) phenol (as an orange-red crystalline solid with a melting point of 335-340 ° C. 581) (90%). ¹ H NMR [(CD ₃ ) ₂ SO] δ 11.80 (br s, 1 H), 11.00 (br s, 1 H), 9.78 (br s, 1 H), 9.27 (br s, 1 H) 8.31 (d, J = 2.4 Hz, 1H), 7.49 (s, 1H), 7.45 (d, J = 8.7 Hz, 1H), 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, 1H). Found: C, 63.25; H, 3.63; N, 6.73. _{C 20 H 11 ClN 2 O 4} . 1/2 H ₂ O. Calculated for 1/4 hexane C, 63.09; H, 3.82; N, 6.84.

  Procedure of scheme 3

  Representative Procedure for Method 11 of Scheme 3

Example 170 2- (4- (2-Chlorophenyl) -9-methoxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) ethylmethane sulfonate (V; Ar = 2- ^{_{chlorophenyl, R 10 = CH 2 CH 2}} OSO 2 CH 3) alcohol was prepared as described in Preparative example 43 (228) (46) (1.10g , 2.61mmol) Was dissolved in anhydrous tetrahydrofuran (80 mL) under nitrogen. The resulting solution was cooled to 0 ° C. and triethylamine (2.0 mL) was added followed by dropwise addition of methanesulfonyl chloride (263 mL, 3.40 mmol). After 30 minutes, additional methanesulfonyl chloride (50 mL) was added, and then after another 30 minutes, the reaction was diluted with saturated sodium bicarbonate and extracted with ethyl acetate. The organic layer was dehydrated, the dehydrating agent was removed, and the solution was concentrated to dryness. Crystallization from ethyl acetate / hexane gave mesylate (228) (0.96 g, 74%) as a yellow solid with a melting point of 254 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.15 (s, 1H), 8.53 (d, J = 2.6 Hz, 1H), 7.90 (s, 1H), 7.74 (d , J = 9.0 Hz, 1H), 7.58 (m, 1H), 7.48 (m, 3H), 7.33 (dd, J = 9.0, 2.6 Hz, 1H), 4.89. (T, J = 5.0 Hz, 2H), 4.56 (m, 2H), 3.91 (s, 3H), 2.94 (s, 3H). Calculated value of FABMS [M + H] ⁺ : 499.0694, 501.0696. Calculated 499.0731,501.0701 of _{C 24 H 19 ClN 2 O 6} S.

Example 171 2- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) ethylmethane Preparation of sulfonate (VII; Ar = 2-chlorophenyl, n = 2, mesylate) (229) Mesylate (228) (1.23 g, 2.48 mmol), prepared as described in Example 170, was reacted at a reaction time of 7 Reaction according to the procedure described in Example 80 except for time, followed by chromatography on silica, eluting with ethyl acetate / hexane (1: 1 → 3: 1), and from ethyl acetate / hexane. Trituration afforded phenol (229) (1.05 g, 87%) as a yellow solid with a melting point of 266 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.09 (br s, 1 H), 9.40 (s, 1 H), 8.39 (d, J = 2.5 Hz, 1 H), 7.84 ( s, 1H), 7.62 (d, J = 8.9 Hz, 1H), 7.58 (m, 1H), 7.48 (m, 3H), 7.14 (dd, J = 8.9, 2.5 Hz, 1H), 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 23 H 17 ClN 2 O 6} S. Calculated for 1/4 hexane C, 58.10; H, 4.08; N, 5.53.

Example 172 6- (3-bromopropyl) -4- (2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VII, Ar = Preparation of 2-chlorophenyl, n = 3, bromide) (58) Alcohol (31) prepared as described in Example 40 was reacted with methanesulfonyl chloride according to the procedure described in Example 170, followed by BBr ₃ To give bromide (58) (81%) as an orange powder with a melting point of 278 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.08 (s, 1H), 9.39 (s, 1H), 8.39 (d, J = 2.4 Hz, 1H), 7.81 (s) , 1H), 7.60 (d, J = 8.7 Hz, 1H), 7.60 to 7.58 (m, 1H), 7.53 to 7.43 (m, 3H), 7.16 (dd , J = 8.7, 2.4 Hz, 1H), 4.55 (t, J = 6.9 Hz, 2H), 3.56 to 3.49 (m, 2H), 2.34 to 2.24 ( m, 2H). Found: C, 56.94; H, 3.45; N, 5.69. Calculated C of _{C 23 H 16 BrClN 2 O 3} , 57.10; H, 3.33; N, 5.79.

Example 173 6- (3-Bromopropyl) -9-hydroxy-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VII; Ar = phenyl, n = 3, Preparation of bromide) (204) Alcohol (202) (0.50 g, 1.25 mmol) prepared as described in Example 83 was reacted according to the procedure described in Example 170, followed by Example 80. The reaction was carried out according to the procedure described in. Chromatography on silica, eluting with ethyl acetate / hexane (1: 1 → 4: 1) followed by crystallization from ethyl acetate / hexane, bromide as an orange powder, mp 280-282 ° C. (204) (0.54 g, 97%) was obtained. ¹ H NMR δ [(CD ₃ ) 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). Found: C, 61.87; H, 3.69; N, 6.59. Calculated _{C 23 H 17 BrN 2 O 3} : C, 61.48; H, 3.81; N, 6.23.

Example 174 2- (9-hydroxy-1,3-dioxo-4-phenyl-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) ethyl methanesulfonate (VII; Preparation of Ar = phenyl, n = 2, mesylate) (205) Alcohol (201) (0.21 g, 0.53 mmol), prepared as described in Example 82, was reacted according to the procedure described in Example 170. This was followed by the procedure described in Example 80. Chromatography on silica, eluting with ethyl acetate / hexane (1: 1 → 4: 1) followed by crystallization from ethyl acetate / hexane to give mesylate as a yellow solid with a melting point of 271-276 ° C. 205) (0.19 g, 80%). ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.08 (s, 1H), 9.37 (br s, 1H), 8.40 (d, J = 2.4 Hz, 1H), 7.86 ( s, 1H), 7.67 (m, 2H), 7.60 (d, J = 8.8 Hz, 1H), 7.46 (m, 3H), 7.13 (dd, J = 8.8, 2.4 Hz, 1H), 4.86 (t, J = 4.8 Hz, 2H), 4.57 (t, J = 4.8 Hz, 2H), 2.97 (s, 3H). Calculated value of FABMS [M + H] ⁺ : 451.0958. Calcd 451.0964 for _{C 23 H 18 N 2 O 6} S.

Example 175 6- (6-Bromohexyl) -9-hydroxy-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VII; Ar = phenyl, n = 6. Preparation of bromide) (206) 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 Example 80. The reaction was carried out using the procedure described in. Chromatography on silica eluting with ethyl acetate / hexane (1: 1 → 4: 1) followed by crystallization from ethyl acetate / hexane as an orange solid of melting point 214-216 ° C. The bromide (206) (0.29 g, 88%) was obtained. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.04 (s, 1H), 9.33 (s, 1H), 8.41 (d, J = 2.4 Hz, 1H), 7.78 (s , 1H), 7.65 (m, 2H), 7.56 (d, J = 8.8 Hz, 1H), 7.46 (m, 3H), 7.13 (dd, J = 8.8, 2 .4 Hz, 1H), 4.46 (t, J = 7.1 Hz, 2H), 3.46 (t, J = 6.7 Hz, 2H), 1.74 (m, 4H), 1.41-1 .29 (m, 4H). Found: C, 63.75; H, 4.72; N, 5.94. Calculated for _{C 26 H 23 BrN 2 O 3} : C, 63.66; H, 4.73; N, 5.71.

Example 176 6- (3-Bromopropyl) -4- (2-chloro-6-methoxyphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione Preparation of (VII; Ar = 2-chloro-6-methoxyphenyl, n = 3, bromide) (207) Alcohol (105) prepared as described in Example 58 (0.20 g, 0.43 mmol) was prepared The reaction was carried out by the procedure described in Example 170. Subsequently, the boron tribromide reaction was carried out at 0 ° C. for 2 hours, and then the procedure was carried out except that the crude product prepared was dissolved in ethyl acetate (100 mL) and lithium bromide (1.0 g) was added thereto. The reaction was carried out using the procedure described in Example 80. This solution is warmed to 50 ° C. for 2 hours, absorbed onto silica, chromatographed and eluted with ethyl acetate / hexane (1: 3 → 1: 1) as a yellow solid of melting point 286-288 ° C. The bromide (207) (132 mg, 60%) was obtained. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.03 (s, 1H), 9.38 (s, 1H), 8.38 (d, J = 2.4 Hz, 1H), 7.77 (s , 1H), 7.58 (d, J = 8.8 Hz, 1H), 7.44 (t, J = 8.8 Hz, 1H), 7.18 (d, J = 8.8 Hz, 1H), 7 .14 (m, 2H), 4.54 (t, J = 7.0 Hz, 2H), 3.52 (t, J = 6.8 Hz, 2H), 2.27 (m, 2H). Calculated value of FABMS [M + H] ⁺ : 513.0182, 515.0192, 517.0169. Calculated _{C 24 H 18 BrClN 2 O 4} 513.0217; 515.0196,515.0187,517.0167.

Example 177 2- (4- (2,6-dichlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) Preparation of ethyl methanesulfonate (VII; Ar = 2,6-dichlorophenyl, n = 2, mesylate) (231) Alcohol (230) (1.0 g, 2.2 mmol) prepared as described in Example 85 was run. The reaction was carried out by the procedure described in Example 170, followed by the procedure described in Example 80 except that the reaction time with boron tribromide was 30 hours. Chromatography on silica, eluting with ethyl acetate / hexane (1: 1 → 4: 1) followed by crystallization from ethyl acetate / hexane to give mesylate as a yellow solid, mp 255-260 ° C. 231) (0.95 g, 83%). ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.16 (br s, 1 H), 9.43 (br s, 1 H), 8.38 (d, J = 2.5 Hz, 1 H), 7.91 (S, 1H), 7.63 (m, 3H), 7.51 (dd, J = 8.7, 7.3 Hz, 1H), 7.16 (dd, J = 8.9, 2.5 Hz, 1H), 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. _{C 23 H 16 Cl 2 N 2} O 6 Calculated S: C, 53.18; H, 3.10; N, 5.39.

Example 178 6- (3-bromopropyl) -4- (2,6-dichlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VII; Preparation of Ar = 2,6-dichlorophenyl, n = 3, bromide) (233) Alcohol (232) (0.77 g, 1.68 mmol) prepared as described in Example 86 was prepared as described in Example 170. Followed by the procedure described in Example 80 except that the reaction time with boron tribromide was 18 hours. Chromatography on silica, eluting with ethyl acetate / hexane (1: 1 → 4: 1) followed by crystallization from ethyl acetate / hexane, bromide as an orange solid, mp 273-276 ° C. (233) (0.70 g, 80%) was obtained. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.15 (br s, 1 H), 9.42 (s, 1 H), 8.38 (d, J = 2.4 Hz, 1 H), 7.87 ( s, 1H), 7.62 (m, 3H), 7.51 (dd, J = 8.9, 7.6 Hz, 1H), 7.18 (dd, J = 8.8, 2.4 Hz, 1H) ), 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. Calculated _{C 23 H 15 BrCl 2 N 2} O 3: C, 53.30; H, 2.92; N, 5.40.

  Representative Procedure for Method 12 of Scheme 3

Example 179 6- [3- (Dimethylamino) propyl] -9-hydroxy-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VIII; Ar = phenyl , N = 3, Z = NMe ₂ ) (208) A solution of bromide (204) prepared as described in Example 173 (204) (0.12 g, 0.27 mmol) in dimethylacetamide (4 mL) was added amine, dimethyl Amine (25 mol equivalent for 40% aqueous solution, 0.85 mL) was added. The reaction vessel was sealed and heated with stirring at 80 ° C. for 18 hours, followed by dilution with water. The resulting solution was then acidified by dropwise addition of concentrated hydrochloric acid, and then solid potassium carbonate was added to adjust the pH to about pH = 9. The precipitated product was collected by filtration, washed with water and diisopropyl ether and dried. Alternatively, the precipitated product was extracted with ethyl acetate. The organic layer was dehydrated, the dehydrating agent was removed, and the solution was concentrated to dryness. Chromatography on silica, eluting with methanol / dichloromethane (1: 9 → 1: 4) followed by trituration in ethyl acetate / hexane to give amine (208) as a yellow powder, mp 185-189 ° C. 52 mg, 47%). ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.05 (s, 1H), 9.34 (s, 1H), 8.41 (d, J = 2.4 Hz, 1H), 7.78 (s , 1H), 7.64 (m, 2H), 7.56 (d, J = 8.9 Hz, 1H), 7.47 (m, 3H), 7.14 (dd, J = 8.9, 2) .4 Hz, 1H), 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. _{C 25 H 23 N 3 O 3} . 1 / 4H ₂ O Calculated: C, 71.84; H, 5.67 ; N, 10.05.

Example 180 6- [2- (Dimethylamino) ethyl] -9-hydroxy-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VIII; Ar = phenyl) , N = 2, Z = NMe ₂ ) (209) Mesylate (205) (70 mg, 0.16 mmol), prepared as described in Example 174, was dissolved in aqueous dimethylamine by the procedure described in Example 179. The reaction gave amine (209) (30 mg, 48%) as a yellow powder with a melting point of 283-286 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.05 (br s, 1H), 9.33 (s, 1H), 8.41 (d, J = 2.4 Hz, 1H), 7.77 ( s, 1H), 7.65 (m, 2H), 7.54 (d, J = 8.8 Hz, 1H), 7.46 (m, 3H), 7.12 (dd, J = 8.8, 2.4 Hz, 1H), 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. Calculated _{C 24 H 21 N 3 O 3} : C, 72.17; H, 5.30; N, 10.52.

Example 181 9-Hydroxy-6- [3- (4-morpholinyl) propyl] -4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VIII; Ar = Preparation of phenyl, n = 3, Z = 4-morpholinyl) (210) The bromide (204) (0.10 g, 0.22 mmol) prepared as described in Example 173 was prepared by the procedure described in Example 179. Reaction with morpholine gave amine (210) (73 mg, 72%) as a yellow powder with a melting point of 252 ° -255 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.04 (br s, 1H), 9.33 (s, 1H), 8.41 (d, J = 2.5 Hz, 1H), 7.81 ( s, 1H), 7.62 (m, 2H), 7.57 (d, J = 8.9 Hz, 1H), 7.47 (m, 3H), 7.12 (dd, J = 8.9, 2.5 Hz, 1H), 4.51 (t, J = 6.3 Hz, 2H), 3.38 (t, J = 4.0 Hz, 4H), 2.18 (br s, 4H), 2.14 (T, J = 6.3 Hz, 2H), 1.93 (m, 2H). Found: C, 71.11; H, 5.46; N, 9.29. Calculated for _{C 27 H 25 N 3 O 4} : C, 71.19; H, 5.53; N, 9.22.

Example 182 9-hydroxy-6- [2- (4-morpholinyl) ethyl] -4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VIII; Ar = Preparation of phenyl, n = 2, Z = 4-morpholinyl) (211) Mesylate (205) (70 mg, 0.16 mmol) prepared as described in Example 174 was prepared with morpholine by the procedure described in Example 179. The reaction gave amine (211) (53 mg, 75%) as a yellow powder with a melting point of 260-262 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.04 (br s, 1 H), 9.33 (s, 1 H), 8.40 (d, J = 2.5 Hz, 1H), 7.78 (s, 1H), 7.64 (m, 2H), 7.54 (d, J = 8.9 Hz, 1H), 7.47 (m, 3H), 7.12 (dd, J = 8.9, 2.5 Hz, 1H), 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 (br t, J = 4 Hz, 4H). Found: C, 70.55; H, 5.25; N, 9.22. Calculated for _{C 26 H 23 N 3 O 4} : C, 70.74; H, 5.25; N, 9.51.

Example 183 9-Hydroxy-6- [3- (1H-imidazol-1-yl) propyl] -4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione ( Preparation of VIII; Ar = phenyl, n = 3, Z = 1-imidazolyl) (212) Bromide (204) (80 mg, 0.18 mmol) prepared as described in Example 173 was described in Example 179. Reaction with imidazole by the procedure gave amine (212) (41 mg, 53%) as a yellow powder with a melting point of 309-311 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.06 (s, 1H), 9.36 (s, 1H), 8.40 (d, J = 2.3 Hz, 1H), 7.69 (s , 1H), 7.64 (m, 3H), 7.47 (m, 4H), 7.22 (s, 1H), 7.14 (dd, J = 8.8, 2.3 Hz, 1H), 6.89 (s, 1H), 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. _{C 26 H 20 N 4 O 3} . Calculated for _1/2 H2O: C, 70.10; H, 4.75; N, 12.57.

Example 184 9-hydroxy-6- [2- (1H-imidazol-1-yl) ethyl] -4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione ( Preparation of VIII; Ar = phenyl, n = 2, Z = 1-imidazolyl) (213) Mesylate (205) (70 mg, 0.16 mmol) prepared as described in Example 174 was described in Example 179. Reaction with imidazole by the procedure gave amine (213) (34 mg, 50%) as a yellow powder with a melting point> 345 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.05 (br s, 1H), 9.34 (s, 1H), 8.39 (d, J = 2.4 Hz, 1H), 7.59 ( m, 2H), 7.45 (m, 5H), 7.27 (s, 1H), 7.06 (dd, J = 8.8, 2.4 Hz, 1H), 7.02 (s, 1H) 6.75 (s, 1H), 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. _{C 25 H 18 N 4 O 3} . 1 / 4H ₂ O Calculated: C, 70.33; H, 4.37 ; N, 13.12.

Example 185 9-Hydroxy-6- [3- (methylamino) propyl] -4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VIII; Ar = phenyl) , N = 3, Z = NHMe) (214) Preparation of bromide (204) (40 mg, 0.09 mmol) prepared as described in Example 173, except that the reaction was carried out in dimethyl sulfoxide at room temperature for 3 hours. Reaction with aqueous methylamine (10 mol equivalents) by the procedure described in Example 179 gave amine (214) (22 mg, 61%) as an orange / yellow powder with a melting point of 265-268 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 9.33 (br s, 1H), 8.41 (d, J = 2.5 Hz, 1H), 7.80 (s, 1H), 7.64 ( m, 2H), 7.57 (d, J = 8.8 Hz, 1H), 7.47 (m, 3H), 7.14 (dd, J = 8.8, 2.5 Hz, 1H), 4. 51 (t, J = 6.8 Hz, 2H), 2.40 (t, J = 6.5 Hz, 2H), 2.20 (s, 3H), 1.88 (m, 2H). Calculated value of FABMS [M + H] ⁺ : 400.1659. Calcd 400.1661 for _{C 24 H 22 N 3 O 3} .

Example 186 9-Hydroxy-4-phenyl-6- [3- (1-piperazinyl) propyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VIII; Ar = Preparation of phenyl, n = 3, Z = 1-piperazinyl) (215) Bromide (204) (70 mg, 0.16 mmol) prepared as described in Example 173, except that the reaction was carried out at room temperature for 20 hours. Reaction with piperazine according to the procedure described in Example 179 gave amine (215) (40 mg, 55%) as a yellow powder with a melting point of 178-183 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.0 (br s, 1 H), 9.35 (br s, 1 H), 8.40 (d, J = 2.4 Hz, 1 H), 7.78 (S, 1H), 7.62 (m, 2H), 7.56 (d, J = 8.8 Hz, 1H), 7.45 (m, 3H), 7.14 (dd, J = 8.8) , 2.4 Hz, 1H), 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. _{C 27 H 26 N 4 O 3} . 4 / 5H ₂ O Calculated: C, 69.16; H, 5.93 ; N, 11.94.

Example 187 6- [3- (Benzylamino) propyl] -9-hydroxy-4-phenylpyrrolo [3,4-c] carbazole-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 173 was used in Example 179 except that the reaction was carried out at room temperature for 20 hours. And reacted with benzylamine to give amine (216) (36 mg, 45%) as a yellow powder with a melting point of 139-144 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.04 (br s, 1 H), 9.33 (br s, 1 H), 8.41 (d, J = 2.4 Hz, 1 H), 7.80 (S, 1H), 7.62 (m, 2H), 7.57 (d, J = 8.8 Hz, 1H), 7.44 (m, 3H), 7.24 to 7.19 (m, 5H) ), 7.11 (dd, J = 8.8, 2.4 Hz, 1H), 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; C 30 H 25 N 3 O 3. 1 / 4H ₂ O Calculated: C, 75.06; H, 5.35 ; N, 8.75.

Example 188 6- (3-anilinopropyl) -9-hydroxy-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VIII; Ar = phenyl, n = 3, Z = NHPh) (217) Preparation of bromide (204) (75 mg, 0.17 mmol) prepared as described in Example 173, described in Example 179 except that the reaction was carried out at room temperature for 20 hours. Reacted with aniline by the procedure described above to give aniline (217) (30 mg, 38%) as a yellow powder with a melting point of 240 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.04 (br s, 1H), 9.33 (s, 1H), 8.40 (d, J = 2.4 Hz, 1H), 7.78 ( s, 1H), 7.59 (d, J = 8.9 Hz, 1H), 7.48 (m, 2H), 7.42 (m, 3H), 7.10 (dd, J = 8.8, 2.4 Hz, 1H), 7.05 (m, 2H), 6.52 (m, 3H), 5.70 (t, J = 5.3 Hz, 1H), 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. _{C 29 H 23 N 3 O 3} . Calculated for _1/2 H2O: C, 74.03; H, 5.14; N, 8.93.

Example 189 4- (2-chloro-6-methoxyphenyl) -6- {3- [cis-3,5-dimethylpiperazinyl] 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) Preparation The bromide (207) (60 mg, 0.12 mmol) prepared as described in Example 176 was prepared according to the procedure described in Example 179 except that the reaction was carried out at room temperature for 20 hours. To give amine (218) (63 mg, 98%) as a yellow powder with a melting point of 199-202 ° C. ¹ H NMR δ [(CD ₃ ) 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, 1H), 7.57 (d, J = 8.8 Hz, 1H), 7.43 (t, J = 8.2 Hz, 1H), 7.15 (m, 3H), 4.45 (t , J = 6.1 Hz, 2H), 3.67 (s, 3H), 2.49 (m, 4H), 2.11 (m, 2H), 1.90 (m, 2H), 1.27 ( m, 2H), 0.79 (m, 6H). Found: C, 61.35; H, 5.68; N, 9.14. _{C 30 H 31 ClN 4 O 4} . Calculated for ₂ 1/4 H ₂ O: C, 61.32; H, 6.09; N, 9.54.

Example 190 4- (2-chloro-6-methoxyphenyl) -9-hydroxy-6- [3- (4-morpholinyl) propyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -Dione (VIII; Ar = 2-chloro-6-methoxyphenyl, n = 3, Z = 4-morpholinyl) (219) Bromide (207) prepared as described in Example 176 (60 mg, 0.12 mmol) was reacted with morpholine according to the procedure described in Example 179 except that the reaction was carried out at 50 ° C. for 6 hours to give amine (219) (40 mg, 66%) as a yellow powder with a melting point of 169-174 ° C. Got. ¹ H NMR δ [(CD ₃ ) 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, 1H), 7.58 (d, J = 8.8 Hz, 1H), 7.44 (t, J = 8.2 Hz, 1H), 7.18 (d, J = 8.2 Hz, 1H) 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 .22-2.11 (m, 6H), 1.91 (m, 2H). Found: C, 63.09; H, 5.26; N, 7.97. _{C 28 H 26 ClN 3 O 5} . 3 / 4H ₂ O Calculated: C, 63.04; H, 5.20 ; N, 7.88.

Example 191 4- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) butanenitrile Preparation of (VIII; Ar = 2-chlorophenyl, n = 3, Z = CN) (241) A solution of bromide 0 (0.13 g, 0.27 mmol) in dimethyl sulfoxide (2 mL) prepared as described in Example 172. A solution of sodium cyanide (15 mg, 0.30 mmol) in dimethyl sulfoxide (2 mL) was added dropwise over 15 minutes. After 30 minutes, the reaction was diluted with water and extracted with ethyl acetate. The organic layer was dehydrated, the dehydrating agent was removed, and the solution was concentrated to dryness. Chromatography on silica, eluting with ethyl acetate / hexane (1: 4 → 1: 1) followed by crystallization from ethyl acetate / hexane to give a nitrile as an orange powder with a melting point of 262-266 ° C. (241) (68 mg, 59%) was obtained. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.08 (br s, 1 H), 9.39 (s, 1 H), 8.39 (d, J = 2.4 Hz, 1 H), 7.83 ( s, 1H), 7.59 (m, 2H), 7.49 (m, 3H), 7.15 (dd, J = 8.8, 2.4 Hz, 1H), 4.50 (t, J = 7.3 Hz, 2H), 2.57 (m, 2H), 2.07 (m, 2H). Calculated value of FABMS [M + H] ⁺ : 430.0927, 432.0916. Calculated 430.0958,432.0929 of _{C 24 H 16 ClN 3 O 3} .

Example 192 4- (2-chlorophenyl) -9-hydroxy-6- [2- (phenylsulfanyl) ethyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VII Preparation of Ar = 2-chlorophenyl, n = 2, Z = SPh) (242) According to the procedure described in Example 179 except that triethylamine (2.0 mL) was added and the reaction was heated at 110 ° C. for 4 days. Mesylate (229) (55 mg, 0.11 mmol) prepared as described in Example 171 was reacted with excess thiophenol (0.10 mL). Water was added followed by extraction of the compound with ethyl acetate. The organic layer was dehydrated, the dehydrating agent was removed, and the solution was concentrated to dryness. The organic layer is dehydrated, the dehydrating agent is removed, the solution is concentrated to dryness followed by chromatography on silica, eluting with ethyl acetate / hexane (1: 4 → 1: 1), Carbazole (242) (16 mg, 27%) was obtained as an orange powder with a melting point of 262-264 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.04 (br s, 1 H), 9.37 (br s, 1 H), 8.34 (d, J = 2.5 Hz, 1 H), 7.58 (M, 1H), 7.46 (m, 5H), 7.19 (m, 2H), 7.12 (m, 3H), 7.05 (m, 1H), 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. _{C 28 H 19 ClN 2 O 3} S. 1 3 / 4H ₂ O Calculated: C, 63.39; H; 4.28 ; N, 5.28.

Example 193 2-{[3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1H)- Yl) propyl] amino} benzoic acid (VIII; Ar = 2-chlorophenyl, n = 3, Z = 2-carboxyanilino) (60).
The bromide (58) prepared as described in Example 172 was reacted with o-anthranilic acid using the procedure described in Example 179 to give aniline (60) (88%) mp 261-263 ° C. Obtained. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.05 (s, 1H), 9.38 (s, 1H), 8.39 (d, J = 2.4 Hz, 1H), 7.76 (m , 1H), 7.75 (s, 1H), 7.59 (d, J = 8.7 Hz, 1H), 7.55 (m, 1H), 7.46 (m, 1H), 7.40 ( m, 1H), 7.33 (m, 1H), 7.27 (m, 1H), 7.12 (dd, J = 8.7, 2.4 Hz, 1H), 6.59 to 6.50 ( m, 2H), 4.57 (t, J = 6.7 Hz, 2H), 3.22 to 3.10 (m, 2H), 2.15 to 2.05 (m, 2H). Calculated for FABMS M ⁺ : 541.1230, 539.1234. Calculated 541.1218,539.1248 of _{C 30 H 22 ClN 3 O 5} .

Example 194 3-{[3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1H)- Iyl) propyl] amino} benzoic acid (VIII; Ar = 2-chlorophenyl, n = 3, Z = 3-carboxyanilino) (61).
The bromide (58) prepared as described in Example 172 was reacted with m-anthranilic acid using the procedure described in Example 179 to give aniline (61) (82%), mp 160-166 ° C. Obtained. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.04 (s, 1H), 9.38 (s, 1H), 8.39 (d, J = 2.4 Hz, 1H), 7.77 (s , 1H), 7.61 (d, J = 8.7 Hz, 1H), 7.54 (m, 1H), 7.45 (m, 1H), 7.27 (m, 1H), 7.14- 7.08 (m, 4H), 6.67 (m, 1H), 5.92 (br s, 1H), 4.58 (m, 2H), 3.09 to 2.92 (m, 2H), 2.12 to 2.02 (m, 2H). Calculated for FABMS M ⁺ : 541.1223, 539.1237. Calculated 541.1218,539.1248 of _{C 30 H 22 ClN 3 O 5} .

Example 195 4-{[3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (IH)- Yl) propyl] amino} benzoic acid (VIII; Ar = 2-chlorophenyl, n = 3, Z = 4-carboxyanilino) (62).
The bromide (58) prepared as described in Example 172 was reacted with p-anthranilic acid using the procedure described in Example 179 to give aniline (62) (77%) mp 160-165 ° C. Obtained. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.06 (br s, 1H), 9.43 (br s, 1H), 8.39 (d, J = 2.4 Hz, 1H), 7.75 (S, 1H), 7.65-7.59 (m, 3H), 7.54 (m, 1H), 7.45 (m, 1H), 7.37 (m, 1H), 7.26 ( m, 1H), 7.13 (dd, J = 8.7, 2.4 Hz, 1H), 6.49 (d, J = 8.7 Hz, 2H), 4.58 (m, 2H), 3. 11 to 2.99 (m, 2H), 2.12 to 2.04 (m, 2H). Found: C, 63.24; H, 4.66; N, 7.95. _{C 30 H 22 ClN 3 O 5} . Of H ₂ O Calcd C, 63.55; H, 4.23; N, 7.41.

Example 196 4- (2-chlorophenyl) -6- {3-[(cis) -3,5-dimethylpiperazinyl] propyl} -9-hydroxypyrrolo [3,4-c] carbazole-1, Preparation of 3 (2H, 6H) -dione (VIII; Ar = 2-chlorophenyl, n = 3, Z = cis-3,5-dimethylpiperazinyl) (63).
The bromide (58) prepared as described in Example 172 was reacted with cis-1,3-dimethylpiperazine using the procedure described in Example 179 to give (63) (65 %). ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.04 (br s, 1 H), 9.36 (br s, 1 H), 8.38 (d, J = 2.4 Hz, 1 H), 7.80 (S, 1H), 7.59 to 7.54 (m, 2H), 7.51 to 7.42 (m, 3H), 7.13 (dd, J = 8.7, 2.4 Hz, 1H) 4.47 (m, 2H), 2.58 to 2.38 (m), 2.09 (t, J = 6.2 Hz, 2H), 1.96 to 1.87 (m, 2H), 1 .32 to 1.23 (m, 2H), 0.81 (d, J = 6.1 Hz, 3H), 0.77 (d, J = 6.1 Hz, 3H). Found: C, 64.09; H, 5.43; N, 10.08. _{C 29 H 28 ClN 4 O 3} . 1.5 H ₂ O Calculated C, 64.14; H, 5.75; N, 10.31.

Example 197 4- (2,6-dichlorophenyl) -6- {3-[(cis) -3,5-dimethylpiperazinyl] propyl} -9-hydroxypyrrolo [3,4-c] carbazole- Preparation of 1,3 (2H, 6H) -dione (VIII; Ar = 2,6-dichlorophenyl, n = 3, Z = cis-3,5-dimethylpiperazinyl) (64).
The bromide (233) prepared as described in Example 178 was reacted with cis-1,3-dimethylpiperazine using the procedure described in Example 179 to give (64) (68 %). ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.11 (br, 1H), 9.39 (br s, 1H), 8.37 (d, J = 2.4 Hz, 1H), 7.85 ( s, 1H), 7.62 (d, J = 8.1 Hz, 2H), 7.59 (d, J = 8.7 Hz, 1H), 7.51 (m, 1H), 7.16 (dd, J = 8.7, 2.4 Hz, 1H), 4.46 (t, J = 5.7 Hz, 2H), 2.55 to 2.42 (m), 2.10 (t, J = 6.4 Hz). , 2H), 1.96 to 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 4} O 3. Of H ₂ O Calcd C, 61.27; H, 5.14; N, 9.85.

(Example 198)
The following amino compounds of general structure VIII were prepared in an array format using the procedure described in Example 179, reacting the appropriate mesylate or bromide with the appropriate amine.

6- (2-Aminoethyl) -9-hydroxy-4-phenylpyrrolo [3,4-c] carbazole-1,3 (by reaction of (205) prepared as described in Example 174 with aqueous ammonia. preparation of Ar = _{phenyl, n = 2, Z = NH} 2) (65); - 2H, 6H) dione (VIII. Actual value: M + H = 372

9-Hydroxy-6- [2- (methylamino) ethyl] -4-phenylpyrrolo [3,4-c] carbazole- by reaction of (205) prepared as described in Example 174 with aqueous methylamine 1,3 (2H, 6H) - dione; preparation of (VIII Ar = phenyl, n = 2, Z = NHCH 3) (66). Actual value: M + H = 386

6- (3-Aminopropyl) -9-hydroxy-4-phenylpyrrolo [3,4-c] carbazole-1,3 (by reaction of (204) prepared as described in Example 173 with aqueous ammonia. 2H, 6H) - dione (VIII, Ar = _{phenyl, n = 3, Z = NH} 2) (67). Actual value: M + H = 386

  9-Hydroxy-4-phenyl-6- [3- (1-pyrrolidinyl) propyl] pyrrolo [3,4-c] carbazole-1 by reaction of (204) prepared as described in Example 173 with pyrrolidine , 3 (2H, 6H) -dione (VIII; Ar = phenyl, n = 3, Z = 1-pyrrolidinyl) (68). Actual value: M + H = 440

6- [3- (Diethylamino) propyl] -9-hydroxy-4-phenylpyrrolo [3,4-c] carbazole-1,3 by reaction of (204) prepared as described in Example 173 with diethylamine. (2H, 6H) - dione (VIII; Ar = _{phenyl, n = 3, Z = n} (CH 2 CH 3) 2) preparation of (69). Found: M + H = 442.

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

  9-Hydroxy-6- [3- (4-methyl-piperazinyl) propyl] -4-phenylpyrrolo [3,4- by reaction of (204) prepared as described in Example 173 with 1-methylpiperazine. c] Preparation of carbazole-1,3 (2H, 6H) -dione (VIII; Ar = phenyl, n = 3, Z = 4-methyl-1-piperazinyl) (71). Actual value: M + H = 469

6- [6- (Dimethylamino) hexyl-9-hydroxy-4-phenylpyrrolo [3,4-c] carbazole-1 by reaction of (206) prepared as described in Example 175 with aqueous dimethylamine , 3 (2H, 6H) - dione (VIII; Ar = _{phenyl, n = 6, Z = n} (CH 3) 2) preparation of (72). Actual value: M + H = 456

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

6- (2-Aminoethyl) -4- (2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole- by reaction of (229) prepared as described in Example 171 with aqueous ammonia. 1,3 (2H, 6H) - dione; preparation of (VIII Ar = _{2-chlorophenyl, n = 2, R = NH} 2) (74). Actual value: MH = 404

4- (2-Chlorophenyl) -9-hydroxy-6- [3- (dimethylamino) ethyl] pyrrolo [3,4- by reaction of (229) prepared as described in Example 171 with aqueous dimethylamine. c] carbazole-1,3 (2H, 6H) - dione (VIII, Ar = _{2-chlorophenyl, n = 2, Z = n} (CH 3) 2) preparation of (75). Found: M + H = 434.

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

  4- (2-Chlorophenyl) -9-hydroxy-6- [2- (4-morpholinyl) ethyl] pyrrolo [3,4-c by reaction of (229) prepared as described in Example 171 with morpholine. Preparation of carbazole-1,3 (2H, 6H) -dione (VIII, Ar = 2-chlorophenyl, n = 2, Z = 4-morpholinyl) (77). Found: M + H = 476.

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

  6- (2-anilinoethyl) -4- (2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1, prepared by reaction of (229) prepared as described in Example 171 with aniline. Preparation of 3 (2H, 6H) -dione (VIII, Ar = 2-chlorophenyl, n = 2, z = anilino) (79). Actual value: M + H = 481

4- (2,6-dichlorophenyl) -9-hydroxy-6- [3- (dimethylamino) ethyl] pyrrolo [3, by reaction of (231) prepared as described in Example 177 with aqueous dimethylamine. 4-c] carbazole-1,3 (2H, 6H) - dione (VIII, Ar = _{2,6-dichlorophenyl, n = 2, Z = n} (CH 3) 2) preparation of (80). Found: M + H = 468.

  4- (2,6-Dichlorophenyl) -9-hydroxy-6- [2- (1H-imidazol-1-yl) ethyl] pyrrolo by reaction of (231) prepared as described in Example 177 with imidazole. Preparation of [3,4-c] carbazol-1,3 (2H, 6H) -dione (VIII, Ar = 2,6-dichlorophenyl, n = 2, Z = 1H-imidazol-1-yl) (81). Found: M + H = 491.

  4- (2,6-Dichlorophenyl) -9-hydroxy-6- [2- (4-morpholinyl) ethyl] pyrrolo [3,4] by reaction of (231) prepared as described in Example 177 with morpholine. -C] Preparation of carbazole-1,3 (2H, 6H) -dione (VIII, Ar = 2,6-dichlorophenyl, n = 2, Z = 4-morpholinyl) (82). Found: M + H = 510.

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

  6- (2-anilinoethyl) -4- (2,6-dichlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole- by reaction of (231) prepared as described in Example 177 with aniline Preparation of 1,3 (2H, 6H) -dione (VIII, Ar = 2,6-dichlorophenyl, n = 2, Z = anilino) (84). Actual value: M + H = 516

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

4- (2-Chlorophenyl) -6- [3- (dimethylamino) propyl] -9-hydroxypyrrolo [3,4] by reaction of (58) prepared as described in Example 172 with aqueous dimethylamine. c] carbazole-1,3 (2H, 6H) - dione (VIII, Ar = _{2-chlorophenyl, n = 3, Z = n} (CH 3) 2) preparation of (86). Found: M + H = 448.

  4- (2-Chlorophenyl) -9-hydroxy-6- [3- (1H-imidazol-1-yl) propyl] pyrrolo [3,4] by reaction of bromo and imidazole prepared as described in Example 172. -C] Preparation of carbazol-1,3 (2H, 6H) -dione (VIII, Ar = 2-chlorophenyl, n = 3, Z = 1H-imidazol-1-yl) (87). Found: M + H = 471.

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

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

  6- (3-anilinopropyl) -4- (2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole- by reaction of (58) prepared as described in Example 172 with aniline Preparation of 1,3 (2H, 6H) -dione (VIII, Ar = 2-chlorophenyl, n = 3, Z = anilino) (90). Found: M + H = 495.

  4- (2,6-dichlorophenyl) -9-hydroxy-6- [3- (methylamino) propyl] pyrrolo [3, by reaction of (233) prepared as described in Example 178 with aqueous methylamine. 4-c] Preparation of carbazole-1,3 (2H, 6H) -dione (VIII, Ar = 2,6-dichlorophenyl, n = 3, Z = NHMe) (91). Found: M + H = 468.

4- (2,6-dichlorophenyl) -6- [3- (dimethylamino) propyl] -9-hydroxypyrrolo [3, prepared by reaction of (233) prepared as described in Example 178 with aqueous dimethylamine. 4-c] carbazole-1,3 (2H, 6H) - dione (VIII, Ar = _{2,6-dichlorophenyl, n = 3, Z = n} (CH 3) 2) preparation of (92). Found: M + H = 482.

  4- (2,6-Dichlorophenyl) -9-hydroxy-6- [3- (1H-imidazol-1-yl) propyl] pyrrolo by reaction of (233) prepared as described in Example 178 with imidazole. Preparation of [3,4-c] carbazol-1,3 (2H, 6H) -dione (VIII, Ar = 2,6-dichlorophenyl, n = 3, Z = 1H-imidazol-1-yl) (93). Found: M + H = 505.

  4- (2,6-Dichlorophenyl) -9-hydroxy-6- [3- (4-morpholinyl) propyl] pyrrolo [3,4] by reaction of (233) prepared as described in Example 178 with morpholine. -C] Preparation of carbazole-1,3 (2H, 6H) -dione (VIII, Ar = 2,6-dichlorophenyl, n = 3, Z = 4-morpholinyl) (94). Found: M + H = 524.

  4- (2,6-dichlorophenyl) -9-hydroxy-6- [3- (4-methyl-1-piperazinyl) by reaction of (233) prepared as described in Example 178 with 1-methylpiperazine Propyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VIII, Ar = 2,6-dichlorophenyl, n = 3, Z = 4-methyl-1-piperazinyl) (95) Preparation. Found M + H = 537.

  6- (3-anilinopropyl) -4- (2,6-dichlorophenyl) -9-hydroxypyrrolo [3,4-c] by reaction of (233) prepared as described in Example 178 with aniline. Preparation of carbazole-1,3 (2H, 6H) -dione (VIII, Ar = 2,6-chlorophenyl, n = 3, Z = anilino) (96). Found: M + H = 530.

Example 199 Combinatorial procedure for aniline substitution of Br and OMs 6- (3-bromopropyl) -4- (chlorophenyl) -9-hydroxy-6H prepared as described in Example 83 in an 8 ml screw-mouth vial. -Pyrrolo [3,4-c] carbazole-1,3-dione (reagent A) (0.048 g, 0.1 mmol) or 2- (9-hydroxy-1, prepared as described in Example 174 3-Dioxo-4-phenyl-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) ethyl methanesulfonate (205) (reagent B) (see Table 2) in anhydrous dimethylacetamide ( 1 ml) solution, the appropriate aniline (0.012 g, 0.1 mmol) in anhydrous dimethylacetamide (0.150 ml) was added. The vial was capped and the reaction mixture was shaken at 100 ° C. for 18 hours. After cooling to room temperature, the solvent was removed under reduced pressure. Purification was performed by reverse phase HPLC (3% eluent in acetonitrile and 3% aqueous n-propanol; C-18 column as eluent). The compound was analyzed by mass spectral analysis.

Example 200 4- (2-Chlorophenyl) -9-hydroxy-6- [3- (methylsulfanyl) propyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VIII Preparation of Ar = 2-chlorophenyl, n = 3, Z = SCH ₃ ) (130) Bromide (58) (60.0 mg, 0.124 mmol) prepared as described in Example 172 and lithium thiomercaptide ( A mixture of 13 mg, 0.2481 mmol) in p-dioxane (5 mL) was refluxed for 16 hours. An additional 10 mg of LiSMe was added and reflux continued for an additional 9 hours. The mixture was diluted with water and extracted with ethyl acetate. The organic layer was dehydrated, the dehydrating agent was removed, and the solution was concentrated to dryness to give sulfide (130 (47.1 mg, 84%) directly, which had a melting point of 218--from ethyl acetate / petroleum ether. Crystallized as an orange powder at 220 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.07 (br s, 1 H), 9.39 (br s, 1 H), 8.39 (d, J = 2.4 Hz, 1H), 7.80 (s, 1H), 7.61 to 7.56 (m, 2H), 7.53 to 7.43 (m, 3H), 7.15 (dd, J = 8.8, 2.4 Hz, 1H), 4.52 (t, J = 6.9 Hz, 2H), 2.45 (t, J = 7.0 Hz, 2H), 2.01 (m, 2H) 2.00 (s, 3H) Calculated value of FABMS [M + H] ⁺ : 453.0840, 451.0859. C ₂₄ Calculated _{H 20 ClN 2 O 3 S 453.0854,451.0883} .

Example 201 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).
P-Dioxane in a mixture of bromide (58) (41 mg, 0.085 mmol), thiophenol (9.5 μL, 0.093 mmol) and triethylamine (0.25 mL, 3.40 mmol) prepared as described in Example 172. The (1.5 mL) solution was refluxed for 16 hours. Water was added and the mixture was extracted with ethyl acetate. The organic layer was dehydrated, the dehydrating agent was removed, and the solution was directly concentrated to dryness to sulfide (131) (37.2 mg, 85%). It crystallized from ethyl acetate / petroleum ether as an orange powder with a melting point of 229-231 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.06 (br s, 1H), 9.37 (s, 1H), 8.37 (d, J = 2.4 Hz, 1H), 7.76 ( s, 1H), 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), 2.01 (m, 2H). Found: C, 67.36; H, 4.29; N, 5.36. _{C 29 H 21 ClN 2 SO 3} . 1 / 4H ₂ O Calculated C, 67.31; H, 4.19; N, 5.41.

Example 202 4- (2-chlorophenyl) -9-hydroxy-6- (3-methoxypropyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VIII; Ar = _{2-chlorophenyl, n = 3, Z = OCH} 3) preparation of (132).
A solution of bromide (58) (50 mg, 0.103 mmol) and sodium methoxide (35.2 mg, 0.65 mmol) in methanol (0.5 mL) and p-dioxane (8 mL) prepared as described in Example 172. Was refluxed for 3 hours. The solution was acidified with 2N HCl, extracted with ethyl acetate, the organic layer was dried, the dehydrating agent was removed, the solution was concentrated to dryness and chromatographed on silica. Elute with ethyl acetate to give an orange powder of anhydride, 4- (2-chlorophenyl) -9-hydroxy-6- (3-methoxypropyl) -1H-furo [3,4-c] carbazole-1,3 (6H) -dione was obtained. ¹ H NMR δ [(CD ₃ ) ₂ SO] 9.57 (br, 1H), 8.24 (d, J = 2.3 Hz, 1H), 8.00 (s, 1H), 7.66-7 .61 (m, 2H), 7.58 to 7.48 (m, 3H), 7.22 (dd, J = 9.0, 2.3 Hz, 1H), 4.56 (t, J = 6. 7 Hz, 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 warmed at this temperature for 3 hours. Water was added and the resulting precipitate was filtered off, adsorbed on silica from a THF solution and chromatographed. Elution with ethyl acetate / petroleum ether (1: 1) gave an orange powder of (132) (32 mg, 71%), mp 260-262 ° C. ¹ H NMR δ [(CD ₃ ) 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). Calculated value of FABMS [M + H] ⁺ : 437.1088, 435.1090. Calculated 437.1082,435.1112 of _{C 24 H 20 ClN 2 O 4} .

  Procedure of scheme 4

  Representative Procedure for Method 13 of Scheme 4

Example 203 3- (9-methoxy-1,3-dioxo-4-phenyl-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) propanoic acid (IX; Ar = Phenyl, n = 2) Preparation of (243) Dess-Martin periodinane (1.91 g, 4.5 mmol) was prepared as described in Example 83 (202) (1.20 g, 3. 0 mmol) in anhydrous tetrahydrofuran (80 mL) was added under nitrogen. After 1 hour at room temperature, a solution of saturated sodium thiosulfate and saturated sodium bicarbonate (1: 1, 100 mL) was added and the reaction mixture was stirred vigorously for 15 minutes followed by extraction with ethyl acetate. The organic layer was dehydrated, the dehydrating agent was removed, and the solution was concentrated to dryness. The resulting crude aldehyde was then dissolved in tert-butanol / tetrahydrofuran (9: 1, 230 mL) and 2-methyl-2-butene (12.0 mmol, 6.0 mL of 2M tetrahydrofuran solution) was added. To this solution was added a solution of sodium chlorite (1.09 g, 12.0 mmol) containing tert-butanol (4 mL) and sodium dihydrogen phosphate (2.5 g, 18.0 mmol) in water (100 mL). The resulting solution was stirred at room temperature for 18 hours, then diluted with brine and extracted with ethyl acetate. The organic layer was dehydrated, the dehydrating agent was removed, and the solution was concentrated to dryness. Chromatography on silica, eluting with ethyl acetate / methanol (1: 0 → 9: 1) followed by crystallization from ethyl acetate / hexane to give acid (243 as a yellow powder with a melting point of 252 ° -255 ° C. ) (0.86 g, 69%). ¹ H NMR δ [(CD ₃ ) ₂ SO] 12.2 (v br s, 1 H), 11.13 (br s, 1 H), 8.55 (d, J = 2.6 Hz, 1 H), 7. 89 (s, 1H), 7.68 (m, 3H), 7.47 (m, 3H), 7.28 (dd, J = 9.0, 2.6 Hz, 1H), 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. _{C 24 H 18 N 2 O 5} . 1 / 2H ₂₎ Calculated C, 68.08; H, 4.52; N, 6.62.

Example 204 3- (4- (2,6-dichlorophenyl) -9-methoxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) Preparation of propanoic acid (IX; Ar = 2,6-dichlorophenyl, n = 2) (244) Alcohol (232) (0.50 g, 1.1 mmol) prepared as described in Example 86 was prepared in Example 203. And chromatographed on silica, eluting with methanol / dichloromethane (3: 97 → 1: 9), triturated with ethyl acetate / hexanes, mp 203-209 ° C. yellow Acid (244) (0.35 g, 66%) was obtained as a powder. ¹ H NMR δ [(CD ₃ ) ₂ SO] 12.3 (v br s, 1H), 11.19 (br s, 1H), 8.50 (d, J = 2.6 Hz, 1H), 7. 94 (s, 1H), 7.74, (d, J = 9.0 Hz, 1H), 7.62 (m, 2H), 7.51 (dd, J = 13.3, 6.1 Hz, 1H) 7.33 (dd, J = 9.0, 2.6 Hz, 1H), 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. _{C 24 H 16 Cl 2 N 2} O 5 Calculated: C, 59.63; H, 3.34 ; N, 5.79.

Example 205 3- (4- (2-Chloro-6-methoxyphenyl) -9-methoxy-1,3-dioxo-2,3-dihydropyrrolo [3c] carbazol-6 (1H) -yl) propane Preparation of acid (IX; Ar = 2-chloro-6-methoxyphenyl, n = 2) (245) Alcohol (105) (2.1 g, 4.5 mmol) prepared as described in Example 58 was Oxidation by the procedure described in 203 gave acid (245) (0.81 g, 38%) as a yellow powder with a melting point of 241-243 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 12.5 (v br s, 1H), 11.07 (br s, 1H), 8.50 (d, J = 2.6 Hz, 1H), 7. 82 (s, 1H), 7.70 (d, J = 9.0 Hz, 1H), 7.44 (t, J = 8.3 Hz, 1H), 7.30 (dd, J = 9.0, 2 .6 Hz, 1H), 7.18 (d, J = 8.3 Hz, 1H), 7.12 (d, J = 8.3 Hz, 1H), 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. C ₂₅ Calculated _{H 19 ClN 2 O 6 C,} 62.70; H, 4.00; N, 5.85.

Example 206 3- (4- (2,6-dichlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) Preparation of propanoic acid (X; Ar = 2,6-dichlorophenyl, n = 2) (246) Acid (244) (90 mg, 0.19 mmol) prepared as described in Example 204 was described in Example 80. Demethylation using the procedure afforded phenol (246) (63 mg, 71%) as an orange / yellow powder with a melting point of 245-253 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 12.2 (v br s, 1 H), 11.13 (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, 1H), 4.66 (t, J = 6.9 Hz, 1H), 2.73 (t, J = 6.9 Hz, 2H). Found: C, 58.98; H, 3.31; N, 5.81. Calculated _{C 23 H 14 Cl 2 N 2} O 5: C, 58.85; H, 3.01; N, 5.97.

  Representative Procedure for Method 14 of Scheme 4

Example 207 N- [2- (dimethylamino) ethyl] -3- (9-methoxy-1,3-dioxo-4-phenyl-2,3-dihydropyrrolo [3,4-c] carbazole-6 Preparation of (1H) -yl) propanamide (XI; Ar = phenyl, n = 2, R ³ = H, R ⁴ = CH ₂ CH ₂ N (CH ₃ ) ₂ ) (247) As described in Example 203 To a solution of acid (243) (100 mg, 0.24 mmol) prepared in anhydrous tetrahydrofuran (20 mL) was added 1 drop of dimethylformamide under nitrogen, followed by dropwise addition of oxalyl chloride (84 uL, 0.96 mmol). The resulting solution was stirred at room temperature for 2 hours and subsequently dried under reduced pressure. To the residue was added anhydrous benzene (20 mL) and the suspension was again evaporated to dryness, then dissolved in anhydrous tetrahydrofuran (20 uL) and flushed with nitrogen. To this solution was added dimethylethylenediamine (105 mL, 0.96 mmol) using a syringe. The reaction mixture was stirred at room temperature for 2 hours, then diluted with water, basified with the addition of solid potassium carbonate and extracted with ethyl acetate. The organic layer was dehydrated, the dehydrating agent was removed, and the solution was concentrated to dryness. Chromatography on silica, eluting with ethyl acetate / methanol / triethylamine (1: 0: 0 → 3: 1: trace) followed by crystallization from ethyl acetate / hexane, mp 206-210 ° C. Amide (247) (85 mg, 73%) was obtained as a yellow powder. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.11 (br s, 1H), 8.54 (d, J = 2.6 Hz, 1H), 7.81 (s, 1H), 7.73 ( t, J = 5.6 Hz, 1H), 7.67 (m, 3H), 7.48 (m, 3H), 7.29 (dd, J = 8.9, 2.6 Hz, 1H), 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. _{C 28 H 28 N 4 O 4} . Of H ₂ O Calculated: C, 66.92; H, 6.02 ; N, 11.14.

Example 208 3- (9-methoxy-1,3-dioxo-4-phenyl-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) propanamide (XI; Ar = Phenyl, n = 2, R ³ = H, R ⁴ = H) (248) Preparation of acid (243) (100 mg, 0.24 mmol) prepared as described in Example 203 was added to ammonia gas tetrahydrofuran ( (20 mL) The reaction was followed by the procedure described in Example 207 except that the saturated solution was added as an amine to give amide (248) (61 mg, 62%) as a yellow powder with a melting point of 266-270 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.11 (br s, 1 H), 8.55 (d, J = 2.6 Hz, 1 H), 7.87 (s, 1 H), 7.68 ( m, 3H), 7.48 (m, 3H), 7.33 (br s, 1H), 7.29 (dd, J = 9.0, 2.6 Hz, 1H), 6.85 (br s, 1H), 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. _{C 24 H 19 N 3 O 4} . Calculated for _1/2 H2O: C, 68.24; H, 4.78; N, 9.94.

Example 209 3- (4- (2-chlorophenyl) -9-methoxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) -N Preparation of-[2- (dimethylamino) ethyl) propanamide (XI; Ar = 2-chlorophenyl, n = 2, R ³ = H, R ⁴ = CH ₂ CH ₂ N (CH ₃ ) ₂ ) (249) Implementation The acid (116) prepared as described in Example 229 (95 mg, 0.21 mmol) was reacted according to the procedure described in Example 207 followed by trituration in diethyl ether to yield a yellow powder with a melting point of 250-252 ° C. As the amide (249) (76 mg, 70%). ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.12 (br s, 1 H), 8.51 (d, J = 2.6 Hz, 1 H), 7.77 (s, 1 H), 7.76 ( Partially unclear t, J = 5.9 Hz, 1H), 7.68 (d, J = 9.0 Hz, 1H), 7.58 (m, 2H), 7.48 (m, 3H), 7.32 (dd, J = 9.0, 2.6 Hz, 1H), 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 (partially unclear t, J = 6.8 Hz, 2H). Found: C, 64.88; H, 5.56 ; N, 10.70: Calculated for _{C 28 H 27 ClN 4 O 4} : C, 64.79; H, 5.24; N, 10.79 .

Example 210 3- (4- (2,6-dichlorophenyl) -9-methoxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) Preparation of Propanamide (XI; Ar = 2,6-dichlorophenyl, n = 2, R ³ = H, R ⁴ = H) (250) Acid (244) prepared as described in Example 204 (0.23 g , 0.48 mmol) was reacted according to the procedure described in Example 207 except that concentrated ammonia as an amine (about 30%, 20 mL) was added to give the amide (250) (0 .17 g, 73%). ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.19 (br s, 1H), 8.50 (d, J = 2.6 Hz, 1H), 7.87 (s, 1H), 7.73 ( d, J = 9.0 Hz, 1H), 7.63 (m, 2H), 7.52 (dd, J = 8.8, 7.3 Hz, 1H), 7.38 (brs, 1H), 7 .33 (dd, J = 9.0, 2.6 Hz, 1H), 6.87 (br s, 1H), 4.69 (t, J = 6.7 Hz, 2H), 3.91 (s, 3H) ), 2.57 (t, J = 6.7 Hz, 2H). Found: C, 59.55; H, 3.79; N, 8.73. Calculated _{C 24 H 17 Cl 2 N 3} O 4: C, 59.75; H, 3.55; N, 8.71.

Example 211 3- (4- (2,6-Dichlorophenyl) -9-methoxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) -N- [2- (dimethylamino) ethyl] propanamide (XI; Ar = 2,6-dichlorophenyl, n = 2, R ³ = H, R ⁴ = CH ₂ CH ₂ N (CH ₃ ) ₂ ) (251 The acid (244) (150 mg, 0.30 mmol) prepared as described in Example 204 was reacted according to the procedure described in Example 207 to give the amide (251) as a yellow powder with a melting point of 141-146 ° C. (91 mg, 55%) was obtained. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.19 (br s, 1 H), 8.50 (d, J = 2.6 Hz, 1 H), 7.82 (s, 1 H), 7.81 ( Partially unclear t, J = 5.6 Hz, 1H), 7.69 (d, J = 9.0 Hz, 1H), 7.62 (m, 2H), 7.52 (dd, J = 8) .8, 7.4 Hz, 1H), 7.34 (dd, J = 9.0, 2.6 Hz, 1H), 4.71 (t, J = 6.4 Hz, 2H), 3.90 (s, 3H), 2.95 (q, 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. _{C 28 H 26 Cl 2 N 4} O 4. Of H ₂ O Calcd C, 58.85; H, 4.94; N, 9.80.

Example 212 3- (4- (2-Chloro-6-methoxyphenyl) -9-methoxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1H) -Yl) -N- [2- (dimethylamino) ethyl] propanamide (XI; Ar = 2-chloro-6-methoxyphenyl, n = 2, R ³ = H, R ⁴ = CH ₂ CH ₂ N (CH ₃ ) Preparation of ₂ ) (252) Acid (245) (160 mg, 0.33 mmol) prepared as described in Example 205 was reacted according to the procedure described in Example 207 to give a yellow melting point of 164-169 ° C. Amide (252) (93 mg, 51%) was obtained as a powder. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.06 (br s, 1H), 8.50 (d, J = 2.6 Hz, 1H), 7.80 (t, J = 5.6 Hz, 1H) ), 7.72 (s, 1H), 7.66 (d, J = 9.0 Hz, 1H), 7.45 (t, J = 8.3 Hz, 1H), 7.30 (dd, J = 9) 0.0, 2.6 Hz, 1H), 7.18 (d, J = 8.3 Hz, 1H), 7.13 (d, J = 8.3 Hz, 1H), 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. _{C 29 H 29 ClN 4 O 5} . Of H ₂ O Calculated: C, 61.43; H, 5.51 ; N, 9.88.

Example 213 3- (4- (2-Chlorophenyl) -9-methoxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) -N - (-5-1H-tetrazole-yl) propanamide (XI; Ar = ^{2-chlorophenyl, n = 2, R 3 =} H, R 4 = 5- tetrazolyl) (253) of the as described in Preparative example 229 Implemented except that acid (116) prepared in (70 mg, 0.16 mmol) was added as an amine to solid 5-aminotetrazole (27 mg, 0.31 mmol) and heated to reflux for 2 hours prior to preparation. Reaction by the procedure described in Example 207 gave amide (253) (52 mg, 63%) as a yellow powder with a melting point of 232 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 15.8 (v br s, 1 H), 11.90 (br s, 1 H), 11.13 (br s, 1 H), 8.52 (d, J = 2.6 Hz, 1H), 7.84 (s, 1H), 7.75 (d, J = 9.0 Hz, 1H), 7.57 (d, J = 7.4 Hz, 1H), 7.50 ˜7.40 (m, 3H), 7.30 (dd, J = 9.0, 2.6 Hz, 1H), 4.83 (t, J = 6.8 Hz, 2H), 3.90 (s, 3H), 2.97 (t, J = 6.8 Hz, 2H). Calculated value of FABMS [M = H] ⁺ = 516.1174, 518.1154. Calculated 516.11.87,518.1158 of _{C 25 H 18 ClN 7 O 4} .

Example 214 N- [2- (dimethylamino) ethyl] -3- (9-hydroxy-1,3-dioxo-4-phenyl-2,3-dihydropyrrolo [3,4-c] carbazole-6 Preparation of (1H) -yl) propanamide (XIII; Ar = phenyl, n = 2, R ³ = H, R ⁴ = CH ₂ CH ₂ N (CH ₃ ) ₂ ) (254) As described in Example 207 The procedure described in Example 81, except that the methyl ether (247) (70 mg, 0.14 mmol)) prepared in 1 was diluted with water, basified with concentrated ammonia and extracted with ethyl acetate. Reacted with. The organic layer was dehydrated, the dehydrating agent was removed, and the solution was concentrated to dryness. Chromatography on silica eluting with ethyl acetate / methanol / triethylamine (1: 0: 0 → 3: l: trace). It was then crystallized from ethyl acetate / hexane to give amide (254) (35 mg, 53%) as an orange powder with a melting point of 176-180 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.06 (br s, 1 H), 9.35 (br s, 1 H), 8.39 (d, J = 2.5 Hz, 1 H), 7.77 (S, 1H), 7.74 (t, J = 5.6 Hz, 1H), 7.66 (m, 2H), 7.53 (d, J = 8.8 Hz, 1H), 7.48 (m 3H), 7.12 (dd, J = 8.8, 2.5 Hz, 1H), 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, 11.47. _{C 27 H 26 N 4 O 4} . 3 / 4H ₂ O Calculated: C, 67.00; H, 5.73 ; N, 11.57.

Example 215 3- (9-hydroxy-1,3-dioxo-4-phenyl-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) propanamide (XIII; Ar = Phenyl, n = 2, R ₁ = H, R ₂ = H) (255) and 3- (9-hydroxy-1,3-dioxo-4-phenyl-2,3-dihydropyrrolo [3,4-c Preparation of carbazol-6 (1H) -yl) propanoic acid (X; Ar = phenyl, n = 2) (256) Methyl ether (248) prepared as described in Example 208 (56 mg, 0.14 mmol) ) By the procedure described in Example 81, followed by chromatography on silica, eluting with ethyl acetate / hexane (4: 1) and then ethyl acetate / methanol (9: 1). Te, firstly, to give amide (255) (11mg, 20%) as orange powder having a melting point of two hundred and eighty-four to two hundred eighty-eight ° C.. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.05 (br s, 1 H), 9.33 (br s, 1 H), 8.40 (d, J = 2.5 Hz, 1 H), 7.82 (S, 1H), 7.67 (m, 2H), 7.56 (d, J = 8.8 Hz, 1H), 7.47 (m, 3H), 7.34 (brs, 1H), 7 .12 (dd, J = 8.8, 2.5 Hz, 1H), 6.86 (br s, 1H), 4.67 (t, J = 6.5 Hz, 2H), 2.58 (t, J = 6.5 Hz, 2H). Calculated value of FABMS [M + H] ⁺ : 400.1307. Calcd 400.1297 for _{C 23 H 17 N 3 O 4} . This was followed by the acid (256) (34 mg, 63%) as an orange powder with a smaller Rf and a melting point of 300-310 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 12.1 (v br s, 1H), 11.06 (br s, 1H), 9.34 (br s, 1H), 8.40 (d, J = 2.4 Hz, 1H), 7.84 (s, 1H), 7.67 (m, 2H), 7.57 (d, J = 8.8 Hz, 1H), 7.46 (m, 3H), 7.12 (dd, J = 8.8, 2.4 Hz, 1H), 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. _{C 23 H 16 N 2 O 5} . Calculated for _1/2 H2O: C, 67.48; H, 4.19; N, 6.84.

Example 216 3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) -N - [2- (dimethylamino) ethyl] propanamide (XIII; Ar = _{^{2-chlorophenyl, n = 2, R 3 =}} H, R 4 = CH 2 CH 2 n (CH 3) 2) preparation of (257) Methyl ether (249) prepared as described in Example 209 (65 mg, 0.13 mmol) was prepared in the same manner as in Example except that the reaction mixture was diluted with water, basified with concentrated ammonia and extracted with ethyl acetate. The reaction was carried out according to the procedure described in 81. The organic layer was dehydrated, the dehydrating agent was removed, and the solution was concentrated to dryness. Chromatography on silica eluting with ethyl acetate / methanol / triethylamine (1: 0: 0 → 3: l: trace). It was then crystallized from ethyl acetate / hexane to give amide (257) (28 mg, 44%) as an orange powder with a melting point of 205-215 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.06 (br s, 1H), 9.35 (s, 1H), 8.37 (d, J = 2.3 Hz, 1H), 7.81 ( br s, 1H), 7.72 (s, 1H), 7.57 (m, 2H), 7.48 (m, 3H), 7.14 (dd, J = 8.9, 2.3 Hz, 1H) ), 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. _{C 27 H 25 ClN 4 O 4} . Calculated for 1 1/4 H ₂ O: C, 61.47; H, 5.26; N, 10.62.

Example 217 3- (4- (2,6-dichlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) Preparation of Propanamide (XIII; Ar = 2,6-dichlorophenyl, n = 2, R ³ = H, R ⁴ = H) (258) Methyl ether (250) prepared as described in Example 210 (80 mg, 0.17 mmol)) is reacted according to the procedure described in Example 80, followed by chromatography on silica, eluting with ethyl acetate and then tetrahydrofuran, triturated from ethyl acetate, mp 327-329 ° C orange Amide (258) (47 mg, 59%) was obtained as a colored powder. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.12 (br s, 1H), 9.39 (s, 1H), 8.36 (d, J = 2.4 Hz, 1H), 7.82 ( s, 1H), 7.61 (m, 3H), 7.51 (dd, J = 8.8, 7.4 Hz, 1H), 7.38 (br s, 1H), 7.15 (dd, J = 8.9, 2.4 Hz, 1H), 6.87 (brs, 1H), 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. _{C 23 H 15 Cl 2 N 3} O 4. 3 / 4H ₂ O Calculated: C, 57.33; H, 3.45 ; N, 8.72.

Example 218 3- (4- (2,6-dichlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) -N- [2- (dimethylamino) ethyl] propanamide (XIII; Ar = 2,6- _{^{dichlorophenyl, n = 2, R 3 =}} H, R 4 = CH 2 CH 2 n (CH 3) 2) (259 ) Methyl ether (251) (70 mg, 0.13 mmol)) prepared as described in Example 211 was reacted for 6 hours and chromatographed to obtain ethyl acetate / methanol / triethylamine (1 : 0: 0 → 3: 1: Trace amount), and the amide (259) (31) as a yellow powder having a melting point of 220 to 226 ° C was reacted according to the procedure described in Example 80. mg, 45%). ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.13 (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, 1H), 7.76 (s, 1H), 7.62 (m, 2H), 7.58 (d, J = 8.9 Hz, 1H), 7.51 (dd, J = 8.9, 7.4 Hz, 1H), 7.16 (dd, J = 8.9, 2.5 Hz, 1H), 4.67 (t, J = 6.5 Hz, 2H), 3.03 (M, 2H), 2.57 (t, J = 6.5 Hz, 2H), 2.16 (brs, 2H), 2.08 (m, 6H). Found: C, 58.09; H, 4.44; N, 9.72. _{C 27 H 24 Cl 2 N 4} O 4. Of H ₂ O Calculated: C, 58.18; H, 4.70 ; N, 10.05.

Example 219 3- (4- (2-Chloro-6-methoxyphenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1H) -Yl) -N- [2- (dimethylamino) ethyl] propanamide (XIII; Ar = 2-chloro-6-methoxyphenyl, n = 2, R ³ = H, R ⁴ = CH ₂ CH ₂ N (CH ₃ ) Preparation of ₂ ) (260) Methyl ether (252) (80 mg, 0.15 mmol) prepared as described in Example 212 was described in Example 80 except that the reaction was performed at 0 ° C. for 2 hours. React by the procedure and chromatograph and elute with ethyl acetate / methanol / triethylamine (1: 0: 0 → 3: 1: trace) to obtain a yellow / orange powder with a melting point of 200-205 ° C. To give amide (260) (65 mg, 83%). ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.00 (br s, 1H), 9.34 (s, 1H), 8.36 (d, J = 2.4 Hz, 1H), 7.87 ( br s, 1H), 7.66 (s, 1H), 7.54 (d, J = 8.9 Hz, 1H), 7.44 (t, J = 8.2 Hz, 1H), 7.18 (dd , J = 8.2, 0.7 Hz, 1H), 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 (v br s, 2H), 2.15 (br s, 6H). Found: C, 58.98; H, 5.12; N, 9.59. _{C 28 H 27 ClN 4 O 5} . 2H ₂ O Calculated: C, 58.90; H, 5.47 ; N, 9.81.

Example 220 N- [2- (dimethylamino) ethyl] -3- (9-hydroxy-4- (2-methoxyphenyl) -1,3-dioxo-2,3-dihydropyrrolo [3,4 c] Carbazol-6 (1H) -yl) propanamide (XIII; Ar = 2-methoxyphenyl, n = 2, R ³ = H, R ⁴ = CH ₂ CH ₂ N (CH ₃ ) ₂ ) (330) Preparation To a solution of 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 (catalyst). The resulting suspension was hydrogenated with stirring at 410 kPa (60 psi) for 4 days and additional Pd-C was added every 24 hours. The reaction mixture was then filtered through celite, concentrated in vacuo, chromatographed on silica, eluting with methanol / ethyl acetate / triethylamine (1: 4: trace) to give the amide as a yellow powder with a melting point of 232-238 ° C. (330) (6 mg, 16%) was obtained. ¹ H NMR δ [(CD ₃ ) ₂ SO] 10.95 (br s, 1 H), 9.33 (br s, 1 H), 8.37 (d, J = 2.4 Hz, 1 H), 8.01 (Br s, 1H), 7.69 (s, 1H), 7.54 (d, J = 8.9 Hz, 1H), 7.43 (m, 1H), 7.34 (dd, J = 7. 5,1.8 Hz, 1H), 7.13 to 7.05 (m, 3H), 4.67 (t, J = 6.2 Hz, 2H), 3.69 (s, 3H), to 3.2 (Unclear m, 2H), 2.60 (t, J = 6.2 Hz, 2H), 2.54 to 2.49 (Unclear m, 8H). Calculated value of FABMS [M + H] ⁺ : 501.2142. Calcd 501.2138 for _{C 28 H 28 N 4 O 5} .

Example 221 3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) -N Preparation of-(1H-tetraazol-5-yl) propanamide (XIII; Ar = 2-chlorophenyl, n = 2, R ³ = H, R ⁴ = 5-tetrazolyl) (261) As described in Example 213 The procedure described in Example 80, except that methyl ether (253) (40 mg, 0.08 mmol)) prepared in 1 was chromatographed and eluted with ethyl acetate / methanol (1: 0 → 9: 1). To give amide (261) (11 mg, 27%) as an orange powder with a melting point of 283 ° C. ¹ H NMR δ [(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, 1H), 7.79 (s, 1H), 7.62 (d, J = 8.8 Hz, 1H), 7.56 (d, J = 7.6 Hz) , 1H), 7.49-7.38 (m, 3H), 7.13 (dd, J = 8.8, 2.3 Hz, 1H), 4.80 (t, J = 6.7 Hz, 2H) 2.96 (t, J = 6.7 Hz, 2H). Calculated value of FABMS M ^<+> : 501.0955, 503.0956. Calculated 501.0952,503.0923 of _{C 24 H 16 ClN 7 O 4} .

  Representative Procedure for Method 15 of Scheme 4

Example 222 N- [3- (4- (2-chlorophenyl) -9-methoxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl ) Propanoyl] Preparation of Methanesulfonamide (XII; Ar = 2-chlorophenyl, n = 2, R ³ = CH ₃ ) (265) Acid (116) prepared as described in Example 229 (0.20 g, 0 .45 mmol), 4-dimethylaminopyridine (DMAP) (165 mg, 1.35 mmol) and methanesulfonamide (86 mg, 0.90 mmol) in dimethylformamide (10 mL) to a stirred solution of 1- (3-dimethylaminopropyl hydrochloride) -3-Ethylcarbodiimide (EDCI.HCl) (259 mg, 1.35 mmol) was added under nitrogen. The resulting mixture was stirred at room temperature for 18 hours, then diluted with water, acidified with 1N hydrochloric acid and extracted with ethyl acetate. The organic phase was dehydrated, the dehydrating agent was removed, and the solution was concentrated to dryness. Chromatography on silica, eluting with ethyl acetate / hexane (4: 1) and then ethyl acetate / methanol (1: 0 → 9: 1) to give acylsulfonamide as a yellow powder with a melting point of 293-295 ° C. (265) (151 mg, 64%) was obtained. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.76 (br s, 1H), 11.14 (br s, 1H), 8.52 (d, J = 2.6 Hz, 1H), 7.87 (S, 1H), 7.73 (d, J = 9.0 Hz, 1H), 7.58 (m, 1H), 7.53 to 7.46 (m, 3H), 7.32 (dd, J = 9.0, 2.6 Hz, 1H), 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. Calculated for _{C 25 H 20 ClN 3 O 6} S: C, 57.08; H, 3.83; N, 7.99.

Example 223 N- [3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl ) Propanoyl] Preparation of benzenesulfonamide (XIV: Ar = 2-chlorophenyl, n = 2, R ³ = Ph) (266) Acid (116) prepared as described in Example 229 (70 mg, 0.16 mmol) Is reacted with benzenesulfonamide by the procedure described in Example 222, followed by demethylation using the procedure described in Example 80, chromatographed on silica, ethyl acetate / hexane (1: 1 → 3: 1) to give acylsulfonamide (266) (63 mg, 70%) as an orange powder with a melting point of 291-293 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 12.15 (br s, 1 H), 11.07 (br s, 1 H), 9.36 (s, 1 H), 8.35 (d, J = 2) .4 Hz, 1H), 7.81 (m, 2H), 7.76 (s, 1H), 7.65 (m, 1H), 7.57-7.46 (m, 7H), 7.06 ( dd, J = 8.9, 2.4 Hz, 1H), 4.59 (m, 2H), 2.75 (t, J = 7.1 Hz, 2H). Found: C, 60.62; H, 3.80; N, 7.20. Calculated for _{C 29 H 20 ClN 3 O 6} S: C, 60.68; H, 3.51; N, 7.32.

Example 224 N- [3- (4- (2-chlorophenyl) -9-methoxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl ) Propanoyl] -2- (dimethylamino) ethanesulfonamide (XII; Ar = 2-chlorophenyl, n = 2, R ³ ═CH ₂ CH ₂ N (CH ₃ ) ₂ ) (267) described in Example 229 The acid (116) prepared as above (70 mg, 0.16 mmol) was prepared according to the procedure described in Example 222 except that the reaction mixture was diluted with brine followed by extraction with ethyl acetate. Reacted with ethanesulfonamide. The organic phase is dehydrated, the dehydrating agent is removed, the solution is concentrated to dryness, chromatographed and eluted with ethyl acetate / methanol (1: 0 → 4: 1), mp 208-213. Acylsulfonamide (267) (43 mg, 47%) was obtained as a yellow powder at 0 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.11 (br s, 1 H), 8.52 (d, J = 2.6 Hz, 1 H), 7.80 (s, 1 H), 7.72 ( d, J = 9.0 Hz, 1H), 7.57 (m, 2H), 7.47 (m, 2H), 7.31 (dd, J = 9.0, 2.6 Hz, 1H), 4. 68 (m, 2H), 3.90 (s, 3H), 3.23 (partly unclear m, 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. _{C 28 H 27 ClN 4 O 6} S. Calculated _{1 / 2C 6 H 14: C} , 59.47; H, 5.47; N, 8.95.

Example 225 N- [4- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl ) Butanoyl] methanesulfonamide (XIV; Ar = 2-chlorophenyl, n = 3, R ³ = CH ₃ ) (268) Preparation of acid (262) prepared as described in Example 87 (50 mg, 0.11 mmol) ) Is reacted by the procedure described in Example 222, followed by demethylation using the procedure described in Example 80, chromatographed on silica, ethyl acetate / hexane (1: 1 → 3: Elution with 1) gave acylsulfonamide (268) (29 mg, 51%) as an orange powder with a melting point of 257-260 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.66 (br s, 1 H), 11.06 (br s, 1 H), 9.37 (s, 1 H), 8.38 (d, J = 2) .4 Hz, 1H), 7.79 (s, 1H), 7.61-7.45 (m, 5H), 7.15 (dd, J = 8.8, 2.4 Hz, 1H), 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. Calculated for _{C 25 H 20 ClN 3 O 6} S: C, 57.09; H, 3.83; N, 7.99.

Example 226 N- [4- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl ) Butanoyl] benzenesulfonamide (XIV; Ar = 2-chlorophenyl, n = 3, R ³ = Ph) Preparation of (269) Acid (262) prepared as described in Example 87 (45 mg, 0.10 mmol) Is reacted with benzenesulfonamide by the procedure described in Example 222, followed by demethylation using the procedure described in Example 80, chromatographed on silica, ethyl acetate / hexane (1: 1 → 3: 1) to give acylsulfonamide (269) (39 mg, 68%) as an orange powder with a melting point of 224-230 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 12.09 (br s, 1 H), 11.05 (br s, 1 H), 9.36 (s, 1 H), 8.36 (d, J = 2 .4 Hz, 1H), 7.88 (m, 2H), 7.73 (s, 1H), 7.67 (m, 1H), 7.57 (m, 3H), 7.52 to 7.43 ( m, 4H), 7.09 (dd, J = 8.8, 2.4 Hz, 1H), 4.33 (t, J = 7.3 Hz, 2H), 2.29 (t, J = 7.2 Hz) , 2H), 1.86 (m, 2H). Found: C, 61.10; H, 3.81; N, 6.91. Calculated for _{C 30 H 22 ClN 3 O 6} S: C, 61.28; H, 3.77; N, 7.15.

Example 227 N- [3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl ) Propanoyl] Methanesulfonamide (XIV; Ar = 2-chlorophenyl, n = 2, R ³ = CH ₃ ) (270) Methyl ether (265) prepared as described in Example 222 (130 mg,. 25 mmol) was reacted according to the procedure described in Example 80 except that it was chromatographed and eluted with methanol / dichloromethane (5: 95 → 1: 9) as an orange powder with a melting point of 290-296 ° C. Acylsulfonamide (270) (83 mg, 66%) was obtained. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.75 (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, 2 H), 7.53 to 7.46 (m, 3 H), 7.14 (dd, J = 8.9, 2 .4 Hz, 1H), 4.69 (t, J = 6.9 Hz, 2H), 3.04 (s, 3H), 2.76 (t, J = 6.9 Hz, 2H). Found: C, 54.70; H, 3.81; N, 7.67. _{C 24 H 18 ClN 3 O 6} S. 3 / 4H ₂ O Calculated: C, 54.85; H, 3.74 ; N, 7.99.

Example 228 N- [3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl ) Propanoyl] -2- (dimethylamino) ethanesulfonamide (XIV; Ar = 2-chlorophenyl, n = 2, R ³ ═CH ₂ CH ₂ N (CH ₃ ) ₂ ) (271) described in Example 224 Methyl ether (267) prepared as such (35 mg, 0.06 mmol) was reacted according to the procedure described in Example 81 except that the reaction mixture was diluted with saturated sodium bicarbonate and extracted with ethyl acetate. The organic phase was dehydrated, the dehydrating agent was removed, and the solution was concentrated to dryness. Chromatography on silica eluting with methanol / dichloromethane (1: 9 → 1: 3) gave acylsulfonamide (271) (8 mg, 23%) as an orange powder with a melting point of 229-233 ° C. . ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.05 (br s, 1H), 9.37 (br s, 1H), 8.37 (d, J = 2.5 Hz, 1H), 7.74 (S, 1H), 7.61 to 7.52 (m, 3H), 7.50 to 7.43 (m, 2H), 7.14 (dd, J = 8.7, 2.5 Hz, 1H) 4.63 (m, 2H), 3.21 (partially unclear m, 2H), 2.81 (m, 2H), 2.59 (t, J = 6.8 Hz, 2H), 2 .38 (s, 6H). Calculated value of FABMS [M + H] ⁺ : 569.1255, 571.1204. Calculated 569.1262,571.1232 of _{C 27 H 25 ClN 4 O 6} S.

Example 229 3- (4- (2-chlorophenyl) -9-methoxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) propanoic acid Preparation of (IX; Ar = 2-chlorophenyl, n = 2) (116) Alcohol (31) prepared as described in Example 40 was oxidized using the procedure described in Example 203 to give a melting point of 277 The acid (116) (62%) was obtained as a yellow solid at 0C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 12.61 (br, 1H), 11.12 (s, 1H), 8.52 (d, J = 2.6 Hz, 1H), 7.86 (s) , 1H), 7.73 (d, J = 9.0 Hz, 1H), 7.58 (m, 1H), 7.54 to 7.44 (m, 3H), 7.31 (dd, J = 9 0.0, 2.6 Hz, 1H), 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. _{C 24 H 17 ClN 2 O 5} . Calculated for _1/2 H2O C, 62.96; H, 3.96; N, 6.12.

Example 230 3- (4- (2-Chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) propanoic acid Preparation of (X; Ar = 2-chlorophenyl, n = 2) (117) (116), prepared as described in Example 229, was dehydrated with pyridinium hydrochloride using the procedure described in Example 81. Methylation gave (117) (50%) as a yellow powder with a melting point of 286 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 12.40 (br, 1 H), 11.06 (br s, 1 H), 9.37 (br s, 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 to 7.43 (m, 3 H) ), 7.13 (dd, J = 8.7, 2.4 Hz, 1H), 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. _{C 23 H 15 C1N 2 O 5} . 1.5 H ₂ O Calculated C, 59.81; H, 3.92; N, 6.06.

Example 231 3- (4- (2-chlorophenyl) -9-methoxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) propanamide Preparation of (XI; Ar = 2-chlorophenyl, n = 2, R ³ = R ⁴ = H) (118) The acid (117) prepared as described in Example 230 was prepared using the procedure described in Example 207. Used to react with oxalyl chloride followed by ammonia to give amide (118) (78%) as a yellow powder with a melting point of 283-286 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.12 (br s, 1H), 8.52 (d, J = 2.6 Hz, 1H), 7.82 (s, 1H), 7.71 ( d, J = 9.0 Hz, 1H), 7.58 (m, 1H), 7.54 to 7.44 (m, 3H), 7.35 (br, 1H), 7.31 (dd, J = 9.0, 2.6 Hz, 1H), 6.86 (br, 1H), 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. _{C 24 H 18 ClN 3 O 4} . 1 / 4H ₂ O Calculated C, 63.72; H, 4.12; N, 9.29.

Example 232 3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) propanamide preparation of; (Ar = ^{2-chlorophenyl, n = 2, R 3 =} R 4 = H XIII) (119).
(118), prepared as described in Example 231, was demethylated using BBr ₃ by the procedure described in Example 80 to give (119) (77 %). ¹ H NMR δ [(CD ₃ ) 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, 1H), 7.60 to 7.55 (m, 2H), 7.52 to 7.43 (m, 3H), 7.35 (br, 1H), 7.13 (dd, J = 8 .8, 2.4 Hz, 1H), 6.87 (br, 1H), 4.65 (t, J = 6.7 Hz, 2H), 2.57 (t, J = 6.7 Hz, 2H). Calculated for FABMS M ⁺ : 435.0833, 433.0828. Calculated 435.0800,433.0829 of _{C 23 H 16 ClN 3 O 4} .

Example 233 3- (4- (2-chlorophenyl) -9-methoxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) -N -[2- (4-morpholinyl) ethyl] propanamide (XI; Ar = 2-chlorophenyl, n = 2, R ³ = H, R ⁴ = CH ₂ CH ₂ N (CH ₂ CH ₂ ) ₂ O) (120 The acid (117) prepared as described in Example 230 is reacted with oxalyl chloride using the procedure described in Example 207 followed by N- (2-aminoethyl) morpholine, mp 174 The amide (120) (73%) was obtained as a yellow powder at ˜176 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.12 (br s, 1 H), 8.51 (d, J = 2.6 Hz, 1 H), 7.77 (s, 1 H), 7.74 ( t, J = 5.6 Hz, 1H), 7.68 (d, J = 9.0 Hz, 1H), 7.58 (m, 1H), 7.53 to 7.44 (m, 3H), 7. 31 (dd, J = 9.0, 2.6 Hz, 1H), 4.71 (t, J = 6.3 Hz, 2H), 3.90 (s, 3H), 3.40 (t, J = 4) .6 Hz, 4H), 2.97 (m, 1H), 2.58 (t, J = 6.3 Hz, 2H), 2.11 (br t, J = 4.6 Hz, 4H), 2.00 ( t, J = 6.7 Hz, 2H). Found: C, 60.46; H, 5.26; N, 9.27. _{C 30 H 29 ClN 4 O 5} . 2H ₂ O Calculated C, 60.35; H, 5.94; N, 9.38.

Example 234 3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) -N -[2- (4-morpholinyl) ethyl] propanamide (XIII; Ar = 2-chlorophenyl, n = 2, R ³ = H, R ⁴ = CH ₂ CH ₂ N (CH ₂ CH ₂ ) ₂ O) (121 (120), prepared as described in Example 233, was demethylated using BBr ₃ by the procedure described in Example 80 except that the reaction time was 16 hours, melting point 143-148 ° C. (121) (64%) was obtained as a yellow powder. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.05 (s, 1H), 9.35 (s, 1H), 8.36 (d, J = 2.4 Hz, 1H), 7.74 (t , J = 5.6 Hz, 1H), 7.71 (s, 1H), 7.60-7.55 (m, 2H), 7.52-7.43 (m, 3H), 7.13 (dd , J = 8.8, 2.4 Hz, 1H), 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, 1H). Found: C, 62.37; H, 4.99; N, 9.82. _{C 29 H 27 ClN 4 O 5} . Calculated for _1/2 H2O C, 62.64; H, 5.08; N, 1.0.08.

Example 235 3- (4- (2-chlorophenyl) -9-methoxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) -N -[2- (Dimethylamino) ethyl] -N-methylpropanamide (XI; Ar = 2-chlorophenyl, n = 2, R ³ = CH ₃ , R ⁴ = CH ₂ CH ₂ N (CH ₃ ) ₂ (122 The acid (117) prepared as described in Example 230 was reacted with oxalyl chloride using the procedure described in Example 207 followed by N, N, N′-trimethylethylenediamine to give a melting point of 146 Amide (122) (77%) was obtained as a yellow powder at ˜152 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.10 (br, 1H), 8.51 (d, J = 2. 6Hz, 1H), 7.8 (S, 0.5H), 7.79 (s, 0.5H), 7.72 (m, 1H), 7.58 (m, 1H), 7.54-7.43 (m, 3H), 7.31 (m, 1H), 4.72 (m, 2H), 3.90 (s, 1H), 3.25 (m, 1H), 3.09 (m, 1H), 2.83 (m , 2H), 2.72 (s, 1.5H), 2.71 (s, 1.5H), 2.13 (t, J = 4.8 Hz, 1H), 2.05 (s, 3H), 2.00 (t, J = 4.8 Hz, 1H), 1.88 (s, 3H) Measured values: C, 63.42; H, 5.46; N, 10.15, C ₂₉ H ₂₉ ClN Calculated for ₄ O ₄ .H ₂ O C, 63.21; H, 5.67; N, 10.17.

Example 236 3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) -N -[2- (Dimethylamino) ethyl] -N-methylpropanamide (XIII; Ar = 2-chlorophenyl, n = 2, R ³ = CH ₃ , R ⁴ = CH ₂ CH ₂ N (CH ₃ ) ₂ (123 (122), prepared as described in Example 236, was demethylated with BBr ₃ by the procedure described in Example 80 except that the reaction time was 48 hours, mp 184-188 ° C. (123) (58%) was obtained as a yellow powder of ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.06 (br s, 1H), 9.36 (br s, 1H), 8.37. (D, J = 2.4 Hz, 1 H), 7.78 (s, 0.5H), 7.74 (s, 0.5H), 7.62 to 7.54 (m, 2H), 7.53 to 7.42 (m, 3H) 7.14 (dd, J = 8.8, 2.4 Hz, 1H), 4.69 (m, 2H), 3.22 (m, 1H), 3.09 (m, 1H), 2.82 (M, 2H), 2.72 (s, 1.5H), 2.71 (s, 1.5H), 2.14 (t, J = 4.8 Hz, 1H), 2.06 (s, 3H) .), 2.00 (t, J = 4.8Hz, 1H), 1.88 (s, 3H) Found: C, 62.23; H, 5.23 ; N, 10.24.C 28 H ₂₇ ClN ₄ O ₄ .1.25H ₂ O calculated C, 62.10; H, 5.49; N, 10.35.

Example 237 3- (4- (2-chlorophenyl) -9-methoxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) -N - (2,2,6,6-tetramethyl-4-piperidinyl) propanamide (XI; Ar = ^{2-chlorophenyl, n = 2, R 3 =} H, R 4 = 2,2,6,6- tetramethyl Preparation of -4-piperidinyl) (124) The acid (117) prepared as described in Example 230 was prepared using the procedure described in Example 207 followed by oxalyl chloride followed by 4-amino- (2,2, Reaction with 6,6-tetramethyl) piperidine gave amide (124) (72%) as a yellow powder with a melting point of 155-160 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.12 (br, 1H), 8.51 (d, J = 2.6 Hz, 1H), 7.78 (s, 1H), 7.67 (d , J = 9.0 Hz, 1H), 7.59-7.44 (m, 6H), 7.31 (dd, J = 9.0, 2.6 Hz, 1H), 4.71 (m, 2H) 3.90 (s, 3H), 3.82 (m, 1H), 2.52 (t, J = 6.2 Hz, 2H), 1.26 (m, 1H), 1.10 (m, 1H) ), 1.03 (s, 3H), 1.02 (s, 3H), 0.91 (s, 3H), 0.96 (s, 3H), 0.64 (t, J = 12.3 Hz, 1H), 0.53 (t, J = 12.3 Hz, 1H). Found: C, 64.37; H, 5.97; N, 9.20. _{C 33 H 35 ClN 4 O 4} . 1.5 H ₂ O Calculated C, 64.54; H, 6.24; N, 9.12.

Example 238 3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -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-piperidinyl) (prepared as described in Preparative example 237 125) (124), except the reaction time was 48 hours demethylated using BBr ₃ by the procedure described in example 80 (125) (47%) was obtained as a yellow powder having a melting point of 293-299 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.08 (br s, 1 H), 9.38 (br s, 1 H), 8.72 (br, 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, 5 H), 7.14 (dd, J = 8.8, 2.4 Hz, 1H), 4.70 (t, J = 5.8 Hz, 2H), 3.90 (m, 1H), 2.54 (t, J = 5.8 Hz, 2H) , 1.45 to 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. _{C 32 H 33 ClN 4 O 4} . 1.25CH ₂ of Cl ₂ Calculated C, 58.79; H, 5.27; N, 8.25.

Example 239 4- (2-chlorophenyl) -6- {3- [cis-3,5-dimethylpiperazinyl] -3-oxopropyl} -9-methoxypyrrolo [3,4-c] carbazole- Preparation of 1,3 (2H, 6H) -dione (XI; Ar = 2-chlorophenyl, n = 2, R ³ R ⁴ = cis-3,5-dimethylpiperazinyl) (126) described in Example 230 The acid (117) prepared in this manner was reacted with oxalyl chloride followed by cis-2,6-dimethylpiperazine using the procedure described in Example 207 to give the amide (126) as a yellow powder with a melting point of 168-173 ° C. ) (76%). ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.13 (br, 1H), 8.52 (d, J = 2.6 Hz, 1H), 7.80 (s, 0.5H), 7.76 (S, 0.5H), 7.71 (m, 1H), 7.58 (m, 1H), 7.54 to 7.43 (m, 3H), 7.31 (dd, J = 9.0) , 2.6 Hz, 1H), 4.71 (m, 2H), 4.17 (m, 1H), 3.89 (s, 3H), 2.94 (m, 1H), 2.75 (m, 1H), 2.23 (m, 1H), 2.08 (m, 1H), 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. _{C 30 H 29 ClN 4 O 4} . Of H ₂ O Calcd C, 64.00; H, 5.55; N, 9.95.

Example 240 4- (2-chlorophenyl) -6- {3-[(3R, 5S) -3,5-dimethylpiperazinyl] -3-oxopropyl} -9-hydroxypyrrolo [3,4 c] Preparation of Carbazole-1,3 (2H, 6H) -dione (XIII; Ar = 2-chlorophenyl, n = 2, R ³ R ⁴ = cis-3,5-dimethylpiperazinyl) (127) Example (126), prepared as described in 239, was demethylated with BBr ₃ according to the procedure described in Example 80, except that the reaction time was 48 hours, as a yellow powder with a melting point of 220-224 ° C. ( 127) (38%). ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.07 (br s, 1 H), 9.36 (br s, 1 H), 8.72 (br, 1 H), 8.34 (br, 1 H), 7.72 (s, 0.5H), 7.71 (s, 0.5H), 7.60 to 7.54 (m, 2H), 7.52 to 7.43 (m, 3H), 7. 13 (dd, J = 8.8, 2.4 Hz, 1H), 4.68 (m, 3H), 4.15, 4.12 (2s, 2H), 2.94 (m, 1H), 2. 72 (m, 1H), 2.19 (m, 1H), 2.00 (m, 1H), 1.84 (m, 1H), 0.86, 0.84 (2d, J = 5.8 Hz, 3H), 0.64 (2d, J = 6.1 Hz, 3H). Found: C, 63.38; H, 5.38; N, 9.96. _{C 29 H 27 ClN 4 O 4} . Of H ₂ O Calcd C, 63.44; H, 5.32; N, 10.20.

Example 241 3- (4- (2-chlorophenyl) -9-methoxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) -N -[2- (1H-imidazol-5-yl) ethyl] propanamide (XI; Ar = 2-chlorophenyl, n = 2, R ³ = H, R ⁴ = (1H-imidazol-5-yl) ethyl) ( 128) The acid (117) prepared as described in Example 230 was reacted with oxalyl chloride using the procedure described in Example 207 followed by histamine as a yellow powder with a melting point of 144-149 ° C. Amide (128) (81%) was obtained. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.12 (br, 1H), 8.52 (d, J = 2.6 Hz, 1H), 7.91 (t, J = 5.5 Hz, 1H) 7.76 (s, 1H), 7.69 (d, J = 9.0 Hz, 1H), 7.58 (m, 1H), 7.52 to 7.42 (m, 4H), 7.32 (Dd, J = 9.0, 2.6 Hz, 1H), 6.56 (s, 1H), 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, 60.73; H, 4.49; N, 11.49. _{C 29 H 24 ClN 5 O 4} . 1 / _2CH 2 of Cl ₂ Calculated C, 60.62; H, 4.31; N, 11.98.

Example 242 3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) -N -[2- (1H-imidazol-5-yl) ethyl] propanamide (XIII; Ar = 2-chlorophenyl, n = 2, R ³ = H, R ⁴ = (1H-imidazol-5-yl) ethyl) ( 129) was prepared as described in Example 241 (128) was demethylated with BBr ₃ by the procedure described in Example 80 except that the reaction time was 48 hours, mp 158-162. (129) (46%) was obtained as a yellow powder at 0C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.75 (br, 1H), 11.05 (br s, 1H), 9.36 (br s, 1H), 8.37 (d, J = 2) .4 Hz, 1H), 7.91 (t, J = 5.3 Hz, 1H), 7.71 (s, 1H), 7.59-7.54 (m, 2H), 7.50-7.42. (M, 4H), 7.14 (dd, J = 8.8, 2.4 Hz, 1H), 6.57 (br, 1H), 4.65 (t, J = 6.5 Hz, 2H), 3 .13 (m, 2H), 2.55 (t, J = 6.5 Hz, 1H), 2.40 (t, J = 6.5 Hz, 1H). Calculated value of FABMS [M + H] ⁺ : 530.1431, 528.1440. Calculated 530.1409,528.1439 of _{C 28 H 23 ClN 5 O 4} .

  Scheme 5 procedure

  Representative Procedure for Method 16 of Scheme 5

Example 243 1,9-dihydroxy-4-phenyl-1,6-dihydropyrrolo [3,4-c] carbazol-3 (2H) -one (XV; Ar = phenyl, R ¹⁰ = H) (133) ) And 3,9-dihydroxy-4-phenyl-3,6-dihydropyrrolo [3,4-c] carbazol-1 (2H) -one (XVI; Ar = phenyl, R ¹⁰ = H) (134) .
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). Sodium borohydride (0.24 g 4 times, total 0.025 mol) was added over 5 hours and the solution was left overnight. Further, sodium borohydride was added four times at 1 hour intervals, and the solution was diluted with water and extracted with ethyl acetate. The organic phase was dehydrated, the dehydrating agent was removed, the solution was concentrated to dryness and chromatographed on silica. Elute starting material (12 mg) with ethyl acetate / petroleum ether (2: 1) followed by elution of creamy powdered 3-hydroxy compound (134) (0.07 g, 14%) with a melting point of 300-310 ° C. It was. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.26 (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 (br d, J = 7.0 Hz, 2 H), 7.53 (s, 1 H), 7.49 to 7.31 (m, 4 H), 6.96 (dd, J = 8.7, 2.3 Hz, 1H), 6.25 (d, J = 9.7 Hz, 1H), 5.87 (d, J = 9.7 Hz, 1H). Found: C, 71.77; H, 4.47; N, 8.14. _{C 20 H 13 N 2 O 3} . 1 / 4H ₂ O Calculated C, 71.95; H, 4.08; N, 8.39.

Elution with ethyl acetate gave a mixed fraction (0.014 g) of (134) and (133), followed by pure 1-hydroxy compound (133) (0. 32 g, 64%). ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.38 (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, 2 H), 7.47-7.35 (m, 4 H), 7.32 (s, 1 H), 6.98 (Dd, J = 8.6, 2.2 Hz, 1H), 6.38 (d, J = 10.3 Hz, 1H), 6.20 (d, J = 10.3 Hz, 1H). Found: C; 68.77; H, 4.66; N, 7.87. _{C 20 H 13 N 2 O 3} . Of H ₂ O Calcd C, 69.15; H, 4.35; N, 8.06.

Example 244 9-Hydroxy-1-methoxy-4-phenyl-1,6-dihydropyrrolo [3,4-c] carbazol-3 (2H) -one (XVII; Ar = phenyl, R ¹⁰ = H) Preparation of (135).
A solution of (133) (0.050 g, 0.16 mmol) and p-toluenesulfonic acid (15 mg), prepared as described in Example 243, in methanol (5 mL) was stirred at room temperature for 30 minutes and then saturated NaHCO 3. ₃ poured into aqueous solution. The mixture was extracted with ethyl acetate. The organic phase was dehydrated, the dehydrating agent was removed, and the solution was concentrated to dryness to give (135). This crystallized from ethyl acetate / petroleum ether as a white solid (0.041 g, 74%) with a melting point of 290-300 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.47 (br s, 1 H), 9.15 (br s, 1 H), 8.75 (s, 1 H), 7.57 to 7.53 (m 3H), 7.44-7.37 (m, 4H), 7.36 (s, 1H), 7.09 (dd, J = 8.7, 2.4 Hz, 1H), 6.26 (s). , 1H), 3.25 (s, 3H). Found: C, 71.34; H, 4.79; N, 7.84. _{C 21 H 15 N 2 O 3} . Calculated for _1/2 H2O C, 71.58; H, 4.57; N, 7.95.

(Example 245) 9-hydroxy-4-phenyl-1,6-dihydro-pyrrolo [3,4-c] carbazole -3 (2H) - on (XVIII, Ar = ^phenyl, R 10 = H) of (136) Preparation.
A solution of (133) (0.20 g, 0.605 mmol), prepared as described in Example 243, in tetrahydrofuran (30 mL) was added to p-toluenesulfonic acid (23 mg, 0.121 mmol) followed by PhSeH (1.48 mL). 4.24 mmol) was added and the solution was stirred at room temperature for 1 hour. After dilution with water, the mixture was extracted with ethyl acetate and the extract was washed with aqueous NaHCO ₃ solution. The organic phase was dehydrated, the dehydrating agent was removed, the solution was concentrated to dryness and chromatographed on silica. Elution with ethyl acetate / petroleum ether (1: 1) followed by ethyl acetate followed by ethyl acetate / methanol (95: 5) gave (136) (0.174 g, 91%) as a white powder, mp 270-280 ° C. ) ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.41 (br s, 1 H), 9.13 (br s, 1 H), 8.27 (br s, 1 H), 7.60 to 7.52 ( m, 2H), 7.47-7.36 (m, 4H), 7.34-7.31 (m, 1H), 7.30 (s, 1H), 6.99 (dd, J = 8. 6, 2, 2 Hz, 1H), 4.78 (brs, 2H). Found: C, 75.19; H, 4.88 ; N, 8.37: C 20 H 14 N 2 O 2. 1 / 4H ₂ O Calculated C, 75.34; H, 4.58; N, 8.78.

Example 246 4- (2-chlorophenyl) -1,9-dihydroxy-6- (3-hydroxypropyl) -1,6-dihydropyrrolo [3,4-c] carbazol-3 (2H) -one ( XV; Ar = ^{_{2-chlorophenyl, R 10 = CH 2 CH 2}} CH 2 OH) (137) and 4- (2-chlorophenyl) -3,9-dihydroxy-6 (3-hydroxypropyl) -3,6 dihydro-pyrrolo [3,4-c] carbazole -1 (2H) - one; preparation of (XVI Ar = ^{_{2-chlorophenyl, R 10 = CH 2 CH 2}} CH 2 OH) (138).
Alcohol (34) prepared as described in Example 243 is reduced with sodium borohydride using the procedure described in the procedure described in Scheme 5 of Example 243, followed by the product on silica. Chromatography first gave the 3-hydroxy compound (138) (11%) as a cream powder with a melting point of 160-164 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 9.08 (br s, 1 H), 8.84 (s, 1 H), 8.54 (d, J = 2.5 Hz, 1 H), 7.62 to 7.36 (m, 6H), 7.03 (dd, J = 8.7, 2.5 Hz, 1H), 5.92 (br, 1H), 5.81 (br, 1H), 4.58 ( t, J = 5.0 Hz, 1H), 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. _{C 23 H 19 ClN 2 O 4} . 1 / 4H ₂ O Calculated C, 64.64; H, 4.60; N, 6.55. Subsequently, (137) (67%) was obtained as a cream powder having a melting point of 240 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 9.18 (br s, 1 H), 8.53 (br s, 1 H), 7.76 (m, 1 H), 7.50 (m, 2 H), 7.43-7.35 (m, 3H), 7.40 (s, 1H), 7.04 (dd, J = 8.7, 2.3 Hz, 1H), 6.52 (d, J = 10 0.0 Hz, 0.5H), 6.40 (d, J = 10.0 Hz, 0.5H), 6.25 (d, J = 10.0 Hz, 0.5H), 6.21 (d, J = 10.0 Hz, 0.5 H), 4.61 (t, J = 4.7 Hz, 1 H), 4.44 (t, J = 6.8 Hz, 2 H), 3.39 (m, 2 H), 1. 88 (m, 2H). Found: C, 65.17; H, 4.80; N, 6.46. Calculated _{C 23 H 19 ClN 2 O 4} C, 65.33; H, 4.53; N, 6.62.

  Procedure of scheme 6

Example 247 Preparation of methyl-2-azido-3- [4 ′-(benzyloxy) -3′-methoxyphenyl] prop-2-enoate (55) 4-Benzyloxy-3-methoxy-benzaldehyde (12 Cold (ice -Salt bath) Added to the sodium methoxide solution over 30 minutes. The reaction mixture was stirred at 0 ° C. for 45 minutes. During this time, a thick creamy precipitate formed which was then left in the freezer overnight. Ice cold water was added and the precipitate was removed by filtration, dried and methyl-2-azido-3- [4 ′-(benzyloxy) -3′-methoxyphenyl] prop-2-enoate (55) (12) 0.2 g, 73%). This was used in the next step without purification.

Example 248 Preparation of Methyl-6- (benzyloxy) -5-methoxyindole-2-carboxylate (56) Azido cinnamic acid ester (55) prepared as described in Example 247 (12.2 g, 36.0 mmol) in xylene (300 mL) was added dropwise to refluxed xylene (100 mL) over 1.5 hours and the reaction mixture was heated at reflux for an additional 15 minutes, followed by distillation of most of the xylene. Removed. The residue was cooled to room temperature and a fine creamy precipitate of methyl-6- (benzyloxy) -5-methoxyindole-2-carboxylate was formed. This was collected by filtration. Residual xylene was removed from the mother liquor by azeotroping with ethanol, and the residue was recrystallized from ethanol to give further methyl-6- (benzyloxy) -5-methoxyindole-2-carboxylate. The mother liquor was concentrated again and the residue was recrystallized. Methyl-6- (benzyloxy) -5-methoxyindole-2-carboxylate (56) (total 9.9 g, 88%) was used in the next step without purification. Found: C, 69.38; H, 5.54; N, 4.55. Calculated for _{C 18 H 17 NO 4 C,} 69.44; H, 5.50; N, 4.50.

Example 249 Preparation of 6- (benzyloxy) -5-methoxy-1H-indole-2-carbaldehyde (57) Ester (56) prepared as described in Example 248 (1.0 g, 3. A suspension of lithium aluminum hydride (0.150 g, 3.86 mmol) in tetrahydrofuran (10 mL) was added dropwise to a solution of 22 mmol) in tetrahydrofuran (10 mL), and the reaction mixture was stirred at room temperature for 20 minutes. Water (1 mL) was added dropwise, then dilute sodium hydroxide (1 mL) was added and the solution was stirred for 10 minutes, then filtered through celite and concentrated. The resulting yellow oil was dissolved in chloroform (20 mL), then manganese dioxide (2.2 g, 26.0 mmol) was added and the reaction mixture was heated at 50 ° C. for 1 h, then filtered through celite and concentrated. did. The residue was recrystallized from dichloromethane to give 6- (benzyloxy) -5-methoxy-1H-indole-2-carbaldehyde (57) (0.74 g, 82%) as pale yellow needles. Found: C, 72.53; H, 5.42; N, 4.92. Calculated C of _{C 17 H 15 NO 3, 72.58} ; H, 5.37; N, 4.98.

  Representative Procedure for Method 16 of Scheme 6

Example 250 Preparation of 6- (benzyloxy) -5-methoxy-2-[(E) -2-phenylethenyl] -1H-indole (XX, Ar = phenyl) (150) described in Example 249 (57) (0.60 g, 2.14 mmol) and benzyltriphenylphosphonium bromide (1.0 g, 2.35 mmol) in dichloromethane (10 mL) were added to a solution of sodium hydroxide (1.1 mL, 18 mmol). 17M solution was added dropwise. The reaction mixture was stirred at room temperature until all starting material was consumed (30 minutes), then it was diluted with water and extracted with dichloromethane (2 × 40 mL). The combined extracts were dried and concentrated to give 6- (benzyloxy) -5-methoxy-2-[(E) -2-phenylethenyl] -1H-indole and 6- (benzyloxy) -5-methoxy. An approximately 1: 1 mixture of -2-[(Z) -2-phenylethenyl] -1H-indole (0.75 g, 99%) was obtained. Recrystallization from dichloromethane gave the clean E-isomer (150), mp 140-145 ° C. (softening), 158-162 ° C. (molten). ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.08 (s, 1H), 7.52 to 7.47 (m, 4H), 7.42 to 7.31 (m, 5H), 7.25 To 7.15 (m, 2H), 7.05 to 7.01 (m, 2H), 6.91 (s, 1H), 6.45 (s, 1H), 5.12 (s, 2H), 3.78 (s, 3H). Found: C, 80.84; H, 6.11; N, 3.04. Calculated _{C 24 H 21 NO 2: C} , 81.10; H, 5.96; N, 3.94.

Example 251 6- (Benzyloxy) -5-methoxy-1-methyl-2-[(E) -2-phenylethenyl] -1H-indole (XXI; Ar = phenyl, R ¹⁰ = Me) ( 151) (150), prepared as described in Example 250, was reacted with sodium hydride followed by iodomethane using the procedure described in Method 3 to give (151) (melting point 142-145 ° C.) 100%). ¹ H NMR δ [(CD ₃ ) ₂ SO] 7.51 to 7.46 (m, 4H), 7.40 to 7.34 (m, 6H), 7.31 to 7.23 (m, 2H) 7.09-7.05 (m, 2H), 7.30 (s, 1H), 5.21 (s, 2H), 3.93 (s, 3H), 3.70 (s, 3H). Found: C, 81.01; H, 6.31; N, 3.79. Calculated for _{C 25 H 23 NO 2: C} , 81.27; H, 6.27; N, 3.79.

Example 252 8- (Benzyloxy) -9-methoxy-6-methyl-4-phenyl-4,5,6,10c-tetrahydropyrrolo [3,4-c] carbazole-1,3 (2H, 3aH Preparation of) -dione (XXII; Ar = phenyl, R ¹⁰ = Me) (152) Prepared as described in Example 251 (151) was reacted with maleimide using the procedure described in Example 69. The adduct (152) was obtained as a yellow solid. This was used without further purification.

Example 253 8- (benzyloxy) -9-methoxy-6-methyl-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (XXIII; Ar = phenyl, Preparation of R ¹⁰ = Me) (153) Crude product (152) prepared as described in Example 252 was aromatized with manganese dioxide by the procedure described in Example 79, mp 263-265 ° C. (153) was obtained as a yellow solid (69% overall from (151). ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.04 (br s, 1H), 8.48 (s, 1H) 7.73 (s, 1H), 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, calcd _{5.95.C 29 H 22 N 2 O 4} : C, 75.31; H, 4.79; N, 6.06.

  Representative Procedure for Method 17 of Scheme 6

Example 254 8-Hydroxy-9-methoxy-6-methyl-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (XXV; Ar = phenyl, R ¹⁰ = Me) Preparation of (154) To a 1: 1 mixture (100 mL) of (153) (1.0 g, 2.16 mmol) in tetrahydrofuran and methanol prepared as described in Example 253, 5% Pd / C ( 200 mg) followed by ammonium formate (1.71 g, 22.0 mmol). The reaction mixture was stirred at room temperature for 2 hours, then filtered through celite and washed 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%), mp 298-301 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.01 (s, 1H), 9.70 (s, 1H), 8.46 (s, 1H), 7.71 (s, 1H), 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. _{C 22 H 16 N 2 O 4} . 1 / 3H ₂ O Calculated: C, 69.83; H, 4.44 ; N, 7.40.

Example 255 Preparation of 6- (Benzyloxy) -2- [2- (2-chlorophenyl) ethenyl] -5-methoxy-1H-indole (XX, Ar = 2-chlorophenyl) (155) The aldehyde (57) prepared as described was reacted with 2′-chlorobenzyltriphenylphosphonium chloride using the procedure described in the procedure described in Example 243 to give a melting point 192 as a mixture of E / Z isomers. A green solid diene of ˜194 ° C. (155) (78%) was obtained. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.25 (s, 1H), 10.70 (s, minor isomer), 7.83 (dd, J = 8.0, 1.4 Hz, 1H) 7.68-7.20 (m), 7.05 (s, 1H), 6.91 (s, 1H), 6.88 (d, J = 2.9 Hz, sub-isomer), 6.64. (D, J = 12.1 Hz, secondary isomer), 6.51 (d, J = 1.4 Hz, 1H), 6.46 (d, J = 12.1 Hz, secondary isomer), 5.89 ( br s, minor isomer), 5.13 (s, 2H), 5.06 (s, minor isomer), 3.78 (s, 3H), 3.71 (s, minor isomer). Found: C, 73.92; H, 5.23; N, 3.63. C ₂₄ H ₁₉ ClNO ₂ Calculated C, 74.13; H, 4.92; N, 3.60.

Example 256 6- (Benzyloxy) -2- [2- (2-chlorophenyl) ethenyl] -5-methoxy-1-methyl-1H-indole (XXI; Ar = 2-chlorophenyl, R ¹⁰ = CH ₃ ) (156).
(155) prepared as described in Example 255 was alkylated with sodium hydride and iodomethane by the procedure described in Method 3 to give (156) (100%) as a yellow solid, mp 143-145 ° C. (Mixture of E / Z isomers) was obtained. ¹ H NMR δ [(CD ₃ ) ₂ SO] 7.98 (dd, J = 7.9, 1.5 Hz, 1H), 7.55 to 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), 3.64 (s). Found: C, 74.04; H, 5.71; N, 3.49. C ₂₅ H ₂₂ ClNO ₂ Calculated C, 74.34; H, 5.49; N, 3.47.

Example 257 8- (benzyloxy) -4- (2-chlorophenyl) -9-methoxy-6-methyl-4,5,6,10c-tetrahydropyrrolo [3,4-c] carbazole-1,3 preparation of; (Ar = _{^{2-chlorophenyl, R 10 = CH 3 XXII)}} (157) - (2H, 3aH) dione.
The diene (156) prepared as described in Example 256 is reacted with maleimide using the procedure described in Example 69 to give the adduct (157) (98%) as a creamy powder with a melting point of 174 ° C. Obtained. This was used without further purification. Found: C, 68.32; H, 4.94; N, 5.51. _{C 29 H 24 ClN 2 O 4} 1 / 2H 2 O Calculated C, 68.43; H, 4.95; N, 5.50.

Example 258 8- (Benzyloxy) -4- (2-chlorophenyl) -9-methoxy-6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (XXIII) ( 158).
(157), prepared as described in Example 257, was aromatized with manganese dioxide by the procedure described in Example 79 to give carbazole (158) (75%) as a yellow powder with a melting point of 282-285 ° C. Got. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.05 (s, 1H), 8.48 (s, 1H), 7.74 (s, 1H), 7.59 to 7.54 (m, 3H) ), 7.52 to 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. Calculated C of _{C 29 H 21 ClN 2 O 4} , 70.09; H, 4.26; N, 5.64.

Example 259 4- (2-chlorophenyl) -8,9-dihydroxy-6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (XXIV; Ar = 2-chlorophenyl, preparation of _{^{R 10 = CH 3) (159}} ).
(158), prepared as described in Example 258, was reacted with pyridinium hydrochloride at 220 ° C. using the procedure described in Example 81 to give (159) (76 as a yellow powder with a melting point of 310-313 ° C. %). ¹ H NMR δ [(CD ₃ ) ₂ SO] 10.95 (s, 1H), 9.57 (br, 1H), 9.18 (br, 1H), 8.32 (s, 1H), 7. 64 (s, 1H), 7.56 (dd, J = 8.1, 2.2 Hz, 1H), 7.50-7.41 (m, 4H), 7.02 (s, 1H), 3. 84 (s, 3H). Found: C, 64.11; H, 3.96; N, 6.54. _{C 21 H 13 ClN 2 O 4} . 1 / _4CH 3 OH Calculated C, 63.67; H, 3.52; N, 6.98.

  Representative Procedure for Method 18 of Scheme 6

Example 260 4- (2-chlorophenyl) -8-hydroxy-9-methoxy-6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (XXV; Ar = 2 ^{chlorophenyl,} R ₁₀ = CH 3) preparation of (160).
A mixture of (158) (1.30 g, 2.62 mmol), concentrated HCl (40 mL) and acetic acid (65 mL), prepared as described in Example 258, was warmed at 100 ° C. for 2 hours. Water was added and the precipitated product was filtered off and dried. The solid was adsorbed on silica from a tetrahydrofuran solution and chromatographed. Elution with ethyl acetate / petroleum ether (3: 2) gave (160) (1.07 g, 85%). This was crystallized from terahydrofuran / petroleum ether as a green solid with a melting point of 280-285 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.01 (s, 1H), 9.73 (s, 1H), 8.44 (s, 1H), 7.69 (s, 1H), 7. 57 (dd, J = 8.0, 2.2 Hz, 1H), 7.51 to 7.41 (m, 4H), 7.09 (s, 1H), 3.93 (s, 3H), 3. 87 (s, 3H). Found: C, 64.53; H, 3.66; N, 6.27. _{C 22 H 15 ClN 2 O 4} . 1 / 4H ₂ O Calculated C, 64.24; H, 3.80; N, 6.81.

Example 261 8- (Benzyloxy) -4- (2-chlorophenyl) -9-methoxy-4,5,6,10c-tetrahydropyrrolo [3,4-c] carbazole-1,3 (2H, 3aH ) - dione (XXII, Ar = ^{2-chlorophenyl,} R 10 = H) preparation of (161).
The diene (155) prepared as described in Example 255 was reacted with maleimide using the procedure described in Example 69 to give the adduct (161) (87%) as a tan powder. This was used without further purification.

Example 262 8- (Benzyloxy) -4- (2-chlorophenyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (XXIII: Ar = 2- Preparation of chlorophenyl, R ¹⁰ = H) (162).
(161), prepared as described in Example 261, was aromatized with manganese dioxide by the procedure described in Example 79 to give carbazole (162) (93% as an orange powder with a melting point of 260-264 ° C. ) ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.86 (s, 1H), 11.01 (s, 1H), 8.43 (s, 1H), 7.58 to 7.34 (m, 10H) ), 7.26 (s, 1H), 5.26 (s, 2H), 3.91 (s, 3H). Found: C, 69.65; H, 3.84; N, 5.61. Calculated for _{C 28 H 19 ClN 2 O 4} C, 69.64; H, 3.97; N, 5.80.

Example 263 4- (2-chlorophenyl) -8-hydroxy-9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (XXV; Ar = 2-chlorophenyl, R ¹⁰ = H) (163) preparation.
(162), prepared as described in Example 262, was debenzylated using HCl in acetic acid according to the procedure described in Example 260 to give (163) (77%) as a yellow powder with a melting point of 194-196 ° C. ) ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.71 (s, 1 H), 10.97, (br s, 1 H), 9.68 (br s, 1 H), 8.38 (s, 1 H) 7.56 (dd., J = 8.0, 2.2 Hz, 1H), 7.49-7.39 (m, 4H), 7.02 (s, 1H), 3.90 (s, 3H) ). Found: C, 63.38; H, 3.38; N, 6.20. _{C 21 H 13 ClN 2 O 4} . 1/4 H ₂ O Calculated C, 63.49; H, 3.42; N, 7.05.

Example 264 6- (Benzyloxy) -2- (2- (2-chlorophenyl) ethenyl] -5-methoxy-1- (2-methoxyethyl) -1H-indole (XXI; Ar = 2-chlorophenyl) preparation of ^{_{R 10 = CH 2 CH 2 OCH}} 3) (164).
The diene (155) prepared as described in Example 255 was alkylated with sodium hydride and 1-bromo-2-methoxyethane by the procedure described in Method 3 to give (164) ( 91%) (mixture of E / Z isomers). This was used without further purification.

Example 265 8- (Benzyloxy) -4- (2-chlorophenyl) -9-methoxy-6- (2-methoxyethyl) -4,5,6,10c-tetrahydropyrrolo [3,4-c] carbazole -1,3 (2H, 3aH) - dione; preparation of (XXII Ar = ^{_{2-chlorophenyl, R 10 = CH 2 CH 2}} OCH 3) (165).
The diene (164) prepared as described in Example 264 was reacted with maleimide using the procedure described in Example 69 to give the adduct (165) as a tan solid (74%). This was used without further purification.

Example 266 8- (Benzyloxy) -4- (2-chlorophenyl) -9-methoxy-6- (2-methoxyethyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) - dione; preparation of (XXIII Ar = ^{_{2-chlorophenyl, R 10 = CH 2 CH 2}} OCH 3) (166).
(165), prepared as described in Example 265, was aromatized with manganese dioxide by the procedure described in Example 79 to give carbazole (166) (89% as an orange powder with a melting point of 252 ° -254 ° C. ) ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.04 (br s, 1 H), 8.49 (s, 1 H), 7.75 (s, 1 H), 7.59 to 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. C ₃₁ H ₂₅ Calculated _{ClN 2 O 5 C, 68.82;} H, 4.66; N, 5.18.

  Representative Procedure for Method 19 of Scheme 6

Example 267 4- (2-chlorophenyl) -8-hydroxy-9-methoxy-6- (2-methoxyethyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione ( XXV; Ar = ^{_{2-chlorophenyl, R 10 = CH 2 CH 2}} OCH 3) preparation of (167).
Ethanethiol (5 mL) and boron trifluoride etherate (2.5 mL) were added to a solution of benzyl ether (155) (0.840 g, 1.55 mmol) prepared in Example 255 in dichloromethane (100 mL). The solution was stirred at room temperature for 16 hours. Petroleum ether (500 mL) was added and the mixture was cooled at −20 ° C. for 3 hours. The solid was isolated by decanting the liquid layer and partitioned between ethyl acetate and saturated aqueous NaHCO ₃ . The organic phase was dehydrated, the dehydrating agent was removed, and the solution was concentrated to dryness to give an oily solid. This was chromatographed on silica. Elution with ethyl acetate / petroleum ether (1: 2) gave foreruns. On the other hand, (167) (805) eluted with ethyl acetate / petroleum ether (1: 1). It crystallized from ethyl acetate / petroleum ether as a yellow powder with a melting point of 249-252 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 10.98 (br, 1H), 9.70 (br, 1H), 8.44 (s, 1H), 7.70 (s, 1H), 7. 57 (dd, J = 8.0, 2.2 Hz, 1H), 7.50-7.41 (m, 3H), 7.12 (s, 1H), 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 Calculated _{ClN 2 O 5 C, 63.93;} H, 4.25; N, 6.21.

  Procedure of Scheme 7

Example 268 4- (2-chlorophenyl) -9-hydroxy-6- (3-hydroxypropyl) -4,5,6,10c-tetrahydropyrrolo [3,4-c] carbazole-1,3 (2H , 3aH) - dione (XIX; preparation of Ar = ^{_{2-chlorophenyl, R 10 = CH 2 CH 2}} CH 2 OH) (139).
4- (2-Chlorophenyl) -6- (3-hydroxypropyl) -9-methoxy-4,5,6,10c-tetrahydropyrrolo [3,4] prepared by the first step of the procedure described in Example 39 -c] carbazole -1,3 (2H, 3aH) - dione (IV; Ar = 2- ^{_{chlorophenyl, R 10 = CH 2 CH 2}} CH 2 OH) and (30), BBr ₃ by the procedure described in example 80 Was followed by acidification to give (139) (77%) as a pink powder with a melting point of 190-196 ° C. ¹ H NMR δ [(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, 1H), 7.39 (m, 1H), 7.31 (m, 1H), 7.21 (d, J = 8.5 Hz, 1H), 7.15 (d, J = 2.3 Hz, 1H), 6.62 (dd, J = 8.5, 2.3 Hz, 1H), 4.57 (t, J = 4.7 Hz, 1H) ), 4.25 (d, J = 7.5 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), 77 (m, 2H). Found: C, 63.57; H, 5.13; N, 6.31. _{C 23 H 21 ClN 2 O 4} . Calculated for _1/2 H2O C, 63.66; H, 5.11; N, 6.45.

  Procedure of Scheme 8

Example 269 Preparation of 4-methoxy-2- [2-phenylethenyl] -1H-indole (XXVI; Ar = phenyl) (141).
4-Methoxyindole-2-carboxaldehyde was reacted with benzyltriphenylphosphonium bromide by the procedure described in Example 37 to give (141) (89%) of a fluorescent oil (mixture of E / Z isomers). Got. This was used without further purification.

Example 270 10-Methoxy-4-phenyl-4,5,6,10c-tetrahydrocyclopenta [c] carbazole-1,3 (2H, 3aH) -dione (XXVIII; Ar = phenyl, R ¹⁰ = H ) (142).
The diene (141) prepared by the procedure described in Example 269 was reacted with maleimide using the procedure described in Method 4 to give the adduct (142) (86%) as a yellow solid. This was used without further purification.

(Example 271) 10-methoxy-4-phenyl-cyclopenta [c] carbazole-1,3 (2H, 6H) - dione; Preparation of (XXVIX Ar = ^{phenyl, R 10 = H) (143} ).
(142), prepared by the procedure described in Example 270, is aromatized using DDQ by the procedure described in Example 70 to give carbazole (143) (78 %). ¹ H NMR δ [(CD ₃ ) ₂ SO] 12.10 (s, 1H), 10.78 (s, 1H), 7.59 (s, 1H), 7.57 (dd, J = 8.0) , 1.8 Hz, 2H), 7.49 (t, J = 7.9 Hz, 1H), 7.47-7.39 (m, 3H), 7.16 (d, J = 7.9 Hz, 1H) 6.80 (d, J = 7.9 Hz, 1H), 3.99 (s, 3H). Found: C, 73.55; H, 4.16; N, 7.93. C ₂₁ H ₁₄ Calculated _{N 2 O 3 C, 73.67;} H, 4.12; N, 8.18.

Example 272 Preparation of 10-Hydroxy-4-phenylcyclopenta [c] carbazole-1,3 (2H, 6H) -dione (XXX; Ar = phenyl, R ¹⁰ = H) (144) (143) prepared by the procedure described was demethylated with BBr ₃ by the procedure described in Example 80 to give (144) (92%) as a yellow / orange solid with a melting point> 300 ° C. Obtained. ¹ H NMR δ [(CD ₃ ) ₂ SO] 12.33 (s, 1H), 12.16 (s, 1H), 11.65 (br, 1H), 7.62 (s, 1H), 7. 60 (dd, J = 7.9, 1.8 Hz, 2H), 7.51 to 7.45 (m, 3H), 7.40 (dd, J = 7.6 Hz, 1H), 7.03 (d , J = 7.6 Hz, 1H), 6.63 (d, J = 7.6 Hz, 1H). Found: C, 72.87; H, 3.76; N, 8.44. C ₂₀ H ₁₂ Calculated _{N 2 O 3 C, 73.16;} H, 3.68; N, 8.53.

Example 273 Preparation of 6-methoxy-2- [2-phenylethenyl] -1H-indole (XXXI; Ar = phenyl) (146).
6-Methoxyindole-2-carboxaldehyde (145) was reacted with benzyltriphenylphosphonium bromide by the procedure described in Example 37 to give (146) (94 %). This was used without further purification.

Example 274 8-methoxy-4-phenyl-4,5,6,10c-tetrahydrocyclopenta [c] carbazole-1,3 (2H, 3aH) -dione (XXXIII; Ar = phenyl, R ¹⁰ = H ) (147).
The diene (146) prepared by the procedure described in Example 273 was reacted with maleimide using the procedure described in Method 4 to give the adduct (147) (61%) as a tan solid. This was used without further purification.

(Example 275) 8-methoxy-4-phenyl-cyclopenta [c] carbazole-1,3 (2H, 6H) - dione; Preparation of (XXXIV Ar = ^{phenyl, R 10 = H) (148} ).
(147) prepared by the procedure described in Example 274 was aromatized with DDQ by the procedure described in Example 70 to give carbazole (148) (65%) as a yellow powder with a melting point of 154-156 ° C. Got. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.87 (br, 1H), 11.02 (br, 1H), 8.75 (d, J = 8.8 Hz, 1H), 7.61 (dd , J = 8.0, 1.8 Hz, 2H), 7.60 (s, 1H), 7.49-7.40 (m, 3H), 7.10 (d, J = 2.2 Hz, 1H) 6.94 (dd, J = 8.8, 2.2 Hz, 1H), 3.90 (s, 3H). Found: C, 72.49; H, 4.14; N, 8.22. _{C 21 H 14 N 2 O 3} . 1 / 4H ₂ O Calculated C, 72.71; H, 4.21; N, 8.07.

Example 276 Preparation of 8-hydroxy-4-phenylcyclopenta [c] carbazole-1,3 (2H, 6H) -dione (XXXV; Ar = phenyl, R ¹⁰ = H) (149) In Example 276 (148) prepared by the described procedure was demethylated with BBr ₃ by the procedure described in Example 80 to give (149) (74%) as a yellow powder with a melting point> 330 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.75 (br, 1H), 10.96 (br, 1H), 10.56 (br, 1H), 8.66 (d, J = 8.6 Hz) , 1H), 7.60 (dd, J = 8.0, 1.8 Hz, 2H), 7.53 (s, 1H), 7.49 to 7.39 (m, 3H), 6.93 (d , J = 2.1 Hz, 1H), 6.79 (dd, J = 8.6, 2.1 Hz, 1H). Elemental analysis: found: C, 72.36; H, 3.82; N, 8.18. _{C 20 H 12 N 2 O 3} . 1 / 4H ₂ O Calculated C, 72.17; H, 3.78; N, 8.41.

Example 277 Preparation of 2-[(E, Z) -2- (2-chlorophenyl) ethenyl] -6-methoxy-1H-indole (XXXI; Ar = 2-chlorophenyl) (841) 6-Methoxyindole- 2-Carboxaldehyde (145) is reacted with 2-chlorobenzyltriphenylphosphonium chloride according to the procedure described in Example 37 to give yellow solid (841) (93%) as a mixture of E / Z isomers. It was. This was used without further purification.

Example 278 2-[(E, Z) -2- (2-chlorophenyl) ethenyl] -6-methoxy-1-methyl-1H-indole (XXXII; Ar = 2-chlorophenyl, R ¹⁰ = CH ₃ ) Preparation of (842) Alkylation of (841) with iodomethane by the procedure described in Method 3 gave (842) (77%) as a yellow solid. This was used without further purification.

Example 279 4- (2-Chlorophenyl) -8-methoxy-6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (XXXIV; Ar = 2-chlorophenyl, R ¹⁰ = CH ₃ ) (844) Preparation (842), prepared as described in Example 278, was reacted with maleimide using the procedure described in Method 4 of Example 68 to give the adduct as a tan powder ( XXXIII; Ar = 2-chlorophenyl, R ¹⁰ = CH ₃ ) (843) was obtained. This was used without further purification. (843) was aromatized with MnO ₂ by the procedure described in Example 79 to give (844) (78% total) as a yellow powder with a melting point> 300 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.07 (br s, 1H), 8.77 (d, J = 8.7 Hz, 1H), 7.76 (s, 1H), 7.59 ( dd, J = 8.0, 2.2 Hz, 1H), 7.52 to 7.43 (m, 3H), 7.27 (d, J = 2.2 Hz, 1H), 7.00 (dd, J = 8.7, 2.2 Hz, 1H), 3.95 (s, 3H), 3.94 (s, 3H). Found: C, 66.86; H, 4.04; N, 6.90; Cl, 9.26. _{C 22 H 15 ClN 2 O 3} . 0.2 H ₂ O Calculated: C, 66.99; H, 3.94 ; N, 7.10; Cl, 8.99.

Example 280 4- (2-Chlorophenyl) -8-hydroxy-6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (XXXV; Ar = 2-chlorophenyl, R ¹⁰ = _CH 3) (prepared as described in Preparative example 279 845) to (844), and demethylation with BBr ₃ by the procedure described in example 80, melting point 304 to 306 ° C. a yellow solid (845) (54%) was obtained. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.02 (br, 1H), 10.08 (br, 1H), 8.69 (d, J = 8.6 Hz, 1H), 7.71 (s , 1H), 7.58 (m, 1H), 7.51 to 7.42 (m, 3H), 6.99 (d, J = 2.0 Hz, 1H), 6.88 (dd, J = 8 .6, 2.0 Hz, 1H), 3.87 (s, 3H). Found: C, 63.93; H, 3.95; N, 7.08; Cl, 9.12. _{C 21 H 13 ClN 2 O 3} . Of H ₂ O Calculated: C, 63.89; H, 3.83 ; N, 7.10; Cl, 8.98.

  Scheme 9 procedure

Example 281 4- (2-Chlorophenyl) -9-hydroxy-6- [2- (1H-tetraazol-5-yl) ethyl] pyrrolo [3,4-c] carbazole-1,3 (2H, Preparation of 6H) -dione (XXXVI; Ar = 2-chlorophenyl, n = 2) (272) Nitrile (238) (0.68 g, 1.63 mmol) of toluene / dimethylformamide prepared as described in Example 98 To the (5: 1, 120 mL) solution, azidotrimethyltin (0.67 g, 3.26 mmol) was added. The resulting solution was heated at reflux for 24 hours followed by the addition of azidotrimethyltin (0.34 g, 1.63 mmol). After refluxing for a further 24 hours, the reaction was diluted with water and extracted with ethyl acetate. The organic phase was dehydrated, the dehydrating agent was removed, and the solution was concentrated to dryness. Chromatography on silica eluting with ethyl acetate / hexane (3: 1) then ethyl acetate / methanol (9: 1) followed by crystallization from ethyl acetate / hexane, mp 230-234 Tetrazole (272) (0.54 g, 72%) was obtained as an orange powder at 0C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.06 (br s, 1 H), 9.37 (br s, 1 H), 8.36 (d, J = 2.4 Hz, 1 H), 7.61 (S, 1H), 7.56 (m, 1H), 7.48 (m, 4H), 7.10 (dd, J = 8.8, 2.4 Hz, 1H), 4.82 (t, J = 6.9 Hz, 2H), 3.32 (unclear t, J = 6.9 Hz, 2H). Found: C, 52.69; H, 4.05; N, 15.91. _{C 23 H 15 ClN 6 O 3} . Calculated for 3 1/2 H ₂ O: C, 52.93; H, 4.25; N, 16.09.

Example 282 4- (2-chlorophenyl) -9-hydroxy-6- [3- (1H-tetraazol-5-yl) propyl] pyrrolo [3,4-c] carbazole-1,3 (2H, Preparation of 6H) -dione (XXXVI; Ar = 2-chlorophenyl, n = 3) (273) Nitrile (241) (60 mg, 0.14 mmol) prepared as described in Example 191 in toluene / dimethylformamide (5 : 1, 35 mL) solution was added azidotrimethyltin (57 mg, 0.28 mmol). The resulting solution was heated at reflux for 72 hours, then diluted with water and extracted with ethyl acetate. The organic phase was dehydrated, the dehydrating agent was removed, and the solution was concentrated to dryness. Chromatography on silica eluting with ethyl acetate / hexane (3: 1) then ethyl acetate / methanol (9: 1) followed by crystallization from tetrahydrofuran / hexane, mp 269-272 ° C. Of tetrazole (273) (29 mg, 44%) as an orange powder. ¹ H NMR δ [(CD ₃ ) ₂ SO] to 16 (v br s, 1 H), 11.07 (s, 1 H), 9.38 (br s, 1 H), 8.39 (d, J = 2) .5 Hz, 1 H), 7.84 (s, 1 H), 7.61 (d, J = 8.9 Hz, 1 H), 7.57 (m, 1 H), 7.53 to 7.43 (m, 3 H) ), 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. _{C 24 H 17 ClN 6 O 3} . 3 / 4H ₂ O Calculated: C, 59.26; H, 3.83 ; N, 17.27.

Example 283 4- (2-chlorophenyl) -9-methoxy-6- [2- (1H-1,2,4-triazol-5-ylsulfanyl) ethyl] pyrrolo [3,4-c] carbazole- Preparation of 1,3 (2H, 6H) -dione (XXXVII; Ar = 2-chlorophenyl, R ³ = 5-1H-1,2,4-triazolyl) (274) Mesylate prepared as described in Example 170 (228) (0.25 g, 0.50 mmol), 1H-1,2,4-triazole-5-thiol (76 mg, 0.75 mmol) and triethylamine (2.0 mL) in p-dioxane (50 mL) Heat at reflux under nitrogen for 48 hours, then dilute with water and extract with ethyl acetate. The organic phase was dehydrated, the dehydrating agent was removed, and the solution was concentrated to dryness. Chromatography on silica, eluting with ethyl acetate / hexane (1: 1 → 1: 0), followed by crystallization from ethyl acetate / hexane to give carbazole as a yellow powder with a melting point of 211-213 ° C. 274) (0.24 g, 95%). ¹ H NMR δ [(CD ₃ ) ₂ SO] 14.09 (br s, 1 H), 11.13 (br s, 1 H), 8.52 (d, J = 2.6 Hz, 1 H), 8.43 (V br s, 1H), 7.88 (s, 1H), 7.80 (d, J = 9.0 Hz, 1H), 7.57 (m, 1H), 7.48 (m, 3H), 7, 31 (dd, J = 9.0, 2.6 Hz, 1H), 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. _{C 25 H 18 ClN 5 O 3} S. 1 / 4H ₂ O Calculated: C, 59.29; H, 3.68 ; N, 13.82.

Example 284 4- (2-chlorophenyl) -6- [2- (1H-imidazol-2-ylsulfanyl) ethyl] -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) - dione (XXXVII; Ar = ^{2-chlorophenyl,} R 3 = 2-imidazolyl) (275) mesylate, prepared as described in Preparative example 170 (228) (0.30g, 0.60mmol) , 2 -A solution of mercaptoimidazole (0.12 g, 1.20 mmol) and triethylamine (2.0 mL) in p-dioxane (25 mL) was heated at reflux under nitrogen for 24 hours followed by dilution with water to give the crude product. Precipitated. This was collected by filtration, washed with water and dried in vacuo. Chromatography on silica eluting with ethyl acetate / hexane (1: 1) followed by trituration from ethyl acetate to give carbazole (275) (0.29 g, 96%) as a yellow powder with a melting point of 245-247 ° C. Got. ¹ H NMR δ [(CD ₃ ) ₂ SO] 12.24 (br s, 1 H), 11.13 (br s, 1 H), 8.51 (d, J = 2.6 Hz, 1 H), 7.92 (S, 1H), 7.75 (d, J = 9.0 Hz, 1H), 7.58 (m, 1H), 7.48 (m, 3H), 7.29 (dd, J = 9.0) , 2.6 Hz, 1H), 7.00 (v br s, 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. _{C 26 H 19 ClN 4 O 3} S. 1 / 4H ₂ O Calculated: C, 61.53; H, 3.87 ; N, 11.03.

Example 285 4- (2-Chlorophenyl) -9-hydroxy-6- [2- (4H-1,2,4-triazol-3-ylsulfanyl) ethyl] pyrrolo [3,4-c] carbazole- Preparation of 1,3 (2H, 6H) -dione (XXXVIII; Ar = 2-chlorophenyl, R ³ = 5-1H-1,2,4-triazolyl) (276) Methyl prepared as described in Example 283 Ether (274) (0.25 g, 0.50 mmol) was reacted according to the procedure described in Example 80, followed by chromatography on silica with ethyl acetate / tetrahydrofuran (1: 0 → 9: 1 → 1: 1). ) And triturated from methanol to give phenol (276) (0.22 g, 90%) as an orange powder with a melting point of 314-319 ° C. . ¹ H NMR δ [(CD ₃ ) ₂ SO] 14.10 (br s, 1 H), 11.07 (br s, 1 H), 9.39 (s, 1 H), 8.42 (v br s, 1 H ), 8.38 (d, J = 2.3 Hz, 1H), 7.83 (s, 1H), 7.68 (d, J = 8.8 Hz, 1H), 7.57 (m, 1H), 7.48 (m, 3H), 7.13 (dd, J = 8.8, 2.3 Hz, 1H), 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. _{C 24 H 16 ClN 5 O 3} S. 2 / 5CH ₄ O Calculated: C, 58.29; H, 3.53 ; N, 13.93.

Example 286 4- (2-chlorophenyl) -9-hydroxy-6- [2- (1H-imidazol-2-ylsulfanyl) ethyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) - dione (XXXVIII; Ar = ^{2-chlorophenyl,} R 3 = 2-imidazolyl) (277) methyl ether (275, prepared as described in Preparative example 284) (130 mg, a 0.24 mmol), the reaction React by the procedure described in Example 80 except that time is 7 hours, perform chromatography and elute with ethyl acetate / hexane (1: 1 → 3: 1), mp 270-275 ° C. Phenol (277) (97 mg, 83%) was obtained as an orange powder. ¹ H NMR δ [(CD ₃ ) 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, 1H), 7.86 (s, 1H), 7.61 (d, J = 8.9 Hz, 1H), 7.57 (m, 1H), 7.48 (m, 3H), 7 .12 (dd, J = 8.9, 2.4 Hz, 1H), 6.98 (v br s, 2H), 4.74 (t, J = 7.7 Hz, 2H), 3.42 (partial (T, J = 7.7 Hz, 2H). Found: C, 60.87; H, 3.72; N, 11.00. _{C 25 H 17 ClN 4 O 3} S. 1 / 4H ₂ O Calculated: C, 60.85; H, 3.57 ; N, 11.35.

Example 287 4- (2-chlorophenyl) -9-hydroxy-6- [2- (1H-1,2,4-triazol-5-ylsulfinyl) ethyl] pyrrolo [3,4-c] carbazole- Preparation of 1,3 (2H, 6H) -dione (XXXIX; Ar = 2-chlorophenyl, m = 1, R ³ = 5-1H-1,2,4-triazolyl) (278) As described in Example 285 To a solution of carbazole (276) (70 mg, 0.14 mmol) prepared in 1) in tetrahydrofuran (30 mL) containing glacial acetic acid (8 mL) was added 35% hydrogen peroxide (2 mL). The resulting solution was stirred at room temperature for 10 hours, then poured onto solid sodium bicarbonate, diluted with water and extracted with ethyl acetate. The organic phase was dehydrated, the dehydrating agent was removed, and the solution was concentrated to dryness. The combined organic layers were concentrated in vacuo to some extent, then adsorbed directly onto silica, chromatographed, eluting with methanol / dichloromethane (5: 95 → 1: 9). Trituration from diethyl ether gave sulfoxide (278) (29 mg, 41%) as an orange powder with a melting point of 237-242 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 14.7 (v br s, 1 H), 11.09 (br s, 1 H), 9.41 (br s, 1 H), 8.69 (br s, 1H), 8.38 (d, J = 2.3 Hz, 1H), 7.79 (d, J = 9.6 Hz, 1H), 7.60-7.46 (m, 5H), 7.15 ( dd, J = 8.8, 2.3 Hz, 1H), 4.89 (m, 2H), 3.71 (m, 2H). Found: C, 56.85; H, 3.79; N, 13.74. _{C 24 H 16 ClN 5 O 4} S. 1 _/ 5C _{4 H 10} O Calculated: C, 57.20; H, 3.48 ; N, 13.45.

Example 288 4- (2-chlorophenyl) -9-hydroxy-6- [2- (1H-1,2,4-triazol-5-ylsulfonyl) ethyl] pyrrolo [3,4-c] carbazole- Preparation of 1,3 (2H, 6H) -dione (XXXIX; Ar = 2-chlorophenyl, m = 2, R ³ = 5-1H-1,2,4-triazolyl) (279) As described in Example 285 To a solution of carbazole (276) (60 mg, 0.12 mmol) prepared in 1) in tetrahydrofuran (30 mL) containing glacial acetic acid (10 mL) was added 35% hydrogen peroxide (2 mL). The resulting solution was stirred at room temperature for 30 hours, followed by addition of 35% hydrogen peroxide (2 mL) and the temperature was raised to 50 ° C. for 18 hours. The reaction was then poured onto solid sodium bicarbonate, diluted with water and extracted with ethyl acetate. The combined organic layers were concentrated in vacuo to some extent then adsorbed directly on silica and chromatographed eluting with ethyl acetate / hexane (1: 1 → 1: 0). Crystallization from ethyl acetate / hexane gave sulfone (279) (45 mg, 72%) as an orange powder with a melting point of 301-304 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 14.9 (v br s, 1H), 11.07 (br s, 1H), 9.38 (br s, 1H), 8.60 (s, 1H) ), 8.34 (d, J = 2.4 Hz, 1H), 7.71 (s, 1H), 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. C ₂₄ H ₁₆ ClN ₅ O ₅ S.I. 1 _/ 4C ₄ H 8 _{O 2} Calculated: C, 55.20; H, 3.34 ; N, 12.88.

Example 289 4- (2-chlorophenyl) -9-hydroxy-6- [2- (1H-imidazol-2-ylsulfonyl) ethyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) - dione (XXXIX; Ar = ^{2-chlorophenyl, m = 2, R 3 =} 2- imidazolyl) (280) and 4- (2-chlorophenyl) -9-hydroxy-6-[2- (1H-imidazol - 2-ylsulfinyl) ethyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (XXXIX; Ar = 2-chlorophenyl, m = 1, R ³ = 2-imidazolyl) (281) Preparation of Carbazole (277) (66 mg, 0.14 mmol) in tetrahydrofuran (30 mL) containing glacial acetic acid (10 mL) prepared as described in Example 286. Was added 35% hydrogen peroxide (2 mL) to L) solution. The resulting solution was stirred at room temperature for 20 hours, then poured onto solid sodium bicarbonate, diluted with water and extracted with ethyl acetate. Concentrate the combined organic layers to some extent, then adsorb directly onto silica, chromatograph and elute with ethyl acetate / hexane (1: 1 → 4: 1) then ethyl acetate / methanol (99: 1) to maximize was obtained sulfone (280) (36mg, 51% ) as an orange powder with a melting point of two hundred and sixty-three to two hundred sixty-five ° C. at the _{R f.} ¹ H NMR δ [(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, 1H), 7.58 (m, 1H), 7.52 to 7.45 (m, 4H), 7.19 (brs, 2H), 7.12 (dd, J = 8.8, 2.4 Hz, 1H), 4.85 (t, J = 6.6 Hz, 2H), 3.96 (m, 2H). Found: C, 57.44; H, 3.87; N, 9.80. _{C 25 H 17 ClN 4 O 5} S. 1 _/ 2C ₄ H 8 _{O 2} Calculated: C, 57.40; H, 3.75 ; N, 9.92. Subsequently, sulfoxide (281) (16 mg, 23%) was obtained as an orange powder having a smaller R _f and a melting point of 254 to 259 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 13.35 (br s, 1 H), 11.10 (br. S, 1 H), 9.42 (s, 1 H), 8.39 (d, J = 2.4 Hz, 1 H), 7.77 (d, J = 12.7 Hz, 1 H), 7.58 (m, 2 H), 7.53 to 7.44 (m, 3 H), 7.24 (br s , 2H), 7.15 (dd, J = 8.8, 2.4 Hz, 1H), 4.85 (m, 2H), 3.69 (m, 2H). Calculated value of FABMS [M + H] ⁺ : 505.0725, 507.0666. Calculated for _{C 25 H 17 ClN 4 O 4} S 505.0737,507.0708.

  Scheme 10 procedure

Example 290 6- (2-Hydroxy-3-methoxypropyl) -9-methoxy-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (XLII; Ar = the Ar = phenyl) (0.20g, 0.80mmol); - _{phenyl, Z} = OCH 3) (225 preparation of) 5-methoxy -2 [(E) -2- phenylethenyl]-1H-indole (II Example 38 Alkylation with epibromohydrin by the procedure described in Example 38 gave the crude epoxide (XL; Ar = phenyl). This was used without further purification. This epoxide was dissolved in methanol (100 mL), and 35% perchloric acid (10 mL) was added thereto. The resulting solution was heated at reflux for 3 hours, then diluted with water and extracted with ethyl acetate. The organic phase was dehydrated, the dehydrating agent was removed, and the solution was concentrated to dryness to give the diene (XLI; Ar = phenyl, Z = OCH ₃ ). This crude material was reacted directly with maleimide (92 mg) according to Method 4a except that the reaction time was 18 hours. The crude Diels-Alder adduct was aromatized by the procedure described in Example 79 to give the material. This material was chromatographed on silica eluting with ethyl acetate / hexane (1: 1). Crystallization from ethyl acetate / hexane gave carbazole (225) (0.10 g, 30%) as a yellow powder with a melting point of 128-136 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.10 (br s, 1 H), 8.55 (d, J = 2.6 Hz, 1 H), 7.81 (s, 1 H), 7.64 ( m, 3H), 7.47 (m, 3H), 7.29 (dd, J = 9.1, 2.6 Hz, 1H), 5.17 (d, J = 5.5 Hz, 1H), 4. 52 (dd, J = 4.2, 15.0 Hz, 1H), 4.43 (dd, J = 7.1, 15.0 Hz, 1H), 4.04 (m, 1H), 3.90 (s) , 3H), 3.32 (m, 2H), 3.26 (s, 3H). Found: C, 69.94; H, 5.45; N, 6.36. Calculated for _{C 25 H 22 N 2 O 5} : C, 69.76; H, 5.15; N, 6.51.

Example 291 6- (2,3-dihydroxypropyl) -9-hydroxy-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (XLIII; Ar = phenyl, Preparation of Z = OH) (226) Alcohol (225) (96 mg, 0.22 mmol) prepared as described in Example 290 was demethylated using the procedure described in Example 80, followed by silica. Chromatography used, eluting with ethyl acetate / hexane (4: 1). Crystallization from ethyl acetate / hexane gave phenol (226) (28 mg, 31%) as an orange / yellow powder with a melting point of 290-295 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.04 (br s, 1H), 9.30 (s, 1H), 8.40 (d, J = 2.4 Hz, 1H), 7.79 ( s, 1H), 7.63 (m, 2H), 7.55 (d, J = 8.8 Hz, 1H), 7.47 (m, 3H), 7.11 (dd, J = 8.8, 2.4 Hz, 1H), 5.00 (d, J = 5.4 Hz, 1H), 4.86 (t, J = 5.4 Hz, 1H), 4.51 (dd, J = 3.8, 14 .9 Hz, 1H), 4.35 (dd, J = 7.5, 14.9 Hz, 1H), 3.89 (m, 1H), 3.41 (m, 2H). Found: C, 67.94; H, 4.69; N, 6.50. _{C 23 H 18 N 2 O 5} . 1 / 4H ₂ O Calculated: C, 67.89; H, 4.58 ; N, 6.88.

Example 292 4- (2-chlorophenyl) -9-hydroxy-6- [2-hydroxy-3- (4-morpholinyl) propyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H Preparation of) -dione (XLIII; Ar = 2-chlorophenyl, Z = 4-morpholinyl) (282) Pure trans-diene (27) prepared as described in Example 37 (0.25 g, 0.88 mmol) Was alkylated with epibromohydrin by the procedure described in Example 38 to give the crude epoxide (XL; Ar = 2-chlorophenyl). This was used without further purification. This epoxide was dissolved in tetrahydrofuran (2 mL), and morpholine (0.5 mL) was added thereto. The resulting solution was heated at 60 ° C. for 48 hours, subsequently diluted with water and extracted with ethyl acetate. The organic phase was dehydrated, the dehydrating agent was removed, and the solution was concentrated to dryness to give the diene (XLI; Ar = 2-chlorophenyl, Z = 4-morpholinyl). This crude material was triturated in diethyl ether / hexane and then reacted directly with maleimide (128 mg) according to the procedure described in Example 68 except that the reaction time was 18 hours and p-dioxane was added as a cosolvent. . The crude Diels-Alder adduct was aromatized using the procedure described in Example 70 to give carbazole (XLII; Ar = 2-chlorophenyl, Z = 4-morpholinyl). This was demethylated using the procedure described in Example 81 to give a crude material. This was chromatographed on silica eluting with ethyl acetate. Crystallization from diethyl ether / hexane gave carbazole (282) (0.10 g, 22%) as a yellow powder with a melting point of 275-278 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.05 (br s, 1H), 9.34 (br s, 1H), 8.37 (d, J = 2.4 Hz, 1H), 7.79 (S, 1H), 7.63-7.56 (m, 2H), 7.47 (m, 3H), 7.12 (m, 1H), 5.01 (t, J = 5.7 Hz, 1H) ), 4.53 (m, 1H), 4.37 (m, 1H), 4.04 (brs, 1H), 3.38 (m, 4H), 2.39 to 2.24 (m, 6H) ). Found: C, 63.90; H, 4.85; N, 8.55. Calculated for _{C 27 H 24 ClN 3 O 5} : C, 64.10; H, 4.78; N, 8.31.

Example 293 4- (2-chlorophenyl) -6- [3- (cis-3,5-dimethyl-1-piperazinyl) -2-hydroxypropyl] -9-hydroxypyrrolo [3,4-c] carbazole Preparation of -1,3 (2H, 6H) -dione (XLIII; Ar = 2-chlorophenyl, Z = cis-3,5-dimethyl-1-piperazinyl) (283) Pure prepared as described in Example 37 Trans-diene (27) (0.25 g, 0.88 mmol) was alkylated with epibromohydrin by the procedure described in Example 38 to give the crude epoxide (XL; Ar = 2-chlorophenyl). . This was used without further purification. This epoxide was dissolved in tetrahydrofuran (2 mL), and cis-2,6-dimethylpiperazine (0.50 g, 4.4 mmol) was added thereto. The resulting solution was heated at 60 ° C. for 48 hours, subsequently diluted with water and extracted with ethyl acetate. The organic phase was dehydrated, the dehydrating 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, then maleimide (0.13 g, 1.5 mmol) according to the procedure described in Example 68 except that the reaction time was 18 hours and p-dioxane was added as a cosolvent. ) Directly. The crude Diels-Alder adduct is aromatized using the procedure described in Example 70 to give carbazole (XLII; Ar = 2-chlorophenyl, Z = cis-3,5-dimethyl-1-piperazinyl). It was. This was demethylated using the procedure described in Example 81 to give a crude material. This was chromatographed on silica eluting with ethyl acetate / methanol / triethylamine (4: 1: trace). Crystallization from ethyl acetate / hexane gave carbazole (283) (65 mg, 14%) as a yellow powder with a melting point of 206-210 ° C. ¹ H NMR δ [(CD ₃ ) 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, 1H), 7.58 (m, 2H), 7.47 (m, 3H), 7.11 (m, 1H), 4.95 (brs, 1H), 4 .52 (m, 1H), 4.34 (m, 1H), 4.04 (m, 1H), 2.71 to 2.53 (m, 4H), 2.33 (m, 1H), 2. 20 (m, 1H), 1.46 (m, 2H), 0.81 (m, 6H). Found: C, 63.76; H, 5.30; N, 10.02. _{C 29 H 29 ClN 4 O 4} . 3 / 4H ₂ O Calculated: C, 63.73; H, 5.63 ; N, 10.25.

Example 294 4- (2-chlorophenyl) -9-hydroxy-6- [2-hydroxy-3- (methylamino) propyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) Preparation of dione (XLIII; Ar = 2-chlorophenyl, Z═NHCH ₃ ) (284) Pure trans-diene (27) (0.25 g, 0.88 mmol) prepared as described in Example 37 was Alkylation with epibromohydrin by the procedure described in Example 38 gave the crude epoxide (XL; Ar = 2-chlorophenyl). This was used without further purification. This epoxide was dissolved in tetrahydrofuran (2 mL), and aqueous methylamine (0.5 mL, 40% solution) was added thereto. The resulting solution was heated at 60 ° C. for 6 hours, then diluted with water and extracted with ethyl acetate. The organic phase was dehydrated, the dehydrating agent was removed, and the solution was concentrated to dryness to give the diene (XLI; Ar = 2-chlorophenyl, Z = NHCH ₃ ). This crude material was triturated in diethyl ether / hexane, then maleimide (0.13 g, 1.5 mmol) according to the procedure described in Example 68 except that the reaction time was 18 hours and p-dioxane was added as a cosolvent. ) Directly. The crude Diels-Alder adduct was aromatized using the procedure described in Example 70 to give carbazole (XLII; Ar = 2-chlorophenyl, Z = NHCH ₃ ). This was demethylated using the procedure described in Example 81 to give a crude material. This was chromatographed on silica eluting with ethyl acetate / methanol / triethylamine (4: 1: trace). Crystallization from ethyl acetate / hexane gave carbazole (284) (61 mg, 15%) as a yellow powder with a melting point of 188-191 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 10.9 (v br s, 1H), 9.36 (br s, 1H), 8.37 (d, J = 2.4 Hz, 1H), 7. 77 (s, 1H), 7.58 (m, 2H), 7.47 (m, 3H), 7.13 (dd, J = 8.8, 2.4 Hz, 1H), 5.09 (br s , 1H), 4.50 (m, 1H), 4.34 (m, 1H), 3.97 (m, 1H), 2.77 to 2.63 (m, 2H), 2.28 (d, J = 2.1 Hz, 3H). Found: C, 62.66; H, 4.64; N, 8.69. _{C 24 H 20 ClN 3 O 4} . 2 / 3H ₂ O Calculated: C, 62.40; H, 4.66 ; N, 9.09.

Example 295 4- (2-chlorophenyl) -6- [3- (dimethylamino) -2-hydroxypropyl] -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) - dione (XLIII; Ar = _{2-chlorophenyl, Z = N (CH 3)} 2) pure trans was prepared as described in Preparative example 37 (285) - diene (27) (0.25 g, 0. 88 mmol) was alkylated with epibromohydrin by the procedure described in Example 38 to give the crude epoxide (XL; Ar = 2-chlorophenyl). This was used without further purification. This epoxide was dissolved in tetrahydrofuran (2 mL), and aqueous methylamine (0.5 mL, 40% solution) was added thereto. The resulting solution was heated at 60 ° C. for 6 hours, then diluted with water and extracted with ethyl acetate. The organic phase was dehydrated, the dehydrating agent was removed, and the solution was concentrated to dryness to give a diene (XLI; Ar = 2-chlorophenyl, Z = N (CH ₃ ) ₂ ). This crude material was triturated in diethyl ether / hexane, then maleimide (0.13 g, 1.5 mmol) according to the procedure described in Example 68 except that the reaction time was 18 hours and p-dioxane was added as a cosolvent. ) Directly. The crude Diels-Alder adduct was aromatized using the procedure described in Example 70 to give carbazole (XLII; Ar = 2-chlorophenyl, Z = N (CH ₃ ) ₂ ). This was demethylated using the procedure described in Example 81 to give a crude material. This was chromatographed on silica eluting with ethyl acetate / methanol / triethylamine (4: 1: trace). Crystallization from ethyl acetate / hexane gave carbazole (285) (165 mg, 40%) as a yellow powder with a melting point of 225-228 ° C. ¹ H NMR δ [(CD ₃ ) 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, 1H), 7.57 (m, 2H), 7.47 (m, 3H), 7.13 (dd, J = 8.8, 2.4 Hz, 1H), 4.91 (br s, 1H), 4.50 (m, 1H), 4.34 (m, 1H), 4.00 (m, 1H), 2.35 (m, 1H), 2.24 (m, 1H), 2. 17 (s, 6H). Calculated; C, 63.54; H, 4.60; N, 8.83. _{C 25 H 22 ClN 3 O 4} . Calculated for _1/2 H2O: C, 63.49; H, 4.90; N, 8.88.

  Scheme 11 procedure

Example 296 4- (2-chlorophenyl) -9-methoxy-4,5,6,10c-tetrahydro-1H-furo [3,4-c] carbazole-1,3 (3aH) -dione (XLIV; Preparation of Ar = 2-chlorophenyl) (286) of trans-diene (27) (0.30 g, 1.06 mmol) and maleic anhydride (0.16 g, 1.59 mmol) prepared as described in Example 37. The xylene (30 mL) solution was heated at reflux for 18 hours, then concentrated in vacuo, chromatographed on silica, eluting with ethyl acetate / hexane (1: 2). It was then crystallized from ethyl acetate / hexane to give the anhydride (286) (0.29 g, 72%) as a light brown powder with a melting point of 189-191 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.16 (br s, 1H), 7.69 (dd, J = 7.7, 1.4 Hz, 1H), 7.51 (dd, J = 7 .7, 1.4 Hz, 1H), 7.43 (ddd, J = 7.7, 7.7, 1.4 Hz, 1H), 7.36 (ddd, J = 7.7, 7.7, 1 .4 Hz, 1H), 7.25 (d, J = 8.6 Hz, 1H), 7.15 (d, J = 2.4 Hz, 1H), 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, 3 H), 3. 71-3.66 (m, 1H), 3.36 (dd, J = 15.9, 13.0 Hz, 1H), 2.99 (dd, J = 15.9, 4.1 Hz, 1H). Found: C, 65.85; H, 3.95; N, 3.70. Calculated _{C 21 H 16 ClNO 4: C} , 66.06; H, 4.22; N, 3.67.

Example 297 4- (2-chlorophenyl) -2- (2,4-dimethoxybenzyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (XLV; Preparation of Ar = 2-chlorophenyl) (287) To a solution of anhydride (286) (2.80 g, 7.42 mmol) prepared as described in Example 296 in glacial acetic acid (70 mL) was added 2,4-dimethoxybenzyl. Amine (1.67 mL, 11.1 mmol) was added. The resulting solution was heated at reflux for 6 hours, then concentrated in vacuo to some extent and diluted with water to precipitate an orange solid. This was collected by filtration, washed with water and dried in vacuo. The crude material was then dissolved in p-dioxane and aromatized by the procedure of Example 79 followed by chromatography on silica eluting with ethyl acetate / hexane (1: 1). Crystallization from methanol then gave carbazole (287) (1.46 g, 37%) as a yellow powder with a melting point of 224-226 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 12.02 (br s, 1H), 8.45 (d, J = 2.6 Hz, 1H), 7.62 (s, 1H), 7.58 ( m, 2H), 7.53 to 7.42 (m, 3H), 7.25 (dd, J = 8.8, 2.6 Hz, 1H), 6.95 (d, J = 8.4 Hz, 1H) ), 6.57 (d, J = 2.3 Hz, 1H), 6.45 (dd, J = 8.4, 2.3 Hz, 1H), 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. Calculated for _{C 30 H 23 ClN 2 O 5} : C, 68.38; H, 4.40; N, 5.32.

  Exemplary Procedure for Method 20 of Scheme 11

Example 298 6-allyl-4- (2-chlorophenyl) -2- (2,4-dimethoxybenzyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H)- Preparation of dione (XLVI; Ar = 2-chlorophenyl, n = 1) (288) To a solution of carbazole (287) (150 mg, 0.28 mmol) prepared as described in Example 297 in dimethylformamide (10 mL) was added carbonic acid. Potassium (0.39 g, 2.80 mmol) and allyl bromide (72 mL, 0.84 mmol) were added under nitrogen. The resulting solution was warmed to 90 ° C. for 3 hours with stirring, then diluted with water and extracted with ethyl acetate. The organic phase was dehydrated, the dehydrating agent was removed, and the solution was concentrated to dryness. Chromatography on silica eluting with ethyl acetate / hexane (1: 2) followed by crystallization from diethyl ether / hexane to give carbazole (288) (90 mg as a yellow powder, mp 171-173 ° C. 57%). ¹ H NMR δ [(CD ₃ ) ₂ SO] 8.51 (d, J = 2.6 Hz, 1H), 7.84 (s, 1H), 7.67 (d, J = 8.9 Hz, 1H) 7.58 (m, 1H), 7.53 to 7.46 (m, 3H), 7.32 (dd, J = 8.9, 2.6 Hz, 1H), 6.97 (d, J = 8.4 Hz, 1H), 6.57 (d, J = 2.4 Hz, 1H), 6.45 (dd, J = 8.4, 2.4 Hz, 1H), 5.99 (m, 1H), 5.18 (d, J = 4.9 Hz, 2H), 5.14 (dd, J = 10.3, 1.3 Hz, 1H), 4.99 (dd, J = 17.2, 1.3 Hz, 1H), 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. Calculated for _{C 33 H 27 ClN 2 O 5} : C, 69.90; H, 4.80; N, 4.94.

Example 299 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) Preparation of carbazole (287) (260 mg, 0.51 mmol), prepared as described in Example 297, in Example 298 Reaction with 4-bromo-1-butene (155 mL, 1.53 mmol) by the procedure described gave carbazole (289) (173 mg, 58%) as a yellow powder with a melting point of 161-164 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 8.50 (d, J = 2.6 Hz, 1H), 7.89 (s, 1H), 7.73 (d, J = 9.0 Hz, 1H) 7.60-7.46 (m, 4H), 7.31 (dd, J = 9.0, 2.6 Hz, 1H), 6.96 (d, J = 8.5 Hz, 1H), 6. 57 (d, J = 2.3 Hz, 1H), 6.44 (dd, J = 8.4, 2.3 Hz, 1H), 5.84 (m, 1H), 4.96 to 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 (partially unclear m, 2H). Found: C, 70.23; H, 5.15; N, 4.91. Calculated for _{C 34 H 29 ClN 2 O 5} : C, 70.28; H; 5.03; N, 4.82.

  Representative Procedure for Method 21 of Scheme 11

Example 300 4- (2-Chlorophenyl) -6- (2,3-dihydroxypropyl) -2- (2,4-dimethoxybenzyl) -9-methoxypyrrolo [3,4-c] carbazole-1, Preparation of 3 (2H, 6H) -dione (XLVII; Ar = 2-chlorophenyl, n = 1) (290) Carbazole (288) described in Example 298 (80 mg, 0.14 mmol) in acetone / water (4 : 1, 20 mL) solution was added N-methylmorpholine N-oxide (33 mg, 0.28 mmol) and osmium tetroxide (176 uL, 4% aqueous solution, about 0.028 mmol). The reaction mixture was stirred at room temperature for 18 hours, then diluted with 1N hydrochloric acid and extracted with ethyl acetate. The organic phase was dehydrated, the dehydrating 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 to give diol (290) (80 mg as a yellow powder, mp 151-156 ° C. 94%). ¹ H NMR δ [(CD ₃ ) ₂ SO] 8.50 (d, J = 2.6 Hz, 1H), 7.82 (s, 1H), 7.69 (br d, J = 9.0 Hz, 1H) ), 7.58 (m, 1H), 7.52 to 7.46 (m, 3H), 7.30 (dd, J = 9.0, 2.6 Hz, 1H), 6.95 (d, J = 8.4 Hz, 1H), 6.57 (d, J = 2.4 Hz, 1H), 6.44 (dd, J = 8.4, 2.4 Hz, 1H), 5.02 (d, J = 5.0 Hz, 1H), 4.87 (brs, 1H), 4.69 (s, 2H), 4.55 (m, 1H), 4.38 (m, 1H), 3.89 (m, 4H), 3.80 (s, 3H), 3.72 (s, 3H), 3.41 (partially unclear m, 2H). Found: C, 65.32; H, 5.00; N, 4.83. _{C 33 H 19 ClN 2 O 7} . 1 / 4H ₂ O Calculated: C, 65.45; H, 4.91 ; N, 4.63.

Example 301 4- (2-Chlorophenyl) -6- (3,4-dihydroxybutyl) -2- (2,4-dimethoxybenzyl) -9-methoxypyrrolo [3,4-c] carbazole-1, Preparation of 3 (2H, 6H) -dione (XLVII; Ar = 2-chlorophenyl, n = 2) (291) The carbazole (289) procedure described in Example 299 (100 mg, 0.17 mmol) was prepared using a reaction time of 48 The reaction was carried out according to the procedure described in Example 300 except for the time to give diol (291) (74 mg, 71%) as a yellow powder with a melting point of 126-131 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 8.51 (d, J = 2.5 Hz, 1H), 7.83 (s, 1H), 7.72 (d, J = 9.0 Hz, 1H) 7.56 (m, 2H), 7.48 (m, 2H), 7.33 (dd, J = 9.0, 2.5 Hz, 1H), 6.94 (d, J = 8.4 Hz, 1H), 6.57 (d, J = 2.3 Hz, 1H), 6.44 (dd, J = 8.4, 2.3 Hz, 1H), 4.76 (t, J = 5.0 Hz, 1H) ), 4.69 (s, 2H), 4.60 to 4.52 (m, 3H), 3.90 (s, 3H), 3.80 (s, 3H), 3.72 (s, 3H) 3.45-3.20 (partially unclear m, 3H), 1.99 (m, 1H), 1.69 (m, 1H). Found: C, 66.39; H, 5.02; N, 4.44. Calculated for _{C 34 H 31 ClN 2 O 7} : C, 66.39; H, 5.08; N, 4.55.

  Representative Procedure for Method 22 of Scheme 11

Example 302 4- (2-Chlorophenyl) -6- (2,3-dihydroxypropyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (XLVIII; Preparation of Ar = 2-chlorophenyl, n = 1) (292) To a solution of 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) was added. The reaction vessel was sealed and heated to 90 ° C. for 18 hours in an oil bath, and then trifluoroacetic acid was removed under reduced pressure. The residue was then 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, then dried over anhydrous sodium sulfate and concentrated under reduced pressure. The aqueous layer was then acidified by adding concentrated hydrochloric acid, extracted with diethyl ether, and treated as described above. The mixed crude material was triturated with diethyl ether / hexane, then dissolved in dichloromethane (20 mL), demethylated by the procedure described in Example 80, and chromatographed on silica with ethyl acetate / hexane (1: 1 → 1: 0) to give phenol (292) (31 mg, 57%) as an orange powder with a melting point of 305-309 ° C. ¹ H NMR δ [(CD ₃ ) 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, 1H), 4.50 (m, 1H), 4.32 (m, 1H), 3.87 (brs, 1H), 3.45-3.36 (m, 2H). Found: C, 63.17; H, 3.94; N, 6.18. C ₂₃ H ₁₇ ClN ₂ O ₅ Calculated: C, 63.24; H, 3.92 ; N, 6.41.

Example 303 4- (2-chlorophenyl) -6- (3,4-dihydroxybutyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (XLVIII; Preparation of Ar = 2-chlorophenyl, n = 2) (293) Diol (291) (35 mg, 0.06 mmol) prepared as described in Example 301 was reacted according to the procedure described in Example 302 to obtain a melting point. Phenol (293) (25 mg, 92%) was obtained as an orange powder at 263-267 ° C. ¹ H NMR δ [(CD ₃ ) 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 (brs, 1H), 1.67 (brs, 1H). Calculated value of FABMS [M + H] ⁺ = 451.014, 453.0211. Calculated 451.1061,453.1031 of _{C 24 H 19 ClN 2 O 5} .

(Example 304)
Carbazole (287) prepared as described in Example 297 (50 mg per reaction, 0.09 mmol) was prepared according to the procedure described in Example 298 except that the reaction time was 18 hours, iodomethane, iodoethane, 1-bromopropane, 1-bromobutane, 1-bromopentane, allyl bromide, (2-bromoethyl) benzene, 3-bromopropyne, 1-bromo-3-methylbutane, 2-bromopropane, 2-iodo-1,1, Array format with 1-trifluoroethane, 5-bromo-1-pentene, iodoacetamide, 4-bromo-1-butene, 1-bromo-2-methylpropane and 1-bromo-4,4,4-trifluorobutane And subsequently using ethyl acetate as the treatment solvent and omitting the 1N potassium hydroxide wash. Was deprotected by the procedure described in 施例 302, respectively,
4- (2-Chlorophenyl) -9-hydroxy-6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = 2-chlorophenyl, R ¹⁰ = CH ₃ ) ( 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, R ¹⁰ = CH ₂ CH ₃ ) (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 ¹⁰ = (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 ¹⁰ = (CH ₂ ) ₃ CH ₃ ) (297). Found: M + H = 419.
4- (2-Chlorophenyl) -9-hydroxy-6-pentylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = 2 chlorophenyl, R ¹⁰ = (CH ₂ ) ₄ CH ₃ ) (298). Found: M + H = 433.
6-allyl-4- (2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = 2-chlorophenyl, R ¹⁰ = CH ₂ CH = _CH 2) (299). Found: M + H = 403.
4- (2-chlorophenyl) -9-hydroxy-6- (2-phenylethyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = 2-chlorophenyl, R _{^{10 = CH 2 CH 2 Ph)}} (300). Found: M + H = 467.
4- (2-Chlorophenyl) -9-hydroxy-6- (2-propynyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = 2-chlorophenyl, R ¹⁰ = CH ₂ C≡CH) (301). Actual value: M + H = 401.
4- (2-Chlorophenyl) -9-hydroxy-6-isopentylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = 2-chlorophenyl, R ¹⁰ = CH _{2 CH 2 CH (CH 3) 2} ) (302). Found: M + H = 433.
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, R 10 = CH 2 CF 3}} ) (304). Found: M + H = 445.
4- (2-Chlorophenyl) -9-hydroxy-6- (4-pentenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = 2-chlorophenyl, R ¹⁰ _{= (CH 2) 3 CH =} CH 2) (305). Found: M + H = 431.
2- (4- (2-Chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) acetamide (VI; Ar = 2 - _{^{chlorophenyl, R 10 = CH 2 CONH 2}} ) (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, R ¹⁰ _{= (CH 2) 2 CH =} CH 2) (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, R ¹⁰ = CH ₂ CH _{(CH 3) 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, R 10 = (CH 2)}} 3 CF 3) (309). Actual measurement value: M + H = 473
Got.

(Example 305)
Carbazole (287) prepared as described in Example 297 (50 mg per reaction, 0.09 mmol) was prepared according to the procedure described in Example 298 except that the reaction time was 48 hours and 2-iodobutane and odor. Reaction with cyclopentyl fluoride in an array format followed by deprotection by the procedure described in Example 302 except that ethyl acetate was used as the treatment solvent and the 1N potassium hydroxide wash was omitted, respectively.
6-sec-butyl-4- (2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = 2-chlorophenyl, R ¹⁰ = CH _{(CH 3) CH 2 CH 3} ) (310). Found: M + H = 419.
4- (2-chlorophenyl) -6-cyclopentyl-9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = 2-chlorophenyl, R ¹⁰ = cyclopentyl) ( 311). Actual value: M + H = 431
Got.

(Example 306)
Carbazole (287) (50 mg, 0.09 mmol), prepared as described in Example 297, was prepared in an array format with 2-bromoethyl methyl ether by the procedure described in Example 298 except that the reaction time was 18 hours. Reaction followed by deprotection by the procedure described in Example 302, except that ethyl acetate was used as the treatment solvent and the 1N potassium hydroxide wash was omitted, and demethylated by the procedure described in Example 81,
6- (2-chloroethyl) -4- (2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = 2-chlorophenyl, R ¹⁰ _{= CH 2 CH 2 Cl) (} 312). Actual value: M + H = 425
Got.

Carbazole (287) prepared as described in Example 297 (50 mg per reaction, 0.09 mmol) was prepared according to the procedure described in Example 298 except that the reaction time was 18 hours. Reaction with 2-propanol, (S) -3-bromo-2-methylpropanol and (R) -3-bromo-2-methylpropanol followed by deprotection by the procedure described in Example 302. And
4- (2-chlorophenyl) -9-hydroxy-6- (2-hydroxypropyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = 2-chlorophenyl, R ^{_{10 = CH 2 CH (OH)}} CH 3) (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, R 10 = CH 2 CH (}} CH 3) CH 2 OH) (314). Found: M + H = 435.
4- (2-Chlorophenyl) -9-hydroxy-6-[(2R) -3-hydroxy-2-methylpropyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI ; Ar = ^{_{2-chlorophenyl, R 10 = CH 2 CH (}} CH 3) CH 2 OH) (315). Actual value: M + H = 435
Got.

  Procedure of scheme 12

  Exemplary Procedure for Method 24 of Scheme 12

Example 307 4- (2-Chlorophenyl) -9-methoxy-6- (2-methoxyethyl) -1,3-dioxo-1,2,3,6-tetrahydropyrrolo [3,4-c] carbazole 8-yl trifluoromethanesulfonate (XLIX; Ar = 2- ^{_{chlorophenyl, R 10 = CH 2 CH 2}} OCH 3 (168) preparation of trifluoromethanesulfonic anhydride (1.30 mL, the 7.77 mmol), example 267 To a solution of phenol (167) (0.50 g, 1.11. Mmol) and pyridine (6.29 mL, 0.077 mol) prepared as described in tetrahydrofuran (50 mL) was added dropwise at 0 ° C. This solution was brought to room temperature. After warming for 1 hour, diluted with 1N HCl and extracted with ethyl acetate, the extract was dehydrated to remove the dehydrating agent, The solution was concentrated to dryness to give a solid which was adsorbed onto silica and chromatographed, eluting with ethyl acetate / petroleum ether (1: 1) as a pale yellow powder, mp 229-231 ° C. Triflate (168) (0.53 g, 82%) was obtained ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.23 (br s, 1 H), 8.78 (s, 1 H), 8. 01 (s, 1H), 7.93 (s, 1H), 7.59 (dd, J = 8.0, 2.2 Hz, 1H), 7.54 to 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) Actual value: C _{, 49.26; H, 2.91; N} , 4.39.C 25 H 18 ClF 3 SN 2 O 7 .1 / 2CH 2 Cl 2 Calculated C, 48.97; H, 3.06; N, 4.48.

Example 308 4- (2-chlorophenyl) -9-methoxy-1,3-dioxo-1,2,3,6-tetrahydropyrrolo [3,4-c] carbazol-8-yl trifluoromethanesulfonate (XLIX) Ar = 2-chlorophenyl, R ¹⁰ = H) (169). Using the procedure described in Example 307, (163) is reacted with trifluoromethanesulfonic anhydride as a yellow solid of melting point 248-252 ° C. Triflate (169) (87%) was obtained. ¹ H NMR δ [(CD ₃ ) ₂ SO] 12.16 (br, 1H), 11.21 (br, 1H), 8.73 (s, 1H), 7.80 (s, 1H), 7. 71 (s, 1H), 7.58 (dd, J = 8.0, 2.2 Hz, 1H), 7.52 to 7.43 (m, 3H), 4.03 (s, 3H). Found: C, 52.32; H, 2.87; N, 4.87. _{C 22 H 12 ClF 3 N 2} SO 6. Calculated for THF C, 52.31; H, 3.38; N, 4.69.

  Representative Procedure for Method 25 of Scheme 12

Example 309 4- (2-chlorophenyl) -8-[(1E) -4-hydroxy-1-butenyl] -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) - dione; preparation of (L Ar = ^{_{2-chlorophenyl, R 10 = H, Z =}} CH 2 CH 2 OH) (170).
Triflate (169) (0.20 g, 0.35 mmol), (3E) -4- (tributylstannyl) -3-buten-1-ol (0.19 g, 0) prepared as described in Example 308 .53 mmol) and lithium chloride (29 mg, 0.70 mmol) in DMF (10 mL) were purged by bubbling nitrogen through the solution for 10 min. Bis (triphenylphosphine) palladium dichloride (12 mg, 0.017 mmol) was added last and the solution was flushed with nitrogen for an additional 2 minutes and then warmed under a nitrogen atmosphere for 3 hours. The mixture was diluted with brine, extracted with ethyl acetate and processed to give an oil. This oil was chromatographed on silica. Elution with ethyl acetate / petroleum ether (1: 5) gave the precursor. On the other hand, increasing ethyl acetate / petroleum ether (1: 1) to pure ethyl acetate gave (170) (0.15 g, 95%) as a yellow solid with a melting point of 271-275 ° C. ¹ H NMR δ [(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, 1H), 7.51 to 7.41 (m, 3H), 6.87 (d, J = 16) 0.0 Hz, 1H), 6.44 (dt, J = 16.0, 7.1 Hz, 1H), 4.62 (t, J = 5.3 Hz, 1H), 3.94 (s, 3H), 3 .58 (m, 2H), 2.42 (m, 2H). Found: C, 67.09; H, 4.36; N, 5.98. C ₂₅ H ₁₉ ClN ₂ Calculated _{O 4 C, 67.19; H,} 4.28; N, 6.27.

  Exemplary Procedure for Method 26 of Scheme 12

Example 310 4- (2-chlorophenyl) -8- (4-hydroxybutyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (LI; Ar = ^{2-chlorophenyl,} R ₁₀ = ^H, was prepared as described in _{Z =} CH 2 CH 2 OH) preparation example 309 (171) (170) (0.15g , 0.33mmol) and _PtO 2 (20 mg) A 1: 1 tetrahydrofuran / methanol (30 mL) solution was shaken under a hydrogen gas atmosphere at a pressure of 280 kPa (40 psi) for 30 minutes. The catalyst was removed by filtration through celite and further washed with solvent. The combined filtrate was processed and chromatographed on silica. Elution with ethyl acetate / petroleum ether (1: 1) gave (171) (0.20 g, 100%) as an orange solid, mp 256-260 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.90 (br, 1H), 11.10 (br, 1H), 8.34 (s, 1H), 7.64-7.40 (m, 6H) ), 4.37 (br, 1H), 3.93 (s, 3H), 3.43 (t, J = 6.3 Hz, 2H), 2.76 (t, J = 7.6 Hz, 2H), 1.66 (m, 1H), 1.50 (m, 2H).

Example 311 4- [4- (2-Chlorophenyl) -9-methoxy-1,3-dioxo-1,2,3,6-tetrahydropyrrolo [3,4-c] carbazol-8-yl] butyl trifluoromethanesulfonate (LIII; Ar = ^{2-chlorophenyl, R 10 = H, n =} 4, Z = OMs) preparation of (172).
(171), prepared as described in Example 310, was mesylated with methanesulfonyl chloride and triethylamine by the procedure described in Scheme 3 of Example 170 to give mesylate (172) (98%) as a yellow solid. Obtained. This was used without further purification.

  Representative Procedure for Method 27 of Scheme 12

Example 312 4- (2-chlorophenyl) -8- (4-iodobutyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (LIII; Ar = 2 - ^{chlorophenyl, R 10 = H, n =} 4, Z = I) preparation of (173).
A solution of mesylate (172) 0.12 g, 0.21 mmol) and sodium iodide (1 g) prepared as described in Example 311 in ethyl acetate (50 mL) was refluxed for 4 hours. The cooled solution was washed with water and treated to give iodide (173). This was crystallized from tetrahydrofuran / petroleum ether as an orange powder (0.10 g, 85%) with a melting point of 142-144 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.86 (s, 1H), 11.05 (s, 1H), 8.43 (s, 1H), 7.58 (m, 1H), 7. 55 (s, 1H), 7.52 to 7.43 (m, 3H), 7.42 (s, 1H), 3.94 (s, 3H). Calculated value of EIMS M ⁺ = 558.0212, 560.0178. Calculated 558.0207,560.0178 of _{C 25 H 20 ClIN 2 O 3} .

Example 313 4- (2-Chlorophenyl) -8- [4- (dimethylamino) butyl] -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (LIV : Preparation of Ar = 2-chlorophenyl, R ¹⁰ = H, n = 4, Z = N (CH ₃ ) ₂ ) (174) Iodide (173) prepared as described in Example 312 was prepared under reaction conditions. Reaction with aqueous dimethylamine by the procedure described in Scheme 3 of Example 179 except for 6 hours at room temperature gave (174) (64%) as an orange powder with a melting point of 162-164 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.85 (s, 1 H), 11.04 (br s, 1 H), 8.42 (s, 1 H), 7.57 (dd, J = 8. 0, 2.2 Hz, 1H), 7.55 (s, 1H), 7.51 to 7.43 (m, 3H), 7.42 (s, 1H), 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). Calculated value of EIMS M ⁺ = 475.1657, 477.1650. Calculated 475.1663,477.1633 of _{C 27 H 26 ClN 3 O 3} .

Example 314 4- (2-chlorophenyl) -8- [4- (dimethylamino) butyl] -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (LV Preparation of: Ar = 2-chlorophenyl, R ¹⁰ = H, n = 4, Z = N (CH ₃ ) ₂ ) (175) Prepared as described in Example 313 (174 ???) Demethylation with pyridine hydrochloride by the procedure described in 81 gave (176) (67%) as a yellow powder with a melting point of 220-226 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.72 (s, 1 H), 10.98 (s, 1 H), 9.33 (br, 1 H), 8.32 (s, 1 H), 7. 56 (dd, J = 8.0, 2.2 Hz, 1H), 7.49 (s, 1H), 7.49-7.40 (m, 3H), 7.33 (s, 1H), 2. 74 (t, J = 7.33 Hz, 2H), 2.54 (m, 2H), 2.34 (brs, 6H), 1.64 (m, 2H), 1.54 (m, 2H). Calculated value of FABMS [M + H] ⁺ : 464.1569, 462.1578. Calculated 464.1555,462.1584 of _{C 26 H 25 ClN 3 O 3} .

Example 315 4- (2-chlorophenyl) -9-methoxy-8- [4- (1-pyrrolidinyl) butyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione ( LIV; Preparation of Ar = 2-chlorophenyl, R ¹⁰ = H, n = 4, Z = 1-pyrrolidinyl) (176) Iodide (173) prepared as described in Example 312 was prepared at reaction conditions at room temperature. Reaction with pyrrolidine by the procedure described in Example 179 except 2 hours gave (176) (75%) as an orange powder with a melting point of 173-178 ° C. This was used without further purification. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.85 (s, 1 H), 11.04 (br s, 1 H), 8.42 (s, 1 H), 7.57 (dd, J = 8. 0, 2.2 Hz, 1H), 7.55 (s, 1H), 7.51 to 7.43 (m, 3H), 7.42 (s, 1H), 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).

Example 316 4- (2-chlorophenyl) -9-hydroxy-8- [4- (1-pyrrolidinyl) butyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione ( LV; Ar = ^{2-chlorophenyl, R 10 = H, n =} 4, Z = 1- pyrrolidinyl) preparation of (177).
(173) prepared as described in Example 312 was demethylated with pyridine hydrochloride by the procedure described in Example 81 to give (177) (72%). ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.70 (s, 1 H), 10.98 (br s, 1 H), 9.30 (br, 1 H), 8.31 (s, 1 H), 7 .57 (dd, J = 8.0, 2.2 Hz, 1H), 7.49 (s, 1H), 7.49-7.40 (m, 3H), 7.32 (s, 1H), 2 .73 (t, J = 7.5 Hz, 2H), 2.44 to 2.36 (m, 6H), 1.69 to 1.61 (m, 6H), 1.51 (m, 2H). The melting point of hydrochloride was 173 to 178 ° C. (decomposition). Found: C, 62.27; H, 5.22; N, 7.74. _{C 28 H 26 C1N 3 O 3} . HCl. Of H ₂ O Calcd C, 62.00; H, 5.39; N, 7.75.

Example 317 4- (2-chlorophenyl) -9-methoxy-6- (2-methoxyethyl) -8-vinylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (L Ar = 2-chlorophenyl, R ¹⁰ = CH ₂ CH ₂ OCH ₃ , Z = H) (178) Preparation of Triflate (168), prepared as described in Example 307, was prepared as described in Example 309; To give a vinyl compound (178) (64%) as a yellow solid. This was used without further purification. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.11 (s, 1H), 8.53 (s, 1H), 7.95 (s, 1H), 7.80 (s, 1H), 7. 58 (dd, J = 8.1, 2.2 Hz, 1H), 7.52 to 7.43 (m, 3H), 7.18 (dd, J = 17.6, 11.2 Hz, 1H), 6 .06 (dd, J = 17.6, 1.3 Hz, 1H), 5.42 (dd, J = 11.2, 1.3 Hz, 1H), 4.71 (t, J = 5.0 Hz, 2H) ), 3.97 (s, 3H), 3.71 (t, J = 5.0 Hz, 2H), 3.16 (s, 3H).

Example 318 4- (2-chlorophenyl) -8- (2-hydroxyethyl) -9-methoxy-6- (2-methoxyethyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) - dione (LI: Ar = ^{2-chlorophenyl, R 10 = H, Z =} OH) preparation of (179).
(178), prepared as described in Example 317, was hydroborated with 9-BBN by the procedure described in Example 344 to give (179) (86%) as a yellow solid, mp 271-273 ° C. Got. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.08 (br, 1H), 8.49 (s, 1H), 7.78 (s, 1H), 7.60 (s, 1H), 7. 57 (dd, J = 8.0, 2.2 Hz, 1H), 7.52 to 7.42 (m, 3H), 4.68 (t, J = 5.2 Hz, 1H), 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 4- (2-chlorophenyl) -9-hydroxy-6,8-bis (2-hydroxyethyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (LII ; Ar = ^{_{2-chlorophenyl, R 10 = CH 2 CH 2}} OH, Z = OH) preparation of (180).
(179), prepared as described in Example 318, was demethylated with BBr ₃ by the procedure described in Example 80 except that the reaction conditions were 12 equivalents of reagent at 0 ° C. for 6 hours, (180) (35%) was obtained as a yellow powder with a melting point of 278-280 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.00 (br s, 1 H), 9.39 (br, 1 H), 8.37 (s, 1 H), 7.72 (s, 1 H), 7 .56 (dd, J = 8.0, 2.2 Hz, 1H), 7.51 to 7.42 (m, 4H), 4.82 (t, J = 5.5 Hz, 1H), 4.72 ( br, 1H), 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). Calculated value of FABMS M ^<+> : 452.0993, 450.0984. Calculated 452.0953,450.0982 of _{C 24 H 19 ClN 2 O 5} .

Example 320 9-Methoxy-6-methyl-1,3-dioxo-4-phenyl-1,2,3,6-tetrahydropyrrolo [3,4-c] carbazol-8-yltrifluoromethanesulfonate (XLIX) Ar = phenyl, R ¹⁰ = CH ₃ ) (185) Preparation (154), prepared as described in Example 254, was reacted with trifluoromethanesulfonic anhydride by the procedure described in Example 307 to obtain a melting point 9-methoxy-6-methyl-1,3-dioxo-4-phenyl-1,2,3,6-tetrahydropyrrolo [3,4-c] carbazol-8-yltrifluoromethane as a yellow solid at 244 to 246 ° C. Sulfonate (85%) was obtained. ¹ H NMR δ [(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 to 7.66 (m, 2H), 7.52 to 7.46 (m, 3H), 4.02 (s, 3H), 3.99 (s, 3H).

Example 321 4- (2-Chlorophenyl) -9-methoxy-6-methyl-1,3-dioxo-1,2,3,6-tetrahydropyrrolo [3,4-c] carbazol-8-yltrifluoro b methanesulfonate (XLIX; Ar = ^{2-chlorophenyl,} R 10 = Me) preparation of (700).
(160), prepared as described in Example 260, was reacted with trifluoromethanesulfonic anhydride by the procedure described in Example 307 to give triflate (700) (89% as a yellow solid with a melting point of 251-253 ° C. ) ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.26 (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. _{C 23 H 14 N 2 ClF 3} O 6 S. Calculated for 1/4 hexane: C, 52.51; H, 3.15; N, 5.00. Calculated value of FABMS [M + H] ⁺ : 539.0262, 541.0240. Calculated 539.0292,541.0262 of _{C 23 H 15 N 2 ClF 3} O 6 S.

Example 322 2,8-diallyl-4- (phenyl) -9-methoxy-6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (LVI; Ar = phenyl) R = Me) (186) and 8-allyl-4- (phenyl) -9-methoxy-6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (LVII; Ar = phenyl) , R ¹⁰ = Me) (187).
The triflate (185) prepared as described in Example 320 was reacted with allyltri-n-butyltin at 100 ° C. for 1 hour by the procedure described in Example 309 to give the crude product. This is chromatographed on silica gel (ethyl acetate / petroleum ether (1: 4) to give (i) pure bis-allyl compound (186) (12%) as an orange solid of melting point 188-189 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 8.52 (s, 1H), 7.81 (s, 1H), 7.66 (dd, J = 8.0, 1.7 Hz, 2H) 7.53 to 7.43 (m, 4H), 6.10 (m, 1H), 5.91 (m, 1H), 5.21 to 5.06 (m, 4H), 4.22 (d , J = 5.1 Hz, 2H), 3.95 (s, 6H), 3.56 (d, J = 6.6 Hz, 2H) Measured values: C, 76.43; H, 5.59; _{, 6.48.C 28 H 24 N 2 O} 3 .1 / 10H 2 O calculated: C, 76.73; H, 5.56 ; N, 6. 9. Subsequently, (ii) pure monoallyl compound, mp 204~208 ℃ (187) (42% ) was _{^{obtained. 1 H NMR δ (CDCl 3}} ) 11.08 (s, 1H), 8.52 ( s, 1H), 7.78 (s, 1H), 7.67-7.64 (m, 2H), 7.50 (s, 1H), 7.49-7.43 (m, 3H), 6 .09 (ddt, J = 6.6 Hz, 1H), 5.15 to 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.C 25 H 20 N 2 O 3 .3 / 2H 2 O calculated C, 73.51; H, 5.26 N, 6.86.

Example 323 4- (phenyl) -9-methoxy-6-methyl-8-vinylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (L; Ar = phenyl, R ¹⁰ = Me, Z = H) (701).
Triflate (185) prepared as described in Example 320 was reacted with tetravinyltin at 100 ° C. for 1 hour according to the procedure described in Example 309 to give the crude product. This was chromatographed on silica gel (ethyl acetate / petroleum ether (1: 2) to give pure 8-vinyl compound (701) (68%) as an orange solid with a melting point of 220 ° C. ¹ H NMR. δ [(CD ₃ ) ₂ SO] 11.12 (br, 1H), 8.57 (s, 1H), 7.92 (s, 1H), 7.79 (s, 1H), 7.69-7 .64 (m, 2H), 7.52 to 7.43 (m, 3H), 7.20 (dd, J = 17.7, 11.2 Hz, 1H), 6.09 (dd, J = 17.7. 7, 1.2 Hz, 1 H), 5.42 (dd, J = 11.2, 1.2 Hz, 1 H), 4.00 (s, 3 H), 3.96 (s, 3 H). _{, 74.45; H, 4.78; N} , 6.94.C 24 H 18 N 2 O 3 .1 / 4H 2 O calculated C, 4.50; H, 4.82; N, 7.24.

(Example 324)

Example 325 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,} R 10 = Me) preparation of (703).
The triflate (700) prepared as in Example 321 was reacted with allyltri-n-butyltin at 100 ° C. for 1 hour according to the procedure described in Example 309 to give the crude product. This is chromatographed on silica gel (ethyl acetate / petroleum ether (1: 3) to give (i) the pure bis-allyl compound (702) (49%) as an orange solid, mp 183-185 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 8.51 (s, 1H), 7.82 (s, 1H), 7.61-7.44 (m, 5H), 6.16-6 .05 (m, 1H), 5.95-5.85 (m, 1H), 5.17-5.07 (m, 4H), 4.21 (brd, J = 5.0 Hz, 2H), 3.96 (s, 6H), 3.57 (d, J = 6.5 Hz, 2H) Measured values: C, 71.53; H, 5.14; N, 6.20. C ₂₈ H ₂₃ N calculated _{2 ClO 3:. C, 71.41} ; H, 4.92; N, 5.95 followed by, (ii) melting point 269-27 ℃ monoallyl compound as a yellow solid (703) (31%) was _{^{obtained. 1 H NMR δ [(CD}} 3) 2 SO] 11.10 (br, 1H), 8.52 (s, 1H), 7. 77 (s, 1H), 7.58 to 7.43 (m, 4H), 6.16 to 6.07 (m, 1H), 5.17 to 5.07 (m, 2H), 3.95 ( . s, 6H), 3.57 ( d, J = 6.5Hz, 2H) Found: C, 69.58; H, 4.55 ; N, the _6.46.C 25 _H 19 _N 2 ClO ₃ Calculated C, 69.69; H, 4.44; N, 6.50.

Example 326 4- (2-chlorophenyl) -9-methoxy-6-methyl-8-vinylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (L; Ar = 2 ^{chlorophenyl, R 10 = Me, Z =} H) preparation of (704).
Triflate (700) prepared as in Example 321 was reacted with tetravinyltin at 100 ° C. for 1 hour according to the procedure described in Example 309 and then treated with excess ammonium acetate at 100 ° C. for an additional hour. To obtain a crude product. This was chromatographed on silica gel (ethyl acetate / petroleum ether) (1: 2) to give pure 8-vinyl compound (704) (78%) as an orange solid of melting point 330 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.12 (br, 1H), 8.53 (s, 1H), 7.94 (s, 1H), 7.78 (s, 1H), 7. 60 to 7.43 (m, 4H), 7.20 (dd, J = 17.7, 11.2 Hz, 1H), 6.10 (dd, J = 17.7, 1.2 Hz, 1H), 5 .43 (dd, J = 11.2, 1.2 Hz, 1H), 3.99 (s, 3H), 3.97 (s, 3H). ). Found: C, 58.54; H, 4.08; N, 6.65. _{C 24 H 17 N 2 ClO 3} . CH ₂ Cl _2. Calculated _{1 / 2NH 3 C, 58.84;} H, 4.05; N, 6.86. Calculated value of FABMS [M + H] ⁺ : 417.0982, 419.0955. Calculated 417.1006,419.0977 of _{C 24 H 17 N 2 ClO 3} .

Example 327 4- (2-chlorophenyl) -8-[(1E) -3-hydroxy-1-propenyl] -9-methoxy-6-methylpyrrolo [3,4-c] carbazole-1,3 (2H , 6H) - dione (L; preparation of Ar = _{^{2-chlorophenyl, R 10 = Me, Z =}} CH 2 OH) (710).
The triflate (700) prepared as in Example 321 was reacted with 3-hydroxyallyltri-n-butyltin for 1 hour at 100 ° C. by the procedure described in Example 309 to give the crude product. This was chromatographed on silica gel (ethyl acetate / petroleum ether) (1: 1) to give pure (710) (42%) as an orange solid, mp 283-285 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.11 (s, 1H), 8.51 (s, 1H), 7.89 (s, 1H), 7.76 (s, 1H), 7. 59-7.43 (m, 4H), 7.05 (brd, J = 16.0 Hz, 1H), 6.67 (dt, J = 16.0, 5.0 Hz, 1H), 4.94 ( t, J = 5.4 Hz, 1H), 4.22 (br t, J = 5.0 Hz, 2H), 3.99 (s, 3H), 3.97 (s, 3H). Calculated for FABMS M ⁺ : 446.1031, 448.1037. Calculated 446.1033,448.1004 of _{C 24 H 17 N 2 ClO 3} .

  Exemplary Procedure for Method 28 of Scheme 12

Example 328 Preparation of Biallyl Compound (LVI; Ar = 2-Chlorophenyl, R = Me) (702) to Dealkylate Monoallyl Compound (LVII; Ar = 2-Chlorophenyl, R ¹⁰ = Me) (703) .
The bisallyl 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 5M KOH (1 mL) and the mixture was stirred at room temperature for 64 hours. Most of the acetonitrile was evaporated under reduced pressure and the residue was diluted with water (3 mL). After acidification with 1N HCl to pH <1, the acidic solution was stirred at 50-60 ° C. (bath) for 3 hours. After partitioning between ethyl acetate and water, the ethyl acetate solution was evaporated and co-evaporated with toluene to give an orange solid. This was treated with a large excess of molten ammonium acetate at 140-145 ° C. (bath) for 3 hours. After cooling to room temperature and partitioning between ethyl acetate and water, the ethyl acetate solution was evaporated to give the crude product. This was chromatographed on silica gel (ethyl acetate-petroleum ether) (1: 3) to give the pure monoallyl compound (703) (52 mg, 79%). R _f , melting point and ¹ H NMR spectrum were identical to the standard sample.

Example 329 Preparation of dealkylation of bisallyl compound (LVI; Ar = phenyl, R = Me) (186) to give monoallyl compound (LVII; Ar = phenyl, R ¹⁰ = Me) (187).
Using the procedure described in Example 328, the bisallyl compound (186) prepared as described in Example 322 was converted to the monoallyl compound (187) (84%). R _f , melting point and ¹ H NMR spectrum were identical to the standard sample.

Example 330 8- (2,3-dihydroxypropyl) -9-methoxy-6-methyl-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (LIX; n = 1, Ar = phenyl, R ¹⁰ = Me) (705).
N-methylmorpholine N-oxide and osmium tetroxide prepared in Example 329 (187), reacted according to the procedure described in Example 300 (5 hours at room temperature), followed by chromatography on silica gel (acetic acid Ethyl) gave (705) (81%) as an orange solid, mp 243-245 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.06 (br, 1H), 8.51 (s, 1H), 7.78 (s, 1H), 7.68-7.63 (m, 2H) ), 7.55 (s, 1H), 7.50-7.42 (m, 3H), 4.58-4.52 (m, 2H), 3.95 (s, 3H), 3.93 ( s, 3H), 3.40 (d, J = 5.3 Hz, 2H), 3.30 (dd, J = 13.5, 5.2 Hz, 1H), 2.77 (dd, J = 13.5) 7.8 Hz, 1H). Found: C, 69.02; H, 5.48; N, 6.44. _{C 25 H 22 N 2 O 5} . 1 / 5H ₂ O Calculated: C, 69.18; H, 5.20 ; N, 6.45.

Example 331 8- (1,2-dihydroxyethyl) -9-methoxy-6-methyl-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (LIX; n = 0, Ar = phenyl, R ¹⁰ = Me) (706).
Prepared as described in Example 321 (701), N-methylmorpholine N-oxide and osmium tetroxide were reacted according to the procedure described in Example 300 (5 hours at room temperature) followed by silica gel. Chromatography (chloroform / methanol) (10: 1) gave (706) (65%) as a yellow solid, mp 242-245 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.09 (s, 1H), 8.53 (s, 1H), 7.81 (s, 1H), 7.74 (s, 1H), 7. 68-7.64 (m, 2H), 7.50-7.41 (m, 3H), 5.35 (d, J = 4.4 Hz, 1H), 5.12-5.06 (m, 1H) ), 4.75 (t, J = 5.3 Hz, 1H), 3.97 (s, 3H), 3.95 (s, 3H), 3.66 to 3.60 (m, 1H), 3. 39-3.33 (m, 1H). Found: C, 69.25; H, 5.14; N, 6.43. Calculated _{C 24 H 20 N 2 O 5} : C, 69.22; H; 4.84; N, 6.73.

Example 332 8- (2,3-dihydroxypropyl) -9-hydroxy-6-methyl-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (LX; n = 1, Ar = phenyl, R ¹⁰ = Me) (707).
(705), prepared as described in Example 300, was reacted with BBr ₃ by the procedure described in Example 80 (4 hours at 0 ° C.) to give phenol as an orange solid with a melting point of 283-285 ° C. 707) (53%). ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.01 (br, 1H), 9.41 (br, 1H), 8.38 (s, 1H), 7.74 (s, 1H), 7. 67-7.62 (m, 2H), 7.50-7.40 (m, 4H), 3.92 (s, 3H), 3.90-3.84 (m, 1H), 3.36 ( d, J = 5.2 Hz, 2H), 2.98 (dd, J = 13.5, 5.0 Hz, 1H), 2.74 (dd, J = 13.5, 7.7 Hz, 1H). Calculated for FABMS M ^<+ > 416.1365. Calcd 416.1372 for _{C 24 H 20 N 2 O 5} .

Example 333 9-hydroxy-8- (2-hydroxyethyl) -6-methyl-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (LII; Ar = ^{phenyl, R 10 = ME, Z =} OH) preparation of (714).
Prepared as described in Example 340 (712) was reacted with BBr ₃ by the procedure described in Example 80 (3 hours at 0 ° C.) followed by chromatography on silica gel (chloroform / methanol) ( 20: 1) to give phenol (714) (31%) as a yellow solid with a melting point of 233-235 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.01 (br, 1H), 9.39 (br, 1H), 8.39 (s, 1H), 7.74 (s, 1H), 7. 64 (dd, J = 7.6, 1.6 Hz, 2H), 7.50-7.42 (m, 4H), 4.73 (br, 1H), 3.92 (s, 3H), 3. 70 (t, J = 7.1 Hz, 2H), 2.94 (t, J = 7.1 Hz, 2H). Calculated for FABMS M ^<+> : 386.1263. Calcd 386.1267 for _{C 23 H 18 N 2 O 4} .

Example 334 4- (2-chlorophenyl) -9-hydroxy-8- (2-hydroxyethyl) -6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (LII ; Ar = ^{2-chlorophenyl, R 10 = Me, Z =} OH) preparation of (715).
(713) prepared as described in Example 341 was reacted with BBr ₃ by the procedure described in Example 80 (3 hours at 0 ° C.) followed by chromatography on silica gel (chloroform / methanol) ( 20: 1) to give phenol (715) (81%) as an orange solid with a melting point of 304-306 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.00 (br, 1H), 9.30 (br, 1H), 8.37 (s, 1H), 7.71 (s, 1H), 7. 57 (dd, J = 7.0, 2.0 Hz, 1H), 7.52 to 7.42 (m, 4H), 4.74 (br, 1H), 3.91 (s, 3H), 3 .71 (t, J = 7.0 Hz, 2H), 2.94 (t, J = 7.0 Hz, 2H). Calculated for FABMS M ⁺ : 420.0866, 422.0875. Calculated 420.0877,422.0847 of _{C 23 H 17 ClN 2 O 4} .

Example 335 4- (2-chlorophenyl) -8-ethyl-9-methoxy-6-methylpyrrolo [3,4-c] carbazole- (1,3 (2H, 6H) -dione (LI; Ar = 2 - ^{chlorophenyl, R 10 = Me, Z =} H) preparation of (708).
The alkene (704) prepared as in Example 326 was hydrogenated with PtO ₂ according to the procedure described in Example 310 (reaction time 45 minutes) as an orange solid with a melting point of 262-264 ° C. The ethyl derivative (708) (97%) was obtained. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.08 (br, 1H), 8.48 (s, 1H), 7.77 (s, 1H), 7.60-7.42 (m, 5H) ), 3.95 (s, 6H), 3.90 to 3.84 (m, 1H), 2.82 (q, J = 7.5 Hz, 2H), 1.28 (t, J = 7.5 Hz) , 3H). Found: C, 68.21; H, 4.38; N, 6.48. _{C 24 H 19 N 2 ClO 3} . 1 / 10H ₂ O Calculated C, 68.52; H, 4.60; N, 6.66.

Example 336 4- (2-chlorophenyl) -8- (3-hydroxypropyl) -9-methoxy-6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (LI ; Ar = _{^{2-chlorophenyl, R 10 = Me, Z =}} CH 2 OH) preparation of (711).
Alkene (710) prepared as in Example 321 was hydrogenated with PtO ₂ by the procedure described in Method 26, followed by chromatography on silica gel (ethyl acetate / petroleum ether) (1: 1). The pure 8- (3-hydroxypropyl) compound (711) (44%) was obtained as an orange solid, mp 260-263 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.08 (s, 1H), 8.48 (s, 1H), 7.77 (s, 1H), 7.59-7.43 (m, 5H) ), 4.50 (t, J = 5.2 Hz, 1H), 3.95 (s, 6H), 3.49 (m, 2H), 2.83 (t, J = 7.7 Hz, 2H), 1.82 (m, 2H). Calculated for FABMS M ⁺ : 448.1194, 450.1200. Calculated 448.1190,450.1160 of _{C 25 H 21 ClN 2 O 4} .

Example 337 4- (2-chlorophenyl) -8-ethyl-9-hydroxy-6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (LII; Ar = 2 ^{chlorophenyl, R 10 = Me, Z =} H) preparation of (709).
(708) prepared as in Example 335 was reacted with pyridinium hydrochloride by the procedure described in Example 81 followed by chromatography on silica gel (ethyl acetate / petroleum ether) (1: 2). Phenol (709) (78%) was obtained as an orange solid with a melting point of 265-268 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.01 (s, 1H), 9.39 (s, 1H), 8.37 (s, 1H), 7.71 (s, 1H), 7. 59-7.55 (m, 1H), 7.52-7.42 (m, 4H), 3.93 (s, 3H), 2.79 (q, J = 7.5 Hz, 2H), 1. 27 (t, J = 7.5 Hz, 3H). Calculated value of EIMS M ⁺ : 404.0925, 406.0905. Calculated 404.0928,406.0898 of _{C 23 H 17 ClN 2 O 3} .

Example 338 8- [3- (dimethylamino) propyl] -9-hydroxy-6-methyl-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (LV Preparation of n = 3, Ar = phenyl, R ¹⁰ = Me, Z = NMe ₂ ) (720);
(717), prepared as described in Example 342, was reacted with pyridinium hydrochloride by the procedure described in Example 81 to give phenol (720) (83%) as an orange solid with a melting point of 315 ° C. It was. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.01 (br, 1H), 9.79 (br, 1H), 8.38 (s, 1H), 7.72 (s, 1H), 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). Calculated value of FABMS [M + H] ⁺ : 428.1972. Calcd 428.1974 for _{C 26 H 26 N 3 O 3} .

Example 339 8- [2- (dimethylamino) ethyl] -9-hydroxy-6-methyl-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (LV Preparation of n = 2, Ar = phenyl, R ¹⁰ = Me, Z = NMe ₂ ) (721);
(719) prepared as described in Example 343 was reacted with pyridinium hydrochloride by the procedure described in Example 81 followed by chromatography on silica gel (chloroform / methanol) (10: 1). Phenol (721) (97%) was obtained as an orange solid having a melting point of 278 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.01 (br, 2H), 8.36 (s, 1H), 7.73 (s, 1H), 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). Calculated value of FABMS [M + H] ⁺ : 414.1821. Calcd 414.1818 for _{C 25 H 24 N 3 O 3} .

Example 340 8- (2-hydroxyethyl) -9-methoxy-6-methyl-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (LI; Ar = ^{phenyl, R 10 = Me, Z =} OH) preparation of (712).
The alkene (701) prepared as described in Example 321 is reacted with 9-BBN according to the procedure described in Method 29 and chromatographed on silica gel (chloroform / methanol) (10: 1), mp 284 The 8- (2-hydroxyethyl) compound (712) (51%) was obtained as a yellow solid at 286 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.09 (s, 1 H), 8.52 (s, 1 H), 7.79 (s, 1 H), 7.66 (br d, J = 6. 4 Hz, 2H), 7.56 (s, 1H), 7.51 to 7.41 (m, 3H), 4.68 (t, J = 5.2 Hz, 1H), 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 Calculated _{O 4 C, 71.99; H,} 5.03; N, 7.00.

Example 341 4- (2-chlorophenyl) -8- (2-hydroxyethyl) -9-methoxy-6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (LI ; Ar = ^{2-chlorophenyl, R 10 = Me, Z =} OH) preparation of (713).
The alkene (704) prepared as in Example 326 is reacted with 9-BBN by the procedure described in Method 29 and chromatographed on silica gel (ethyl acetate / petroleum ether) (2: 1), mp 270 The 8- (2-hydroxyethyl) compound (713) (50%) was obtained as an orange solid at ˜272 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.08 (s, 1H), 8.49 (s, 1H), 7.77 (s, 1H), 7.59-7.55 (m, 2H) ), 7.53 to 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). Found: C, 66.14; H, 4.69; N, 6.51. Calculated _{C 24 H 19 N 2 ClO 4} : C, 66.29; H, 4.40; N, 6.44.

Example 342 8- [3- (dimethylamino) propyl] -9-methoxy-6-methyl-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (LIV Preparation of n = 3, Ar = phenyl, R ¹⁰ = Me, Z = NMe ₂ ) (717);
(188), prepared as described in Example 344, was reacted with methanesulfonyl chloride using the procedure described in Example 170 to give intermediate LIII (n = 3, Ar = phenyl, R ¹⁰ = Me, Z = OSO ₂ CH ₃ ) was obtained. This was further reacted with a 40% aqueous dimethylamine solution (using the procedure described in Example 179) at room temperature for 5 hours. The crude product was obtained after normal treatment. This was refluxed in toluene for 23 hours in the presence of excess ammonium acetate. Chromatography on silica gel (chloroform / methanol) (10: 1) gave pure dimethylaminopropyl compound (717) (60%) with a melting point of 175-178 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.07 (s, 1H), 8.51 (s, 1H), 7.78 (s, 1H), 7.68-7.63 (m, 2H) ), 7.55 (s, 1H), 7.51 to 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, 6.64; N, 9.05. _{C 27 H 27 N 3 O 3} . 3 / 2H ₂ O Calculated C, 69.21, H, 6.45; N, 8.97.

Example 343 8- [2- (dimethylamino) ethyl] -9-methoxy-6-methyl-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (LIV Ar = phenyl, R ¹⁰ = Me, Z = NMe ₂ , n = 2) (719).
Prepared as described in Example 340 (712) was reacted with methanesulfonyl chloride using the procedure described in Example 170 to give intermediate LIII (Ar = phenyl, n = 2, R ¹⁰ = Me, Z = OSO ₂ CH ₃ ) was obtained. This was further reacted with a 40% aqueous dimethylamine solution (using the procedure described in Example 179) at room temperature for 25 hours. The crude product was obtained after normal treatment. This was refluxed in toluene for 18 hours in the presence of excess ammonium acetate. Chromatography on silica gel (chloroform / methanol) (10: 1) gave the pure dimethylaminoethyl compound (719) (15%), mp 233-236 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.08 (s, 1H), 8.51 (s, 1H), 7.78 (s, 1H), 7.68-7.63 (m, 2H) ), 7.58 (s, 1H), 7.50-7.41 (m, 3H), 3.96 (s, 3H), 3.04 (s, 3H), 2.93 (t, J = 8.0 Hz, 2H), 2.54 (t, J = 8.0 Hz, 2H), 2.23 (s, 6H). Calculated value of EIMS M ⁺ : 427.1890. Calcd 427.1896 for _{C 26 H 25 N 3 O 3} .

  Representative Procedure for Method 29 of Scheme 12

Example 344 8- (3-hydroxypropyl) -9-methoxy-6-methyl-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (LVIII; Ar = ^phenyl, R ₁₀ = CH 3) preparation of (188).
A 9-borabicyclo [3.3.1] nonane solution (0.5 M tetrahydrofuran solution 1 mL, 0.49 mmol) was prepared as described in Example 329 (187) (65 mg, 0.16 mmol) in tetrahydrofuran (5 mL). ) Added to the solution. The reaction mixture was stirred at room temperature for 2 hours and 20 minutes, then 3M sodium acetate (1.5 mL) and 35% hydrogen peroxide (1.0 mL) were added. The mixture was stirred at room temperature for 1 hour 30 minutes, then diluted with brine and extracted with ethyl acetate (3 × 30 mL). The combined extract was dehydrated and concentrated. The residue was purified by column chromatography on silica, eluting with ethyl acetate / dichloromethane 1: 5 to soften melting point 105-110 ° C., melting point 130-134 ° C. 8- (3-hydroxypropyl)- 9-methoxy-6-methyl-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (58 mg, 85%) was obtained. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.06 (s, 1H), 8.51 (s, 1H), 7.78 (s, 1H), 7.66-7.64 (m, 2H) ), 7.53 (s, 1H), 7.50-7.44 (m, 3H), 4.52 (t, J = 5.1 Hz, 1H), 3.96 (s, 3H), 3. 94 (s, 3H), 3.52 to 3.45 (m, 2H), 2.82 (br t, 7.8 Hz, 2H), 1.82 (br dt, J = 7.8 Hz, 2H). Found: C, 70.93; H, 5.40; N, 6.54. _{C 25 H 12 N 2 O 4} . Calculated for _1/2 H2O: C, 70.91; H, 5.47; N, 6.62.

Example 345 9-hydroxy-8- (3-hydroxypropyl) -6-methyl-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (LII; Ar = Preparation of Phenyl, R ¹⁰ ═CH ₃ , Z═CH ₂ OH) (189) (188), prepared as described in Example 344, was demethylated using BBr ₃ by the procedure described in Example 80. To give (189) as a yellow solid. ¹ H NMR δ [(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 (brs, 1H), 3.92 (s, 3H), 3.49-3 .44 (m, 2H), 2.78 (br t, J = 7.9 Hz, 2H), 1.82 (br dt, J = 7.8 Hz, 2H).

Example 346 8-Ethyl-9-methoxy-6-methyl-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (LI; Ar = phenyl, R ¹⁰ = _{CH 3, Z = H) (} 190) triflate, prepared as described in example 320 of the (185), is reacted with tetraethyl tin by the procedure described in example 309, the melting point of 251 to 253 ° C. (190) (83%) was obtained as a yellow solid. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.07 (s, 1H), 8.53 (s, 1H), 7.77 (s, 1H), 7.67-7.64 (m, 2H) ), 7.53 (s, 1H), 7.50-7.42 (m, 3H), 3.95 (s, 3H), 3.94 (s, 3H), 2.81 (q, J = 7.5 Hz, 2H), 1.27 (t, J = 7.5 Hz, 3H). Found: C, 74.48; H, 5.20; N, 7.24. _{C 24 H 20 N 2 O 3} . 1 / 6H ₂ O Calculated: C, 74.40; H, 5.29 ; N, 7.23.

Example 347 8-ethyl-9-hydroxy-6-methyl-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (LII; Ar = phenyl, R ¹⁰ = _{CH 3, Z = H) (} 191) was prepared as condemned in example 346 of the (190), and demethylation with BBr ₃ by the procedure described in example 80, mp 278-283 (191) (92%) was obtained as a yellow solid at 0 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.00 (br s, 1H), 9.36 (s, 1H), 8.40 (s, 1H), 7.73 (s, 1H), 7 .66 to 7.63 (m, 2H), 7.49 to 7.41 (m, 4H), 3.93 (s, 3H), 2.78 (q, J = 7.5 Hz, 2H), 1 .27 (t, J = 7.5 Hz, 3H). Found: C, 74.36; H, 5.10; N, 7.45. Calculated _{C 23 H 18 N 2 O 3} : C, 74.58; H, 4.90; N, 7.56.

  Procedure of scheme 13

Example 348 4- (2-chlorophenyl) -8- (3-hydroxypropoxy) -2- (3-hydroxypropyl) -9-methoxy-6- (2-methoxyethyl) pyrrolo [3,4-c Preparation of carbazole-1,3 (2H, 6H) -dione (LXV: Ar = 2-chlorophenyl, R ¹⁰ = CH ₂ CH ₂ OCH ₃ , n = 3) (181) Prepared as described in Example 267 (167) was alkylated with 3-bromopropanol by the procedure described in Example 298 to give (181) (92%) as a yellow oil. This was used without further purification.

Example 349 4- (2-chlorophenyl) -8- (3-hydroxypropoxy) -9-methoxy-6- (2-methoxyethyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -Dione (LXVI; Ar = 2-chlorophenyl, R ¹⁰ = CH ₂ CH ₂ OCH ₃ , n = 3) (182) Preparation of (182) (182) by a series of reactions outlined in the procedure described in Example 328 Treatment gave (182) (58%) as an orange powder with a melting point of 251-257 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.03 (br s, 1 H), 8.46 (s, 1 H), 7.74 (s, 1 H), 7.57 (dd, J = 8. 0, 2.1 Hz, 1H), 7.51 to 7.42 (m, 3H), 7.36 (s, 1H), 4.67 (t, J = 4.9 Hz, 2H), 4.61 ( br, 1H), 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). Calculated value of EIMS: M ⁺ = 508.1398, 5101358. Calculated 508.1401,510.1371 of _{C 27 H 25 ClN 2 O 6} .

Example 350 4- (2-Chlorophenyl) -9-methoxy-6- (2-methoxyethyl) -8- [3- (4-morpholinyl) propoxy] pyrrolo [3,4-c] carbazole-1, 3 (2H, 6H) - dione; prepared as described in (LXIII Ar = ^{_{2-chlorophenyl, R 10 = CH 2 CH 2}} OCH 3, Z = 4- morpholinyl) preparation example 349 (183) (182 ) Is converted to the corresponding mesylate by reaction with methanesulfonyl chloride using the procedure described in Example 170 and reacted with morpholine by the procedure described in Example 179 as a yellow powder with a melting point of 271-275 ° C. (183) (71%) was obtained. This was immediately demethylated.

Example 351 4- (2-chlorophenyl) -9-hydroxy-6- (2-hydroxyethyl) -8- [3- (4-morpholinyl) propoxy] pyrrolo [3,4-c] carbazole-1, 3 (2H, 6H) - dione; prepared as described in (LXIV Ar = ^{_{2-chlorophenyl, R 10 = CH 2 CH 2}} OCH 3, Z = 4- morpholinyl) preparation example 350 (184) (183 ) Was demethylated with BBr ₃ by the procedure described in Example 80 except that the reaction conditions were 2 hours at 0 ° C. to give (184) (36%) as a yellow solid, mp 253-255 ° C. Obtained. ¹ H NMR δ [(CD ₃ ) ₂ SO] 10.97 (br s, 1 H), 8.94 (br s, 1 H), 8.34 (s, 1 H), 7.69 (s, 1 H), 7.56 (dd, J = 8.1, 2.2 Hz, 1H), 7.49 to 7.42 (m, 3H), 7.29 (s, 1H), 4.83 (br, 1H), 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). Calculated value of FABMS [M + H] ⁺ : 552.1732, 550 to 1740. Calculated 552.1715,550.1745 of _{C 29 H 29 ClN 3 O 6} .

Example 352 8- (3-bromopropoxy) -2- (3-bromopropyl) -9-methoxy-6-methyl-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, preparation of Ar = ^{phenyl, R 10 = Me, n =} 3) (722); - 6H) dione (LXI.
(154), prepared as described in Example 254, was alkylated with 1,3-dibromopropane (3.0 eq) (4 days at room temperature) by the procedure described in Example 298, after which the silica gel was Chromatography used (dichloromethane / petroleum ether) (3: 1) gave (722) (47%) as an orange solid, mp 158-160 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 8.50 (s, 1H), 7.76 (s, 1H), 7.69-7.64 (m, 2H), 7.51-7.43 (M, 3H), 7.39 (s, 1H), 4.31 (t, J = 6.0 Hz, 2H), 3.98 (s, 3H), 3.92 (s, 3H), 3. 77 to 3.71 (m, 4H), 3.59 (t, J = 6.5 Hz, 2H), 2.41 to 2.34 (m, 2H), 2.23 to 2.15 (m, 2H) ). Found: C, 57.16; H, 4.58; N, 4.73. _{C 28 H 16 N 2 Br 2} O 4. Calculated for 1/2 hexane: C, 56.64; H, 5.06; N, 4.26. Calculated value of FABMS M ^<+> : 612.0255, 614.0249, 616.0252. Calculated 612.0259,614.0239,616.0218 of _{C 28 H 26 Br 2 N 2} O 4.

Example 353 8- (3-bromopropoxy) -2- (3-bromopropyl) -4- (2-chlorophenyl) -9-methoxy-6-methylpyrrolo [3,4-c] carbazole-1,3 preparation of; (Ar = ^{2-chlorophenyl, R 10 = Me, n =} 3 LXI) (723) - (2H, 6H) dione.
(160), prepared as described in Example 260, was alkylated (1,5 eq) with 1,3-dibromopropane (15 eq) according to the procedure described in Example 298, after which silica gel was used. Chromatography (dichloromethane / petroleum ether) (3: 1) gave (723) (65%) as an orange solid, mp 165-167 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 8.47 (s, 1H), 7.76 (s, 1H), 7.60-7.57 (m, 1H), 7.53-7.43 (M, 3H), 7.41 (s, 1H), 4.31 (t, J = 6.0 Hz, 2H), 3.97 (s, 3H), 3.93 (s, 3H), 3. 77 to 3.68 (m, 4H), 3.56 (t, J = 6.5 Hz, 2H), 2.42 to 2.34 (m, 2H), 2.20 to 2.12 (m, 2H) ). Found: C, 53.54; H, 4.28; N, 4.20. _{C 28 H 25 N 2 ClBr 2} O 4. Calculated for 1/2 hexane: C, 53.82; H, 4.66; N, 4.05. Calculated value of FABMS M ⁺ : 645.9866, 647.9868, 6499.934: Calculated value of C ₂₈ H ₂₅ N ₂ ClBr ₂ O ₄ 9820.

Example 354 4- (2-chlorophenyl) -8- (3-hydroxypropoxy) -2- (3-hydroxypropyl) -9-methoxy-6-methylpyrrolo [3,4-c] carbazole-1,3 preparation of; (Ar = ^{2-chlorophenyl, R 10 = Me, n =} 3 LXV) (724) - (2H, 6H) dione.
(160), prepared as described in Example 260, was alkylated with 3-bromopropanol (2.2 equivalents) by the procedure described in Example 298 (31 hours at room temperature) before using silica gel. Chromatography (chloroform / methanol) (20: 1) gave (724) (98%) as an orange solid, mp 180-183 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 8.47 (s, 1H), 7.74 (s, 1H), 7.60 to 7.57 (m, 1H), 7.53 to 7.43 (M, 3H), 7.36 (s, 1H), 4.60 (t, J = 5.1 Hz, 1H), 4.50 (t, J = 5.0 Hz, 1H), 4.25 (t , J = 6.3 Hz, 2H), 3.96 (s, 3H), 3.92 (s, 3H), 3.67 to 3.60 (m, 4H), 3.47 to 3.41 (m) , 1H), 2.02-1.95 (m, 2H), 1.79-1.71 (m, 2H). Found: C, 64.03; H, 5.21; N, 5.25. Calculated C of _{C 28 H 27 N 2 ClO 6} , 64.31; H, 5.20; N, 5.36.

Example 355 4- (2-chlorophenyl) -8- (3-hydroxypropoxy) -9-methoxy-6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (LXVI Ar = 2-chlorophenyl, R ¹⁰ = Me, n = 3) (725).
Prepared as described in Example 354 (724) was converted to the series of reactions described in the procedure described in Example 328 (5M KOH / MeOH / reflux / 3 hours; 1N HCl / 100 ° C./3 hours; NH ₄ OAc / 150 ° C./20 min) to give (725) (85%) as an orange solid with a melting point of 285-287 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.02 (br, 1H), 8.46 (s, 1H), 7.72 (s, 1H), 7.59-7.55 (m, 1H ), 7.51-7.42 (m, 3H), 7.34 (s, 1H), 4.60 (t, J = 5.1 Hz, 1H), 4.25 (t, J = 6.3 Hz) , 2H), 3.95 (s, 3H), 3.91 (s, 3H), 3.67 to 3.61 (m, 2H), 2.02 to 1.95 (m, 2H). Found: C, 64.69; H, 4.60; N, 6.11. Calculated for _{C 25 H 21 N 2 ClO 5} : C, 64.31; H, 5.20; N, 5.36.

Example 356 8- [3- (dimethylamino) propoxy] -2- [3- (dimethylamino) propyl] -9-methoxy-6-methyl-4-phenylpyrrolo [3,4-c] carbazole- 1,3 (2H, 6H) - dione; preparation of (LXII Ar = _{^{phenyl, R 10 = Me, Z =}} NMe 2, n = 3) (726).
(722), prepared as described in Example 352, was reacted with excess dimethylamine HCl in DMF in the presence of triethylamine and 4A molecular sieves at room temperature for 66 hours (Method 30?), Mp 278- (726) (35%) was obtained as the dihydrochloride salt at 281 ° C. (decomposition). ¹ H NMR δ [(CD ₃ ) ₂ SO] 9.95 (br, 2H), 8.51 (s, 1H), 7.81 (s, 1H), 7.70-7.65 (m, 2H) ), 7.52 to 7.43 (m, 3H), 7.40 (s, 1H), 4.28 (t, J = 6.1 Hz, 2H), 3.99 (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 to 2.20 (m, 2H), 2.26 to 1.97 (m, 2H). Found: C, 59.07; H, 6.68; N, 8.44. Calculated for _{C 32 H 40 N 4 Cl 2} O 4: C, 58.98; H, 6.81; N, 8.60.

Example 357 4- (2-chlorophenyl) -8- [3- (dimethylamino) propoxy] -2- [3- (dimethylamino) propyl] -9-methoxy-6-methylpyrrolo [3,4-c ] carbazole -1,3 (2H, 6H) - dione; preparation of (LXII Ar = _{^{2-chlorophenyl, R 10 = Me, Z =}} NMe 2, n = 3) (727).
(723) prepared as described in Example 353 was reacted with excess dimethylamine HCl in DMF in the presence of triethylamine and 4A molecular sieve for 6 days at room temperature (Method 30?) Followed by silica gel ( Chromatography with chloroform / methanol / triethylamine (10: 1: 0.1) gave (727) (63%) as the dihydrochloride salt with a melting point of 207-210 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 9.89 (br, 2H), 8.48 (s, 1H), 7.79 (s, 1H), 7.61 to 7.56 (m, 1H) ), 7.53 to 7.44 (m, 3H), 7.41 (s, 1H), 4.28 (t, J = 6.0 Hz, 2H), 3.97 (s, 3H), 3. 94 (s, 3H), 3.65 (t, J = 6.6 Hz, 2H), 3.23 (br, 2H), 3.34 (br, 2H), 2.80 (s, 6H), 2 .69 (s, 6H), 2.28 to 2.19 (m, 2H), 2.03 to 1.92 (m, 2H). Found: C, 58.09; H, 6.13; N, 8.44. _{C 32 H 37 N 4 ClO 4} . 2.2 Calculated for HCl: C, 58.47; H, 6.01; N, 8.52. Found: C, 59.07; H, 6.68; N, 8.44. Calculated for _{C 32 H 40 N 4 Cl 2} O 4: C, 58.98; H, 6.81; N, 8.60.

Example 358 4- (2-chlorophenyl) -8- [3- (dimethylamino) propoxy] -2- [3- (dimethylamino) propyl] -9-methoxy-6-methylpyrrolo [3,4-c ] carbazole -1,3 (2H, 6H) - dione; preparation of (LXII Ar = _{^{2-chlorophenyl, R 10 = Me, Z =}} NMe 2, n = 3) (727).
On a large scale, (727) was prepared from (160) prepared as described in Example 260 in the presence of excess anhydrous potassium carbonate and 4A molecular sieves in 3-dimethylaminopropyl chloride (7. 3 equivalents) and 60-70 ° C. (bath temperature) for 3 hours. The crude product yield was 96%. This was used in the next step without further purification.

Example 359 4- (2-chlorophenyl) -8- [3- (dimethylamino) propoxy] -9-methoxy-6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H)- preparation of; (Ar = _{^{2-chlorophenyl, R 10 = Me, Z =}} NMe 2, n = 3 LXIII) (728) dione.
After acid treatment, the reaction mixture was evaporated to dryness and a series of reactions as described in Example 328 (5M KOH / MeOH / reflux / 3 hours; 1N HCl / 100, with the modification of fusing with NH ₄ OAc). ° C. / 3 _hours; NH 4 by OAc / 170 ℃ / 10 hours), to process the prepared (727) as described in example 358, followed by chromatography on silica (dichloromethane / MeOH = 5: 1 ) To give (728) (97%) as an orange solid with a melting point of 288-290 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.04 (br, 1H), 8.46 (s, 1H), 7.72 (s, 1H), 7.59-7.55 (m, 1H) ), 7.51-7.42 (m, 3H), 7.33 (s, 1H), 4.21 (t, J = 6.5 Hz, 2H), 3.95 (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. _{C 27 H 26 N 3 ClO 4} . Calculated for hexane: C, 68.58; H, 6.97; N, 7.27. Calculated value of FABMS [M + H] ⁺ : 492.1689, 494.1675. Calculated 492.1690,494.1661 of _{C 27 H 27 N 3 ClO 4} .

Example 360 4- (2-Chlorophenyl) -9-methoxy-6-methyl-8- [3- (4-morpholinyl) propoxy] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H preparation of Ar = ^{2-chlorophenyl, R 10 = Me, Z =} 4- morpholinyl, n = 3) (729) ; -) dione (LXIII.
(725), prepared as described in Example 355, was converted to the corresponding mesylate by reaction with methanesulfonyl chloride using the procedure described in Example 170 Example 170 and by the procedure described in Example 179. React with morpholine and treat the crude product with NH ₄ OAc at 160-170 ° C. for 2 hours (silica column; after chloroform / MeOH = 10: 1) as orange powder with melting point 293-295 ° C. (729) (76%) was obtained. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.04 (br, 1H), 8.47 (s, 1H), 7.72 (s, 1H), 7.59-7.55 (m, 1H) ), 7.52 to 7.42 (m, 3H), 7.34 (s, 1H), 4.22 (t, J = 6.4 Hz, 2H), 3.96 (s, 3H), 3. 91 (s, 3H), 3.59 (br t, J = 4.6 Hz, 4H), 2.60 to 2.36 (m, 6H), 2.03 to 1.95 (m, 2H). Calculated value of FABMS [M + H] ⁺ : 534.1792, 536.1769. Calculated 534.1796,536.1766 of _{C 29 H 29 N 3 ClO 5} .

Example 361 4- (2-Chlorophenyl) -9-methoxy-6-methyl-8- [3- (1-pyrrolidinyl) propoxy] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H preparation of Ar = ^{2-chlorophenyl, R 10 = Me, Z =} 1- pyrrolidinyl, n = 3) (730) ; -) dione (LXIII.
Prepared as described in Example 355 (725) was converted to the corresponding mesylate by reaction with methanesulfonyl chloride using the procedure described in Example 170 and by the procedure described in Scheme 3 of Example 179. Reaction with pyrrolidine and treatment of the crude product with NH ₄ OAc at 160-170 ° C. for 4 hours (silica column; after chloroform / MeOH = 10: 1) as an orange powder with a melting point of 273-275 ° C. (730) (78%) was obtained. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.03 (br, 1H), 8.45 (s, 1H), 7.73 (s, 1H), 7.59 to 7.55 (m, 1H) ), 7.52 to 7.42 (m, 3H), 7.34 (s, 1H), 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 to 1.96 (m, 2H), 1.73 to 1. 67 (m, 4H). Found: C, 66.40; H, 5.47; N, 7.85. _{C 29 H 28 N 3 ClO 4} . Calculated for _1/2 H2O C, 66.09; H, 5.55; N, 7.97.

Example 362 8- [3- (dimethylamino) propoxy] -9-methoxy-6-methyl-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (LXIII) ; Ar = _{^{2-phenyl, R 10 = Me, Z =}} NMe 2, n = 3) preparation of (731).
After acid treatment, the reaction mixture was evaporated to dryness and a series of reactions as described in Example 328 (5M KOH / MeOH / reflux / 3 hours; 1N HCl / 100, with the modification of fusing with NH ₄ OAc). (726) prepared as described in Example 356 by treatment with 720 ° C./3 h; NH ₄ OAc / 170 ° C./10 h) and after a silica column (dichloromethane / MeOH = 5: 1) hygroscopic solids Of (731) (37%) was obtained. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.04 (br, 1H), 8.48 (s, 1H), 7.75 (s, 1H), 7.68-7.62 (m, 2H) ), 7.51 to 7.42 (m, 3H), 7.33 (s, 1H), 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), 2.61 to 1.93 (m, 2H). LCMS (APCI) m / z: 458.101 [M + H] ^< +>.

Example 363 4- (2-Chlorophenyl) -8- [3- (dimethylamino) propoxy] -9-hydroxy-6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H)- preparation of; (Ar = _{^{2-chlorophenyl, R 10 = Me, Z =}} NMe 2, n = 3 LXIV) (732) dione.
(728), prepared as described in Example 359, was demethylated using BBr ₃ by the procedure described in Example 80 except that the reaction conditions were 2 hours at 0 ° C., mp 259-262 ° C. Gave (732) (83%) as an orange solid. ¹ H NMR δ [(CD ₃ ) ₂ SO] 10.99 (s, 1 H), 9.22 (br, 1 H), 8.35 (s, 1 H), 7.70 (s, 1 H), 7. 58 to 7.54 (m, 1H), 7.51 to 7.42 (m, 3H), 7.29 (s, 1H), 4.22 (t, J = 6.0 Hz, 2H); 92 (s, 3H), 2.89 (br, 2H), 2.50 (br, 6H), 2.13 to 2.03 (m, 2H). Calculated value of FABMS [M + H] ⁺ : 478.1532, 480.1519. Calculated 478.1534,480.1504 of _{C 26 H 25 N 3 ClO 4} .

Example 364 8- [3- (dimethylamino) propoxy] -9-hydroxy-6-methyl-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (LXIV Ar = phenyl, R ¹⁰ = Me, Z = NMe ₂ , n = 3) (733).
(731), prepared as described in Example 362, was demethylated with BBr ₃ by the procedure described in Example 80 except that the reaction conditions were 2 hours at 0 ° C., melting point 303-304 ° C. Gave (733) (56%) as an orange solid. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.00 (s, 1H), 9.00 (br, 2H), 8.39 (s, 1H), 7.73 (s, 1H), 7. 66 to 7.61 (m, 2H), 7.50 to 7.41 (m, 3H), 7.29 (s, 1H), 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 to 2.14 (m, 2H). Found: C, 60.61; H, 5.05; N, 7.82. Calculated for _{C 26 H 25 N 3 O 4} : C, 60.48; H, 5.06; N, 8.14.

Example 365 4- (2-Chlorophenyl) -9-hydroxy-6-methyl-8- [3- (4-morpholinyl) propoxy] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H preparation of Ar = ^{2-chlorophenyl, R 10 = Me, Z =} 4- morpholinyl, n = 3) (734) ; -) dione (LXIV.
(729), prepared as described in Example 360, was demethylated using BBr ₃ according to the procedure described in Example 80 except that the reaction conditions were 2 hours at 0 ° C., melting point 235-237 ° C. Gave (734) (60%) as an orange solid. ¹ H NMR δ [(CD ₃ ) ₂ SO] 10.98 (s, 1 H), 8.97 (br, 1 H), 8.33 (s, 1 H), 7.69 (s, 1 H), 7. 59 to 7.54 (m, 1H), 7.51 to 7.42 (m, 3H), 7.28 (s, 1H), 4.21 (t, J = 6.1 Hz, 2H); 92 (s, 3H), 3.61 (br, 4H), 2.58 to 2.37 (m, 6H), 2.05 to 1.95 (m, 2H). Calculated value of FABMS [M + H] ⁺ : 520.1648, 522.1635. Calculated 520.1639,522.1610 of _{C 28 H 27 N 3 ClO 5} .

Example 366 4- (2-Chlorophenyl) -9-hydroxy-6-methyl-8- [3- (1-pyrrolidinyl) propoxy] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H preparation of Ar = ^{2-chlorophenyl, R 10 = Me, Z =} 1- pyrrolidinyl, n = 3) (735) ; -) dione (LXIV.
(730), prepared as described in Example 361, was demethylated with BBr ₃ by the procedure described in Example 80 except that the reaction conditions were 2 hours at 0 ° C., melting point 234-236 ° C. Gave (735) (60%) as an orange solid. ¹ H NMR δ [(CD ₃ ) ₂ SO] 10.98 (br, 1 H), 9.27 (br, 1 H), 8.33 (s, 1 H), 7.68 (s, 1 H), 7. 58 to 7.55 (m, 1H), 7.51 to 7.42 (m, 3H), 7.30 (s, 1H), 4.20 (t, J = 6.2 Hz, 2H); 92 (s, 3H), 2.66 (t, J = 6.8 Hz, 2H), 2.54 to 2.35 (m, 4H), 2.04 to 1.96 (m, 2H), 1. 75-1.68 (m, 4H). Calculated value of FABMS [M + H] ⁺ : 504.1687, 506.1661. Calculated 504.1690,506.1661 of _{C 28 H 27 N 3 ClO 4} .

  Procedure of scheme 14

  Representative Procedure for Method 31 of Scheme 14

Preparation of; (Ar- ^{phenyl, R 8 = H, Y 1} = O LXVIII) (828) - ( Example 367) 5-methoxy -2 [(E, Z) -2- phenylethenyl] -1-benzofuran To a suspension of benzyltriphenylphosphonium bromide (1.85 g, 4.26 mmol) in tetrahydrofuran (30 mL), a solution of lithium bis (thymethylsilyl) amide (1 M tetrahydrofuran solution 4 mL, 3.98 mmol) was added. The solution turned bright orange / red. The reaction mixture was stirred at room temperature for 30 minutes and then a solution of 5-methoxy-1-benzofuran-2-carbaldehyde (827) (0.50 g, 2.84 mmol) in tetrahydrofuran (10 mL) was added. Then, 20 minutes later, water was added and tetrahydrofuran was removed under reduced pressure. The residue was extracted with ethyl acetate (2 × 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) (0.63 g, 0.62 g, mp 124-128 ° C. as a 1: 2 mixture of Z- and E-isomers. 89%). Found: C, 81.60; H, 5.61. C ₁₇ H ₁₄ O ₂ Calculated C, 81.58, H, 5.64.

Example 368 9-Methoxy-4-phenyl-1H- [1] benzofuro [3,2-e] isoindole-1,3 (2H) -dione (LXX; Ar = phenyl, R ⁸ = H, Y ¹ = O) (830) Preparation A diene mixture (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). , R ⁸ = H, Y ¹ = O) (829). This was used without further purification. This crude Diels-Alder adduct was aromatized with MnO ₂ by the procedure described in Scheme 2 of Example 79 to give dibenzofuran (830) (53%) as a yellow solid with a melting point of 271-275 ° C. . ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.41 (br s, 1H), 8.24 (d, J = 2.7 Hz, 1H), 7.98 (s, 1H), 7.77 ( d, J = 9.0 Hz, 1H), 7.67-7.65 (M, 2H), 7.51-7.45 (m, 3H), 7.30 (dd, J = 9.0, 2) .7 Hz, 1H), 3.91 (s, 3H). Found: C, 72.09; H, 3.84; N, 4.04. C ₂₁ H ₁₃ NO _4. 1 / 3H ₂ O Calculated: C, 72.20; H, 3.94 ; N, 4.01.

Example 369 9-Hydroxy-4-phenyl-1H- [1] benzofuro [3,2-e] isoindole-1,3 (2H) -dione (LXXI; Ar = phenyl, R ⁸ = H, Y ¹ = O) Preparation of (831) (830), prepared as described in Example 368, was demethylated with BBr ₃ by the procedure described in Example 80 to give a yellow solid of melting point 288-290 ° C. (831) (100%) was obtained. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.37 (br s, 1H), 9.74 (s, 1H), 8.13 (d, J = 2.6 Hz, 1H), 7.94 ( s, 1H), 7.66 to 7.63 (m, 3H), 7.51 to 7.44 (m, 3H), 7.11 (dd, J = 8.9, 2.6 Hz, 1H). Found: C, 71.17; H, 3.48; N, 4.07. C ₂₀ H ₁₁ NO _4. Calculated for _1/2 H2O: C, 71.00; H, 3.58; N, 4.14.

(Example 370) 2 - [(E, Z) -2- (2- chlorophenyl) ethenyl] -5-methoxy-1-benzofuran (LXVIII; Ar = ^{2-chlorophenyl, R 8 = H, Y 1} = O) Preparation of (832) 5-Methoxy-1-benzofuran-2-carbaldehyde (827) prepared as described in the examples was reacted with 2-chlorobenzyltriphenylphosphonium bromide by the procedure described in the method. , (832) (24%) with a melting point of 90-92 ° C. was obtained as a 1: 2 mixture of Z: E isomers. This was used without further purification.

Example 371 4- (2-chlorophenyl) -9-methoxy-1H- [1] benzofuro [3,2-e] isoindole-1,3 (2H) -dione (LXX; Ar = 2-chlorophenyl, Preparation of R ⁸ = H, Y ¹ = 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, R ⁸ = H, Y ¹ = O) (833) was obtained. This was used without further purification. This crude Diels-Alder adduct was aromatized with MnO ₂ by the procedure described in Scheme 2 of Example 79 to give dibenzofuran (834) (49%) as a yellow solid with a melting point of 246-248 ° C. . ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.46 (br s, 1 H), 8.22 (d, J = 2.7 Hz, 1 H), 7.99 (s, 1 H), 7.80 ( d, J = 9.0 Hz, 1H), 7.61 to 7.58 (m, 1H), 7.53 to 7.44 (m, 3H), 7.33 (dd, J = 9.0, 2 .7 Hz, 1H), 3.92 (s, 3H). Found: C, 66.53; H, 3.41; N, 3.54. Calculated _{C 21 H 12 ClNO 4: C} , 66.77; H, 3.20; N, 3.71.

Example 372 4- (2-chlorophenyl) -9-hydroxy-1H- [1] benzofuro [3,2-e] isoindole-1,3 (2H) -dione (LXXI; Ar = 2-chlorophenyl) Preparation of R ⁸ = H, Y ¹ = O) (835) Prepared as described in Example 371 (834) was demethylated with BBr ₃ by the procedure described in Example 80 to give a melting point of 140 (835) (89%) was obtained as a yellow solid at ˜145 ° C. ¹ H NMR δ [(CD ₃ ) 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, 1H), 7.66 (d, J = 8.9 Hz, 1H), 7.60 to 7.58 (m, 1H), 7.52 to 7.43 (m, 3H), 7.13 ( dd, J = 8.9, 2.6 Hz, 1H), calculated values of EIMS M ⁺ : 363.0294, 365.0269. Calculated for _{C 20 H 10 ClNO 4: 363.0298,3.65.0289} .

Example 373 2-[(E, Z) -2- (2-chlorophenyl) ethenyl] -5-methoxy-1-benzothiophene (LXVIII; Ar = 2-chlorophenyl, R ⁸ = H, Y ¹ = S ) (837) Preparation 5-methoxy-1-benzothiophene-2-carbaldehyde (836) was reacted with 2-chlorobenzyltriphenylphosphonium chloride by the procedure described in Example 37 to give an E / Z mixture of Diene (837) (63%) was obtained. ¹ H NMR δ (CDCl ₃ ) subisomers: 7.6 (d, 1H), 7.4 (m, 5H), 7.15 (s, 1H), 7.05 (s, 1H), 6. 9 (d, 1H), 6.75 (m, 2H), 3.85 (s, 3H). Main isomers: 7.75 (d, J = 9 Hz, 1H), 7.55 (m, 2H), 7.25 to 7.4 (m, 3H), 7.18 (m, 2H), 7. 05 (s, 1H), 6.95 (m, 2H).

Example 374 4- (2-chlorophenyl) -9-methoxy-1H- [1] benzothieno [3,2-e] isoindole-1,3 (2H) -dione (LXX; Ar = 2-chlorophenyl) Preparation of R ⁸ = H, Y ¹ = S) (839) Prepared (837) as described in Example 373 using maleimide and the procedure described in Method 4 except that the reaction time was 6 days. Reaction was performed to obtain an adduct (LXIX; Ar = 2-chlorophenyl, R ⁸ = H, Y ¹ = S) (838). This was used without further purification. (838) was aromatized with DDQ according to the procedure described in Scheme 2 of Example 70 except that the solvent was chloroform and the reaction conditions were 40 ° C. for 5 days to give (839) (44 %). ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.46 (s, 1H), 9.37 (d, J = 2.5 Hz, 1H), 8.38 (s, 1H), 8.2 (d , J = 9 Hz, 1H), 7.62 (m, 2H), 7.48 (m, 3H), 7.31 (dd, J = 2.5, 9.0 Hz, 1H), 3.94 (s) , 3H).

Example 375 4- (2-chlorophenyl) -9-hydroxy-1H- [1] benzothieno [3,2-e] isoindole-1,3 (2H) -dione (LXXI; Ar = 2-chlorophenyl, ^{R 8 = H, Y 1 =} S) preparation of (840).
(839), prepared as described in Example 374, was demethylated with BBr ₃ according to the procedure described in Example 80 except that the reaction time was 48 hours to give a yellow solid with a melting point of 311-313 ° C. As a result, (840) (65%) was obtained. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.42 (s, 1H), 9.85 (s, 1H), 9.17 (d, J = 2.5 Hz, 1H), 8.32 (s , 1H), 7.9 (d, J = 9 Hz, 1H), 7.62 (m, 2H), 7.5 (m, 3H), 7.17 (dd, J = 2.5, 9 Hz, 1H) ). MH ⁺ 346. Calculated C, 68.75; H, 3.43; N, 3.89; S, 9.35. C ₂₀ H ₁₁ NO ₃ S. 0.2 H ₂ O Calculated: C, 68.83; H, 3.29 ; N, 4.01; S, 9.19.

Example 376 6- (Benzyloxy) -2-[(E, Z) -2- (chlorophenyl) ethenyl] -5-methoxy-1-benzofuran (LXVIII; R ⁸ = OCH ₂ Ph, Y ¹ = O , Ar = 2-chlorophenyl) (601) 6- (Benzyloxy) -5-methoxy-1-benzofuran-2-carbaldehyde (LXVIII; Y ¹ ═O, R ⁸ ═OCH ₂ Ph) was prepared according to Method 2. And reacted with 2-chlorobenzyltriphenylphosphonium chloride for 4 hours reaction time to give (601) (83%) as a pale yellow solid, mp 130-135 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 7.88 (d, J = 6.4 Hz, 1H), 7.51 to 7.31 (m, 12H), 7.18 (s, 1H), 6 .93 (s, 1H), 5.17 (s, 2H), 3.78 (s, 3H). Calculated value of EIMS: M ⁺ = 3900.1021. Calcd 390.1023 for C ₂₄ H ₁₉ ClO _3.

Example 377 8- (benzyloxy) -4- (2-chlorophenyl) -9-methoxy-1H- [1] benzofuro [3,2-e] isoindole-1,3 (2H) -dione (LXX Preparation of R ⁸ ═OCH ₂ Ph, Y ¹ ═O, Ar = 2-chlorophenyl (603) Using the procedure described in Method 4a using xylene as the solvent, from (601) to compound (602) (LXIX _{^{;.. R 8 = OCH 2}} Ph, Y 1 = O, Ar = 2- chlorophenyl) were prepared to give a brown solid which was used without further purification the crude Diels - Alder adduct Aromatization with MnO ₂ by the procedure described in Example 79 gave (603) (24%) as a light yellow solid with a melting point of 296-300 ° C. ¹ H NMR δ [(CD ₃ ) ₂ S ] 11.38 (s, 1H), 8.17 (s, 1H), 7.94 (s, 1H), 7.67 (s, 1H), 7.58 to 7.36 (m, 13H), 5.28 (s, 2H), 3.93 (s, 3H): Calculated value for EIMS: M ⁺ = 483.0871. Calculated value for C ₂₈ H ₁₈ ClNO ₅ 483.0873.

  Scheme 15 procedure

Example 378 4- (2-chlorophenyl) -8-hydroxy-9-methoxy-1H- [1] benzofuro [3, -e] isoindole-1,3 (H) -dione (LXXII; Ar = 2 -Chlorophenyl) (604) Preparation The benzyl ether group of (603) prepared as described in Example 377 was removed using the procedure described in Example 260 to yield a yellow solid of melting point 294-298 ° C. (604) (86%) was obtained. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.34 (s, 1 H), 10.40 (s, 1 H), 8.12 (s, 1 H), 7.87 (s, 1 H), 7. 59-7.30 (m, 4H), 7.23 (s, 1H), 3.96 (s, 3H). Calculated value of EIMS: M ⁺ = 393.0400. Calcd 393.0404 for C ₂₁ H ₁₂ ClNO _5.

Example 379 4- (2-Chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydro-1H- [1] benzofuro [3,2-e] isoindol-8-yltrifluoromethane Preparation of Sulfonate (LXXIII; Ar = 2-chlorophenyl) (605) Using the procedure described in Example 307, compound (605) (88%) was prepared from (604) as a light brown solid with a melting point of 237-240 ° C. did. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.55 (s, 1 H), 8.47 (s, 1 H), 8.29 (s, 1 H), 8.11 (s, 1 H), 7. 62-7.45 (m, 4H), 4.07 (s, 3H). Calculated for FABMS: [M + H] ⁺ = 525.9958, 527.9940. Calculated 525.9975,527.9946 of _{C 22 H 12 ClF 3 NSO 7} .

Example 380 4- (2-Chlorophenyl) -8-ethyl-9-methoxy-1H- [1] benzofuro [3,2-e] isoindole-1,3 (2H) -dione (LXXV; Z = Preparation of H, Ar = 2-chlorophenyl) (606) From (605) prepared as described in Example 379, using the procedure described in Example 309 and tetraethyltin as the tin hydride, mp 252-257. Compound 606 (87%) was prepared as a yellow solid at 0C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.45-11.15 (br, 1H), 8.16 (s, 1H), 7.91 (s, 1H), 7.60-7.56 (M, 1H), 7.54 (s, 1H), 7.52 to 7.41 (m, 3H), 4.23 (s, 3H), 3.92 (m, 2H), 2.16 to 2.09 (m, 3H). Calculated value of EMS: M ⁺ = 405.0766. Calcd 405.0768 for C ₂₃ H ₁₆ ClNO _4.

Example 381 4- (2-Chlorophenyl) -8-ethyl-9-hydroxy-1H- [1] benzofuro [3,2-e] isoindole-1,3 (2H) -dione (LXXVIII; n = 2, Z = H, Ar = 2-chlorophenyl) (607) Prepared as described in Example 380 (606) was demethylated by the procedure described in Example 80 to give a melting point of 265-268 ° C. (607) (32%) was obtained as a yellow solid. ¹ H NMR δ [(CD ₃ ) ₂ SO] 8.13 (s, 1H), 7.68 (s, 1H), 7.57 to 7.52 (m, 3H), 7.44 to 7.31 (M, 4H), 2.85 (q, J = 7.6 Hz, 2H), 1.35 (t, J = 7.6 Hz, 3H). Calculated value of EMS: M ⁺ = 391.0612. Calcd 391.0611 for C ₂₂ H ₁₄ ClNO _4.

Example 382 4- (2-chlorophenyl) -8-[(1E) -4-hydroxy-1-butenyl] -9-methoxy-1H- [1] benzofuro [3,2-e] isoindole-1 , 3 (2H) -dione (LXXIV; Z = CH ₂ CH ₂ OH, Ar = 2-chlorophenyl) (608) From the triflate (605) prepared as described in Example 379, Compound 608 (84%) was prepared as a yellow solid with a melting point of 247-250 [deg.] C using the described procedure and (3E) -4- (tributylstannyl) -3-buten-1-ol as tin hydride. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.43 (s, 1H), 8.23 (s, 1H), 7.92 (s, 1H), 7.86 (s, 1H), 7. 58 (d, J = 6.5 Hz, 1H), 7.48-7.42 (m, 3H), 6.85 (d, J = 16.0 Hz, 1H), 6.53 (m, 1H), 4.35 (br, 1H), 3.97 (s, 3H), 3.57 (t, J = 6.6 Hz, 2H), 2.41 (m, 2H). Calculated value of EIMS: M ⁺ = 447.0886. Calcd 447.0873 for C ₂₅ H ₁₈ ClNO _5.

Example 383 4- (2-Chlorophenyl) -8- (4-hydroxybutyl) -9-methoxy-1H- [1] benzofuro [3,2-e] isoindole-1,3 (2H) -dione Preparation of (LXXV; Z = CH ₂ CH ₂ OH, Ar = 2-chlorophenyl) (609) Prepared as described in Example 382 (608) was hydrogenated by the procedure described in Example 310 to give a melting point (609) (96%) was obtained as a yellow solid at 158-162 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.40 (s, 1H), 8.29 (s, 1H), 7.71 (s, 1H), 7.60 (s, 1H), 7. 56-7.39 (m, 4H), 4.36 (br, 1H), 3.95 (s, 3H), 3.39 (m, 2H), 2.75 (t, J = 7.6 Hz, 2H), 1.65 (m, 2H), 1.51 (m, 2H). Calculated for FABMS: [M + H] ⁺ = 450.1083, 452.1078. Calculated 450.1108,452.1079 of C ₂₅ H ₂₁ ClNO _5.

Example 384 4- (2-chlorophenyl) -9-hydroxy-8- (4-hydroxybutyl) -1H- [1] benzofuro [3,2-e] isoindole-1,3 (2H) -dione Preparation of (LXXVIII; n = 4, Z = OH, Ar = 2-chlorophenyl) (610) Prepared as described in Example 383 (609) was demethylated using the procedure described in Example 80. Thus, (610) (38%) was obtained as a yellow solid having a melting point of 256 to 259 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.40 (br, 1H), 9.80 (s, 1H), 8.13 (s, 1H), 7.90 (s, 1H), 7. 60 to 7.56 (m, 1H), 7.54 (s, 1H), 7.52 to 7.42 (m, 3H), 4.38 (s, 1H), 3.44 (m, 2H) 2.72 (t, J = 7.4 Hz, 2H), 1.66 (m, 2H), 1.50 (m, 2H). Calculated for FABMS: [M + H] ⁺ = 436.0942, 483.0922. Calculated 436.0952,438.0915 of C ₂₄ H ₁₉ ClNO _5.

Example 385 8- (3-bromopropoxy) -2- (3-bromopropyl) -4- (2-chlorophenyl) -9-methoxy-1H- [1] benzofuro [3,2-e] isoindole Preparation of -1,3 (2H) -dione (LXXIX; Ar = 2-chlorophenyl, n = 3) (331) Phenol (604) (245 mg, 0.62 mmol) prepared as described in Example 378 was The reaction was carried out with 1,3-dibromopropane (excess, 3.0 mL) by the procedure described in Example 298 except that the reaction was carried out with refluxing acetone (80 mL) to give a yellow powder having a melting point of 180-182 ° C. The bromide (331) (300 mg, 76%) was obtained. ¹ H NMR δ [(CD ₃ ) ₂ SO] 8.16 (s, 1H), 7.96 (s, 1H), 7.60 (m, 2H), 7.53 to 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. Calculated for _{C 27 H 22 Br 2 ClNO 5} : C, 51.01; H, 3.49; N, 2.20.

Example 386 4- (2-chlorophenyl) -8- [3- (dimethylamino) propoxy] -9-methoxy-1H- [1] benzofuro [3,2-e] isoindole-1,3 (2H ) -Dione (LXXXI; Ar = 2-chlorophenyl, n = 3, Z = N (CH) ₃ ) ₂ ) (332) Preparation of dibromide (331) (100 mg, 0 prepared as described in Example 385) .16 mmol) was reacted with aqueous dimethylamine (40%, 5.0 mL) by the procedure described in Example 179 except that the reaction was carried out in tetrahydrofuran (50 mL) at room temperature for 30 hours to give crude diamine (LXXX; Ar = give 2-chlorophenyl, n = 3, Z = n and _{(CH 3) 2).} This was used as a tetrahydrofuran solution without further purification. To this solution was added 5N potassium hydroxide (2.5 mL), followed by chromatography and methanol / dichloromethane / concentrated ammonia (15 according to the procedure outlined in Example 328 except HCl treatment was for 24 hours. : 85: Trace amount). Trituration from ethyl acetate gave amine (332) (64 mg, 84%) as a yellow powder with a melting point of 251-253 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.37 (br s, 1 H), 8.15 (s, 1 H), 7.93 (s, 1 H), 7.59 (m, 1 H), 7 .55 (s, 1H), 7.52 to 7.43 (m, 3H), 4.18 (t, J = 6.4 Hz, 2H), 3.93 (s, 3H), 2.5 (non- Clear m, 2H), 2.23 (brs, 6H), 1.96 (m, 2H). Found: C, 65.03; H, 4.79; N, 6.00. C ₂₆ H ₂₃ ClN ₂ O ₅ Calculated: C, 65.21; H, 4.84 ; N, 5.85.

Example 387 4- (2-chlorophenyl) -9-methoxy-8- [3- (1-pyrrolidinyl) propoxy] -1H- [1] benzofuro [3,2-e] isoindole-1,3 ( Preparation of 2H) -dione (LXXXI; Ar = 2-chlorophenyl, n = 3, Z = 1-pyrrolidinyl) (333) Dibromide (331) prepared as described in Example 385 (110 mg, 0.17 mmol) Was reacted with pyrrolidine (361 uL, 4.33 mmol) by the procedure described in Example 179 except that the reaction was carried out in tetrahydrofuran (50 mL) at room temperature for 3 days to give crude diamine (LXXX; Ar = 2-chlorophenyl, n = 3, Z = 1-pyrrolidinyl). This was used as a tetrahydrofuran solution without further purification. To this solution was added 5N potassium hydroxide (2.5 mL), followed by chromatography and methanol / dichloromethane / concentrated ammonia (15 according to the procedure outlined in Example 328 except HCl treatment was for 24 hours. : 85: Trace amount). Crystallization from ethyl acetate / hexane afforded amine (333) (51 mg, 59%) as a yellow powder with a melting point of 252-255 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.35 (br s, 1 H), 8.15 (s, 1 H), 7.91 (s, 1 H), 7.58 (m, 1 H), 7 .54 (s, 1H), 7.52 to 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. Calcd C of _{C 28 H 25 ClN 2 O 5} , 66.60; H, 4.99; N, 5.55.

Example 388 4- (2-chlorophenyl) -8- [3- (dimethylamino) propoxy] -9-hydroxy-1H- [1] benzofuro [3,2-e] isoindole-1,3 (2H Preparation of) -dione (LXXXII; Ar = 2-chlorophenyl, n = 3, Z = N (CH ₃ ) ₂ ) (334) Amine (332) prepared as described in Example 386 (70 mg, 0.15 mmol) ) Was demethylated by the procedure described in Example 80 except that the reaction was carried out at 0 ° C. for 8 hours, chromatographed and eluted with methanol / dichloromethane / triethylamine (15: 85: trace) to give a yellow Amine (334) (48 mg, 71%) was obtained as a powder. This was converted to the hydrochloride salt with a melting point of 255-258 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.34 (br s, 1 H), 9.96 (br s, 1 H), 9.44 (br s, 1 H), 8.10 (s, 1 H) 7.91 (s, 1H), 7.58 (m, 1H), 7.51 to 7.43 (m, 4H), 4.23 (t, J = 5.9 Hz, 2H),. 3 (unclear m, 2H), 2.81 (s, 6H), 2.21 (m, 2H). Found: C, 58.86; H, 4.68; N, 5.35. _{C 25 H 21 ClN 2 O 5} . HCl. Calculated for _1/2 H2O: C, 58.84; H, 4.54; N, 5.49.

Example 389 4- (2-chlorophenyl) -9-hydroxy-8- [3- (1-pyrrolidinyl) propoxy] -1H- [1] benzofuro [3,2-e] isoindole-1,3 ( Preparation of 2H) -dione (LXXXII; Ar = 2-chlorophenyl, n = 3, Z = 1-pyrrolidinyl) (335) Amine (333) prepared as described in Example 387 (50 mg, 0.10 mmol) was prepared. Demethylated by the procedure described in Example 80, except that the reaction was carried out at 0 ° C. for 6 hours, chromatographed and eluted with methanol / dichloromethane / triethylamine (15: 85: trace) as a yellow powder. Amine (335) (mg,%) was obtained. This was converted to the hydrochloride salt with a melting point of 302-304 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.34 (s, 1H), 9.99 (br, 1H), 9.47 (br, 1H), 8.10 (s, 1H), 7. 90 (s, 1H), 7.58 (m, 1H), 7.51 (s, 1H), 7.52 to 7.42 (m, 3H), 4.24 (t, J = 5.7 Hz, 2H), 3.6 (br, 2H), 3.03 (br, 2H), 2.22 (m, 2H), 2.08 to 1.81 (m, 6H). Found: C, 61.18; H, 4.56; N, 5.16. _{C 27 H 23 ClN 2 O 5} . Calculated value for HCl C; 61.49; H, 4.59; N, 5.31.

  Procedure of scheme 16

Example 390 4- (2-chlorophenyl) -6-methyl-1,3-dioxo-1,2,3,6-tetrahydropyrrolo [3,4-c] carbazol-8-yl trifluoromethanesulfonate (LXXXIII) Preparation of Ar = 2-chlorophenyl, R ¹⁰ = CH ₃ ) (316) Phenol (845) (0.25 g, 0.66 mmol) prepared as described in Example 280 was prepared according to the procedure described in Example 307. To give the triflate (316) (323 mg, 96%) as a pale yellow solid with a melting point of 230-233 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.26 (br s, 1H), 9.04 (d, J = 8.7 Hz, 1H), 8.03 (d, J = 2.3 Hz, 1H) ), 7.94 (s, 1H), 7.59 (m, 1H), 7.50 (m, 4H), 4.04 (s, 3H). Found: C, 51.98; H, 2.29; N, 5.41. C ₂₂ H ₁₂ ClF ₃ Calculated _{N 2 SO 5 C, 51.93;} H, 2.38; N, 5.51.

Example 391 4- (2-chlorophenyl) -6-methyl-8-vinylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (LXXXIV; Ar = 2-chlorophenyl, R ¹⁰ = CH ₃ ) (317) Preparation Triflate (316) (0.32 g, 0.63 mmol) prepared as described in Example 390 was prepared according to the procedure described in Example 309 using tetravinyltin (172 mL, 0 .94 mmol) gave alkene (317) (193 mg, 79%) as a pale yellow solid with a melting point of 276-282 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.13 (br s, 1H), 8.86 (d, J = 8.2 Hz, 1H), 7.84 (m, 2H), 7.60 to 7.46 (m, SH), 6.98 (dd, J = 17.6, 10.9 Hz, 1H), 6.09 (d, J = 17.6 Hz, 1H), 5.42 (d, J = 10.9 Hz, 1H), 4.00 (s, 3H). Found: C, 69.64; H, 4.03; N, 6.88. _{C 23 H 15 ClN 2 O 2} . Calculated for _1/2 H2O: C, 69.79; H, 4.07; N, 7.08.

Example 392 4- (2-chlorophenyl) -8- (2-hydroxyethyl) -6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (LXXXV; Ar = 2 Preparation of -chlorophenyl, R ¹⁰ = CH ₃ ) (318) Alkene (317) (60 mg, 0.16 mmol) prepared as described in Example 391 was reacted according to the procedure described in Example 344 to give a melting point of 289 Alcohol (318) (36 mg, 57%) was obtained as a pale yellow solid at ˜292 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.10 (br s, 1H), 8.81 (d, J = 8.1 Hz, 1H), 7.82 (s, 1H), 7.58 ( m, 2H), 7.49 (m, 3H), 7.27 (d, J = 8.1 Hz, 1H), 4.73 (t, J = 5.2 Hz, 1H), 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. _{C 23 H 17 ClN 2 O 3} . 1 / 4H ₂ O Calculated: C, 67.49; H, 4.31 ; N, 6.84.

Example 393 4- (2-chlorophenyl) -8- (1,2-dihydroxyethyl) -6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (LXXXVI; Ar = 2-Chlorophenyl, R ¹⁰ = CH ₃ ) (319) Preparation Alkene (317) (50 mg, 0.13 mmol) prepared as described in Example 391 was reacted according to the procedure described in Example 300, Diol (319) (40 mg, 74%) was obtained as a pale yellow solid having a melting point of 252 to 255 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.11 (br s, 1 H), 8.84 (d, J = 8.2 Hz, 1 H), 7.84 (s, 1 H), 7.71 ( br s, 1H), 7.58 (m, 1H), 7.49 (m, 3H), 7.39 (brd, J = 8.2 Hz, 1H), 5.46 (d, J = 4. 2 Hz, 1H), 4.79 (m, 2H), 3.98 (s, 3H), 3.57 (m, 2H). Found: C, 65.72; H, 4.50; N, 6.32. Calculated _{C 23 H 17 ClN 2 O 4} : C, 65.64; H, 4.07; N, 6.66.

Example 394 4- (2-chlorophenyl) -8- (hydroxymethyl) -6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (LXXXVII; Ar = 2-chlorophenyl) , R ¹⁰ = CH ₃ ) (320) through a solution of alkene (317) (60 mg, 0.16 mmol) in methanol / dichloromethane (1: 1, 40 mL) prepared as described in Example 391 at −78 ° C. Ozone was bubbled for 10 minutes. During this 10 minutes, the solution changed from yellow to yellow-green. Excess ozone was removed from the solution by bubbling nitrogen through the solution 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 warmed to room temperature for 20 minutes, then it was diluted with water and extracted with ethyl acetate. The organic phase was dehydrated, the dehydrating agent was removed, and the solution was concentrated to dryness. Chromatography on silica, eluting with ethyl acetate / hexane (3: 1 → 1: 0), followed by crystallization from ethyl acetate / hexane to give the alcohol as a pale yellow solid with a melting point of 291-294 ° C. 320) (39 mg, 62%). ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.11 (br s, 1H), 8.85 (d, J = 8.1 Hz, 1H), 7.84 (s, 1H), 7.70 ( br s, 1H), 7.58 (m, 1H), 7.49 (m, 3H), 7.35 (brd, J = 8.1 Hz, 1H), 5.42 (t, J = 5. 6 Hz, 1H), 4.77 (d, J = 5.6 Hz, 2H), 3.98 (s, 3H). Found: C, 67.74; H, 4.11; N, 7.13. Calculated for _{C 22 H 15 ClN 2 O 3} : C, 67.61; H, 3.87; N, 7.17.

Example 395 4- (2-Chlorophenyl) -8- (3-hydroxypropoxy) -2- (3-hydroxypropyl) -6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H Preparation of) -dione (LXXXVIII; Ar = 2-chlorophenyl, R ¹⁰ = CH ₃ ) (321) Phenol (845) (0.53 g, 1.41 mmol) prepared as described in Example 280 was Reaction with 3-bromopropan-1-ol (280 mL, 3.10 mmol) by the procedure described in 298 gave diol (321) (0.29 g, 42%) as a yellow powder with a melting point of 136-140 ° C. . ¹ H NMR δ [(CD ₃ ) ₂ SO] 8.77 (d, J = 8.7 Hz, 1H), 7.76 (s, 1H), 7.58 (m, 1H), 7.49 (m 3H), 7.28 (d, J = 2.0 Hz, 1H), 7.00 (dd, J = 8.7, 2.0 Hz, 1H), 4.61 (t, J = 5.1 Hz, 1H), 4.49 (t, J = 5.0 Hz, 1H), 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. _{C 27 H 25 ClN 2 O 4} . 1 / 4H ₂ O Calculated C, 65.19; H, 5.17; N; 5.63.

Example 396 4- (2-chlorophenyl) -8- (3-hydroxypropoxy) -6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (LXXXIX; Ar = 2 - _{^{chlorophenyl, R 10 = CH 3) (}} 322 diol was prepared as described in Preparative example 395) (321) (270mg, the 0.55 mmol), HCl processed using ethanol instead of acetonitrile for 18 hours A crude material was obtained by reaction according to the procedure described in Example 328 except for. This was dissolved in methanol / dichloromethane (4: 1, 80 mL) and to this was added 1M potassium carbonate (2.0 mL) (to hydrolyze the small amount of acetate as measured by tlc). The resulting solution was stirred at room temperature for 2 hours, subsequently diluted with water and extracted with ethyl acetate. The organic phase was dehydrated, the dehydrating agent was removed, and the solution was concentrated to dryness. Chromatography on silica, eluting with ethyl acetate / hexane (2: 1), followed by crystallization from ethyl acetate / hexane, gave alcohol (322) (136 mg) as a yellow solid, mp 274-276 ° C. 57%). ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.06 (br s, 1H), 8.75 (d, J = 8.7 Hz, 1H), 7.75 (s, 1H), 7.57 ( m, 1H), 7.48 (m, 3H), 7.27 (d, J = 2.1 Hz, 1H), 7.00 (dd, J = 8.7, 2.1 Hz, 1H), 4. 61 (t, J = 4.9 Hz, 1H), 4.24 (t, J = 6.3 Hz, 2H), 3.94 (s, 3H), 3.63 (m, 2H), 1.96 ( m, 2H). Found: C, 66.01; H, 4.41; N, 6.41. Calculated _{C 24 H 19 ClN 2 O 4} : C, 66.29; H, 4.40; N, 6.44.

Example 397 4- (2-chlorophenyl) -8- (3-iodopropoxy) -6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (XC; Ar = 2 Preparation of -chlorophenyl, R ¹⁰ = CH ₃ ) (323) Alcohol (322) prepared as described in Example 396 (82 mg, 0.19 mmol) was reacted according to the procedure described in Example 170, followed by Iodide (323) (92 mg, 89%) as a yellow solid with a melting point of 264-266 ° C. using the procedure described in Method 27 and chromatographing on silica eluting with ethyl acetate / hexane (2: 1). ) ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.07 (br s, 1H), 8.77 (d, J = 8.7 Hz, 1H), 7.76 (s, 1H), 7.58 ( m, 1H), 7.47 (m, 3H), 7.31 (d, J = 2. IHz, 1H), 7.02 (dd, J = 8.7, 2.1 Hz, 1H), 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. Calculated _{C 24 H 18 ClIN 2 O 3} : C, 52.91; H, 3.33; N, 5.14.

Example 398 4- (2-chlorophenyl) -8- [3- (dimethylamino) propoxy] -6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (XCI; Preparation of Ar = 2-chlorophenyl, R ¹⁰ = CH ₃ , Z = N (CH ₃ ) ₂ ) (324) Iodide (323) prepared as described in Example 397 (50 mg, 0.09 mmol) was Reacted with dimethylamine by the procedure described in Example 179 except that the reaction was carried out at room temperature for 2 hours and chromatographed using alumina (grades II-III) and ethyl acetate / methanol (1: 0 → 9). 1) to give amine (324) as a yellow powder. This was crystallized from methanol / diethyl ether / hexane as hydrochloride (43 mg, 96%), mp 262-265 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.08 (br s, 1 H), 10.0 (br s, 1 H), 8.78 (d, J = 8.7 Hz, 1 H), 7.78 (S, 1H), 7.58 (m, 1H), 7.48 (m, 3H), 7.29 (d, J = 2.1 Hz, 1H), 7.02 (dd, J = 8.7) , 2.1 Hz, 1H), 4.26 (t, J = 6.0 Hz, 2H), 3.96 (s, 3H), 3.28 (partially unclear m, 2H), 2.82. (S, 6H), 2.22 (m, 2H). Found: C, 59.62; H, 5.01; N, 8.02. _{C 26 H 24 ClN 3 O 3} . HCl. 1.5 H ₂ O Calculated: C, 59.43; H, 5.37 ; N, 8.00.

Example 399 4- (2-chlorophenyl) -6-methyl-8- [3- (methylamino) propoxy] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (XCI) ; Ar = ^{_{2-chlorophenyl, R 10 = CH 3, Z}} = NHCH 3) ( iodide, prepared as described in Preparative example 397 325) (323) (17mg, 0.03mmol) in tetrahydrofuran and the reaction Reaction with aqueous methylamine (40%, 54 uL) according to the procedure described in Example 179 except for 20 hours at medium room temperature to give amine (325) (6 mg, 43%) as a yellow powder with a melting point of 269-271 ° C. Got. ¹ H NMR δ [(CD ₃ ) ₂ SO] 8.75 (d, J = 8.1 Hz, 1H), 7.76 (s, 1H), 7.57 (m, 1H), 7.47 (m 3H), 7.27 (d, J = 2.1 Hz, 1H), 8.99 (dd, J = 8.7, 2.1 Hz, 1H), 4.22 (t, J = 6.4 Hz, 2H), 3.94 (s, 3H), 2.67 (t, J = 6.7 Hz, 2H), 2.32 (s, 3H), 1.94 (m, 2H). Calculated for FABMS: [M + H] ⁺ = 448.1447, 450.1428. Calculated 448.1428,450.1398 of _{C 25 H 22 ClN 3 O 3} .

Example 400 4- (2-Chlorophenyl) -8- [3- (cis-3,5-dimethyl-1-piperazinyl) propoxy] -6-methylpyrrolo [3,4-c] carbazole-1,3 ( Preparation of 2H, 6H) -dione (XCI; Ar = 2-chlorophenyl, R ¹⁰ = CH ₃ , Z = cis-3,5-dimethyl-1-piperazinyl) (326) Prepared as described in Example 397. Iodide (323) (17 mg, 0.03 mmol) was combined with cis-2,6-dimethylpiperazine (71 mg, 0.62 mmol) by the procedure described in Example 179 except that the reaction was carried out in tetrahydrofuran at room temperature for 20 hours. React and chromatograph with alumina (grade II-III) eluting with ethyl acetate / methanol (1: 0 → 9: 1) Allowed to give the amine (326) (15mg, 91%) as a yellow powder having a melting point of 225 to 227 ° C.. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.06 (br s, 1H), 8.75 (d, J = 8.7 Hz, 1H), 7.76 (s, 1H), 7.57 ( m, 1H), 7.47 (m, 3H), 7.25 (d, J = 2.1 Hz, 1H), 8.99 (dd, J = 8.7, 2.1 Hz, 1H), 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). Calculated for FABMS: [M + H] ⁺ = 531.2166, 533.2162. Calculated 531.2163,533.2133 of _{C 30 H 31 ClN 4 O 3} .

Example 401 8- (allyloxy) -4- (2-chlorophenyl) -6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (XCIII; Ar = 2-chlorophenyl, Preparation of R ¹⁰ = CH ₃ ) (327) Phenol (845) (250 mg, 0.66 mmol) prepared as described in Example 280 was reacted with allyl bromide by the procedure described in Example 298, A bis-allyl derivative (XCII; Ar = 2-chlorophenyl, R = CH ₃ ) was obtained. This was used without further purification. This crude material was reacted according to the procedure described in Example 328 to give the alkene (327) (216 mg, 79%) as a yellow powder with a melting point of 253-256 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.07 (br s, 1 H), 8.77 (d, J = 8.7 Hz, 1 H), 7.76 (s, 1 H), 7.57 ( m, 1H), 7.47 (m, 3H), 7.30 (d, J = 2.2 Hz, 1H), 7.03 (dd, J = 8.7, 2.2 Hz, 1H), 6. 20-6.11 (m, 1H), 5.51 (m, 1H), 5.33 (m, 1H), 4.77 (m, 2H), 3.92 (s, 3H). Found: C, 69.42; H, 4.27; N, 6.50. Calculated _{C 24 H 17 ClN 2 O 3} : C, 69.15; H, 4.11; N, 6.72.

Example 402 4- (2-Chlorophenyl) -8- (2-hydroxyethoxy) -6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (XCIV; Ar = 2 - _{^{chlorophenyl, R 10 = CH 3) (}} 328 alkenes (327) prepared as described in Preparative example 401) (50 mg, methanol / dichloromethane 0.12 mmol) (1: 1, 40 mL) -78 through the solution Ozone was bubbled at 10 ° C for 10 minutes. During this 10 minutes, the solution changed from yellow to yellow-green. Excess ozone was removed from the solution by bubbling nitrogen through the solution 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 warmed to room temperature for 45 minutes, then it was diluted with water and extracted with ethyl acetate. The organic phase was dehydrated, the dehydrating agent was removed, and the solution was concentrated to dryness. Chromatography on silica eluting with ethyl acetate / hexane (1: 1 → 3: 1) followed by trituration from diethyl ether gave alcohol (328) (11 mg, 22 mg) as a yellow solid of melting point 309-312 ° C. %). ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.06 (br s, 1H), 8.77 (d, J = 8.7 Hz, 1H), 7.75 (s, 1H), 7.57 ( m, 1H), 7.47 (m, 3H), 7.28 (d, J = 2.0 Hz, 1H), 7.01 (dd, J = 8.7, 2.0 Hz, 1H), 4. 94 (t, J = 5.4 Hz, 1H), 4.19 (t, J = 5.1 Hz, 2H), 3.95 (s, 3H), 3.81 (m, 2H). Calculated value of FABMS [M + H] ⁺ : 421.0932, 423.0912. Calculated 421.0955,423.0926 of _{C 23 H 17 ON 2 O 4} .

Example 403 4- (2-chlorophenyl) -8- (2,3-dihydroxypropoxy) -6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (XCV; Ar = 2-Chlorophenyl, R ¹⁰ = CH ₃ ) (329) Preparation Alkene (327) (30 mg, 0.07 mmol) prepared as described in Example 401 was reacted according to the procedure described in Example 300. Diol (329) (19 mg, 60%) was obtained as a yellow solid, mp 287-290 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.06 (br s, 1H), 8.77 (d, J = 8.7 Hz, 1H), 7.76 (s, 1H), 7.57 ( m, 1H), 7.47 (m, 3H), 7.27 (d, J = 2.2 Hz, 1H), 7.00 (dd, J = 8.7, 2.2 Hz, 1H), 5. 04 (d, J = 5.1 Hz, 1H), 4.73 (t, J = 5.6 Hz, 1H), 4.20 (dd, J = 8.8, 4.5 Hz, 1H), 4.07 (Dd, J = 9.9, 6.1 Hz, 1H), 3.95 (s, 3H), 3.89 (m, 2H), 3.52 (t, J = 5.6 Hz, 2H). Calculated value of FABMS [M + H] ⁺ : 451.1052, 453.1039. Calculated 451.1061,453.1031 of _{C 24 H 19 ClN 2 O 5} .

  Procedure of scheme 17

  Exemplary Procedure for Method 32 of Scheme 17

(Example 404) 1- (5-methoxy -1H- indol-2-yl) ethanone _{^{(XCVI; R 2 = CH 3}} ) (800) Preparation of 5-methoxy -1H- indole-2-carbaldehyde (1) To a solution of (2.0 g, 11.0 mmol) in tetrahydrofuran (30 mL), a methylmagnesium bromide solution (3 M ether solution 11 mL, 34.0 mmol) was added dropwise at 0 ° C. The cold bath was removed and the reaction mixture was warmed to room temperature for 50 minutes. Saturated ammonium chloride was added and then the tetrahydrofuran was removed under reduced pressure. The residue was extracted with ethyl acetate (2 × 60 mL) and the combined extracts were washed, dried and concentrated. The crude alcohol was dissolved in chloroform (40 mL), manganese dioxide (15 g, 0.171 mol) was added, and the reaction mixture was heated at reflux for 40 minutes. 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%), mp 170-172 ° C. ¹ H NMR δ [(CD ₃ ) 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, 1H), 6.94 (dd, J = 9.0, 2.4 Hz, 1H), 3.77 (s, 3H), 2.52 (s, 3H). Found: C, 69.77; H, 5.95; N, 7.54. Calculated for _{C 11 H 11 NO 2: C} , 69.83; H, 5.86; N, 7.40.

  Representative Procedure for Method 33 of Scheme 17

Example 405 Methyl 2-[(E, Z) -1-methyl-2-phenylethenyl] -1H-indol-5-yl ether (XCVII; R ² = CH ₃ , R ¹ = phenyl) (801 The LDA solution (4.9 mL of 1.5 M cyclohexane solution, 7.4 mmol) was added to a suspension of benzyltriphenylphosphonium bromide (3.4 g, 7.9 mmol) in tetrahydrofuran (30 mL). The red / orange reaction mixture was stirred for 10 minutes and then a solution of ketone (1.0 g, 5.3 mmol) in tetrahydrofuran (15 mL) was added. The mixture was heated at reflux overnight, then water was added and the solvent removed in vacuo. The organic material was extracted with ethyl acetate (3 × 50 mL). The combined extract was dehydrated 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. This was used without further purification.

(Example 406) 9-methoxy-5-methyl-4-phenyl-pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) - dione _{^{(XCIX; R 2 = CH 3}} , R 1 = phenyl) Preparation of (803).
(801), prepared as described in Example 405, was reacted with maleimide for 40 minutes at 180 ° C. using the procedure described in Example 69 to give the adduct (XCVIII; R ² = CH ₃ , R ¹ = Phenyl) (802) was obtained. This was used without further purification. This crude Diels-Alder adduct was reacted with MnO ₂ by the procedure described in Scheme 2 of Example 79 to aromatize to give (803) (69%).

Example 407 9-Hydroxy-5-methyl-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (C; R ² = CH ₃ , R ¹ = phenyl) Preparation of (804) (803), prepared as described in Example 406, was demethylated with BBr ₃ by the procedure described in Example 69 to give (804) (90%), mp 270-280 ° C. ) ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.60 (s, 1 H), 10.82 (s, 1 H), 9.22 (s, 1 H), 8.31 (d, J = 2.0 Hz) , 1H), 7.47-7.42 (m, 4H), 7.36-7.23 (m, 2H), 7.06 (dd, J. = 8.7, 2.0 Hz, 1H), 2.32 (s, 3H). Calculated value of EIMS M ⁺ : 342.1005. Calculated _{C 21 H 14 N 2 O 3} : 342.1004.

(Example 408) (5-methoxy -1H- indol-2-yl) (phenyl) methanone; and (XCVI ^{R 2} = phenyl) Preparation of 5-methoxy -1H- indole-2-carbaldehyde (805), carried Reaction with phenylmagnesium bromide using the procedure described in Example 404 gave (805) (91%), mp 159-161 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.86 (s, 1H), 7.94-7.91 (m, 2H), 7.71-7.66 (m, 1H), 7.61 -7.57 (m, 2H), 7.42 (d, J = 8.9 Hz, 1H), 7.16 (d, J = 2.4 Hz, 1H), 7.03 (s, 1H), 6 .99 (dd, J = 8.9, 2.4 Hz, 1H), 3.77 (s, 3H). Found: C, 76.28; H, 5.21; N, 5.42. Calculated for _{C 16 H 13 NO 2: C} , 76.48; H, 5.21; N, 5.57.

Example 409 Preparation of 2-[(E) -1,2-diphenylethenyl] -5-methoxy-1H-indole (XCVII; R ¹ = R ² = phenyl) (806) Freshly Washed Magnesium Ribbon To a solution of (magnesium turning) (0.29 g, 12 mmol) and iodine crystals in ether (20 mL) was added benzyl chloride (1.4 mL, 12 mmol) at a rate to maintain reflux of the reaction mixture. After complete addition of benzyl chloride, the reaction mixture was heated at reflux for an additional 3 hours, then it was added to a solution of ketone (1.0 g, 3.98 mmol) in tetrahydrofuran (20 mL). The reaction mixture was stirred at room temperature for 1 hour and then 2M hydrochloric acid (2 mL) was added. The mixture was filtered and then the solvent was removed under reduced pressure. This yellow crude oily alcohol was dissolved in ethanol / tetrahydrofuran / 2M HCl (2: 2: 1), stirred at room temperature for 15 minutes, water was added and the organic solvent was removed in vacuo. The organic material was extracted with ethyl acetate (3 × 50 mL) and the combined extract was dried and concentrated. The residue was purified by recrystallization from dichloromethane (0.95 g, 73%). Mp 144-147 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.24 (s, 1H), 7.49-7.42 (m, 3H), 7.29-7.26 (m, 4H), 7.17 To 7.08 (m, 3H), 6.97 to 6.95 (m, 2H), 6.92 (d, J = 2.4 Hz, 1H), 6.75 (dd, J = 8.7, 2.4 Hz, 1H), 5.81 (s, 1H), 3.70 (s, 3H). Found: C, 84.30; H, 5.85; N, 4.36. C ₂₃ H ₁₉ NO. 1 / 10H ₂ O Calculated: C, 84.43; H, 5.91 ; N, 4.28.

Example 410 Preparation of 9-methoxy-4,5-diphenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (XCIX; R ¹ = R ² = phenyl) (808) .
(806), prepared as described in Example 409, was reacted with maleimide at 180 ° C. using the procedure described in Example 69 to give the adduct (XCVIII; R ¹ = R ² = phenyl) (807) Got. This was used without further purification. This crude Diels-Alder adduct was reacted with MnO ₂ by the procedure described in Scheme 2 of Example 79 to aromatize to give (808) (77%). ¹ H NMR ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.08 (s, 1 H), 11.02 (br s, 1 H), 8.52 (d, J = 2.6 Hz, 1 H), 7 .50 (d, J = 8.9 Hz, 1H), 7.36-7.28 (m, 3H), 7.21-7.11 (m, 8H), 3.89 (s, 3H).

Example 411 Preparation of 9-hydroxy-4,5-diphenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (C; R ¹ = R ² = phenyl) (809) (807), prepared as described in Example 410, was demethylated using BBr ₃ by the procedure described in Example 80 to give (809) (87%) as a yellow powder with a melting point> 300 ° C. It was. ¹ H NMR δ [(CD ₃ ) ₂ SO] 10.96 (s, 1 H), 10.94 (s, 1 H), 9.23 (s, 1 H), 8.37 (d, J = 2.4 Hz) , 1H), 7.39 (d, J = 8.7 Hz, 1H), 7.35 to 7.29 (m, 3H), 7.22 to 7.10 (m, 7H), 7.03 (dd , J = 8.7, 2.4 Hz, 1H). Found: C, 77.16; H, 4.00; N, 6.83. Calculated for _{C 26 H 16 N 2 O 3} : C, 77.22; H, 3.99; N, 6.93.

Example 412 Preparation of 5-methoxy-2-[(1E) -1-phenyl-1-propenyl] -1H-indole (XCVII; R ² = phenyl, R ¹ = CH ₃ ) (810) Example 408 (805) prepared as described in Example 405 was reacted with ethyltriphenylphosphonium bromide using the procedure described in Example 405 to give (810) (72%), mp 128-130 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 10.97 (s, 1H), 7.47-7.39 (m, 3H), 7.28-7.19 (m, 3H), 6.88 (D, J = 2.4 Hz, 1H), 6.69 (dd, J = 8.7, 2.4 Hz, 1H), 6.38 (q, J = 6.9 Hz, 1H), 5.69 ( s, 1H), 3.69 (s, 3H), 1.67 (d, J = 6.9 Hz, 3H). Found: C, 81.78; H, 6.26; N, 5.33. Calculated for _{C 18 H 17 NO: C,} 82.10; H, 6.51; N, 5.32.

Example 413 9-Methoxy-4-methyl-5-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (XCVIII; (XCVIII; R ² = phenyl, R ¹ = Preparation of CH ₃ ) (812) (810) prepared as described in Example 412 was reacted with maleimide at 180 ° C. using the procedure described in Example 69 to give the adduct (XCIV; R ² = Phenyl, R ¹ = CH ₃ ) (811) was obtained, which was used without further purification, and this crude Diels-Alder adduct was used with MnO ₂ by the procedure described in Scheme 2 of Example 79. To obtain (812) (74%) having a melting point of 284 to 286 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.06 (br s, 1H), 10.93 (s) , 1H ), 8.43 (d, J = 2.6 Hz, 1H), 7.64 to 7.54 (m, 3H), 7.45 to 7.42 (m, 3H), 7.14 (dd, J = 8.9, 2.6 Hz, 1H), 3.32 (s, 3H), 2.48 (s, 3H) Measured values: C, 73.13; H, 4.32; N, 7.72. _{.C 22 H 16 N 2 O 3} .1 / 3H 2 O calculated: C, 72.92; H, 4.64 ; N, 7.73.

Example 414 9-Hydroxy-4-methyl-5-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (C; R ² = phenyl, R ¹ = CH ₃ ) (812), prepared as described in Example 413, was demethylated with BBr ₃ by the procedure described in Example 80 to give (813) (85%) with a melting point> 300 ° C. . ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.01 (s, 1H), 10.79 (s, 1H), 9.17 (s, 1H), 8.28 (d, J = 2.4 Hz) , 1H), 7.34-7.60 (m, 2H), 7.57-7.52 (m, 1H), 7.43-7.41 (m, 2H), 7.34 (d, J = 8.7 Hz, 1H), 6.98 (dd, J = 8.7, 2.4 Hz, 1H), 2.26 (s, 3H). Calculated value of EIMS M ⁺ : 342.1003. Calculated _{C 21 H 14 N 2 O 3} : 342.1004.

Example 415 Preparation of 5-methoxy-2-vinyl-1H-indole (XCVII; R ¹ = R ² = H) (814) 5-Methoxy-1H-indole-2-carbaldehyde is described in Method 33. And reacted with methyltriphenylphosphonium bromide to give (814) (87%), mp 80-81 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.09 (s, 1H), 7.21 (d, J = 8.7 Hz, 1H), 6.97 (d, J = 2.3 Hz, 1H) 6.75-6.66 (m, 2H), 6.37 (s, 1H), 5.76 (d, J = 17.3 Hz, 1H), 5.21 (d, J = 11.6, 1H), 3.73 (s, 3H). Found: C, 76.34; H, 6.24; N, 8.11. Calculated for C ₁₁ H ₁₁ NO: C, 76.28; H, 6.40; N, 8.09.

Example 416 Preparation of 9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (XCIX; R ¹ = R ² = H) (816) Described in Example 415 (814) prepared as described above was reacted with maleimide at 180 ° C. by the procedure described in Example 69 to give the adduct (XCVIII; R = R ′ = H) (814). This was used without further purification. This crude Diels-Alder adduct was aromatized with MnO ₂ by the procedure described in Example 79 to give (815 ??) (76%), mp 260-270 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.91 (s, 1H), 11.10 (s, 1H), 8.38 (d, J = 2.6 Hz, 1H), 7.81 (d , J = 8.2 Hz, 1H), 7.76 (d, J = 8.2 Hz, 1H), 7.54 (d, J = 8.8 Hz, 1H), 7.22 (dd, J = 8. 8, 2.6 Hz, 1H), 3.88 (s, 3H). Found: C, 65.44; H, 3.96; N, 10.30. _{C 15 H 10 N 2 O 3} . Calculated for _1/2 H2O: C, 65.45; H; 4.03; N, 10.18.

Example 417 Preparation of 9-Hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (C; R ¹ = R ² = H) (817) Described in Example 416 (816) prepared as described above was demethylated using BBr ₃ by the procedure described in Example 80 to give (817) (79%), mp 335-345 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.77 (s, 1H), 11.04 (s, 1H), 9.23 (s, 1H), 8.24 (d, J = 2.3 Hz) , 1H), 7.75 (2d, J = 8.2 Hz, 2H), 7.43 (d, J = 8.7 Hz, 1H), 7.05 (dd, J = 8.7, 2.3 Hz, 1H). Found: C, 64.44; H, 3.45; N, 10.41. _{C 14 H 8 N 2 O 3} . Calculated for _1/2 H2O: C, 64.37; H, 3.47; N, 10.72.

Example 418 Preparation of methyl 2- (1-phenylvinyl) -1H-indol-5-yl ether (XCVII; R ² = phenyl, R ¹ = H) (818) Prepared as described in Example 408. (805) was reacted with methyltriphenylphosphonium bromide by the procedure described in Example 405 to give (818) (95%), mp 119-121 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.13 (s, 1H), 7.47-7.39 (m, 5H), 7.26 (d, J = 8.8 Hz, 1H), 6 .97 (d, J = 2.4 Hz, 1H), 6.76 (dd, J = 8.8, 2.4 Hz, 1H), 6.12 (s, 1H), 5.77 (s, 1H) 5.30 (s, 1H), 3.72 (s, 3H). Found: C, 81.83; H, 6.22; N, 5.59. Calculated for _{C 17 H 15 NO: C,} 81.90; H, 6.06; N, 5.62.

(Example 419) 9-methoxy-5-phenyl-pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) - dione; Preparation of (XCIX ^{R 2} = ^{phenyl, R 1 = H) (820} ) (818), prepared as described in Example 418, was reacted with maleimide at 180 ° C. by the procedure described in Example 69 to give the adduct (XCVIII; R = phenyl, R ′ = H) (819). Obtained. This was used without further purification. This crude Diels-Alder adduct was aromatized with MnO ₂ by the procedure described in Example 79 to give (820) (73%), mp 281-285 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.63 (br s, 1 H), 11.15 (br s, 1 H), 8.45 (d, J = 2.5 Hz, 1 H), 7.78 ˜7.76 (m, 2H), 7.68 (s, 1H), 7.65 to 7.62 (m, 2H), 7.57 to 7.53 (m, 2H), 7.22 (dd , J = 8.8, 2.5 Hz, 1H), 3.89 (s, 3H). Found: C, 72.06; H, 4.57; N, 7.69. _{C 21 H 14 N 2 O 3} . 1 / 3H ₂ O Calculated: C, 72.41; H, 4.24 ; N, 8.04.

Preparation of; ^{(R 2} = ^{phenyl, R 1 = H C) (} 821) dione - (Example 420) 9-hydroxy-5-phenyl-pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) 820, prepared as described in Example 419, was demethylated using BBr ₃ by the procedure described in Example 80 to give (821) (89%), mp 335-345 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.50 (s, 1H), 11.10 (s, 1H), 9.26 (d, J = 2.4 Hz, 1H), 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, 1 = 8.7 Hz, 1H), 7.06 (dd, J = 8.7, 2.4 Hz, 1H). Found: C, 72.71; H, 3.55; N, 8.16. Calculated for _{C 20 H 12 N 2 O 3} : C, 73.16; H, 3.68; N, 8.53.

(Example 421) 1- (5-methoxy -1H- indol-2-yl) -1-propanone ^{_{(XCVI; R 2 = CH 2}} CH 3) Preparation of (822) 5-methoxy -1H- indole-2 Carbaldehyde was reacted with ethylmagnesium bromide by the procedure described in Example 404 to give (822) (82%), mp 170-171.5 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.56 (s, 1H), 7.34 (d, J = 9.1 Hz, 1H), 7.22 (d, J = 1.7 Hz, 1H) 7.11 (d, J = 2.4 Hz, 1H), 6.93 (d, J = 9.1, 2.4 Hz, 1H), 3.77 (s, 3H), 2.96 (q, J = 7.3 Hz, 2H), 1.13 (t, J = 7.3 Hz, 3H). Found: C, 71.15; H, 6.45; N, 7.07. Calculated for _{C 12 H 13 NO 2: C} , 70.92; H, 6.45; N, 6.89.

(Example 422) 2 - [(E, Z) -1- ethyl-2-phenylethenyl] -5-methoxy -1H- indole ^{_{(XCVII; R 2 = CH 2}} CH 3, R 1 = phenyl) (823 (822), prepared as described in Example 421, was reacted with benzyltriphenylphosphonium bromide by the procedure described in Example 404 to give (823) (38%), mp 95-97 ° C. Got. Found: C, 82.28; H, 6.98; N, 5.07. Calculated for C ₁₉ H ₁₉ NO C, 82.28; H, 6.90; N, 5.05.

(Example 423) 5-Ethyl-9-methoxy-4-phenyl-pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) - dione ^{_{(XCIX; R 2 = CH 2}} CH 3, R 1 = Preparation of (Phenyl) (825) (823), prepared as described in Example 422, was reacted with maleimide at 180 ° C. by the procedure described in Example 69 to give the adduct (XCVIII; R═CH ₂ CH ₃ , R ′ = phenyl) (824). This was used without further purification. This crude Diels-Alder adduct was aromatized with MnO ₂ by the procedure described in Example 79 to give (825) (68%), mp 301-303 ° C. ¹ H NMR δ ((CD ₃ ) ₂ SO] 11.78 (s, 1H), 10.87 (s, 1H), 8.47 (d, J = 2.6 Hz, 1H), 7.56 (d , J = 8.8 Hz, 1H), 7.48-7.41 (m, 3H), 7.32-7.30 (m, 2H), 7.23 (dd, J = 8.8, 2.H). 6 Hz, 1H), 3.89 (s, 3H), 2.76 (q, J = 7.4 Hz, 2H), 1.07 (t, J = 7.4 Hz, 3H).

Example 424 5-ethyl-9-hydroxy-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (C; R ² = CH ₂ CH ₃ , R ¹ = Preparation of (Phenyl) (826) (825), prepared as described in Example 423, was demethylated with BBr ₃ by the procedure described in Example 80 to give (826) (mp) 190-196 ° C. 97%). ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.63 (s, 1H), 10.81 (s, 1H), 9.21 (s, 1H), 8.31 (d, J = 2.4 Hz) , 1H), 7.48-7.40 (m, 4H), 7.31-7.29 (m, 2H), 7.06 (dd, J = 8.7, 2.4 Hz, 1H), 2 .74 (q, J = 7.4 Hz, 2H), 1.06 (t, J = 7.4 Hz, 3H). Found: C, 72.43; H, 4.54; N, 7.54. _{C 22 H 16 N 2 O 3} . Calculated for _1/2 H2O: C, 72.32; H, 4.69; N, 7.67.

  Procedure of scheme 18

Example 425 Preparation of 5- (benzyloxy) -2-[(E, Z) -2- (2-methoxyphenyl) ethenyl] -1H-indole (CI; Ar = 2-methoxyphenyl) (847) 5- (Benzyloxy) -1H-indole-2-carbaldehyde (846) is reacted with 2-methoxybenzyltriphenylphosphonium bromide by the procedure described in Example 37 to give a cream colored solid (E / Z (847) (89%) of a mixture of isomers). This was used without further purification. ¹ H NMR δ [(CD ₃ ) ₂ SO] (major isomer) 11.26 (s, 1H), 7.62 (d, J = 6.8 Hz, 1H), 7.48 (m), 7. 41 to 7.15 (m), 7.08 to 7.02 (m), 6.97 (m, 1H), 6.81 (dd, J = 8.7, 2.4 Hz, 1H), 6. 45 (s, 1H), 5.08 (s, 2H), 3.87 (s, 3H).

Example 426 5- (benzyloxy) -2-[(E, Z) -2- (2-methoxyphenyl) ethenyl] -1- [2- (4-morpholinyl) ethyl] -1H-indole (CII Preparation of Ar = 2-methoxyphenyl, R ¹⁰ = CH ₂ CH ₂ N (CH ₂ CH ₂ ) ₂ O) (848) Prepared as described in Example 425 (847) was described in Method 3. Alkylation with 4- (2-chloroethyl) morpholine by the procedure afforded (848) (87%) as a pale yellow solid. This was used without further purification.

Example 427 9- (Benzyloxy) -4- (2-methoxyphenyl) -6- [2- (4-morpholinyl) ethyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H ) - dione; prepared as described in (CIV ^{_{Ar-2-methoxyphenyl, R 10 = CH 2 CH 2}} N (CH 2 CH 2) 2 O) preparation example 426 (850) to (848), Reaction with maleimide using the procedure described in Method 4a gave the adduct (CIII; Ar = 2-methoxyphenyl, R ¹⁰ = CH ₂ CH ₂ N (CH ₂ CH ₂ ) ₂ O) (849). . This was used without further purification. (849) was reacted with MnO ₂ and aromatized by the procedure described in Example 79 to give (850) (36%) as a yellow solid with a melting point of 170-172 ° C.

Example 428 9-Hydroxy-4- (2-methoxyphenyl) -6- [2- (4-morpholinyl) ethyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Preparation of Ar = 2-methoxyphenyl, R ¹⁰ = CH ₂ CH ₂ N (CH ₂ CH ₂ ) ₂ O (851) The benzyl ether group of (850), prepared as described in Example 427, was Removal by hydrogenolysis using the procedure described in Example 254 afforded (851) (66%) as a yellow powder with a melting point of 262-264 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 10.92 (br s, 1 H), 9.31 (br s, 1 H), 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, 1 H), 7.33 (dd, J = 7.4, 1.7 Hz, 1H), 7.12 to 7.08 (m, 2H), 7.05 (m, 1H), 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 (br t, 4H) calculated .EIMS M ^+: calcd _{471.1789.C 27 H 25 N 3 O 5} 471.1794.

Example 429 5- (benzyloxy) -2-{(E) -2- [2- (2-methoxyethoxy) phenyl] ethenyl} -1H-indole (CI; Ar = 2- (2- (methoxy) Preparation of (Ethoxy) phenyl) (852) 5- (Benzyloxy) -1H-indole-2-carbaldehyde (846) was prepared according to the procedure described in Example 37 2- (2-methoxyethoxy) benzyltriphenyl bromide. Reaction with phosphonium gave (847) (86%) of a cream solid (mixture of E / Z isomers) which was used without further purification.

Example 430 9- (Benzyloxy) -4- [2- (2-methoxyethoxy) phenyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (CIV; Ar = Preparation of 2- (2-methoxyethoxy) phenyl, R ¹⁰ = H) (854) (852) is reacted with maleimide using the procedure described in Method 4a to give the adduct (CIII; Ar = 2- (2 - give methoxyethoxy) ^phenyl, R 10 = H) and (853). This was used without further purification. (853) was reacted with MnO ₂ by the procedure described in Example 79 to aromatize to give (854) (46%) as an orange solid with a melting point of 157-159 ° C. This was used without further purification.

Example 431 9-hydroxy-4- [2- (2-methoxyethoxy) phenyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (VI; Ar = 2- ( = 2-methoxyethoxy) ^phenyl, R 10 H) preparation of (855).
The benzyl ether group of (854), prepared as described in Example 430, was removed by hydrogenolysis using the procedure described in Example 254 as a yellow powder with a melting point of 275-279 ° C. (855) ( 53%). ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.71 (br s, 1 H), 10.89 (br s, 1 H), 9.22 (br s, 1 H), 8.31 (d, J = 2.2 Hz, 1H), 7.51 (s, 1H), 7.43 (d, J = 8.5 Hz, 1H), 7.39 (m, 1H), 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, 2 H), 4.04 (m, 2 H), 3.45 (t , J = 4.7 Hz, 2H), 3.10 (s, 3H). Calculated value of EIMS M ⁺ : 402.213. Calcd 402.1215 for _{C 23 H 18 N 2 O 5} .

Example 432 Preparation of (2-Methoxy-4-nitrobenzyl) (triphenyl) phosphonium bromide (582) (2-Methoxy-4-nitrophenyl) methanol was brominated with 30% HBr in acetic acid and then The crude bromide was reacted with triphenylphosphine using the procedure described in Example 112 except that the substitution conditions were 20 ° C. for 3 days followed by 55 ° C. for 1 day to obtain a melting point (CH ₂ Cl ₂ / benzene). The phosphonium salt (582) (84%) was obtained as a yellow solid at 194-196 ° C. _{^{1 H NMR (CDCl 3) δ7.83~7.63}} (m, 17H), 7.45 (br s, 1H), 5.52 (d, J = 15.0Hz, 2H). Found: C, 61.10; H, 4.73; N, 3.05. Calculated for _{C 26 H 23 BrNO 3 P C} , 61.43; H, 4.56; N, 2.76.

Example 433 5- (benzyloxy) -2-[(E) -2- (2-methoxy-4-nitrophenyl) ethenyl] -1H-indole (583) (CI, Ar = 2-methoxy-4 -Nitrophenyl) Preparation of LDA and aldehyde (sequentially) at 0 ° C., with LDA: aldehyde ratio of 1.5: 1 and reaction time of 5 hours, according to the procedure described in Method 2. Aldehyde (846) is reacted with (2-methoxy-4-nitrobenzyl) (triphenyl) phosphonium bromide (582) prepared as described in Example 432 to give (CH ₂ Cl ₂ / pentane). After crystallization, the diene (583) (63%) was obtained as an orange solid (pure E isomer) with a melting point of 156-159 ° C. ¹ H NMR (CDCl ₃ ) δ 8.23 (br s, 1H), 7.87 (dd, J = 8.5, 2.1 Hz, 1H), 7.76 (d, J = 2.2 Hz, 1H) 7.68 (d, J = 8.6 Hz, 1H), 7.48 (d, J = 7.3 Hz, 2H), 7.39 (t, J = 7.3 Hz, 2H), 7.32 ( t, J = 7.2 Hz, 1H), 7.28 (d, J = 17.1 Hz, 1H), 7.26 (d, J = 8.7 Hz, 1H), 7.20 (d, J = 16) .7 Hz, 1 H), 7.12 (d, J = 2.4 Hz, 1 H), 6.97 (dd, J = 8.7, 2.5 Hz, 1 H), 6.63 (br s, 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 Calculated _{O 4 C, 71.99; H,} 5.03; N, 7.00.

Example 434 9- (Benzyloxy) -4- (2-methoxy-4-nitrophenyl) -4,5,6,10c-tetrahydropyrrolo [3,4-c] carbazole-1,3 (2H, 3aH) -dione (584) (CIII, R ¹⁰ = H, Ar = 2-methoxy-4-nitrophenyl) and 9-benzyloxy-4- (2-methoxy-4-nitrophenyl) pyrrolo [3,4 c] Preparation of carbazole-1,3 (2H, 6H) -dione (585) (CIV, R ¹⁰ = H, Ar = 2-methoxy-4-nitrophenyl) Pure prepared as described in Example 433 A solution of a mixture of E diene (583) (185 mg, 0.463 mmol) and maleimide (260 mg, 2.68 mmol) in anhydrous toluene (3 mL) was covered with foil and sealed vials. It was stirred for 22 hours while in refluxed (Method 4a). The resulting thick suspension (by the procedure of Example 79) was transferred to a flask with dioxane (7 mL) and then treated with manganese dioxide (900 mg, 10.4 mmol) and stirred at reflux for 24 hours ( After treatment) a mixture was obtained. This was adsorbed on silica and subjected to gel chromatography. Elution with 0-0.25% MeOH / CH ₂ Cl ₂ gave the precursor. It was then further eluted with 0.25 to 33% MeOH / CH ₂ Cl ₂ (after crystallizing from THF / CH ₂ Cl ₂ / pentane) to give the crude product (585) (64 mg). This was further purified by chromatography on silica gel (eluting with 20% EtOAc / petroleum ether) (after crystallizing from THF / CH ₂ Cl / pentane) as a yellow solid of melting point 301-303 ° C. Pure material (585) (58 mg, 25%) was obtained. ¹ H NMR [(CD ₃ ) ₂ SO] δ 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, 1H), 7.88 (d, J = 2.2 Hz, 1H), 7.64 (d, J = 8.2 Hz, 1H), 7.63 (s) , 1H), 7.58 (d, J = 8.8 Hz, 1H), 7.56 (brd, J = 7.1 Hz, 2H), 7.42 (t, J = 7.4 Hz, 2H), 7.35 (t, J = 7.4 Hz, 1H), 7.32 (dd, J = 8.9, 2.7 Hz, 1H), 5.23 (s, 2H), 3.83 (s, 3H) ). Found: C, 68.14; H, 3.89; N, 8.41. Calculated C of _{C 28 H 19 N 3 O 6} , 68.15; H, 3.88; N, 8.52.

Further eluting with 1% MeOH / CH ₂ Cl ₂ (after crystallization from MeOH / CH ₂ Cl ₂ / petroleum ether) recovered the adduct (584) (72 mg, 31%) as a pale yellow solid ( This was directly aromatized with 5 equivalents of DDQ by the procedure described in Example 70 to give further product in 79% yield). ¹ H NMR [(CD ₃ ) ₂ SO] δ 10.96 (br s, 1 H), 10.86 (br s, 1 H), 7.90 (dd, J = 8.5, 2.3 Hz, 1 H), 7.78 (d, J = 2.2 Hz, 1H), 7.72 (d, J = 8.6 Hz, 1H), 7.50 (d, J = 7.1 Hz, 2H), 7.40 (t , J = 7.3 Hz, 2H), 7.34 (d, J = 2.4 Hz, 1H), 7.33 (t, J = 7.4 Hz, 1H), 7.21 (d, J = 8. 7 Hz, 1H), 6.80 (dd, J = 8.7, 2.5 Hz, 1H), 5.09 (s, 2H), 4.27 (d, J = 7.6 Hz, 1H), 3. 98 (dd, J = 7.6, 3.6 Hz, 1H), 3.97 (s, 3H), 3.54 (dt, J = 12.9, 3.8 Hz, 1H), 3.24 (br dd, J = 15. , 13.5Hz, 1H), 2.89 (dd, J = 15.4,3.6Hz, 1H). Calculated for FABMS: M ⁺ = 497.1601. Calcd 497.1587 for _{C 28 H 23 N 3 O 6} .

Example 435 9-Hydroxy-4- (2-methoxy-4-nitrophenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (586) (VI, R ¹⁰ = H, Ar = 2-methoxy-4-nitrophenyl) A suspension of benzyl ether (585) (55 mg, 0.112 mmol) in ice AcOH (11.2 mL) prepared as described in Example 434 was Treated with concentrated HCl (36% 6.7 mL) with stirring at 100 ° C. for 50 minutes (using the procedure described in Scheme 18 in Example 260). The cooled solution was slowly added to ice / aqueous NaHCO ₃ (150 mL) and then extracted with EtOAc (5 × 100 mL). The extract was washed with water and then adsorbed onto silica gel and chromatographed. Eluting with 0~1% MeOH / _{CH 2} Cl 2 to obtain a precursor. Phenol (586) (86%) was then eluted as an orange solid with a melting point of 242 ° -244 ° C. (after crystallization from THF / CH ₂ Cl ₂ / pentane) eluting with 1.5% MeOH / CH ₂ Cl _2. ) ¹ H NMR [(CD ₃ ) ₂ SO] δ 11.84 (br s, 1 H), 11.02 (br s, 1 H), 9.28 (br s, 1 H), 8.31 (d, J = 2) .4 Hz, 1H), 7.93 (dd, J = 8.2, 2.1 Hz, 1H), 7.87 (d, J = 2.1 Hz, 1H), 7.63 (d, J = 8. 2 Hz, 1H), 7.58 (s, 1H), 7.45 (d, J = 8.7 Hz, 1H), 7.08 (dd, J = 8.7, 2.4 Hz, 1H); 83 (s, 3H). Found: C, 62.55; H; 3.22; N, 10.13. Calculated C of _{C 21 H 13 N 3 O 6} , 62.53; H, 3.25; N, 10.42.

Example 436 4- (4-amino-2-methoxyphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (587) (VI, R ¹⁰ = Preparation of H, Ar = 4-amino-2-methoxyphenyl) Nitro derivative (586) (31 mg, 0.0769 mmol) prepared as described in Example 435, freshly prepared (wet) nickel boride (242 mg) ) In MeOH (2.4 mL) and 1M HCl (0.6 mL) was stirred at reflux for 1 hour. 6 drops of concentrated HCl were added and the mixture was then stirred at reflux for an additional hour. Concentrated aqueous ammonia and aqueous NaHCO ₃ (100 mL) were added and the mixture was extracted with EtOAc (8 × 100 mL). The extract was concentrated, adsorbed on silica and subjected to gel chromatography. Elution with 0-2% MeOH / CH ₂ Cl ₂ gave the precursor. The amine (587) was then eluted as a yellow-orange solid with a melting point of 308-316 ° C. (after crystallization from MeOH / THF / CH ₂ Cl ₂ / pentane) eluting with a further 2-3% MeOH / CH ₂ Cl _2. ) (77%). ¹ H NMR [(CD ₃ ) ₂ SO] δ 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, 1H), 7.43 (s, 1H), 7.39 (d, J = 8.7 Hz, 1H), 7.02 (dd, J = 8.7, 2.5 Hz, 1H), 6 .95 (d, J = 7.9 Hz, 1H), 6.30 (d, J = 2.0 Hz, 1H), 6.22 (dd, J = 8.0, 1.9 Hz, 1H), 5. 26 (br s, 2H), 3.59 (s, 3H). Found: C, 67.65; H, 4.06; N, 11.01. Calculated _{C 21 H 15 N 3 O 4} C, 67.56; H, 4.05; N, 11.25.

  Scheme 19 Procedure

Example 437 Preparation of methyl 7-bromo-5-methoxy-1-benzofuran-2-carboxylate (856) With 3-bromo-2-hydroxy-5-methoxy-benzaldehyde (94.7 g, 0.410 mol) To a solution of dimethyl bromomalonate (103 g, 0.492 mol) in toluene (1.2 L) was added freshly powdered potassium carbonate (85 g, 0.615 mol) and tetra-n-butylammonium bromide (13. 2 g, 0.041 mol) was added. The reaction was heated at reflux for 48 hours under a Dean-Stark trap. The reaction was concentrated and the residue was dissolved with dichloromethane (about 0.5 L), filtered through celite and washed with dichloromethane (about 0.5 L). The filtrate was washed with 1 L of 1M sodium hydroxide and water (2 × 1 L). The organic phase was then passed through a 400 g silica gel pad, washed with dichloromethane (ca. 1 L), and the filtrate was concentrated to give the desired benzofuran (64 g, 56%) as an orange solid of melting point 107-111 ° C. Got. ¹ H NMR δ (CDCl ₃ ) 7.50 (s, 1H), 7.23 (d, 1H), 7.03 (d, 1H), 3.98 (s, 3H), 3.82 (s, 3H).

Example 438 Preparation of 7-bromo-2-hydroxymethyl-5-methoxybenzofuran and 7-bromo-5-methoxybenzofuran-2-carbaldehyde (858).
A solution of ester (857) (69 g, 242 mmol) in anhydrous tetrahydrofuran (2.5 L) prepared as described in Example 856 was cooled to -78 ° C. A solution of 1M lithium aluminum hydride in tetrahydrofuran (242 mL, 242 mmol) was added for 30 minutes. The reaction was stirred at −78 ° C. for 1.25 hours and carefully quenched with 50 mL of water. The mixture was poured into 1 L of ice-cold 1M hydrochloric acid solution and extracted with ethyl acetate (4 × 500 mL). The combined organic phase was dried (Na ₂ SO ₄ ) and concentrated under reduced pressure to give 67 g of an orange solid. The residue was adsorbed onto 200 g of silica gel, added to a silica gel (1 kg, 70-230 mesh) column and eluted with 1: 9, 1: 4 and 1: 3 ethyl acetate-heptane. This first gave 25 g (41%) of the final aldehyde (858) as a pale yellow solid with a melting point of 119-121 ° C. ¹ H NMR δ (CDCl ₃ ) 9.90 (s, 1H), 7.55 (s, 1H), 7.38 (d, 1H), 7.10 (s, 1H), 3.85 (s, 3H). Found: C, 47.06; H, 2.66; Br, 31.41. Calculated for C ₁₀ H ₇ BrO ₃ C, 47.09; H, 2.77; N, 31.33; After this, 20 g (33%) of the expected alcohol was obtained. ¹ H NMR δ (CDCl ₃ ) 7.08 (m, 1H), 6.9 (m, 1H), 6.68 (s, 1H), 4.78 (s, 2H), 3.85 (s, 3H).

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

  Exemplary Procedure for Method 34 of Scheme 19

Example 440 Preparation of 7-bromo-2-[(E) -2- (2-chlorophenyl) ethenyl] -5-methoxy-1-benzofuran (CV; Ar = 2-chlorophenyl) (859) Diethyl 2- To a solution of chlorobenzyl phosphate (4.91 g, 0.018 mol) and 7-bromo-5-methoxybenzofuran-2-carbaldehyde (11.27 g, 0.016 mol) in tetrahydrofuran (80 mL) was added sodium hydride (mineral oil). Medium dispersion 60%, 0.74 g, 0.0185 mol) was added. After 5 minutes, the reaction mixture was warmed to 60 ° C. for 1 hour. The reaction mixture was cooled to room temperature and water (10 mL) was added carefully to remove the tetrahydrofuran. Water (50 mL) was added and the mixture was extracted with ethyl acetate (3 × 100 mL). The mixed ethyl acetate extract was washed with brine (50 mL), dried over magnesium sulfate, filtered and concentrated to dryness. Solid material was obtained by trituration with diethyl ether (20 mL). This solid material was further washed with diethyl ether (20 ml). The liquid was concentrated and triturated with diethyl ether (10 mL) to recover the solid. (859) (4.89 g, 84%) was obtained from the mixed solid. ¹ H NMR δ (CDCl ₃ ) 7.70 (d, J = 16 Hz, 1H), 7.65 (dd, J = 7.7, 1.5 Hz, 1H), 7.4 (dd, J = 6. 0, 1 Hz, 1H), 7.23 (m, 2H), 7.05 (d, J = 2.3 Hz, 1H), 6.94 (d, J = 16 Hz, 1H), 6.92 (d, J = 2.3 Hz, 1H), 6.72 (s, 1H), 3.82 (s, 3H), MH ⁺ : 364.9, 362.9 MH ⁻ : 362.9, 360.9.

Example 441 7-Bromo-4- (2-chlorophenyl) -9-methoxy-3a, 4,5,10c-tetrahydro-1H- [1] benzofuro [3,2-e] isoindole-1,3 Preparation of (2H) -dione (CVI; Ar = 2-chlorophenyl) (860) Prepared as described in Example 441 (859) (4.89 g, 0.0185 mol), maleimide (1.44 g, .0. 02 mol) and tin (II) chloride (2.8 g, 0.02 mol) in xylene (40 mL) were heated to 150 ° C. overnight. After further addition of maleimide (1.44 g, 0.02 mol) and tin (II) chloride (1.44 g, 0.01 mol), the reaction was again heated to 150 ° C. overnight. The formed solid was collected, washed with xylene (20 mL) and 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 and 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 δ (CDCl ₃ ) 7.60 (d, J = 6.5 Hz, 1H), 7.40 (m, 2H), 7.25 (m, 1H), 7.1 (m, 2H), 4.36 (dd, J = 7, 3, 1 Hz, 1H), 4.0 (m, 1H), 3.86 (s, 3H), 3.81 (m, 1H), 3.45 (m, 1H), 3.10 (dd, J = 4.7, 17 Hz, 1H), MH ⁺ : 462, 460.

Example 442 7-Bromo-4- (2-chlorophenyl) -9-methoxy-1H- [1] benzofuro [3,2-e] isoindole-1,3 (2H) -dione (CVII; Ar = 2-Chlorophenyl) (861).
(860) prepared as described in Example 442 was aromatized with MnO ₂ by the procedure described in Example 79 to give dibenzofuran (861) as a yellow solid (67%). ¹ H NMR δ [(CD ₃ ) ₂ SO] 8.22 (d, J = 2.6 Hz, 1H), 8.14 (s, 1H), 7.62 (m, 2H), 7.48 (m , 3H), 3.98 (s, 3H). MH < ^- >: 458, 457, 456, 454.

Example 443 7-Bromo-4- (2-chlorophenyl) -9-hydroxy-1H- [1] benzofuro [3,2-e] isoindole-1,3 (2H) -dione (CVIII; Ar = 2-Chlorophenyl) (862) Preparation (861), prepared as described in Example 442, was demethylated with BBr ₃ by the procedure described in Example 80 to give (862) (98%). It was. This was used without further purification. ¹ H NMR δ [(CD ₃ ) ₂ SO] 8.04 (d, J = 2.3 Hz, 1H), 7.91 (s, 1H), 7.56 (d, J = 8 Hz, 1H), 7 .45 (m, 3H), 7.2 (d, J = 2.5 Hz, 1H). MH < ^- >: 443.9, 441.9, 439.9.

Example 444 4- (2-chlorophenyl) -9-hydroxy-7-vinyl-1H- [1] benzofuro [3,2-e] isoindole-1,3 (2H) -dione (CIX; Ar = 2-Chlorophenyl, Z = H) (863).
(862), prepared as described in Example 443, was reacted with tributylvinyltin using the procedure described in Example 309 to give (863) (79%). ¹ H NMR δ [(CD ₃ ) ₂ SO] 9.80 (s, 1H), 8.04 (d, J = 2.7 Hz, 1H), 7.91 (s, 1H), 7.56 (d , J = 8 Hz, 1H), 7.45 (m, 3H), 7.2 (d, J = 2.5 Hz, 1H), 6.96 (dd, J = 18, 11 Hz, 1H), 6.25. (D, J = 18 Hz, 1H), 5.52 (d, J = 11 Hz, 1H). MH < ^- >: 390, 388.

Example 445 4- (2-Chlorophenyl) -7-ethyl-9-hydroxy-1H- [1] benzofuro [3,2-e] isoindole-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 methanol: tetrahydrofuran mixture (1: 1, 4 mL) was hydrogenated using Raney nickel (100 mg) and hydrogen. The product was purified by column chromatography using a 0-100% gradient of ethyl acetate / dichloromethane to give (864) (0.032 g, 59%). ¹ H NMR δ [(CD ₃ ) ₂ SO] 9.65 (s, 1H), 7.92 (m, 1H), 7.56 (d, J = 3.0 Hz, 1H), 7.43 (m , 3H), 6.96 (d, J = 2.5 Hz, 1H), 2.90 (q, 2H), 1.5 (t, 3H). MH < ^- >: 392, 390.

Example 446 4- (2-chlorophenyl) -7- (1,2-dihydroxyethyl) -9-hydroxy-1H- [1] benzofuro [3,2-e] isoindole-1,3 (2H) -Preparation of dione (CXI; Ar = 2-chlorophenyl, Z = H) (865).
(863), prepared as described in Example 444, was reacted with OsO ₄ using the procedure described in Example 300 to give (865) (35%). ¹ H NMR δ [(CD ₃ ) ₂ SO] 9.68 (s, 1H), 7.96 (d, J = 2.5 Hz, 1H), 7.9 (s, 1H), 7.55 (d , J = 7.8 Hz, 1H), 7.45 (m, 3H), 7.17 (d, J = 2.5 Hz, 1H), 5.55 (d, J = 4.6 Hz, 1H), 5 .06 (m, 1H), 4.87 (t, J = 5.7 Hz, 1H), 3.65 (m, 1H), 3.55 (m, 1H). MH < ^- >: 424, 422.

  Procedure of scheme 20

Example 447 Dibenzyl 1,3-dioxo-4-phenyl-1,2,3,6-tetrahydropyrrolo [3,4-c] carbazol-9-yl phosphate (CXII; Ar = phenyl) (336) Preparation 9-Hydroxy-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (I; Ar = phenyl) (0.50 g, 1.52 mmol) in pyridine (30 mL) To this was added phosphorus oxychloride (140 mL, 1.52 mmol) dropwise under nitrogen. After stirring at room temperature for 40 minutes, more phosphorus oxychloride (40 mL) was added, and then 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 is dehydrated, the dehydrating agent is removed, the solution is concentrated to dryness, chromatographed on silica, eluting with methanol / dichloromethane (3:97), a pale yellow powder with a melting point of 193-194 ° C. As dibenzyl phosphate (336) (284 mg, 32%). ¹ H NMR δ [(CD ₃ ) ₂ SO] 12.12 (bfs, 1H), 11.15 (brs, 1H), 8.81 (brs, 1H), 7.69 (s, 1H) , 7.63 (m, 3H), 7.48~7.34 (m, 14H), 5.22 (d, J H-F = 8.3Hz, 4H). Found: C, 69.65; H, 4.37; N, 4.88; P, 5.26. _{C 34 H 25 N 2 O 6} P Calculated: C, 69.38; H, 4.28 ; N, 4.76; P, 5.26.

Example 448 1,3-Dioxo-4-phenyl-1,2,3,6-tetrahydropyrrolo [3,4-c] carbazol-9-yl dihydrogen phosphate (CXIII; Ar = phenyl) (337) A solution of dibenzyl phosphate (336) (100 mg, 0.17 mmol) in methanol / tetrahydrofuran (3: 1, 70 mL) prepared as described in Example 447 was stirred with Pd—C (5%, catalyst). ) At 410 kPa (60 psi) for 3 hours. The reaction mixture was then filtered through celite and concentrated in vacuo. Trituration from ethyl acetate / hexanes afforded phosphate (337) (49 mg, 71%) as a yellow solid, mp 285-295 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 12.01 (br s, 1 H), 11.09 (br s, 1 H), 8.66 (br s, 1 H), 7.63 (m, 3 H) 7.57 (brd, J = 8.6 Hz, 1H), 7.50-7.44 (m, 4H). Found: C, 55.19; H, 3.29; N, 6.34; P, 6.84. _{C 20 H 13 N 2 O 6} P. Calculated for 1 1/2 H ₂ O: C, 55.18; H, 3.71; N, 6.43; P, 7.12.

Example 449 6-acetyl-4- (2-chlorophenyl) -9-methoxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (CXIV; Ar = 2-chlorophenyl) ( Preparation of 338) To a solution of carbazole (33) (45 mg, 0.12 mmol) prepared 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, poured onto ice water, basified with the addition of solid potassium bicarbonate and extracted with ethyl acetate. The organic phase was dehydrated, the dehydrating agent was removed, and the solution was concentrated to dryness. Chromatography on silica eluting with ethyl acetate / hexane (2: 3) followed by trituration from ethyl acetate gave acetamide (338) (40 mg, 80%) as a pale yellow powder with a melting point of 277-280 ° C. Obtained. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.46 (br s, 1H), 8.74 (d, J = 2.8 Hz, 1H), 8.53 (s, 1H), 8.17 ( d, J = 9.2 Hz, 1H), 7.60 (m, 1H), 7.54-7.47 (m, 3H), 7.32 (dd, J = 9.2, 2.8 Hz, 1H) ), 3.93 (s, 3H), 2.91 (s, 3H). Found: C, 65.50; H, 3.49; N, 6.61. _{C 23 H 15 ClN 2 O 4} . 1 / 4H ₂ O Calculated: C, 65.26; H, 3.69 ; N, 6.62.

Example 450 6-acetyl-4- (2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (CXV; Ar = 2-chlorophenyl) ( Acetamide (338) (35 mg, 0.08 mmol) prepared as described in Example 449 was demethylated and chromatographed by the procedure described in Example 80 except that the reaction time was 24 hours. And eluted with ethyl acetate / hexane (1: 2 → 2: 1) to give phenol (339) (22 mg, 65%) as a pale yellow powder, mp 258-261 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.41 (br s, 1 H), 9.80 (br s, 1 H), 8.59 (d, J = 2.6 Hz, 1 H), 8.53 (S, 1H), 8.07 (d, J = 9.1 Hz, 1H), 7.59 (m, 1H), 7.53 to 7.46 (m, 3H), 7.15 (dd, J = 9.1, 2.6 Hz, 1H), 2.89 (s, 3H). Found: C, 65.03; H, 3.14; N, 6.68. Calculated for _{C 22 H 13 ClN 2 O 4} : C, 65.28; H, 3.24; N, 6.92.

  Procedure of scheme 21

Example 451 Preparation of Ethyl (2E) -2-[(4-nitrophenyl) hydrazono] propanoate (901) Para-nitroaniline (900) (10.0 g, 72.0 mmol), ice (72 g) and 15 A mixture of% hydrochloric acid (72 mL) was treated with aqueous sodium nitrite (5.4 g, 78.0 mmol) in water (15 mL) at a rate that the temperature did not exceed 7 ° C. The reaction mixture was stirred for an additional 5 minutes and then filtered through celite to give a clear light yellow / brown solution. This was quickly added to a slurry of sodium 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 hours and then extracted with dichloromethane (3 × 100 mL). The combined extract was dehydrated and concentrated to give a red oil (18 g). When this red oil was dissolved in ethanol (40 mL) and concentrated hydrochloric acid (15 mL) was added, a fine orange / yellow precipitate formed immediately. The reaction mixture was heated at reflux for 15 minutes and then poured onto 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 δ [(CD ₃ ) ₂ SO] 10.50 (s, 1H), 8.20 (m, 2H), 7.40 (m, 2H), 4.23 (q, J = 7.2 Hz) , 2H), 2.13 (s, 3H), 1.29 (t, J = 7 Hz, 3H).

Example 452 Ethyl 5-nitro-1H-indole-2-carboxylate (902)
Ethyl (2E) -2-[(4-nitrophenyl) hydrazono] propanoate (901) (10.6 g, 42 mmol) prepared as described in Example 451 was measured until no starting material remained as measured by tlc. Heated at 110 ° C. in polyphosphoric acid (70 g) (40 minutes). Ice (500 g) was added with vigorous stirring and a dark brown precipitate formed. This was removed by filtration and dried to give ethyl 5-nitro-1H-indole-2-carboxylate (902) (6.04 g, 61%). This material was used in the next step without purification. ¹ H NMR δ [(CD ₃ ) ₂ SO] 12.59 (br, 1H), 8.73 (d, J = 2.4 Hz, 1H), 8.13 (dd, J = 9.2, 2. 4 Hz, 1H), 7.61 (d, J = 9.2 Hz, 1H), 7.44 (s, 1H), 4.38 (q, J = 7.0 Hz, 2H), 1.36 (t, J = 7.0 Hz, 3H).

Example 453 Preparation of (5-Nitro-1H-indol-2-yl) methanol (903) Ethyl 5-nitro-1H-indole-2-carboxylate (9.8 g, 42.0 mmol) in methanol (300 mL) ) To the solution was added 2M potassium hydroxide (31 mL, 63.0 mmol) solution. The reaction mixture was heated at reflux for 2 hours, then the hot solution was filtered, poured onto ice and acidified. The resulting fine light brown precipitate was collected by filtration and dried. The crude acid was dissolved in tetrahydrofuran (250 mL) and stirred with 1,1′-carbonyldiimidazole (10.2 g, 63.0 mmol) for 2 hours while warming lightly. Water (100 mL) was added, then solid sodium borohydride (7.9 g, 0.21 mol) was added in portions over 30 minutes and the reaction mixture was stirred for an additional 40 minutes and then quenched with 1M hydrochloric acid. Tetrahydrofuran was removed under reduced pressure and the residue was dissolved in ethyl acetate, washed, dried and concentrated to give (5-nitro-1H-indol-2-yl) methanol (903). This material was used in the next step without purification.

Example 454 Preparation of 5-Nitro-1H-indole-2-carbaldehyde (904) Crude (5-Nitro-1H-indole-2-yl) methanol (3.60 g, 18.7 mmol) in chloroform (200 mL) ) The solution was heated with manganese dioxide (20 g, 0.23 mol) at 50 ° C. for 3 hours. The reaction mixture was then filtered through celite and concentrated to give 5-nitro-1H-indole-2-carbaldehyde (904) (2.04 g, 57% via two steps). ¹ H NMR δ [(CD ₃ ) ₂ SO] 12.64 (br, 1H), 9.96 (s, 1H), 8.83 (d, J = 2.3 Hz, 1H), 8.18 (dd , J = 9.0 Hz, 2.3 Hz, 1H), 7.69 (d, J = 0.7 Hz, 1H), 7.62 (d, J = 9.0 Hz, 1H).

Example 455 Preparation of 2- [2- (2-chlorophenyl) ethenyl] -5-nitro-1H-indole (CXVI; Ar = 2-chlorophenyl) (905) Aldehyde prepared as described in Example 454 (904) was reacted with 2-chlorobenzyltriphenylphosphonium chloride (at room temperature) by the procedure described in Example 37 to give the yellow solid diene (905) (95%) as a mixture of E / Z isomers. Obtained. Crystallization from aqueous methanol gave the pure E-isomer (80%) as yellow needles of melting point 230-232 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 12.28 (br s, 1H), 8.55 (d, J = 2.3 Hz, 1H), 8.03 (dd, J = 9.1, 2) .3 Hz, 1 H), 7.91 (dd, J = 7.8, 1.5 Hz, 1 H), 7.32 to 7.61 (m, 6 H), 6.92 (s, 1 H). Found: C, 64.59; H, 5.68; N, 9.49. Calculated for C ₁₆ H ₁₁ ClN ₂ O ₂ C, 64.33; H, 5.68; N, 9.49.

Example 456 Preparation of methyl 2- [2- (5-nitro-1H-indol-2-yl) ethenyl] phenyl ether (CXVI; Ar = 2-methoxyphenyl) (906) As described in Example 454 The aldehyde prepared in 904 (904) was reacted with 2-methoxybenzyltriphenylphosphonium bromide by the procedure described in Example 37 to give a yellow solid diene (905) (95%) as a mixture of E / Z isomers. Got. This was used without further purification.

Example 457 Methyl 2- [2- (1-methyl-5-nitro-1H-indol-2-yl) ethenyl] phenyl ether (CXVII; Ar = 2-methoxyphenyl, R ¹⁰ = Me) (907) The diene (906) prepared as described in Example 456 was alkylated with methyl iodide by the procedure described in Method 3 to give the corresponding diene as a yellow solid (mixture of E / Z isomers). (908) (94%) was obtained. This was used without further purification.

Preparation Example of; (Ar = ^{2-chlorophenyl, R 10 = Me CXVII) (} 908) ( Example 458) 2- [2- (2-chlorophenyl) ethenyl] -1-methyl-5-nitro -1H- indole The diene (905) prepared as described in 455 was alkylated with methyl iodide by the procedure described in Example 38 to give the corresponding diene (908) (99%) as a yellow solid. The sample was crystallized from methanol as orange needles with a melting point of 161-163 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 8.53 (d, J = 2.3 Hz, 1H), 8.05 (dd, J = 7.7, 1.6 Hz, 1H), 8.02 ( dd, J = 9.1, 2.3 Hz, 1H), 7.67 (d, J = 9.1 Hz, 1H), 7.46-7.64 (m, 3H), 7.43 (dt, J = 7.7, 1.6 Hz, 1H), 7.36 (dt, J = 7.7, 1.6 Hz, 1H), 7.22 (s, 1H), 3.95 (s, 3H). Found: C, 65.55; H, 4.19; N, 8.90. C ₁₇ H ₁₃ ClN ₂ O ₂ Calculated C, 65.28; H, 4.19; N, 8.96.

Example 459 4- (2-methoxyphenyl) -6-methyl-9-nitro-4,5,6,10c-tetrahydropyrrolo [3,4-c] carbazole-1,3 (2H, 3aH)- Preparation of dione (CXVIII; Ar = 2-methoxyphenyl, R ¹⁰ = Me) (909) The diene (907) prepared as described in Example 457 was reacted with maleimide by the procedure described in Example 68. A glassy solid adduct (909) (84%) was obtained. This was immediately aromatized.

Example 460 4- (2-Chlorophenyl) -6-methyl-9-nitro-4,5,6,10c-tetrahydropyrrolo [3,4-c] carbazole-1,3 (2H, 3aH) -dione Preparation of (CXVIII; Ar = 2-chlorophenyl, R ¹⁰ = Me) (910) A diene (908) prepared as described in Example 458 was reacted with maleimide by the procedure described in Example 68 to produce a glass. A dark solid adduct (910) (88%) was obtained. This was immediately aromatized.

Example 461 4- (2-chlorophenyl) -9-nitro-4,5,6,10c-tetrahydropyrrolo [3,4-c] carbazole-1,3 (2H, 3aH) -dione (CXVIII; Ar = 2-Chlorophenyl, R ¹⁰ = H) (917) The diene (905) prepared as described in Example 455 was reacted with maleimide by the procedure described in Example 68 to give an adduct of dark solid. (917) (74%) was obtained. This was immediately aromatized.

Example 462 4- (2-methoxyphenyl) -6-methyl-9-nitropyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (CXIX; Ar = 2-methoxyphenyl, Preparation of R ¹⁰ = Me) (911) An adduct (909) prepared as described in Example 459 was prepared using manganese dioxide according to the procedure described in Example 79 except that the reaction time was only 4 hours. Aromatization gave nitrocarbazole (911) (50%) as a brown solid with a melting point of 320-330 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.24 (s, 1H), 9.76 (d, J = 2 Hz, 1H), 8.50 (dd, J = 9.1, 2.2 Hz, 1H), 7.93 (s, 1H), 7.91 (d, J = 9.1 Hz, 1H), 7.46 (t, J = 7.3 Hz, 1H), 7.38 (d, J = 7.3 Hz, 1H), 7.13 (d, J = 7.3 Hz, 1H), 7.08 (t, J = 7.3 Hz, 1H), 4.05 (s, 3H), 3.70 ( s, 3H). Found: C; 65.76; H, 3.83; N, 9.30. Calculated for _{C 22 H 15 N 3 O 5} : C, 65.83; H, 3.77; N, 10.47.

Example 463 4- (2-Chlorophenyl) -6-methyl-9-nitropyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (CXIX; Ar = 2-chlorophenyl, R ¹⁰ = Me) Preparation of (912) The adduct (910) prepared as described in Example 460 is aromatic using manganese dioxide according to the procedure described in Example 79 except that the reaction time is only 4 hours. To give nitrocarbazole (912) (78%) as an orange solid with a melting point> 320 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.35 (s, 1H), 9.68 (d, J = 2.3 Hz, 1H), 8.46 (dd, J = 9.1, 2. 3 Hz, 1 H), 8.00 (s, 1 H), 7.88 (d, J = 9.1 Hz, 1 H), 7.47 to 7.62 (m, 4 H), 4.04 (s, 3 H) . Found: C, 58.90; H, 3.28; N, 10.30. _{C 21 H 12 ClN 3 O 4} . Of H ₂ O Calculated: C, 59.57; H, 3.30 ; N, 9.93.

Example 464 4- (2-chlorophenyl) -9-nitropyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (CXIX; Ar = 2-chlorophenyl, R ¹⁰ = H) ( Preparation of 918) The adduct (917) prepared as described in Example 463 was aromatized with manganese dioxide by the procedure described in Example 79 except that the reaction time was only 4 hours, and the melting point Nitrocarbazole (918) (84%) was obtained as a yellow solid at 253-258 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 12.78 (s, 1H), 11.33 (s, 1H), 9.74 (d, J = 2.5 Hz, 1H), 8.45 (dd , J = 9.1, 2.5 Hz, 1H), 7.80 (d, J = 9.1 Hz, 1H), 7.77 (s, 1H), 7.60 (dd, J = 7.2). 1.5 Hz, 1H), 7.45 to 7.54 (m, 3H). Found: C, 62.39; H, 3.03; N, 10.10. _{C 20 H 10 ClN 3 O 4} . Calculated for 1/6 hexane: C, 62.22; H, 3.04; N, 10.37.

  Representative Procedure for Method 34 of Scheme 21

Example 465 9-amino-4- (2-chlorophenyl) -6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (CXX; Ar = 2-chlorophenyl, R ¹⁰ = Me) Preparation of (914) Nitrocarbazole (912) (0.055 g, 0.14 mmol) prepared as described in Example 463 was suspended in an ethanol: water (4: 1, 20 mL) mixture, Refluxed. After 15 minutes, iron powder (0.076 g, 1.4 mmol) was added, followed by acetic acid (0.041 g, 0.70 mmol). The red solution turned to dark when refluxed for 1 hour. The cooled solution was filtered through celite and washed with ethyl acetate (2 × 100 mL). The solvent was evaporated under reduced pressure leaving a brown residue. This was dissolved in ethyl acetate (200 mL). The solution was washed with saturated aqueous sodium bicarbonate and saturated aqueous sodium chloride, then dried and processed to give amine (914) as a red solid with a melting point of 208-216 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.00 (s, 1H), 8.15 (d, J = 2.2 Hz, 1H), 7.68 (s, 1H), 7.56 (dd , J = 7.0, 1.9 Hz, 1H), 7.43-7.49 (m, 4H), 7.02 (dd, J = 8.7, 2.2 Hz, 1H), 5.03 ( br s, 2H, exchanged with D ₂ O), 3.88 (s, 3H). Found: C, 64.48; H, 3.82; N, 10.32. _{C 21 H 14 ClN 3 O 2} . Of H ₂ O Calculated: C, 64.12; H, 4.07 ; N, 10.68.

Example 466 9-amino-4- (2-methoxyphenyl) -6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (CXX; Ar = 2-methoxyphenyl) Preparation of R ¹⁰ = Me) (913) Nitrocarbazole (911), prepared as described in Example 462, was reduced with iron powder according to the procedure described in Method 34 to give a brown melting point of 188-192 ° C. Amine (913) (74%) was obtained as a solid. ¹ H NMR δ [(CD ₃ ) ₂ SO] 10.87 (s, 1H), 8.14 (d, J = 1.7 Hz, 1H), 7.61 (s, 1H), 7.40-7 .42 (m, 2H), 7.33 (dd, J = 7.3, 1.6 Hz, 1H), 6.98 to 7.10 (m, 3H), 5.00 (broad s, 2H, D) ₂ O and exchange), 3.86 (s, 3H) , 3.68 (s, 3H). Found: C, 69.61; H, 4.66; N, 9.32. _{C 22 H 17 N 3 O 3} . 1 / _2C 4 _{H 8} O Calculated: C, 69.40; H, 5.06 ; N, 10.12.

Example 467 9-amino-4- (2-chlorophenyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (CXX; Ar = 2-chlorophenyl, R ¹⁰ = H) Preparation of (919) Nitrocarbazole (918) prepared as described in Example 464 was reduced with iron powder for 45 minutes according to the procedure described in Example 465. The product was precipitated from THF: petroleum ether to give amine (919) (91%) as a brown solid, mp 216-222 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.66 (s, 1H), 10.96 (s, 1H), 8.09 (d, J = 2.3 Hz, 1H), 7.57 (dd , J = 8.1, 1.8 Hz, 1H), 7.40-7.50 (m, 4H), 7.35 (d, J = 8.6 Hz, 1H), 6.95 (dd, J = 8.6, 2.3 Hz, 1H), 4.95 (brs, 2H). Calculated values for EIMS: M ⁺ = 361.0611, 363.0587. Calculated 361.0818,363.0589 of _{C 20 H 12 ClN 3 O 2} .

  Representative Procedure for Method 35 of Scheme 21

Example 468 N- [4- (2-methoxyphenyl) -6-methyl-1,3-dioxo-1,2,3,6-tetrahydropyrrolo [3,4-c] carbazol-9-yl Preparation of Acetamide (CXXI; Ar = 2-methoxyphenyl, R ¹⁰ = Me, R ⁴ = Me) (916) Acetic acid (1 mL) and acetic anhydride (1 mL) were mixed at 0 ° C. under nitrogen and the solution was 0 ° C. For 1 hour. Amine (913) (0.06 g, 0.16 mmol), prepared as described in Example 466, in anhydrous dichloromethane was added and the mixture was warmed at room temperature for 2 hours, then the solvent was evaporated under reduced pressure. The resulting yellow solid was purified by column chromatography on silica gel eluting with petroleum ether: ethyl acetate (100: 0 → 0: 100). The product (916) was then precipitated from tetrahydrofuran with petroleum ether to give a yellow powder (0.044 g, 67%), mp 300-304 ° C. ¹ H NMR δ [(CD ₃ ) 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, 1H), 7.74 (s, 1H), 7.66 (d, J = 8.8 Hz, 1H), 7.43 (dt, J = 7.4). 1.7 Hz, 1H), 7.34 (dd, J = 7.4, 1.7 Hz, 1H), 7.12 (d, J = 8.1 Hz, 1H), 7.05 (t, J = 8) .1 Hz, 1H), 3.95 (s, 3H), 3.68 (s, 3H), 2.10 (s, 3H). Found: C, 66.10; H, 4.60; N, 9.44. _{C 24 H 19 N 3 O 4} . Of H ₂ O Calculated: C, 66.82; H, 4.41 ; N, 9.74.

Example 469 4- (2-chlorophenyl) -6-methyl-1,3-dioxo-1,2,3,6-tetrahydropyrrolo [3,4-c] carbazol-9-ylformamide (CXXI; Ar = 2-chlorophenyl, R ¹⁰ = Me, R ⁴ = H) (920) Preparation The amine (914) prepared as described in Example 465 and formic acid were reacted for 16 hours according to the procedure described in Method 35. Formamide (920) (92%) was obtained as a yellow powder with a melting point of 345-348 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.16 (s, 0.5 H), 11.12 (s, 1 H), 10.36 (m, 1.5 H), 9.08 (d, J = 2.0 Hz, 1 H), 8.72 (m, 0.5 H), 8.32 (d, J = 1.8 Hz, 1 H), 7.99 (dd, J = 8.8, 2.0 Hz, 1H), 7.85 (s, 0.5H), 7.83 (s, 1H), 7.70-7.73 (m, 1.5H), 7.46-7.60 (m, 7H) 3.98 (s, 1.5H), 3.98 (s, 3H). Calculated for FABMS: [M + H] ⁺ = 404.0790, 406.0777. Calculated 404.0802,406.0772 of _{C 22 H 15 ClN 3 O 3} .

Example 470 4- (2-Chlorophenyl) -1,3-dioxo-1,2,3,6-tetrahydropyrrolo [3,4-c] carbazol-9-ylformamide (CXXI; Ar = 2-chlorophenyl) , R ¹⁰ = H, R ⁴ = H) (921) The amine (919) prepared as described in Example 467 and formic acid were reacted for 4 hours using the procedure described in Example 468, Formamide (921) (54%) was obtained as a yellow powder having a melting point of 293 to 297 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 12.11 (s, 0.5 H), 12.08 (s, 1 H), 11.12 (s, 0.5 H), 11.08 (s, 1 H) ), 10.34 (s, 1H), 10.30 (s, 0.5H), 9.03 (d, J = 1.9 Hz, 1H), 8.69 (m, 0.5H), 8. 31 (d, J = 1.8 Hz, 1.5H), 7.92 (dd, J = 8.8, 1.9 Hz, 1H), 7.42-7.65 (m, 9.5H). Found: C, 64.78; H, 3.53; N, 9.96. _{C 21 H 12 ClN 3 O 3} . Calculated for 1/4 THF: C, 64.86; H, 3.44; N, 10.32.

Example 471 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, R ¹⁰ = Me, R ⁴ = Me) Preparation of (923) The amine (914) and acetic acid prepared as described in Example 465 and the procedure described in Example 468 were used. And reacted for 14 hours to give acetamide (923) (85%) as a yellow powder with a melting point of 338-340 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.10 (exchanged with br s, D ₂ O, 1H), 10.14 (exchanged with s, D ₂ O, 1H), 9.01 (d, J = 2.0 Hz, 1H), 7.99 (dd, J = 8.9, 2.0 Hz, 1H), 7.82 (s, 1H), 7.68 (d, J = 8.9 Hz, 1H) 7.57 (dd, J = 7.2, 1.9 Hz, 1H), 7.44 to 7.53 (m, 3H), 3.93 (s, 3H), 2.10 (s, 3H) . Found: C, 64.44; H, 4.08; N, 8.98. _{C 23 H 16 ClN 3 O 3} . 1 _/ 2CH 3 COOH Calculated C, 64.43; H, 4.03; N, 9.39.

Example 472 N- [4- (2-chlorophenyl) -1,3-dioxo-1,2,3,6-tetrahydropyrrolo [3,4-c] carbazol-9-yl] acetamide (CXXI; Ar = 2-chlorophenyl, R ¹⁰ = H, R ⁴ = Me) (926) Preparation of amine (919) and acetic acid prepared as described in Example 467 using the procedure described in Example 468 for 4 hours. The reaction gave acetamide (926) (43%) as a yellow powder with a melting point of 240-245 ° C. ¹ H NMR δ [(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 Hz, 1 H), 7.90 (dd, J = 8.8, 2.1 Hz, 1 H), 7.58 (m, 2 H), 7.42 to 7.51 (m, 4 H), 2.10 (S, 3H). Calculated for FABMS: [M + H] ⁺ = 404.0787, 406.0776. Calculated 404.0802,406.0772 of _{C 22 H 15 ClN 3 O 3} .

  Representative Procedure for Method 36 of Scheme 21

Example 473 N- [4- (2-chlorophenyl) -6-methyl-1,3-dioxo-1,2,3,6-tetrahydropyrrolo [3,4-c] carbazol-9-yl]- Preparation of 3- (1-piperidinyl) propanamide (CXXI; Ar = 2-chlorophenyl, R ¹⁰ = Me, R ⁴ = 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) mixed in anhydrous dimethylformamide (2 mL) at 0 ° C. under a nitrogen atmosphere. And left to stir for 1 hour. A solution of amine (914) (0.085 g, 0.23 mmol) in anhydrous dimethylformamide (3 mL) was added to the reaction mixture. The solution was warmed to room temperature for 16 hours. The solvent was removed under reduced pressure and the residue was adsorbed on silica. Purify by column chromatography eluting with ethyl acetate: methanol: triethylamine (100: 0: 0 → 75: 24: 1) to obtain (925) (0.036 g, 30%) as a yellow solid with a melting point of 241 ° -246 ° C. ) ¹ H NMR δ [(C03) 2SO] 11.12 (s, 1H), 10.46 (s, 1H), 9.92 (broad s, 1H), 9.09 (d, J = 2.0 Hz, 1H), 7.98 (dd, J = 8.9, 2.0 Hz, 1H), 7.83 (s, 1H), 7.71 (d, J = 8.9 Hz, 1H), 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). Calculated for FABMS: [M + H] ⁺ = 515.1842, 517.1833. Calculated 515.1850,517.1820 of _{C 29 H 28 ClN 4 O 3} .

Example 474 N- [4- (2-Chlorophenyl) -6-methyl-1,3-dioxo-1,2,3,6-tetrahydropyrrolo [3,4-c] carbazol-9-yl] hydrochloride 4- (dimethylamino) butanamide (CXXI; Ar = ^{2-chlorophenyl, R 10 = Me, R 4} = 4- dimethylamino-butyl) (928) amine, prepared as described in Preparative example 465 (914) Was reacted with EDCI and 4-dimethylaminobutyric acid hydrochloride using the procedure described in Example 473 to give amide (928) (44%) as an orange powder with a melting point of 331-333 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.11 (s, 1 H), 10.25 (s, 1 H), 9.82 (br s, 1 H), 9.07 (d, J = 2. 0 Hz, 1H), 7.98 (dd, J = 9.0, 2.0 Hz, 1H), 7.83 (s, 1H), 7.70 (d, J = 9.0 Hz, 1H), 7. 58 (m, 1H), 7.44 to 7.52 (m, 3H), 3.97 (s, 3H), 2.99 to 3.11 (m, 4H), 2.77 (s, 6H) 2.00 (m, 2H). Calculated for FABMS: [M + H] ⁺ = 489.1689, 491.1681. Calculated 489.1693,491.1664 of _{C 27 H 26 ClN 4 O 3} .

  Representative Procedure for Method 37 of Scheme 21

Example 475 4- (2-chlorophenyl) -6-methyl-9- (methylamino) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (CXXII; Ar = chlorophenyl, Preparation of R ¹⁰ = Me, R ⁴ = H) (922) Borane methyl sulfide complex (0.074 mL, 0.78 mmol) and trimethyl borate (0.089 mL, 0.78 mmol) were as described in Example 469. Was added to a solution of amide (920) (0.105 g, 0.26 mmol) in anhydrous tetrahydrofuran (10 mL) at 0 ° C. under a nitrogen atmosphere. After stirring at 0 ° C. for 30 minutes, the solution was warmed to room temperature for 16 hours. Methanol (200 mL) was added and the reaction mixture was stirred for 12 hours. The solvent was removed in vacuo and the yellow residue was purified by column chromatography on silica eluting with petroleum ether: ethyl acetate (100: 0 → 0: 100) to give a red solid of melting point 293-296 ° C. As (922) (0.053 g, 45%). ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.01 (br s, 1 H), 8.10 (d, J = 2.3 Hz, 1 H), 7.69 (s, 1 H), 7.57 ( dd, J = 7.1, 2.0 Hz, 1H), 7.42-7.52 (m, 4H), 7.02 (dd, J = 8.8, 2.3 Hz, 1H), 5.61 (Q, J = 5.2 Hz, 1H), 3.90 (s, 3H), 2.81 (d, J = 5.2 Hz, 3H). Calculated value of EIMS: M ⁺ = 389.929, 391.0905. Calculated 389.0931,391.0902 of _{C 22 H 16 ClN 3 O 2} .

Example 476 4- (2-chlorophenyl) -9- (ethylamino) -6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (CXXII; Ar = chlorophenyl, R ¹⁰ = Me, R ⁴ = Me) (924) Preparation amide (923) prepared as described in Example 471 was prepared using the borane methyl sulfide complex according to the procedure described in Method 37, mp 232-236 ° C. As a red powder, amine (924) was obtained. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.00 (exchanged with s, D ₂ O, 1H), 8.13 (d, J = 2.2 Hz, 1H), 7.69 (s, 1H) 7.57 (dd, J = 7.0, 2.0 Hz, 1H), 7.42-7.51 (m, 4H), 7.05 (dd, J = 8.8, 2.2 Hz, 1H) ), 5.51 (t, J = 5.4 Hz, exchange with D ₂ O, 1H), 3.15 (m, 2H), 1.27 (t, J = 7.1 Hz, 3H). Calculated value of EIMS: M ⁺ = 403.1080, 405.1061. Calculated 403.1087,405.1058 of _{C 23 H 18 ClN 3 O 2} .

Example 477 4- (2-chlorophenyl) -9- (methylamino) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (CXXII; Ar = chlorophenyl, R ¹⁰ = H , R ⁴ = H) (927) The amide (921) (0.051 g, 0.13 mmol) prepared as described in Example 470 was reacted with the borane methyl sulfide complex by the procedure described in Method 37. Thus, amine (927) (0.021 g, 43%) was obtained as an orange powder having a melting point of 182 to 184 ° C. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.69 (broad s, 1H), 10.97 (broad s, 1H), 8.05 (d, J = 2.1 Hz, 1H), 7.40 7.57 (m, 5H), 6.97 (dd, J = 8.7, 2.4 Hz, 1H), 5.55 (q, J = 4.9 Hz, 1H), 2.80 (d, J = 5.2 Hz, 3H). Calculated value of EIMS: M ⁺ = 375.0768, 377.0749. Calculated 375.0774,377.0745 of _{C 21 H 14 ClN 3 O 2} .

  Representative Procedure for Method 38 of Scheme 21

Example 478 9- (dimethylamino) -4- (2-methoxyphenyl) -6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (CXXIII; Ar = methoxyphenyl) , R ¹⁰ = Me, R ³ = H) (915) Preparation Amine (913) (0.049 g, 0.13 mmol) prepared as described in Example 466 was suspended in methanol (15 mL) at 0 ° C. And stirred. Formaldehyde (37% aqueous solution 0.01 mL, 0.13 mmol) was added, followed immediately by sodium cyanoborohydride (0.022 g, 3.5 mmol) and the mixture was stirred at room temperature for 14 hours. The solvent was removed under reduced pressure and the residue was dissolved in ethyl acetate (100 mL). The solution was washed with water (2 × 100 mL), saturated aqueous sodium chloride solution (2 × 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 (100: 0 → 0: 100) to give (915) as a red solid (0.017 g, 33%), mp 246-251 ° C. Obtained. ¹ H NMR δ [(CD ₃ ) ₂ SO] 10.92 (s, 1H), 8.39 (d, J = 2.5 Hz, 1H), 7.67 (s, 1H), 7.58 (d , J = 9.0 Hz, 1H), 7.41 (dt, J = 7.4, 1.7 Hz, 1H), 7.37 (dd, J = 7.4, 1.7 Hz, 1H), 7. 25 (dd, J = 9.0, 2.5 Hz, 1H), 7.10 (d, J = 7.4 Hz, 1H), 7.04 (t, J = 7.4 Hz, 1H), 3.91 (S, 3H), 3.68 (s, 3H), 2.99 (s, 6H). Calculated value of EIMS M ⁺ : 399.1580. Calcd 399.1583 for _{C 24 H 21 N 3 O 3} .

  Procedure of scheme 22

Example 479 4- (2-chlorophenyl) -1,3-dioxo-1,2,3,6-tetrahydropyrrolo [3,4-c] carbazol-9-yl trifluoromethanesulfonate (CXXIV; Ar = 2 -Preparation of (Chlorophenyl) (615) Compound (615) was prepared from (9) (I; (Ar = 2-chlorophenyl) prepared as described in Example 8 by the procedure described in Example 307. A yellow oil was obtained ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.83 (s, 1 H), 11.03 (s, 1 H), 8.28 (s, 1 H), 8.32 (S 1H), 7.6-7.4 (m, 5H), 7.07 (s, 1H) Calculated EIMS: M ⁺ = 493.9946. C ₂₁ H ₁₀ ClF ₃ N ₂ SO ₅ Calculated value 493.9951.

Example 480 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 as described in Example 479 using tetraethyltin as tin hydride (prepared from (615) using the procedure described in Example 309 to give a yellow oil. ¹ H NMR δ [(CD ₃ ) ₂ SO] 11.71 (s, 1H), 11.48 (br, 1H), 8.23 (s, 1H), 8.78, (s, 1H), 7 .99 (s, 1H), 7.62 to 7.43 (m, 5H), 7.2 to 7.1 (m, 1H), 6.10 (d, J = 17.6 Hz, 1H), 5 .46 (d, J = 11.3 Hz, 1H) Calculated value of EIMS: M ⁺ = 372.0661.C ₂₂ H ₁₃ ClN ₂ O ₂ Calculated 372.0666.

Example 481 4- (2-chlorophenyl) -9- (1,2-dihydroxyethyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (CXXVI; Ar = 2- Preparation of (Chlorophenyl) (617) Diol (617) was prepared from (616) as described in Example 480 using the procedure described in Example 300 and was a yellow solid of melting point 265-268 ° C. Got. ¹ H NMR δ [(CD ₃ ) ₂ SO] 12.06 (br, 1H), 11.08 (br, 1H), 8.87 (s, 1H), 7.60-7.40 (m, 7H) ), 5.32 (d, J = 3.8.Hz, 1H), 4.74 (m, 2H), 3.55 (m, 2H). Calculated value of EIMS: M ⁺ = 406.0718. Calcd 406.0720 for _{C 22 H 15 ClN 2 O 4} .

Example 482 4- (2-chlorophenyl) -9- (2-hydroxyethyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (CXXVII; Ar = 2-chlorophenyl) Preparation of (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 of melting point 253-257 ° C. It was. ¹ H NMR δ [(CD ₃ ) ₂ SO] 12.03 (br, 1H), 11.08 (br, 1H), 8.73 (s, 1H), 7.60-7.40 (m, 6H) ), 4.69 (t, J = 5.2 Hz, 1H), 3.71 (m, 2H), 2.93 (t, J = 7.2 Hz, 2H). Calculated value of EIMS: M ⁺ = 390.0769. Calc'd for C ₂₂ H ₁₅ ClN ₂ O ₃ 390.0771.

Example 483 Other Novel Checkpoint Inhibitors Listed below are other checkpoint inhibitors of the present invention. These can be prepared by methods known in the art, the methods described herein, or a combination of the above methods. One of ordinary skill in the art should understand how to prepare each compound by referring to the disclosure herein.

Example 484 Wee1 Inhibition Filter Binding Assay (OY) Testing Wee1 Inhibitory Activity
This assay measures the inhibitory ability of a test compound against isolated Wee1 kinase.

The Weel kinase assay measures tyrosine enzyme-mediated phosphorylation on synthetic peptide substrates in the presence of test compounds. This assay was performed in 96-well filter microtiter plates (Millipore #MADP NOB10). The compound was dissolved and diluted with DMSO. 10 μL of 3 × EDB buffer (150 mM Tris, pH 8.0, 30 mM NaCl, 30 mM MgCl ₂ , 3 mM DTT), 18 μl water and 2 μl diluted drug were added to the test wells and mixed well. 10 μl of enzyme substrate mixture was added to the wells. The Wee1 enzyme (human Wee1 kinase aa215-647, Onyx Pharmaceuticals) expressed in and purified from the baculovirus protein expression system has a concentration of 0.01 μg / μl, substrate (polyornithine: tyrosine (4: 1), Sigma Chemical Co.) was 0.6 μg / μl in 1 × EDB buffer. The plates were mixed thoroughly for 5 minutes at room temperature. The reaction was initiated by the addition of 10 μl of 1 × EDB buffer containing 47.5 μM ATP (Sigma) and 0.026 μCi / μl γ- ³² P-ATP (ICN Biomedicals, Inc.). These plates were mixed for 20 minutes at room temperature. The reaction was stopped by adding 50 μL of ice-cold 20% TCA containing 0.1 M tetrasodium pyrophosphate. Plates were incubated on ice or refrigerated at 4 ° C. for 1 hour. The liquid reaction mixture was removed on a vacuum manifold and the precipitated phosphorylated substrate was rinsed 5 times with 200 μl of ice-cold 10% TCA containing 0.1 M tetrasodium pyrophosphate. 25 μl of liquid scintillation cocktail was added to the membrane bound substrate and the plate was read using a Microbeta (Perkin-Elmer) plate reader. The activity of the compound in each assay was calculated relative to an uninhibited control measurement.

The data shown in Table 3 is Wee1 activity (IC ₅₀ ) from less than 0.1 μM up to 1.65 μM. However, compound X having the highest Wee1 activity in this table is a representative compound of US Pat. No. 4,912,107. Compound X is neither structurally nor as a checkpoint inhibitor of the present invention within the scope of the present invention. The activity of Compound X against Wee1 kinase in this assay is weaker than the upper limit of preferred compounds. According to the data in Table 3, modification of the nuclear structure results in unexpected Wee1 kinase inhibitory potency and at least 10-fold selectivity over PKC enzyme inhibition.

The compounds of the present invention may be used alone or in combination with one or more other antineoplastic physiotherapy to treat cell proliferative diseases in animals when the Wee1 activity has an IC ₅₀ of less than 1 μM in the above assay. Appropriate to use. Preferably, the compound has an IC ₅₀ of less than 0.5 μM, most preferably an IC ₅₀ of less than 0.1 μM.

Example 485 Chk1 Enzyme Inhibition Assay In order to determine the inhibitory activity of compounds of the present invention against Chk1, the following assay was performed to measure the inhibition of isolated Chk1 enzyme.

The assay was performed in round bottom polypropylene 96 well plates (Costar). The compounds were tested starting at a high concentration of 50 μM, followed by serial dilutions up to nine 3-fold dilutions. The compound was dissolved in DMSO and diluted. 2 μl of drug is dropped into the bottom of the assay plate, then diluted with 58 μl of Chk1 buffer (20 mM Tris, pH 8.0, 50 mM NaCl, 10% glycerin, 10 mM MgCl ₂ , 5 mM dithiothreitol) and mixed for 1 minute at room temperature . 20 μl of buffer containing 250 ηg / well of Chk1 enzyme (Onyx Pharmaceutical) and 1 μg / well of GST-Cdc25 substrate (Onyx) were added. The contents of the wells were mixed for 1 minute and incubated at room temperature for 10 minutes. 20 μl of buffer containing 20 μM ATP and 0.4 μCi ATP [γ- ³³ P] were added. The contents were mixed for 1 minute and incubated at 30 ° C. for 30 minutes. The reaction was stopped by adding 50 μl of 120 mM EDTA to each well, except for control wells already containing EDTA. 140 μl of the contents of the wells were transferred to the wells of a Reacti-Bind glutathione coated white 96 well plate (Pierce). The contents were mixed for 1 minute and incubated at room temperature for 1 hour. All wells were rinsed 3 times with 300 μl PBS each time and allowed to air dry. 200 μl of MicroScint 20 (Packard) was placed in the well. Plates were sealed with an adhesive cover and counted on a Top Count microplate scintillation counter (Packard). The activity of the compound in each assay was calculated relative to an uninhibited control measurement.

The data shown in Table 4 are Chk1 activities (IC ₅₀ ) from less than 0.002 μM up to 0.297 μM. However, compound X with the highest Chk1 activity in this table is a representative compound of US Pat. No. 4,912,107. Compound X is neither structurally nor as a checkpoint inhibitor of the present invention within the scope of the present invention. The activity of Compound X against Chk1 kinase in this assay is less potent than the upper limit of the preferred compound. According to the data in Table 4, modification of the nuclear structure results in an unexpected Chkl kinase inhibitory titer and at least a 10-fold selectivity over PKC enzyme inhibition.

The compounds of the present invention are considered suitable for use in the treatment of cell proliferative diseases in animals in combination with other antineoplastic physiotherapy when Chk1 activity has an IC ₅₀ of less than 0.275 μM in the above assay. It is done. Preferably, the compound has an IC ₅₀ of less than 0.2 μM, most preferably an IC ₅₀ of less than 0.1 μM.

Some of the compounds of the present invention are dual inhibitors and selectively inhibit the activity of both Wee1 and Chk1. These compounds can be as potent as compounds that selectively inhibit Wee1 or Chk1, even if the activity on either enzyme is higher than that desired for a single inhibitor. It is preferred that the dual inhibitor has an IC ₅₀ of less than 1 μM, more preferably less than 500 nM, most preferably less than 100 nM.

Example 486 Myt-1 Inhibition Scintillation Proximity Assay for Testing Myt-1 Inhibitory Activity This assay measures the inhibitory activity of a test compound against isolated Myt-1 kinase.

The assay was performed in Wallac 96 well SPA (Scintillation Proximity Assay) plates. Compounds were tested at 50 μM, followed by up to nine 3-fold dilutions (ie 50, 16.67, 5.56, 1.85, 0.617, etc.). The drug was dissolved in DMSO and diluted. 2 μl of drug was placed on the bottom of the well of the SPA plate. 30 μl of MB buffer (50 mM Tris, pH 8.0, 100 mM NaCl, 0.1% Tween 20, 1 mM MgCl ₂ , 100 μM DTT) containing 27 μM cold ATP was added to each well and then 177.8 ηM Myt-1 enzyme 9 μl of MB buffer containing (MW = 54.6 kDa) was added. Plates were mixed for 1 minute at room temperature and then incubated for 5-15 minutes at room temperature. Add 9 μl of MHKB buffer (50 mM Tris, pH 8.0, 1 mM MgCl ₂ , 100 μM DTT, 0.1 mM Na ₃ VO ₄ ) containing 88.9 ηM Cdc2 / B (MW = 84.5 kDa) for 1 minute at room temperature Mixed. The plate was centrifuged at up to 2400 RPM and incubated at 30 ° C. for 30 minutes. 30 μl of MHKB buffer containing 1 μM biotinylated histone H1 (Amersham) peptide substrate (stock solution: 1 mM) and 10 μCi / μl ATP [γ- ³³ P]) were added. Plates were mixed for 1 minute at room temperature, centrifuged at up to 2400 RPM and incubated at 30 ° C. for 30 minutes. Stop buffer 200 μl, containing at least 20 μg / ml streptavidin SPA beads (Amersham) 5 mM EDTA and 0.1% Triton (from 10 × stock solution of 50 mM EDTA and 1.0% Triton X-100 diluted in PBS) The reaction was stopped with X-100 and 50 μM ATP. The plate was sealed with an adhesive cover, mixed 10 times by inversion, and incubated at room temperature for 10 minutes. Plates were centrifuged at 2400 RPM for 15 minutes at room temperature and counted on a Wallac Microbeta Trilux counter. The activity of the compound in each assay was calculated relative to an uninhibited control measurement.

None of the compounds of the invention had an IC _{50 for} Myt-1 activity of less than 10 μM in this assay. Since phosphorylation of thr 14 on cdc2 (catalyzed by Myt-1 kinase) is also a checkpoint establishing event, compounds that inhibit both Wee1 kinase and Myt-1 kinase are It may be a checkpoint inhibitor because of its original inhibitory activity. Thus, the lack of Myt-1 inhibition excludes Myt-1's contribution to checkpoint inhibition. The lack of significant Myt-1 inhibitory activity of the compounds of the present invention indicates the selectivity of these compounds as Wee1 kinase and Chk1 kinase inhibitors.

Example 487 Protein Kinase C (PKC) Assay The PKC assay measures the inhibitory activity of a test compound against PKC contained in a rat brain preparation.

Enzymes were prepared from 0.5 μg rat brain preparation (Promega) diluted with 1.6 ml 10 mM Hepes buffer pH 7.5. Reaction buffer is, 150 mM Hepes _{buffer, 4mM CaCl 2, 15mM MgCl 2} , 3mM EDTA, made 3.75 mM EGTA, is pH 7.5. The histone substrate was prepared by dissolving histone H1 (Sigma) in water at 1.5 mg / ml. 10mg / ml the CHCl ₃ solution 75μ1 of phosphatidylserine (Sigma), 2.5 mg / ml dioleate was mixed with CHCl ₃ solution (Sigma) and glass vials, phosphatidylserine by evaporating the CHCl ₃ under _{N 2} / Diolein liposomes were prepared. This membrane was suspended in 1 ml of water and sonicated for 6 × 15 seconds at room temperature using a microchip probe.

To perform the assay, 50 μl of buffer, 20 μl of histone, 20 μl of liposome, and inhibitor or solvent control, as needed, in 96 well filter plates (Millipore) with enough water to make a final volume of 110 μl. Added to wells. 20 μl of enzyme preparation solution was added and incubated for 10 minutes at room temperature. Subsequently, ³² P ATP (75 μM ATP aqueous solution, 25 μCi / ml labeled ATP) was added and incubated at room temperature for 15 minutes. The reaction was stopped by adding 50 μl of 40% (w / v) trichloroacetic acid. The filter was washed by filtration under reduced pressure using 5 × 125 μl of ice-cold 10% (w / v) trichloroacetic acid. The filter was placed in a scintillation fluorophore and counted to determine the precipitated labeled phosphate incorporated into the substrate. Percent inhibition was calculated relative to uninhibited controls.

Example 488 Cell-Based 96-well Cdc2 Histone H1 Kinase Assay for G2 Checkpoint Inhibition This cellular assay measures the effect of a test compound on Cdc2 / cyclin B complex activity against histone H1, one of its physiological substrates. To do.

20,000 HT-29 cells / well (NUNCLON ™ catalog number 163320 96-well plate) were added to medium [Dulbecco's modified Eagle medium 4500 mg / L glucose (DME high glucose), 1% penicillin and streptomycin, 2% L- Glutamate, 10% FBS] 171 μl. Plates were incubated for 24 hours at 37 ° C. 9 μl of 5 μM adriamycin solution was added to each well (final concentration 250 nM) and incubated for an additional 16 hours at 37 ° C. Next, 20 μl of 500 ng / mL nocodazole was added per well and immediately 5 μl of the test compound was added. The plate was incubated at 37 ° C. for 4 hours. The plate was removed from the incubator and rotated in a Beckman GS-6R centrifuge at 4 ° C. for 10 minutes at 800 rpm. The medium was removed and the plate surface was wiped dry. 100 μL of PBS was added to each well. The plate was rotated as described above. PBS was removed from the plate and the plate surface was allowed to dry. Next, 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 pephablock, 1 mM DTT, 0.1 mM sodium orthovanadate, 20 μl of 10 μg / ml aprotinin, 20 μM leupeptin) was added to each well, followed by rocking at 4 ° C. for 45 minutes at medium speed. After lysis, 30 μL of kinase assay buffer (50 mM Hepes, 22 mM MgCl ₂ , 1 mM DTT, 166.7 ng / μl histone H1, 83 μM ATP, 0.033 μCi / μl [γ- ³³ P] ATP) was added. Plates were incubated for 25 minutes on a 32 ° C plate warmer. 80 μl of 100 mM EDTA pH 7.8 was added to each well to stop the kinase reaction. The lysate was placed on a pre-moistened Wallac P-30 filter mat (Wallac 1450-523, glass fiber filter with negatively charged P30 active groups, size 90 × 120 mm) using 75 mM H ₃ PO _4. Seconds were collected followed by aspiration for 10 seconds. Place the filter mat in a 75 mM H ₃ PO ₄ bath and gently shake at room temperature for 10 minutes, then place in a folded single sheet paper towel and place in high power microwave for 2-3 minutes, or filter mat Until it is dry. The filter mat was placed in a sample bag (Wallac 1450-432), 5 ml of non-aqueous scintillation fluid was added to the sample bag, and the bag was sealed. The sample was read using a Wallac 1450 MicroBeta liquid scintillation counter. The data in Table 6 show the cellular effects of Wee1 and / or Chk1 inhibitors on the physiological substrate of cdc2 / cyclin B, the complex itself being a substrate of Wee1 kinase.

Example 489 Procedure for Clonogenic Assay in HT-29 Cells ± Adriamycin This cellular assay measures the toxicity of a test compound in the absence and presence of DNA damage induced by conventional chemotherapeutic agents. Is.

HT-29 cells were grown in Dulbecco's modified Eagle's medium containing high glucose supplemented with 1 mM sodium pyruvate, 2 mM L-glutamine, 16 mM HEPES, 8 mM MOPS and 10% fetal calf serum. Cells were incubated at 37 ° C. in a 5% CO ₂ atmosphere and 100% relative humidity.

Two or three T-75 tissue culture flasks were seeded at about 50% confluency in 30 ml medium and incubated for about 24 hours. Adriamycin (ADR) (dissolved in distilled water (dH ₂ O) at 5 mM) was added to the flask to a final concentration of 1 μM or 500 nM. One flask contained no ADR. Cells were incubated with ADR for 1 hour. All flasks were then washed twice with 20 ml of medium and incubated for an additional 16 hours in 30 ml of medium.

  Raw material agar (3.2% Seaplane GTG agarose (BioWhittaker Molecular Applications)) was suspended in distilled water and treated in an autoclave for 20 minutes. After melting the agar, it was used in a microwave oven. The agar at the bottom of the medium was a 1: 4 dilution of the raw material agar, and enough fetal bovine serum was added to make the solution 10%. One microliter was dispensed into each well of a 6-well tissue culture plate and the plate was allowed to harden. An agar medium for cloning (1: 8 dilution of stock agar medium in medium, supplemented with 10% fetal calf serum) was maintained at 40 ° C. until use.

Cells were trypsinized using trypsin-EDTA and the concentration was adjusted to 75,000 cells / μL medium. 100 μL of each cell suspension was placed in a sterile 15 ml plastic centrifuge tube. 25 μL of each test compound was added to the appropriate tube, followed by 5 ml of warmed cloning agar medium. The tubes were mixed well and 2 ml of agar / cell suspension was added to duplicate wells of a 6-well plate that had been coated with agar. The plate was rotated and placed in the refrigerator for 5 minutes. Plates were returned to room temperature and incubated for 10-14 days until colonies were visible. Colonies (dissolved at 1mg / ml in dH ₂ O, and filter sterilized) INT (p-iodonitrotetrazolium violet) were stained with. 1 ml of INT was added to each well and the plates were incubated overnight at 37 ° C., 5% CO ₂ , 100% relative humidity. Colonies were counted using a Hamamatsu video imaging system and ImageQuant software.

Example 490 Western blot measurement of phosphotyrosine 15 on Cdc-2 and mobility shift of Myt-1.
These Western blot assays measure the phosphorylation status of the physiological substrate of Wee1: tyrosine 15 on Cdc2 kinase. This is performed using a phospho-specific antibody and the signal is normalized to the total amount of Cdc2 in the sample to be detected. The shift of Myt-1 protein toward the smaller mobility on the Western blot is used as an indicator of progression to the M phase of the cell cycle.

A. Detection Procedure of Phosphotyrosine 15, Myt-1 Shift and Total Cdc-2 from Cultured HT-29 Cells in Response to Checkpoint Inhibitor Candidate ± Adriamycin and / or Nocodazole HT-29 cells were treated with 1 mM sodium pyruvate, 2 mM L Grow in high glucose Dulbecco's modified Eagle's medium supplemented with glutamine, 16 mM HEPES, 8 mM MOPS, and 10% fetal calf serum. The cells were incubated at 37 ° C., 5% CO ₂ and 100% relative humidity.

  Cells were grown and processed in 6-well tissue culture plates. Cells were seeded at a concentration of 200,000 cells / mL in 3 mL of medium. After seeding, the cells were allowed to attach for 24 hours.

  All treatments were performed in duplicate wells. Wells treated with adriamycin (ADR) were exposed to 1 μM ADR for 1 hour. ADR was dissolved in sterile distilled water. After 1 hour incubation, the cells were washed twice with 2 ml medium and then incubated for 16 hours in 3 ml medium. After 16 hours of incubation, the cells were treated with various concentrations of inhibitor ± 50 ng / ml nocodazole (NOC). Inhibitors were dissolved in dimethyl sulfoxide (DMSO) at a concentration of 10 mM and diluted with growth medium prior to addition to the cells. NOC was dissolved in DMSO at 1 mg / mL and diluted with growth medium prior to administration to cells. Cells were incubated for 6 hours with inhibitors and NOC. Duplicate wells were scraped on ice and mixed into a 15 ml centrifuge tube. Wells were rinsed with Dulbecco's phosphate buffered saline (DPBS) without calcium and magnesium. The rinse solution was mixed with the scraped cells. Cells were centrifuged at 200 xg for 5 minutes at 4 ° C. The supernatant was discarded and the pellet was resuspended in 100 μL DPBS. The cell suspension was then transferred to a 1.5 ml Eppendorf centrifuge tube and centrifuged at 4 ° C. and 4000 rpm for 4 minutes. After removing the supernatant, the pellet was frozen on dry ice and stored at -80 ° C.

  The pellet was thawed on ice and then dissolved. Dissolution buffer ELB (2.5 mM HEPES (7.5), 150 mM NaCl, 25 μM NaF and supplemented with 1 mM AEBSF, 1 mM sodium orthovanadate, and 1 mM dithiothreitol, and complete protease inhibitor cocktail tablets (Roche Biochemicals) 0.5% NP 40. Tablets were dissolved in 2 mL of distilled water and diluted 1:25 with lysis buffer, pellets were suspended in 100 μl complete lysis buffer and incubated on ice for 30 minutes. The liquid was centrifuged for 15 minutes at 14,000 rpm at 4 ° C. The supernatant liquid was collected and the protein concentration was determined using the Pierce BCA protein assay kit according to the manufacturer's instructions. adjusted to mL, then Samples were diluted 1: 1 with Invitrogen 2 × tris-glycine sample buffer supplemented with 50 μl / ml 2-mercaptoethanol, boiled for 3 minutes and stored frozen at −20 ° C.

  30 micrograms of protein per lane was transferred to pre-formed Novex 12%, 1.5 mm, 10 well, tris-glycine poly using Novex flow buffer and Invitrogen (see Blue Plus 2 molecular weight standard). It was made to flow on an acrylimide gel. The gel was allowed to flow for 30 minutes at 100 volts and then for 1.5 hours at 125 volts. The protein was transferred to a 0.45 μm pore nitrocellulose membrane using Novex transcription buffer and Novex X-Cell II blot module. The nitrocellulose membrane was 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 gel was cut with a razor blade and the top was treated with anti-Myt-1 antibody diluted 1: 5000 with blocking buffer. The lower part of the gel was treated with biotinylated antiphosphotyrosine 15, also diluted 1: 5000 with blocking buffer. The membrane was incubated for 2 hours at room temperature with constant peristalsis. The antibody solution was removed and the membrane was washed 3 times with TNT buffer for 20 minutes each. TNT buffer consisted of 50 mM Tris (8.0), 150 mM NaCl, and 0.1% Tween 20. The secondary antibody was then added to the blocking buffer. 1: 40,000 neutravidin HRP was used for biotinylated phosphotyrosine 15 blots and 1: 10,000 BioRad goat anti-rabbit was used for Myt-1 blots. The blot was left in the secondary antibody for 1 hour at room temperature and washed 20 times 3 times with TNT buffer. Protein bands were detected using Amersham Pharmacia ECL detection kit and Kodak Bio Max film according to manufacturer's instructions.

  The membrane of phosphotyrosine 15 was peeled using a Chemicon International Re-Blot kit according to the manufacturer's instructions. The blot was then washed twice with TNT buffer and once with blocking buffer for 20 minutes each. Anti-Cdc-2 (cdk1; Labvision Corporation) was diluted 150 μl per 50 ml blocking buffer and incubated with the blot for 2 hours at room temperature, followed by three 20 minute washes with TNT buffer. The secondary antibody was Bio Rad goat anti-mouse HRP, diluted 1: 10,000 with blocking buffer and incubated with the blot for 1 hour at room temperature. Washing for 20 minutes was performed 3 times before ECL detection.

B. Procedure for Detection of MPM_2 in Cultured HT-29 Cells +/- Checkpoint Inhibitor Candidates, Adriamycin and Nocodazole This assay uses polyclonal antibodies to determine the mitotic index (cell division seen in mitosis). M phase specific histological markers are quantified.

HT-29 cells were grown in high glucose Dulbecco's modified Eagle's medium supplemented with 1 mM sodium pyruvate, 2 mM L-glutamine, 16 mM HEPES, 8 mM MOPS, and 10% fetal calf serum. The cells were incubated at 37 ° C., 5% CO ₂ atmosphere, 100% relative humidity.

  Cells were seeded in 96-well tissue culture plates at 100 μl / well at a concentration of 40,000 / ml. Cells were allowed to attach and start growing for 24 hours. 100 μl of 2 μM (final 1 pM) adriamycin (ADR) was added to the test cells and the cells were incubated for 1 hour as described above. After incubation, the plate was washed twice with growth medium. The medium was replaced with 100 μl fresh medium and incubated for an additional 16 hours. Serial 2-fold dilutions of inhibitor candidates were added to the test wells. The column with nocodazole (NOC) contains 2 μl NOC at 2.5 μg / ml. The plate was then incubated for an additional 6 hours. After incubation, the plates were centrifuged at 200 g for 5 minutes at 4 ° C. Carnoy fixative 100 microliters, 3 parts methanol per part acetic acid were added directly to each well and left at room temperature for 15 minutes. The media / fix solution mixture was removed by aspiration and replaced with ice-cold 20: 1 ethanol: acetic acid. Plates were stored at 4 ° C. until stained.

  Fixed cell MPM-2 was stained using the Upstate Biotechnology MPM-2 rhodamine detection kit according to the manufacturer's instructions. Briefly, cells were washed with Dulbecco's phosphate buffered saline (DPBS) containing calcium and magnesium, followed by incubation with a blocking buffer consisting of 8% bovine serum albumin (BSA) for a minimum of 1 hour. Cells were then washed once with PBS and treated overnight at 4 ° C. with 5 μg / ml (100 μl / well) primary antibody diluted in DPBS containing 1% BSA. Cells were then washed twice with DPBS for 15 minutes each and then incubated for 1 hour with rhodamine-conjugated goat anti-mouse IgG diluted 1: 1000 in DPBS containing 1% BSA. The secondary antibody was washed away by washing with DPBS for 30 minutes three times. The cells were then counterstained using a Molecular Probes Mycoflour kit and the nuclei stained according to the kit instructions.

  Stained cells were observed with a fluorescence microscope using appropriate fluorescent filters to detect rhodamine staining and DAPI staining. Images were input using a Spot digital camera and analyzed with ImageQuant to quantify all nuclei and count MPM-2 positive cells.

Example 491 In Vivo Testing Procedure of Wee1, Wee1 / Chk1 or Chk1 Inhibitor and Adriamycin or Cisplatin In these experiments, the in vivo changes of Py15 on Cdc2 in tumors were measured and used in combination with conventional agents The therapeutic effect of a Wee1, Wee1 / Chk1 or Chk1 inhibitor was evaluated. The therapeutic effect is measured by prolonging the life of the treated animal.

In Vivo Experiments In Vivo Methods Early in vivo experiments were performed by examining changes in downstream targets (ie, phosphorylation status of Cdc2 tyrosine 15) and cell cycle effects in L1210 murine leukemia tumor cells. Shows biochemical and physiological evidence of Wee1 / Chk1 or Chk1 inhibition. L1210 was selected because it lacks p53 function, has significant G2 accumulation in response to DNA damage, is easy to grow in mice, and has a short cycle time. CD2F1 mice weighing 25-26 g were inoculated intraperitoneally (ip) with 10 ⁵ or 5 × 10 ⁵ L1210 cells and randomized into treatment groups containing 3 mice each. Four, five or six days after tumor implantation, mice were given a single dose of DNA damaging agent (cisplatin, 8 or 6 mg / kg iv), one or more injections (20 mg / kg ip) of the compound of Example 80. , Sc, or iv), or both reagents. Injection of the compound of Example 80 was started at 3-8 hour intervals, simultaneously with the DNA damaging agent, or delayed by 8 or 16 hours. Control animals were injected intravenously with 0.2 ml saline only. The DNA damaging reagent was dissolved in saline and the compound of Example 80 was converted into two vehicles: (1) 10% cremaphor, 10% ethanol and 80% H ₂ O, or (2) 5% dimethylacetamide, 25 % Propylene glycol and 70% polyvinylpyrrolidine (30% w / v H ₂ O aqueous solution). Mice were sacrificed at several time points 8-40 hours after the start of treatment and tumor cells were collected in phosphate buffered saline containing 1 mM sodium orthovanadate and 5 mM EDTA. L1210 cells were counted in a Coulter counter, aliquots of 2.5 × 10 ⁷ cells of each group were centrifuged and frozen as pellets, and 2.5 × 10 ⁶ aliquots were -80 in Vindelov's citrate buffer ¹ Freeze at 0 ° C.

A larger pellet was sonicated using a 25 mM Tris (base) pH 7.4, 350 mM sodium chloride, 1% nonidet P40, 5 mM EDTA (tetrasodium), 0.5% sodium deoxycholate, 0.1% In cold lysis buffer (RIPA) containing H ₂ O solution of sodium dodecyl sulfate, 1 mM AEBSF, 1 mM sodium fluoride, 0.5 mM sodium orthovanadate, 15 μg / ml aprotinin, 20 μM leupeptin, 10 mM β-glycerophosphate and 1 mM DTT For 30 seconds. When the lysate is diluted to 4 parts RIPA and to the working concentration, 5 parts containing 2% sodium dodecyl sulfate, 0.0025% bromophenol blue, 10% glycerin and 60 mM dithiothreitol in H ₂ O. Five parts 2 times diluted 1:10 in a mixture with Novex electrophoresis sample buffer. The sample was heated at 98 ° for 5 minutes. Duplicate Novex 4% -20% polyacrylamide Tris-Glycine 15 well 1 mm minigel was loaded at 15 μl / well and run at 200 V (constant) for 45 minutes. The protein was transferred to a nitrocellulose membrane at 25V (constant) in Novex transcription buffer for 2 hours. One of each membrane was blotted for total Cdc2 protein using 1: 200 LabVision MS-110P antibody followed by 1: 10,000 BioRad 172-1011 goat anti-mouse IgG-HRP. The other membrane was prepared using Cdc2 phosphotyrosine 15 (PTyr15) using 1: 5000 biotinylated rabbit polyclonal antibody supplied by Onyx Pharmaceutical, followed by 1: 20,000 (50 ng / ml) Pierce 31001 Neutravidin-HRP. ). These antibodies were detected using Amersham ECL reagent. Blot images were taken on Kodak BioMax MR film and projected on a Molecular Dynamics personal densitometer SI. Concentration measurements were performed using Molecular Dynamics Image QUANT software. Cdc2 Ptyr15 concentration measurements were normalized to the total Cdc2 protein (divided by the total Cdc2 value to give the phospho: total Cdc2 ratio) and divided by the ratio of the control sample (control phosphorylation value for each tumor sample ( The ratio of phosphorylation value) was determined.

  Smaller pellets were stained for DNA content by the method of Vindelov (Vindelov LL, Christensen IJ, and Nissen NI. A detergent-trypsin method for the 3rd of the preparation of the 3rd. . The propidium iodide fluorescence was analyzed using a Beckman-Coulter Elite flow cytometer. Cell cycle distribution was estimated using the Bagwell extended trapezoid model (KD Bayer, R. E. Duque, edited by T. V. Shankey, edited by T. V. Shanke, run by the Verity Software House program ModFit LT. (Clinical Flow Cytometry: Principles and Applications. Bagwell, CB Theoretical Aspects of Flow Cytometry data analysis. Walimes, 19: 93).

Subsequently, an in vivo experiment was designed to determine whether incorporating a Wee1, Wee1 / Chk1 or Chk1 inhibitor with a DNA damaging reagent into standard chemotherapy would provide a therapeutic benefit. CD2F1 mice weighing 24 to 26 g were inoculated intraperitoneally with 10 ⁴ L1210 cells and randomized into treatment groups containing 6 mice each. Three, seven and eleven days after transplantation, one of three dose levels of DNA damaging agent (cisplatin or doxorubicin) alone or in combination with two intraperitoneal injections of one of the two dose levels of the compound of Example 80 The mice were treated with a single intravenous injection. Control mice received the appropriate vehicle instead of the active reagent. Dose levels were based on average group weight. Mortality data was collected for 3 weeks and the median survival time for each group was calculated. Efficacy data (% T / C) was recorded by dividing the median life of treated animals by the median life of control animals and multiplying by 100. The maximum% T / C of the combination group was then compared with the maximum% T / C of DNA damage. As shown in Table 9, the only group that provides an indication of therapeutic benefit is associated with the addition of the Wee1, Wee1 / Chk1 or Chk1 inhibitors of the present invention.

  Cell cycle distribution of L1210 cells treated in vivo with 6 mg / kg cisplatin and 20 mg / kg of the compound of Example 80. Cells were tested 24 hours after drug and compound administration. The value is the percent of cells tested.

  All of the compositions and / or methods disclosed and claimed herein can be prepared and executed without undue experimentation with reference to the present disclosure. While the compositions and methods of the present invention have been described with reference to preferred embodiments, it will be apparent to those skilled in the art that changes can be made in the compositions and / or methods and steps or sequence of steps of preparing these compounds. It is.

FIG. 10 shows a Western blot of tumor cells treated in vivo with cisplatin and the compound of Example 80. FIG. 10 shows a Western blot of cells treated in vitro with adriamycin and the compound of Example 80. FIG. 10 shows a Western blot of tumor cells treated in vivo with cpt-11 and the compound of Example 362. 2 is a graph of survival in animals treated with the compound of Example 80.

Claims (15)

A compound of formula I.

(In the formula, each broken line may represent a bond,
R ¹ is hydrogen, halogen, alkyl, NR ⁵ R ⁶ , or halogen, alkyl, haloalkyl, hydroxyl, nitro, cyano, C (O) R ³ , OR ³ , S (O) _m R ³ , NR ³ R ⁴ , OC (O) R ³ , NR ³ (CO) OR ⁴ , CH ₂ NR ³ R ⁴ , CH ₂ OR ³ , COOR ³ , CONR ³ R ⁴ , NR ³ COR ⁴ , SO ₂ NR ³ R ⁴ , CONHSO ₂ An aryl or heteroaryl ring optionally substituted with up to 5 substituents selected from R ³ , NR ³ S (O) _m R ⁴ , NHCONR ³ R ⁴ , NR ³ CONHR ⁴ , or halogen, alkyl , haloalkyl, hydroxyl, nitro, _{^{cyano, C (O) R 3,}} OR 3, S (O) m R 3, NR 3 R 4, OC (O) R 3, NR 3 ( _{^{O) OR 4, CH 2 NR}} 3 R 4, CH 2 OR 3 COOR 3, CONR 3 R 4, NR 3 COR 4, SO 2 NR 3 R 4, CONHSO 2 R 3, NR 3 S (O) m R 4 , A cycloalkyl or cycloalkenyl ring optionally substituted with up to 5 substituents selected from NHCONR ³ R ⁴ , NR ³ CONHR ⁴ , or halogen, alkyl, haloalkyl, hydroxyl, nitro, cyano, C ( O) R ³ , OR ³ , S (O) _m R ³ , NR ³ R ⁴ , OC (O) R ³ , NR ³ (CO) OR ⁴ , CH ₂ NR ³ R ⁴ , CH ₂ OR ³ , COOR ³ , CONR ³ R ⁴ , NR ³ COR ⁴ , SO ₂ NR ³ R ⁴ , CONHSO ₂ R ³ , NR ³ S (O) _m R ⁴ , NHCONR ³ R ⁴ , N A heterocyclic ring optionally substituted with up to 5 substituents selected from R ³ CONHR ⁴ ;
m is 0-2,
X is hydrogen or halogen;
Y ¹ is O, S (O) m or NR ¹⁰ ;
R ⁹ is hydrogen, hydroxyl, halogen, NR ³ C (O) R ⁴ , NHCONR ³ R ⁴ , (C═NR ³ ) NHR 4, NH (C═NR ³ ) NHR 4, NH (C═NH) NR ³ R ⁴ , NH (C ^{= O) OR3, NR 5 R} 6, a _{^{(CR 5 R 6) r -Z}} ,
r is 0-6,
R ² , R ⁷ , R ⁸ and R ¹⁰ are in each case independently selected from ((CR ⁵ R ⁶ ) _n T) _a (CR ¹¹ R ¹² ) _b ) -Z, the sum of n, a and b Is less than 10 in each case,
T may not be present, and when present, in each case O, CONR ³ , CONHSO ₂ , S (O) _m , NR ³ , NR ³ —O, OS—S (O) _m , S (O) _m ^-O, is selected from NR 3 -S _{(O) 2} or _{S (O)} 2 -NR ³ independently,
n is independently 0 to 6 in each case;
a is independently 0 to 6 in each case;
b is independently 0 to 6 in each case;
Z is hydrogen, halogen, alkyl, haloalkyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl, heteroaryl, cyano, nitro, hydroxy, C (O) R ³ , CONHSO ₂ R ³ , OR ³ , S (O) mR ³ , OSO ₂ R ³ , NR ³ R ⁴ , CO ₂ R ³ , CONR ³ R ⁴ , NR ³ COR ⁴ , SO ₂ NR ³ R ⁴ , OPO (OR ³ ) (OR ⁴ ), CH = CR ³ R ^{4 , CCR 3, (C = NR} 3) NHR 4, NH (C = NR 3) is selected from NHR 4, NH (C = NH ) NR 3 R 4, said alkyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl or heteroaryl group, halogen, alkyl, hydroxyl, nitro, _{^{cyano, OR 3, S (O)}} m R 3, NR 3 ^{4, OC (O) R 3} , NR 3 (CO) OR 4, C (O) R 3, COOR 3, CONR 3 R 4, NR 3 COR 4, SO 2 NR 3 R 4, CONHSO 2 R 3, NR Optionally substituted with up to 4 groups independently selected from ³ S (O) _m R ⁴ , CH ₂ NR ³ R ⁴ , CH ₂ OR ³ , NHCONR ³ R ⁴ , NR ³ CONHR ⁴ ;
R ⁵ , R ⁶ , R ¹¹ and R ¹² are in each case hydrogen, hydroxyl, alkyl, haloalkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, halogen, cyano, nitro, CH ₂ NR ³ R ⁴ , CH ₂ OR ³ , C (O) R ³ , OR ³ , S (O) _m R ³ , NR ³ R ⁴ , COOR ³ , CONR ³ R ⁴ , SO ₂ NR ³ R ⁴ , NHCONR ³ R ⁴ , NR ³ independently selected from ⁴ CONHR ⁴ ;
The alkyl, haloalkyl, cycloalkyl, cycloalkenyl, heterocyclyl, aryl or heteroaryl group is halogen, alkyl, hydroxyl, nitro, cyano, OR ³ , S (O) _m R ³ , NR ³ R ⁴ , OC (O) R ³ , NR ³ (CO) OR ⁴ , C (O) R ³ , COOR ³ , CONR ³ R ⁴ , NR ³ COR ⁴ , SO ₂ NR ³ R ⁴ , CONHSO ₂ R ³ , NR ³ S (O) _m Optionally substituted with up to 4 groups independently selected from R ⁴ , NHCONR ³ R ⁴ , NR ³ CONHR ⁴ ;
R ⁵ and R ⁶ or R ¹¹ and R ¹² can form a carbonyl group with the carbon atom to which they are bonded, or can form a cycloalkyl group or a heterocyclyl group with the carbon or heteratom to which they are bonded. The carbonyl group, cycloalkyl group or heterocyclyl group can be halogen, hydroxyl, nitro, cyano, alkyl, haloalkyl, alkyl, nitro, cyano, OR ³ , S (O) _m R ³ , NR ³ R ⁴ , OC (O) R ³ , NR ³ (CO) OR ⁴ , C (O) R ³ , COOR ³ , CONR ³ R ⁴ , NR ³ COR ⁴ , SO ₂ NR ³ R ⁴ , CONHSO ₂ R ³ , NR ³ Up to ^four independently selected from S (O) _m R ⁴ , NHCONR ³ R ⁴ , NR ³ CONHR ⁴ Optionally substituted with a group
R ³ , R ⁴ are independently selected from hydrogen, alkyl, haloalkyl, or a substituted or unsubstituted carbocyclic group selected from cycloalkyl, cycloalkenyl, heterocyclyl, aryl and heteroaryl, wherein the alkyl or substituent is is selected from halogen, hydroxyl, nitro, cyano, alkyl, haloalkyl, alkyloxy, _{carboxy, COOH, CONH 2, NHCOCH 3} , N (CH 3) 2, NHCH 3, thiomethyl, _thioethyl, from SOCH _{3, SO} 2 CH 3 May be substituted with up to 4 groups,
R ³ and R ⁴ together with the carbon atom or hetero atom to which they are attached, halogen, hydroxyl, nitro, cyano, alkyl, haloalkyl, alkyloxy, formyl, carboxy, acetyl, CH ₂ NH ₂ , CH ₂ OH, _{COOH, CONH 2, NHCOCH 3,} N (CH 3) 2, thiomethyl, _{thioethyl, SOCH 3, SO 2 CH 3} , alkoxycarbonyl, alkylcarbonyl, alkynyl, aminoalkyl, aminoalkylcarbonyl, amino, mono or dialkylamino Can form a cycloalkyl or heterocyclyl group substituted with up to four independently selected groups, or R ³ and R ⁴ together with the nitrogen to which they are attached, 3-8 members To form a heterocycle containing children And up to four of the members may be a carbonyl group or a heteroatom independently selected from oxygen, sulfur, S (O), S (O) ₂ and nitrogen, and the carbocyclic The group is unsubstituted or independently selected from halogen, hydroxy, hydroxyalkyl, alkyl, haloalkyl, alkoxy, alkoxycarbonyl, alkylcarbonyl, alkynylamino, aminoalkyl, aminoalkylcarbonyl, amino, mono or dialkylamino Substituted with up to 4 groups) The R ¹ 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 NR ³ R ^4. 1. The compound according to 1. R ⁹ is hydrogen, hydroxyl, is selected from halogen or NHCHO group A compound according to claim 1. The compound of claim 1, wherein Y ¹ is oxygen. The compound of claim 1, wherein Y ¹ is sulfur. The compound of claim 1, wherein Y ¹ is NR ¹⁰ . The compound of claim 1, wherein R ⁹ is NR ⁵ R ⁶ or OH, R ¹ is aryl, and Y ¹ is NR ¹⁰ . The compound according to claim 1, wherein R ⁹ is hydroxyl, Y ¹ is NR ¹⁰ and the bond (C—O) indicated by the dashed line is absent. R ⁹ is hydroxyl, R ⁸ is not hydrogen A compound according to claim 3. The compound of claim 1, wherein R ⁸ is not hydrogen and R ⁹ is hydrogen. R ⁹ is hydrogen, R ⁸ is ((CR ⁵ R ⁶ ) _n T) _a (CR ¹¹ R ¹² ) _b ) -Z, T may be absent or O, and Z is NR ³ The compound of claim 1, which is R ⁴ . 2. The method of claim 1, wherein R ⁹ is selected from halogen or hydroxyl, and R ⁸ is ((CR ⁵ R ⁶ ) _n T) _a (CR ¹¹ R ¹² ) _b ) Z, wherein T and Z are absent. Compound. R ⁹ is selected from NR ⁵ R ⁶ and OH, R ⁷ is ((CR ⁵ R ⁶ ) _n T) _a (CR ¹¹ R ¹² ) _b ) Z, and Y is selected from O and NR ¹⁰ The compound of claim 1. Compound:
2- (4- (2,6-dichlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) ethyl methanesulfonate;
2- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) ethyl methanesulfonate;
3- (4- (2,6-dichlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) -N- [2 -(Dimethylamino) ethyl] propanamide;
3- (4- (2-Chloro-6-methoxyphenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) -N -[2- (dimethylamino) ethyl] propanamide;
3- (4- (2-Chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) -N- (1H-tetrazole -5-yl) propanamide;
3- (4- (2-Chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) -N- [2- ( 1H-imidazol-5-yl) ethyl] propanamide (129);
3- (4- (2-Chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) -N- [2- ( 4-morpholinyl) ethyl] propanamide (121);
3- (4- (2-Chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) -N- [2- ( Dimethylamino) ethyl] propanamide;
3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) propanenitrile;
3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) propanoic acid;
3- (9-hydroxy-1,3-dioxo-4-phenyl-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) propanamide;
3- (9-hydroxy-1,3-dioxo-4-phenyl-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -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-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2,6-dibromophenyl) -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- (2,6-dichloro-4-hydroxyphenyl) -9-hydroxypyrrolo [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) -dione;
4- (2,6-dichlorophenyl) -9-hydroxy-6- [3- (1H-imidazol-1-yl) propyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione ;
4- (2,6-dichlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2,6-dimethoxyphenyl) -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-6-hydroxyphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2-chloro-6-methoxyphenyl) -9-hydroxy-6- (2-hydroxyethyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (112);
4- (2-chloro-6-methoxyphenyl) -9-hydroxy-6- (3-hydroxypropyl) pyrrolo [3,4-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) -dione;
4- (2-chloro-6-methoxyphenyl) -9-hydroxypyrrolo [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-chlorophenyl) -6- (3,4-dihydroxybutyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2-chlorophenyl) -6-ethyl-9-hydroxypyrrolo [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 (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-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 (314 )
4- (2-Chlorophenyl) -9-hydroxy-6- [2- (1H-1,2,4-triazol-5-ylsulfinyl) ethyl] pyrrolo [3,4-c] carbazole-1,3 (2H , 6H) -dione;
4- (2-Chlorophenyl) -9-hydroxy-6- [2- (1H-1,2,4-triazol-5-ylsulfonyl) ethyl] pyrrolo [3,4-c] carbazole-1,3 (2H , 6H) -dione;
4- (2-chlorophenyl) -9-hydroxy-6- [2- (1H-imidazol-2-ylsulfanyl) ethyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2-chlorophenyl) -9-hydroxy-6- [2- (1H-imidazol-2-ylsulfinyl) ethyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2-chlorophenyl) -9-hydroxy-6- [2- (1H-imidazol-2-ylsulfonyl) ethyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2-chlorophenyl) -9-hydroxy-6- [2- (1H-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-morpholinyl) propyl] pyrrolo [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-1,3 (2H, 6H) -dione (284);
4- (2-chlorophenyl) -9-hydroxy-6- [3- (1H-imidazol-1-yl) propyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2-chlorophenyl) -9-hydroxy-6- [3- (1H-tetrazol-5-yl) propyl] pyrrolo [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) -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-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- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) butanenitrile (241);
4- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -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-chlorophenyl) -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-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-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, 3H) -dione;
Methyl 3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) propanoate (264);
N- [3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) propanoyl] -2 -(Dimethylamino) ethanesulfonamide;
N- [3- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) propanoyl] benzenesulfone An amide;
N- [3- (4- (2-Chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) propanoyl] methanesulfone An amide;
N- [4- (4- (2-Chlorophenyl-9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) butanoyl) benzenesulfonamide ;
N- [4- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) butanoyl] methanesulfone An amide;
2- (9-hydroxy-1,3-dioxo-1,2,3,6-tetrahydropyrrolo [3,4-c] carbazol-4-yl) benzonitrile;
3- (9-hydroxy-1,3-dioxo-1,2,3,6-tetrahydro-pyrrolo [3,4-c] carbazol-4-yl) benzonitrile;
4- (2,3-dichlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione (18);
4- (2-chloro-5-hydroxyphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2,6-dibromophenyl) -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- (2,6-dichloro-4-hydroxyphenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2,6-dichlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2,6-dimethoxyphenyl) -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;
4- (2-acetyl-phenyl) -9-hydroxy-6H-pyrrolo [3,4-c] carbazole-1,3-dione;
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;
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-ethoxyphenyl) -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- (4-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-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- [1,1c-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-phenyl) -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-trifluoromethylphenyl) 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;
And 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-hydroxymethylphenyl) 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- (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- (methylsulfinyl) 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-dihydroxyethyl) -9-hydroxy-1H- [1] benzofuro [3,2e] isoindole-1,3 (2H) -dione;
4- (2-chlorophenyl) -7-ethyl-9-hydroxy-1H- [1] benzofuro [3,2-e] isoindole-1,3 (2H) -dione;
4- (2-chlorophenyl) -8- [3- (dimethylamino) propoxy] -9-hydroxy-1H [1] benzofuro [3,2-e] isoindole-1,3 (2H) -dione;
And 4- (2-chlorophenyl) -8-ethyl-9-hydroxy-1H- [1] benzofuro [3,2-e] isoindole-1,3 (2H) -dione;
4- (2-chlorophenyl) -9-hydroxy-1H- [1] benzofuro [3,2-e] isoindole-1,3 (2H) -dione;
4- (2-chlorophenyl) -9-hydroxy-8- (4-hydroxybutyl) -1H- [1] benzofuro [3,2e] isoindole-1,3 (2H) -dione;
9-hydroxy-4-phenyl-1H- [1] benzofuro [3,2-e] isoindole-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] carbazol-9-yldihydrogen phosphate;
2- (4- (2-chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) acetamide;
2-{[3- (4- (2-Chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) propyl] amino ]benzoic acid;
3- (4- (2,6-dichlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) propanoic acid;
3- (4- (2-Chlorophenyl) -9- (formylamino) -1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) -N- [ 2- (dimethylamino) ethyl] propanamide;
3- (4- (2-Chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) -N- (2,2 , 6,6-tetramethyl-4-piperidinyl);
3- (4- (2-Chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) -N- [2- ( 1H-imidazol-5-yl) ethyl] propanamide;
3- (4- (2-Chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) -N- [2- ( Dimethylamino) ethyl] -N-methylpropanamide;
3- (9-Amino-4- (2-chlorophenyl) -1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) -N- [2- ( Dimethylamino) ethyl] propanamide;
3,9-dihydroxy-4-phenyl-3,6-dihydropyrrolo [3,4-c] carbazol-1 (2H) -one;
3- [4- (2-chloro-phenyl) -9-nitro-1,3-dioxo-2,3-dihydro-1H-pyrrolo [3,4-c] carbazol-6-yl] -propionic acid;
3-{[3- (4- (2-Chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) propyl) amino )benzoic acid;
4- (2,6-dichlorophenyl) -6- [3- (dimethylamino) 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;
4- (2,6-dichlorophenyl) -8- [3- (dimethylamino) propoxy] -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2,6-dichlorophenyl) -8- [4- (dimethylamino) butyl] -9-hydroxy-6-methylpyrrolo [3,4-c] carbazole-1,3 (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) -dione ;
4- (2,6-dichlorophenyl) -9-hydroxy-6- [2- (4-morpholinyl) ethyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2,6-dichlorophenyl) -9-hydroxy-6- [3- (1H-imidazol-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) -dione;
4- (2,6-dichlorophenyl) -9-hydroxy-6- [3- (4-morpholinyl) propyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2,6-dichlorophenyl) -9-hydroxy-6- [3- (dimethylamino) 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-dichlorophenyl) -9-hydroxy-6-methyl-8- [3 (methylamino) 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-methylpyrrolo [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- (dimethylamino) butyl] -9-hydroxypyrrolo [3,4-c] 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) -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-hydroxyphenyl) -8- [4- (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) -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) butyl] -9-hydroxy-6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H)- 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- (4morpholinyl) 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] carbazole-1,3 (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] carbazol-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- Dione;
4- (2-chlorophenyl) -6- (3-hydroxypropyl) -8- [3 (methylamino) propoxy] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2-chloro-phenyl) -6- (3-hydroxy-propyl) -8-methoxy-6H-pyrrolo [3,4-c] carbazole-1,3-dione;
4- (2-chloro-phenyl) -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-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) -6- [3- (dimethylamino) propyl] -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2-Chlorophenyl) -6- (3-[(cis) -3,5-dimethylpiperazinyl] propyl} -9-hydroxypyrrolo [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-[(1E) -4- (methylamino) -1-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-c] carbazole-9- Ilformamide;
4- (2-chlorophenyl) -6-methyl-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-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-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) -dione;
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] carbazole-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-hydroxypropoxy) -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-[(1E) -4- (dimethylamino) -1-butenyl] -6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2-chlorophenyl) -8-[(1E) -4- (methylamino) -1-butenyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2-chlorophenyl) -8-[(1E) -4-hydroxy-1-butenyl] -6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2-chlorophenyl) -8-[(1E) -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)- Dione;
4- (2-Chlorophenyl) -8- [3- (dimethylamino) propoxy] -6-methyl-1,3-dioxo-1,2,3,6-tetrahydropyrrolo [3,4-c] carbazole-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- (2hydroxyethyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H)- Dione;
4- (2-Chlorophenyl) -8- [3- (dimethylamino) propoxy] -9-hydroxy-6- (3hydroxypropyl) 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;
4- (2-chlorophenyl) -8- [3- (dimethylamino) propoxy] -9-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- (dimethylamino) butanoyl] -9-hydroxy-6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2-chlorophenyl) -8- [4- (dimethylamino) butyl] -6-methylpyrrolo [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) butyl] 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-phenyl) -8-hydroxy-6- (3-hydroxy-propyl) -6H-pyrrolo [3,4-c] carbazole-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-chlorophenyl) -9-{[4- (dimethylamino) butyl] amino} -6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2-Chlorophenyl) -9-fluoro-6- (3-hydroxypropyl) -8- [4 (methylamino) butyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H)- Dione;
4- (2-chlorophenyl) -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-yl-propoxy) -6H-pyrrolo [3,4-c] carbazole-1,3-dione;
4- (2-chlorophenyl) -9-fluoro-6-methyl-8- [3- (methylamino) propoxy] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2-chlorophenyl) -9-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) propoxy] -6- [3 (methylamino) propyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
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-trifluoroethyl) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2-Chloro-phenyl) -9-hydroxy-6- (2-hydroxy-ethyl) -8- [3- (4-methylpiperazin-1-yl) -propoxy] -6H-pyrrolo [3,4 -C] carbazole-1,3-dione;
4- (2-Chlorophenyl) -9-hydroxy-6- (2-hydroxyethyl) -8- [3- (4morpholinyl) propoxy] 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)- Dione;
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) -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, 3H) -dione;
4- (2-Chloro-phenyl) -9-hydroxy-6- (3-hydroxy-propyl) -8- (3-pyrrolidin-1-ylpropoxy) -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-methylpiperazin-1-yl) -propoxy] -6H-pyrrolo [3,4 -C] carbazole-1,3-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-phenyl) -9-hydroxy-6- (3-hydroxy-propyl) -8-piperidin-4-yl-6H-pyrrolo [3,4-c] carbazol-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-chlorophenyl) -9-hydroxy-6- (4-pentenyl) pyrrolo [3,4-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- (1H-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-hydroxy-6- [3- (4-methyl-1-piperazinyl) propyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2-chlorophenyl) -9-hydroxy-6- [3- (4-morpholinyl) propyl] pyrrolo [3,4-c] carbazole-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-chlorophenyl) -9-hydroxy-6- [3- (methylamino) propyl] pyrrolo [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-chlorophenyl) -9-hydroxy-6-isopentylpyrrolo [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-1,3 (2H, 6H) -dione;
4- (2-chlorophenyl) -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-chlorophenyl) -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) butyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2-Chlorophenyl) -9-hydroxy-6-methyl-8-{[3- (methylamino) propyl] sulfonyl} pyrrolo [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;
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- (l-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) -ethyl] -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- (methylamino) propoxy] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2-chlorophenyl) -9-hydroxy-8- [4- (1-pyrrolidinyl) butyl] -1H [1] benzofuro [3,2-e] isoindole-1,3 (2H) -dione;
4- (2-chlorophenyl) -9-hydroxy-8- [4- (1-pyrrolidinyl) butyl] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2-chlorophenyl-)-9-hydroxy-8- [4- (methylamino) butyl] -6-propylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (2-chlorophenyl) -9-hydroxy-8- [4- (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] carbazol-9-ylformamide;
4- (2-methoxyphenyl) -6-methyl-9- (methylamino) pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
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-amino-2-chlorophenyl) -9-fluoro-8- [3 (methylamino) propoxy] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
4- (3-amino-2-chlorophenyl) -9-fluoro-8- [4- (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-{[3- (4- (2-Chlorophenyl) -9-hydroxy-1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl) propyl] amino }benzoic acid;
6- (2-aminoethyl) -4- (2-chlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
6- (2-anilinoethyl))-4- (2,6-dichlorophenyl) -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -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-phenylpyrrolo [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 -Dione;
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) propoxy] -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
6-butyl-4- (2,6-dichlorophenyl) -8- [4- (dimethylamino) butyl] -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
6-butyl-4- (2,6-dichlorophenyl) -9-hydroxy-8- [3 (methylamino) propoxy] pyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
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-6methoxyphenyl-)-8- [3- (dimethylamino) propoxy] -9-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- (dimethylamino) propoxy] -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
6-butyl-4- (2-chlorophenyl) -8- [4- (dimethylamino) butyl] -9-hydroxypyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
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-1,3 (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- [c] fluorene-1,3-dione;
8- (1-aminomethyl-2-hydroxy-ethyl) -4- (2-chlorophenyl) -6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione;
8- (2,3-dihydroxypropyl) -9-hydroxy-6-methyl-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
8- (4-aminobutyl) -4- (2-chlorophenyl) -9-hydroxy-1H- [1] benzofuro [3,2e] isoindole-1,3 (2H) -dione;
8- (4-aminobutyl) -4- (2-chlorophenyl) -9-hydroxy-6-methylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
8- (4-aminobutyl) -4- (2-chlorophenyl) -9-hydroxypyrrolo [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;
8- [3- (dimethylamino) propoxy] -9-hydroxy-6-methyl-4-phenylpyrrolo [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- {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-hydroxyphenyl) -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) -dione;
9-hydroxy-4,5-diphenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
9-hydroxy-4-phenyl-6- [3- (1-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) -dione;
9-hydroxy-5-methyl-4-phenylpyrrolo [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-hydroxyhexyl) -4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
9-hydroxy-6- [2- (1H-imidazol-1-yl) ethyl] -4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
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- (1H-imidazol-1-yl) propyl] -4-phenylpyrrolo [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;
9-hydroxy-6- [3- (4-morpholinyl) 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-6- [6- (4-methyl-1-piperazinyl) hexyl] -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;
9-hydroxy-8- (2-hydroxyethyl) -6-methyl-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) -dione;
9-hydroxy-8- (3-hydroxypropyl) -6-methyl-4-phenylpyrrolo [3,4-c] carbazole 1,3 (2H, 6H) -dione;
N- [2- (dimethylamino) ethyl] -3- (9-hydroxy-1,3-dioxo-4-phenyl-2,3-dihydropyrrolo [3,4-c] carbazol-6 (1H) -yl ) Propanamide;
N- [2- (dimethylamino) ethyl] -3- (9-hydroxy-4- (2-methoxyphenyl) -1,3-dioxo-2,3-dihydropyrrolo [3,4-c] carbazole-6 (1H) -yl) propanamide;
N- [4- (2-chlorophenyl) -6- (3-hydroxy-propyl) -1,3-dioxo-1,2,3,6-tetrahydropyrrolo [3,4-c] carbazol-9-yl] -Formamide; and 6- (2-aminoethyl) -9-hydroxy-4-phenylpyrrolo [3,4-c] carbazole-1,3 (2H, 6H) dione. Compound:
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-1,3-dioxo-1,2,3,6-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;
4- (2-Chloro-phenyl) -8- [3- (3,5-dimethyl-piperazin-1-yl) -propoxy] -9-hydroxy-6-methyl-6H-pyrrolo [3,4-c] Carbazole-1,3-dione;
4- (2-chloro-phenyl) -9-hydroxy-8- (3-hydroxy-propoxy) -6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione;
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-c] carbazole-1,3-dione;
Acetic acid 4- (2-chloro-phenyl) -1,3-dioxo-1,2,3,6-tetrahydro-pyrrolo [3,4-c] carbazol-9-yl ester;
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-piperidin-3-yl-6H-pyrrolo [3,4-c] carbazole-1,3-dione;
8- (3-amino-pyrrolidine-1-carbonyl) -4- (2-chloro-phenyl) -6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; hydrochloride;
4- (2-chloro-phenyl) -9-pyridin-2-yl-6H-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 [3,4-c] carbazole-1,3- Dione;
4- (2-chloro-phenyl) -6-methyl-9-pyridin-2-yl-6H-pyrrolo [3,4-c] carbazol-1,3-dione;
4- (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] carbazol-9-yl] -3piperidin-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-butyl-1-enyl) -6-methyl-6H-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- Dione;
6- (3-Bromo-propyl) -4- (2-chloro-phenyl) -8- (3-dimethylamino-propoxy) -9-hydroxy-6H-pyrrolo [3,4-c] carbazole-1,3- Dione;
4- (2-chloro-phenyl) -8- (4-dimethylamino-3-hydroxy-butoxy) -6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; hydrochloride;
4- (2-chloro-phenyl) -8-hydroxy-6- (3-hydroxy-propyl) -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-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- (3hydroxy-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-dioxo-2,3-dihydro-1H-pyrrolo [3,4-c] carbazol-6-yl] -propionic acid;
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-propoxy) -6H-pyrrolo [3,4-c] carbazole-1,3- 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-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;
4- (2-chloro-phenyl) -9-fluoro-6-methyl-8- (3-pyrrolidin-1-yl-propoxy) -6H-pyrrolo [3,4-c] carbazole-1,3-dione;
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-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] carbazole- 9-yl] -formamide;
4- (2-chloro-phenyl) -6-methyl-8-pyridin-4-yl-6H-pyrrolo [3,4-c] carbazol-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-dione; Hydrochloride salt;
8- (3- (S) amino-pyrrolidine-1-carbonyl) -4- (2-chloro-phenyl) -6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; hydrochloric acid 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;
4- (2-chloro-phenyl) -8- (4-dimethylamino-butyl) -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-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-1,3-dione;
4- (2-chloro-phenyl) -6- (3-methoxy-propyl) -8-piperidin-3-yl-6H-pyrrolo [3,4-c] carbazol-1,3-dione; hydrochloride;
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 -Dione;
4- [4- (2-Chloro-phenyl) -6-methyl-1,3-dioxo-1,2,3,6-tetrahydro-pyrrolo [3,4-c] carbazol-8-ylmethyl] -piperidine- 1-carboxylic acid tert-butyl ester;
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;
4- (2-chloro-phenyl) -6- (3-hydroxy-propyl) -8-piperidin-3-yl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; hydrochloride;
4- (2-chloro-phenyl) -6- (3-hydroxy-propyl) -8-piperidin-4-yl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; hydrochloride;
4- (2-Chloro-phenyl) -6-methyl-8- (perhydro-1,4-diazepine-1-carbonyl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione; hydrochloride ;
4- (2-Chloro-phenyl) -9-hydroxy-6-methyl-8- [4- (4-methyl-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-dione;
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 [3,4-c] carbazole-8-carboxylic acid (2-dimethylamino- Ethyl) -methyl-amide; compound with trifluoroacetic acid;
8-((S) -3-Amino-pyrrolidine-1-carbonyl) -4- (2-chloro-phenyl) -6- (2-hydroxy-ethyl) 6H-pyrrolo [3,4-c] carbazole-1 , 3-dione; hydrobromide;
4- (2-Chloro-phenyl) -6- (2-hydroxy-ethyl) -8-piperidin-4-yl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; hydrobromic acid 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-dioxo-2,3-dihydro-1H-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-1H-pyrrolo [3,4-c] carbazol-6-yl] -N- ( 2-dimethylamino-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-1H-pyrrolo [3,4 -C] carbazol-6-yl] -propionamide;
4- (2-chloro-phenyl) -6-methyl-8-pyrrolidin-3-yl-6H-pyrrolo [3,4-c] carbazole-1,3-dione; trifluoroacetate 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-tetrahydropyrrolo [3,4-c] carbazol-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-tetrahydropyrrolo [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-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-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-yl-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] carbazol-1,3-dione;
8- (4-amino-butyl) -4- (2-chloro-phenyl) -6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3dione;
2-Dimethylamino-ethanesulfonic acid {3- [9-amino-4- (2-chloro-phenyl) -1,3-dioxo-2,3-dihydro-1H-pyrrolo [3,4-c] carbazole- 6-yl] -propionyl} -amide;
2-Dimethylamino-ethanesulfonic acid {3- [4- (2-chloro-phenyl) -9-formylamino-1,3-dioxo-2,3-dihydro-1H-pyrrolo [3,4-c] carbazole -6-yl] -propionyl) -amide;
4- (2-Chloro-phenyl) -9-hydroxy-6-methyl-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-hydroxy-2,2-dimethyl-propoxy) -6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3- Dione;
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-pyrrolo [3,4-c] carbazole-8-carboxylic acid (2 -Pyrrolidin-1-yl-ethyl) -amide;
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-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-tetrahydro-pyrrolo [3,4-c] carbazole-8-carboxylic acid (2 -Pyrrolidin-1-yl-ethyl) -amide;
N- [4- (2-Chloro-phenyl) -7-hydroxy-6-methyl-1,3-dioxo-1,2,3,6-tetrahydropyrrolo [3,4-c] carbazol-9-yl] -Formamide;
4- (2-Chloro-phenyl) -6- (2-hydroxy-ethyl) -1,3-dioxo-1,2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole-8-carboxylic acid Methyl ester;
4- (2-Chloro-phenyl) -6-methyl-1,3-dioxo-1,2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole 8-carboxylic acid (2-pyrrolidine-1- Yl-ethyl) -amide;
3- [4- (2-Chloro-phenyl) -8- (3-dimethylamino-propoxy) -9-hydroxy-1,3-dioxo-2,3-dihydro-1H-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- Dione;
9-hydroxy-6-methyl-4-phenyl-8- (3-pyrrolidin-1-yl-propoxy) -6H-pyrrolo [3,4-c] carbazole-1,3-dione;
9-amino-4- (2-chloro-phenyl) -6-methyl-7-vinyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione;
4- (2-Chloro-phenyl) -8- (3- (R) dimethylamino-pyrrolidine-1-carbonyl) -6- (2-hydroxyethyl) -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] carbazol-9-yl ] -Formamide;
N- [4- (2-Chloro-phenyl) -7- (1,2-dihydroxy-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-tetrahydropyrrolo [3,4-c] carbazole-8-carbonyl] -Methanesulfonamide;
2-Dimethylamino-ethanesulfonic acid [4- (2-chloro-phenyl) -9-hydroxy-6-methyl-1,3-dioxo-1,2,3,6-tetrahydro-pyrrolo [3,4-c Carbazole-8-carbonyl] -amide;
4- (2-Chloro-phenyl) -9-hydroxy-6-methyl-1,3-dioxo-1,2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole-8-carboxylic acid dimethylamide ;
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-dione;
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-1,3 -Dione;
4- (2-Chloro-phenyl) -6-methyl-1,3-dioxo-1,2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole 8-carboxylic acid (2-diethylamino-ethyl) An amide;
4- (2-Chloro-phenyl) -6-methyl-1,3-dioxo-1,2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole 8-carboxylic acid [3- (4-methyl -Piperazin-1-yl) -propyl] -amide;
4- (2-Chloro-phenyl) -6-methyl-1,3-dioxo-1,2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole 8-carboxylic acid (3-diethylamino-2- Hydroxy-propyl) -amide;
4- (2-Chloro-phenyl) -6-methyl-1,3-dioxo-1,2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole 8-carboxylic acid (3-pyrrolidine-1- Yl-propyl) -amide;
4- (2-Chloro-phenyl) -8- (3- (S) -dimethylamino-pyrrolidine-1-carbonyl) -6- (2-hydroxyethyl) -6H-pyrrolo [3,4-c] carbazole- 1,3-dione; trifluoroacetate;
4- (2-Chloro-phenyl) -6- (2-hydroxy-ethyl) -1,3-dioxo-1,2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole-8-carboxylic acid (2-pyrrolidin-1-yl-ethyl) -amide;
4- (2-Chloro-phenyl) -6- (2-hydroxy-ethyl) -1,3-dioxo-1,2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole-8-carboxylic acid An amide;
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-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-tetrahydropyrrolo [3,4-c] carbazol-9-yl] -Formamide;
4- (2-chloro-phenyl) -9-hydroxy-8- (3-hydroxy-propoxy) -6H-pyrrolo [3,4-c] carbazole-1,3-dione;
4- (2-Chloro-phenyl) -9-hydroxy-6-methyl-1,3-dioxo-1,2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole-8-carboxylic acid (2 -Dimethylamino-ethyl) -methyl-amide;
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;
4- (2-Chloro-phenyl) -9-hydroxy-6-methyl-1,3-dioxo-1,2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole-8-carboxylic acid (3 -Diethylamino-propyl) -amide;
4- (2-chloro-phenyl) -9-hydroxy-6-methyl-8- (1H-tetrazol-5-yl) -6H-pyrrolo [3,4-c] carbazole-1,3-dione;
4- (2-Chloro-phenyl) -9-hydroxy-6-methyl-1,3-dioxo-1,2,3,6-tetrahydro-pyrrolo [3,4-c] carbazole-8-carboxylic acid (2 -(1-methyl-pyrrolidin-2-yl) -ethyl) -amide;
4- (2-Chloro-phenyl) -9-hydroxy-6- (2-hydroxy-ethyl) -8- {3-[(2-hydroxy-ethyl) -methylamino] -propoxy} -6H-pyrrolo [3 , 4-c] carbazole-1,3-dione;
4- (2-Chloro-phenyl) -9-hydroxy-8- {3-[(2-hydroxy-ethyl) -methyl-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-piperidin-1-yl-propoxy) 6H-pyrrolo [3,4-c] carbazole-1 , 3-dione;
4- (2-Chloro-phenyl) -9-hydroxy-6-methyl-8- (3-piperidin-1.-yl-propoxy) -6H-pyrrolo [3,4-c] carbazole-1,3-dione ;
8- [3- (Benzyl-methyl-amino) -propoxy] -4- (2-chloro-phenyl) -9-hydroxy-6- (2-hydroxyethyl) -6H-pyrrolo [3,4-c] carbazole -1,3-dione;
8- [3- (Benzyl-methyl-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- (2-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-8- [3- (4-pyridin-2-yl-piperazin-1-yl) propoxy] -6H-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) -8- (3-dipentylamino-propoxy) -9-hydroxy-6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione;
4- (2-Chloro-phenyl) -8- {3-[(2-dimethylamino-ethyl) -methyl-amino] -propoxy) -9hydroxy-6- (2-hydroxy-ethyl) -6H-pyrrolo [ 3,4-c] carbazole-1,3-dione;
4- (2-Chloro-phenyl) -8- {3-[(2-dimethylamino-ethyl) -methyl-amino] -propoxy} -9hydroxy-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- (2hydroxy-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- Dione
4- (2-Chloro-phenyl) -9-hydroxy-6- (2-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-8- [3- (2-methyl-piperidin-1-yl) -propoxy] 6H-pyrrolo [3,4-c] carbazole-1 , 3-dione;
4- (2-Chloro-phenyl) -9-hydroxy-6- (2-hydroxy-ethyl) -8- [3- (2-hydroxymethylpiperidin-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- (methyl-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-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-hydroxymethylpyrrolidin-1-yl) -propoxy] -6H-pyrrolo [3 4-c] carbazole-1,3-dione;
4- (2-Chloro-phenyl) -9-hydroxy-8- [3- (2-hydroxymethyl-pyrrolidin-1-yl) -propoxymethyl-6H-pyrrolo [3,4-c] carbazole-1,3 -Dione;
4- (2-Chloro-phenyl) -8- [3- (ethyl-methyl-amino) -propoxy] -9-hydroxy-6- (2-hydroxyethyl) -6H-pyrrolo [3,4-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-1,3- Dione;
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-dipropylamino-propoxy) -9-hydroxy-6-methyl-6H-pyrrolo [3,4-c] carbazole_1,3-dione;
4- (2-chloro-phenyl) -8- (3-diethylamino-propoxy) -9-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-dione;
4- (2-Chloro-phenyl) -8- [3- (2,6-dimethyl-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-piperidin-1-yl) -propoxy] -9-hydroxy-6-methyl-6H-pyrrolo [3,4-c] Carbazole-1,3-dione;
9-hydroxy-6- (2-hydroxy-ethyl) -4-phenyl-8- (3-pyrrolidin-1-yl-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 -Diones; trifluoro-acetates;
4- (2-Chloro-phenyl) -8- (3-diisopropylamino-propoxy) -9-hydroxy-6- (2-hydroxyethyl) -6H-pyrrolo [3,4-c] carbazole-1,3- Dione; trifluoro-acetate 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-phenyl) -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-pyrrolo [3,4-c] carbazole-8-sulfonic acid (2 -Pyrrolidin-1-yl-ethyl) -amide;
4- (2-chloro-phenyl) -8- (3-cyclohexylamino-propoxy) -9-hydroxy-6-methyl-6H-pyrrolo [3,4-c] carbazole-1,3-dione;
4- (2-Chloro-phenyl) -9-hydroxy-6-methyl-8- (3-pyrrolidin-1-yl-propane-1-sulfinyl) 6H-pyrrolo [3,4-c] carbazole-1,3 -Dione
4- (2-Chloro-phenyl) -9-hydroxy-6-methyl-8- (3-pyrrolidin-1-yl-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) -6H-pyrrolo [3,4-c] carbazole- 1,3-dione;
4- (2-Chloro-phenyl) -9-hydroxy-6- (2-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-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-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-1-yl-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-methyl-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] carbazol-9-yl) -formamide;
N- [4- (2-Chloro-phenyl) -6-methyl-8- (4-morpholin-4-yl-butyl) -1,3-dioxo-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-phenyl) -7- (4-hydroxy-butyl) -6-methyl-1,3-dioxo-1,2,3,6-tetrahydropyrrolo [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) -butyl] -1,3-dioxo-1,2,3,6 -Tetrahydro-pyrrolo [3,4-c] carbazol-9-yl} -formamide;
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-phenyl) -6-methyl-7- [4- (4-methyl-piperazin-1-yl) -butyl] -6H-pyrrolo [3,4-c] carbazole- 1,3-dione;
9-amino-4- (2-chloro-phenyl) -7- (4-dimethylamino-butyl) -6-methyl-6H-pyrrolo [3,4-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.

Images