Seven-ring compound containing azine and indoline structural units and synthesis method and anti-cancer activity thereof

Abstract

The invention discloses a heptacyclic compound containing azine and indoline structural units, and a synthesis method and anticancer activity thereof, and belongs to the technical field of organic synthesis and drug discovery. The preparation method comprises the following steps: mixing an indoline-1-yl (aryl) methylenimine compound 1, a diazoindane diketone compound 2, a catalyst, an additive and an organic solvent, and carrying out heating reaction to prepare a heptacyclic compound 3 containing azine and indoline structural units; and carrying out oxidative aromatization in the presence of manganese dioxide to prepare a heptacyclic compound 4 containing azine and indoline structural units. The heptacyclic compound containing azine and indoline structural units is synthesized through a one-pot cascade reaction, and the process is simple and efficient; the method is mild in reaction condition, simple and convenient to operate, wide in substrate application range and good in functional group tolerance. The compounds 3 and 4 prepared by adopting the method have the activity of obviously inhibiting proliferation of three cancer cells such as Hela, A549 and HCT-116, so that the compounds have the anti-cancer activity on cervical cancer, lung cancer and colon cancer, have potential medicinal value and provide a new structural unit for drug screening.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis and drug discovery, and specifically relates to a seven-ring compound containing azocine and indoline structural units, a synthesis method thereof and anticancer activity. Background Art

[0002] Azine and its fused polycyclic derivatives have unique rigidity and isomerism in three-dimensional structure and conformation, and are often used to prepare catalyst ligands, functional dyes, fluorescent probes, semiconductors and photovoltaic materials. On the other hand, indoline is the core structural skeleton of many clinical drugs and natural alkaloids, and is one of the most noteworthy advantageous structures in new drug research and development. Based on the importance of azine and indoline, the design and synthesis of new hybrid compounds that integrate these two types of advantageous structural units has important theoretical significance and application prospects.

[0003] Due to the unfavorable enthalpy, entropy and cross-ring stress in the structure of azinine and indoline, its efficient synthesis is a challenging task. At present, the synthesis methods of this type of compounds are still very limited, and often require the use of highly functionalized raw materials and harsh reaction conditions. Not only are the steps lengthy and the operation cumbersome, but also a large amount of by-products and waste will be generated. In addition, the synthesis method and anticancer activity research of the seven-ring compound containing azinine and indoline structural units have not been reported yet.

[0004] Therefore, it is of great theoretical significance and application value to study and develop a new efficient and sustainable atom-economical method for synthesizing seven-ring compounds containing azocine and indoline structural units from simple and readily available raw materials under mild reaction conditions, and to study their biological activity and medicinal value. Summary of the invention

[0005] In order to solve the problems existing in the prior art, one of the purposes of the present invention is to provide a seven-ring compound containing azocine and indoline structural units, which has anticancer activity.

[0006] The second object of the present invention is to provide the use of a seven-ring compound containing azocine and indoline structural units in the preparation of anticancer drugs.

[0007] The third object of the present invention is to provide a pharmaceutical composition for treating cervical cancer, lung cancer and colon cancer, wherein the active ingredient is the seven-ring compound containing azocine and indoline structural units provided by the present invention.

[0008] A fourth object of the present invention is to provide a method for synthesizing a seven-ring compound containing azocine and indoline structural units.

[0009] In order to achieve the above object, the technical solution adopted by the present invention is as follows:

[0010] A seven-ring compound 3 and 4 containing azocine and indoline structural units, the general chemical structure of which is:

[0011]

[0012] Where: R 1 is phenyl, substituted phenyl or thienyl, the substituent on the substituted phenyl ring is C 1-4 Alkyl, C 1-4 Alkoxy, C 1-4 Alkylthio, phenyl, halogen, phenylethynyl or phenylthio, R 1 is a single or multiple substitution; R 2 For hydrogen, C 1-4 Alkyl, C 1-4 Alkoxy or halogen; R 3 is hydrogen or C 1-4 Alkyl, R 3 is a mono- or di-substituted; R 4 is hydrogen or C 1-4 Alkyl, R 4 is a mono- or di-substituted; R 5 For hydrogen, C 1-4 Alkyl, C 1-4 Alkoxy, C 1-4 Alkylthio, phenyl or halogen, R 5 It is a one- or multiple-element replacement.

[0013] Furthermore, in the above general structure, in the most preferred case, the following specific structures are selected:

[0014]

[0015] The present invention designs experiments to verify that the compounds provided by the present invention have the activity of inhibiting the proliferation of three cancer cells, Hela, A549 and HCT-116, indicating that the compounds of the present invention can be used as active ingredients of drugs for treating cancers such as cervical cancer, lung cancer and colon cancer. In particular, the above-mentioned preferred compounds can significantly inhibit the growth and proliferation of Hela, A549 and HCT-116, indicating that such compounds as active ingredients of anticancer drugs have the effects of preventing, treating and inhibiting the progression of cervical cancer, lung cancer and colon cancer.

[0016] The synthesis method of the seven-ring compound 3 containing azocine and indoline structural units of the present invention is prepared by using an indoline-1-yl (aryl) azomethine compound and an indole dione compound as raw materials. The synthesis method comprises: mixing an indoline-1-yl (aryl) azomethine compound 1, an indole dione compound 2, a catalyst, an additive and an organic solvent, and heating the mixture to obtain the seven-ring compound 3 containing azocine and indoline structural units, and the reaction equation is:

[0017]

[0018] Where: R 1 is phenyl, substituted phenyl or thienyl, the substituent on the substituted phenyl ring is C 1-4 Alkyl, C 1-4 Alkoxy, C 1-4 Alkylthio, phenyl, halogen, phenylethynyl or phenylthio, R 1 is a single or multiple substitution; R 2 For hydrogen, C 1-4 Alkyl, C 1-4 Alkoxy or halogen; R 3 is hydrogen or C 1-4 Alkyl, R 3 is a mono- or di-substituted; R 4 is hydrogen or C 1-4 Alkyl, R 4 is a mono- or di-substituted; R 5 For hydrogen, C 1-4 Alkyl, C 1-4 Alkoxy, C 1-4 Alkylthio, phenyl or halogen, R 5 It is a one- or multiple-element replacement.

[0019] Furthermore, in the above technical solution, the additive is silver hexafluoroantimonate, silver bis(trifluoromethanesulfonyl)imide, silver acetate, silver tetrafluoroborate, silver p-toluenesulfonate, silver trifluoromethanesulfonate, silver fluoride, silver trifluoroacetate or acetic acid.

[0020] Furthermore, in the above technical solution, the organic solvent is preferably 1,2-dichloroethane, ethyl acetate, acetonitrile, toluene or dichloromethane.

[0021] Furthermore, in the above technical scheme, the catalyst is dichloro(pentamethylcyclopentadienyl)rhodium(III) dimer ([RhCp*Cl2]2), dichloro(pentamethylcyclopentadienyl)iridium(III) dimer ([IrCp*Cl2]2) or dichlorobis(4-methylisopropylphenyl)ruthenium(II) ([Ru(p-cymene)Cl2]2).

[0022] Furthermore, in the above technical solution, the molar ratio of the indolin-1-yl (aryl) azomethine compound 1, the indoledione compound 2, the catalyst and the additive is 1:1.5-2.5:0.025-0.05:0.1-0.2.

[0023] Furthermore, in the above technical solution, the reaction temperature is 60-130°C.

[0024] Furthermore, in the above technical solution, the reaction is carried out in an atmosphere of air, oxygen or an inert gas.

[0025] The synthesis method of the seven-ring compound 4 containing azocine and indoline structural units of the present invention is prepared by oxidative aromatization on the basis of the compound 3 prepared by the above method. The synthesis method comprises: heating the seven-ring compound 3 containing azocine and indoline structural units in an organic solvent in the presence of an oxidant to obtain the seven-ring compound 4 containing azocine and indoline structural units. The reaction equation is:

[0026]

[0027] Where: R 1 -R 5 The substituents are the same as described above.

[0028] Furthermore, in the above technical solution, the oxidant is selected from manganese dioxide; and the organic solvent is acetic acid.

[0029] Furthermore, in the above technical solution, the reaction temperature is 90-120°C.

[0030] Beneficial effects of the invention:

[0031] (1) The seven-ring compound containing azocine and indoline structural units provided by the present invention is screened for compounds having various substituents and verified by anticancer cell activity tests. The compound provided by the present invention has the activity of significantly inhibiting the proliferation of three cancer cells, namely Hela, A549 and HCT-116, indicating that the compound of the present invention has anticancer activity against cervical cancer, lung cancer and colon cancer, has potential medicinal value, and provides a new structural unit for drug screening;

[0032] (2) The synthesis method provided by the present invention uses indolin-1-yl (aryl) azomethine compounds and indole dione as raw materials, and synthesizes a seven-ring compound containing azocine and indole structural units through a one-pot cascade reaction. The process is simple and efficient;

[0033] (3) The synthetic method provided by the present invention has cheap and readily available raw materials, mild reaction conditions, simple operation, a wide range of substrate applicability, and good functional group tolerance. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] Figure 1 It is the X-ray single crystal diffraction pattern of compound 3a in Example 1 and Example 2. DETAILED DESCRIPTION

[0035] The above contents of the present invention are further described in detail below through examples, but this should not be understood as the scope of the above subject matter of the present invention being limited to the following examples, and all technologies implemented based on the above contents of the present invention belong to the scope of the present invention.

[0036] Example 1

[0037]

[0038] Compounds 1a, 2a, catalyst, additives and solvent were added to a 15 mL reaction tube in sequence, the reaction tube was sealed, and the mixture was placed in an oil bath and heated and stirred for reaction. After the reaction was completed, the mixture was cooled to room temperature, filtered through diatomaceous earth, the filtrate was concentrated, and separated through a silica gel column (eluent: dichloromethane) to obtain a red solid product 3a.

[0039] By changing the reaction conditions such as the catalyst, additives, organic solvent, gas atmosphere and the amount of each substance, a series of results were obtained, as shown in Table 1.

[0040] Table 1 Synthesis of 3a under different conditions a

[0041]

[0042]

[0043] Example 2

[0044]

[0045] 1a (44.5 mg, 0.2 mmol), 2a (75.7 mg, 0.44 mmol), [RhCp*Cl2]2 (3.1 mg, 0.005 mmol), silver hexafluoroantimonate (6.9 mg, 0.02 mmol) and dichloromethane (2 mL) were added to a 15 mL pressure tube in sequence, and then the reaction tube was sealed and placed in a 120 ° C oil bath for 4 h. After the reaction, the reaction system was cooled to room temperature, filtered through diatomaceous earth, the filtrate was concentrated, and separated by silica gel column (eluent: dichloromethane) to obtain a red solid product 3a (80.8 mg, 82%). The characterization data of this compound are: 1H NMR (600MHz, CDCl3): δ8.14 (dd, J1=6.6Hz, J2=1.8Hz, 1H), 7.96 (dd, J1=6.6Hz, J2=1.8Hz, 1H), 7.81-7.76 (m, 2H), 7.5 6(d,J=7.8Hz,1H),7.31(d,J=7.8Hz,1H),7.23(tt,J1=7.2Hz,J2=1.8Hz,2H),7.17-7.14(m,1H),7.03-7.01(m,1H),6 .94(td,J1=7.8Hz,J2=1.2Hz,1H),6.92-6.88(m,2H),6.74(t,J=7.8Hz,1H),6.59(d,J=7.2Hz,1H),6.37(d,J=7.8Hz, 1H),3.98(td,J1=10.2Hz,J2=4.8Hz,1H),3.45(td,J1=10.2Hz,J2=7.8Hz,1H),3.25-3.20(m,1H),3.10-3.05(m,1H). 13 C{ 1 H}NMR (100MHz, CDCl3): δ200.2,195.8,182.5,167.0,151.5,144.2,142.4,141.8,139.6,136.7,135.6,134.3,133.5,131.0,130.5,130.3 ,129.7,128.5,128.2,127.63,127.59,126.0,124.9,124.82,124.76,124.4,123.7,117.1,110.4,63.0,49.0,28.3.HRMS(ESI)m / z:[M+Na] + Calcd for C 33 H 20 N2NaO3 + 515.1366; Found 515.1360.

[0046] Example 3

[0047] According to the method and steps of Example 2 a,b By changing reactant 1 and reactant 2, various seven-ring compounds 3 containing azine and indoline structural units can be synthesized. The specific results are as follows:

[0048]

[0049]

[0050] Representative product characterization data are as follows:

[0051] (Z)-4-(p-Tolyl)-1H-benzo[6,7]indeno[1',2':2,3]azocino[4,3-c]pyrrolo[3,2,1-ij]quino line-5,10,16(2H)-trione(3b)

[0052] 1 H NMR(400MHz,CDCl3):δ8.15-8.13(m,1H),7.97-7.95(m,1H),7.82-7.76(m,2H),7.56(d,J=7.6Hz,1H),7.25-7.19(m,2H),7.05-7.01(m,2H),6.96(t,J=7.6Hz,1H),6.80(d,J=7.6Hz,1H),6.74(t,J=7.6Hz,1H),6.69(d,J=8.0Hz,1H),6.61(d,J=7.6Hz,1H),6.37(d,J=7.6Hz,1H),4.00(td,J1=10.4Hz,J2=4.4Hz,1H),3.49-3.42(m,1H),3.27-3.18(m,1H),3.11-3.04(m,1H),2.23(s,3H). 13 C{ 1 H}NMR(100MHz,CDCl3):δ200.3,195.9,182.6,167.1,151.8,144.2,142.6,141.8,139.9,139.7,136.6,135.6,134.2,131.1,131.0,130.6,130.4,130.0,129.0,128.9,127.5,127.4,126.0,124.9,124.8,124.7,124.3,123.7,117.1,110.4,63.0,48.9,28.2,21.3.HRMS(ESI)m / z:[M+Na] + Calcd forC 34 H 22 N2NaO3 + 529.1523;Found529.1525.

[0053] (Z)-4-(4-Ethylphenyl)-1H-benzo[6,7]indeno[1',2':2,3]azocino[4,3-c]pyrrolo[3,2,1-ij]quinoline-5,10,16(2H)-trione(3c)

[0054] 1 H NMR(600MHz,CDCl3):δ8.15-8.13(m,1H),7.96-7.95(m,1H),7.81-7.76(m,2H),7.76-7.55(m,1H),7.23-7.21(m,2H),7.06(dd,J1=7.8Hz,J2=1.2Hz,1H),7.02(d,J=7.8Hz,1H),6.93(td,J1=7.8 Hz,J2=1.2 Hz,1H),6.82(dd,J1=7.8 Hz,J2=1.8 Hz,1H),6.74(t,J=7.8 Hz,1H),6.71(dd,J1=7.8 Hz,J2=1.2 Hz,1H),6.60-6.59(m,1H),6.37(d,J=7.8 Hz,1H),4.01(td,J1=10.2 Hz,J2=4.2 Hz,1H),3.47(td,J1=10.2 Hz,J2=7.8Hz,1H),3.25-3.20(m,1H),3.10-3.05(m,1H),2.51(q,J=7.2 Hz,2H),1.14(t,J=7.2 Hz,3H). 13 C{ 1 H}NMR(150 MHz,CDCl3):δ200.3,195.9,182.5,167.1,151.8,146.4,144.2,142.6,141.8,139.7,136.5,135.6,134.3,131.1,131.0,130.9,130.3,130.1,127.9,127.8,127.6,126.0,124.9,124.8,124.7,124.3,123.6,117.1,110.5,63.0,49.0,28.7,28.2,15.7.HRMS(ESI)m / z:[M+Na] + Calcd for C 35 H 24 N2NaO3 + 543.1679;Found 543.1681.

[0055] (Z)-4-(4-(tert-Butyl)phenyl)-1H-benzo[6,7]indeno[1',2':2,3]azocino[4,3-c]pyrrolo[3,2,1-ij]quinoline-5,10,16(2H)-trione(3d)

[0056] 1 H NMR(600 MHz,CDCl3):δ8.14(d,J=7.2 Hz,1H),7.96(d,J=7.2 Hz,1H),7.81-7.76(m,2H),7.55(d,J=7.8 Hz,1H),7.23-7.18(m,3H),7.02(d,J=7.2 Hz,1H),6.91-6.88(m,2H),6.84(d,J=7.8 Hz,1H),6.74(t,J=7.8 Hz,1H),6.57(d,J=7.2 Hz,1H),6.38(d,J=7.8 Hz,1H),4.04(td,J1=10.8 Hz,J2=4.8 Hz,1H),3.52-3.47(m,1H),3.26-3.21(m,1H),3.11-3.06(m,1H),1.22(s,9H). 13 C{ 1 H}NMR(100 MHz,CDCl3):δ200.3,195.9,182.5,167.1,153.1,151.8,144.3,142.6,141.8,139.7,136.5,135.6,134.2,131.0,130.9,130.6,130.14,130.08,127.6,127.3,125.9,125.3,125.1,124.9,124.8,124.7,124.3,123.7,117.1,110.5,63.0,49.0,34.7,31.2,28.2.HRMS(ESI)m / z:[M+Na] + Calcdfor C 37 H 28 N2NaO3 + 571.1992;Found571.1991.

[0057] (Z)-4-(4-Ethoxyphenyl)-1H-benzo[6,7]indeno[1',2':2,3]azocino[4,3-c]pyrrolo[3,2,1-ij]quinoline-5,10,16(2H)-trione(3e)

[0058] 1H NMR(600 MHz,CDCl3):δ8.14(d,J=7.2 Hz,1H),7.96(d,J=7.2 Hz,1H),7.81-7.76(m,2H),7.57(d,J=7.2 Hz,1H),7.25-7.21(m,2H),7.01(t,J=7.8 Hz,2H),6.83(d,J=7.8 Hz,1H),6.74(t,J=7.2 Hz,2H),6.67(d,J=7.8 Hz,1H),6.41(d,J=7.2 Hz,1H),6.37(d,J=7.8 Hz,1H),4.02-3.92(m,3H),3.49-3.44(m,1H),3.26-3.20(m,1H),3.10-3.05(m,1H),1.38(t,J=7.2 Hz,3H). 13 C{ 1 H}NMR(100MHz,CDCl3):δ200.3,195.9,182.6,167.1,160.1,151.7,144.2,142.8,141.8,139.8,136.5,135.5,134.2,132.6,131.0,130.4,130.2,129.0,127.6,125.9,125.7,124.9,124.8,124.7,124.3,123.7,117.1,115.0,113.7,110.4,63.6,63.0,49.0,28.3,14.6.HRMS(ESI)m / z:[M+Na] + Calcd forC 35 H 24 N2NaO4 + 559.1628;Found 559.1627.

[0059] (Z)-4-(4-(Methylthio)phenyl)-1H-benzo[6,7]indeno[1',2':2,3]azocino[4,3-c]pyrrolo[3,2,1-ij]quinoline-5,10,16(2H)-trione(3f)

[0060] 1H NMR(600 MHz,CDCl3):δ8.15-8.13(m,1H),7.97-7.95(m,1H),7.81-7.76(m,2H),7.57(d,J=7.2 Hz,1H),7.27-7.24(m,1H),7.22(dd,J1=8.4 Hz,J2=1.8 Hz,1H),7.09(dd,J1=7.8 Hz,J2=1.2 Hz,1H),7.04-7.01(m,2H),6.81(dd,J1=8.4 Hz,J2=1.8Hz,1H),6.76-6.73(m,2H),6.67(d,J=7.2 Hz,1H),6.37(d,J=7.8 Hz,1H),3.98(td,J1=10.2 Hz,J2=4.2 Hz,1H),3.46(td,J1=10.2 Hz,J2=8.4 Hz,1H),3.25-3.20(m,1H),3.11-3.05(m,1H),2.41(s,3H). 13 C{ 1 H}NMR(150 MHz,CDCl3):δ200.1,195.8,182.5,167.1,151.2,144.2,142.5,141.8,141.5,139.6,136.6,135.6,134.3,131.4,131.0,130.5,130.2,129.8,127.8,127.6,126.1,125.9,125.5,124.9,124.83,124.78,124.4,123.7,117.1,110.6,63.0,49.0,28.3,15.3.HRMS(ESI)m / z:[M+Na] + Calcd for C 34 H 22 N2NaO3S + 561.1243;Found 561.1251.

[0061] (Z)-4-([1,1'-Biphenyl]-4-yl)-1H-benzo[6,7]indeno[1',2':2,3]azocino[4,3-c]pyrrolo[3,2,1-ij]quinoline-5,10,16(2H)-trione(3g)

[0062] 1H NMR(600 MHz,CDCl3):δ8.16-8.15(m,1H),7.98-7.96(m,1H),7.81-7.77(m,2H),7.59(d,J=7.8 Hz,1H),7.46-7.43(m,5H),7.39-7.36(m,2H),7.23(t,J=7.8Hz,1H),7.09(dd,J1=8.4 Hz,J2=1.8 Hz,1H),7.04(d,J=7.2 Hz,1H),6.98(dd,J1=8.4 Hz,J2=1.8 Hz,1H),6.91(t,J=7.2 Hz,1H),6.76(t,J=7.2 Hz,1H),6.63(d,J=7.8 Hz,1H),6.39(d,J=8.4 Hz,1H),4.05(td,J1=10.2 Hz,J2=4.2 Hz,1H),3.53(td,J1=10.8 Hz,J2=8.4 Hz,1H),3.28-3.23(m,1H),3.13-3.08(m,1H). 13 C{ 1 H}NMR(150 MHz,CDCl3):δ200.2,195.8,182.5,167.1,151.4,144.2,142.7,142.6,141.8,140.2,139.6,136.7,135.6,134.3,132.4,131.5,131.0,130.4,130.1,129.0,128.1,128.0,127.7,127.1,127.0,126.1,124.9,124.84,124.81,124.5,123.7,117.1,110.8,63.0,49.1,28.3.HRMS(ESI)m / z:[M+Na] + Calcd for C 39 H 24 N2NaO3 + 591.1679;Found 591.1690.

[0063] (Z)-4-(4-Fluorophenyl)-1H-benzo[6,7]indeno[1',2':2,3]azocino[4,3-c]pyrrolo[3,2,1-ij]quinoline-5,10,16(2H)-trione(3h)

[0064] 1H NMR(400 MHz,CDCl3):δ8.16-8.14(m,1H),7.98-7.96(m,1H),7.83-7.77(m,2H),7.59(d,J=7.2 Hz,1H),7.33-7.29(m,2H),7.05(t,J=7.6 Hz,2H),6.97-6.91(m,2H),6.76(t,J=8.0 Hz,1H),6.67(d,J=7.2 Hz,1H),6.61(td,J1=8.4 Hz,J2=2.8 Hz,1H),6.38(d,J=8.0 Hz,1H),3.95(td,J1=10.0 Hz,J2=4.4 Hz,1H),3.47(td,J1=10.4Hz,J2=8.0 Hz,1H),3.27-3.21(m,1H),3.14-3.09(m,1H). 13 C{ 1 H}NMR(100 MHz,CDCl3):δ200.0,195.6,182.4,167.0,163.4(d, 1 J C-F =249.5 Hz),150.5,144.2,142.4,141.8,139.5,136.8,135.7,134.3,132.9(d, 3 J C-F =8.2 Hz),130.9,130.8,130.4,129.8(d, 3 J C-F =8.8 Hz),129.6(d, 4 J C-F =4.2 Hz),127.7,125.9,124.93,124.87,124.8,124.6,123.7,117.1,115.6(d, 2 J C-F =23.2 Hz),115.4(d, 2 J C-F =21.6Hz),110.7,63.0,49.0,28.3. 19 FNMR(376 MHz,CDCl3):δ-109.96--110.04(m).HRMS(ESI)m / z:[M+Na] + Calcd forC 33 H 19 FN2NaO3 + 533.1272;Found 533.1275.

[0065] (Z)-4-(4-Chlorophenyl)-1H-benzo[6,7]indeno[1',2':2,3]azocino[4,3-c]pyrrolo[3,2,1-ij]quinoline-5,10,16(2H)-trione(3i)

[0066] 1 H NMR(400 MHz,CDCl3):δ8.15-8.13(m,1H),7.97-7.95(m,1H),7.82-7.76(m,2H),7.58(d,J=7.6 Hz,1H),7.31-7.22(m,3H),7.07-7.02(m,2H),6.87(t,J=9.6Hz,2H),6.75(t,J=7.6 Hz,1H),6.67(d,J=7.6 Hz,1H),6.37(d,J=8.0 Hz,1H),3.93(td,J1=10.0 Hz,J2=4.4 Hz,1H),3.48-3.41(m,1H),3.27-3.18(m,1H),3.12-3.04(m,1H). 13 C{ 1 H}NMR(100 MHz,CDCl3):δ199.9,195.6,182.4,166.9,150.3,144.1,142.3,141.7,139.4,136.8,136.1,135.7,134.4,132.2,131.9,131.0,130.8,130.3,129.0,128.7,128.6,127.7,126.0,124.9,124.8,124.6,123.7,117.1,110.8,63.0,49.0,28.3.HRMS(ESI)m / z:[M+Na] + Calcd for C 33 H 19 ClN2NaO3 + 549.0976;Found 549.0980.

[0067] (Z)-4-(4-Bromophenyl)-1H-benzo[6,7]indeno[1',2':2,3]azocino[4,3-c]pyrrolo[3,2,1-ij]quinoline-5,10,16(2H)-trione(3j)

[0068] 1H NMR(600 MHz,CDCl3):δ8.13(d,J=6.6 Hz,1H),7.96(d,J=6.6 Hz,1H),7.81-7.77(m,2H),7.58(d,J=7.8 Hz,1H),7.39(dd,J1=8.4 Hz,J2=1.8 Hz,1H),7.30(t,J=7.8 Hz,1H),7.19(dd,J1=8.4 Hz,J2=1.8 Hz,1H),7.06(t,J=7.2 Hz,1H),7.03-7.02(m,2H),6.79(dd,J1=8.4 Hz,J2=2.4 Hz,1H),6.75(t,J=7.8 Hz,1H),6.67(d,J=7.2 Hz,1H),6.37(d,J=7.8 Hz,1H),3.92(td,J1=10.2 Hz,J2=4.8Hz,1H),3.46-3.41(m,1H),3.24-3.19(m,1H),3.10-3.05(m,1H). 13 C{ 1 H}NMR(100 MHz,CDCl3):δ199.9,195.6,182.3,167.0,150.2,144.1,142.3,141.7,139.4,136.8,135.7,134.4,132.4,131.7,131.5,131.0,130.8,130.3,129.2,127.7,126.1,124.9,124.8,124.6,124.4,123.7,117.1,110.8,63.0,49.0,28.3.HRMS(ESI)m / z:[M+Na] + Calcd for C 33 H 19 BrN2NaO3 + 593.0471;Found593.0487.

[0069] (Z)-4-(m-Tolyl)-1H-benzo[6,7]indeno[1',2':2,3]azocino[4,3-c]pyrrolo[3,2,1-ij]quinoline-5,10,16(2H)-trione(3k)

[0070] 1H NMR(600 MHz,CDCl3):δ8.16-8.14(m,1.8H),7.97-7.96(m,1.8H),7.82-7.77(m,3.6H),7.61(d,J=7.8 Hz,1H),7.56(d,J=7.2 Hz,0.8H),7.28-7.25(m,1H),7.23(td,J1=7.8 Hz,J2=1.2 Hz,0.8H),7.14(s,0.8H),7.12-7.11(m,2H),7.03(d,J=7.2 Hz,1.8H),6.98-6.96(m,2.6H),6.94(td,J1=7.2 Hz,J2=0.6 Hz,1H),6.78(d,J=7.8 Hz,0.8H),6.75(t,J=7.8 Hz,1.8H),6.71(d,J=7.8 Hz,0.8H),6.66(s,1H),6.60(d,J=7.2Hz,0.8H),6.56(d,J=7.2 Hz,1H),6.38(d,J=8.4 Hz,1.8H),4.02-3.96(m,1.8H),3.50-3.44(m,1.8H),3.26-3.21(m,1.8H),3.12-3.06(m,1.8H),2.29(s,2.4H),2.01(s,3H). 13 C{ 1 H}NMR(100 MHz,CDCl3):δ200.4,200.2,195.8,182.5,167.3,167.0,151.8,151.7,144.3,144.2,142.5,142.4,141.8,139.63,139.60,138.3,138.0,136.74,136.69,135.6,134.3,133.6,133.4,132.2,131.7,131.00,130.98,130.6,130.4,130.23,130.20,130.1,129.9,128.4,128.24,128.17,127.9,127.64,127.56,125.9,125.7,124.9,124.82,124.80,124.7,124.6,124.4,123.7,123.6,120.5,117.1,110.5,110.3,63.02,62.97,49.0,48.9,28.2,21.1,20.8.HRMS(ESI)m / z:[M+Na] + Calcd for C 34 H 22 N2NaO3+ 529.1523;Found529.1525.

[0071] (Z)-4-(3-Methoxyphenyl)-1H-benzo[6,7]indeno[1',2':2,3]azocino[4,3-c]pyrrolo[3,2,1-ij]quinoline-5,10,16(2H)-trione(3l)

[0072] 1 H NMR(400 MHz,CDCl3):δ8.13-8.11(m,1H),7.99-7.97(m,1H),7.81-7.76(m,2H),7.62(d,J=7.6 Hz,1H),7.28-7.25(m,2H),7.19-7.14(m,1H),7.00(d,J=6.8Hz,1H),6.94(td,J1=7.2 Hz,J2=0.8 Hz,1H),6.88-6.85(m,1H),6.71(t,J=7.6 Hz,1H),6.55-6.53(m,1H),6.38(d,J=8.0 Hz,1H),6.33(d,J=8.4 Hz,1H),3.90(td,J1=10.0 Hz,J2=6.4 Hz,1H),3.58(td,J1=10.4 Hz,J2=6.0 Hz,1H),3.48(s,3H),3.21-3.17(m,1H),3.14-3.10(m,1H). 13 C{ 1 H}NMR(100 MHz,CDCl3):δ200.5,196.1,180.5,166.9,156.1,148.9,144.8,142.2,141.1,139.8,136.5,135.4,134.2,133.4,131.7,131.0,130.2,129.5,127.5,125.1,125.0,124.6,124.5,123.9,123.6,122.2,120.4,116.8,110.4,109.9,62.8,54.9,47.8,28.3.HRMS(ESI)m / z:[M+Na] + Calcd for C 34 H 22 N2NaO4 + 545.1472;Found545.1471.

[0073] (Z)-4-(3-Fluorophenyl)-1H-benzo[6,7]indeno[1',2':2,3]azocino[4,3-c]pyrrolo[3,2,1-ij]quinoline-5,10,16(2H)-trione(3m)

[0074] 1 H NMR(400 MHz,CDCl3):δ8.15-8.14(m,1.8H),7.98-7.96(m,1.8H),7.83-7.77(m,3.6H),7.64(d,J=7.6 Hz,1H),7.58(d,J=7.2 Hz,0.8H),7.34-7.30(m,1H),7.28-7.19(m,1.6H),7.12(d,J=7.6 Hz,1H),7.09-6.99(m,4.6H),6.91-6.84(m,2.6H),6.78-6.72(m,3.4H),6.62(d,J=7.6 Hz,2H),6.38(d,J=7.6 Hz,1.8H),4.00-3.93(m,1.8H),3.47(td,J1=10.0 Hz,J2=8.0 Hz,1.8H),3.29-3.19(m,1.8H),3.14-3.06(m,1.8H). 13 C{ 1 H}NMR(100 MHz,CDCl3):δ199.8,195.6,195.5,182.3,166.93,166.85,162.4(d, 1 J C-F =246.7 Hz),162.0(d, 1 J C-F =247.3 Hz),149.9(d, 4 J C-F =2.2 Hz),149.8(d, 4 J C-F =2.1 Hz),144.1,142.2,142.0,141.7,139.4,136.9(d, 3 J C-F =8.6 Hz),135.7,135.6,135.3(d, 3 J C-F =8.6 Hz),134.39,134.37,131.0,130.8,130.7,130.5,130.32(d, 3 J C-F=7.4 Hz),130.31,130.0(d, 3 J C-F =7.8 Hz),127.9,127.8,126.79,126.77,125.9,125.8,125.0,124.9,124.8,124.6,123.7,123.54,123.51,118.2(d, 2 J C-F =22.5 Hz),117.2(d, 2 J C-F =21.4 Hz),117.0,116.3(d, 2 J C-F =20.7 Hz),114.4(d, 2 J C-F =22.2 Hz),110.7,110.5,62.97,62.95,49.04,48.99,28.2. 19 F NMR(565 MHz,CDCl3):δ-111.78-111.82(m),-112.11--112.15(m).HRMS(ESI)m / z:[M+Na] + Calcd for C 33 H 19 FN2NaO3 + 533.1272;Found 533.1275.

[0075] (Z)-4-(3-Chlorophenyl)-1H-benzo[6,7]indeno[1',2':2,3]azocino[4,3-c]pyrrolo[3,2,1-ij]quinoline-5,10,16(2H)-trione(3n)

[0076] 1H NMR(400 MHz,CDCl3):δ8.16-8.13(m,1.8H),7.98-7.95(m,1.8H),7.83-7.77(m,3.6H),7.67(d,J=7.2 Hz,1H),7.57(d,J=7.2 Hz,0.8H),7.38-7.35(m,1.8H),7.26-7.18(m,2.6H),7.16-7.12(m,2H),7.06-6.98(m,3.6H),6.87-6.82(m,2.6H),6.78-6.73(m,2.6H),6.60(d,J=7.2 Hz,1H),6.38(d,J=8.0 Hz,1.8H),3.95(td,J1=10.4 Hz,J2=4.8Hz,1.8H),3.51-3.43(m,1.8H),3.29-3.19(m,1.8H),3.14-3.06(m,1.8H). 13 C{ 1 H}NMR(150MHz,CDCl3):δ199.8,195.6,195.5,182.3,167.1,166.9,149.82,149.80,144.1,142.2,141.9,141.7,139.39,139.35,136.9,136.8,135.71,135.69,135.3,135.2,134.5,134.42,134.38,131.0,130.8,130.72,130.70,130.5,130.3,130.0,129.8,129.63,129.57,129.0,127.9,127.8,127.6,125.8,125.0,124.92,124.85,124.7,123.7,117.0,110.9,110.8,63.00,62.95,49.1,49.0,28.3,28.2.HRMS(ESI)m / z:[M+Na] + Calcd for C 33 H 19 ClN2NaO3 + 549.0976;Found 549.0974.

[0077] (Z)-4-(3-Bromophenyl)-1H-benzo[6,7]indeno[1',2':2,3]azocino[4,3-c]pyrrolo[3,2,1-ij]quinoline-5,10,16(2H)-trione(3o)

[0078] 1 H NMR(600 MHz,CDCl3):δ8.17-8.14(m,1.75H),7.99-7.97(m,1.75H),7.83-7.78(m,3.50H),7.69-7.68(m,1H),7.58-7.57(m,0.75H),7.51(t,J=1.2 Hz,0.75H),7.39(td,J1=7.8 Hz,J2=1.2 Hz,1H),7.32-7.29(m,2H),7.27-7.25(m,1.50H),7.12(t,J=7.8 Hz,1H),7.06-6.99(m,4.50H),6.89(dd,J1=6.6 Hz,J2=1.2 Hz,0.75H),6.80-6.74(m,3.25H),6.60(dd,J1=7.8 Hz,J2=0.6 Hz,1H),6.38(d,J=8.4 Hz,1.75H),3.97-3.93(m,1.75H),3.51-3.45(m,1.75H),3.29-3.22(m,1.75H),3.14-3.09(m,1.75H). 13 C{ 1 H}NMR(150MHz,CDCl3):δ199.8,199.7,195.7,195.5,182.3,167.1,166.9,149.75,149.72,144.2,142.2,141.9,141.77,141.75,139.40,139.35,136.8,136.7,135.7,135.45,135.42,134.40,134.36,133.5,132.9,132.6,131.0,130.94,130.91,130.7,130.6,130.5,130.3,130.0,129.8,129.4,128.0,127.8,126.3,125.83,125.76,125.0,124.93,124.87,124.85,124.8,124.7,123.7,122.49,122.46,117.0,111.0,110.9,63.0,62.9,49.1,49.0,28.27,28.25.HRMS(ESI)m / z:[M+Na] + Calcd for C 33 H 19 BrN2NaO3 + 593.0471;Found 593.0468.

[0079] (Z)-4-(2-Methoxyphenyl)-1H-benzo[6,7]indeno[1',2':2,3]azocino[4,3-c]pyrrolo[3,2,1-ij]quinoline-5,10,16(2H)-trione(3p)

[0080] 1 H NMR(400 MHz,CDCl3):δ8.12-8.10(m,1H),7.98-7.95(m,1H),7.80-7.75(m,2H),7.62(d,J=7.2 Hz,1H),7.28-7.24(m,2H),7.18-7.14(m,1H),6.99(d,J=7.2Hz,1H),6.93(td,J1=7.2 Hz,J2=0.8 Hz,1H),6.86(t,J=7.2 Hz,1H),6.70(t,J=7.6 Hz,1H),6.53(d,J=7.2 Hz,1H),6.37(d,J=8.0 Hz,1H),6.32(d,J=8.0 Hz,1H),3.89(td,J1=10.4 Hz,J2=6.4 Hz,1H),3.56(td,J1=10.0 Hz,J2=6.0 Hz,1H),3.47(s,3H),3.23-3.15(m,1H),3.12-3.06(m,1H). 13 C{ 1 H}NMR(100 MHz,CDCl3):δ200.5,196.1,180.5,167.0,156.1,148.9,144.8,142.2,141.1,139.8,136.5,135.4,134.2,133.4,131.7,131.1,130.2,129.5,127.4,125.1,125.0,124.7,124.5,123.9,123.6,122.2,120.4,116.8,110.3,109.9,62.8,54.9,47.8,28.3.HRMS(ESI)m / z:[M+Na] + Calcd for C 34 H 22 N2NaO4 + 545.1472;Found 545.1470.

[0081] (Z)-4-(2-Bromophenyl)-1H-benzo[6,7]indeno[1',2':2,3]azocino[4,3-c]pyrrolo[3,2,1-ij]quinoline-5,10,16(2H)-trione(3q)

[0082] 1 H NMR(400 MHz,CDCl3):δ8.15-8.13(m,1H),7.99-7.97(m,1H),7.82-7.77(m,2H),7.67(d,J=7.2 Hz,1H),7.52(d,J=7.6 Hz,1H),7.32(td,J1=7.6 Hz,J2=1.2Hz,1H),7.04-6.99(m,3H),6.83-6.74(m,3H),6.72(d,J=6.8 Hz,1H),6.40(d,J=7.6 Hz,1H),3.70(td,J1=10.4 Hz,J2=5.6 Hz,1H),3.52(td,J1=10.0 Hz,J2=7.2Hz,1H),3.21-3.13(m,2H). 13 C{ 1 H}NMR(100 MHz,CDCl3):δ198.7,194.7,182.5,167.2,147.5,144.4,142.4,141.7,139.3,137.2,135.5,134.3,133.9,132.9,131.0,130.9,130.7,130.6,129.8,128.0,126.8,125.1,125.0,124.8,124.7,124.5,124.0,123.7,117.0,110.7,63.0,48.6,28.3.HRMS(ESI)m / z:[M+Na] + Calcd forC 33 H 19 BrN2NaO3 + 593.0471;Found 593.0473.

[0083] (Z)-4-(3,5-Dimethylphenyl)-1H-benzo[6,7]indeno[1',2':2,3]azocino[4,3-c]pyrrolo[3,2,1-ij]quinoline-5,10,16(2H)-trione(3r)

[0084] 1H NMR(600 MHz,CDCl3):δ8.15(d,J=7.2 Hz,1H),7.97(d,J=6.6 Hz,1H),7.81-7.77(m,2H),7.60(d,J=7.2 Hz,1H),7.26-7.24(m,1H),7.02(d,J=7.2,1H),6.97-6.94(m,2H),6.77(s,1H),6.74(t,J=7.8 Hz,1H),6.55(d,J=7.8 Hz,1H),6.45(s,1H),6.38(d,J=7.8 Hz,1H),3.99(td,J1=10.8 Hz,J2=4.8 Hz,1H),3.50-3.45(m,1H),3.26-3.20(m,1H),3.11-3.06(m,1H),2.24(s,3H),1.97(s,3H). 13 C{ 1 H}NMR(100 MHz,CDCl3):δ200.3,195.9,182.5,167.3,151.9,144.3,142.5,141.8,139.6,138.2,137.9,136.7,135.5,134.2,133.5,131.2,131.0,130.1,129.8,129.0,127.6,125.6,124.93,124.85,124.8,124.7,124.3,123.7,117.1,110.4,63.0,48.9,28.2,20.9,20.7.HRMS(ESI)m / z:[M+Na] + Calcd for C 35 H 24 N2NaO3 + 543.1679;Found 543.1685.

[0085] (Z)-4-(3,5-Dimethoxyphenyl)-1H-benzo[6,7]indeno[1',2':2,3]azocino[4,3-c]pyrrolo[3,2,1-ij]quinoline-5,10,16(2H)-trione(3s)

[0086] 1H NMR(400 MHz,CDCl3):δ8.15-8.13(m,1H),7.98-7.96(m,1H),7.82-7.77(m,2H),7.60(d,J=7.6 Hz,1H),7.30-7.27(m,1H),7.07-7.02(m,2H),6.75(t,J=7.6Hz,1H),6.70(d,J=7.2 Hz,1H),6.47(d,J=0.8 Hz,1H),6.38(d,J=7.6 Hz,1H),6.24(t,J=2.0Hz,1H),6.00(s,1H),4.02(td,J1=10.4 Hz,J2=4.4 Hz,1H),3.73(s,3H),3.56-3.47(m,4H),3.29-3.21(m,1H),3.13-3.07(m,1H). 13 C{ 1 H}NMR(100MHz,CDCl3):δ200.0,195.9,182.4,167.0,160.7,160.4,151.2,144.3,142.3,141.7,139.5,137.2,135.6,135.3,134.3,131.1,130.33,130.29,127.5,126.0,124.9,124.83,124.75,124.4,123.7,117.1,110.1,109.6,104.3,102.8,62.9,55.7,55.4,48.9,28.2.HRMS(ESI)m / z:[M+Na] + Calcdfor C 35 H 24 N2NaO5 + 575.1577;Found 575.1582.

[0087] (Z)-4-(3,5-Dichlorophenyl)-1H-benzo[6,7]indeno[1',2':2,3]azocino[4,3-c]pyrrolo[3,2,1-ij]quinoline-5,10,16(2H)-trione(3t)

[0088] 1H NMR(600 MHz,CDCl3):δ8.16-8.15(m,1H),7.98-7.97(m,1H),7.84-7.79(m,2H),7.67(d,J=7.8 Hz,1H),7.38(t,J=7.8 Hz,1H),7.25(s,1H),7.16(t,J=1.8 Hz,1H),7.09(t,J=7.2 Hz,1H),7.05(d,J=7.2 Hz,1H),6.79-6.77(m,2H),6.74(d,J=7.2Hz,1H),6.38(d,J=7.8 Hz,1H),3.93(td,J1=10.2 Hz,J2=4.2 Hz,1H),3.50(td,J1=10.2 Hz,J2=7.8 Hz,1H),3.29-3.23(m,1H),3.15-3.10(m,1H). 13 C{ 1 H}NMR(100 MHz,CDCl3):δ199.3,195.4,182.1,166.9,148.4,144.1,141.72,141.70,139.2,137.0,136.3,135.8,135.3,135.2,134.5,131.1,130.9,130.5,129.7,128.9,128.1,126.0,125.6,125.0,124.92,124.89,124.87,123.7,117.0,110.2,63.0,49.1,28.3.HRMS(ESI)m / z:[M+Na] + Calcd for C 33 H 18 Cl2N2NaO3 + 583.0587;Found 583.0582.(Z)-4-(Thiophen-2-yl)-1H-benzo[6,7]indeno[1',2':2,3]azocino[4,3-c]pyrrolo[3,2,1-ij]quinoline-5,10,16(2H)-trione(3u)

[0089] 1H NMR(600 MHz,CDCl3):δ8.15-8.14(m,1H),7.98-7.96(m,1H),7.82-7.78(m,2H),7.60(d,J=7.8 Hz,1H),7.31-7.28(m,1H),7.24-7.23(m,1H),7.12-7.09(m,1H),7.04-6.97(m,2H),6.80-6.74(m,3H),6.37(d,J=7.8 Hz,1H),4.17(td,J1=10.2 Hz,J2=4.2 Hz,1H),3.60(td,J1=10.2 Hz,J2=7.8 Hz,1H),3.29-3.23(m,1H),3.14-3.09(m,1H). 13 C{ 1 H}NMR(150 MHz,CDCl3):δ199.7,195.7,182.3,166.8,144.8,144.2,141.9,141.6,139.7,136.5,135.7,134.3,131.1,130.44,130.39,127.7,127.2,126.4,125.0,124.8,124.5,123.6,117.0,111.6,62.9,49.3,28.3.HRMS(ESI)m / z:[M+Na] + Calcd forC 31 H 18 N2NaO3S + 521.0930;Found 521.0938.

[0090] (Z)-18-Methyl-4-phenyl-1H-benzo[6,7]indeno[1',2':2,3]azocino[4,3-c]pyrrolo[3,2,1-ij]quinoline-5,10,16(2H)-trione(3v)

[0091] 1H NMR(400 MHz,CDCl3):δ8.17-8.15(m,1H),7.98-7.96(m,1H),7.83-7.77(m,2H),7.57(d,J=7.2 Hz,1H),7.31(d,J=7.6 Hz,1H),7.25-7.20(m,2H),7.18-7.14(m,1H),6.96-6.89(m,3H),6.85(s,1H),6.59(d,J=7.2 Hz,1H),6.15(s,1H),3.98(td,J1=10.4 Hz,J2=4.8 Hz,1H),3.45(td,J1=10.0 Hz,J2=7.6 Hz,1H),3.24-3.16(m,1H),3.08-3.00(m,1H),2.08(s,3H). 13 C{ 1 H}NMR(100 MHz,CDCl3):δ200.3,196.2,182.6,167.4,151.5,144.2,142.6,141.8,137.4,136.7,135.6,134.4,134.3,133.7,131.1,131.0,130.4,130.2,129.6,128.4,128.2,127.62,127.59,125.9,125.7,124.9,124.8,123.9,116.8,110.3,63.0,49.1,28.2,21.3.HRMS(ESI)m / z:[M+Na] + Calcd for C 34 H 22 N2NaO3 + 529.1523;Found 529.1521.

[0092] (Z)-18-Methoxy-4-phenyl-1H-benzo[6,7]indeno[1',2':2,3]azocino[4,3-c]pyrrolo[3,2,1-ij]quinoline-5,10,16(2H)-trione(3w)

[0093] 1H NMR(400 MHz,CDCl3):δ8.16-8.14(m,1H),7.97-7.95(m,1H),7.82-7.76(m,2H),7.60(d,J=7.6 Hz,1H),7.32(d,J=7.6 Hz,1H),7.26-7.21(m,2H),7.19-7.15(m,1H),6.96-6.87(m,3H),6.66(s,1H),6.59(d,J=7.6 Hz,1H),5.93(d,J=2.0 Hz,1H),4.01(td,J1=10.4 Hz,J2=4.8 Hz,1H),3.56(s,3H),3.48(td,J1=10.0 Hz,J2=8.0 Hz,1H),3.27-3.19(m,1H),3.11-3.03(m,1H). 13 C{ 1 H}NMR(100 MHz,CDCl3):δ200.4,195.9,182.7,167.3,157.4,151.4,144.1,142.7,141.6,136.7,135.6,134.3,133.7,132.3,131.0,130.4,130.2,129.6,128.4,128.2,127.62,127.59,125.9,124.9,124.8,117.5,111.0,109.6,109.4,63.2,55.7,49.1,28.5.HRMS(ESI)m / z:[M+Na] + Calcd for C 34 H 22 N2NaO4 + 545.1472;Found 545.1478.

[0094] (Z)-18-Fluoro-4-phenyl-1H-benzo[6,7]indeno[1',2':2,3]azocino[4,3-c]pyrrolo[3,2,1-ij]quinoline-5,10,16(2H)-trione(3x)

[0095] 1H NMR(400 MHz,CDCl3):δ8.17-8.15(m,1H),7.99-7.97(m,1H),7.85-7.79(m,2H),7.58(d,J=7.2 Hz,1H),7.31(d,J=7.6 Hz,1H),7.26-7.23(m,2H),7.20-7.16(m,1H),6.96(td,J1=7.6 Hz,J2=0.8 Hz,1H),6.91-6.90(m,2H),6.79(d,J=7.2 Hz,1H),6.60(d,J=7.6 Hz,1H),6.10(dd,J1=9.2 Hz,J2=2.0 Hz,1H),4.01(td,J1=10.4 Hz,J2=4.4 Hz,1H),3.50(td,J1=10.4 Hz,J2=7.6 Hz,1H),3.29-3.20(m,1H),3.13-3.07(m,1H). 13 C{ 1 H}NMR(150 MHz,CDCl3):δ200.1,195.4,182.5,166.6,160.0(d, 1 J C-F =240.3 Hz),151.4,143.9,142.3,141.4,136.6,136.1,135.9,134.6,133.3,132.8(d, 3 J C-F =9.0 Hz),131.0,130.6,130.3,129.8,128.5,128.3,127.6,127.5,126.0,125.1,124.9,117.3(d, 3 J C-F =8.4 Hz),112.8(d, 2 J C-F =24.9 Hz),110.3(d, 2 J C-F =25.5 Hz),109.5,62.9,49.2,28.2. 19 F NMR(565 MHz,CDCl3):δ-117.68(t,J=7.9 Hz).HRMS(ESI)m / z:[M+Na] + Calcdfor C 33 H 19 FN2NaO3 + 533.1272;Found533.1270.

[0096] (Z)-18-Chloro-4-phenyl-1H-benzo[6,7]indeno[1',2':2,3]azocino[4,3-c]pyrrolo[3,2,1-ij]quinoline-5,10,16(2H)-trione(3y)

[0097] 1 H NMR(400 MHz,CDCl3):δ8.17-8.15(m,1H),7.99-7.96(m,1H),7.85-7.80(m,2H),7.58(d,J=7.6 Hz,1H),7.30(d,J=7.6 Hz,1H),7.26-7.23(m,2H),7.19-7.16(m,1H),7.02(s,1H),6.96(t,J=7.2 Hz,1H),6.93-6.89(m,2H),6.59(d,J=7.6 Hz,1H),6.34(s,1H),4.00(td,J1=10.4 Hz,J2=4.8 Hz,1H),3.48(td,J1=10.0 Hz,J2=7.6 Hz,1H),3.27-3.18(m,1H),3.12-3.04(m,1H). 13 C{ 1 H}NMR(100 MHz,CDCl3):δ199.8,195.4,182.4,166.5,151.1,144.0,142.1,141.3,138.6,136.5,135.9,134.6,133.2,132.6,131.0,130.6,130.4,129.8,129.1,128.5,128.3,127.6,127.5,126.0,125.3,125.2,125.0,123.7,117.8,110.3,62.6,49.1,28.1.HRMS(ESI)m / z:[M+Na] + Calcd for C 33 H 19 ClN2NaO3 + 549.0976;Found 549.0977.

[0098] (Z)-18-Bromo-4-phenyl-1H-benzo[6,7]indeno[1',2':2,3]azocino[4,3-c]pyrrolo[3,2,1-ij]quinoline-5,10,16(2H)-trione(3z)

[0099] 1 H NMR(400 MHz,CDCl3):δ8.17-8.15(m,1H),7.99-7.96(m,1H),7.85-7.80(m,2H),7.58(d,J=7.6 Hz,1H),7.30(d,J=7.2 Hz,1H),7.26-7.23(m,2H),7.19-7.17(m,2H),6.96(t,J=7.6 Hz,1H),6.93-6.89(m,2H),6.59(d,J=7.2 Hz,1H),6.47(s,1H),3.99(td,J1=10.8 Hz,J2=4.8 Hz,1H),3.47(td,J1=10.0 Hz,J2=8.0 Hz,1H),3.27-3.19(m,1H),3.12-3.04(m,1H). 13 C{ 1 H}NMR(100 MHz,CDCl3):δ199.8,195.4,182.4,166.5,151.0,144.0,142.1,141.3,139.0,136.6,135.9,134.6,133.2,133.0,131.0,130.6,130.4,129.8,128.5,128.3,128.1,127.6,127.5,126.5,126.0,125.2,125.0,118.4,116.4,110.5,62.4,49.1,28.0.HRMS(ESI)m / z:[M+Na] + Calcdfor C 33 H 19 BrN2NaO3 + 593.0471;Found593.0473.

[0100] (Z)-19-Methyl-4-phenyl-1H-benzo[6,7]indeno[1',2':2,3]azocino[4,3-c]pyrrolo[3,2,1-ij]quinoline-5,10,16(2H)-trione(3aa)

[0101] 1H NMR(400 MHz,CDCl3):δ8.15-8.13(m,1H),7.96-7.94(m,1H),7.81-7.75(m,2H),7.56(d,J=7.6 Hz,1H),7.31(d,J=7.2 Hz,1H),7.25-7.21(m,2H),7.18-7.14(m,1H),6.96-6.87(m,3H),6.59(d,J=7.6 Hz,1H),6.57(d,J=8.4 Hz,1H),6.29(d,J=8.0Hz,1H),4.01(td,J1=10.0 Hz,J2=4.4 Hz,1H),3.46(td,J1=10.0 Hz,J2=7.6 Hz,1H),3.14-3.08(m,1H),3.03-2.98(m,1H),2.13(s,3H). 13 C{ 1 H}NMR(150MHz,CDCl3):δ200.3,195.9,182.6,167.2,151.6,144.2,142.5,141.8,139.1,136.7,135.5,134.6,134.2,133.6,131.0,130.4,130.2,129.6,129.5,128.4,128.2,127.6,125.9,125.6,124.9,124.8,123.8,114.6,110.3,62.9,49.0,27.2,18.2.HRMS(ESI)m / z:[M+Na] + Calcd forC 34 H 22 N2NaO3 + 529.1523;Found 529.1524.

[0102] (Z)-19-Chloro-4-phenyl-1H-benzo[6,7]indeno[1',2':2,3]azocino[4,3-c]pyrrolo[3,2,1-ij]quinoline-5,10,16(2H)-trione(3bb)

[0103] 1H NMR(400 MHz,CDCl3):δ8.16-8.14(m,1H),7.98-7.96(m,1H),7.84-7.78(m,2H),7.58(d,J=7.6 Hz,1H),7.30(d,J=7.6 Hz,1H),7.26-7.23(m,2H),7.20-7.16(m,1H),6.96(td,J1=7.6 Hz,J2=0.8 Hz,1H),6.93-6.90(m,2H),6.72(d,J=8.4 Hz,1H),6.60(d,J=7.2 Hz,1H),6.34(d,J=8.0 Hz,1H),4.02(td,J1=10.4 Hz,J2=4.8Hz,1H),3.50(td,J1=10.4 Hz,J2=7.6 Hz,1H),3.28-3.19(m,1H),3.16-3.08(m,1H). 13 C{ 1 H}NMR(100 MHz,CDCl3):δ199.8,195.4,182.4,166.5,151.2,144.1,142.1,141.5,140.9,136.6,135.8,134.5,133.1,131.0,130.7,130.6,130.4,129.9,129.1,128.6,128.3,127.7,127.4,126.0,125.3,125.0,124.9,124.2,115.4,110.6,62.5,48.9,27.8.HRMS(ESI)m / z:[M+Na] + Calcd for C 33 H 19 ClN2NaO3 + 549.0976;Found 549.0980.

[0104] (Z)-19-Bromo-4-phenyl-1H-benzo[6,7]indeno[1',2':2,3]azocino[4,3-c]pyrrolo[3,2,1-ij]quinoline-5,10,16(2H)-trione(3cc)

[0105] 1H NMR(400 MHz,CDCl3):δ8.15-8.13(m,1H),7.98-7.96(m,1H),7.83-7.78(m,2H),7.58(d,J=7.6 Hz,1H),7.30(d,J=7.2 Hz,1H),7.27-7.23(m,2H),7.19-7.16(m,1H),6.96(t,J=7.2 Hz,1H),6.93-6.90(m,2H),6.87(d,J=8.0 Hz,1H),6.60(d,J=7.2Hz,1H),6.26(d,J=8.4 Hz,1H),4.01(td,J1=10.4 Hz,J2=4.8 Hz,1H),3.49(td,J1=10.4 Hz,J2=8.0 Hz,1H),3.24-3.15(m,1H),3.11-3.05(m,1H). 13 C{ 1 H}NMR(100 MHz,CDCl3):δ199.8,195.4,182.4,166.4,151.3,144.1,142.1,141.5,140.7,136.6,135.8,134.5,133.0,131.5,131.0,130.7,130.4,129.9,128.6,128.3,127.7,127.4,126.9,126.0,125.5,125.0,124.9,119.4,115.9,110.5,62.5,48.6,29.6.HRMS(ESI)m / z:[M+Na] + Calcd for C 33 H 19 BrN2NaO3 + 593.0471;Found593.0470.

[0106] (Z)-2-Methyl-4-phenyl-1H-benzo[6,7]indeno[1',2':2,3]azocino[4,3-c]pyrrolo[3,2,1-ij]quinoline-5,10,16(2H)-trione(3dd)

[0107] 1H NMR(600 MHz,CDCl3):δ8.14-8.11(m,1.75H),7.98-7.95(m,1.75H),7.81-7.76(m,3.50H),7.69(d,J=7.8 Hz,1H),7.54(d,J=7.8 Hz,0.75H),7.39-7.36(m,1.75H),7.31(d,J=7.2 Hz,1H),7.28-7.20(m,2.50H),7.19-7.13(m,1.75H),7.04-7.02(m,2.75H),6.96-6.90(m,2.50H),6.79-6.73(m,3.50H),6.60-6.58(m,1.75H),6.38(d,J=8.4Hz,1.75H),4.35-4.33(m,0.75H),3.94-3.91(m,1H),3.44(dd,J1=16.2 Hz,J2=9.0 Hz,0.75H),3.29(dd,J1=16.2 Hz,J2=9.0 Hz,1H),2.71(dd,J1=15.6 Hz,J2=3.0 Hz,1H),2.66(d,J=16.2 Hz,0.75H),1.25(d,J=6.6 Hz,3H),0.87(d,J=6.6 Hz,2.25H). 13 C{ 1 H}NMR(150 MHz,CDCl3):δ200.4,200.0,195.4,195.2,182.42,182.38,167.1,166.6,151.4,150.5,144.4,144.1,142.6,142.4,141.8,141.7,139.0,138.6,137.8,136.4,135.6,135.5,134.3,134.2,133.8,132.6,131.4,131.3,131.0,130.5,130.4,130.3,129.7,129.64,129.62,129.0,128.9,128.39,128.38,127.8,127.6,127.4,126.9,126.0,125.7,125.1,124.9,124.84,124.80,124.7,124.5,124.4,123.7,123.6,117.4,117.1,111.6,109.8,63.2,62.8,57.7,56.8,37.9,36.7,24.8,20.2.HRMS(ESI)m / z:[M+Na] + Calcd forC 34H 22 N2NaO3 + 529.1523;Found 529.1520.

[0108] (Z)-1-Methyl-4-phenyl-1H-benzo[6,7]indeno[1',2':2,3]azocino[4,3-c]pyrrolo[3,2,1-ij]quinoline-5,10,16(2H)-trione(3ee)

[0109] 1 H NMR(400 MHz,CDCl3):δ8.17-8.15(m,1.65H),7.98-7.96(m,1.65H),7.82-7.77(m,3.30H),7.57(d,J=7.2 Hz,1.65H),7.32(d,J=7.8 Hz,1.65H),7.25-7.22(m,3.30H),7.19-7.16(m,1.65H),7.03-7.00(m,1.65H),6.97-6.90(m,4.95H),6.78(t,J=7.8 Hz,1.65H),6.62(d,J=7.2 Hz,1.65H),6.40-6.38(m,1.65H),4.11(dd,J1=10.8 Hz,J2=9.6Hz,1H),3.64-3.60(m,1.65H),3.57(dd,J1=10.2 Hz,J2=4.2 Hz,0.65H),3.45-3.42(m,0.65H),3.03(dd,J1=10.2 Hz,J2=8.4 Hz,1H),1.35(d,J=6.6 Hz,1.95H),1.28(d,J=7.2 Hz,3H). 13 C{ 1H}NMR(150 MHz,CDCl3):δ200.4,200.1,195.74,195.69,182.7,182.4,167.0,166.9,151.6,151.5,144.23,144.18,142.48,142.46,141.90,141.87,139.4,138.8,136.8,136.7,136.1,135.9,135.6,134.2,133.7,133.5,131.03,131.01,130.50,130.48,130.2,129.7,129.6,128.45,128.43,128.23,128.20,127.8,127.7,127.63,127.57,126.0,124.90,124.88,124.8,124.6,124.5,123.85,123.78,123.76,123.5,117.1,117.0,110.7,110.3,63.1,63.0,57.1,56.9,35.8,35.6,20.8,18.5.HRMS(ESI)m / z:[M+Na] + Calcd for C 34 H 22 N2NaO3 + 529.1523;Found 529.1522.

[0110] (Z)-1,1-Dimethyl-4-phenyl-1H-benzo[6,7]indeno[1',2':2,3]azocino[4,3-c]pyrrolo[3,2,1-ij]quinoline-5,10,16(2H)-trione(3ff)

[0111] 1H NMR(600 MHz,CDCl3):δ8.16-8.15(m,1H),7.96-7.95(m,1H),7.81-7.76(m,2H),7.56(dd,J1=7.8 Hz,J2=0.6 Hz,1H),7.32(d,J=7.8 Hz,1H),7.23(t,J=7.2Hz,2H),7.18-7.15(m,1H),6.99(dd,J1=7.2 Hz,J2=1.2 Hz,1H),6.97-6.94(m,2H),6.92(t,J=7.8 Hz,1H),6.79(t,J=7.8 Hz,1H),6.63(dd,J1=7.2 Hz,J2=0.6Hz,1H),6.39(dd,J1=7.8 Hz,J2=0.6 Hz,1H),3.69(d,J=10.2 Hz,1H),3.25(d,J=10.2 Hz,1H),1.39(s,3H),1.31(s,3H). 13 C{ 1 H}NMR(150 MHz,CDCl3):δ200.3,195.7,182.7,166.9,151.9,144.1,142.5,142.01,139.97,138.3,136.9,135.6,134.2,133.6,131.0,130.5,130.2,129.7,128.4,128.2,127.9,127.5,126.1,124.90,124.85,124.7,123.8,122.0,117.1,110.8,63.5,63.0,41.9,29.6,26.2.HRMS(ESI)m / z:[M+Na] + Calcd for C 35 H 24 N2NaO3 + 543.1679;Found 543.1686.

[0112] (Z)-7,8,13,14-Tetrafluoro-4-phenyl-1H-benzo[6,7]indeno[1',2':2,3]azocino[4,3-c]pyrrolo[3,2,1-ij]quinoline-5,10,16(2H)-trione(3gg)

[0113] 1H NMR(600 MHz,CDCl3):δ7.93(t,J=7.8 Hz,1H),7.74(t,J=7.8 Hz,1H),7.39(dd,J1=9.6 Hz,J2=7.2 Hz,1H),7.34-7.29(m,3H),7.09-7.06(m,2H),6.96(d,J=7.8Hz,1H),6.82(t,J=7.8 Hz,1H),6.41-6.38(m,2H),4.04(td,J1=10.2 Hz,J2=4.2 Hz,1H),3.51(td,J1=10.8 Hz,J2=7.8 Hz,1H),3.31-3.25(m,1H),3.16-3.11(m,1H). 13 C{ 1 H}NMR(150 MHz,CDCl3):δ197.4,193.1,179.5,165.8,155.8(dd, 1 J C-F =262.5 Hz, 2 J C-F =14.7Hz),155.2(dd, 1 J C-F =263.0 Hz, 2 J C-F =13.8 Hz),152.1,151.2(dd, 1 J C-F =254.3 Hz, 2 J C-F =13.2 Hz),150.8(dd, 1 J C-F =254.0 Hz, 2 J C-F =14.3Hz),141.1(dd, 3 J C-F =7.2 Hz, 4 J C-F =2.0 Hz),139.6-139.5(m),139.2,138.88-138.86(m),133.52-133.46(m),133.2,131.4,131.0,130.3,128.8,128.5,127.4,125.3,125.0,123.5,117.0(d, 2 J C-F =19.1 Hz),116.4,115.0(d, 2 J C-F =18.6 Hz),113.5(d, 2J C-F =15.8 Hz),113.4(d, 2 J C-F =19.2 Hz),109.8,62.9,49.1,28.2. 19 F NMR(565 MHz,CDCl3):δ-121.71--121.77(m),-123.70--123.76(m),-131.93--132.00(m),-133.36--133.43(m).HRMS(ESI)m / z:[M+Na] + Calcd forC 33 H 16 F4N2NaO3 + 587.0989;Found 587.0991.

[0114] (Z)-7,8,13,14-Tetrafluoro-1,1-dimethyl-4-phenyl-1H-benzo[6,7]indeno[1',2':2,3]azocino[4,3-c]pyrrolo[3,2,1-ij]quinoline-5,10,16(2H)-trione(3hh)

[0115] 1 H NMR(600 MHz,CDCl3):δ7.94(t,J=7.8 Hz,1H),7.74-7.71(m,1H),7.38(dd,J1=9.6 Hz,J2=7.2 Hz,1H),7.31-7.30(m,3H),7.10-7.07(m,1H),7.04(d,J=7.2Hz,1H),6.98(d,J=7.8 Hz,1H),6.86(t,J=7.8 Hz,1H),6.42-6.40(m,2H),3.73(d,J=10.8 Hz,1H),3.29(d,J=10.2 Hz,1H),1.40(s,3H),1.34(s,3H). 13 C{ 1 H}NMR(150 MHz,CDCl3):δ197.5,193.1,179.6,165.7,155.9(dd, 1 J C-F =262.7 Hz, 2 J C-F =14.3 Hz),155.2(dd, 1 J C-F =261.2 Hz, 2 JC-F =14.6 Hz),152.5,151.2(dd, 1 J C-F =253.5Hz, 2 J C-F =13.4 Hz),150.8(dd, 1 J C-F =254.9 Hz, 2 J C-F =12.8 Hz),141.1-141.0(m),140.4,139.64-139.59(m),139.1(d, 3 J C-F =5.0 Hz),138.0,133.70-133.65(m),133.3,131.1,130.4,128.8,128.5,127.7,125.3,123.6,122.5,116.9(d, 2 J C-F =18.8 Hz),116.5,115.1(d, 2 J C-F =18.6 Hz),113.5(d, 2 J C-F =16.7 Hz),113.4(d, 2 J C-F =18.0 Hz),110.1,63.5,62.9,42.0,29.5,26.3. 19 F NMR(565 MHz,CDCl3):δ-121.65--121.71(m),-123.75-123.81(m),-131.87-131.93(m),-133.47--133.52(m).HRMS(ESI)m / z:[M+Na] + Calcd for C 35 H 20 F4N2NaO3 + 615.1302;Found615.1300.

[0116] (Z)-19-Methyl-4-(p-tolyl)-1H-benzo[6,7]indeno[1',2':2,3]azocino[4,3-c]pyrrolo[3,2,1-ij]quinoline-5,10,16(2H)-trione(3ii)

[0117] 1H NMR(600 MHz,CDCl3):δ8.15-8.14(m,1H),7.96-7.95(m,1H),7.81-7.76(m,2H),7.56(d,J=7.8 Hz,1H),7.23(td,J1=7.8 Hz,J2=1.2 Hz,1H),7.19(dd,J1=7.8 Hz,J2=1.8 Hz,1H),7.04(d,J=7.8 Hz,1H),6.95(td,J1=7.2 Hz,J2=1.2 Hz,1H),6.79(dd,J1=7.8 Hz,J2=1.2 Hz,1H),6.69(d,J=7.2 Hz,1H),6.61(d,J=7.2Hz,1H),6.56(d,J=8.4 Hz,1H),6.29(d,J=7.8 Hz,1H),4.02(td,J1=10.8 Hz,J2=4.8 Hz,1H),3.47(td,J1=10.2 Hz,J2=7.8 Hz,1H),3.15-3.10(m,1H),3.03-2.98(m,1H),2.23(s,3H),2.14(s,3H). 13 C{ 1 H}NMR(100 MHz,CDCl3):δ200.4,196.0,182.6,167.3,151.9,144.3,142.7,141.9,139.9,139.2,136.7,135.5,134.6,134.2,131.1,130.7,130.3,129.9,129.5,128.94,128.92,127.6,127.5,126.0,125.5,124.84,124.78,123.8,114.7,110.3,62.9,48.9,27.2,21.3,18.2.HRMS(ESI)m / z:[M+Na] + Calcd for C 35 H 24 N2NaO3 + 543.1679;Found543.1677.

[0118] (Z)-19-Chloro-4-(4-chlorophenyl)-1H-benzo[6,7]indeno[1',2':2,3]azocino[4,3-c]pyrrolo[3,2,1-ij]quinoline-5,10,16(2H)-trione(3jj)

[0119] 1H NMR(600 MHz,CDCl3):δ8.15-8.14(m,1H),7.98-7.96(m,1H),7.83-7.79(m,2H),7.59(d,J=7.8 Hz,1H),7.31(td,J1=7.2 Hz,J2=0.6 Hz,1H),7.26-7.23(m,2H),7.06(td,J1=7.8 Hz,J2=1.2 Hz,1H),6.89(d,J=8.4 Hz,1H),6.84(t,J=8.4Hz,1H),6.73(d,J=8.4 Hz,1H),6.67(d,J=7.8 Hz,1H),6.33(d,J=8.4 Hz,1H),3.97(td,J1=10.8 Hz,J2=4.8 Hz,1H),3.50(td,J1=10.8 Hz,J2=7.8 Hz,1H),3.26-3.20(m,1H),3.16-3.11(m,1H). 13 C{ 1 H}NMR(100 MHz,CDCl3):δ199.5,195.3,182.3,166.4,150.0,144.0,141.9,141.5,140.7,136.7,136.3,135.9,134.6,132.2,131.5,131.0,130.8,130.4,129.1,128.9,128.8,128.7,127.8,126.1,125.3,125.1,124.9,124.4,115.3,110.9,62.5,48.9,27.8.HRMS(ESI)m / z:[M+Na] + Calcdfor C 33 H 18 Cl2N2NaO3 + 583.0587;Found583.0588.

[0120] (Z)-4-(4-Bromophenyl)-19-methyl-1H-benzo[6,7]indeno[1',2':2,3]azocino[4,3-c]pyrrolo[3,2,1-ij]quinoline-5,10,16(2H)-trione(3kk)

[0121] 1H NMR(600 MHz,CDCl3):δ8.15-8.14(m,1H),7.97-7.96(m,1H),7.82-7.77(m,2H),7.58(dd,J1=7.8 Hz,J2=0.6 Hz,1H),7.40(dd,J1=8.4 Hz,J2=2.4 Hz,1H),7.30(td,J1=7.2 Hz,J2=0.6 Hz,1H),7.20(dd,J1=7.8 Hz,J2=1.8 Hz,1H),7.06(td,J1=7.8Hz,J2=1.2 Hz,1H),7.03(dd,J1=8.4 Hz,J2=1.8 Hz,1H),6.79(dd,J1=8.4 Hz,J2=2.4Hz,1H),6.66(dd,J1=7.2 Hz,J2=0.6 Hz,1H),6.58(d,J=8.4 Hz,1H),6.29(d,J=7.8Hz,1H),3.96(td,J1=10.2 Hz,J2=4.8 Hz,1H),3.48(td,J1=10.2 Hz,J2=7.8 Hz,1H),3.17-3.11(m,1H),3.05-3.00(m,1H),2.15(s,3H). 13 C{ 1 H}NMR(100 MHz,CDCl3):δ200.0,195.8,182.4,167.1,150.3,144.1,142.3,141.8,139.0,136.9,135.6,134.7,134.3,132.5,132.4,131.6,131.5,130.8,130.3,129.5,129.2,127.8,126.0,125.8,124.9,124.8,124.3,123.8,114.6,110.6,62.9,49.0,27.3,18.2.HRMS(ESI)m / z:[M+Na] + Calcdfor C 34 H 21 BrN2NaO3 + 607.0628;Found607.0630.

[0122] (Z)-18-Fluoro-4-(4-(methylthio)phenyl)-1H-benzo[6,7]indeno[1',2':2,3]azocino[4,3-c]pyrrolo[3,2,1-ij]quinoline-5,10,16(2H)-trione(3ll)

[0123] 1 H NMR(600 MHz,CDCl3):δ8.15-8.14(m,1H),7.98-7.96(m,1H),7.84-7.79(m,2H),7.57-7.56(m,1H),7.26(td,J1=7.8 Hz,J2=1.2 Hz,1H),7.21(dd,J1=8.4 Hz,J2=1.8 Hz,1H),7.09(dd,J1=8.4 Hz,J2=1.8 Hz,1H),7.03(td,J1=7.8 Hz,J2=1.2 Hz,1H),6.80-6.78(m,2H),6.75(dd,J1=8.4 Hz,J2=1.8 Hz,1H),6.66-6.65(m,1H),6.10(dd,J1=9.6 Hz,J2=2.4 Hz,1H),4.00(td,J1=10.2 Hz,J2=4.8 Hz,1H),3.50(td,J1=10.2Hz,J2=8.4 Hz,1H),3.25-3.20(m,1H),3.10-3.05(m,1H),2.41(s,3H). 13 C{ 1 H}NMR(100MHz,CDCl3):δ200.0,195.4,182.5,166.7,160.0(d, 1 J C-F =241.1 Hz),151.0,143.9,142.4,141.7,141.3,136.5,136.1(d, 4 J C-F =1.7 Hz),135.9,134.6,132.8(d, 3 J C-F =9.3 Hz),131.3,130.6,130.3,129.6,127.7,127.6,126.1,125.9,125.5,125.1,124.9,117.3(d, 3 J C-F =8.8 Hz),112.8(d, 2 J C-F =25.2 Hz),110.3(d, 2 J C-F =25.2 Hz),109.6,62.9,49.2,28.2,15.3. 19F NMR(376 MHz,CDCl3):δ-117.61(t,J=9.0 Hz).HRMS(ESI)m / z:[M+Na] + Calcd for C 34 H 21 FN2NaO3S + 579.1149;Found 579.1152.

[0124] (Z)-4-(4-Chlorophenyl)-18-methyl-1H-benzo[6,7]indeno[1',2':2,3]azocino[4,3-c]pyrrolo[3,2,1-ij]quinoline-5,10,16(2H)-trione(3mm)

[0125] 1 H NMR(600 MHz,CDCl3):δ8.15(d,J=7.2 Hz,1H),7.97(d,J=6.6 Hz,1H),7.82-7.78(m,2H),7.58(d,J=7.2 Hz,1H),7.31-7.29(m,1H),7.27-7.25(m,1H),7.23(d,J=7.8Hz,1H),7.05(t,J=7.2 Hz,1H),6.88-6.84(m,3H),6.66(d,J=7.2Hz,1H),6.15(s,1H),3.93(td,J1=10.2 Hz,J2=4.8 Hz,1H),3.47-3.42(m,1H),3.22-3.16(m,1H),3.07-3.02(m,1H),2.08(s,3H). 13 C{ 1 H}NMR(100 MHz,CDCl3):δ200.0,196.0,182.4,167.3,150.2,144.1,142.4,141.7,137.3,136.8,136.0,135.7,134.6,134.4,132.2,132.1,131.0,130.7,130.3,129.0,128.6,128.5,127.7,126.0,125.8,124.9,124.8,123.9,116.7,110.6,63.0,49.1,28.2,21.3.HRMS(ESI)m / z:[M+Na] + Calcd for C 34 H 21 ClN2NaO3 +563.1133; Found 563.1130.

[0126] (Z)-4-(4-Bromophenyl)-1,1-dimethyl-1H-benzo[6,7]indeno[1',2':2,3]azocino[4,3-c]pyrrolo[3,2,1-ij]quinoline-5,10,16(2H)-trione (3nn)

[0127] 1 H NMR (600 MHz, CDCl3): δ 8.16 (d, J = 7.2 Hz, 1H), 7.96 (d, J = 6.6 Hz, 1H), 7.82 - 7.78 (m, 2H), 7.58 (d, J = 7.8 Hz, 1H), 7.39 (dd, J1 = 7.8 Hz, J2 = 1.2 Hz, 1H), 7.30 (t, J = 7.2 Hz, 1H), 7.20 (dd, J1 = 8.4 Hz, J2 = 2.4 Hz, 1H), 7.08 - 7.04 (m, 2H), 6.99 (d, J = 7.2 Hz, 1H), 6.83 - 6.79 (m, 2H), 6.70 (d, J = 7.2 Hz, 1H), 6.39 (d, J = 7.8 Hz, 1H), 3.63 (d, J = 10.2 Hz, 1H), 3.25 (d, J = 10.2 Hz, 1H), 1.38 (s, 3H), 1.32 (s, 3H). 13 C{ 1 H}NMR (100 MHz, CDCl3): δ 199.9, 195.5, 182.5, 166.8, 150.6, 144.0, 142.3, 142.0, 139.9, 138.2, 137.0, 135.7, 134.3, 132.44, 132.38, 131.6, 131.5, 130.9, 130.3, 129.4, 127.7, 126.2, 124.94, 124.90, 124.88, 124.4, 123.8, 122.1, 117.1, 111.1, 63.5, 63.0, 42.0, 29.5, 26.2. HRMS (ESI) m / z: [M+Na] + Calcd for C 35 H 23 BrN2NaO3 + 621.0784; Found 621.0780.

[0128] Example 4

[0129]

[0130] 3a (98.5 mg, 0.2 mmol), manganese dioxide (34.8 mg, 0.4 mmol) and acetic acid (2 mL) were added to a 15 mL pressure tube in sequence, the reaction tube was sealed, and placed in a 100 ° C oil bath for 12 hours. After the reaction, the reaction system was cooled to room temperature, water was added to quench the reaction, and it was extracted three times with dichloromethane. The organic phase was washed with a saturated sodium chloride solution, the organic phases were combined, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated and separated by a silica gel column (eluent: dichloromethane) to obtain a yellow solid product 4a (37.5 mg, 38%). The characterization data of the compound are: 1 H NMR (600MHz, CDCl3): δ8.19-8.17(m,1H),8.04-8.03(m,1H),7.83-7.82(m,2H),7.56(dd, J1=7.8Hz,J2=0.6Hz,1H),7.46(d,J=7.8Hz,1H),7.42-7.41(m,1H),7.32(td,J1=7.2Hz,J 2=0.6Hz,1H),7.29-7.25(m,2H),7.03-6.98(m,3H),6.94(d,J=7.8Hz,1H),6.80(d,J=3.6 Hz,1H),6.73(dd,J1=7.8Hz,J2=0.6Hz,1H),6.49(d,J=3.0Hz,1H),6.44(d,J=7.8Hz,1H). 13 C{ 1 H}NMR (150MHz, CDCl3): δ198.8,192.4,180.9,163.7,145.8,144.6,141.8,140.7,136.1,135.9,134.5,131.7,131.2,131.0,130.5,1 30.4,129.3,128.9,128.4,128.3,128.0,126.7,125.8,125.0,124.5,123.9,121.1,118.7,116.6,107.2,62.6.HRMS(ESI)m / z:[M+Na] + Calcd for C 33 H 18 N2NaO3 + 513.1210; Found 513.1208.

[0131] Example 5

[0132]

[0133] 3j (57.1 mg, 0.1 mmol), phenylacetylene (16.5 μL, 0.15 mmol), triphenylphosphine (5.2 mg, 0.02 mmol), potassium phosphate (25.5 mg, 0.12 mmol), palladium acetate (1.1 mg, 0.005 mmol) and dimethyl sulfoxide (1 mL) were added to a 15 mL pressure tube in sequence. The reaction tube was evacuated and filled with argon, sealed, and placed in an 80 ° C oil bath for 24 hours. After the reaction, the reaction system was cooled to room temperature, water was added to quench the reaction, filtered, extracted three times with ethyl acetate, the organic phase was washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, the filtrate was concentrated, and separated by silica gel column (eluent: dichloromethane) to obtain a red solid product 3A (46.6 mg, 79%). The characterization data of this compound are: 1 H NMR (600MHz, CDCl3): δ8.15-8.14(m,1H),7.97-7.96(m,1H),7.81-7.77(m,2H),7.59(d,J=7.2Hz,1H),7.53-7. 51(m,2H),7.41(dd,J1=7.8Hz,J2=1.8Hz,1H),7.37-7.34(m,3H),7.32-7.28(m,2H),7.06-7.02(m,3H),6.91(d d, J1=7.8Hz, J2=1.2Hz, 1H), 6.76 (t, J=7.8Hz, 1H), 6.69 (dd, J1=7.8Hz, J2=0.6Hz, 1H), 6.38 (d, J=8.4Hz, 1H), 3 .97(td,J1=10.2Hz,J2=4.8Hz,1H),3.45(td,J1=10.2Hz,J2=7.8Hz,1H),3.26-3.20(m,1H),3.11-3.06(m,1H). 13 C{ 1 H}NMR (150MHz, CDCl3): δ200.0,195.7,182.5,167.0,150.9,144.2,142.4,141.8 ,139.5,136.8,135.7,134.4,133.2,131.7,131.6,131.3,131.00,130.99,130.8, 130.5,128.7,128.5,127.7,127.6,126.1,124.92,124.89,124.85,124.8,124.6 ,123.7,122.7,117.1,110.7,91.3,88.5,63.0,49.0,28.3.HRMS(ESI)m / z:[M+Na] + Calcd for C 41H 24 N2NaO3 + 615.1679; Found 615.1676.

[0134] Example 6

[0135]

[0136] 3j (57.1 mg, 0.1 mmol), styrene (11.5 μL, 0.1 mmol), 1,1-bis(diphenylphosphine)diphenylferropalladium dichloride (7.3 mg, 0.01 mmol), triethylamine (20.2 mg, 0.2 mmol) and N,N-dimethylformamide (1 mL) were added to a 15 mL pressure tube in sequence. The reaction tube was evacuated and sealed after filling with argon, and placed in a 100 ° C oil bath for 24 hours. After the reaction was completed, the reaction system was cooled to room temperature, water was added to quench the reaction, filtered, extracted three times with dichloromethane, the organic phase was washed with saturated sodium chloride solution, dried over anhydrous sodium sulfate, filtered, the filtrate was concentrated, and separated by silica gel column (eluent: dichloromethane) to obtain a red solid product 3B (40.7 mg, 69%). The characterization data of this compound are: 1 H NMR (600MHz, CDCl3): δ8.16-8.14(m,1H),7.97-7.96(m,1H),7.81-7.76(m,2H),7.58(dd,J1=7.8Hz,J2=0.6Hz,1H),7. 51(d,J=7.2Hz,2H),7.38-7.36(m,3H),7.31-7.27(m,2H),7.24(td,J1=7.8Hz,J2=1.2Hz,1H),7.06-7.02(m,3H),6.98- 6.94(m,2H),6.90(dd,J1=8.4Hz,J2=2.4Hz,1H),6.76-6.74(m,1H),6.66(dd,J1=7.8Hz,J2=1.2Hz,1H),6.39(d,J=7.8H z,1H),4.01(td,J1=10.2Hz,J2=4.2Hz,1H),3.48(td,J1=10.2Hz,J2=8.4Hz,1H),3.27-3.21(m,1H),3.11-3.06(m,1H). 13 C{ 1H}NMR (150MHz, CDCl3): δ200.2,195.8,182.5,167.1,151,4,144.2,142.5,141 .8,139.7,138.8,136.8,136.7,135.6,134.3,132.5,131.5,131.0,130.5,130. 3,128.8,128.2,128.0,127.6,127.4,126.7,126.3,126.2,126.1,124.9,124.8 4,124,79,124.4,123.7,117.1,110.6,63.0,49.0,28.3.HRMS(ESI)m / z:[M+Na] + Calcd for C 41 H 26 N2NaO3 + 617.1836; Found 617.1837.

[0137] Example 7

[0138] The anticancer activity of the compounds provided by the present invention was evaluated by studying the cell antiproliferative activity using CCK-8 assay.

[0139] The specific method is as follows: First, Hela, A549 or HCT-116 cells were inoculated into 96-well plates with 100 μL of culture medium per well at a density of 4000 cells per well, and incubated overnight at 37°C and 5% CO2. On the second day, 100 μL of the test compound prepared in culture medium at different concentrations was added to each well according to the plate map. Next, the cells were incubated at 37°C and 5% CO2 for 48 hours. After the 96-well plate was equilibrated to room temperature, 10 μL of CCK-8 was added to each well and shaken on an orbital shaker for 2 minutes to induce cell lysis. Incubate for 1.5 hours at 37°C and 5% CO2, measure the absorbance at 450 nm with a multifunction microplate reader (PerkinElmer), and calculate the IC using GraphPad Prism 6.0 software. 50 All experiments were performed with two parallel samples and repeated twice. 5-Fluorouracil (5-FU) was used as a positive control for the drug.

[0140] The anticancer activity results of some compounds are as follows:

[0141]

[0142]

[0143] The activity results show that the seven-ring compounds 3 and 4 containing azocine and indoline structural units provided by the present invention can inhibit the proliferation activity of three cancer cells, Hela, A549 and HCT-116, among which compounds 3a, 3d, 3g, 3h, 3i, 3k, 3n, 3o, 3q, 3r, 3s, 3t, 3u, 3v, 3w, 3x, 3y, 3z, 3ee, 3ff, 3kk, 4a, 3A and 3B have significant anti-proliferation activity against Hela and HCT-116 cancer cells; compounds 3a, 3g, 3h, 3i, 3k, 3n, 3o, 3r, 3s, 3u, 3v, 3w, 3x, 3y, 3z, 3kk and 4a have the effect of significantly inhibiting the proliferation of A549 cancer cells, indicating that the compounds have medicinal value for preventing, treating and inhibiting the progression of cancer, especially cervical cancer, lung cancer and colon cancer.

[0144] The above embodiments describe the basic principles, main features and advantages of the present invention. Those skilled in the art should understand that the present invention is not limited by the above embodiments, and the above embodiments and descriptions are only for explaining the principles of the present invention. Without departing from the scope of the principles of the present invention, the present invention may have various changes and improvements, and these changes and improvements all fall within the scope of protection of the present invention.

Claims

1. A seven-ring compound containing azcine and indoline structural units, characterized in that: Its chemical structure is as follows: Where: R 1 is phenyl, substituted phenyl or thienyl, the substituent on the substituted phenyl ring is C 1-4 Alkyl, C 1-4 Alkoxy, C 1-4 Alkylthio, phenyl, halogen, phenylethynyl or phenylthio, R 1 is a single or multiple substitution; R 2 For hydrogen, C 1-4 Alkyl, C 1-4 Alkoxy or halogen; R 3 is hydrogen or C 1-4 Alkyl, R 3 is a mono- or di-substituted; R 4 is hydrogen or C 1-4 Alkyl, R 4 is a mono- or di-substituted; R 5 For hydrogen, C 1-4 Alkyl, C 1-4 Alkoxy, C 1-4 Alkylthio, phenyl or halogen, R 5 It is a one- or multiple-element replacement.

2. Use of the seven-ring compound containing azocine and indoline structural units as claimed in claim 1 in the preparation of anticancer active drugs.

3. The use of the seven-ring compound containing azocine and indoline structural units in the preparation of anticancer active drugs according to claim 2, characterized in that: Anticancer activity is against cervical cancer, lung cancer and colon cancer.

4. The use of the seven-ring compound containing azocine and indoline structural units in the preparation of anticancer active drugs according to claim 3, characterized in that: The anti-cervical cancer, lung cancer and colon cancer correspond to the anti-Hela, A549 and HCT-116 cancer cells, respectively.

5. A pharmaceutical composition for treating cervical cancer, lung cancer and colon cancer, wherein the active ingredient comprises the seven-ring compound containing azocine and indoline structural units as claimed in claim 1.

6. The method for synthesizing the seven-ring compound 3 containing azocine and indoline structural units as claimed in claim 1, characterized in that: The method comprises the following steps: mixing an indolin-1-yl (aryl) azomethine compound 1, an indole dione compound 2, a catalyst, an additive and an organic solvent, and heating the mixture to react to obtain a seven-ring compound 3 containing azocine and indolinium structural units; the reaction equation is: Where: R 1 is phenyl, substituted phenyl or thienyl, the substituent on the substituted phenyl ring is C 1-4 Alkyl, C 1-4 Alkoxy, C 1-4 Alkylthio, phenyl, halogen, phenylethynyl or phenylthio, R 1 is a single or multiple substitution; R 2 For hydrogen, C 1-4 Alkyl, C 1-4 Alkoxy or halogen; R 3 is hydrogen or C 1-4 Alkyl, R 3 is a mono- or di-substituted; R 4 is hydrogen or C 1-4 Alkyl, R 4 is a mono- or di-substituted; R 5 For hydrogen, C 1-4 Alkyl, C 1-4 Alkoxy, C 1-4 Alkylthio, phenyl or halogen, R 5 It is a one- or multiple-element replacement.

7. The method for synthesizing the seven-ring compound 3 containing azocine and indoline structural units according to claim 6, characterized in that: The catalyst is selected from [RhCp*Cl2]2, [IrCp*Cl2]2 or [Ru(p-cymene)Cl2]2; the additive is silver hexafluoroantimonate, silver bis(trifluoromethanesulfonyl)imide, silver acetate, silver tetrafluoroborate, silver p-toluenesulfonate, silver trifluoromethanesulfonate, silver fluoride, silver trifluoroacetate or acetic acid; the organic solvent is selected from 1,2-dichloroethane, ethyl acetate, acetonitrile, toluene or dichloromethane.

8. The method for synthesizing the seven-ring compound 3 containing azocine and indoline structural units according to claim 6, characterized in that: The molar ratio of the indolin-1-yl (aryl) azomethine compound 1, the indole dione compound 2, the catalyst and the additive is 1:1.5-2.5:0.025-0.05:0.1-0.2; and the reaction temperature is 60-130°C.

9. The method for synthesizing the seven-ring compound 4 containing azocine and indoline structural units as claimed in claim 1, characterized in that: The method comprises the following steps: preparing a seven-ring compound 3 containing azocine and indoline structural units by the method described in any one of claims 6 to 8; then heating the seven-ring compound 3 containing azocine and indoline structural units in an organic solvent in the presence of an oxidant to obtain a seven-ring compound 4 containing azocine and indoline structural units; the reaction equation is: Where: R 1 -R 5 The substituents are the same as those in Example 6.

10. The method for synthesizing the seven-ring compound 4 containing azocine and indoline structural units according to claim 9, characterized in that: The oxidant is selected from manganese dioxide; the organic solvent is acetic acid; and the reaction temperature is 90-120°C.

Images