CN101565402B - Indeno isoquinolone compound and preparation method and medical application thereof - Google Patents

Indeno isoquinolone compound and preparation method and medical application thereof Download PDF

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CN101565402B
CN101565402B CN2009100278887A CN200910027888A CN101565402B CN 101565402 B CN101565402 B CN 101565402B CN 2009100278887 A CN2009100278887 A CN 2009100278887A CN 200910027888 A CN200910027888 A CN 200910027888A CN 101565402 B CN101565402 B CN 101565402B
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CN101565402A (en
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李志裕
王汝冰
刘潇
尤启冬
郭青龙
高源�
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China Pharmaceutical University
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China Pharmaceutical University
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Abstract

The invention relates to the field of pharmaceutical chemistry, in particular to indeno isoquinolone compounds (I) with antineoplastic activity, wherein the definitions of R[1], R[2], R[3], R[4] and nare shown in specifications. A pharmacological test proves that the compound has strong antineoplastic activity. The invention also relates to a method for preparing the indeno isoquinolone compoundsand antineoplastic application.

Description

Indenoisoquinoline ketone compound, its preparation method and medicinal use
Technical field
The present invention relates to the pharmaceutical chemistry field, be specifically related to the indenoisoquinoline ketone compound that a class has anti-tumor activity.
Background technology
Being applied to clinical Topo I inhibitor at present mainly is the derivative of camptothecine (CPT) class, as topotecan (Topotecan), irinotecan (Irinotecan) etc., although they have shown powerful therapeutic action for noumenal tumour, but still existing such as tumor response rate lowly, dose-limiting toxicities etc. are weak point obviously.Trace sth. to its source, just be that the CPT compound exists two defectives: the one, the unstable of its compound itself, in the pH of physiological condition value, exist the balance that open loop and closed loop transform mutually, the ring-opening product alcohol acid form of formation has high-affinity to human serum albumin; The 2nd, the ternary complex that CPT and Topo I, DNA form can be reversed after drug level reduces very soon, and this causes the increase of the administration frequency and time.In addition, have been found that resistance has appearred to some tumour in treatment to CPT, thereby this may be that the susceptibility of the sudden change reduction enzyme of Topo I to medicine has taken place, or the translocator BCRP on the cytolemma, MXR produces resistance thereby ABCG2 etc. can transport out the CPT compounds cell.
The more stable medicine of antitumor better, the chemical property of clinical needs own.
Summary of the invention
The invention discloses a class indenoisoquinoline ketone compound, pharmacological evaluation proves, this compounds has good anti-tumor activity, part of compounds of the present invention has stronger anti-tumor activity than camptothecine (CPT) and other camptothecin derivatives, better blood stability, littler toxic side effect.Product with preparation method's preparation of the present invention is easy and simple to handle, and product postprocessing is simple, and yield is higher.
Structural formula of compound general formula of the present invention is as follows:
Figure G2009100278887D00011
R wherein 1Represent nitro, amino, methoxyl group or acetamido;
R 2Represent hydrogen, hydroxyl, methoxyl group, fluorine, chlorine, bromine, amino, itrile group, methylol, aldehyde radical or carboxyl;
R 3Represent hydrogen, hydroxyl, methoxyl group, halogen, amino, itrile group, aldehyde radical or carboxyl;
R 2And R 3Can also form the ether, five yuan of five yuan or six-ring or the lactone of six-ring together;
R 4Represent morpholinyl, imidazolyl, pyrrolidyl, piperazinyl, methylpiperazine base, alcohol amido, diethanolamino, ethyl piperazidine base, C 1-4The alkyl amino or the C that replace 2-4The alkylene substituted-amino;
n＝1-4。
N preferably represents 3.
R 2Preferred representation methoxy, fluorine or chlorine.
R 3The preferred hydrogen of representing.
R 2And R 3The preferred ether that forms five yuan or six-ring together, R 2And R 3Also preferably form the lactone of five yuan or six-ring together.
R 4Preferred morpholinyl, imidazolyl, alcohol amido, pyrrolidyl, piperazinyl or the methylpiperazine base represented.。The preferred structural formula of compound of part is as follows:
Compound of the present invention can also exist with the form of pharmacy acceptable salt, and preferred salt is acetate, hydrochloride, vitriol or phosphoric acid salt.
Compound of the present invention can prepare in order to the below method:
Figure G2009100278887D00031
R wherein 1, R 2, R 3, R 4, n definition the same.
Be the part pharmacology test and the result of The compounds of this invention below.
The structure of the compound code name correspondence of pharmacological testing part sees Table 1, and these code names are not corresponding with code name among the embodiment.
Figure G2009100278887D00032
The structure of table 1 part of compounds code name correspondence
Figure G2009100278887D00033
The antitumor test of compound:
Measure and adopt bromination tetrazole indigo plant (MTT) method routinely, screened human breast cell's strain (231), human hepatoma cell strain (Hepg2), human colon cancer cell strain (CACO-2).The activity that this method has been widely used in some biologically active factorss detects, large-scale screening anti-tumor medicine, cell toxicity test and tumor radiosensitivity mensuration etc.Positive control is topotecan (TPT), 10-hydroxycamptothecine (HCPT), and these two kinds is widely used clinically at present antitumor drug.
Tested its activity with the method for tumour cell in-vitro screening.Three kinds of cell strains have been screened: human breast cancer cell strain (231), human hepatoma cell strain (Hepg2), human colon cancer cell strain (CACO-2).Measure bromination tetrazole indigo plant (MTT) method that adopts routinely.Succinodehydrogenase in the viable cell plastosome can make exogenous bromination tetrazole be reduced to the bluish voilet crystallisate of insoluble and be deposited in the cell, and dead cell does not have this function.Purple crystal thing in the dimethyl sulfoxide (DMSO) energy dissolved cell is measured its absorbance value with enzyme-linked immunosorbent assay instrument at 570nm wavelength place, can reflect viable cell quantity indirectly.The activity that this method has been widely used in some biologically active factorss detects, large-scale screening anti-tumor medicine, cell toxicity test and tumor radiosensitivity mensuration etc.Cell inhibitory rate calculates
Inhibiting rate=(the average OD value of the control group-average OD value of administration group)/average OD value of control group
Be the IC of part of compounds below 50Value:
Table 2 antitumor activity of compound (IC 50Value, μ mol/L)
Figure G2009100278887D00041
Note: only to primary dcreening operation as a result cell inhibitory rate calculate IC more than or equal to 50% compound 50.IC 50The value unit: μ mol, " * " be expressed as primary dcreening operation as a result cell inhibitory rate can't calculate IC less than 50% 50Value.
Above-mentioned pharmacology test shows, compound of the present invention all shows well the inhibition activity of antitumor cell, can be used for treating tumor disease, and preferred tumor disease is cancer of the stomach, mammary cancer, liver cancer or colorectal carcinoma.
The present invention also provides the medicinal compositions that comprises with acceptable carrier combinations pharmaceutically or bonded The compounds of this invention.Say in more detail, the invention provides a kind of medicinal compositions, wherein contain The compounds of this invention or its pharmacy acceptable salt and the pharmaceutically acceptable carrier of treatment.Wherein The compounds of this invention also can exist with the form of pharmacy acceptable salt.
The compounds of this invention can be made preparation for administration separately or with one or more pharmaceutically acceptable carrier combinations.For example, solvent, thinner etc., but can use tablet, capsule dispersed powders, granule, injection formulation.Can contain for example activeconstituents of 0.05% to 90% weight with carrier combinations in these medicinal preparationss, the activeconstituents of weight between more common about 15% to 60%.The compounds of this invention dosage can be 0.001～100mg/kg/ days, also can depart from this dosage range according to the difference of disease degree or the difference of formulation.
Embodiment
Embodiment 1
The preparation of 3-nitro-6-(3-chloropropyl)-9-fluoro-5H--indeno [1,2-c] isoquinoline 99.9-5,11 (6H)-diketone (compound 1)
In reaction flask, add successively 4.2g (0.01mol) suitable-2-(3-chloropropyl)-3-(4-fluorophenyl)-7-nitro-1,2,3,4-tetrahydroisoquinoline-1-ketone-4-carboxylic acid, 160ml dry toluene and 13ml SOCl 2, stirring, about 1h that refluxes after the dissolving, removes toluene and SOCl under reduced pressure fully 2, adding 120ml oil of mirbane, the ice bath temperature control adds 3.7gAlCl down 3, after a quarter, remove ice bath, 100 ℃ of reaction 1h, reaction is finished, and adds water 560ml, CH 2Cl 2It is colourless substantially to be extracted to water layer, merges organic layer, uses NaHCO successively 3Saturated solution, the washing of NaCl saturated solution remove CH under reduced pressure after the organic layer drying 2Cl 2, add about 500ml hexanaphthene, leave standstill, suction filtration, the filter cake oven dry gets bright red solid 1.96g, yield 49.1%.mp258-260℃；IR(KBr)：3078，2962，1678，1502，1336，804cm -1； 1H-NMR(300MHz，DMSO-d 6)：δ8.89(s，1H，Ar-H)，8.70(d，2H，J＝9Hz?Ar-H)，8.59(t，J＝8.7Hz，1H，Ar-H)，7.554(d，1H，J＝5.4Hz，Ar-H)，7.532(m，1H，J＝7.1Hz，Ar-H)，4.63(t，2H，J＝7.5Hz，CON-CH 2-)，3.90(t，2H，J＝6.6Hz，-CH 2-Cl)，2.28(t，2H，J＝6.0Hz-CH 2-C H 2-CH 2-)；MS-EI(m/z)：386[M] +
Embodiment 2
The preparation of 3-nitro-9-fluoro-6-(3-methylpiperazine base propyl group)-5H-indeno [1,2-c] isoquinoline 99.9-5,11 (6H)-diketone (compound 2)
In reaction flask, drop into 0.10g (0.259mmol) compound 1,0.07g (0.7mmol) methylpiperazine, 0.21g (1.52mmol) anhydrous K successively 2CO 3, about 30ml dioxane and a little NaI, 100 ℃ of stirring reaction 24h.Remove solvent under reduced pressure, the chloroform recrystallization gets orange solid 0.10g, yield 85.8%.mp236-239℃；IR(KBr)：3415，2816，1667，1613，1500，1347，795cm-1；1H-NMR(300MHz，CDCl3)：δ9.16(s，1H，Ar-H)，8.82(d，1H，J＝8.7Hz，Ar-H)，8.49(dd，1H，J＝8.7Hz，Ar-H)，7.94(dd，1H，J＝8.4Hz，Ar-H)，7.43(dd，1H，J＝6.6Hz?Ar-H)，7.21(m，1H，Ar-H)，4.64(t，2H，J＝7.8Hz，CON-CH 2-)，2.61(br，13H，piperazine-H)，2.04(m，2H，-CH 2-C H 2-CH 2-)；EI-MS(m/z)：450[M] +
Embodiment 3
The preparation of 3-nitro-9-fluoro-6-(3-alcohol amido propyl group)-5H-indeno [1,2-c] isoquinoline 99.9-5,11 (6H)-diketone (compound 3)
In reaction flask, drop into 0.12g (0.310mmol) compound 1,0.027g (0.443mmol) thanomin, 0.08g (0.580mmol) anhydrous K successively 2CO 3, about 20ml dioxane and a little NaI, 100 ℃ of stirring reaction 24h.Reaction finishes, suction filtration, and filtrate decompression is steamed and is desolventized, and the chloroform recrystallization gets product 0.06g, yield 47.0%.mp283-285℃；IR(KBr)：3417，2961，1687，1611，1504，1338，801cm -1； 1H-NMR(300MHz，DMSO-d 6)δ：8.88(d，1H，J＝2.1Hz，Ar-H)，8.70(d，1H，J＝8.1Hz，Ar-H)，8.60(m，1H，Ar-H)，7.98(m，1H，Ar-H)，7.56(m，1H，Ar-H)，7.49(m，1H，Ar-H)，5.22(s，1H，-N HCH 2CH 2OH)，4.58(t，2H，J＝7.5Hz，-CON-C H 2 -)，3.62(s，2H，-NHCH 2C H 2OH)，3.14(s，2H，-NHC H 2CH 2OH)，2.98(t，2H，-CH 2-CH 2-C H 2N-)，2.19(s，2H，-CH 2-C H 2-CH 2-)；MS(EI)m/z：393[M-18] +
Embodiment 4
The preparation of 3-nitro-6-(3-methylpiperazine base propyl group)-9-fluoro-5H-indeno [1,2-c] isoquinoline 99.9-5,11 (6H)-diketone (compound 4)
In reaction flask, drop into 0.10g (0.259mmol) compound 1,0.07g (0.7mmol) methylpiperazine, 0.21g (1.52mmol) anhydrous K successively 2CO 3, about 30ml dioxane and a little NaI, 100 ℃ of stirring reaction 24h.Reaction finishes, suction filtration, and filtrate decompression is steamed and is desolventized, and the chloroform recrystallization gets product 0.10g, yield 85.8%.mp236-239℃；IR(KBr)：3415，2816，1667，1613，1500，1347，795cm -1； 1H-NMR(300MHz，CDCl 3)：δ9.16(s，1H，Ar-H)，8.82(d，1H，J＝8.7Hz，Ar-H)，8.49(dd，1H，J＝8.7Hz，Ar-H)，7.94(dd，1H，J＝8.4Hz，Ar-H)，7.43(dd，1H，J＝6.6Hz?Ar-H)，7.21(m，1H，Ar-H)，4.64(t，2H，J＝7.8Hz，CON-CH 2-)，2.61(br，13H，piperazine-H)，2.04(m，2H，-CH 2-C h 2-CH 2-)；EI-MS(m/z)：450[M] +
Embodiment 5
The preparation of 3-nitro-6-(3-(1-1H-imidazolyl) propyl group)-9-fluoro-5H-indeno [1,2-c] isoquinoline 99.9-5,11 (6H)-diketone (compound 5)
In reaction flask, drop into 0.20g (0.517mmol) compound 1,0.09g (1.32mmol) imidazoles, 0.29g (2.10mmol) anhydrous K successively 2CO 3, about 25ml dioxane and a little TBAI, 100 ℃ of stirring reaction 24h.Reaction finishes, suction filtration, and filtrate decompression is steamed and is desolventized, and the chloroform recrystallization gets product 0.15g, yield 42.5%.mp269-272 ℃; IR (KBr): 3480,2961,1658,1612,1490,1337,804cm -1 1H-NMR (300MHz, DMSO-d 6): δ 8.88 (d, J=1.8Hz, 1H, Ar-H), 8.70 (d, 1H, J=9.3Hz, Ar-H), 8.59 (dd, 1H, J=8.7Hz, Ar-H), 7.73 (s, 1H, Ar-H), 7.53 (dd, 1H, J=5.4Hz, Ar-H), 7.39 (dd, 1H, J=6.9Hz, Ar-H), 7.39 (s, 2H, imidazole-H), 6.96 (s, 1H, imidazole-H), 4.51 (t, 2H, J=6.3Hz, CON-CH 2-), 3.53 (t, 2H, J=6Hz, imidazole-C H 2), 2.26 (m, 2H ,-CH 2-C H 2-CH 2-); EI-MS (m/z): 418[M] +
Embodiment 6
The preparation of 3-nitro-6-(3-diisopropylaminoethyl propyl group)-9-fluoro-5H-indeno [1,2-c] isoquinoline 99.9-5,11 (6H)-diketone (compound 6)
In reaction flask, drop into 0.15g (0.388mmol) compound 1,0.106g (0.99mmol) Diisopropylamine, 0.32g (2.32mmol) anhydrous K successively 2CO 3, about 30ml dioxane and a little NaI, 100 ℃ of stirring reaction 24h reactions finish, suction filtration, filtrate decompression is steamed and is desolventized, the chloroform recrystallization gets product 0.07g, yield 40.0%.mp218-222 ℃; IR (KBr): 3467,3417,2963,1678,1613,1510,1336,803cm -1 1H-NMR (300MHz, CDCl 3): δ 9.09 (s, 1H, Ar-H), 8.72 (d, 2H, J=8.7Hz, Ar-H), 8.40 (d, J=9Hz, 1H, Ar-H), 8.0 (s, 1H, Ar-H), 7.32 (d, 1H, J=6.3Hz, Ar-H), 7.08 (d, 1H, J=8.4Hz, Ar-H), 4.48 (t, 2H, J=8.1Hz, CON-CH 2-), 3.05 (s, 2H ,-CH 2-CH 2-CH 2 -N-), 2.65 (s, 2H ,-C H(CH 3) 2* 2), 1.90 (s, 2H ,-CH 2-C H 2-CH 2-), 1.04 (s, 12H ,-CH (C H 3) * 2); MS-EI (m/z): 451[M] +
Embodiment 7
The preparation of 3-nitro-6-(3-diethylin propyl group)-9-fluorine 5H--indeno [1,2-c] isoquinoline 99.9-5,11 (6H)-diketone (compound 7)
In reaction flask, drop into 0.16g (0.414mmol) compound 1,0.14g (1.656mmol) diethylamine, 0.32g (2.32mmol) anhydrous K successively 2CO 3, about 30ml dioxane and a little NaI, 100 ℃ of stirring reaction 24h.Reaction finishes, suction filtration, and filtrate decompression is steamed and is desolventized, and the chloroform recrystallization gets product 0.10g, yield 57.1%.mp225-228℃；IR(KBr)：3439，2971，1673，1612，1502，1349，802cm -1； 1H-NMR(300MHz，CDCl 3)：δ9.09(s，1H，Ar-H)，8.72(d，2H，J＝3Hz，Ar-H)，8.43(dd，1H，J＝9Hz，Ar-H)，8.09(dd，1H J＝8.4Hz，，Ar-H)，7.34(dd，1H，J＝6.9Hz，Ar-H)，7.08(m，1H，Ar-H)，4.54(t，2H，J＝8.4Hz，CON-CH 2-)，2.59(m，6H，-CH 2-C H 2-N(C H 2CH 3) 2-)，1.94(s，2H，-CH 2-C H 2-CH 2-)；EI-MS(m/z)：423[M] +
Embodiment 8
The preparation of 3-nitro-6-(3-diethanolamino propyl group)-9-fluoro-5H-indeno [1,2-c] isoquinoline 99.9-5,11 (6H)-diketone (compound 8)
In reaction flask, drop into 0.30g (0.776mmol) compound 1,0.45g (4.29mmol) diethanolamine, 0.74g (5.36mmol) anhydrous K successively 2CO 3, about 30ml dioxane and a little NaI, 100 ℃ of stirring reaction 24h.Reaction finishes, suction filtration, and filtrate decompression is steamed and is desolventized, and the chloroform recrystallization gets product 0.15g, yield 42.5%.mp207-209℃；IR(KBr)：3371，2922，1671，1611，1504，1335，805cm -1； 1H-NMR(300MHz，DMSO-d 6)：δ8.87(d，J＝2.4Hz?1H，Ar-H)，8.68(d，1H，J＝9Hz，Ar-H)，8.57(dd，1H，J＝8.7Hz，Ar-H)，8.12(t，1H?J＝4.2Hz，，Ar-H)，7.52(m，2H，Ar-H)，4.54(s，2H，CH 2C H 2OH)，4.45(t，2H，J＝4.8Hz，CON-CH 2-)，3.53(m，4H，-N(CH 2C H 2OH) 2)，2.72(s，2H，-CH 2-CH 2-C H 2N-)，2.60(t，4H，J＝6Hz，-N(C H 2CH 2OH) 2)，1.89(s，2H，-CH 2-CH 2-C H 2-)；MS-EI(m/z)：424[M-31] +
Embodiment 9
The preparation of 3-nitro-6-(3-chloropropyl)-9-chloro-5H--indeno [1,2-c] isoquinoline 99.9-5,11 (6H)-diketone (compound 9)
In reaction flask, add successively 3.5g (8.2mmol) suitable-2-(3-chloropropyl)-3-(4-fluorophenyl)-7-nitro-1,2,3,4-tetrahydroisoquinoline-1-ketone-4-carboxylic acid, 120ml dry toluene and 10ml SOCl 2, stirring, about 1h that refluxes after the dissolving, removes toluene and SOCl under reduced pressure fully 2, adding 80ml oil of mirbane, the ice bath temperature control adds 3.1g AlCl down 3, after a quarter, remove ice bath, 100 ℃ of reaction 1h, reaction is finished, and adds water 200ml, CH 2Cl 2It is colourless substantially to be extracted to water layer, merges organic layer, uses NaHCO successively 3Saturated solution, the washing of NaCl saturated solution remove CH under reduced pressure after the organic layer drying 2Cl 2, add about 500ml hexanaphthene, leave standstill, suction filtration, the filter cake oven dry gets vermilion red solid 1.64g, yield 49.7%.mp266-268℃；IR(KBr)：2962，1679，1608，1505，1338，1193，743，842cm -1； 1H-NMR(300MHz，DMSO-d 6)：δ9.22(s，1H，Ar-H)，8.78(d，1H，J＝9Hz?Ar-H)，8.44(dd，1H，J＝9Hz，Ar-H)，7.78(d，1H，J＝8.1Hz，Ar-H)，7.61(d，1H，J＝1.8Hz，Ar-H)，7.48(m，1H，Ar-H)，4.64(t，2H，J＝8.1Hz，CON-CH 2-)，3.78(t，2H，J＝6.0Hz，-CH 2-Cl)，2.28(m，2H，-CH 2-C H 2-CH 2-)；MS-EI(m/z)：402[M] +
Embodiment 10
The preparation of 3-nitro-6-(morpholinyl propyl group)-9-chloro-5H--indeno [1,2-c] isoquinoline 99.9-5,11 (6H)-diketone (compound 10)
In reaction flask, drop into 0.10g (0.249mmol) compound 9,0.06g (0.71mmol) morpholine, 0.21g (1.52mmol) anhydrous K successively 2CO 3, about 25ml dioxane and a little NaI, 100 ℃ of stirring reaction 24h.Reaction finishes, suction filtration, and filtrate decompression is steamed and is desolventized, and the chloroform recrystallization gets product 0.09g, yield 79.8%.mp270-273 ℃; IR (KBr): 3415,3467,2836,1673,1608,1505,1332,1116,854,747cm -1 1H-NMR (300MHz, CDCl 3): δ 9.19 (d, 1H, J=2.1Hz, Ar-H), 8.84 (d, 1H, J=9Hz, Ar-H), 8.51 (dd, 1H, J=8.7Hz, Ar-H), 7.85 (d, 1H, J=8.1Hz, Ar-H), 7.68 (s, 1H, Ar-H), 7.49 (d, 1H, J=5.4Hz, Ar-H), 4.64 (t, 2H, J=8.1Hz, CON-CH 2-), 3.71 (s, 4H ,-C H 2-O-C H 2-), 2.55 (m, 6H ,-C H 2N (C H 2) 2), 2.05 (s, 2H ,-CH 2-C H 2-CH 2-); MS-EI (m/z): 453[M] +
Embodiment 11
The preparation of 3-nitro-6-(3-Tri N-Propyl Amine base propyl group)-9-chloro-5H--indeno [1,2-c] isoquinoline 99.9-5,11 (6H)-diketone (compound 11)
In reaction flask, drop into 0.11g (0.274mmol) compound 9,0.04g (0.68mmol) Tri N-Propyl Amine, 0.23g (1.67mmol) anhydrous K successively 2CO 3, about 30ml dioxane and a little NaI, 100 ℃ of stirring reaction 24h.Reaction finishes, suction filtration, and filtrate decompression is steamed and is desolventized, and the chloroform recrystallization gets product 0.05g, yield 42.93%.mp210-213 ℃; IR (KBr): 3417,2935,1678,1504,1339,792,750cm -1 1H-NMR (300MHz, DMSO-d 6): δ 8.86 (d, J=2.1Hz, 1H, Ar-H), 8.70 (dd, 1H, J=9Hz, Ar-H), 8.56 (dd, 1H, J=8.7Hz, Ar-H), 8.06 (d, J=7.5Hz, 1H, Ar-H), 7.65 (m, 2H, Ar-H), 4.53 (t, 2H, J=7.8Hz, CON-CH 2-), 2.76 (t, 2H, J=6Hz ,-CH 2-CH 2-C H 2-N-), 2.51. (t, 2H, J=6Hz ,-N-C H 2-CH 2-CH 3), 1.95 (m, 2H ,-CH 2-C H 2-CH 2-N-), 1.45 (m, 2H ,-N-CH 2-C H 2-CH 3), 0.88 (t, 3H, J=6.6Hz ,-N-CH 2-CH 2-C H 3); MS-EI (m/z): 425[M] +
Embodiment 12
The preparation of 3-nitro-6-(3-diethylin propyl group)-9-chloro-5H--indeno [1,2-c] isoquinoline 99.9-5,11 (6H)-diketone (compound 12)
In reaction flask, drop into 0.10g (0.249mmol) compound 9,0.05g (0.69mmol) diethylamine, 0.22g (1.59mmol) anhydrous K successively 2CO 3, about 30ml dioxane and a little NaI, 100 ℃ of stirring reaction 24h.Reaction finishes, suction filtration, and filtrate decompression is steamed and is desolventized, and the chloroform recrystallization gets product 0.07g, yield 64.0%.mp237-239 ℃; IR (KBr): 3466,3415,2966,1671,1503,1345,1092,795cm -1 1H-NMR (300MHz, CDCl 3): δ 9.2 (d, J=2.4Hz, 1H, Ar-H), 8.81 (dd, 1H, J=9Hz, Ar-H), 8.49 (dd, 1H, J=9Hz, Ar-H), 8.12 (dd, J=8.1Hz, 1H, Ar-H), 7.65 (d, 1H, J=2.1Hz, Ar-H), 7.47 (dd, 1H, J=8.1Hz, Ar-H), 4.58 (t, 2H, J=8.7Hz, CON-CH 2-), 2.61 (m, 6H ,-C H 2N (C H 2CH 3) 2), 1.99. (s, 2H ,-CH 2-C H 2-CH 2), 1.09 (t, 6H, J=6.6Hz ,-N-(CH 2-C H 3) 2), MS-EI (m/z): 439[M] +
Embodiment 13
The preparation of 3-nitro-6-(3-imidazolyl propyl group)-9-chloro-5H--indeno [1,2-c] isoquinoline 99.9-5,11 (6H)-diketone (compound 13)
In reaction flask, drop into 0.15g (0.373mmol) compound 9,0.06g (0.88mmol) imidazoles, 0.31g (2.24mmol) anhydrous K successively 2CO 3, about 30ml dioxane and a little NaI, 100 ℃ of stirring reaction 24h.Remove solvent under reduced pressure, the chloroform recrystallization gets orange solid 0.07g, yield 43.2%.mp267-270 ℃; IR (KBr): 3415,3467,1676,1504,1338,1082,748cm -1 1H-NMR (300MHz, CDCl 3): δ 9.2 (d, 1H, J=2.1Hz, Ar-H), 8.83 (d, 1H, J=9Hz, Ar-H), 8.51 (dd, 1H, J=8.7Hz, Ar-H), 7.63 (m,, 2H, Ar-H), 7.33 (d, 1H, J=1.8Hz, Ar-H), 7.30 (d, J=2.1Hz, 1H, imidazole-H), 7.07 (s, 1H, imidazole-H), 6.45 (d, 1H, J=8.1Hz, imidazole-H), 4.52 (t, 2H, J=8.1Hz, CON-CH 2-), 4.28 (t, 2H, J=6.0Hz ,-CH 2-CH 2-C H 2-Cl), 2.36 (m, 2H ,-CH 2-C H 2-CH 2-Cl); MS-EI (m/z): 434[M] +
Embodiment 14
The preparation of 3-nitro-6-(3-methylpiperazine base propyl group)-9-chloro-5H--indeno [1,2-c] isoquinoline 99.9-5,11 (6H)-diketone (compound 14)
In reaction flask, drop into 0.09g (0.224mmol) compound 9,0.06g (0.60mmol) methylpiperazine, 0.18g (1.81mmol) anhydrous K successively 2CO 3, about 20ml dioxane and a little NaI, 100 ℃ of stirring reaction 24h.Suction filtration removes solvent under reduced pressure, and the chloroform recrystallization gets orange solid 0.09g, yield 86.2%.mp235-239 ℃; IR (KBr): 3415,2816,1667,1613,1500,1347,795cm -1 1H-NMR (300MHz, CDCl 3): δ 9.18 (d, 1H, J=2.1Hz, Ar-H), 8.82 (d, 1H, J=9Hz, Ar-H), 8.49 (dd, 1H, J=9Hz, Ar-H), 7.84 (dd, 1H, J=8.1Hz, Ar-H), 7.66 (d, 1H, J=1.8Hz, Ar-H), 7.48 (dd, 1H, J=8.1Hz, Ar-H), 4.62 (t, 2H, J=7.8Hz, CON-CH 2-), 2.60 (br, 13H, piperazine-H), 2.04 (m, 2H ,-CH 2-C H 2-CH 2-); MS-EI (m/z): 466[M] +
Embodiment 15
The preparation of 3-nitro-6-(3-chloropropyl)-9-methoxyl group-5H--indeno [1,2-c] isoquinoline 99.9-5,11 (6H)-diketone (compound 15)
In reaction flask, add successively 3.6g (9.0mmol) suitable-2-(3-chloropropyl)-3-(4-fluorophenyl)-7-nitro-1,2,3,4-tetrahydroisoquinoline-1-ketone-4-carboxylic acid, 120ml dry toluene and 11ml SOCl 2, stirring, about 1h that refluxes after the dissolving, removes toluene and SOCl under reduced pressure fully 2, adding 100ml oil of mirbane, the ice bath temperature control adds 3.5gAlCl down 3, after a quarter, remove ice bath, 100 ℃ of reaction 1h, reaction is finished, and adds water 250ml, CH 2Cl 2It is colourless substantially to be extracted to water layer, merges organic layer, uses NaHCO successively 3Saturated solution, the washing of NaCl saturated solution remove CH under reduced pressure after the organic layer drying 2Cl 2, add about 500ml hexanaphthene, leave standstill, suction filtration, the filter cake oven dry gets red solid 1.81g, yield 50.5%.mp287-289℃；IR(KBr)：2872，1664，1493，1268，1120，754cm -1； 1H-NMR(300MHz，DMSO-d 6)：δ9.17(s，1H，Ar-H)，8.81(d，1H，J＝9Hz?Ar-H)，8.47(d，J＝7.5Hz，1H，Ar-H)，7.79(d，1H，J＝8.4Hz，Ar-H)，7.27(s，1H，Ar-H)，6.94(d，1H，J＝8.1Hz，Ar-H)，4.69(t，2H，J＝7.8Hz，CON-CH 2-)，3.93(s，3H，-OC H 3)，3.84(t，2H，J＝5.4Hz，-CH 2-Cl)，2.40(m，2H，-CH 2-C H 2-CH 2-)；MS-EI(m/z)：398[M] +
Embodiment 16
The preparation of 3-nitro-6-(3-methylpiperazine base propyl group)-9-methoxyl group-5H--indeno [1,2-c] isoquinoline 99.9-5,11 (6H)-diketone (compound 16)
In reaction flask, drop into 0.08g (0.20mmol) compound 15,0.06g (0.69mmol) methylpiperazine, 0.17g (1.23mmol) anhydrous K successively 2CO 3, about 30ml dioxane and a little NaI, 100 ℃ of stirring reaction 24h.Remove solvent under reduced pressure, add an amount of chloroform dissolving, filter, filtrate decompression is steamed and is desolventized, and the chloroform recrystallization gets orange solid 0.08g, yield 86.1%.mp197-199 ℃; IR (KBr): 3466,3417,2840,1675,1609,1506,1332,1121,853,791cm -1 1H-NMR (300MHz, CDCl 3): δ 9.16 (d, 1H, J=1.8Hz, Ar-H), 8.78 (dd, 1H, J=9Hz, Ar-H), 8.44 (dd, 1H, J=8.7Hz, Ar-H), 7.76 (dd, 1H, J=8.4Hz, Ar-H), 7.26 (s, 1H, Ar-H), 6.92 (dd, 1H, J=8.4Hz, Ar-H), 4.60 (t, 2H, J=7.5Hz, CON-CH 2-), 3.94 (s, 3H ,-OCH 3), 2.51 (br, 13H, piperazine-H), 2.06 (m, 2H ,-CH 2-C H 2-CH 2-); MS-EI (m/z): 462[M] +
Embodiment 17
The preparation of 3-nitro-6-(3-pyrrolidyl propyl group)-9-methoxyl group-5H--indeno [1,2-c] isoquinoline 99.9-5,11 (6H)-diketone (compound 17)
In reaction flask, drop into 0.10g (0.25mmol) compound 8-c (V-1), 0.05g (0.70mmol) tetramethyleneimine, 0.21g (1.52mmol) anhydrous K successively 2CO 3, about 30ml dioxane and a little NaI, 100 ℃ of stirring reaction 24h.Reaction finishes, suction filtration, and filtrate decompression is steamed and is desolventized, and the chloroform recrystallization gets product 0.09g, yield 83.14%.mp224-226 ℃; IR (KBr): 3469,3414,2955,1678,1612,1507,1334,1228,846,792cm -1 1H-NMR (300MHz, CDCl 3): δ 9.15 (d, 1H, J=2.4Hz, Ar-H), 8.77 (dd, 1H, J=9Hz, Ar-H), 8.44 (dd, 1H, J=9Hz, Ar-H), 7.80 (dd, 1H, J=8.7Hz Ar-H), 7.25 (s, 1H, Ar-H), 6.90 (dd, 1H, J=8.4Hz, Ar-H), 4.60 (t, 2H, J=7.8Hz, CON-CH 2-), 2.98 (s, 3H ,-OCH 3), 2.74 (m, 6H ,-C H 2-N-(C H 2) 2-), 2.14 (m, 2H ,-CH 2C H 2CH 2-), 1.83 (m, 4H ,-C H 2N-C H 2-); MS-EI (m/z): 433[M] +
Embodiment 18
The preparation of 3-nitro-6-(3-Tri N-Propyl Amine base propyl group)-9-methoxyl group-5H--indeno [1,2-c] isoquinoline 99.9-5,11 (6H)-diketone (compound)
In reaction flask, drop into 0.12g (0.30mmol) compound 15,0.05g (0.85mmol) Tri N-Propyl Amine, 0.25g (1.80mmol) anhydrous K successively 2CO 3, about 30ml dioxane and a little NaI, 100 ℃ of stirring reaction 24h.Reaction finishes, suction filtration, and filtrate decompression is steamed and is desolventized, and the chloroform recrystallization gets product 0.05g, yield 39.5%.mp210-213 ℃; IR (KBr): 3465,3419,2940,1670,1612,1331,1080,789cm -1 1H-NMR (300MHz, CDCl 3): δ 9.14 (d, J=2.1Hz, 1H, Ar-H), 8.75 (dd, 1H, J=9Hz, Ar-H), 8.43 (dd, 1H, J=9Hz, Ar-H), 7.84 (dd, J=8.4Hz, 1H, Ar-H), 7.65 (d, 1H, J=2.4Hz, Ar-H), 6.88 (dd, 1H, J=8.4Hz, Ar-H), 4.60 (t, 2H, J=7.8Hz, CON-CH 2-), 3.91 (s, 3H ,-OCH 3), 2.83 (t, 2H, J=6Hz ,-CH 2-CH 2-C H 2N-), 2.62. (t, 2H, J=7.2Hz ,-N-C H 2-CH 2-CH 3), 2.03 (m, 2H ,-CH 2-C H 2-CH 2-), 1.56 (m, 2H ,-N-CH 2-C H 2-CH 3), 0.88 (t, 3H, J=7.2Hz ,-N-CH 2-CH 2-C H 3); MS-EI (m/z): 421[M] +
Embodiment 19
The preparation of 3-amino-6-(3-chloropropyl)-9-fluoro-5H--indeno [1,2-c] isoquinoline 99.9-5,11 (6H)-diketone (compound 19)
In reaction flask, add the iron powder that 2.2g (5.6mmol) compound 1,2.6 (46mmol) g handled successively, 32ml (0.55mol) Glacial acetic acid, DMF 350ml, 68 ℃ were reacted 10 hours, and reaction finishes, suction filtration, filtrate decompression is steamed and is desolventized, and ethyl alcohol recrystallization gets product 1.84g, yield 90.6%.mp176-179℃；IR(KBr)：3415，1650，1580，1285，788； 1H-NMR(300MHz，DMSO-d 6)：δ8.22(d，1H，J＝8.7Hz，，Ar-H)，7.66(dd，1H，J＝7.5Hz，Ar-H)，7.29(m，3H，Ar-H)，7.08(dd，1H，J＝8.7Hz，Ar-H)，5.76(s，2H，Ar-N H 2)，4.51(t，2H，J＝7.2Hz，CON-CH 2-)，3.86(t，2H，J＝6.3Hz，-CH 2-Cl)，2.22(t，2H，J＝6.6Hz，-CH 2-C H 2-CH 2-)；MS-EI(m/z)：356[M] +
Embodiment 20
The preparation of 3-amino-6-(3-methylpiperazine base propyl group)-9-fluoro-5H-indeno [1,2-c] isoquinoline 99.9-5,11 (6H)-diketone (compound 20)
In reaction flask, drop into 0.08g (0.217mmol) compound 19,0.06g (0.6mmol) methylpiperazine, 0.18g (1.3mmol) anhydrous K successively 2CO 3, about 30ml dioxane and a little NaI, 100 ℃ of stirring reaction 24h.Reaction finishes, suction filtration, and filtrate decompression is steamed and is desolventized, and ethyl alcohol recrystallization gets product 0.08g, yield 85.3%.mp240-242℃；IR(KBr)：3412，3327，1646，1449，1291，831，794cm -1； 1H-NMR(300MHz，DMSO-d 6)：δ8.23(d，1H，J＝8.7Hz，Ar-H)，7.73(m，1H，Ar-H)，7.31(m，3H，Ar-H)，7.09(dd，J＝8.7Hz，1H)，5.78(s，2H，Ar-N H 2)，4.45(t?J＝6.6Hz，2H，CON-CH 2-)，2.61(br，13H，piperazine-H)，1.96(s，2H，-CH 2-C H 2-CH 2-)；EI-MS(m/z)：420[M] +
Embodiment 21
The preparation of 3-amino-6-(3-diethanolamino propyl group)-9-fluoro-5H-indeno [1,2-c] isoquinoline 99.9-5,11 (6H)-diketone (compound 21)
In reaction flask, drop into 0.10g (0.28mmol) compound 19,0.16g (1.52mmol) diethanolamine, 0.25g (1.81mmol) anhydrous K successively 2CO 3, about 30ml dioxane and a little NaI, 100 ℃ of stirring reaction 24h.Reaction finishes, suction filtration, and filtrate decompression is steamed and is desolventized, and ethyl alcohol recrystallization gets product 0.06g, yield 50.4%.mp245-247 ℃; IR (KBr): 3419,1645,1583,1208,1068,794; 1H-NMR (300MHz, DMSO-d 6): δ 8.24 (d, 1H, J=8.7Hz,, Ar-H), 7.75 (dd, 1H, J=7.5Hz, Ar-H), 7.29 (m, 3H, Ar-H), 7.10 (d, 1H, J=6.6Hz, Ar-H), 5.79 (s, 2H, Ar-N H 2), 4.43 (s, 2H, CON-CH 2-), 3.52 (s, 2H ,-CH 2-Cl), 3.08 (s, 4H ,-N-CH 2-C H 2-OH), 2.70 (s, 4H ,-N-C H 2-CH 2-OH), 2.22 (s, 2H ,-CH 2-C H 2-CH 2-); MS-EI (m/z): 394[M-36] +
Embodiment 22
The preparation of 3-amino-6-(3-pyrrolidyl propyl group)-9-fluoro-5H-indeno [1,2-c] isoquinoline 99.9-5,11 (6H)-diketone (compound 22)
In reaction flask, drop into 0.11g (0.309mmol) compound 19,0.05g (0.71mmol) Diisopropylamine, 0.25g (1.81mmol) anhydrous K successively 2CO 3, about 30ml dioxane and a little NaI, 100 ℃ of stirring reaction 24h reactions finish, suction filtration, filtrate decompression is steamed and is desolventized, ethyl alcohol recrystallization gets product 0.10g, yield 82.8%.mp169-172 ℃; IR (KBr): 3450,3414,2964,1639,1580,1517,1387,834cm -1 1H-NMR (300MHz, DMSO-d 6): δ 8.33 (d, 1H, J=8.7Hz, Ar-H), 7.73 (m, 1H, Ar-H), 7.30 (m, 3H, Ar-H), 7.09 (dd, 1H, J=8.7Hz, Ar-H), 5.76 (s, 2H, Ar-N H 2), 4.45 (t, 2H, J=8.4Hz, CON-CH 2-), 3.33 (s, 2H, J=8.1Hz ,-CH 2-CH 2-C H 2-), 2.60 (s, 4H ,-N-C H 2-CH 2-CH 2-C H 2N-), 1.90 (s, 2H ,-CH 2-C H 2-CH 2-), 1.67 (s, 4H ,-N-CH 2-C H 2-C H 2-CH 2-N-); MS-EI (m/z): 391[M] +
Embodiment 23
The preparation of 3-amino-6-(3-imidazolyl propyl group)-9-fluoro-5H-indeno [1,2-c] isoquinoline 99.9-5,11 (6H)-diketone (compound 23)
In reaction flask, drop into 0.08g (0.224mmol) compound 19,0.04g (0.588mmol) imidazoles, 0.18g (1.3mmol) anhydrous K successively 2CO 3, about 30ml dioxane and a little NaI, 100 ℃ of stirring reaction 24h.Reaction finishes, suction filtration, and filtrate decompression is steamed and is desolventized, and ethyl alcohol recrystallization gets product 0.07g, yield 80.54%.mp265-268 ℃; IR (KBr): 3450,3196,2920,1639,1442,1058,832cm -1 1H-NMR (300MHz, DMSO-d 6): δ 8.23 (d, J=8.7Hz, 1H, Ar-H), 7.84 (s, 1H, imidazole-H), 7.32 (m, 3H, Ar-H), 7.09 (m, 4H, Ar-H and imidazole-H), 5.79 (s, 2H, Ar-N H 2), 4.40 (m, 2H, CON-CH 2-), 4.19 (t, 2H, J=6.6Hz, imidazole-C H 2), 2.18 (m, 2H ,-CH 2-C H 2-CH 2-); EI-MS (m/z): 388[M] +
Embodiment 24
The preparation of 3-amino-6-(morpholinyl propyl group)-9-fluoro-5H-indeno [1,2-c] isoquinoline 99.9-5,11 (6H)-diketone (compound 24)
In reaction flask, drop into 0.12g (0.337mmol) compound 19,0.07g (0.81mmol) morpholine, 0.23g (1.68mmol) anhydrous K successively 2CO 3, about 30ml dioxane and a little, 100 ℃ of stirring reaction 24h.Reaction finishes, suction filtration, and filtrate decompression is steamed and is desolventized, and ethyl alcohol recrystallization gets product 0.11g, yield 80.2%.mp208-210℃；IR(KBr)：3421，2810，1642，1515，1333，1108，835cm -1； 1H-NMR(300MHz，DMSO-d 6)：δ8.24(d，1H，J＝8.7Hz，Ar-H)，7.71(m，1H，Ar-H)，7.30(m，3H，Ar-H)，7.09(dd，1H，J＝8.4Hz，Ar-H)，5.76(s，2H，Ar-N H 2)，7.21(m，1H，Ar-H)，4.66(t，2H，J＝8.1Hz，CON-CH 2-)，5.76(s，2H，Ar-N H 2)，4.15(m，4H，-C H 2-O-C H 2-)，2.36(m，4H，-C H 2N-C H 2)，1.90(s，2H，-CH 2-C H 2-CH 2-)；EI-MS(m/z)：407[M] +
Embodiment 25
The preparation of 3-amino-6-(3-alcohol amido propyl group)-9-fluoro-5H-indeno [1,2-c] isoquinoline 99.9-5,11 (6H)-diketone (compound 25)
In reaction flask, drop into 0.10g (0.28mmol) compound 19,0.04g (0.66mmol) thanomin, 0.24g (1.74mmol) anhydrous K successively 2CO 3, about 25ml dioxane and a little NaI, 100 ℃ of stirring reaction 24h.Reaction finishes, suction filtration, and filtrate decompression is steamed and is desolventized, and ethyl alcohol recrystallization gets product 0.05g, yield 47.0%.mp255-258℃；IR(KBr)：3352，2960，1650，1444，1208，840； 1H-NMR(300MHz，DMSO-d 6)：δ8.29(d，1H，J＝8.7Hz，，Ar-H)，7.76(m，1H，，Ar-H)，7.29(m，3H，Ar-H)，7.09(dd，1H，J＝8.7Hz，Ar-H)，5.78(s，2H，Ar-N H 2)，4.46(t，2H，J＝6.9Hz，CON-CH 2-)，3.52(t，2H，J＝5.4Hz，-NH 2-CH 2C H 2-OH)，2.78(s，4H，-C H 2--NH 2-C H 2)1.94(m，2H，-CH 2-C H 2-CH 2-)；MS-EI(m/z)：381[M] +
Embodiment 26
The preparation of 3-amino-6-(3-chloropropyl)-9-chloro-5H--indeno [1,2-c] isoquinoline 99.9-5,11 (6H)-diketone (compound 26)
In reaction flask, add 1.2g (2.98mmol) compound 9 successively, the iron powder 1.3g (23.2mmol) that handled, Glacial acetic acid 16ml (0.28mol), DMF 200ml, 68 ℃ were reacted 8 hours, and the TLC detection reaction is complete, suction filtration while hot, filtrate decompression is steamed and is desolventized, and ethyl alcohol recrystallization gets product 0.99g, yield 89.6%.mp225-228℃；IR(KBr)：3414，1639，1577，1512，1280，813； 1H-NMR(300MHz，DMSO-d 6)：δ8.48(d，1H，J＝8.4Hz，Ar-H)，7.60(d，1H，J＝8.1Hz，Ar-H)，7.51(dd，2H，J＝5.4Hz，Ar-H)，7.37(dd，2H，J＝5.4Hz，Ar-H)，7.10(dd，1H，J＝8.4Hz，Ar-H)，4.62(t，2H，J＝7.8Hz，CON-CH 2-)，4.02(s，2H，Ar-N H 2)，3.80(t，2H，J＝6.0Hz，-CH 2-Cl)，2.35(m，2H，-CH 2-C H 2-CH 2-)；MS-EI(m/z)：372[M] +
Embodiment 27
The preparation of 3-amino-6-(3-methylpiperazine base propyl group)-9-chloro-5H--indeno [1,2-c] isoquinoline 99.9-5,11 (6H)-diketone (compound 27)
In reaction flask, drop into 0.10g (0.269mmol) compound 26,0.07g (0.70mmol) methylpiperazine, 0.22g (1.59mmol) anhydrous K successively 2CO 3, about 30ml dioxane and a little NaI, 100 ℃ of stirring reaction 24h.Remove solvent under reduced pressure, add an amount of chloroform dissolving, filter, the filter filtrate decompression is steamed and is desolventized, and ethyl alcohol recrystallization gets product 0.10g, yield 85.3%.mp203-205 ℃; IR (KBr): 3467,3426,2298,1644,1578,1514,1398,790cm -1 1H-NMR (300MHz, CDCl 3): δ 8.41 (d, 1H, J=8.4Hz, Ar-H), 7.53 (d, 1H, J=7.8Hz, Ar-H), 7.44 (dd, 2H, J=9Hz, Ar-H), 7.25 (dd, 1H, J=8.1Hz, Ar-H), 7.02 (dd, 1H, J=9Hz, Ar-H), 3.93 (s, 2H, Ar-NH 2), 4.44 (t, 2H, J=6.6Hz, CON-CH 2-), 2.46 (br, 13H, piperazine-H), 1.93 (m, 2H ,-CH 2-C H 2-CH 2-); MS-EI (m/z): 436[M] +
Embodiment 28
The preparation of 3-amino-6-(morpholinyl propyl group)-9-chloro-5H--indeno [1,2-c] isoquinoline 99.9-5,11 (6H)-diketone (compound 28)
In reaction flask, drop into 0.10g (0.269mmol) compound 26,0.06g (0.69mmol) morpholine, 0.23g (1.67mmol) anhydrous K successively 2CO 3, about 30ml dioxane and a little NaI, 100 ℃ of stirring reaction 24h.Remove solvent under reduced pressure, add an amount of chloroform dissolving, filter, filtrate decompression is steamed and is desolventized, and ethyl alcohol recrystallization gets product 0.09g, yield 77.5%.mp254-259 ℃; IR (KBr): 3435,3350,2845,1639,1581,1515,1399,1111,844,801cm -1 1H-NMR (300MHz, CDCl 3): δ 8.24 (d, 1H, J=8.4Hz, Ar-H), 7.70 (dd, 1H, J=8.7Hz, Ar-H), 7.54 (dd, 1H, J=8.4Hz, Ar-H), 7.43 (s, 1H, Ar-H), 7.33 (s, 1H, Ar-H), 7.10 (dd, 1H, J=10.5Hz, Ar-H), 5.8 (s, 2H, Ar-NH 2), 4.46 (s, 2H, CON-CH 2-), 3.51 (s, 4H ,-C H 2-O-C H 2-), 3.33 (s, 2H ,-CH 2CH 2C H 2-N (CH 2) 2), 2.33 (m, 4H ,-CH 2N (C H 2) 2), 1.88 (m, 2H ,-CH 2-C H 2-CH 2-); MS-EI (m/z): 432[M] +
Embodiment 29
The preparation of 3-amino-6-(3-chloropropyl)-9-methoxyl group-5H--indeno [1,2-c] isoquinoline 99.9-5,11 (6H)-diketone (compound 29)
In reaction flask, add 1.0g (2.5mmol) compound 15 successively, the iron powder 1.1g (19.6mmol) that handled, Glacial acetic acid 13ml (0.22mol), DMF 180ml, 68 ℃ were reacted 6 hours, and the TLC detection reaction is complete, suction filtration while hot, filtrate decompression is steamed and is desolventized, and ethyl alcohol recrystallization gets product 0.84g, yield 91.3%.mp286-289℃；IR(KBr)：3458，3357，2956，1646，1469，1301，1221，798cm -1； 1H-NMR(300MHz，DMSO-d 6)：δ8.22(d，1H，J＝7.8Hz，Ar-H)，7.56(d，1H，J＝8.4Hz，Ar-H)，7.31(d，J＝2.4Hz，1H，Ar-H)，7.08(dd，1H，J＝8.4Hz，Ar-H)，7.00(d，1H，J＝2.4Hz，Ar-H)，6.85(dd，1H，J＝6.6Hz，Ar-H)，5.76(s，2H，Ar-N H 2)，4.50(t，2H，J＝5.1Hz，CON-CH 2-)，3.83(s，3H，-OC H 3)，3.85(m，2H，-CH 2-Cl)，2.20(t，2H，J＝7.2Hz，-CH 2-C H 2-CH 2-)；MS-EI(m/z)：368[M] +
Embodiment 30
The preparation of 3-amino-6-(3-tetramethyleneimine propyl group)-9-methoxyl group-5H--indeno [1,2-c] isoquinoline 99.9-5,11 (6H)-diketone (compound 30)
In reaction flask, drop into 0.10g (0.272mmol) compound 29,0.05g (0.70mmol) tetramethyleneimine, 0.23g (1.67mmol) anhydrous K successively 2CO 3, about 30ml dioxane and a little NaI, 100 ℃ of stirring reaction 24h.Remove solvent under reduced pressure, add an amount of chloroform dissolving, filter, filtrate decompression is steamed and is desolventized, and ethyl alcohol recrystallization gets product 0.09g, yield 82.1%.mp229-232 ℃; IR (KBr): 3464,3416,2950,1639,1516,1296,1020,827cm -1 1H-NMR (300MHz, CDCl 3): δ 8.46 (d, 1H, J=8.7Hz, Ar-H), 7.53 (m, 2H, Ar-H), 7.14 (d, 1H, J=2.4Hz, Ar-H), 7.08 (dd, 1H, J=8.7Hz, Ar-H), 6.73 (dd, 1H, J=8.1Hz, Ar-H), 4.52 (t, 2H, J=7.8Hz, CON-CH 2-), 3.94 (s, 2H, Ar-N H 2), 3.87 (s, 3H ,-OCH 3), 2.65 (m, 2H ,-CH 2-CH 2-C H 2-), 2.05 (m, 2H ,-CH 2-C H 2-CH 2-), 2.54 (s, 4H ,-N-C H 2-CH 2-CH 2-C H 2-N-), 1.79 (s, 4H ,-N-CH 2-C H 2-C H 2-CH 2-N-); MS-EI (m/z): 403[M] +
Embodiment 31
The preparation of 3-amino-9-methoxyl group-6-(3-methylpiperazine base propyl group)-5H--indeno [1,2-c] isoquinoline 99.9-5,11 (6H)-diketone (compound 31)
In reaction flask, drop into 0.08g (0.269mmol) compound 29,0.06g (0.60mmol) methylpiperazine, 0.18g (1.3mmol) anhydrous K successively 2CO 3, about 30ml dioxane and a little NaI, 100 ℃ of stirring reaction 24h.Remove solvent under reduced pressure, add an amount of chloroform dissolving, filter, filtrate decompression is steamed and is desolventized, and ethyl alcohol recrystallization must get orange solid 0.08g, yield 85.3%.mp240-242 ℃; IR (KBr): 3470,3397,2929,1650,1578,1515,1305,1222,1014,796cm -1 1H-NMR (300MHz, DMSO-d 6): δ 8.47 (d, 1H, J=8.7Hz, Ar-H), 7.52 (m, 2H, Ar-H), 7.16 (d, 1H, J=2.4Hz, Ar-H), 7.09 (dd, 1H, J=8.4Hz, Ar-H), 6.77 (dd, 1H, J=8.1Hz, Ar-H), 4.52 (t, 2H, J=7.5Hz, CON-CH 2-), 3.94 (s, 2H, Ar-NH 2), 3.88 (s, 3H ,-OCH 3), 2.51 (br, 13H, piperazine-H), 2.01 (m, 2H ,-CH 2-C H 2-CH 2-); MS-EI (m/z): 432[M] +
Embodiment 32
The preparation of 3-amino-6-(morpholinyl propyl group)-9-methoxyl group-5H--indeno [1,2-c] isoquinoline 99.9-5,11 (6H)-diketone (VI-3)
In reaction flask, drop into 0.12g (0.326mmol) compound 29,0.07g (0.80mmol) morpholine, 0.27g (1.96mmol) anhydrous K successively 2CO 3, about 30ml dioxane and a little NaI, 100 ℃ of stirring reaction 24h.Reaction finishes, suction filtration, and filtrate decompression is steamed and is desolventized, and ethyl alcohol recrystallization gets product 0.12g, yield 87.9%.mp234-236 ℃; IR (KBr): 3412,3360,2960,1646,1580,1516,1305,1113,842,792cm -1 1H-NMR (300MHz, CDCl 3): δ 8.47 (d, 1H, J=8.7Hz, Ar-H), 7.51 (m, 2H, Ar-H), 7.15 (d, 1H, J=2.7Hz, Ar-H), 7.08 (dd, 1H, J=8.7Hz, Ar-H), 6.75 (dd, 1H, J=8.4Hz, Ar-H), 4.53 (t, 2H, J=7.8Hz, CON-CH 2-), 3.95 (s, 2H, Ar-N H 2), 3.87 (s, 3H ,-OCH 3), 3.73 (t, 4H, J=4.5Hz ,-C H 2-O-C H 2-), 2.54 (m, 6H ,-CH 2CH 2C H 2-N (C H 2) 2), 2.03 (m, 2H ,-CH 2-C H 2-CH 2-); MS-EI (m/z): 419[M] +
Embodiment 33
The preparation of 3-amino-9-methoxyl group-6-(3-diethylin propyl group)-5H--indeno [1,2-c] isoquinoline 99.9-5,11 (6H)-diketone (compound 33)
In reaction flask, drop into 0.10g (0.272mmol) compound 29,0.05g (0.69mmol) diethylamino, 0.23g (1.67mmol) anhydrous K successively 2CO 3, about 30ml dioxane and a little NaI, 100 ℃ of stirring reaction 24h.Reaction finishes, suction filtration, and filtrate decompression is steamed and is desolventized, and ethyl alcohol recrystallization gets product 0.06g, yield 54.5%.mp263-265 ℃; IR (KBr): 3419,3317,3202,1639,1396,1228,1020,790cm -1 1H-NMR (300MHz, CDCl 3): δ 8.24 (d, J=8.7Hz, 1H, Ar-H), 7.55 (d, 1H, J=8.4Hz, Ar-H), 7.32 (d, 1H, J=2.4Hz, Ar-H), 7.08 (m, 2H, Ar-H), 6.90 (dd, 1H, J=8.4Hz, Ar-H), 5.72 (s, 2H, Ar-NH 2), 4.46 (t, 2H, J=8.7Hz, CON-CH 2-), 3.86 (s, 3H ,-OCH 3), 3.13 (m, 6H ,-C H 2N (C H 2CH 3) 2), 2.12 (s, 2H ,-CH 2-C H 2-CH 2), 1.18 (t, 6H, J=6.6Hz, N-(CH 2-C H 3) 2); MS-EI (m/z): 405[M] +
Embodiment 34
The preparation of 3-amino-6-(3-imidazolyl propyl group)-9-methoxyl group-5H--indeno [1,2-c] isoquinoline 99.9-5,11 (6H)-diketone (VI-5)
In reaction flask, drop into 0.15g (0.408mmol) compound 29,0.07g (1.03mmol) imidazoles, 0.34g (2.46mmol) anhydrous K successively 2CO 3, about 30ml dioxane and a little NaI, 100 ℃ of stirring reaction 24h.Reaction finishes, suction filtration, and filtrate decompression is steamed and is desolventized, and ethyl alcohol recrystallization gets product 0.14g, yield 85.8%.mp245-248 ℃; IR (KBr): 3469,3414,1632,1467,1386,1224,617cm -1 1H-NMR (300MHz, DMSO-d 6): δ 8.21 (d, J=8.7Hz, 1H, Ar-H), 7.77 (s, 2H, Ar-H), 7.32 (m, 4H, Ar-H and imidazole-H), 6.73 (m, 1H, Ar-H), 5.72 (s, 2H, Ar-N H 2), 4.37 (t, 2H, J=8.1Hz, CON-CH 2-), 4.20 (t, 2H, J=6.6Hz ,-CH 2-CH 2-C H 2-imidazole), 3.83 (s, 3H ,-OCH 3) 2.16 (t, 2H, J=6.6Hz ,-CH 2-C H 2-CH 2-); MS-EI (m/z): 400[M] +
Embodiment 35
6-(3-chloropropyl)-5,6-dihydro-3-nitro-5,11-dicarbapentaborane-8, the preparation of 9-methylene-dioxy-11H-indeno [1,2-c] isoquinolines (compound 35)
With suitable-N-(3-chloropropyl)-4-carboxyl-3,4-dihydro--7-nitro-3-(3, the 4-methylene-dioxy)-1 (4g 9mmol) adds dry toluene (200ml), reflux 30min with sulfur oxychloride (10ml) to (2H) isoquinolines, concentrating under reduced pressure boils off solvent, add oil of mirbane (100ml) in the residuum, and adding aluminum chloride under the ice bath (2.8g, 21mmol), be heated to 100 ℃ of 1h, cooling carefully adds entry 50ml, dichloromethane extraction (200ml * 4), the organic layer saturated sodium bicarbonate solution is washed (100ml), saturated sodium-chloride is washed (100ml), anhydrous magnesium sulfate drying, concentrating under reduced pressure, add hexanaphthene (600ml), leave standstill, separate out the cotton-shaped solid of rust red, filter, get rust red crystal I 1.4g, yield 37.7%.mp281-283℃；IR(KBr)：3075，2962，2915，1680，1608，1501，848，791cm -1； 1H-NMR(300MHz，DMSO-d 6)：δ8.87(d，1H，J＝2.4Hz，Ar-H)，8.59(m，2H，Ar-H)，7.59(s，1H，Ar-H)，7.27(s，1H，Ar-H)，6.31(s，2H，O-CH 2-O)，4.63(t，2H，J＝4.2Hz，CON-CH 2-)，3.96(t，2H，J＝6.3Hz，-CH 2-Cl)，2.33(m，2H，-CH 2-C H 2-CH 2-)；MS(EI)m/z：412[M] +.
Embodiment 36
6-(3-methylpiperazine-1-propyl group)-5,6-dihydro-3-nitro-5,11-dicarbapentaborane-8, the preparation of 9-methylene-dioxy-11H-indeno [1,2-c] isoquinolines (compound 36)
With compound 35 (0.082g, 0.2mmol), methylpiperazine (0.06g, 0.6mmol), Anhydrous potassium carbonate (0.17g, 1.2mmol) place no Shui diox (20ml), reflux 24h, reaction finishes, suction filtration, filtrate steaming removal solvent, the chloroform recrystallization gets product 0.093g, yield 97.7%.mp249-253 ℃, IR (KBr): 3072,2960,2817,1667,1611,1498,1307,793cm -1, 1H-NMR (300MHz, CDCl 3): δ 9.09 (d, 1H, J=2.1Hz, Ar-H), 8.69 (d, 1H, J=9Hz, Ar-H), 8.37 (dd, 1H, J=2.1,9Hz, Ar-H), 7.45 (s, 1H, Ar-H), 7.11 (s, 1H, Ar-H), 6.09 (s, 2H, O-CH 2-O), 4.48 (t, 2H, J=7.8Hz, CON-CH 2-), 2.50 (t, 2H, J=5.7Hz ,-(CH 2) 2-C H 2-N), 2.40 (br s, 8H, N-C H 2-C H 2-N * 2), 2.21 (s, 3H, N-CH 3), 1.97 (m, 2H ,-CH 2-C H 2-CH 2-); MS (EI) m/z:476[M] +
Embodiment 37
6-(3-imidazolyl-1-propyl group)-5,6-dihydro-3-nitro-5,11-dicarbapentaborane-8, the preparation of 9-methylene-dioxy-11H-indeno [1,2-c] isoquinolines (compound 37)
With compound 35 (0.082g, 0.2mmol), imidazoles (0.05g, 0.6mmol), (0.17g 1.2mmol) places no Shui diox (20ml) to Anhydrous potassium carbonate, reflux 24h, reaction finishes, suction filtration, filtrate steaming removal solvent, the chloroform recrystallization gets product 0.072g, yield 81.5%.mp311-313℃；IR(KBr)：3077，2916，1678，1610，1504，1308，847cm -1； 1H-NMR(300MHz，DMSO-d 6)δ8.83(s，1H，Ar-H)，8.53(m，2H，Ar-H)，7.70(s，1H，imidazole-H)，7.23(m，3H，imidazole-H，Ar-H)，6.91(s，1H，Ar-H)，6.31(s，2H，O-CH 2-O)，4.45(t，2H，J＝4.2Hz，CON-CH 2-)，4.21(t，2H，J＝6.3Hz，-(CH 2) 2-C H 2-N)，2.23(m，2H，-CH 2-C H 2-CH 2-)；MS(EI)m/z：444[M] +
Embodiment 38
6-(3-piperidyl-1-propyl group)-5,6-dihydro-3-nitro-5,11-dicarbapentaborane-8, the preparation of 9-methylene-dioxy-11H-indeno [1,2-c] isoquinolines (compound 38)
With compound 35 (0.082g, 0.2mmol), piperidines (0.06g, 0.6mmol), (0.17g 1.2mmol) places no Shui diox (20ml) to Anhydrous potassium carbonate, reflux 24h, reaction finishes, suction filtration, filtrate steaming removal solvent, the chloroform recrystallization gets product 0.085g, yield 82.6%.mp273-276℃；IR(KBr)：2917，2849，1675，1609，1500，1337，1035，849cm -1； 1H-NMR(300MHz，CDCl 3)δ9.16(d，1H，J＝2.4Hz，Ar-H)，8.75(d，1H，J＝9Hz，Ar-H)，8.44(dd，1H，J＝2.4，9Hz，Ar-H)，7.62(s，1H，Ar-H)，7.18(s，1H，Ar-H)，6.15(s，2H，O-CH 2-O)，4.54(t，2H，J＝7.8Hz，CON-CH 2-)，2.49(m，6H，-CH 2-N-CH 2-，-(CH 2) 2-C H 2-N)，2.01(m，2H，N-CH 2-C H 2-CH 2-N)，1.61(m，4H，-CH 2-C H 2-CH 2-C H 2-CH 2-)，1.45(m，2H，-CH 2-CH 2-C H 2-CH 2-CH 2-)；MS(EI)m/z：461[M] +
Embodiment 39
6-(morpholinyl-1-propyl group)-5,6-dihydro-3-nitro-5,11-dicarbapentaborane-8, the preparation of 9-methylene-dioxy-11H-indeno [1,2-c] isoquinolines (compound 39)
With compound 35 (0.082g, 0.2mmol), morpholine (0.05g, 0.6mmol), Anhydrous potassium carbonate (0.17g, 1.2mmol) place no Shui diox (20ml), reflux 24h, reaction finishes, suction filtration, filtrate steaming removal solvent, the chloroform recrystallization gets product 0.080g, yield 86.8%.mp319-321 ℃; IR (KBr): 3431,3329,2934,1646,1581,1489,1294,849cm -1 1H-NMR (300MHz, CDCl 3): δ 9.09 (d, 1H, J=2.1Hz, Ar-H), 8.69 (d, 1H, J=9Hz, Ar-H), 8.37 (dd, 1H, J=2.1,9Hz, Ar-H), 7.5 (s, 1H, Ar-H), 7.12 (s, 1H, Ar-H), 6.1 (s, 2H, O-CH 2-O), 4.61 (t, 2H, J=7.8Hz, CON-CH 2-), 3.69 (br s, 4H ,-CH 2-O-CH 2-), 2.45 (m, 6H ,-CH 2-N-CH 2-,-(CH 2) 2-C H 2-N), 1.97 (m, 2H ,-CH 2-C H 2-CH2-); MS (EI) m/z:463[M] +
Embodiment 40
6-(3-alcohol amido-1-propyl group)-5,6-dihydro-3-nitro-5,11-dicarbapentaborane-8, the preparation of 9-methylene-dioxy-11H-indeno [1,2-c] isoquinolines (compound 40)
With compound 35 (0.082g, 0.2mmol), thanomin (0.04g, 0.6mmol), (0.17g 1.2mmol) places no Shui diox (20ml) to Anhydrous potassium carbonate, reflux 24h, reaction finishes, suction filtration, filtrate steaming removal solvent, the chloroform recrystallization gets product 0.056g, yield 64.4%; Mp262-264 ℃; IR (KBr): 3370,2959,1678,1609,1503,1307,792cm -1 1H-NMR (300MHz, DMSO-d 6): δ 8.76 (d, 1H, J=2.4Hz, Ar-H), 8.48 (m, 2H, Ar-H), 7.57 (s, 1H, Ar-H), 7.15 (s, 1H, Ar-H), 6.24 (s, 2H, O-CH 2-O), 4.94 (br s, 1H, OH) 4.47 (t, 2H, J=4.2Hz, CON-CH 2-), 3.57 (s, 2H ,-C H 2-OH), 2.96 (t, 2H, J=6.3Hz ,-(CH 2) 2-C H 2-N), 2.73 (s, 2H, N-C H 2-CH 2-OH), 2.05 (m, 2H ,-CH 2-C H 2-CH 2-); MS (EI): 419[M-18] +
Embodiment 41
6-(3-diethanolamino-1-propyl group)-5,6-dihydro-3-nitro-5,11-dicarbapentaborane-8, the preparation of 9-methylene-dioxy-11H-indeno [1,2-c] isoquinolines (compound 41)
With compound 35 (0.082g, 0.2mmol), diethanolamine (0.06g, 0.6mmol), (0.17g 1.2mmol) places no Shui diox (20ml) to Anhydrous potassium carbonate, reflux 24h, reaction finishes, suction filtration, filtrate steaming removal solvent, the chloroform recrystallization gets product 0.047g, yield 49.1%.mp275-277℃；IR(KBr)：3327，2907，2819，1672，1610，1510，1034，791cm -1； 1H-NMR(300MHz，DMSO-d 6)：δ8.80(d，1H，J＝2.4Hz，Ar-H)，8.52(m，2H，Ar-H)，7.51(s，1H，Ar-H)，7.22(s，1H，Ar-H)，6.26(s，2H，O-CH 2-O)，5.22(br?s，2H，OH×2)，4.50(t，2H，J＝4.2Hz，CON-CH 2-)，3.71(br?s，4H，-C H 2-OH×2)，3.41(t，2H，J＝6.3Hz，-(CH 2) 2-C H 2-N)，3.21(s，4H，N-C H 2-CH 2-OH×2)，2.21(m，2H，-CH 2-C H 2-CH 2-)；MS(EI)m/z：463[M-18] +
Embodiment 42
6-(3-pyrrolidyl-1-propyl group)-5,6-dihydro-3-nitro-5,11-dicarbapentaborane-8, the preparation of 9-methylene-dioxy-11H-indeno [1,2-c] isoquinolines (compound 42)
With compound 35 (0.082g, 0.2mmol), tetramethyleneimine (0.04g, 0.6mmol), Anhydrous potassium carbonate (0.17g, 1.2mmol) place no Shui diox (20ml), reflux 24h, reaction finishes, suction filtration, filtrate steaming removal solvent, the chloroform recrystallization gets product 0.080g, yield 89.9%.mp258-261 ℃; IR (KBr): 2916,2847,1673,1609,1506,1337,851cm -1 1H-NMR (300MHz, CDCl 3): δ 9.15 (d, 1H, J=2.4Hz, Ar-H), 8.74 (d, 1H, J=9Hz, Ar-H), 8.43 (dd, 1H, J=2.4,9Hz, Ar-H), 7.65 (s, 1H, Ar-H), 7.15 (s, 1H, Ar-H), 6.21 (s, 2H, O-CH 2-O), 4.53 (t, 2H, J=7.8Hz, CON-CH 2-), 2.69 (t, 2H, J=6Hz ,-(CH 2) 2-C H 2-N), 2.57 (s, 4H, CH 2-N-CH 2), 2.02 (m, 2H ,-CH 2-C H 2-CH 2-), 1.85 (s, 4H ,-CH 2-C H 2-C H 2-CH 2-); MS (EI) m/z:447[M] +
Embodiment 43
6-(3-n-propylamine base-1-propyl group)-5,6-dihydro-3-nitro-5,11-dicarbapentaborane-8, the preparation of 9-methylene-dioxy-11H-indeno [1,2-c] isoquinolines (compound 43)
With compound 35 (0.082g, 0.2mmol), Tri N-Propyl Amine (0.06g, 0.6mmol), Anhydrous potassium carbonate (0.17g, 1.2mmol) place no Shui diox (20ml), reflux 24h, reaction finishes, suction filtration, filtrate steaming removal solvent, the chloroform recrystallization gets product 0.043g, yield 49.7%.mp278-281 ℃; IR (KBr): 2917,1848,1675,1610,1502,1331,1033,791cm -1 1H-NMR (300MHz, DMSO-d 6): δ 8.83 (d, 1H, J=2.4Hz, Ar-H), 8.53 (m, 2H, Ar-H), 7.68 (s, 1H, Ar-H), 7.24 (s, 1H, Ar-H), 6.26 (s, 2H, O-CH 2-O), 4.51 (t, 2H, J=7.5Hz, CON-CH 2-), 2.88 (m, 2H, N-C H 2-C 2H 5), 2.65 (t, 2H, J=7.5Hz ,-(CH 2) 2-C H 2-N), 2.00 (m, 2H ,-CH 2-C H 2-CH 2-), 1.49 (m, 2H, N-CH 2-C H 2-CH 3), 0.88 (t, 3H, J=7.5Hz, N-(CH 2) 2-C H 3); MS (EI) m/z:435[M] +
Embodiment 44
6-(3-diethylin-1-propyl group)-5,6-dihydro-3-nitro-5,11-dicarbapentaborane-8, the preparation of 9-methylene-dioxy-11H-indeno [1,2-c] isoquinolines (compound 44)
With compound 35 (0.082g, 0.2mmol), diethylamide (0.04g, 0.6mmol), Anhydrous potassium carbonate (0.17g, 1.2mmol) place no Shui diox (20ml), reflux 24h, reaction finishes, suction filtration, filtrate steaming removal solvent, the chloroform recrystallization gets product 0.074g, yield 82.8%.mp262-265 ℃; IR (KBr): 2963,2914,1679,1611,1511,1033,800cm -1 1H-NMR (300MHz, CDCl 3): δ 9.29 (d, 1H, J=2.4Hz, Ar-H), 8.65 (d, 1H, J=9Hz, Ar-H), 8.35 (dd, 1H, J=2.4,9Hz, Ar-H), 7.78 (s, 1H, Ar-H), 7.07 (s, 1H, Ar-H), 6.07 (s, 2H, O-CH 2-O), 4.45 (t, 2H, J=8.1Hz, CON-CH 2-), 2.57 (m, 6H, CH 2-N-CH 2,-(CH 2) 2-C H 2-N), 1.89 (m, 2H ,-CH 2-C H 2-CH 2-), 1.00 (t, 6H, J=6.9Hz ,-CH 3* 2); MS (EI) m/z:449[M] +
Embodiment 45
6-(3-chloropropyl)-5,6-dihydro-3-amino-5,11-dicarbapentaborane-8, the preparation of 9-methylene-dioxy-11H-indeno [1,2-c] isoquinolines (compound 45)
(10%Pd-C (0.01g), normal temperature and pressure are hydrogenated to TLC and detect the raw material disappearance, filter for 0.082g, 0.2mmol) the middle DMF (30ml) that adds, and the filtrate decompression steaming desolventizes, and ethyl alcohol recrystallization gets product 0.062g, yield 80.1% to compound 35.mp352-354℃；IR(KBr)：3456，3356，2957，1643，1583，1484，1027，789cm-1；1H-NMR(300MHz，DMSO-d6)：δ8.18(d，1H，J＝8.7Hz，Ar-H)，7.29(s，2H，Ar-H)，7.04(m，2H，Ar-H)，6.16(s，2H，O-CH2-O)，5.70(s，2H，NH2)，4.47(t，2H，J＝7.5Hz，CON-CH2-)，3.86(t，2H，J＝6Hz，-CH2-Cl)，2.19(m，2H，-CH2-CH2-CH2-)；MS(EI)m/z：382[M]+
Embodiment 46
6-[3-(1-methylpiperazine)-1-propyl group]-5,6-dihydro-3-amino-5,11-dicarbapentaborane-8, the preparation of 9-methylene-dioxy-11H-indeno [1,2-c] isoquinolines (compound 46)
(10%Pd-C (0.01g), normal temperature and pressure are hydrogenated to TLC and detect the raw material disappearance, filter for 0.094g, 0.2mmol) the middle DMF (30ml) that adds, and the filtrate decompression steaming desolventizes, and ethyl alcohol recrystallization gets product 0.068g, yield 76.3% to compound 36.mp271-274℃；IR(KBr)：3404，3162，2925，1648，1582，1297，1023，799cm-1；1H-NMR(300MHz，CDCl3)δ8.37(d，1H，J＝8.7Hz，Ar-H)，7.54(s，1H，Ar-H)，7.25(s，1H，Ar-H)，7.01(m，2H，Ar-H)，6.01(s，2H，O-CH2-O)，4.43(t，2H，J＝7.5Hz，CON-CH2-)，3.86(s，2H，NH2)，2.45(m，10H，piperazine-H，-(CH2)2-CH2-N)，2.22(s，3H，N-CH3)，2.09(m，2H，-CH2-CH2-CH2-)；MS(EI)m/z：446[M]+
Embodiment 47
6-(morpholinyl-1-propyl group)-5,6-dihydro-3-amino-5,11-dicarbapentaborane-8, the preparation of 9-methylene-dioxy-11H-indeno [1,2-c] isoquinolines (compound 47)
(10%Pd-C (0.01g), normal temperature and pressure are hydrogenated to TLC and detect the raw material disappearance, filter for 0.092g, 0.2mmol) the middle DMF (30ml) that adds, and the filtrate decompression steaming desolventizes, and ethyl alcohol recrystallization gets product 0.068g, yield 78.2%mp276-280 ℃ to compound 37; IR (KBr): 3431,3329,2934,1646,1581,1489,1294,849cm-1; 1H-NMR (300MHz, CDCl3): δ 8.44 (d, 1H, J=8.7Hz, Ar-H), 7.49 (s, 1H, Ar-H), 7.37 (s, 1H, Ar-H), 7.09 (m, 2H, Ar-H), 6.08 (s, 2H, O-CH2-O), 4.53 (t, 2H, J=7.5Hz, CON-CH2-), 3.94 (s, 2H, NH2), 3.77 (s, 4H, morpholine-H), 2.52 (m, 6H, morpholine-H ,-(CH2) 2-CH2-N), 2.09 (m, 2H ,-CH2-CH2-CH2-); MS (EI) m/z:433[M]+
Embodiment 48
6-(3-pyrrolidyl-1-propyl group)-5,6-dihydro-3-amino-5,11-dicarbapentaborane-8, the preparation of 9-methylene-dioxy-11H-indeno [1,2-c] isoquinolines (compound 48)
(10%Pd-C (0.01g), normal temperature and pressure are hydrogenated to TLC and detect the raw material disappearance, filter for 0.085g, 0.2mmol) the middle DMF (30ml) that adds, and the filtrate decompression steaming desolventizes, and ethyl alcohol recrystallization gets product 0.061g, yield 72.8% to compound 42.mp260-263℃；IR(KBr)：3455，3354，2960，1642，1581，1485，1307，835cm-1；1H-NMR(300MHz，DMSO-d6)：δ8.18(d，1H，J＝8.7Hz，Ar-H)，7.45(s，1H，Ar-H)，7.29(d，1H，J＝2.1Hz，Ar-H)，7.04(m，2H，Ar-H)，6.15(s，2H，O-CH2-O)，5.67(s，2H，NH2)，4.39(t，2H，J＝7.5Hz，CON-CH2-)，2.57(t，2H，J＝6Hz，-(CH2)2-CH2-N)，2.45(s，4H，pyrolidine-H)，1.86(m，2H，-CH2-CH2-CH2-)，1.69(s，4H，pyrolidine-H)；MS(EI)m/z：417[M]+
Embodiment 49
6-(3-piperidyl-1-propyl group)-5,6-dihydro-3-amino-5,11-dicarbapentaborane-8, the preparation of 9-methylene-dioxy-11H-indeno [1,2-c] isoquinolines (compound 49)
(10%Pd-C (0.01g), normal temperature and pressure are hydrogenated to TLC and detect the raw material disappearance, filter for 0.092g, 0.2mmol) the middle DMF (30ml) that adds, and the filtrate decompression steaming desolventizes, and ethyl alcohol recrystallization gets product 0.071g, yield 82.4% to compound 38.mp271-274℃；IR(KBr)：3417，3355，2930，1643，1582，1292，1033，827cm-1；1H-NMR(300MHz，CDCl3)：δ8.43(d，1H，J＝8.7Hz，Ar-H)，7.51(d，1H，J＝2.1Hz，Ar-H)，7.38(s，1H，Ar-H)，7.09(m，2H，Ar-H)，6.11(s，2H，O-CH2-O)，4.46(t，2H，J＝8.1Hz，CON-CH2-)，3.94(br?s，2H，NH2)，2.45(m，6H，piperidine-H，-(CH2)2-CH2-N)，1.99(m，2H，-CH2-CH2-CH2-)，1.62(br?s，4H，piperidine-H)，1.44(br?s，2H，piperidine-H)；MS(EI)m/z：431[M]+
Embodiment 50
6-(3-diethylin-1-propyl group)-5,6-dihydro-3-amino-5,11-dicarbapentaborane-8, the preparation of 9-methylene-dioxy-11H-indeno [1,2-c] isoquinolines (compound 50)
(10%Pd-C (0.01g), normal temperature and pressure are hydrogenated to TLC and detect the raw material disappearance, filter for 0.089g, 0.2mmol) the middle DMF (30ml) that adds, and the filtrate decompression steaming desolventizes, and ethyl alcohol recrystallization gets product 0.063g, yield 75.1% to 0.082g compound 44.mp248-250℃；IR(KBr)：3428，3334，2928，1636，1582，1380，1028，801cm-1；1H-NMR(300MHz，CDCl3)：δ8.36(d，1H，J＝8.7Hz，Ar-H)，7.51(s，1H，Ar-H)，7.44(d，1H，J＝2.1Hz，Ar-H)，7.02(m，2H，Ar-H)，5.99(s，2H，O-CH2-O)，4.38(t，2H，J＝8.1Hz，CON-CH2-)，3.87(br s，2H，NH2)，2.55(m，6H，CH2-N-CH2，-(CH2)2-CH2-N)，2.22(s，3H)，1.89(m，2H，-CH2-CH2-CH2-)，1.01(t，6H，J＝6.9Hz，CH3×2)；MS(EI)m/z：419[M]+
Embodiment 51
6-(3-chloropropyl)-5,6-dihydro-3-acetamido-5,11-dicarbapentaborane-8, the preparation of 9-methylene-dioxy-11H-indeno [1,2-c] isoquinolines (compound 51)
With compound 45 (0.076g, 0.2mmol) be dissolved in anhydrous methylene chloride (80ml), (0.044g 0.44mmol), adds Acetyl Chloride 98Min. (0.017g again to add triethylamine, 0.22mmol) TLC detects raw material and disappears behind the stirring at room 6h, with saturated sodium bicarbonate solution washing (50ml * 2), saturated common salt water washing (50ml) anhydrous sodium sulfate drying, pressure reducing and steaming solvent, ethyl alcohol recrystallization gets product 0.076g, yield 89.6%.mp281-285℃；IR(KBr)：3347，2911，1651，1577，1523，1306，840cm-1；1H-NMR(300MHz，DMSO-d6)：δ10.25(br?s，1H，CONH)，8.49(d，1H，J＝1.8Hz，Ar-H)，8.35(d，1H，J＝8.7Hz，Ar-H)，8.32(s，1H，Ar-H)，7.88(dd，1H，J＝1.8，8.7Hz，Ar-H)，7.11(s，1H，Ar-H)，6.19(s，2H，O-CH2-O)，4.52(t，2H，J＝7.5Hz，CON-CH2-)，3.87(t，2H，J＝6Hz，-CH2-Cl)，2.23(m，2H，-CH2-CH2-CH2-)；MS(EI)m/z：424[M]+
Embodiment 52
6-(3-methylpiperazine-1-propyl group)-5,6-dihydro-3-acetamido-5,11-dicarbapentaborane-8, the preparation of 9-methylene-dioxy-11H-indeno [1,2-c] isoquinolines (compound 52)
With compound 46 (0.089g, 0.2mmol) be dissolved in anhydrous methylene chloride (80ml), (0.044g 0.44mmol), adds Acetyl Chloride 98Min. (0.017g again to add triethylamine, 0.22mmol) TLC detects raw material and disappears behind the stirring at room 6h, with saturated sodium bicarbonate solution washing (50ml * 2), saturated common salt water washing (50ml) anhydrous sodium sulfate drying, pressure reducing and steaming solvent, ethyl alcohol recrystallization gets product 0.094g, yield 96.8%.mp264-267℃；IR(KBr)：3417，2823，1654，1577，1303，1034，791cm-1；1H-NMR(300MHz，DMSO-d6)：δ10.24(br?s，1H，CONH)，8.52(d，1H，J＝1.8Hz，Ar-H)，8.37(d，1H，J＝8.7Hz，Ar-H)，7.87(dd，1H，J＝1.8，8.7Hz，Ar-H)，7.50(s，1H，Ar-H)，7.13(s，1H，Ar-H)，6.21(s，2H，O-CH2-O)，4.44(t，2H，J＝7.5Hz，CON-CH2-)，2.47(br?s，8H，piperazine-H)，2.27(m，2H，-(CH2)2-CH2-N)，2.08(s，3H，CH3CO)，1.90(m，2H，-CH2-CH2-CH2-)；MS(EI)m/z：488[M]+
Embodiment 53
6-(morpholinyl-1-propyl group)-5,6-dihydro-3-acetamido-5,11-dicarbapentaborane-8, the preparation of 9-methylene-dioxy-11H-indeno [1,2-c] isoquinolines (compound 53)
With compound 47 (0.086g, 0.2mmol) be dissolved in anhydrous methylene chloride (80ml), (0.044g 0.44mmol), adds Acetyl Chloride 98Min. (0.017g again to add triethylamine, 0.22mmol) TLC detects raw material and disappears behind the stirring at room 6h, with saturated sodium bicarbonate solution washing (50ml * 2), saturated common salt water washing (50ml) anhydrous sodium sulfate drying, pressure reducing and steaming solvent, ethyl alcohol recrystallization gets product 0.081g, yield 85.7%.mp259-261℃；IR(KBr)：3376，2962，1653，1585，1261，1024，801cm-1；1H-NMR(300MHz，DMSO-d6)：δ10.29(br?s，1H，CONH)，8.55(d，1H，J＝1.8Hz，Ar-H)，8.39(d，1H，J＝8.7Hz，Ar-H)，7.91(dd，1H，J＝1.8，8.7Hz，Ar-H)，7.55(s，1H，Ar-H)，7.13(s，1H，Ar-H)，6.25(s，2H，O-CH2-O)，4.45(t，2H，J＝7.5Hz，CON-CH2-)，3.60(s，4H，morpholine-H)，2.25(br?s，6H，morpholine-H，-(CH2)2-CH2-N)，2.14(s，3H，CH3CO)，1.94(m，2H，-CH2-CH2-CH2-).；MS(EI)m/z：475[M]+
Embodiment 54
6-(3-pyrrolidyl-1-propyl group)-5,6-dihydro-3-acetamido-5,11-dicarbapentaborane-8, the preparation of 9-methylene-dioxy-11H-indeno [1,2-c] isoquinolines (compound 54)
With compound 48 (0.083g, 0.2mmol) be dissolved in anhydrous methylene chloride (80ml), (0.044g 0.44mmol), adds Acetyl Chloride 98Min. (0.017g again to add triethylamine, 0.22mmol) TLC detects raw material and disappears behind the stirring at room 6h, with saturated sodium bicarbonate solution washing (50ml * 2), saturated common salt water washing (50ml) anhydrous sodium sulfate drying, pressure reducing and steaming solvent, ethyl alcohol recrystallization gets product 0.082g, yield 89.2%.mp200-203℃；IR(KBr)：3415，1964，1652，1582，1525，1384，1032，802cm-1；1H-NMR(300MHz，DMSO-d6)：δ10.28(br?s，1H，CONH)，8.51(d，1H，J＝1.8Hz，Ar-H)，8.34(d，1H，J＝8.7Hz，Ar-H)，7.87(dd，1H，J＝1.8，8.7Hz，Ar-H)，7.52(s，1H，Ar-H)，7.07(s，1H，Ar-H)，6.23(s，2H，O-CH2-O)，4.23(t，2H，J＝7.5Hz，CON-CH2-)，2.60(m，6H，pyrolidine-H，-(CH2)2-CH2-N)，2.13(s，3H，CH3CO)，1.93(m，2H，-CH2-CH2-CH2-)，1.75(br?s，4H，pyrolidine-H)；MS(EI)m/z：459[M]+
Embodiment 55
6-(3-piperidyl-1-propyl group)-5,6-dihydro-3-acetamido-5,11-dicarbapentaborane-8, the preparation of 9-methylene-dioxy-11H-indeno [1,2-c] isoquinolines (compound 55)
With compound 49 (0.086g, 0.2mmol) be dissolved in anhydrous methylene chloride (80ml), (0.044g 0.44mmol), adds Acetyl Chloride 98Min. (0.017g again to add triethylamine, 0.22mmol) TLC detects raw material and disappears behind the stirring at room 6h, with saturated sodium bicarbonate solution washing (50ml * 2), saturated common salt water washing (50ml) anhydrous sodium sulfate drying, pressure reducing and steaming solvent, ethyl alcohol recrystallization gets product 0.085g, yield 90.2%.mp286-288℃；IR(KBr)：3433，2931，1657，1581，1526，1383，1033，841cm-1；1H-NMR(300MHz，DMSO-d6)：δ10.22(br?s，1H，CONH)，8.48(d，1H，J＝1.8Hz，Ar-H)，8.33(d，1H，J＝8.7Hz，Ar-H)，7.85(dd，1H，J＝1.8，8.7Hz，Ar-H)，7.49(s，1H，Ar-H)，7.08(s，1H，Ar-H)，6.18(s，2H，O-CH2-O)，4.40(t，2H，J＝7.5Hz，CON-CH2-)，2.37(m，6H，piperidine-H，-(CH2)2-CH2-N)，2.08(s，3H，CH3CO)，1.88(m，2H，-CH2-CH2-CH2-)，1.47(br?s，4H，piperidine-H)，1.36(br?s，2H，piperidine-H)；MS(EI)m/z：473[M]+
Embodiment 56
6-(3-diethylin-1-propyl group)-5,6-dihydro-3-amino-5,11-dicarbapentaborane-8, the preparation of 9-methylene-dioxy-11H-indeno [1,2-c] isoquinolines (compound 56)
With compound 50 (0.083g, 0.2mmol) be dissolved in anhydrous methylene chloride (80ml), (0.044g 0.44mmol), adds Acetyl Chloride 98Min. (0.017g again to add triethylamine, 0.22mmol) TLC detects raw material and disappears behind the stirring at room 6h, with saturated sodium bicarbonate solution washing (50ml * 2), saturated common salt water washing (50ml) anhydrous sodium sulfate drying, pressure reducing and steaming solvent, ethyl alcohol recrystallization gets product 0.086g, yield 93.4%.mp279-281℃；IR(KBr)：3314，2971，1642，1593，1517，1301，801cm-1；1H-NMR(300MHz，DMSO-d6)：δ10.24(br?s，1H，CONH)，8.48(d，1H，J＝1.8Hz，Ar-H)，8.35(d，1H，J＝8.7Hz，Ar-H)，7.86(dd，1H，J＝1.8，8.7Hz，Ar-H)，7.65(s，1H，Ar-H)，7.09(s，1H，Ar-H)，6.19(s，2H，O-CH2-O)，4.39(t，2H，J＝7.5Hz，CON-CH2-)，2.54(m，6H，CH2-N-CH2，-(CH2)2-CH2-N)，2.05(s，3H，CH3CO)，1.82(m，2H，-CH2-CH2-CH2-)，0.99(t，6H，J＝7.2Hz，CH3×2)；MS(EI)m/z：461[M]+
Embodiment 57
6-(3-chloropropyl)-5,6-dihydro-3-methoxyl group-5,11-dicarbapentaborane-8, the preparation of 9-methylene-dioxy-11H-indeno [1,2-c] isoquinolines (compound 57)
With suitable-N-(3-chloropropyl)-4-carboxyl-3,4-dihydro-7-methoxyl group-3-(3, the 4-methylene-dioxy)-1 (2.0g 4.9mmol) adds dry toluene (100ml), reflux 1h with sulfur oxychloride (10ml) to (2H) isoquinolines, concentrating under reduced pressure boils off solvent, add oil of mirbane (50ml) in the residuum, and adding aluminum chloride under the ice bath (1.4g, 11mol), be heated to 100 ℃ of 1h, cooling carefully adds entry 30ml, dichloromethane extraction (50ml * 4), the organic layer saturated sodium bicarbonate solution is washed (50ml), saturated sodium-chloride is washed (50ml), anhydrous magnesium sulfate drying, concentrating under reduced pressure, add hexanaphthene (300ml), leave standstill, separate out the cotton-shaped solid of purple, filter, get product 1.05g, yield 53.8%.mp279-281℃；IR：3415，1675，1382，1278，1033，620cm-1； 1H-NMR(CDCl 3)δ8.48(d，1H，J＝9Hz，Ar-H)，7.61(d，1H，J＝2.7Hz，Ar-H)，7.25(dd，1H，J＝2.7，9Hz，Ar-H)，7.19(s，1H，Ar-H)，7.02(s，1H，Ar-H)，6.03(s，2H，O-CH 2-O)，4.54(t，2H，J＝7.5Hz，CON-CH 2-)，3.84(s，3H，CH 3O)，3.74(t，2H，J＝6Hz，CH 2-Cl)，2.30(m，2H，-CH 2-C H 2-CH 2-)；MS(EI)m/z：397[M] +
Embodiment 58
6-(3-methylpiperazine base-1-propyl group)-5,6-dihydro-3-methoxyl group-5,11-dicarbapentaborane-8, the preparation of 9-methylene-dioxy-11H-indeno [1,2-c] isoquinolines (compound 58)
With compound 57 (0.079g, 0.2mmol), methylpiperazine (0.6mmol), (0.17g 1.2mmol) places no Shui diox (20ml) to Anhydrous potassium carbonate, reflux 24h, suction filtration, filtrate steaming removal solvent, the chloroform recrystallization gets product 0.066g, yield 71.6%.mp268-271℃；IR(KBr)：3451，2924，1660，1456，1026，805cm-1；1H-NMR(300MHz，DMSO-d6)：δ8.41(d，1H，J＝8.7Hz，Ar-H)，8.56(d，1H，J＝2.7Hz，Ar-H)，7.45(m，2H，Ar-H)，7.14(s，1H，Ar-H)，6.21(s，2H，O-CH2-O)，4.47(t，2H，J＝7.5Hz，CON-CH2-)，3.87(s，3H，OCH3)，2.72(s，10H，piperazine-H，-(CH2)2-CH2-N)，1.90(m，2H，-CH2-CH2-CH2-)；MS(EI)m/z：461[M]+
Embodiment 59
6-(3-piperidyl-1-propyl group)-5,6-dihydro-3-methoxyl group-5,11-dicarbapentaborane-8, the preparation of 9-methylene-dioxy-11H-indeno [1,2-c] isoquinolines (compound 59)
With compound 57 (0.079g, 0.2mmol), methylpiperazine (0.6mmol), (0.17g 1.2mmol) places no Shui diox (20ml) to Anhydrous potassium carbonate, reflux 24h, suction filtration, filtrate steaming removal solvent, the chloroform recrystallization gets product 0.064g, yield 72.4%.mp227-230 ℃; IR (KBr): 3415,2942,1652,1497,1304,1028,801cm-1; 1H-NMR (300MHz, DMSO-d6): δ 8.38 (d, 1H, J=9Hz, Ar-H), 7.55 (d, 1H, J=2.7Hz, Ar-H), 7.50 (s, 1H, Ar-H), 7.39 (dd, 1H, J=2.7,9Hz, Ar-H), 7.09 (s, 1H, Ar-H), 6.19 (s, 2H, O-CH2-O), 4.41 (t, 2H, J=7.5Hz, CON-CH2-), 3.86 (s, 3H, CH3O), (2.41 t, 2H, J=5.6Hz ,-(CH2) 2-CH2-N), 2.32 (br s, 4H, piperidine-H), 1.86 (m, 2H ,-CH2-CH2-CH2-), 1.46 (br s, 4H, piperidine-H), 1.35 (br s, 2H, piperidine-H); MS (EI) m/z:446[M]+
Embodiment 60
6-(3-pyrrolidyl-1-propyl group)-5,6-dihydro-3-methoxyl group-5,11-dicarbapentaborane-8, the preparation of 9-methylene-dioxy-11H-indeno [1,2-c] isoquinolines (compound 60)
With compound 57 (0.079g, 0.2mmol), methylpiperazine (0.6mmol), (0.17g 1.2mmol) places no Shui diox (20ml) to Anhydrous potassium carbonate, reflux 24h, suction filtration, filtrate steaming removal solvent, the chloroform recrystallization gets product 0.059g, yield 68.7%.mp292-295℃；IR(KBr)：3418，2963，1651，1263，1026，803cm-1；1H-NMR(300MHz，DMSO-d6)：δ8.43(d，1H，J＝9Hz，Ar-H)，7.57(d，1H，J＝2.7Hz，Ar-H)，7.45(dd，1H，J＝2.7，9Hz，Ar-H)，7.40(s，1H，Ar-H)，7.16(s，1H，Ar-H)，6.22(s，2H，O-CH2-O)，4.51(t，2H，J＝7.5Hz，CON-CH2)，3.87(s，3H，CH3O)，3.5(br?s，2H，-(CH2)2-CH2-N)，3.0(br?s，4H，pyrolidine-H)，2.15(m，2H，-CH2-CH2-CH2)，1.90(m，4H，pyrolidine-H)；MS(EI)m/z：432[M]+
Embodiment 61
6-(morpholinyl-1-propyl group)-5,6-dihydro-3-methoxyl group-5,11-dicarbapentaborane-8, the preparation of 9-methylene-dioxy-11H-indeno [1,2-c] isoquinolines (compound 61)
With compound 57 (0.079g, 0.2mmol), methylpiperazine (0.6mmol), (0.17g 1.2mmol) places no Shui diox (20ml) to Anhydrous potassium carbonate, reflux 24h, suction filtration, filtrate steaming removal solvent, the chloroform recrystallization gets product 0.063g, yield 70.3%.mp285-287 ℃, IR (KBr): 3414,2963,1649,1380,1028,804cm-1; 1H-NMR (300MHz, CDCl3): δ 8.53 (d, 1H, J=9Hz, Ar-H), 7.68 (d, 1H, J=2.7Hz, Ar-H), 7.41 (s, 1H, Ar-H), 7.32 (dd, 1H, J=2.7,9Hz, Ar-H), 7.09 (s, 1H, Ar-H), 6.09 (s, 2H, O-CH2-O), 4.53 (t, 2H, J=7.5Hz, CON-CH2), 3.91 (s, 3H, CH3O), 3.70 (s, 4H, morpholine-H), 2.54 (s, 6H, morpholine-H ,-(CH2) 2-CH2-N), 2.04 (m, 2H ,-CH2-CH2-CH2); MS (EI) m/z:448[M]+
Embodiment 62
6-(3-diethylin-1-propyl group)-5,6-dihydro-3-methoxyl group-5,11-dicarbapentaborane-8, the preparation of 9-methylene-dioxy-11H-indeno [1,2-c] isoquinolines (compound 62)
With compound 57 (0.079g, 0.2mmol), methylpiperazine (0.6mmol), (0.17g 1.2mmol) places no Shui diox (20ml) to Anhydrous potassium carbonate, reflux 24h, suction filtration, filtrate steaming removal solvent, the chloroform recrystallization gets product 0.060g, yield 69.5%.mp.225-228 ℃; IR (KBr): 3415,2966,1651,1380,1030,610cm-1; Mp225-228 ℃; 1H-NMR (300MHz, CDCl3) δ 8.53 (d, 1H, J=9Hz, Ar-H), 7.69 (d, 1H, J=2.7Hz, Ar-H), 7.63 (s, 1H, Ar-H), 7.32 (dd, 1H, J=2.7,9Hz, Ar-H), 7.08 (s, 1H, Ar-H), 6.07 (s, 2H, O-CH2-O), 4.48 (t, 2H, J=7.5Hz, CON-CH2), 3.91 (s, 3H, CH3O), 2.59 (m, 6H,, CH2-N-CH2 ,-(CH2) 2-CH2-N), 1.97 (m, 2H ,-CH2-CH2-CH2), 1.08 (t, 6H, J=7.2Hz, CH3 * 2); MS (EI) m/z:434[M]+

Claims (5)

1. the indenoisoquinoline ketone compound of structural formula (I) or its pharmacy acceptable salt:
Figure FSB00000419743600011
2. the indenoisoquinoline ketone compound of claim 1 or its pharmacy acceptable salt, wherein pharmacy acceptable salt is acetate, hydrochloride, vitriol or phosphoric acid salt.
3. pharmaceutical composition is comprising indenoisoquinoline ketone compound or its pharmacy acceptable salt and the pharmaceutically acceptable carrier of claim 1.
4. the indenoisoquinoline ketone compound of claim 1 or its pharmacy acceptable salt are used to prepare the purposes of the medicine for the treatment of tumor disease.
5. the purposes of claim 4, wherein tumor disease is cancer of the stomach, mammary cancer, liver cancer or colorectal carcinoma.
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