CN103450093A - 2-aminobenzimidazoles and applications thereof - Google Patents
2-aminobenzimidazoles and applications thereof Download PDFInfo
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Abstract
The invention relates to the field of medicinal chemistry and particularly relates to 2-aminobenzimidazoles, preparation methods thereof, medicinal compositions with the 2-aminobenzimidazoles and medical applications of the 2-aminobenzimidazoles.
Description
Technical field
The present invention relates to the pharmaceutical chemistry field, provide a class to there is the structure of anti-tumor activity.
Background technology
Along with the progress of medical science, general communicate illness is controlled gradually, and malignant tumour becomes one of principal disease of day by day common and serious threat human life and quality of life.According to World Health Organization's report, tumour is the main cause of death in one, the whole world.Die ten thousand deaths and die in sum in the whole world 5800 in 2005, the number of dying from tumour is 7,600,000 (approximately 13%)., in following decades, estimate that whole world tumor mortality number will continue to increase, within 2015, will there be 8,500,000 people to die from tumour, the year two thousand thirty will reach 1,450 ten thousand people.
Antitumour drug refers to the medicine of anti-malignant tumor, claims again anticarcinogen.After the forties mustargen is used for the treatment of malignant lymphoma, chemotherapy in decades makes great progress, and by single chemotherapy, has been entered the stage of comprehensive chemotherapy, and can successful healing the sick or significantly extend patient's life.In recent years, along with the development of Protocols in Molecular Biology with to Tumorigenesis and in the further understanding of cellular and molecular level, new drug development by traditional substrate-acceptor-gene pharmaceutical research pattern to this reverse molecular pharmacology Mode change of gene-acceptor-medicine.And the research of antitumor drug also just develops from traditional cell toxicity medicament towards the new type antineoplastic medicine for a plurality of link targets tumor development mechanism.
Yet existing antitumor drug exists the problems such as selectivity is poor, toxic side effect, resistance.The antitumor drug of finding high-efficiency low-toxicity is still the important topic that scientist faces.The invention provides 2-benzyl amino phenyl imidazoles structure with anti-tumor activity, there is important development prospect.
Summary of the invention
The 2-benzyl amino phenyl that provides a class to have anti-tumor activity imidazoles structure are provided.
Another object of the present invention is to provide the preparation method of above-claimed cpd.
Another purpose of the present invention is to provide the pharmaceutical composition that comprises above-claimed cpd or its pharmacy acceptable salt.
An also purpose of the present invention is, provides the medical use of above-claimed cpd or its pharmaceutically-acceptable salts and medicinal compositions thereof, especially the purposes in the medicine for the treatment of tumour.
For achieving the above object, the invention provides compound or its pharmacy acceptable salt with structure shown in general formula I:
Wherein, R
1mean H, nitro, amino, formamido group, kharophen, ethanoyl; R
2expression-H, methyl, ethyl, cyclopentyl, phenyl, benzyl, 3-first carbamyl phenyl, 4-first carbamyl phenyl; R
3expression-H, methoxyl group; R
4mean H, methoxyl group, the first carbamyl, carbamyl, the second carbamyl, encircle penta carbamyl, 3-methoxy propyl carbamyl, morpholinyl the third carbamyl, N-methyl piperidine-4-formamyl, tertiary fourth carbamyl.
According to the present invention, pharmacy acceptable salt comprises the acid salt that compound of Formula I and following acid form: hydrochloric acid, Hydrogen bromide, sulfuric acid, phosphoric acid, methylsulfonic acid, Phenylsulfonic acid, tosic acid, naphthene sulfonic acid, citric acid, tartrate, lactic acid, pyruvic acid, acetic acid, toxilic acid or succsinic acid, fumaric acid, Whitfield's ointment, phenylacetic acid, tussol.The acid salt that comprises in addition mineral alkali, as: basic metal positively charged ion, alkaline earth metal cation, ammonium cation salt contained.
The compound of above-mentioned general formula I can be:
Part of compounds preparation method of the present invention is as follows:
Scheme1
Reagents?and?conditions：
(i)BrCN，MeCN，H
2O，90℃，2h；(ii)subsititued?benzaldehyde，toluene，reflux，8h；then?KBH
4，MeOH，0℃，30min；(iii)methylamine，rt，10h；(iv)ammonium?hydroxide，sealed?tube，40℃，12h.
Scheme2
Reagents?and?conditions：
(i)aliphatic?amine，THF，0℃～rt，5h／aromatic?amine，t-BuOK，DMF，90℃，5h；(ii)Fe，NH
4Cl，EtOH，reflux，6h；(iii)BrCN，MeCN，H
2O，90℃，2h；(iV)subsititued?benzaldehyde，toluene，reflux，8h；then?KBH
4，MeOH，0℃，30min；(v)methylamine?or?ethylamine，rt，10h／ammonium?hydroxide，sealed?tube，40℃，12h；(vi)KOH，H
2O，EtOH，reflux，2h；(vii)subsititued?primary?amine，HATU，DIPEA，DMF,rt，12h.
The compounds of this invention can prepare by above-mentioned or similar above-mentioned preparation method, according to the difference of substituent difference and substituting group position, selects corresponding raw material to get final product.
The Pharmacodynamics in vitro evidence: such medicine has obvious restraining effect to colorectal carcinoma, ovarian cancer and acute myeloid leukaemia, has good antitumour activity.The compounds of this invention can be used for treating various parenchymatous organ's cancers, comprising melanoma, liver cancer, kidney, lung cancer, prostate cancer, thyroid carcinoma, skin carcinoma, colorectal carcinoma, carcinoma of the pancreas, ovarian cancer, mammary cancer, carcinoma of testis, osteocarcinoma, the cancer of the brain, the esophageal carcinoma, gastrointestinal cancer, soft-tissue tumor, leukemia, lymphatic cancer etc.Therefore, the present invention proposes, and the compounds of this invention and pharmacy acceptable salt thereof can be used for the preparation of cancer therapy drug.
The pharmacology test of compound is as follows:
Tumor cell in vitro suppresses active testing
The compounds of this invention is in vitro to the inhibition activity of tumor cell line.
The I experiment material
96 porocyte culture plates (Corning, USA), T25 Tissue Culture Flask (Corning, USA), T75 Tissue Culture Flask (Corning, USA), centrifuge tube (Corning, USA), transfer pipet (Corning, USA)
dyestuff (Invitrogen, USA), 3%SDS phosphate buffered saline buffer (Invitrogen, USA), the black wall culture plate (Corning, USA) in 384 holes, rifle head (Axygen, USA), Multidrop sample injector (Thermo, USA), Janus liquid processing system (Perkinelmer, USA), the long microwell plate plate reading of Safire2 all-wave (Tecan, Switzerland).
The II experimental procedure
Before detecting, cell is processed 24-72 hour with testing compound,
add in cell culture medium 5%CO according to ten times of Dilution ratios
2with 37 ℃, lucifuge is hatched 1-4 hour.Adopt the long microwell plate plate reading of all-wave (Safire2, Switzerland) to detect fluorescent value, instrument setting: excitation wavelength (excitaion)=540nm, wavelength of transmitted light (emission)=585nm.Adopt inhibiting rate and the IC of Prism5.0 (Graphpad Software, USA) statistical analysis software computerized compound
50value.
Activity data is as shown in the table:
(in table, the compound code name is corresponding to the compound code name of front)
Embodiment
Fusing point is measured with b shape melting point tube, and medium is methyl-silicone oil, and thermometer is not proofreaied and correct;
1for HNMR, JEOL FX90Q type fourier transform NMR instrument, BRUKER ACF-300 type nuclear magnetic resonance analyser and BRUKER AM-500 type nuclear magnetic resonance analyser complete (mark in TMS); MS measures with Nicolet2000 type Fourier transform mass spectrometer and MAT-212 type mass spectrograph.
Embodiment 1
1H-benzo [d] imidazoles-2-amine (1a)
Add water 20ml, acetonitrile 5ml and O-Phenylene Diamine 0.70g (6.5mmol) in the 50ml reaction flask, the rear BrCN0.69g (6.5mmol) that slowly in batches adds stirs, finish and be warming up to 100 ℃, backflow 2h, TLC shows that raw material is without residue, stopped reaction, cooling rear extremely alkaline with ammoniacal liquor adjusting PH, separate out white deep, suction filtration, filtrate is with ethyl acetate extraction (80ml * 3), the anhydrous MgSO of organic phase
4drying, filter and concentrating under reduced pressure, with filter cake, merges, and ethyl alcohol recrystallization, obtain white crystal 0.70g, yield 81.0%, mp.223～226 ℃, MS[M+H]
+134.05.
Embodiment 2
5-nitro-1H-benzo [d] imidazoles-2-amine (1b)
The preparation method is similar to the preparation of 1a, light red solid, yield 45.5%, mp.212～214 ℃.
Embodiment 3
2-amino-1H-benzo [d] imidazoles-5-ethyl formate (1c)
The preparation method is similar to the preparation of 1a, white solid, yield 62.9%, mp.216～218 ℃, MS[M+H]
+206.08.
Embodiment 4
4-(1H-benzo [d] imidazoles-2-base aminomethyl) methyl benzoate (2a)
Single neck bottle in 100ml adds 1H-benzo [d] imidazoles-2-amine (1a) 1.33g (10mmol), toluene 50ml, p formylbenzoic acid methyl esters 1.97g (12mmol); back flow reaction 4h, concentrated, then add methyl alcohol 50ml; under ice bath; add excessive POTASSIUM BOROHYDRIDE, reaction 30min, filter in batches; column chromatography (PE:EA=1:5) after filtrate is concentrated; obtain white solid 2.4g, yield 84.7%, mp.235～236 ℃.
1HNMR(300MHz?DMSO-d
6)δ：11.08(1H，s，ArH)，7.94(2H，d，ArH)，7.50(2H，d，ArH)，7.32(1H，s，imidazole)，7.12(2H，m，ArH)，6.88(2H，m，ArH)，4.60(2H，d，-NHC
H 2)，3.83(3H，s，-OCH
3).
Embodiment 5
2-(4-methoxybenzyl amino)-1H-benzo [d] imidazoles-5-ethyl formate (2b)
The preparation method is similar to the preparation of 2a, white solid, and yield 86.0%, purifying does not directly carry out next step reaction.
Embodiment 6
2-methylamino-aniline (3a)
Add aqueous methylamine solution 20ml in the three-necked bottle of 50ml, cryosel is bathed cooling 10min, slowly drips wherein the THF solution 10ml of o-fluoronitrobenzene 1.41g (10mmol), stir 5h, concentrating under reduced pressure, and, with ethyl acetate extraction (20ml * 3), organic phase is with anhydrous MgSO
4drying, suction filtration, concentrating under reduced pressure obtains yellow liquid 1.2g.
Add upper step product 1.2g (7.9mmol), 75% aqueous ethanolic solution 30ml, ammonium chloride 1.27g (23.7mmol) and reduced iron powder 1.33g (23.7mmol) in the 250ml reaction flask, mechanical stirring also is warming up to 100 ℃, after 6h, stop, suction filtration while hot, and with hot ethyl acetate washing leaching cake, filtrate decompression concentrates to obtain light brown liquid 0.87g, and purifying is not directly used in next step.
Embodiment 7
2-ethylamino aniline (3b)
The preparation method is similar to the preparation of 3a, light brown liquid, and yield 85%, purifying does not directly carry out next step reaction.
Embodiment 8
2-cyclopentyl aniline (3c)
The preparation method is similar to the preparation of 3a, light brown liquid, yield 83%, MS[M+H]
+177.1.
Embodiment 9
2-phenylaniline (3d)
Add o-fluoronitrobenzene 1.41g (10mmol), aniline 0.93g (10mmol) and dry DMF 20ml in the 50ml three-necked bottle, stirring at room is even, adds potassium tert.-butoxide 1.34g (12mmol) in batches, finishes and is warming up to 90 ℃, after 5h, stops.Filter fast reaction solution with short silicagel column, filtrate concentrates to obtain red liquid 1.72g, yield 80.3%.
By upper step product 1.72g (8mmol), 75% aqueous ethanolic solution 30ml, ammonium chloride 1.28g (24mmol) and reduced iron powder 1.34g (24mmol), mechanical stirring also is warming up to 100 ℃, after 6h, stop, suction filtration while hot, and with hot ethyl acetate washing leaching cake, concentrated light brown solid 1.32g, mp.87～88 ℃ of obtaining of filtrate decompression, yield 90%, purifying is not directly used in next step.
Embodiment 10
2-benzylaniline (3e)
The preparation method is similar to the preparation of 3d, light brown solid, mp.52～54 ℃ (document
[7]mp.50～52 ℃), yield 70%.
Embodiment 11
4-(2-amino phenyl amino) methyl benzoate (3f)
The preparation method is similar to the preparation of 3d, faint yellow oily matter, yield 65%, MS[M+H]
+257.2.
Embodiment 12
3-(2-amino phenyl amino) methyl benzoate (3g)
The preparation method is similar to the preparation of 3d, white solid, mp.89～90 ℃, yield 62%, MS[M+H]
+243.2.
Embodiment 13
2-ethylamino-4-N-methyl-p-nitroaniline (3h)
The fluoro-5-N-methyl-p-nitroaniline of 2-1.56g (10mmol), ethylamine solution 15ml and THF2ml are added in reaction flask, stirring at room 4h, column chromatography (PE:EA=2:1) after concentrated, obtain garnet solid 1.19g, mp.136～138 ℃ (document mp.139 ℃), yield 65.7%, MS[M+H]
+182.1, MS[M-H]
-180.1.
Embodiment 14
1-methyl isophthalic acid H-benzo [d] imidazoles-2-amine (4a)
The preparation method is similar to the preparation of 1a, white solid, yield 86%, mp.203～205 ℃.
Embodiment 15
1-ethyl-1H-benzo [d] imidazoles-2-amine (4b)
The preparation method is similar to the preparation of 1a, white solid, yield 86%, mp.146～148 ℃.
1HNMR(300MHz?DMSO-d
6)δ：7.99(1H，s，ArH)，7.74(1H，d，ArH)，7.62(2H，s，ArH)，4.72(2H，q，-C
H 2CH
3)，1.45(3H，t，-CH
2C
H 3).
Embodiment 16
1-cyclopentyl-1H-benzo [d] imidazoles-2-amine (4c)
The preparation method is similar to the preparation of 1a, white solid, yield 74%, mp.146～148 ℃, MS[M+H]
+202.1.
Embodiment 17
1-phenyl-1H-benzo [d] imidazoles-2-amine (4d)
The preparation method is similar to the preparation of 1a, light brown solid, yield 76.3%, mp.152～154 ℃.
Embodiment 18
1-benzyl-1H-benzo [d] imidazoles-2-amine (4e)
The preparation method is similar to the preparation of 1a, light brown solid, yield 80.5%, mp.192～193 ℃.
Embodiment 19
4-(2-amino-1H-benzo [d] imidazoles-1-yl) ethyl benzoate (4f)
The preparation method is similar to the preparation of 1a, white crystal, yield 50.9%, mp.162～164 ℃, MS[M+H]
+282.2.
Embodiment 20
3-(2-amino-1H-benzo [d] imidazoles-1-yl) methyl benzoate (4g)
The preparation method is similar to the preparation of 1a, white crystal, yield 71.3%, mp.164～166 ℃, MS[M+H]
+268.2.
Embodiment 21
N-(4-methoxy-benzyl)-1-ethyl-1H-benzo [d] imidazoles-2-amine (BZ-1)
The preparation method is similar to the preparation of 2a, white solid, yield 82.0%, mp.169～170 ℃.
1HNMR(300MHz?DMSO-d
6)δ：7.30(2H，d，ArH)，7.13-7.17(3H，m，ArH?and-NH-)，6.86-6.94(4H，m，ArH)，4.51(2H，d，-NHC
H 2)，4.04(2H，q，-C
H 2CH
3)，3.71(3H，s，-OCH
3)，1.97(3H，t，-CH
2C
H 3).MS[M+H]
+282.2.IR(KBr，cm
-1)742.62，1026.16，1082.10，1176.62，1249.91，1269.20，1338.64，1398.44，1464.02，1516.10，1566.25，1600.97，1614.47，2906.82，2966.62，3009.05，3180.72，3448.84.
Embodiment 22
N-(4-methoxy-benzyl)-1H-benzo [d] imidazoles-2-amine (BZ-2)
The preparation method is similar to the preparation of 2a, white solid, yield 80.0%, mp.190～191 ℃.
1HNMR(300MHz?DMSO-d
6)δ：10.73(1H，s，imidazole)，7.29(2H，d，ArH)，7.10(2H，s，ArH)，6.70(1H，t，-NH-)，6.86-6.91(5H，m，ArH)，4.42(2H，d，-CH
2-)，3.71(3H，s，-OCH
3).MS[M+H]
+254.2.IR(KBr，cm
-1)455.22，742.62，1022.31，1244.13，1271.13，1346.36，1465.95，1508.38，1579.75，1602.90，1637.62，2960.83，3005.20，3421.83.
Embodiment 23
N-methyl-4-(1H-benzo [d] imidazoles-2-base aminomethyl) benzamide (BZ-3)
Intermediate 2a0.12g (0.5mmol) is added in the 5ml aqueous methylamine solution, and add 0.5ml methyl alcohol hydrotropy, stirring at room 5h, with DCM extraction (20ml * 3), organic phase is with anhydrous magnesium sulfate drying, and column chromatography after concentrating under reduced pressure (DCM:MeOH=100:1), obtain white solid 0.056g, yield 40.1%, mp.123～124 ℃.
1HNMR(300MHz?DMSO-d
6)δ：10.88(1H，s，imidazole)，8.36(1H，s，-CONH)，7.76-7.79(2H，d，ArH)，7.41-7.44(2H，d，ArH)，7.10-7.19(3H，m，ArH?and-CH
2N
H)，6.84-6.89(2H，m，ArH)，4.55(2H，d，-C
H 2NH)，2.76(3H，d，-CONHC
H 3).MS[M+H]
+280.1.IR(KBr，cm
-1)746.48，852.56，1018.45，1157.33，1215.19，1346.36，1410.01，1506.46，1568.18，1627.97，1678.13，2928.04，2999.41，3045.70，3091.99.
Embodiment 24
2-(4-methoxybenzyl amino)-1H-benzo [d] imidazoles-5-methane amide (BZ-4)
Intermediate 2b0.20g (0.6mmol), ammoniacal liquor 5ml and ethanol 2ml are placed in tube sealing, and 70 ℃ are stirred 12h, suction filtration, and filter cake column chromatography (DCM:MeOH=30:1), obtain white solid 0.062g, yield 35.0%, mp.198～200 ℃.
1HNMR(300MHz?DMSO-d
6)δ：10.98(1H，s，imidazole)，7.70(2H，d，-CONH
2)，7.49(1H，s，-NH-)，6.87-7.31(7H，m，ArH)，4.44(2H，d，-NHC
H 2-)，3.72(3H，s，-OCH
3).MS[M+H]
+297.2，MS[M-H]
-295.2.IR(KBr，cm
-1)1024.24，1233.52，1289.46，1354.07，1384.94，1513.21，1568.18，1603.86，1641.48，3366.86.
Embodiment 25
N-(4-methoxy-benzyl)-5-nitro-1H-benzo [d] imidazoles-2-amine (BZ-5)
The preparation method is similar to the preparation of 2a, faint yellow solid, yield 29.8%, mp.197～198 ℃.
1HNMR(300MHz?DMSO-d
6)δ：11.4(1H，m，NH)，8.0(2H，m，ArH)，7.9(2H，m，ArH)，7.8(2H，m，ArH)，6.8(1H，m，NH)，6.8(2H，m，ArH)，4.5(2H，d，-CH
2-)，3.7(3H，s，-CH
3).MS[M+H]
+299.2.IR(KBr，cm
-1)1246.06，1288.49，1303.92，1329.00，1469.81，1512.24，1579.75，1591.33，1614.47，1649.19，3394.83，3408.33.
Embodiment 26
N-(4-methoxy-benzyl)-1-methyl isophthalic acid H-benzo [d] imidazoles-2-amine (BZ-6)
The preparation method is similar to the preparation of 2a, faint yellow solid, yield 58.3%, mp.169～170 ℃.
1HNMR(300MHz?DMSO-d
6)δ：7.30-7.34(2H，d，ArH)，7.11-7.17(3H，m，ArH?and-NH
2)，6.86-6.95(4H，m，ArH)，4.50(2H，d，-NHC
H 2)，3.71(3H，s，-OCH
3)，3.51(3H，s，-CH
3).MS[M+H]
+268.2.IR(KBr，cm
-1)688.61，742.62，1180.47，1240.27，1288.49，1386.86，1444.73，1473.66，1575.89，1612.54，1693.56，2947.33，3169.15.
Embodiment 27
N-benzyl-1-ethyl-1H-benzo [d] imidazoles-2-amine (BZ-7)
The preparation method is similar to the preparation of 2a, white needle-like crystals, yield 65%, mp.155～157 ℃.
1HNMR(300MHz?DMSO-d
6)δ：7.29-7.39(4H，m，ArH)，7.23(2H，m，ArH)，7.14-7.17(2H，m，ArH)，6.87-6.95(2H，m，ArH?and-NH)，4.59(2H，d，-NHC
H 2-)，4.06(2H，q，-C
H 2CH
3)，1.22(3H，t，-CH
2C
H 3).MS[M+H]
+252.2.IR(KBr，cm
-1)694.40，738.76，1014.59，1074.39，1130.32，1219.05，1238.34，1273.06，1346.36，1390.72，1467.88，1521.89，1573.97，1604.83，2972.40，3167.22，3412.19.
Embodiment 28
N-(3,4-dimethoxy-benzyl)-1-ethyl-1H-benzo [d] imidazoles-2-amine (BZ-8)
The preparation method is similar to the preparation of 2a, white crystal, yield 63.4%, mp.179～182 ℃.
1HNMR(300MHz?DMSO-d
6)δ：7.15(3H，s，ArH)，7.03(1H，s，-NH
2-)，6.90(4H，m，ArH)，4.51(2H，d，-NHC
H 2-)，4.05(2H，m，-C
H 2CH
3)，3.72(6H，d，-OCH
3×2)，1.21(3H，t，-CH
2C
H 3).MS[M+H]
+3122IR(KRr，cm
-1)738.76，761.91，1030.02，1134.18，1242.20，1269.20，1398.44，1444.73，1465.95，1518.03，1560.461597.11，1614.47，2966.62，2980.12，3151.79.
Embodiment 29
N-methyl-4-((1-ethyl-1H-benzo [d] imidazoles)-2-base aminomethyl) benzamide (BZ-9)
The preparation method is similar to the preparation of BZ-3, white crystal, yield 62%, mp.235～238 ℃.
1HNMR(300MHz?DMSO-d
6)δ：8.36(1H，m，-CONH)，7.77(2H，d，ArH)，7.45(2H，d，ArH)，7.33(1H，t，-N
HCH
2)，6.92(2H，m，ArH)，4.64(2H，d，-NHC
H 2)，4.07(2H，q，-C
H 2CH
3)，2.76(3H，d，-NHC
H 3)，1.23(3H，t，-CH
2C
H 3).MS[M+H]
+309.2.IR(KBr，cm-1)758.05，1080.17，1203.62，1238.34，1271.13，1305.85，1327.07，1381.08，1400.37，1464.02，1527.67，1560.46，1599.04，1618.33，1641.48，2964.69，3153.723300.31.
Embodiment 30
4-((1-ethyl-1H-benzo [d] imidazoles)-2-base aminomethyl) benzamide (BZ-10)
The preparation method is similar to the preparation of BZ-4, white crystal, yield 37.5%, mp.252～253 ℃.
1HNMR(300MHz?DMSO-d
6)δ：7.8(1H，t，-NH-)，7.7(2H，s，-CONH
2)，7.5(2H，m，ArH)，7.3(2H，m，ArH)，7.1(2H，m，ArH)，6.9(2H，m，ArH)，4.65(2H，d，-CH
2-)，4.1(2H，q，-C
H 2CH
3)，1.2(3H，t，-CH
3).MS[M+H]
+291.5.IR(KBr，cm
-1)1384.94，1464.02，1556.61，1597.11，1618.33，1672.34，3456.55.
Embodiment 31
N-(4-methoxy-benzyl)-1-ethyl-5-nitro-1H-benzo [d] imidazoles-2-amine (BZ-11)
The preparation method is similar to the preparation of 2a, yellow crystals, yield 86.1%, mp.168～170 ℃.
1HNMR(300MHz?DMSO-d
6)δ：7.97(1H，d，ArH)，7.90(1H，dd，ArH)，7.74(1H，t，-N
HCH
2)，7.38(1H，d，ArH)，7.31(2H，d，ArH)，6.90(2H，m，ArH)，4.56(2H，d，-NHC
H 2)，4.14(2H，q，-C
H 2CH
3-)，3.72(3H，s，-OCH
3)，1.23(3H，t，-CH
2C
H 3).MS[M+H]
+327.2，MS[M-H]
-325.2.IR(KBr，cm
-1)252.81，1276.92，1335.75，1461.13，1516.10，1542.14，1563.36，1569.14，1574.93，1609.65.
Embodiment 32
N
2-(4-methoxy-benzyl)-1-ethyl-1H-benzo [d] imidazoles-2,5-diamines (BZ-12)
The preparation method is similar to 6 preparation, light brown crystal, yield 95.5%, mp.157～159 ℃.
1HNMR(300MHz?DMSO-d
6)δ：7.28(2H，d，ArH)，6.87(3H，m，ArH?and-N
HCH
2)，6.78(1H，d，ArH)，6.44(1H，d，ArH)，6.21(1H，dd，ArH)，4.56(2H，d，-NHC
H 2-)，4.38(2H，s，-NH
2)，3.90(2H，q，-C
H 2CH
3)，3.71(3H，s，-OCH
3)，1.16(3H，t，-CH
2C
H 3).MS[M+H]
+297.1，MS[M-H]
-295.2.IR(KBr，cm
-1)1172.76，1247.02，1341.54，1398.44，1456.30，1471.74，1487.17，1511.28，1543.10，1559.50，1603.86，1633.76，1650.16，1684.88，3365.90，3419.90，3446.91.
Embodiment 33
N-methyl-4-((1-ethyl-5-amino-1H-benzo [d] imidazoles)-2-base aminomethyl) benzamide (BZ-13)
The preparation method is similar to the preparation of BZ-3, yellow solid, yield 46.0%, mp.125～127 ℃.
1HNMR(300MHz?DMSO-d
6)δ：8.33(1H，d，-CONH)，7.76(2H，d，ArH)，7.41(2H，d，ArH)，7.03(1H，t，-NH)，6.80(1H，d，ArH)，6.42(1H，d，ArH)，6.22(1H，dd，ArH)，4.58(2H，d，-NHC
H 2-)，4.38(2H，s，-NH
2)，3.94(2H，q，-C
H 2CH
3)，2.75(3H，d，-NHC
H 3)，1.18(3H，t，-CH
2C
H 3).MS[M+H]
+324.2，MS[M-H]
-322.2.IR(KBr，cm
-1)1247.99，1304.89，1321.28，1370.47，1415.80，1459.20，1504.53，1541.18，1560.46，1597.11，1636.65，1653.05，3260.77，3315.74.
Embodiment 34
N-(1-ethyl-2-(4-methoxybenzyl amino)-1H-benzo [d] imidazoles)-5-yl) ethanamide (BZ-14)
Add compd B Z-120.3g (1mmol), triethylamine 1ml and THF3ml in the mono-neck bottle of 10ml, the cooling 10min of ice bath, dropwise drip diacetyl oxide 1ml, stir 1h, remove solvent under reduced pressure, add frozen water 5ml, and regulate PH to 8, separate out a large amount of white solids, suction filtration, the filter cake infrared drying, obtain white powder 0.3g, yield 88.7%, mp.247～248 ℃.
1HNMR(300MHz?DMSO-d
6)δ：9.65(1H，d，-CONH-)，7.43(1H，d，-NH-)，6.86-7.31(7H，m，ArH)，4.49(2H，d，-NHC
H 2-)，4.00(2H，d，-C
H 2CH
3)，3.71(3H，s，-OCH
3)，2.00(3H，s，-COC
H 3)，1.18(3H，t，-CH2C
H 3).MS[M+H]
+339.2.IR(KBr，cm
-1)1245.09，1281.74，1437.98，1472.70，1487.17，1512.24，1543.10，1558.54，1575.89，1610.61，1636.65，1652.09，1665.59，3295.49.
Embodiment 35
N-ethyl-4-((1-ethyl-1H-benzo [d] imidazoles)-2-base aminomethyl) benzamide (BZ-15)
The preparation method is similar to the preparation of BZ-3, white crystal, yield 60%, mp.221～222 ℃.
1HNMR(300MHz?DMSO-d
6)δ：8.4(1H，s，-CONH-)，7.8(2H，m，ArH)，7.5(2H，m，ArH)，7.3(1H，t，-NH-)，7.1(2H，m，ArH)，6.9(2H，m，ArH)，4.65(2H，d，-CH
2-)，4.2(2H，q，-CH
2CH
3)，3.3(2H，q，-CH
2CH
3)，1.2(3H，t，-CH
3)，1.1(3H，t，-CH
3).MS[M-H]
+321.1.IR(KBr，cm
-1)1288.49，1552.75，1570.11，1602.90，1620.26，1633.76，3244.38，3325.39，3414.12，3468.13.
Embodiment 36
N-cyclopentyl-4-((1-ethyl-1H-benzo [d] imidazoles)-2-base aminomethyl) benzamide (BZ-16)
Add intermediate 5b0.62g (2mmol), water 10ml, KOH0.22g (4mmol) in the mono-neck bottle of 25ml, backflow 5h, be cooled to room temperature, reaction solution is adjusted PH to 3 with 6mol/L hydrochloric acid, separates out white solid, suction filtration, vacuum-drying, obtain white powdery solid 0.5g, yield 85%, be not further purified.
Get step product 0.5g (1.7mmol), HATU0.77g (2.0mmol), DIPEA1ml and DMF20ml, add cyclopentamine 0.17g (2.0mmol) after stirring, stirring at room 12h, TLC shows that raw material disappears, the pressure reducing and steaming solvent, through column chromatography, (DCM: MeOH=1: 2) purifying obtains the 0.42g white solid to crude product, yield 75%, mp.199～200 ℃
1HNMR(300MHz?DMSO-d
6)δ：7.7(2H，m，ArH)，7.5(2H，m，ArH)，7.3(1H，t，-NH-)，7.1(2H，m，ArH)，6.9(2H，m，ArH)，4.75(2H，d，-CH
2-)，4.1(2H，q，-CH
2CH
3)，1.45(8H，m，-CH
2-)，1.45(1H，m，CH)，1.3(3H，t，-CH
3).MS[M+H]
+363.2.IR(KBr，cm
-1)1523.82，1539.25，1548.89，1566.25，1600.97，1618.33，1633.76，3313.82.
Embodiment 37
N-(3-methoxy-propyl)-4-((1-ethyl-1H-benzo [d] imidazoles)-2-base aminomethyl) benzamide (BZ-17)
The preparation method is similar to the preparation of BZ-16, white solid, yield 66%, mp.171～172 ℃.
1HNMR(300MHz?DMSO-d
6)δ：8.4(1H，s，-CONH-)，7.7(2H，m，ArH)，7.5(2H，m，ArH)，7.3(1H，t，-NH-)，7.1(2H，m，ArH)，6.9(2H，m，ArH)，4.75(2H，d，-CH
2-)，3.3(2H，m，-CH
2-)，3.2(3H，s，-CH
3)，3.1(3H，m，-CH2CH
3)，3.1(2H，m，-CH
2C
H 3)，1.72(2H，q，-C
H 2CH
3)，1.25(3H，t，-CH
3).MS[M+H]
+367.1.IR(KBr，cm
-1)1552.75，1566.25，1602.90，1618.33，1641.48，3329.25，3414.12，3468.13.
Embodiment 38
N-(3-morpholine propyl group)-4-((1-ethyl-1H-benzo [d] imidazoles)-2-base aminomethyl) benzamide (BZ-18)
The preparation method is similar to the preparation of BZ-16, white solid, yield 65%, mp.178～179 ℃.
1HNMR(300MHz?DMSO-d
6)δ：8.35(1H，s，-CONH-)，7.8(2H，m，ArH)，7.5(2H，m，ArH)，7.3(1H，t，-NH-)，7.1(2H，m，ArH)，6.9(2H，m，ArH)，4.75(2H，d，-CH
2-)，4.1(2H，q，-CH
2CH
3)，3.65(2H，m，-CH
2-)，3.3(2H，m，-CH
2-)，2.5(2H，m，-CH
2-)，2.5(4H，m，-CH
2-)，2.5(2H，m，-CH
2-)，1.6(2H，q，-CH
2-)，1.25(3H，t，-CH
3).MS[M-H]
-420.1.IR(KBr，cm
-1)1556.61，1566.25，1602.90，1618.33，1629.90，3290.67，3342.75，3416.05.
Embodiment 39
N-(1-methyl piperidine-4-yl)-4-((1-ethyl-1H-benzo [d] imidazoles)-2-base aminomethyl) benzamide (BZ-19)
The preparation method is similar to the preparation of BZ-16, white solid, yield 58%, mp.189～190 ℃.
1HNMR(300MHz?DMSO-d
6)δ：7.8(2H，m，ArH)，7.5(2H，m，ArH)，7.3(1H，t，-NH-)，7.1(2H，m，ArH)，6.9(2H，m，ArH)，4.65(2H，d，-CH
2-)，4.1(2H，q，-CH
2CH
3)，3.9(H，m，-CH)，3.2(2H，m，-CH
2-)，2.65(2H，m，-CH
2-)，2.1(2H，m，-CH
2-)，1.8(2H，m，-CH
2-)，1.35(3H，t，-CH
3).MS[M-H]
+390.1.IR(KBr，cm
-1)1546.96，1570.11，1602.90，1618.33，1629.90，3242.45，3269.45，3304.17，3416.05，3456.55.
Embodiment 40
N-(4-methoxy-benzyl)-1-cyclopentyl-1H-benzo [d] imidazoles-2-amine (BZ-20)
The preparation method is similar to the preparation of 2a, white crystal, yield 82.6%, mp.185～186 ℃.
1HNMR(300MHz?DMSO-d
6)δ：7.31(2H，d，ArH)，7.16-7.20(2H，m，ArH)，7.70(1H，t，ArH)，6.93(1H，t，ArH)，6.89(3H，m，ArH?and-NH)，4.80(1H，m，-cyclopentane)，4.50(2H，d，-NHC
H 2-)，3.72(3H，s，-OCH
3)，?2.06(2H，m，cyclopentane)，1.94(4H，m，cyclopentane)，1.68(2H，m，cyclopentane).MS[M+H]
+322.2.IR(KBr，cm
-1)738.76，813.99，1031.95，1247.99，1284.63，1464.02，1514.17，1570.11，1614.47，2956.97，3277.17.
Embodiment 41
N-methyl-4-((1-cyclopentyl-1H-benzo [d] imidazoles)-2-base aminomethyl) benzamide (BZ-21)
The preparation method is similar to the preparation of BZ-3, white crystal, yield 59%, mp.245～247 ℃.
1HNMR(300MHz?CD
3OD)δ：7.76(2H，d，ArH)，7.47(2H，d，ArH)，7.22(2H，m，ArH)，6.99(2H，m，ArH)，4.77(1H，m，cyclopentane)，4.70(2H，d，-CH
2-)，2.90(3H，s，-CH
3)，1.80-2.18(8H，m，cyclopentane).MS[M+H]
+349.2.IR(KBr，cm
-1)738.69，1026.06，1463.87，1514.02，1569.95，1614.31，1958.60，3282.62.
Embodiment 42
4-((1-cyclopentyl-1H-benzo [d] imidazoles)-2-base aminomethyl) benzamide (BZ-22)
The preparation method is similar to the preparation of BZ-4, white solid, yield 41.5%, mp.189～190 ℃.
1HNMR(300MHz?DMSO-d
6)δ：7.9(1H，s，-CONH-)，7.75(2H，m，ArH)，7.5(2H，m，ArH)，7.3(1H，t，-NH-)，7.1(2H，m，ArH)，6.9(2H，m，ArH)，4.8(1H，m，CH)，4.6(2H，d，-CH
2-)，2.0(2H，m，-CH
2-)，2.0(2H，m，-CH
2-)，2.0(2H，m，-CH
2-)，1.65(2H，m，-CH
2-).MS[M+H]
+335.1.IR(KBr，cm
-1)748.41，1566.25，1597.11，1616.40，3304.17，3350.46，3369.75.
Embodiment 43
The N-tertiary butyl-4-((1-cyclopentyl-1H-benzo [d] imidazoles)-2-base aminomethyl) benzamide (BZ-23)
The preparation method is similar to the preparation of BZ-16, white solid, yield 83.6%, mp.221～222 ℃.
1HNMR(300MHz?DMSO-d
6)δ：8.1(1H，s，-CONH-)，7.75(2H，m，ArH)，7.54(2H，m，ArH)，7.1(1H，d，-NH-)，7.1(2H，m，ArH)，6.9(2H，m，ArH)，4.6(2H，d，-CH
2-)，4.1(1H，m，CH)，4.08(1H，m，CH)，4.0(1H，m，CH)，2.0(8H，m，-CH
2-)，1.6(4H，m，-CH
2-)，1.5(4H，m，-CH
2-).MS[M+H]
+403.1.IR(KBr，cm
-1)1537.32，1568.18，1614.47，1631.83，3292.60.
Embodiment 44
N-cyclopentyl-4-((1-cyclopentyl-1H-benzo [d] imidazoles)-2-base aminomethyl) benzamide (BZ-24)
The preparation method is similar to the preparation of BZ-16, white solid, yield 64%, mp.198～199 ℃.
1HNMR(300MHz?DMSO-d
6)δ：8.1(2H，m，ArH)，7.6(1H，s，-CONH-)，7.4(2H，m，ArH)，7.15(1H，m，ArH)，7.1(1H，m，ArH)，7.0(2H，m，ArH)，6.1(1H，d，-NH-)，4.7(2H，d，-CH
2-)，4.5(1H，t，CH)，2.1(4H，m，-CH
2-)，2.1(2H，m，-CH
2-)，1.7(2H，m，-CH
2-)，1.5(9H，s，-CH
3).MS[M+H]
+391.1.1R(KBr，cm
-1)736.83，1282.71，1375.29，1464.02，1519.96，1543.10，1568.18，1599.04，1614.47，1639.55，2966.62，3255.95，3331.18.
Embodiment 45
N-(4-methoxy-benzyl)-1-phenyl-1H-benzo [d] imidazoles-2-amine (BZ-25)
The preparation method is similar to the preparation of 2a, white solid, yield 79.5%, mp.102～103 ℃.
1HNMR(300MHz?DMSO-d
6)δ：7.61-7.67(2H，t，ArH)，7.48-7.60(3H，m，ArH)，7.25-7.31(3H，m，ArH)，7.00(1H，t，-NH)，6.81-6.87(5H，m，ArH)，4.47(2H，d，-CH
2-)，3.71(3H，s，-OCH
3).MS[M+H]
+330.1.IR(KBr，cm-1)742.62，1033.88，1168.90，1247.99，1296.21，1361.79，1425.44，1460.16，1506.46，1562.39，1597.11，1620.26，2953.12，3043.77，3319.60.
Embodiment 46
N-methyl-4-((1-phenyl-1H-benzo [d] imidazoles)-2-base aminomethyl) benzamide (BZ-26)
The preparation method is similar to the preparation of BZ-3, white solid, yield 80%, mp.195～198 ℃.
1HNMR(300MHz?DMSO-d
6)δ：9.03(1H，s，-CONH)，8.45(1H，s，-NH-)，6.95-7.85(13H，m，ArH)，4.74(2H，d，-NHCH
2-)，2.76(3H，d，-NHCH
3).MS[M-H]
-355.3.IR(KBr,cm-1)748.41，1334.78，1388.79，1564.32，1610.61，1662.69，2758.30，3063.06，3169.15.
Embodiment 47
4-((1-phenyl-1H-benzo [d] imidazoles)-2-base aminomethyl) benzamide (BZ-27)
The preparation method is similar to the preparation of BZ-4, white solid, yield 36%, mp.184～185 ℃.
1HNMR(300MHz?DMSO-d
6)δ：7.9(1H，m，ArH)，7.8(1H，s，-NH-)，7.7(2H，m，ArH)，7.55(3H，m，ArH)，7.35(1H，m，ArH)，7.2(1H，t，-NH-)，7.1(1H，m，ArH)，6.8(2H，m，ArH)，4.6(2H，d，-CH
2-).MS[M+H]
+343.1.IR(KBr,cm
-1)738.76，1072.46，1105.25，1180.47，1261.49，1286.56，1336.71，1386.86，1415.80，1460.16，1506.46，1552.75，1602.90，1672.34，3045.70，3163.36，3352.39，3412.19.
Embodiment 48
The N-tertiary butyl-4-((1-phenyl-1H-benzo [d] imidazoles)-2-base aminomethyl) benzamide (BZ-28)
The preparation method is similar to the preparation of BZ-16, white solid, yield 86.7%, mp.173～174 ℃.
1HNMR(300MHz?DMSO-d
6)δ：7.75(4H，m，ArH)，7.7(1H，m，ArH)，7.4(2H，m，ArH)，7.35(1H，m，ArH)，7.0(1H，m，ArH)，6.9(1H，m，ArH)，6.8(1H，m，ArH)，4.，8(2H，d，-CH
2-)，1.3(9H，s，-CH
3).MS[M+H]
+399.3.IR(KBr,cm
-1)1383.01，1462.09，1502.60，1537.32，1546.96，1566.25，1602.90，1618.33，1641.48，2929.97，2974.33，3049.56，3063.06.
Embodiment 49
N-methyl-3-(2-(4-methoxybenzyl amino)-1H-benzo [d] imidazoles-1-yl) benzamide (BZ-29)
The preparation method is similar to the preparation of BZ-3, white solid, yield 65%, mp.198～199 ℃.
1HNMR(300MHz?DMSO-d
6)δ：8.57(1H，d，-CONH)，7.97(1H，d，ArH)，7.93(1H，s，ArH)，7.72(1H，t,ArH)，7.64(1H，d，ArH)，7.28(3H，t，ArH)，7.02(1H，t，-N
HCH
2)，6,92(1H，d，ArH)，6.84(4H，m，ArH)，4.67(2H，d，-NHC
H 2-)，3.71(3H，s，-OCH
3)，2.80(3H，d，-NHC
H 3).MS[M+H]
+387.2.IR(KBr,cm
-1)1247.99，1390.72，1464.02，1516.10，1531.53，1564.32，1608.69，1641.48，3221.23.
Embodiment 50
N-methyl-3-(2-(4-formamido group benzyl amino)-1H-benzo [d] imidazoles-1-yl) benzamide (BZ-30)
The preparation method is similar to the preparation of BZ-3, white solid, yield 54.8%, mp.152～153 ℃.
1HNMR(300MHz?DMSO-d
6)δ：8.6(1H，s，-CONH-)，8.1(2H，m，ArH)，7.6(2H，m，ArH)7.3(1H，m，NH)，7.3(2H，m，ArH)，7.0(2H，m，ArH)，6.8(2H，m，ArH)，6.8(2H，m，ArH)，4.5(2H，d，-CH
2-)，2.8(3H，s，-NHC
H 3)，2.7(3H，s，-NCH
3).MS[M+H]
+414.1.IR(KBr,cm-1)1506.46，1556.61，1614.47，3144.07，3176.87，3209.66，3234.73.
Embodiment 51
N-methyl-4-(2-(4-methoxybenzyl amino)-1H-benzo [d] imidazoles-1-yl) benzamide (BZ-31)
The preparation method is similar to the preparation of BZ-3, white solid, yield 70%, mp.148～149 ℃.
1HNMR(300MHz?DMSO-d
6)δ：8.6(1H，s，-CONH-)，8.1(2H，m，ArH)，7.6(2H，m，ArH)，7.3(1H，m，NH)，7.3(2H，m，ArH)，7.0(2H，m，ArH)，6.8(2H，m，ArH)，6.8(2H，m，ArH)，4.45(2H，d，-CH
2-)，3.7(3H，s，-NHCH
3)，2.8(3H，s，-OCH
3).MS[M+H]
+387.1.IR(KBr,cm
-1)742.62，823.63，854.49，1037.74，1172.76，1249.91，?1296.21，1363.72，1413.87，1437.02，1462.09，1506.46，1560.46，1610.61，1643.41，2956.97，3049.56，3304.17，3419.90.
Embodiment 52
N-methyl-4-(2-(4-formamido group benzyl amino)-1H-benzo [d] imidazoles-1-yl) benzamide (BZ-32)
The preparation method is similar to the preparation of BZ-3, white solid, yield 53%, mp.235～236 ℃.
1HNMR(300MHz?DMSO-d
6)δ：8.6(1H，s，-CONH-)，8.1(2H，m，ArH)，7.6(2H，m，ArH)，7.3(2H，m，NH)，7.3(2H，m，ArH)，7.0(2H，m，ArH)，6.8(2H，m，ArH)，6.8(2H，m，ArH)，4.5(2H，d，-CH
2-)，2.8(3H，s，-NHCH
3)，2.7(3H，s，-NCH
3).MS[M+H]
+414.1.IR(KBr,cm
-1)732.97，837.13，1151.54，1238.34，1282.71，1317.43，1383.01，1408.08，1462.09，1506.46，1558.54，1612.54，1643.41，2899.11，2956.97，3061.13，3294.53.
Embodiment 53
4-((1-benzyl-1H-benzo [d] imidazoles)-2-base aminomethyl) benzamide (BZ-33)
The preparation method is similar to the preparation of BZ-4, white solid, yield 38%, mp.250～251 ℃.
1HNMR(300MHz?DMSO-d
6)δ：7.8(1H，m，-NH-)，7.7(1H，m，-CONH2)，7.35(2H，m，ArH)，7.35(5H，m，ArH)，7.0(2H，m，ArH)，6.8(2H，m，ArH)，5.3(2H，d，-CH
2-)，4.6(2H，d，-CH
2-).MS[M+H]
+357.2.IR(KBr,cm
-1)746.48，1384.94，1465.95，1562.39，1599.04，1618.33，1689.70，3066.92，3126.71.
Embodiment 54
N-ethyl-4-((1-benzyl-1H-benzo [d] imidazoles)-2-base aminomethyl) benzamide (BZ-34)
The preparation method is similar to the preparation of BZ-3, white solid, yield 53.8%, mp.185～186 ℃.
1HNMR(300MHz?DMSO-d
6)δ：8.4(1H，s，-CONH-)，7.75(2H，m，ArH)，7.3(1H，t，-NH-)，7.3(5H，m，ArH)，7.1(2H，m，ArH)，7.1(1H，m，ArH)，7.0(1H，m，ArH)，6.9(1H，m，ArH)，6.8(1H，m，ArH)，5.3(2H，m，-CH
2-)，4.6(2H，m，-CH
2-)，3.35(2H，m，-CH
2-)，3.35(2H，m，-CH
2-)，3.35(3H，m，-CH
2CH
3)，1.7(2H，m，-CH
2-).MS[M+H]
+385.2.IR(KBr，cm
-1)1288.49，1552.75，1570.11，1602.90，1620.26，1633.76，3244.38，3325.39，3414.12，3468.13.
Embodiment 55
N-(3-methoxy-propyl)-4-((1-benzyl-1H-benzo [d] imidazoles)-2-base aminomethyl) benzamide (BZ-35)
The preparation method is similar to the preparation of BZ-16, white solid, yield 67%, mp.163～164 ℃.
1HNMR(300MHz?DMSO-d
6)δ：7.8(1H，m，-NH-)，7.7(1H，m，-CONH
2)，7.35(2H，m，ArH)，7.35(5H，m，ArH)，7.0(2H，m，ArH)，6.8(2H，m，ArH)，5.3(2H，d，-CH
2-)，4.6(2H，d，-CH
2-).MS[M+H]
+429.3.1R(KBr,cm
-1)746.48，1384.94，1465.95，1562.39，1599.04，1618.33,1689.70，3066.92，3126.71。
Claims (6)
1. the compound of general formula (I) or its pharmacy acceptable salt:
Wherein, R
1mean H, nitro, amino, formamido group, kharophen, ethanoyl; R
2expression-H, methyl, ethyl, cyclopentyl, phenyl, benzyl, 3-first carbamyl phenyl, 4-first carbamyl phenyl; R
3expression-H, methoxyl group; R
4mean H, methoxyl group, the first carbamyl, carbamyl, the second carbamyl, encircle penta carbamyl, 3-methoxy propyl carbamyl, morpholinyl the third carbamyl, N-methyl piperidine-4-formamyl, tertiary fourth carbamyl.
2. the compound of claim 1, its structure is:
N-(4-methoxy-benzyl)-1-ethyl-1H-benzo [d] imidazoles-2-amine (BZ-1)
N-(4-methoxy-benzyl)-1H-benzo [d] imidazoles-2-amine (BZ-2)
N-methyl-4-(1H-benzo [d] imidazoles-2-base aminomethyl) benzamide (BZ-3)
2-(4-methoxybenzyl amino)-1H-benzo [d] imidazoles-5-methane amide (BZ-4)
N-(4-methoxy-benzyl)-5-nitro-1H-benzo [d] imidazoles-2-amine (BZ-5)
N-(4-methoxy-benzyl)-1-methyl isophthalic acid H-benzo [d] imidazoles-2-amine (BZ-6)
N-benzyl-1-ethyl-1H-benzo [d] imidazoles-2-amine (BZ-7)
N-(3,4-dimethoxy-benzyl)-1-ethyl-1H-benzo [d] imidazoles-2-amine (BZ-8)
N-methyl-4-((1-ethyl-1H-benzo [d] imidazoles)-2-base aminomethyl) benzamide (BZ-9)
4-((1-ethyl-1H-benzo [d] imidazoles)-2-base aminomethyl) benzamide (BZ-10)
N-(4-methoxy-benzyl)-1-ethyl-5-nitro-1H-benzo [d] imidazoles-2-amine (BZ-11)
N
2-(4-methoxy-benzyl)-1-ethyl-1H-benzo [d] imidazoles-2,5-diamines (BZ-12)
N-methyl-4-((1-ethyl-5-amino-1H-benzo [d] imidazoles)-2-base aminomethyl) benzamide (BZ-13)
N-(1-ethyl-2-(4-methoxybenzyl amino)-1H-benzo [d] imidazoles)-5-yl) ethanamide (BZ-14)
N-ethyl-4-((1-ethyl-1H-benzo [d] imidazoles)-2-base aminomethyl) benzamide (BZ-15)
N-cyclopentyl-4-((1-ethyl-1H-benzo [d] imidazoles)-2-base aminomethyl) benzamide (BZ-16)
N-(3-methoxy-propyl)-4-((1-ethyl-1H-benzo [d] imidazoles)-2-base aminomethyl) benzamide (BZ-17)
N-(3-morpholine propyl group)-4-((1-ethyl-1H-benzo [d] imidazoles)-2-base aminomethyl) benzamide (BZ-18)
N-(1-methyl piperidine-4-yl)-4-((1-ethyl-1H-benzo [d] imidazoles)-2-base aminomethyl) benzamide (BZ-19)
N-(4-methoxy-benzyl)-1-cyclopentyl-1H-benzo [d] imidazoles-2-amine (BZ-20)
N-methyl-4-((1-cyclopentyl-1H-benzo [d] imidazoles)-2-base aminomethyl) benzamide (BZ-21)
4-((1-cyclopentyl-1H-benzo [d] imidazoles)-2-base aminomethyl) benzamide (BZ-22)
The N-tertiary butyl-4-((1-cyclopentyl-1H-benzo [d] imidazoles)-2-base aminomethyl) benzamide (BZ-23)
N-cyclopentyl-4-((1-cyclopentyl-1H-benzo [d] imidazoles)-2-base aminomethyl) benzamide (BZ-24)
N-(4-methoxy-benzyl)-1-phenyl-1H-benzo [d] imidazoles-2-amine (BZ-25)
N-methyl-4-((1-phenyl-1H-benzo [d] imidazoles)-2-base aminomethyl) benzamide (BZ-26)
4-((1-phenyl-1H-benzo [d] imidazoles)-2-base aminomethyl) benzamide (BZ-27)
The N-tertiary butyl-4-((1-phenyl-1H-benzo [d] imidazoles)-2-base aminomethyl) benzamide (BZ-28)
N-methyl-3-(2-(4-methoxybenzyl amino)-1H-benzo [d] imidazoles-1-yl) benzamide (BZ-29)
N-methyl-3-(2-(4-formamido group benzyl amino)-1H-benzo [d] imidazoles-1-yl) benzamide (BZ-30)
N-methyl-4-(2-(4-methoxybenzyl amino)-1H-benzo [d] imidazoles-1-yl) benzamide (BZ-31)
N-methyl-4-(2-(4-formamido group benzyl amino)-1H-benzo [d] imidazoles-1-yl) benzamide (BZ-32)
4-((1-benzyl-1H-benzo [d] imidazoles)-2-base aminomethyl) benzamide (BZ-33)
N-ethyl-4-((1-benzyl-1H-benzo [d] imidazoles)-2-base aminomethyl) benzamide (BZ-34)
N-(3-methoxy-propyl)-4-((1-benzyl-1H-benzo [d] imidazoles)-2-base aminomethyl) benzamide (BZ-35).
3. the compound of claim 1 or its pharmacy acceptable salt, wherein pharmacy acceptable salt comprises the acid salt that general formula (I) compound and following acid form: hydrochloric acid, Hydrogen bromide, sulfuric acid, phosphoric acid, methylsulfonic acid, tosic acid, naphthene sulfonic acid, citric acid, tartrate, lactic acid, pyruvic acid, acetic acid, toxilic acid or Phenylsulfonic acid, succsinic acid, fumaric acid, Whitfield's ointment, phenylacetic acid or tussol.
4. a pharmaceutical composition, wherein contain general formula (I) compound or its pharmacy acceptable salt and the pharmaceutically acceptable carrier of claim 1.
The compound of the general formula of claim 1 (I) or its pharmacy acceptable salt for the preparation of the prevention or the treatment tumour medicine in purposes.
Purpose 5 6 claim wherein the swollen harmartoma be melanoma, liver cancer, kidney cancer, leukemia, non-small cell lung cancer, prostate cancer, thyroid cancer, skin cancer, colorectal cancer, pancreatic cancer, ovarian cancer, breast cancer , myelodysplastic syndrome, esophageal cancer, mesothelioma.
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| JP2017522339A (en) * | 2014-07-31 | 2017-08-10 | インスティチュート パスツール コリア | 2-Amino-benzimidazole derivatives and their use as 5-lipoxygenase and / or prostaglandin E synthase inhibitors |
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