CN1076728C - Derivative of 2-aryl imidazo [2,1-a] isoquinoline and its use - Google Patents
Derivative of 2-aryl imidazo [2,1-a] isoquinoline and its use Download PDFInfo
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- CN1076728C CN1076728C CN99102522A CN99102522A CN1076728C CN 1076728 C CN1076728 C CN 1076728C CN 99102522 A CN99102522 A CN 99102522A CN 99102522 A CN99102522 A CN 99102522A CN 1076728 C CN1076728 C CN 1076728C
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- isoquinoline
- imidazo
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- pregnancy
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- BYLPZVAKOZYZPH-UHFFFAOYSA-N imidazo[2,1-a]isoquinoline Chemical compound C1=CC=C2C3=NC=CN3C=CC2=C1 BYLPZVAKOZYZPH-UHFFFAOYSA-N 0.000 claims abstract description 13
- 230000035935 pregnancy Effects 0.000 claims abstract description 13
- 239000003814 drug Substances 0.000 claims abstract description 9
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 17
- 230000002158 anti-implantation Effects 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 4
- 230000000694 effects Effects 0.000 abstract description 9
- 150000001875 compounds Chemical class 0.000 abstract description 8
- 238000002474 experimental method Methods 0.000 abstract description 3
- 238000010579 first pass effect Methods 0.000 abstract description 3
- 230000003285 pharmacodynamic effect Effects 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 29
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
- 239000007787 solid Substances 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 4
- 229960000583 acetic acid Drugs 0.000 description 4
- 235000011114 ammonium hydroxide Nutrition 0.000 description 4
- 229960001701 chloroform Drugs 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- 239000003208 petroleum Substances 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 150000003852 triazoles Chemical class 0.000 description 4
- 239000013078 crystal Substances 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 150000002518 isoindoles Chemical class 0.000 description 3
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical compound C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 description 2
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Natural products CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 2
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
- BQSXZEPZUABAOO-UHFFFAOYSA-N CCCC1=CC=CC(C(C)=O)=C1Br Chemical compound CCCC1=CC=CC(C(C)=O)=C1Br BQSXZEPZUABAOO-UHFFFAOYSA-N 0.000 description 2
- 206010013786 Dry skin Diseases 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
- 239000012346 acetyl chloride Substances 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 150000001793 charged compounds Chemical class 0.000 description 2
- 230000006837 decompression Effects 0.000 description 2
- 230000003292 diminished effect Effects 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 238000009413 insulation Methods 0.000 description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 2
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 2
- ODLMAHJVESYWTB-UHFFFAOYSA-N propylbenzene Chemical compound CCCC1=CC=CC=C1 ODLMAHJVESYWTB-UHFFFAOYSA-N 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- GCBNIIKPVIHBGR-UHFFFAOYSA-N 1,3-oxazole Chemical compound C1=COC=N1.C1=COC=N1 GCBNIIKPVIHBGR-UHFFFAOYSA-N 0.000 description 1
- UBOQZJCKVLWPLH-UHFFFAOYSA-N 1-isoquinolin-1-ylethanone Chemical compound C1=CC=C2C(C(=O)C)=NC=CC2=C1 UBOQZJCKVLWPLH-UHFFFAOYSA-N 0.000 description 1
- MOMFXATYAINJML-UHFFFAOYSA-N 2-Acetylthiazole Chemical group CC(=O)C1=NC=CS1 MOMFXATYAINJML-UHFFFAOYSA-N 0.000 description 1
- 206010000234 Abortion spontaneous Diseases 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- MTUJNEOMBMNFDO-UHFFFAOYSA-N N=1C=CN2C1C1=CC=CC=C1C=C2.CC2=CC=CC(=C2)C Chemical compound N=1C=CN2C1C1=CC=CC=C1C=C2.CC2=CC=CC(=C2)C MTUJNEOMBMNFDO-UHFFFAOYSA-N 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000010495 camellia oil Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000002224 dissection Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 150000002460 imidazoles Chemical class 0.000 description 1
- 150000002475 indoles Chemical class 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 208000015994 miscarriage Diseases 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- -1 prostaglandin compound Chemical class 0.000 description 1
- 150000003217 pyrazoles Chemical class 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 208000000995 spontaneous abortion Diseases 0.000 description 1
- 238000010025 steaming Methods 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention discloses a derivate of 2-aryl imidazo [2, 1-a] isoquinoline and a usage thereof, and also discloses a derivate of 2-(4'-propyl benzene) imidazo [2, 1-a] isoquinoline or 2-(2', 4'-dimethylbenzene) imidazo [2, 1-a] isoquinoline and an application of the derivate in preparing medicines for resisting early pregnancy and nidationis. A pharmacodynamics experiment of the present invention on NIH mouses indicates that the two compounds both have high activity for terminating pregnancy, and further experiment also indicates that the two compounds have high activity for resisting nidationis and have low first pass effects.
Description
The present invention relates to compound and uses thereof, relate in particular to the also derivative and uses thereof of [2,1-a] isoquinoline 99.9 of 2-Aryimidazole.
The medicine that is used for emergency contraception and miscarriage belongs to steroid and prostaglandin compound mostly.Lerner and Galliani etc. report [Nature, 1975,256:130]: 2-(3-anisole)-5-H-s-triazole is [5,1-a] isoindole (L10492) and 2-(3-anisole)-5 also, 6-dihydro-s-triazole also [5,1-a] isoquinoline 99.9 (L10503) has the termination of pregnancy activity.
Later found in succession that again a series of novel non-steroidal compounds also have similar termination of pregnancy activity, mainly be symmetrical triazole condense thing and bioisostere thereof, comprise 2-Aryimidazole also [2,1-a] iloquinoline derivative and isoindoles [2], 2-aryl-s-triazole also [5,1-a] isoindoles and iloquinoline derivative, the 2-arylpyrazole is [5,1-a] isoindoles and iloquinoline derivative also, 2-arylpyrazole also [1,5-a] indoles and quinoline, 3,5-diaryl-s-3-triazole compounds etc.
Compare with L10492 and L10593, change of molecular structure is mainly with following several forms or its array mode:
1) substituting group changes on the phenyl ring.
2) symmetrical triazole ring becomes other bioisostere, as pyrazoles (Pyrazole), and imidazoles (Imidazole) ， oxazole (Oxazole) etc.
3) can be five yuan, hexa-atomic saturated or unsaturated ring with triazole (or its bioisostere) condensed ring.
4) open and triazole (or its bioisostere) condensed ring, can keep suitable residue.
The purpose of this invention is to provide the also derivative and uses thereof of [2,1-a] isoquinoline 99.9 of a kind of 2-Aryimidazole.
In order to achieve the above object, the present invention takes following measures:
Antiearly pregnancy/anti-implantation medicine is 2-(4 '-n-propylbenzene) imidazo [2,1-a] isoquinoline 99.9 or 2-(2 ', 4 '-dimethyl benzene) imidazo [2,1-a] isoquinoline 99.9.The application of 2-(4 '-n-propylbenzene) imidazo [2,1-a] isoquinoline 99.9 in preparation antiearly pregnancy/anti-implantation medicine.The application of 2-(2 ', 4 '-dimethyl benzene) imidazo [2,1-a] isoquinoline 99.9 in preparation antiearly pregnancy/anti-implantation medicine.
Advantage of the present invention:
The pharmacodynamics test that the NIH mouse is carried out shows that these two compounds all have very high termination of pregnancy activity; Further test shows that also they have higher anti-implantation activity simultaneously, and first pass effect is also lower.
Elaborate below in conjunction with embodiment:
The present invention has obtained the also derivative I of [2,1-a] isoquinoline 99.9 of two 2-Aryimidazoles, II.
The synthetic route that adopts:
The synthetic embodiment of 2-(4 '-n-propylbenzene) imidazo [2,1-a] isoquinoline 99.9 (I) [embodiment 1]
1,4-n-propyl phenyl methyl ketone (Ia) is synthetic,
At belt stirrer, addition funnel drops into n-propylbenzene 116g, AlCl in the round-bottomed flask of thermometer
3145g, sherwood oil 100mL, dripping acetyl chloride 90g in 1 hour, control still temperature is 10～30 ℃ during dropping.Insulation reaction is 1～2 hour under the room temperature.Drip 200mL water, the still temperature is no more than 50 ℃ during dropping.In still liquid impouring 1000mL beaker, continue and add suitable quantity of water, tell petroleum ether layer, an amount of petroleum ether extraction of water layer.Merge sherwood oil liquid, rectification under vacuum gets 95.5% (GC) Ia 140g, yield 87.7%.
2,4-positive propyl bromo acetylbenzene (Ib) is synthetic.
Drop into Ia 21g in the round-bottomed flask of belt stirrer, methyl alcohol 140mL treats to drip the methanol solution that contains 19.8g liquid bromine after the stirring and dissolving, and the control dropping temperature is no more than 30 ℃, and the dropping time is 1 hour.Add 75mL water, refrigated cooling to 2 ℃ is separated out solid Ib; With this solid frozen recrystallization in sherwood oil, content can be increased to＞93%, yield 85.1%.
3,4 '-n-propylbenzene ethanoyl isoquinoline 99.9 bromide (Ic) is synthetic
Drop into isoquinoline 99.9 in the round-bottomed flask of belt stirrer, be less than the Ib and an amount of methylene dichloride of theoretical molar amount, back flow reaction 3 hours adds an amount of ether, to there being solid Ic to separate out.The supernatant liquid that inclines, solid is washed till ether with ether and is colourless, 100 ℃ of dryings 1 hour.The melting range of Ic is 131.2～141.4 ℃.
4,2-(4 '-n-propylbenzene) imidazo [2,1-a] isoquinoline 99.9 (I) is synthetic
In the pressurized vessel of 100mL, drop into glacial acetic acid 50.5g, Ic6.2g, anhydrous acetic acid ammonium 13g, FERRIC CHLORIDE ANHYDROUS 10g is heated to 150 ℃, isothermal reaction 6 hours under stirring.Pressure is 3～4bar in the reactor.Be cooled to room temperature, filtration under diminished pressure.Solid with an amount of acetic acid, water washing, is filtered.With methylene dichloride and ammoniacal liquor extraction.Tell dichloromethane layer, most of methylene dichloride is removed in decompression, adds an amount of 10% hydrochloric acid, and I promptly separates out with the form of hydrochloride.Filter solid ether and ammoniacal liquor extracting and separating.The cooling diethyl ether solution is promptly separated out the slightly blue needle crystal of I, gets I 2.5g, yield 52.2% (Ic is with 100% cubage) after the oven dry.[embodiment 2]
Change the solvent in example 1 step 2 into chloroform, other condition is identical, and the yield of Ia is 82.3%.[embodiment 3]
The reaction times of example 1 step 4 is shortened to 4 hours, and other condition is identical, and the yield of I is 38.5%.
The melting range of I is 112.7～113.7 ℃.
Detect through the GC-MS combined instrument, do not record impurity peaks.Molecular ion peak M
+M/z=286.
Ultimate analysis: calculated value N, 9.78%; C, 83.88%; H, 6.34%.
Measured value N, 9.81%; C, 83.91%; H, 6.31%.
1H NMR schemes to resolve: δ 1.02 (t, 3H, CH
3), 1.80 (m, 2H, CH
2), 2.70 (t, 2H, Ar-CH
2), 6.93 (d, 1H, CH-6), 7.32～7.78 (m, 7H, ArH), 7.85 (2H, the overlapping peakss of CH-3 and CH-5), 8.88 (m, 1H, CH-10)
The synthetic embodiment of (2 ', 4 '-dimethyl benzene) imidazo [2,1-a] isoquinoline 99.9 (II) [embodiment 4]
1,2,4-dimethylated phenyl methyl ketone (IIa) synthetic
At belt stirrer, addition funnel, dimethyl benzene 110g between dropping in the round-bottomed flask of thermometer, AlCl
3115g, sherwood oil 150mL, dripping acetyl chloride 105g in 1 hour, the still temperature is no more than 22 ℃ during dropping.Insulation reaction is 15 minutes under the room temperature.Drip 200mL water, the still temperature is no more than 50 ℃ during dropping.In still liquid impouring 1000mL beaker, continue and add suitable quantity of water, tell petroleum ether layer with separating funnel, an amount of petroleum ether extraction of water layer.Merge sherwood oil liquid, rectification under vacuum gets 95.5% (GC) IIa 135g, yield 88.7%.
2, (2-acetyl bromide)-2,4-dimethyl benzene (IIb) synthetic
Drop into IIa 19.5g in the round-bottomed flask of belt stirrer, methyl alcohol 140mL treats to drip the methanol solution that contains 21.5g liquid bromine after the stirring and dissolving, and the control dropping temperature is no more than 30 ℃, and the dropping time is 1 hour 20 minutes.Add 90mL water, pressure reducing and steaming part first alcohol and water, refrigated cooling filters to such an extent that content is 94.3% white plates crystal IIb30g, yield 94.7%.
3,2 ', 4 '-dimethyl benzene ethanoyl isoquinoline 99.9 bromide (IIc) is synthetic
In the round-bottomed flask of belt stirrer, drop into 14.5g isoquinoline 99.9,17g IIb and 75mL methylene dichloride, about 2～3 hours of back flow reaction.Add the 30mL ether, refrigated cooling filters, and solid is washed till ether with a small amount of ether and is colourless, gets IIc23.5g, yield 93.1% (in IIb).100 ℃ of dryings 1 hour.The melting range of IIc is 226.2～228.4 ℃.
4,2-(2 ', 4 '-dimethyl benzene) imidazo [2,1-a] isoquinoline 99.9 (II) is synthetic
In the pressurized vessel of 100mL, drop into glacial acetic acid 39g, IIc 4.7g, anhydrous acetic acid ammonium 9.5g, FERRIC CHLORIDE ANHYDROUS 7.7g.Be heated to 150 ℃, isothermal reaction 6 hours under stirring.Be cooled to room temperature, filtration under diminished pressure.Solid with an amount of acetic acid, water washing, is filtered.With trichloromethane and ammoniacal liquor extraction.Tell the trichloromethane layer, most of trichloromethane is removed in decompression, adds an amount of 10% hydrochloric acid, and I promptly separates out with the form of hydrochloride.Filter, get the hydrochloride 2.5g of II after the oven dry, yield 61%.With ether and ammoniacal liquor extracting and separating.Naturally ether is removed in volatilization, and solid recrystallization in aqueous ethanolic solution gets the white, needle-shaped crystals of II.[embodiment 5]
With the dropping time lengthening in example 4 steps 1 is 1.5 hours, and temperature of reaction is controlled at 20～40 ℃, and other condition is identical, the color burn of crude product, and through rectification under vacuum, the yield of IIa is 90.3%.[embodiment 6]
The reflux time of example 4 steps 3 is shortened to 0.5 hour, and other condition is identical, and the yield of IIc is 85.9%.
The melting range of II is 101.8～102.9 ℃.
Detect through the GC-MS combined instrument, do not record impurity peaks.Molecular ion peak M
+M/z=272.Ultimate analysis: calculated value N, 10.29%; C, 83.79%; H, 5.92%.
Measured value N, 10.15%; C, 83.77%; H, 5.81%.
1H NMR schemes to resolve: δ 2.33 (s, 3H, CH
3), 2.51 (s, 3H, CH
3), 6.85～7.67 (m, 7H, the overlapping peakss of CH-6 and Ar-H), 7.67～8.0 (m, 2H, CH-3, the overlapping peakss of CH-5), 8.80 (m, 1H, CH-10)
Biological activity
1, medicine and animal
Animal is the NIH mouse, and every afternoon, the ratio with 1: 4 (male: female) mated mouse, checked cloudy bolt morning next day, serves as conceived first day (pregnant d1) to find cloudy bolt.
With refining tea oil medicine is mixed with solution.0.1ml/10g is made into different concns by mouse intramuscularly (i.m.).
2, the active detection
A) the antiearly pregnancy activity is from pregnant d4 to pregnant d6 intramuscular injection (i.m.) three days, and be administered once every day, 8 pregnant mouse of each dosage.At pregnant d14 experiment mice is put to death, the dissection uterus, record tire alive, stillborn foetus and absorption tire number surpass 50% as the termination of pregnancy significant figure with stillborn foetus and absorption tire.The results are shown in Table-1.
Table-1 Compound I, II stops NIH mouse early pregnancy activity test result
| Compound | ED 50﹠ (95% fiducial interval) (mg/kg/day) sends out |
| I | 0.943(0.728～1.201) |
| II | 1.099(0.855～1.469) |
B) the anti-implantation activity gavages (i.g.) administration from pregnant d1 to pregnant d3, once a day.Cutd open extremely at the 12nd day, look into pregnant situation.Two compounds are at institute's test dose 50.0,25.0, and 12.5mg/kg/day * 3days equal 100% is effective, all have the active and lower first pass effect of higher anti-implantation.
Claims (3)
1. the 2-Aryimidazole derivative of [2,1-a] isoquinoline 99.9 also is characterized in that it is 2-(4 '-n-propylbenzene) imidazo [2,1-a] isoquinoline 99.9 or 2-(2 ', 4 '-dimethyl benzene) imidazo [2,1-a] isoquinoline 99.9.
The application of (2.2-4 '-n-propylbenzene) imidazo [2,1-a] isoquinoline 99.9 in preparation antiearly pregnancy/anti-implantation medicine.
The application of (3.2-2 ', 4 '-dimethyl benzene) imidazo [2,1-a] isoquinoline 99.9 in preparation antiearly pregnancy/anti-implantation medicine.
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| Application Number | Priority Date | Filing Date | Title |
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| CN99102522A CN1076728C (en) | 1999-02-05 | 1999-02-05 | Derivative of 2-aryl imidazo [2,1-a] isoquinoline and its use |
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| CN1076728C true CN1076728C (en) | 2001-12-26 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100432074C (en) * | 2006-06-29 | 2008-11-12 | 浙江大学 | Method for synthesizeing aryl imidazo [2, 1 a] isoquinoline |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100434429C (en) * | 2007-04-30 | 2008-11-19 | 浙江大学宁波理工学院 | Method for preparing 2-arylimidazo [2,1-alpha] isoquinoline |
| CN105037369B (en) * | 2015-06-23 | 2017-07-07 | 河南师范大学 | A kind of synthetic method of pyrazolo [5,1 a] Carbox amide of iso-indoles 3 |
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|---|---|---|---|---|
| US4686227A (en) * | 1984-06-18 | 1987-08-11 | Fujisawa Pharmaceutical Co., Ltd. | Imidazoisoquinoline compounds useful as anti-ulcerative agents |
| EP0258175A2 (en) * | 1986-07-14 | 1988-03-02 | Sandoz Ag | 5-hetero- or aryl-substituted-imidazo[2,1-a]isoquinolines |
| WO1988006157A1 (en) * | 1987-02-11 | 1988-08-25 | Sandoz-Erfindungen Verwaltungsgesellschaft M.B.H. | 5-HETERO- OR ARYL-SUBSTITUTED-IMIDAZO[2,1-a]ISOQUINOLINES |
| US4910206A (en) * | 1986-07-14 | 1990-03-20 | Sandoz Pharmaceuticals Corp. | 5-hetero-or aryl-substituted-imidazo(2,1-a)isoquinolines and their use as PAF receptor antagonists |
-
1999
- 1999-02-05 CN CN99102522A patent/CN1076728C/en not_active Expired - Fee Related
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4686227A (en) * | 1984-06-18 | 1987-08-11 | Fujisawa Pharmaceutical Co., Ltd. | Imidazoisoquinoline compounds useful as anti-ulcerative agents |
| US4738967A (en) * | 1984-06-18 | 1988-04-19 | Fujisawa Pharmaceutical Co., Ltd. | Imidazoisoquinoline compounds useful as anti-ulcerative agents |
| EP0258175A2 (en) * | 1986-07-14 | 1988-03-02 | Sandoz Ag | 5-hetero- or aryl-substituted-imidazo[2,1-a]isoquinolines |
| US4910206A (en) * | 1986-07-14 | 1990-03-20 | Sandoz Pharmaceuticals Corp. | 5-hetero-or aryl-substituted-imidazo(2,1-a)isoquinolines and their use as PAF receptor antagonists |
| WO1988006157A1 (en) * | 1987-02-11 | 1988-08-25 | Sandoz-Erfindungen Verwaltungsgesellschaft M.B.H. | 5-HETERO- OR ARYL-SUBSTITUTED-IMIDAZO[2,1-a]ISOQUINOLINES |
Non-Patent Citations (1)
| Title |
|---|
| CHEMICAL ABSTRACT 99:19879F 1983.1.1 Synthesis and Pregnancy * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100432074C (en) * | 2006-06-29 | 2008-11-12 | 浙江大学 | Method for synthesizeing aryl imidazo [2, 1 a] isoquinoline |
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| Publication number | Publication date |
|---|---|
| CN1228431A (en) | 1999-09-15 |
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