CN1182121C - Compound with activity for resisting platelet agregation and its preparation method - Google Patents
Compound with activity for resisting platelet agregation and its preparation method Download PDFInfo
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- CN1182121C CN1182121C CNB03132021XA CN03132021A CN1182121C CN 1182121 C CN1182121 C CN 1182121C CN B03132021X A CNB03132021X A CN B03132021XA CN 03132021 A CN03132021 A CN 03132021A CN 1182121 C CN1182121 C CN 1182121C
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- tqp
- platelet aggregation
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- 230000002401 inhibitory effect Effects 0.000 claims abstract description 22
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- 238000000034 method Methods 0.000 claims abstract description 10
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- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 15
- 239000003146 anticoagulant agent Substances 0.000 claims description 5
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
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- 239000003153 chemical reaction reagent Substances 0.000 claims description 3
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Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention belongs to the technical field of medical preparation through chemical synthesis. The present invention relates to a route of the chemical synthesis of a compound with platelet aggregation inhibiting activity and a method for preparing the compound. The present invention also relates to an external test of the platelet aggregation inhibiting activity of the compound. A Bron method is adopted, and a platelet aggregation device is utilized to measure the platelet aggregation inhibiting activity of the compound, wherein the IC50 of the compound 1-ortho-chlorophenyl-m-bromo-benzoyl-1, 2, 3, 4-tetrahydroisoquinoline-(TQP-3) is 0.206 (+/-) 0.033 nmol/L, and the activity of the compound is much higher than that of aspirin (the IC50 of which is 9.673 (+/-) 3.285 nmol/L). The structure of the compound of the present invention is obviously different from that of the existing platelet aggregation inhibiting medicines, such as inolin, ticlopidine, clopidogrel, aspirin, etc. The compound TQP-3 has strong medicinal activity of inhibiting platelet aggregation and is expected to be developed into a novel medicine for inhibiting platelet aggregation, which can be used as a thrombus inhibiting medicine for treating myocardial infarction, cerebral apoplexy, thrombi, etc.
Description
One, technical field:
The invention belongs to chemosynthesis pharmaceutical technology field.
Two, background technology
Along with social senilization and growth in the living standard, the M ﹠ M of the cardiovascular and cerebrovascular disease of China rises just day by day.The major cause that causes cardiovascular and cerebrovascular diseases is that clinical manifestation is Acute Myocardial Infarction, cerebral thrombosis apoplexy and vascular embolization owing to form thrombus in the blood vessel.Thrombosis mechanism mainly comprises: 1. vessel wall changes: 2. blood ingredient change, platelet activation, factor activator, scleroproein form; 3. blood flow changes (slow blood flow or stagnation form whirlpool).Thrombosis is not an independently clinical disease, and it is the cause of disease or the complication of multiple disease, as dvt formation and pulmonary infarction etc. after atherosclerosis, coronary heart disease, cerebro-vascular diseases, operation or the wound.Therefore, suppress the important target that thrombosis has become the various cardiovascular disordeies of prevention.
In the pathogenesis of the acute thrombotic cardiovascular and cerebrovascular incident that atherosclerotic plaque initiation thrombosis causes, thrombocyte plays a crucial role, antiplatelet drug can prevent thrombosis, improve the blood supply state of hemorheology and ischemic myocardium, so become the important measures of control thrombotic diseases.Therefore, the development of new antithrombotic reagent becomes one of current important subject.
Antiplatelet drug claims platelet function inhibitor (platelet function inhibitors) again.This class medicine can suppress hematoblastic adhesion, gathering and release function, prevent thrombosis, and can prolong the thrombocyte lifetime that the thrombotic diseases patient has shortened.As antiplatelet drug, should require does not have obvious influence to the hemorrhage coagulation process of body under clinical application dosage, and untoward reaction such as promptly do not cause bleeding.Antiplatelet drug can be divided into five classes by its mechanism of action: (1) suppresses the medicine of thrombocyte arachidonic acid metabolism, as acetylsalicylic acid and sulfinpyrazone; (2) TXA
2Synthetase inhibitors is as sulfinpyrazone; (3) increase the medicine of cyclic nucleotide content in the thrombocyte, as prostacyclin PGI2 and Dipyridamole; (4) medicine of special inhibition ADP activated blood platelet is as ticlopidine and clopidogrel; (5) platelet membrane fibrinogen deceptor antagonist is as monoclonal antibody C7E3, Integrelin, Triofiban and Sibrafiban etc.
At present, have been found that the alkaloid compound that extracts in the natural product has platelet aggregation inhibitory activity, as R-(+)-trimethoquinol significantly antiplatelet aggregative activity is arranged, Tetrrine has calcium antagonism preferably, tries out clinically in treatment hypertension.They all contain the tetrahydroisoquinoline structure, and, the parent nucleus of tetrahydroisoquinoline and ticlopidine belongs to isostere, simultaneously, by to existing structure activity study with platelet aggregation inhibitory activity tetrahydroisoquinolicompounds compounds, we have designed and synthesized a series of tetrahydroisoquinolicompounds compounds, and structure is measured through ultimate analysis, Fourier transform infrared spectroscopy, mass spectrum and 300,000,000 nuclear magnetic resonance techniques, and the structure of having proved conclusively institute's synthetic compound is accurate.Experiment in vitro shows that part of compounds has stronger platelet aggregation inhibitory activity, and the activity of one of them compound is higher than acetylsalicylic acid.
Three, summary of the invention
The objective of the invention is synthetic compound with brand new, and wherein part of compounds has higher platelet aggregation inhibitory activity, wish the original new drug that acquisition has independent intellectual property right, and can be used in treatment myocardial infarction, cerebral apoplexy and thrombotic diseases etc. in the future.
Technical scheme of the present invention is at first to adopt Bischler-Napieralski reaction method to synthesize 1-Chloro-O-Phenyl-3,4-dihydro-isoquinoline parent nucleus; Secondly, through KBH
4Catalytic reduction prepares intermediate 1-Chloro-O-Phenyl-1,2,3,4-tetrahydroisoquinoline parent nucleus; Carry out alkylation reaction again and prepare 1-Chloro-O-Phenyl-2-benzyl-1,2,3,4-tetrahydroisoquinoline (TQP-1), perhaps chlorobenzene formacyl-1 through between the synthetic respectively 1-Chloro-O-Phenyl-2-of acylation reaction, 2,3, benzoyl bromide-1,2 between 4-tetrahydro isoquinoline compound (TQP-2) and 1-Chloro-O-Phenyl-2-, 3,4-tetrahydro isoquinoline compound (TQP-3); At last, the hydrochloride (See Figure) for preparing this analog derivative.
Fig. 1. compound synthesizes route
1-Chloro-O-Phenyl-2-benzyl-1,2,3, the character of 4-tetrahydroisoquinoline (TQP-1): white crystals, 118 ℃ of fusing points, molecular formula C
22H
20ClN, molecular weight 333.9.Water insoluble, be slightly soluble in ethanol, the acetone, be soluble in methylene dichloride and the chloroform.Through ultimate analysis, Fourier transform infrared spectroscopy, mass spectrum and and 300,000,000 nuclear magnetic resonance techniques measure, structure is accurate, and is as follows.
Chlorobenzene formacyl between 1-Chloro-O-Phenyl-2--1,2,3, the character of 4-tetrahydroisoquinoline (TQP-2): white crystal, 160 ℃ of fusing points, molecular formula C
22H
17Cl
2NO, molecular weight 382.3.Water insoluble, be slightly soluble in ethanol, the acetone, be soluble in methylene dichloride and the chloroform.Through ultimate analysis, Fourier transform infrared spectroscopy, mass spectrum and and 300,000,000 nuclear magnetic resonance techniques measure, structure is accurate, and is as follows.
Benzoyl bromide between 1-Chloro-O-Phenyl-2--1,2,3, the character of 4-tetrahydroisoquinoline (TQP-3): white crystal, 120 ℃ of fusing points, molecular formula C
22H
17BrClNO, molecular weight 426.7.Water insoluble, be slightly soluble in ethanol, the acetone, be soluble in methylene dichloride and the chloroform.Through ultimate analysis, Fourier transform infrared spectroscopy, mass spectrum and and 300,000,000 nuclear magnetic resonance techniques measure, structure is accurate, and is as follows.
The preliminary vitro inhibition platelet aggregation activity of the present invention experimental result shows that the platelet aggregation inhibitory activity of compound TQCP-3 is far above the activity of acetylsalicylic acid.Adopt the Bron method, blood with health adult prepares platelet poor plasma (PPP) and platelet rich plasma (PRP), with ADP (final concentration 10 μ mol/L) is inductor, utilizes platelet aggregation instrument (Beijing Puli gives birth to LBY-NJ2 four-way blood pool instrument) to measure the platelet aggregation inhibitory activity of compound.The IC of acetylsalicylic acid
50Be 9.673 ± 3.285nmol/L, the IC of compound TQP-1, TQP-2 and TQP-3
50Be respectively 60.60 ± 25.23,54.21 ± 18.72 and 0.206 ± 0.033nmol/L.Wherein the platelet aggregation inhibitory activity of compound TQP-3 is far above the activity of acetylsalicylic acid, and the activity of compound TQP-1 and TQP-2 is lower than acetylsalicylic acid.
The compound that the present invention relates to is the compound of brand new, with the structure of known medicament for resisting platelet aggregation remarkable difference is arranged, and is different from trimethoquinol, ticlopidine, clopidogrel and acetylsalicylic acid etc., has novelty.Particularly compound TQP-3 has very strong medicament for resisting platelet aggregation activity, and far above the activity of acetylsalicylic acid, being expected to exploitation becomes medicament for resisting platelet aggregation of new generation.
Four, embodiment
Organic synthesis
Fusing point is with measuring on the melting point tube, and thermometer reading is calibrated.Infrared spectrometer is Nexus 870 FT-IR, the KBr compressing tablet.Mass spectrograph is that the Britain ZAB-HS of VG company type is inverted double focusing high-resolution mass spectrometer resolving power 1000, acceleration voltage 8kv scope 600-400-600amu.300,000,000 nuclear magnetic resonance analyser are the FX-900 type, and TMS is interior mark.Thin-layer chromatography is with the silica GF254 of Haiyang Chemical Plant, Qingdao's production and the aqueous solution bed board of CMC-Na (0.8%), and standby in 110 ℃ of rearmounted moisture eliminators of activation 30min, the 254nm ultraviolet lamp develops the color down.
Experimental raw: the 2-phenylethylamine, chemical plant, Wujin, Jiangsu produces, and purity is greater than 98%, and 178 ℃ of products of fractionation seal standby.0-chloro-benzoic acid, Singma company produces, chemical pure 98%.O-bromobenzoic acid (CP), m-bromobenzoic acid (CP), parabromobenzoic acid (CP), m-chlorobenzoic acid (CP), Chlorodracylic acid (CP), reagent company in Shanghai produces.Benzene sulfonyl chloride (CP), sulfur oxychloride (AR), benzyl chlorine (CP), and o-chloro benzyl chloride (CP) is available from SIGAMA company.
1, midbody compound is synthetic
The preparation of N-styroyl-adjacent chlorobenzamide: 0-chloro-benzoic acid 10g, sulfur oxychloride 11.4g, back flow reaction 1h, the sulfur oxychloride that pressure reducing and steaming is unnecessary gets colourless or weak yellow liquid, i.e. o-chlorobenzoyl chloride (stand-by).β phenylethylamine 7.8g, triethylamine 10ml and methylene dichloride 80ml are mixed, and ice bath stirs down, drips the mixed solution of o-chlorobenzoyl chloride (prepared fresh) and 15ml methylene dichloride.Dropwise, room temperature reaction 3 hours, the pressure reducing and steaming solvent, cold slightly, separate out a large amount of white crystals, suction filtration, the washing, ether is washed, dry white mealy crystal, N-styroyl-adjacent chlorobenzamide, fusing point 99-101 ℃.
1-Chloro-O-Phenyl-3, the preparation of 4-dihydro-isoquinoline: with N-styroyl-adjacent chlorobenzamide 20g, the phosphorus oxychloride 40ml of dry toluene solvent 40ml and prepared fresh mixes, back flow reaction 6 hours, the pressure reducing and steaming solvent obtains thick resistates.Add the 10ml acetone solution, example is gone into frozen water again, transfers PH9-10 with strong aqua, and oily matter is appeared on the upper strata in one's mind, ether extraction three times, and combined ether liquid is washed activated carbon decolorizing, anhydrous MgSO three times
4Drying is filtered, and filtrate concentrates, and obtains light yellow viscous material (put for a long time, separate out needle-like solid), i.e. 1-Chloro-O-Phenyl-3,4-dihydro-isoquinoline, yield 54%.Gained free alkali crude product need not made with extra care, and can be directly used in next step reaction.
HNMR(δppm)：2.75(m，2H，CH
2N)，3.70(m，2H，ArCH
2)，7.45(m，8H，aromatic)
1-Chloro-O-Phenyl-1,2,3, the preparation of 4-tetrahydroisoquinoline: with 1-Chloro-O-Phenyl-3,4-dihydro-isoquinoline 4.485g mixes heating for dissolving with the 30ml anhydrous methanol, add diethylamine and transfer about PH8.5 (about 2), slowly add the POTASSIUM BOROHYDRIDE (KBH of 1.5g (0.027mol) again
4), and emit a large amount of bubbles, add, restir reaction 3 hours, solution colour by pale yellow become faint yellow.The pressure reducing and steaming solvent gets yellow mashed prod.The mixture that adds entry 60ml and acetone 5ml fully stirs to decompose unnecessary KHB
4, and oily matter is appeared on the upper strata in one's mind.Ether extraction three times, combined ether liquid is washed activated carbon decolorizing, anhydrous MgSO three times
4Drying is filtered, and filtrate concentrates, and gets flaxen viscous material, 1-Chloro-O-Phenyl-1,2,3, and the 4-tetrahydroisoquinoline, 3.519g (78.10%), prepared thick alkali need not made with extra care can be directly used in next step reaction.
2, the purpose compound is synthetic
1-Chloro-O-Phenyl-2-benzyl-1,2,3, the preparation of 4-tetrahydroisoquinoline (TQP-1): with 1-Chloro-O-Phenyl-1,2,3,4-tetrahydroisoquinoline 3.48g and equimolar benzyl chlorine are dissolved in the 50ml dehydrated alcohol, back flow reaction 6h, solution colour becomes Vandyke brown, reacts completely.The pressure reducing and steaming solvent gets the tawny viscous material.Add the 5ml acetone solution, ether extraction three times, combined ether liquid is washed anhydrous MgSO three times
4Drying, activated carbon decolorizing gets pale yellow solution.Filtrate concentrates, and leaves standstill, and separates out white crystals (being product) 0.78g, yield 15.9%, 118 ℃ of fusing points.Anal (C
22H
20ClN=333.9; C%, H%, N%): Req79.15,6.04,4.20; Found 79.30,6.20, and 4.14; IR (KBr, cm
-1): 2938 (υ as-CH2-), 2861 (υ s-CH2-); 1603,1495.8,1456 (phenyl ring skeletal vibrations); 757,707 (out-of-plane deformation vibrations of phenyl ring C-H): HNMR (CDCl
3, δ ppm): δ 2.501 (m, 2H, AR-CH
2-C (H
2)-); 3.093 (m, 2H, AR-C (H
2)-CH
2-N-); 3.282 (d, 2H ,-N-CH
2-AR) 5.311 (s, 1H, C
1-H); 6.767 (d, 1H, C
7-H); 7.134 (m, 1H, Chloro-O-Phenyl C
5-H); 7.194 (2H, C
8-H, Chloro-O-Phenyl C
6-H); 7.226 (2H, Chloro-O-Phenyl C
4-H and C
5-H); 7.258 (d, 1H; 7.306 (d, 4H, benzyl C
2-H, C
3-H, C
5-H, C
6-H); 7.417 (d, 1H, Chloro-O-Phenyl C
3-H); 7.486 (m, 1H, C
6-H); MS (SCI, m/Z): 333 (M
-1), 334 (M), 335 (M
+ 1).
Chlorobenzene formacyl between 1-Chloro-O-Phenyl-2--1,2,3; the preparation of 4-tetrahydroisoquinoline (TQP-2): with 1-Chloro-O-Phenyl-1,2,3; 4-tetrahydroisoquinoline 3.46g is dissolved in the 30ml methylene dichloride; add excessive a little triethylamine, ice bath stirs down, drips the m-chlorobenzoyl chloride (prepared fresh) of equimolar amount and the mixed solution of 5ml methylene dichloride; finish; room temperature reaction 3 hours, solution colour deepens, and reacts completely.The pressure reducing and steaming dichloromethane solvent gets the brown viscous material.Dichloromethane extraction three times, 5%NaHCO
3It is inferior to give a baby a bath on the third day after its birth, and washes anhydrous MgSO three times
4Drying, activated carbon decolorizing, filtrate concentrates, and leaves standstill and separates out solid.The dehydrated alcohol recrystallization is separated out white crystal (being product), 0.61g, yield 11.23%, 160 ℃ of fusing points.Anal (C
22H
17Cl
2NO=382.3; C%, H%, N%): Req 69.12,4.48, and 3.66; Found 69.23,5.51,3.50:IR (KBr, cm
-1): 2945,2836 (CH
2-); 1637 (C=O stretching vibrations), 1593,1475,1455 (phenyl ring skeletal vibrations); HNMR (CDCl
3, δ ppm): δ 2.193 (s, 1H C
1-H); 2.826 (d, 2H, C
4-H); 3.446 (d, 2H, C
3-h); 6.890 (d, 1H, C
7-H); 7.067 (s, 1H, C
5-H); 7.138 (m, 5H, 1C6-H, 1C8-H, 2 Chloro-O-Phenyl C
4, C
5, C
6Last three H); 7.341 (m, 5H, 2 Chloro-O-Phenyl C
3-H, 3 interdigit chlorobenzene formacyl C
2, C
4, C
5, C
6Four hydrogen); MS (SCI, m/Z): 381 (M
-1), 382 (M), 383 (M
+ 1).
Benzoyl bromide between 1-Chloro-O-Phenyl-2--1,2,3; the preparation of 4-tetrahydroisoquinoline (TQP-3): with 1-Chloro-O-Phenyl-1,2,3; 4-tetrahydroisoquinoline 3.51g is dissolved in the 30ml dichloromethane solution; add excessive a little triethylamine, ice bath stirs down, drips the m-bromo-benzoyl chloride (prepared fresh) of equimolar amount and the mixed solution of 5ml methylene dichloride; add; room temperature reaction 3 hours, solution colour deepens, and reacts completely.The pressure reducing and steaming dichloromethane solvent gets the brown viscous material.Dichloromethane extraction three times, 5%NaHCO
3It is inferior to give a baby a bath on the third day after its birth, and washes anhydrous MgSO three times
4Drying, activated carbon decolorizing, filtrate concentrates, and leaves standstill and separates out solid.The dehydrated alcohol recrystallization is separated out white crystal (being product), 0.68g, yield 11.06%, 120 ℃ of fusing points.Anal (C
22H
17BrClNO=426.7; C%, H%, N%): Req 61.92,4.02, and 3.28; Found 59.69,4.60, and 3.06; IR (KBr, cm
-1): 1673 (C=O stretching vibrations); 1595,1469,1434 (phenyl ring skeletal vibrations); HNMR (CDCl
3, δ ppm): δ 2.191 (s, 1H, C
1-H); 3.226 (m, 2H, 2C
4-H); 3.843 (m, 2H, 2C
3-H); 7.254 (m, 3H, C5-H, C7-H, C8-H); 7.315 (d, 1H, 2 Chloro-O-Phenyl C
6-H); 7.490 (m, 4H, C6-H, adjacent chlorobenzene formacyl C
3, C, C
5Last 3 hydrogen); 7.534 (m, 1H, 2 interdigit benzoyl bromide C
5-H); 7.763 (d, 2H, 2 interdigit benzoyl bromide C
4, C
6Last two hydrogen); 7.992 (s, 1H, 2 interdigit benzoyl bromide C
2Last hydrogen); MS (SCI, m/Z): 425.8 (M
+), 426.7 (M
+ 1).
3, platelet aggregation inhibitory activity detects
The platelet aggregation-against test of compound adopts platelet aggregation instrument (Beijing Puli gives birth to LBY-NJ2 four-way blood pool instrument) to measure.ADP and trisodium citrate be available from Sigama company, the physiological saline autogamy, and ASPIRIN is provided by the institute for drug control, Jiangsu Province.
The collection of blood specimen: blood sample is taken from adult human body, the preceding medicine that cut out anticoagulant in 10 days of platelet aggregation test, greasy, smoking of diet the day before yesterday etc.Each blood supplier took a blood sample in test morning on the same day on an empty stomach, got blood 30ml from preceding ulnar vein, added antithrombotics 3.28% Trisodium Citrate according to 1: 9 ratio.
Blood plasma preparation: the preparation of platelet rich plasma (PRP): centrifugal under 25 ℃ of-32 ℃ of temperature, rotating speed is 500-800 rev/min, be controlled on the time principle 10 minutes, treat that whizzer stops the back naturally and takes out (should take a blood sample again as haemolysis occurring), with pipettor the centrifugal PRP that goes out is drawn onto in another test tube, as far as possible with the whole sucking-offs of PRP.The preparation of platelet poor plasma (PPP): the blood that will draw PRP is centrifugal again, and rotating speed is 2000-2500 rev/min, and the time was controlled at about 10 minutes, takes out supernatant and is PPP.With platelet count among the PPP adjustment PRP is 250 * 10
9Individual/L.Produce behind the PRP behind the 30min beginning platelet aggregation and measure, whole survey lives through journey and finished in 3 hours.
Experimentation: carry out PAgT according to the Born turbidimetry: add 350 μ, 1 PPP in blank pipe, 37 ℃ are incubated and set transmittance is 100%.Measure adding 300 μ l PRP in the pipe, add each respectively for test sample product 30 μ l, calculate the respective sample final concentration, setting transmittance is 0%.37 ℃ of insulations of sample 3 minutes, add 20 μ l platelet aggregation inductor ADP (final concentration 10 μ mol/L) and collagen (final concentration 3 μ g/ml), begin to detect, detect 5 minutes altogether, write down hematoblastic MA in 5 minutes (Maximum Aggregation Rate MAR).(NS) compares with physiological saline.Calculating anticoagulant rate (Aggregation Inhibition Rate, AIR).Draw concentration by sample concentration and suppress curve, calculate maximal percentage inhibition and 503nhibiting concentration (IC
50).
Experimental result: vitro inhibition platelet aggregation activity result shows, the IC of acetylsalicylic acid
50Be 9.673 ± 3.285nmol/L, the IC of compound TQP-1, TQP-2 and TQP-3
50Be respectively 60.60 ± 25.23,54.21 ± 18.72 and 0.206 ± 0.033nmol/L.As seen the platelet aggregation inhibitory activity of compound TQP-3 is far above the activity of acetylsalicylic acid.The activity of compound TQP-1 and TQP-2 is lower than acetylsalicylic acid.
Claims (3)
1, a kind of compound with platelet aggregation inhibitory activity, the compound that it is characterized in that platelet aggregation inhibitory activity are 1-Chloro-O-Phenyl-2-benzyl-1,2; 3; chlorobenzene formacyl-1,2 between 4-tetrahydroisoquinoline (TQP-1), 1-Chloro-O-Phenyl-2-, 3; benzoyl bromide-1 between 4-tetrahydroisoquinoline (TQP-2) and 1-Chloro-O-Phenyl-2-; 2,3,4-tetrahydroisoquinoline (TQP-3); perhaps their hydrochlorides separately, its structural formula is respectively:
2, a kind of preparation method with compound of platelet aggregation inhibitory activity is characterized in that: adopt the synthetic 1-Chloro-O-Phenyl-3 of Bischler-Napieralski reaction method, 4-dihydro-isoquinoline parent nucleus; Secondly, prepare intermediate 1-Chloro-O-Phenyl-1,2,3 through the KBH4 catalytic reduction, 4-tetrahydroisoquinoline parent nucleus; Carry out alkylation reaction again and prepare 1-Chloro-O-Phenyl-2-benzyl-1,2,3,4-tetrahydroisoquinoline (TQP-1), perhaps chlorobenzene formacyl-1 through between the synthetic respectively 1-Chloro-O-Phenyl-2-of acylation reaction, 2,3, benzoyl bromide-1,2 between 4-tetrahydro isoquinoline compound (TQP-2) and 1-Chloro-O-Phenyl-2-, 3,4-tetrahydro isoquinoline compound (TQP-3); At last, the hydrochloride for preparing this analog derivative; Synthetic route is as follows:
3, a kind of have a platelet aggregation inhibitory activity application of compound; it is characterized in that platelet aggregation inhibitory activity compound 1-Chloro-O-Phenyl-2-benzyl-1; 2; 3; chlorobenzene formacyl-1 between 4-tetrahydroisoquinoline (TQP-1), 1-Chloro-O-Phenyl-2-; 2; 3; benzoyl bromide-1 between 4-tetrahydroisoquinoline (TQP-2) and 1-Chloro-O-Phenyl-2-; 2,3,4-tetrahydroisoquinoline (TQP-3); perhaps their hydrochloride can be used as antithrombotic reagent and is used to prepare the medicine for the treatment of myocardial infarction, cerebral apoplexy or thrombotic diseases.
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