CN104072432B - Containing compound, the Preparation Method And The Use of phenyl substituted triazole schiff bases class formation - Google Patents
Containing compound, the Preparation Method And The Use of phenyl substituted triazole schiff bases class formation Download PDFInfo
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- CN104072432B CN104072432B CN201410352128.4A CN201410352128A CN104072432B CN 104072432 B CN104072432 B CN 104072432B CN 201410352128 A CN201410352128 A CN 201410352128A CN 104072432 B CN104072432 B CN 104072432B
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- schiff bases
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- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- 150000001875 compounds Chemical class 0.000 title claims description 25
- 239000002262 Schiff base Substances 0.000 title abstract description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 title abstract description 5
- -1 triazole schiff bases Chemical class 0.000 title abstract description 4
- 230000015572 biosynthetic process Effects 0.000 title description 2
- 150000003839 salts Chemical class 0.000 claims description 10
- 239000003146 anticoagulant agent Substances 0.000 claims description 8
- 230000002785 anti-thrombosis Effects 0.000 claims description 5
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 239000003153 chemical reaction reagent Substances 0.000 claims description 3
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 208000007536 Thrombosis Diseases 0.000 abstract description 15
- 239000003814 drug Substances 0.000 abstract description 9
- 229940098892 Protease-activated receptor-1 antagonist Drugs 0.000 abstract description 5
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 2
- 210000001772 blood platelet Anatomy 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- 102100037136 Proteinase-activated receptor 1 Human genes 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 101710121440 Proteinase-activated receptor 1 Proteins 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 230000000702 anti-platelet effect Effects 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 208000032843 Hemorrhage Diseases 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 108010070519 PAR-1 Receptor Proteins 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 102000002020 Protease-activated receptors Human genes 0.000 description 2
- 108050009310 Protease-activated receptors Proteins 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 102000003790 Thrombin receptors Human genes 0.000 description 2
- 108090000166 Thrombin receptors Proteins 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 208000034158 bleeding Diseases 0.000 description 2
- 230000000740 bleeding effect Effects 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 230000015271 coagulation Effects 0.000 description 2
- 238000005345 coagulation Methods 0.000 description 2
- 239000000470 constituent Substances 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 210000002381 plasma Anatomy 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 230000000630 rising effect Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- OVBICQMTCPFEBS-SATRDZAXSA-N (2s)-1-[(2s)-2-[[(2s)-2-[[(2r)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-[[(2r)-2-[[(2r)-2-acetamido-3-naphthalen-2-ylpropanoyl]amino]-3-(4-chlorophenyl)propanoyl]amino]-3-pyridin-3-ylpropanoyl]amino]-3-hydroxypropanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-6-[bi Chemical compound CC(O)=O.CC(O)=O.C([C@@H](C(=O)N[C@H](CCCCN=C(NCC)NCC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN=C(NCC)NCC)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)C1=CC=C(O)C=C1 OVBICQMTCPFEBS-SATRDZAXSA-N 0.000 description 1
- 208000004476 Acute Coronary Syndrome Diseases 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 239000005552 B01AC04 - Clopidogrel Substances 0.000 description 1
- 229940123900 Direct thrombin inhibitor Drugs 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 241000282414 Homo sapiens Species 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 102000032626 PAR-1 Receptor Human genes 0.000 description 1
- 206010050661 Platelet aggregation inhibition Diseases 0.000 description 1
- 102000007466 Purinergic P2 Receptors Human genes 0.000 description 1
- 108010085249 Purinergic P2 Receptors Proteins 0.000 description 1
- 150000004753 Schiff bases Chemical class 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 108090000190 Thrombin Proteins 0.000 description 1
- 208000035896 Twin-reversed arterial perfusion sequence Diseases 0.000 description 1
- 229930003448 Vitamin K Natural products 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 230000010100 anticoagulation Effects 0.000 description 1
- 229940127218 antiplatelet drug Drugs 0.000 description 1
- 210000001367 artery Anatomy 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000023555 blood coagulation Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- QNEFNFIKZWUAEQ-UHFFFAOYSA-N carbonic acid;potassium Chemical compound [K].OC(O)=O QNEFNFIKZWUAEQ-UHFFFAOYSA-N 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000006285 cell suspension Substances 0.000 description 1
- GKTWGGQPFAXNFI-HNNXBMFYSA-N clopidogrel Chemical compound C1([C@H](N2CC=3C=CSC=3CC2)C(=O)OC)=CC=CC=C1Cl GKTWGGQPFAXNFI-HNNXBMFYSA-N 0.000 description 1
- 229960003009 clopidogrel Drugs 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 239000003260 cyclooxygenase 1 inhibitor Substances 0.000 description 1
- 229960000935 dehydrated alcohol Drugs 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000003203 everyday effect Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000003527 fibrinolytic agent Substances 0.000 description 1
- 108700032141 ganirelix Proteins 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000012447 hatching Effects 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- SHUZOJHMOBOZST-UHFFFAOYSA-N phylloquinone Natural products CC(C)CCCCC(C)CCC(C)CCCC(=CCC1=C(C)C(=O)c2ccccc2C1=O)C SHUZOJHMOBOZST-UHFFFAOYSA-N 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000000611 regression analysis Methods 0.000 description 1
- 230000000452 restraining effect Effects 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 229960004072 thrombin Drugs 0.000 description 1
- 239000003868 thrombin inhibitor Substances 0.000 description 1
- 230000001732 thrombotic effect Effects 0.000 description 1
- 238000012549 training Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 235000019168 vitamin K Nutrition 0.000 description 1
- 239000011712 vitamin K Substances 0.000 description 1
- 150000003721 vitamin K derivatives Chemical class 0.000 description 1
- 229940046010 vitamin k Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D249/12—Oxygen or sulfur atoms
Abstract
The present invention relates to the pharmaceutical field relevant to thrombotic diseases.The invention belongs to triazole schiff base compounds and the derivative thereof of the brand-new skeleton of a class, in particular to a class containing the PAR-1 antagonist of phenyl substituted triazole schiff bases structure, its preparation method and containing their pharmaceutical composition and their purposes in preparation treatment thrombotic diseases medicine.
Description
Technical field
The present invention relates to the pharmaceutical field relevant to thrombus disease.The invention belongs to triazole schiff base compounds and the derivative thereof of the brand-new skeleton of a class, specifically, relate to the PAR-1 antagonist medicative class of thrombotic diseases being contained to the triazole schiff bases structure that phenyl replaces and preparation method thereof, and contain their pharmaceutical composition.
Background technology
Proteinase activated receptors 1 (ProteaseActivatedAcceptor-1, PAR-1) is the novel targets of the antiplatelet class antithrombotic reagent found recently.Proteinase activated receptors 1 is thrombin receptor again, zymoplasm by coagulation cascade activate after by PAR-1 receptor acting in thrombocyte thus activate thrombocyte, cause platelet aggregation thus cause thrombus and blood coagulation.Being rich in platelet component in the thrombus that PAR-1 causes, is the main reason of arterial thrombus.PAR-1 antagonist can block thrombin activation thrombocyte, thus interruption artery thrombosis, may be used for treatment acute coronary artery disease (AcuteCoronarySyndrome).Several PAR-1 inhibitor has been had to be in clinical study (ChackalamannilS., ThrombinReceptor (ProteaseActivatedReceptor-1) AntagonistsasPotentAntithromboticAgentswithStrongAntipla teletEffects
j.Med.Chem.,
2006,
49 (18), 5389-5403).
Traditional is divided three classes for the medicine preventing and treating thrombotic diseases.The first kind is anticoagulation class, be divided into direct thrombin inhibitor and indirect thrombin inhibitors, such medicine carrys out inhibition thrombosis by the different links acting on coagulation cascade, has and suppresses various thrombotic effect, as vitamin K antagon and Xa factor inhibitor etc.; Equations of The Second Kind is antiplatelet class, and as COX-1 inhibitor and adp receptor antagonist etc., such medicine is mainly used in preventing and treating arterial thrombus; 3rd class is fibrinolytic agent, is mainly used in the scleroproein formed in lysed blood.
Mostly antiplatelet drug is traditional arterial thrombus protective agents, as clopidogrel and acetylsalicylic acid etc.The shortcoming of these medicines is that bleeding risk is larger.And as the PAR-1 antagonist of newfound antiplatelet class antithrombotic reagent, then there is less bleeding risk, therefore this compounds can as the very promising medicine for the treatment of arterial thrombus.
The invention discloses the PAR-1 antagonist of the triazole schiff bases structure that a class replaces containing phenyl, may be used for the medicine preparing anti-arterial thrombus disease.
Summary of the invention
An object of the present invention is to provide a kind of there is good anti-thrombosis activity there is general formula
icompound and pharmaceutically acceptable salt.
Another object of the present invention is to provide preparation and has general formula
icompound and the method for pharmaceutically acceptable salt.
Another object of the present invention is to provide containing general formula
icompound and pharmaceutically acceptable salt as effective constituent, and the medicinal compositions of one or more pharmaceutically acceptable carrier, vehicle or thinners, and the application in treatment arterial thrombus.
Now in conjunction with object of the present invention, content of the present invention is specifically described.
The compound that the present invention has general formula I has following structural formula:
。
（I）
Wherein,
R
1be selected from the alkyl of H, C1-C5, the cycloalkyl of C3-C5, halogenic substituent.
The compound of general formula I and pharmaceutically acceptable salt, preferably from:
R
1be selected from the alkyl of H, C1-C3, F, Cl, Br.
Preferably following have general formula
icompound,
Preferred following compounds further,
General formula of the present invention
icompound is synthesized by following steps:
。
Compound
iIand compound
iIIacid or alkali catalysis under react, obtain schiff bases
iV;
iVwith
vbe obtained by reacting compound in the presence of a base
i.
Formula of the present invention
ithe pharmacy acceptable salt of compound, include, but are not limited to the salt formed with various mineral acid example hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, Hydrogen bromide etc., also comprise the salt formed as acetic acid, succsinic acid, toxilic acid, oxysuccinic acid and each seed amino acid etc. with various organic acid.
General formula of the present invention
icompound has the antagonistic action of PAR-1, can be used as the medicine of effective constituent for the preparation of antithrombotic aspect.General formula of the present invention
ithe activity of compound is verified by external model.
General formula of the present invention
icompound is effective in quite wide dosage range.The dosage that such as every day takes, within the scope of 1mg-500mg/ people, is divided into once or administration for several times.Actually take general formula of the present invention
ithe dosage of compound can be decided according to relevant situation by doctor.These situations comprise: the physical state of patient, route of administration, age, body weight, individual reaction to medicine, the severity etc. of symptom.
Embodiment
Below in conjunction with embodiment, the present invention is further illustrated.It should be noted that, following embodiment be only for illustration of, and not for limiting the present invention.The various changes that those skilled in the art's training centre according to the present invention is made all should within the protection domain required by the application's claim.
embodiment 1
。
Reaction raw materials: self-control, ordinary method.
1.06g (10mmol) compound
iIwith 1.92g (10mmol) compound
iII-1be dissolved in 20mL Glacial acetic acid, temperature rising reflux spends the night.After reaction mixture is slightly cold, pour in 200mL frozen water, stir, collected by suction solid, recrystallization from dehydrated alcohol, ambient temperature in vacuum is dry, obtains product
iV-1, white crystal.MS,
m/z=295([M+H]
+)。
1.48g (5mmol) compound
iV-1, 1.85g (5mmol) compound
vstir in 15mL acetonitrile with 2.07g (15mmol) solid carbonic acid potassium and spend the night, then temperature rising reflux 3 hours.
Be poured into after reaction mixture is slightly cold in 200mL frozen water, stir, regulate pH=4 with concentrated hydrochloric acid, the dichloromethane extraction of 50mL × 3, merge organic phase, brine It, anhydrous sodium sulfate drying, boil off solvent on a rotary evaporator, the resistates obtained, through column chromatography purification, obtains sterling
i-1, white solid, MS,
m/z=583 ([M+NH
4]
+).
embodiment 2-7
With reference to the method for embodiment 1, can synthesize and there is general formula
ifollowing compounds:
。
embodiment 8 extracorporeal platelet aggregation inhibition test
In 96 orifice plates, the platelet aggregation of inducing at TRAP (Glycoprotein) concentrates the pharmacology test carrying out material.The sodium citrate solution of 3.13% is added in advance, then the blood of suction 20mL healthy volunteer, 1500 in syringe
glower centrifugal 20 minutes, separate being rich in hematoblastic blood plasma (PRP) and processing with the amount of 1 μ LPGE1 solution (ethanolic solns of 500 μ g/mL)/mLPRP.After at room temperature hatching 5 minutes, by its under 1200g centrifugal 20 minutes with except leucocyte-removing.To not transfer in the PP pipe of 15mL with 5mL/ part containing leukocytic PRP in batches, and centrifugally under 3600g make pellet platelets.Then, drain upper plasma, the pellet platelets deriving from 5mLPRP is suspended in 1mLTyrode (120mMNaCl, 2.6mMKCl, 12mMNaHCO3 again, 0.39mMNaH2PO4,10mMHEPES, 0.35%BSA, 5.5mM glucose, pH=7.4) in, and the platelet count of 3 ' 105/ μ L is adjusted to Tyrode.By the 10mMCaCl2 solution-treated of this for 13mL cell suspension with 866 μ L, be drawn in 96 orifice plates with the amount of every hole 120 μ L, in the hole of 96 orifice plates, added 15 μ L material to be tested in advance.At room temperature hatch 30 minutes in dark, add 15 μ LTRAP solution (70-100 μM) as agonist, vibrate 20 minutes under 37 ° of C in SpectraMax, kinetics is noted down under 650nm, calculate the area under curve of negative control (tyrode/DMSO) and positive control (15 μ L agonist/DMSO), and difference is decided to be 100%.Aspirated with the form of serial dilution thing by compound to be tested, measure in duplicate, the same AUC measuring each material concentration, the AUC calculated compared with the control suppresses %.IC50 value is calculated according to 4 parametric equations by nonlinear regression analysis by this suppression %.Following table gives result:
As can be seen from the above table, compound of the present invention shows obvious restraining effect in platelet aggregation test.
Claims (5)
1. there is compound and the pharmaceutically acceptable salt thereof of general formula I,
Wherein,
R1 is selected from alkyl, the halogenic substituent of H, C1-C5.
2. the compound with general formula I that claim 1 defines and pharmaceutically acceptable salt,
Wherein,
R1 is selected from alkyl, F, Cl, Br of H, C1-C3.
3. the compound of Formula I that defines of claim 2, is selected from following compounds,
4. compound described in claim 3, is selected from:
5. the compound of Formula I that defines of claim 1-4 and the pharmaceutically purposes of acceptable salt in preparation treatment antithrombotic reagent.
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|---|---|---|---|
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| CN104529928A (en) * | 2015-01-13 | 2015-04-22 | 佛山市赛维斯医药科技有限公司 | One category of oxadiazole sulfoxide compounds, and preparation method and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102442965A (en) * | 2010-09-30 | 2012-05-09 | 天津药物研究院 | PAR-1 (protease-activated receptor-1) antagonists for treating thrombotic diseases, as well as preparation and application thereof |
| CN103613553A (en) * | 2013-12-09 | 2014-03-05 | 兴义民族师范学院 | S-triazole Schiff base bisamide derivative as well as preparation method and usage thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102442965A (en) * | 2010-09-30 | 2012-05-09 | 天津药物研究院 | PAR-1 (protease-activated receptor-1) antagonists for treating thrombotic diseases, as well as preparation and application thereof |
| CN103613553A (en) * | 2013-12-09 | 2014-03-05 | 兴义民族师范学院 | S-triazole Schiff base bisamide derivative as well as preparation method and usage thereof |
Non-Patent Citations (2)
| Title |
|---|
| 3-甲基-4-氨基-5-乙氧羰基甲硫基三唑席夫碱的合成及生物活性;杨清翠等;《化学通报》;20131231;第76卷(第8期);第758-761页 * |
| Thrombin Receptor (Protease Activated Receptor-1) Antagonists as Potent Antithrombotic Agents with Strong Antiplatelet Effects;Samuel Chackalamannil;《Journal of Medicinal Chemistry》;20060907;第49卷(第18期);第5389-5403页 * |
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