CN101885730B - Compound for resisting thrombus - Google Patents
Compound for resisting thrombus Download PDFInfo
- Publication number
- CN101885730B CN101885730B CN2009101384385A CN200910138438A CN101885730B CN 101885730 B CN101885730 B CN 101885730B CN 2009101384385 A CN2009101384385 A CN 2009101384385A CN 200910138438 A CN200910138438 A CN 200910138438A CN 101885730 B CN101885730 B CN 101885730B
- Authority
- CN
- China
- Prior art keywords
- compound
- formula
- acceptable salt
- pharmacy acceptable
- pharmaceutical composition
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 25
- 208000007536 Thrombosis Diseases 0.000 title claims abstract description 7
- 238000002360 preparation method Methods 0.000 claims abstract description 13
- 150000003839 salts Chemical class 0.000 claims abstract description 9
- 239000003814 drug Substances 0.000 claims abstract description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
- 239000003513 alkali Substances 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 6
- XONPDZSGENTBNJ-UHFFFAOYSA-N molecular hydrogen;sodium Chemical compound [Na].[H][H] XONPDZSGENTBNJ-UHFFFAOYSA-N 0.000 claims description 6
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 5
- -1 methoxyl group Chemical group 0.000 claims description 5
- 239000011707 mineral Substances 0.000 claims description 5
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 4
- 229910052801 chlorine Chemical group 0.000 claims description 4
- 150000007530 organic bases Chemical class 0.000 claims description 4
- 239000000460 chlorine Chemical group 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 239000011737 fluorine Substances 0.000 claims description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims description 2
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 2
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 claims description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 claims description 2
- 238000000034 method Methods 0.000 claims 4
- 230000002265 prevention Effects 0.000 claims 2
- 125000001153 fluoro group Chemical group F* 0.000 claims 1
- 125000003545 alkoxy group Chemical group 0.000 abstract description 3
- 125000000217 alkyl group Chemical group 0.000 abstract description 3
- 208000010110 spontaneous platelet aggregation Diseases 0.000 abstract description 3
- 229910052736 halogen Inorganic materials 0.000 abstract description 2
- 230000002401 inhibitory effect Effects 0.000 abstract description 2
- 125000000753 cycloalkyl group Chemical group 0.000 abstract 1
- 125000005843 halogen group Chemical group 0.000 abstract 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 20
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 10
- 239000003146 anticoagulant agent Substances 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- 241000282472 Canis lupus familiaris Species 0.000 description 4
- 230000000702 anti-platelet effect Effects 0.000 description 4
- 230000002785 anti-thrombosis Effects 0.000 description 4
- 229940127218 antiplatelet drug Drugs 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000005465 B01AC22 - Prasugrel Substances 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 229940073608 benzyl chloride Drugs 0.000 description 3
- 238000001816 cooling Methods 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 150000002431 hydrogen Chemical class 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- DTGLZDAWLRGWQN-UHFFFAOYSA-N prasugrel Chemical compound C1CC=2SC(OC(=O)C)=CC=2CN1C(C=1C(=CC=CC=1)F)C(=O)C1CC1 DTGLZDAWLRGWQN-UHFFFAOYSA-N 0.000 description 3
- 229960004197 prasugrel Drugs 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 0 *C(C(c1c(*)cccc1)N(CC1)Cc2c1[s]c(OC(C1CC1)=O)c2)=O Chemical compound *C(C(c1c(*)cccc1)N(CC1)Cc2c1[s]c(OC(C1CC1)=O)c2)=O 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- 239000005552 B01AC04 - Clopidogrel Substances 0.000 description 2
- 101000783577 Dendroaspis angusticeps Thrombostatin Proteins 0.000 description 2
- 101000783578 Dendroaspis jamesoni kaimosae Dendroaspin Proteins 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 229960003009 clopidogrel Drugs 0.000 description 2
- 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 2
- 229940125904 compound 1 Drugs 0.000 description 2
- 229940125782 compound 2 Drugs 0.000 description 2
- 125000000000 cycloalkoxy group Chemical group 0.000 description 2
- 230000006837 decompression Effects 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 2
- 235000019796 monopotassium phosphate Nutrition 0.000 description 2
- 239000012044 organic layer Substances 0.000 description 2
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 2
- 239000000106 platelet aggregation inhibitor Substances 0.000 description 2
- 210000004623 platelet-rich plasma Anatomy 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 210000003462 vein Anatomy 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- UPZFLZYXYGBAPL-UHFFFAOYSA-N 2-ethyl-2-methyl-1,3-dioxolane Chemical compound CCC1(C)OCCO1 UPZFLZYXYGBAPL-UHFFFAOYSA-N 0.000 description 1
- 239000005528 B01AC05 - Ticlopidine Substances 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 238000000692 Student's t-test Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 229960003328 benzoyl peroxide Drugs 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000003194 forelimb Anatomy 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 150000002367 halogens Chemical group 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000009987 spinning Methods 0.000 description 1
- 238000012109 statistical procedure Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 230000002537 thrombolytic effect Effects 0.000 description 1
- 229960005001 ticlopidine Drugs 0.000 description 1
- PHWBOXQYWZNQIN-UHFFFAOYSA-N ticlopidine Chemical compound ClC1=CC=CC=C1CN1CC(C=CS2)=C2CC1 PHWBOXQYWZNQIN-UHFFFAOYSA-N 0.000 description 1
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
Abstract
The invention relates to a compound for resisting thrombus, in particular to a compound shown in formula (I) or salt thereof which is pharmaceutically acceptable, a preparation method, a pharmaceutical composition and usage thereof in the aspect of medicine, wherein R1 is selected from alkyl, cycloalkyl, alkoxy or ring-alkoxy; and X is halogen. The compound has the platelet aggregation inhibitoryaction.
Description
Technical field
The present invention relates to antithrombotic compound, its preparation method and pharmaceutical use.
Background technology
Thrombus can make main organs generation ischemic and infraction, also can cause oedema and impaired function of vein, thereby causes various dysfunctions.Antithrombotic reagent is made up of anti-freezing medicine, antiplatelet drug and thrombolysis medicine three major types, and wherein antiplatelet drug is the emphasis that people study always.
THTP with platelet aggregation inhibitor effect that has gone on the market and pyridine derivate have ticlopidine (chemistry 5-(2-benzyl chloride base)-4,5,6 by name; The 7-THTP is [3,2-c] pyridine also), clopidogrel (chemistry (α S)-α by name-(2-chloro-phenyl-)-(α-4,5; 6, the 7-THTP is [3,2-c] pyridine-5 also)-methyl acetate); Prasugrel (chemistry 2-acetoxyl group-5-by name (the adjacent luorobenzyl of α-cyclopropyl carbonyl)-4,5,6; The 7-THTP is [3,2-c] pyridine also) demonstrate activity, tolerance and the security that is superior to clopidogrel in clinical three phases, be expected to become a good antithrombotic.
Summary of the invention
The inventor is a purpose with the compound that exploitation has good platelet aggregation inhibitor effect, and THTP and pyridine derivate have been carried out deep research, and the compound shown in the discoverable type (I) has the effect that good platelet aggregation suppresses as a result
Wherein,
R
1Be selected from alkyl, naphthenic base, alkoxyl group or cycloalkyloxy, preferably (C
1-4) alkyl, (C
3-7) naphthenic base, (C
1-4) alkoxyl group or (C
3-7) cycloalkyloxy, more preferably cyclopropyl or methoxyl group;
X is a halogen, like fluorine, chlorine, bromine, and preferred fluorine or chlorine atom.
Formula of the present invention (I) compound is made by formula (II) compound or its isomer or salt and the reaction of formula (III) compound,
R in its Chinese style (II) compound, formula (III) compound
1, X such as general formula (I) definition; Be reflected at alkali and exist down and carry out, used alkali is selected from organic bases or mineral alkali, and organic bases is selected from but non-limiting following kind also: sodium ethylate, potassium tert.-butoxide, n-Butyl Lithium, sodium amide etc.; Mineral alkali be selected from but and non-limiting following kind: sodium hydroxide, sodium hydrogen, Pottasium Hydroxide etc., preferred sodium hydrogen.
Formula of the present invention (I) compound, its pharmacy acceptable salt, solvolyte, racemic mixture, enantiomer or its mixture can be used for preparing the medicine that can prevent and treat thrombotic diseases.
Formula of the present invention (I) compound, its pharmacy acceptable salt, solvolyte, racemic mixture, enantiomer are as above-mentioned treatment of diseases or prophylactic agent use the time; Can with its with suitable pharmacology on acceptable vehicle, thinner etc. mix, with oral administrations such as tablet, capsule, granule, powder or syrups or with injection or the non-oral way administration of suppository.
Further, the invention still further relates to a kind of pharmaceutical composition, this pharmaceutical composition comprises formula (I) compound, its pharmacy acceptable salt, racemic mixture, enantiomer or its mixture and pharmaceutically acceptable carrier.This pharmaceutical composition can be used for preparing the medicine that can prevent and treat thrombotic diseases.
Embodiment
Preferred embodiment with concrete operations with reference to following embodiment, but the present invention is not limited to the following example.
Preparation example 1
The preparation of ethylene-acetic acid acid anhydride
Ethylene-acetic acid (7.7g), triethylamine (9.1g) are dissolved in the ETHYLE ACETATE (100ml), and ice-water bath cooling adds TRIPHOSGENE 99.5 (4.5g) down in batches, stirs after 0.5 hour stirring at room 2 hours.Filter and wash with ETHYLE ACETATE, filtrating is concentrated into the dried oily matter 6.9g that obtains, yield 99.5%.
Embodiment 1
2-(cyclopropyl methanoyl)-5-(α-cyclopropyl carbonyl-2-luorobenzyl)-4,5,6, the 7-THTP is the preparation of [3,2-c] pyridine also
With 5-(α-cyclopropyl carbonyl-2-luorobenzyl)-2-oxygen-2,4,5,6; 7,7a-six hydrogen thieno-s [3,2-c] pyridines (0.5g) are dissolved in DMF (4ml); Add ethylene-acetic acid acid anhydride (0.46g), the ice-water bath cooling adds 60% sodium hydrogen (0.12g), stirring at room 3 hours down in batches.Add ETHYLE ACETATE (50ml), potassium dihydrogen phosphate (30ml), separatory, water layer extracts with ETHYLE ACETATE (20ml).Merge organic layer, with saturated sodium bicarbonate solution (20ml * 3), water (20ml) washing, anhydrous magnesium sulfate drying.Filter, filtrate decompression is concentrated into dried oily matter 0.6g.Obtain title compound: 0.38g, white solid, compound 1 with the silica gel column chromatography separation.
MS(m/z)：426(M+1)；
1HNMR(CDCl
3)δ：0.824～1.204(m，8H)，1.782～1.846(m，1H)，2.298～2.320(m，1H)，2.826～2.956(m，4H)，3.556～3.617(m，2H)，4.866(s，1H)，6.290(s，1H)，7.117～7.539(m，4H)。
Embodiment 2
(α S)-2-(cyclopropyl methanoyl)-5-(α-methoxycarbonyl-2-benzyl chloride base)-4,5,6, the 7-THTP is the preparation of [3,2-c] pyridine also
With (α S)-α-(2-chloro-phenyl-)-2,3,6; 7-tetrahydrochysene-2-oxygen-thieno-[3,2-c] pyridines-5 (4H)-methyl acetate) (0.5g) be dissolved in DMF (4ml), add ethylene-acetic acid acid anhydride (0.46g); The ice-water bath cooling adds 60% sodium hydrogen (0.12g), stirring at room 3 hours down in batches.Add ETHYLE ACETATE (50ml), potassium dihydrogen phosphate (30ml), separatory, water layer extracts with ETHYLE ACETATE (20ml).Merge organic layer, with saturated sodium bicarbonate solution (20ml * 3), water (20ml) washing, anhydrous magnesium sulfate drying.Filter, filtrate decompression is concentrated into dried, gained oily matter.Obtain title compound: 0.35g, compound 2 with the silica gel column chromatography separation.
MS(m/z)：406(M+1)；
1HNMR(CDCl
3)δ：1.024～1.200(m，4H)，1.778～1.829(m，1H)，2.799(s，2H)，2.957(s，2H)，3.598～3.809(m，5H)，4.970(t，1H)，6.284(s，1H)，7.266～7.7337(m，4H)。
Embodiment 3
2-(cyclopropyl methanoyl)-5-(α-ethyl carbonyl-2-luorobenzyl)-4,5,6, the 7-THTP is the preparation of [3,2-c] pyridine also
The preparation method is with experimental example 1, and difference is raw material by 5-(α-cyclopropyl carbonyl-2-luorobenzyl)-2-oxygen-2,4,5,6; 7,7a-six hydrogen thieno-s [3,2-c] pyridine changes 5-(α-ethyl base carbonyl-2-luorobenzyl)-2-oxygen-2,4,5 into; 6,7,7a-six hydrogen thieno-s [3,2-c] pyridine.
MS(m/z)：412(M+1)。
Embodiment 4
(α S)-2-(cyclopropyl methanoyl)-5-(α-cyclopropyl oxygen carbonyl-2-benzyl chloride base)-4,5,6, the 7-THTP is the preparation of [3,2-c] pyridine also
The preparation method is with embodiment 2, and difference is raw material by (α S)-α-(2-chloro-phenyl-)-2,3; 6,7-tetrahydrochysene-2-oxygen-thieno-[3,2-c] pyridines-5 (4H)-methyl acetate changes (α S)-α-(2-chloro-phenyl-)-2 into; 3; 6,7-tetrahydrochysene-2-oxygen-thieno-[3,2-c] pyridines-5 (4H)-acetate cyclopropyl ester.
MS(m/z)：434(M+1)。
Test Example one
Inhibiting evaluation to ADP (ADP) inductive dog platelet aggregation
TP: fasting 12h before the experiment of Beagle dog, but can't help water.Irritate the clothes administration morning on an empty stomach, the forelimb vein of 2,5 hours clear-headed dogs is got blood before administration and after the administration respectively, and spinning platelet rich plasma (PRP) and platelet poor plasma (PPP) are assembled with the ADP induced platelet, carries out PAR and measures.
The sample preparation: all samples is capsule
Experimental animal: 4 of healthy Beagle dogs; Age 9-10 month; Body weight 8-11kg,
Data and statistical procedures: experimental data representes that with x ± SD Student t test carries out test of significance.
Test-results: see table 1, table 2.
Table 1: antiplatelet aggregative activity in the body of oral administration 2h
*P＜0.05,
*P＜0.01 vs blank group
Table 2: antiplatelet aggregative activity in the body of oral administration 5h
*P＜0.05,
*P＜0.01 vs blank group
Conclusion (of pressure testing): oral administration was compared with prasugrel after 2 hours, and compound 1 has antiplatelet aggregative activity in the better body; Behind the oral administration 5 hours, compare with prasugrel, compound 2 has antiplatelet aggregative activity in the better body.
Claims (8)
1. the compound shown in the formula (I), its pharmacy acceptable salt or racemic mixture:
Wherein,
R
1Be selected from cyclopropyl, X is selected from fluorine or chlorine; Perhaps,
R
1Be selected from methoxyl group, X is a chlorine.
2. method for preparing formula as claimed in claim 1 (I) compound is characterized in that formula (II) compound or its isomer or its pharmacy acceptable salt and formula III compound react to obtain formula (I) compound in the presence of alkali
Wherein, R
1, X such as claim 1 definition.
3. method according to claim 2 is characterized in that said alkali is selected from organic bases or mineral alkali.
4. method according to claim 3 is characterized in that said organic bases is selected from sodium ethylate, potassium tert.-butoxide or n-Butyl Lithium; Said mineral alkali is selected from sodium amide, sodium hydroxide, sodium hydrogen or Pottasium Hydroxide.
5. method according to claim 4 is characterized in that said mineral alkali is a sodium hydrogen.
6. pharmaceutical composition, this pharmaceutical composition includes formula as claimed in claim 1 (I) compound, its pharmacy acceptable salt or racemic mixture and pharmaceutically acceptable carrier.
7. formula as claimed in claim 1 (I) compound, its pharmacy acceptable salt or the racemic mixture purposes in the medicine of preparation prevention and treatment thrombotic diseases.
8. the purposes of pharmaceutical composition as claimed in claim 6 in the medicine of preparation prevention and treatment thrombotic diseases.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009101384385A CN101885730B (en) | 2009-05-13 | 2009-05-13 | Compound for resisting thrombus |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009101384385A CN101885730B (en) | 2009-05-13 | 2009-05-13 | Compound for resisting thrombus |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101885730A CN101885730A (en) | 2010-11-17 |
| CN101885730B true CN101885730B (en) | 2012-07-04 |
Family
ID=43071845
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2009101384385A Expired - Fee Related CN101885730B (en) | 2009-05-13 | 2009-05-13 | Compound for resisting thrombus |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101885730B (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102120744B (en) | 2010-02-02 | 2013-01-09 | 江苏威凯尔医药科技有限公司 | Optical-activity 2-hydroxytetrahydrothienopyridine derivative, preparation method and application thereof in pharmacy |
| CN102212069A (en) * | 2010-04-06 | 2011-10-12 | 刘桂坤 | Cycloalkane derivative, preparation method thereof and application thereof in medicaments for cardiovascular and cerebrovascular diseases |
| MX349974B (en) | 2010-08-26 | 2017-08-22 | Ipca Laboratories Ltd * | Methods for the treatment or prophylaxis of thrombosis or embolism. |
| SG195257A1 (en) * | 2011-06-27 | 2013-12-30 | Ipca Lab Ltd | Anti-thrombotic compounds |
| CN104447867B (en) * | 2013-09-17 | 2017-12-26 | 江苏天士力帝益药业有限公司 | A kind of thieno piperidine derivative, preparation method and applications |
| CN107698620A (en) | 2015-06-23 | 2018-02-16 | 江苏天士力帝益药业有限公司 | A kind of deuterated thieno piperidine derivative, preparation method and applications |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4847265A (en) * | 1987-02-17 | 1989-07-11 | Sanofi | Dextro-rotatory enantiomer of methyl alpha-5 (4,5,6,7-tetrahydro (3,2-c) thieno pyridyl) (2-chlorophenyl)-acetate and the pharmaceutical compositions containing it |
| CN1074446A (en) * | 1991-09-09 | 1993-07-21 | 三共株式会社 | Tetrahydrothienopyriderivatives derivatives |
| CN101402556A (en) * | 2008-11-11 | 2009-04-08 | 上海现代制药股份有限公司 | New compound 1-cyclopropyl-2-(2-fluorine phenyl)-2-hydroxyl ethanone, preparation method and application thereof |
-
2009
- 2009-05-13 CN CN2009101384385A patent/CN101885730B/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4847265A (en) * | 1987-02-17 | 1989-07-11 | Sanofi | Dextro-rotatory enantiomer of methyl alpha-5 (4,5,6,7-tetrahydro (3,2-c) thieno pyridyl) (2-chlorophenyl)-acetate and the pharmaceutical compositions containing it |
| CN1074446A (en) * | 1991-09-09 | 1993-07-21 | 三共株式会社 | Tetrahydrothienopyriderivatives derivatives |
| CN101402556A (en) * | 2008-11-11 | 2009-04-08 | 上海现代制药股份有限公司 | New compound 1-cyclopropyl-2-(2-fluorine phenyl)-2-hydroxyl ethanone, preparation method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101885730A (en) | 2010-11-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101885730B (en) | Compound for resisting thrombus | |
| CN101591344B (en) | Antithrombotic compound as well as preparation method and application thereof | |
| ES2602503T3 (en) | Organic compounds | |
| JP5995728B2 (en) | Inhibitors of catechol O-methyltransferase and their use in the treatment of mental disorders | |
| CN101242839B (en) | Azaindazole compounds and methods of use | |
| TW202122388A (en) | Rip1 inhibitory compounds and methods for making and using the same | |
| KR102087918B1 (en) | Fused ring derivatives, methods for their preparation, intermediates, drug compositions and applications | |
| BR112018015283B1 (en) | ORGANIC COMPOUNDS, PHARMACEUTICAL COMPOSITION COMPRISING SAID COMPOUNDS AND USE THEREOF FOR THE TREATMENT OR PROPHYLAXIS OF A DISORDER OF THE CENTRAL NERVOUS SYSTEM | |
| JP6966423B2 (en) | Condensed ring pyrimidine amino derivative, its production method, intermediate, pharmaceutical composition and application | |
| TW202003430A (en) | Methods of reducing inflammation of the digestive system with inhibitors of HIF-2-alpha | |
| KR20190060874A (en) | Optically active 2-hydroxytetrahydrothienopyridine derivatives, preparation method and use in manufacture of medicament thereof | |
| RU2720488C2 (en) | Substituted amino six-member saturated heteroalicycles as long-acting dpp-iv inhibitors | |
| JP2013521286A (en) | Inhibitors of catechol O-methyltransferase and their use in the treatment of mental disorders | |
| JP2007517887A5 (en) | ||
| KR20180049056A (en) | Tricyclic condensed pyridine-2-one derivatives and their use as BRD4 inhibitors | |
| JPH0565288A (en) | New acylamino-substituted hetrazepine derivative, process for producing same and medicinal composition containing same | |
| HUT53078A (en) | Process for producing piperidine derivatives | |
| SG181715A1 (en) | Bicyclic thiazoles as allosteric modulators of mglur5 receptors | |
| TW200815457A (en) | Substituted 3-amino-thieno[2,3-b]pyridine-2-carboxylic acid amide compounds and processes for preparing and their uses | |
| US20240010658A1 (en) | Abhd6 antagonist | |
| JP2019536759A (en) | Substituted bicyclic heteroaryl nicotinic acetylcholine receptor allosteric modulators | |
| PT92793A (en) | PROCESS FOR THE PREPARATION OF PYRID (2,3-D) PYRIMIDINES REPLACED | |
| JP2021525784A (en) | Thieno [2,3-c] pyridazine-4 (1H) -one derivative and its use | |
| KR20030053530A (en) | Indole derivatives and use thereof in medicines | |
| US8536342B2 (en) | Process for producing thiabenzoazulene-propionic acid derivative |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| ASS | Succession or assignment of patent right |
Owner name: JIANGSU HANSOH MEDICAL GROUP CO.,LTD. Free format text: FORMER OWNER: LIANYUNGANG HENGBANG PHARMACEUTICAL TECHNOLOGY CO., LTD. Effective date: 20131113 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20131113 Address after: 222047 Lianyungang Development Zone, Jiangsu Patentee after: Jiangsu Hansoh Medical Group Co.,Ltd. Address before: 222047 tenth Industrial Zone, Lianyungang economic and Technological Development Zone, Jiangsu Patentee before: Lianyungang Hengbang Pharmaceutical Technology Co., Ltd. |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20160315 Address after: 222047 Lianyungang economic and Technological Development Zone, Jiangsu Patentee after: JIANGSU HANSOH PHARMACEUTICAL GROUP LIANYUNGANG HONGCHUANG PHARMACEUTICAL CO., LTD. Address before: 222047 Lianyungang Development Zone, Jiangsu Patentee before: Jiangsu Hansoh Medical Group Co.,Ltd. |
|
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20120704 Termination date: 20170513 |
|
| CF01 | Termination of patent right due to non-payment of annual fee |