CN104072434B - 间位取代的四氮唑苯乙酮化合物、其制备方法和用途 - Google Patents
间位取代的四氮唑苯乙酮化合物、其制备方法和用途 Download PDFInfo
- Publication number
- CN104072434B CN104072434B CN201410352042.1A CN201410352042A CN104072434B CN 104072434 B CN104072434 B CN 104072434B CN 201410352042 A CN201410352042 A CN 201410352042A CN 104072434 B CN104072434 B CN 104072434B
- Authority
- CN
- China
- Prior art keywords
- compound
- present
- preparation
- tetrazole
- general formula
- 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
- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Natural products CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 title description 2
- -1 tetrazole acetophenone compound Chemical class 0.000 title description 2
- 239000003814 drug Substances 0.000 claims abstract description 10
- 150000001875 compounds Chemical class 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 7
- 230000001732 thrombotic effect Effects 0.000 claims description 2
- 208000007536 Thrombosis Diseases 0.000 abstract description 15
- 229940098892 Protease-activated receptor-1 antagonist Drugs 0.000 abstract description 5
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 2
- 239000003146 anticoagulant agent Substances 0.000 description 7
- 210000001772 blood platelet Anatomy 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- 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
- 125000000217 alkyl group Chemical group 0.000 description 4
- 230000002785 anti-thrombosis Effects 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 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
- 208000010110 spontaneous platelet aggregation Diseases 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
- 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
- 239000003153 chemical reaction reagent Substances 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
- 125000000753 cycloalkyl group Chemical group 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
- 239000007787 solid Substances 0.000 description 2
- 238000003756 stirring Methods 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
- 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
- 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
- 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
- 239000003260 cyclooxygenase 1 inhibitor Substances 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
- 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
- 239000011541 reaction mixture Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000000611 regression analysis Methods 0.000 description 1
- 230000000452 restraining effect Effects 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 239000011734 sodium Substances 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
- 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
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D257/04—Five-membered rings
Abstract
Description
Claims (3)
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201410352042.1A CN104072434B (zh) | 2014-07-23 | 2014-07-23 | 间位取代的四氮唑苯乙酮化合物、其制备方法和用途 |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201410352042.1A CN104072434B (zh) | 2014-07-23 | 2014-07-23 | 间位取代的四氮唑苯乙酮化合物、其制备方法和用途 |
Publications (2)
Publication Number | Publication Date |
---|---|
CN104072434A CN104072434A (zh) | 2014-10-01 |
CN104072434B true CN104072434B (zh) | 2015-12-02 |
Family
ID=51594082
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201410352042.1A Expired - Fee Related CN104072434B (zh) | 2014-07-23 | 2014-07-23 | 间位取代的四氮唑苯乙酮化合物、其制备方法和用途 |
Country Status (1)
Country | Link |
---|---|
CN (1) | CN104072434B (zh) |
Families Citing this family (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104513212B (zh) * | 2015-01-13 | 2016-03-09 | 佛山市赛维斯医药科技有限公司 | 一类含硝基苯的恶二唑亚砜化合物、其制备方法和用途 |
CN104496927B (zh) * | 2015-01-13 | 2016-03-30 | 佛山市赛维斯医药科技有限公司 | 二烯四氮唑卤苯类化合物、其制备方法和用途 |
CN104496925B (zh) * | 2015-01-13 | 2016-04-06 | 佛山市赛维斯医药科技有限公司 | 二烯四氮唑类化合物、其制备方法和用途 |
CN104529928A (zh) * | 2015-01-13 | 2015-04-22 | 佛山市赛维斯医药科技有限公司 | 一类恶二唑亚砜化合物、其制备方法和用途 |
CN104478819B (zh) * | 2015-01-13 | 2016-03-30 | 佛山市赛维斯医药科技有限公司 | 二烯四氮唑苯胺类化合物、其制备方法和用途 |
CN104529930B (zh) * | 2015-01-13 | 2016-03-09 | 佛山市赛维斯医药科技有限公司 | 一类含腈基苯的噁二唑亚砜化合物、其制备方法和用途 |
CN104496923B (zh) * | 2015-01-13 | 2016-04-06 | 佛山市赛维斯医药科技有限公司 | 硝基苯二烯四氮唑类化合物、其制备方法和用途 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102241621A (zh) * | 2010-05-11 | 2011-11-16 | 江苏恒瑞医药股份有限公司 | 5,5-双取代-2-亚氨基吡咯烷类衍生物、其制备方法及其在医药上的应用 |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
HRP980334A2 (en) * | 1997-06-19 | 1999-04-30 | Mimi Lifen Quan | INHIBITORS OF FACTOR Xa WITH A NEUTRAL P1 SPECIFICITY GROUP |
US8673890B2 (en) * | 2009-10-29 | 2014-03-18 | Janssen Pharmaceutica Nv | 2,3-dihydro-1H-isoindol-1-imine derivatives useful as thrombin PAR-1 receptor antagonist |
-
2014
- 2014-07-23 CN CN201410352042.1A patent/CN104072434B/zh not_active Expired - Fee Related
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102241621A (zh) * | 2010-05-11 | 2011-11-16 | 江苏恒瑞医药股份有限公司 | 5,5-双取代-2-亚氨基吡咯烷类衍生物、其制备方法及其在医药上的应用 |
Also Published As
Publication number | Publication date |
---|---|
CN104072434A (zh) | 2014-10-01 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN104072434B (zh) | 间位取代的四氮唑苯乙酮化合物、其制备方法和用途 | |
CN104072436B (zh) | 对位取代的四氮唑苯乙酮化合物、其制备方法和用途 | |
CN104098520B (zh) | 苯基三唑希夫碱类化合物、其制备方法和用途 | |
CN104529927B (zh) | 一类含卤代苯的恶二唑亚砜化合物、其制备方法和用途 | |
CN104072438B (zh) | 二烷氧代四氮唑苯乙酮化合物、其制备方法和用途 | |
CN104086503B (zh) | Par-1拮抗剂及其用途 | |
CN104072439B (zh) | 卤素取代的四氮唑苯乙酮化合物、其制备方法和用途 | |
CN104072437B (zh) | 双取代的四氮唑苯乙酮化合物、其制备方法和用途 | |
CN104086500B (zh) | 一种par-1拮抗剂及其用途 | |
CN104072435B (zh) | 双烷基取代的四氮唑苯乙酮化合物和用途 | |
CN104086502B (zh) | 卤代四氮唑苯乙酮化合物、其制备方法和用途 | |
CN104086497B (zh) | 三唑希夫碱类化合物、其制备方法和用途 | |
CN104072432B (zh) | 含苯基取代三唑希夫碱类结构的化合物、其制备方法和用途 | |
CN104086494B (zh) | 末端双取代的甲基三唑希夫碱结构化合物、其制备方法和用途 | |
CN104072431B (zh) | 烷氧基取代的苯基三唑希夫碱结构的化合物及用途 | |
CN104086498B (zh) | 末端取代的三唑希夫碱类结构的化合物、其制备方法和用途 | |
CN104140398B (zh) | 甲基三唑希夫碱类结构的化合物、其制备方法和用途 | |
CN104086495B (zh) | 末端双取代的三唑希夫碱结构化合物、其制备方法和用途 | |
CN104529931B (zh) | 一类含烷氧对位取代苯的恶二唑亚砜化合物、其制备方法和用途 | |
CN104529929B (zh) | 含烷氧取代苯的恶二唑亚砜化合物、其制备方法和用途 | |
CN104513212B (zh) | 一类含硝基苯的恶二唑亚砜化合物、其制备方法和用途 | |
CN104529930B (zh) | 一类含腈基苯的噁二唑亚砜化合物、其制备方法和用途 | |
CN104086493A (zh) | 末端取代的苯基三唑希夫碱结构的化合物及其用途 | |
CN104529928A (zh) | 一类恶二唑亚砜化合物、其制备方法和用途 | |
CN104496932A (zh) | 一类含胺基对位取代苯的恶二唑亚砜化合物、其制备方法和用途 |
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 | ||
TR01 | Transfer of patent right |
Effective date of registration: 20170803 Address after: 510640 Guangdong City, Tianhe District Province, No. five, road, public education building, unit 371-1, unit 2401 Patentee after: Guangdong Gaohang Intellectual Property Operation Co., Ltd. Address before: 528000 Guangdong, Foshan District, Pu Lan Road, the first floor of the first floor, No. 5, Chancheng Patentee before: Zhang Yuanqiang |
|
TR01 | Transfer of patent right | ||
CB03 | Change of inventor or designer information | ||
CB03 | Change of inventor or designer information |
Inventor after: Hu Wan Inventor before: Zhang Yuanqiang |
|
TR01 | Transfer of patent right | ||
TR01 | Transfer of patent right |
Effective date of registration: 20170822 Address after: 110000 3-3-2, 21-3 Heilongjiang street, Huanggu District, Liaoning, Shenyang Patentee after: Hu Wan Address before: 510640 Guangdong City, Tianhe District Province, No. five, road, public education building, unit 371-1, unit 2401 Patentee before: Guangdong Gaohang Intellectual Property Operation Co., Ltd. |
|
CF01 | Termination of patent right due to non-payment of annual fee | ||
CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20151202 Termination date: 20180723 |