JPS63208520A - ピラジン誘導体を含有する血小板凝集抑制剤 - Google Patents
ピラジン誘導体を含有する血小板凝集抑制剤Info
- Publication number
- JPS63208520A JPS63208520A JP4155087A JP4155087A JPS63208520A JP S63208520 A JPS63208520 A JP S63208520A JP 4155087 A JP4155087 A JP 4155087A JP 4155087 A JP4155087 A JP 4155087A JP S63208520 A JPS63208520 A JP S63208520A
- Authority
- JP
- Japan
- Prior art keywords
- formula
- blood platelet
- pyrazine derivative
- expressed
- platelet agglutination
- 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.)
- Granted
Links
- 150000003216 pyrazines Chemical class 0.000 title claims abstract description 22
- 229940127218 antiplatelet drug Drugs 0.000 title claims abstract description 9
- 210000001772 blood platelet Anatomy 0.000 title abstract 3
- 101000783577 Dendroaspis angusticeps Thrombostatin Proteins 0.000 claims description 7
- 101000783578 Dendroaspis jamesoni kaimosae Dendroaspin Proteins 0.000 claims description 7
- 239000000106 platelet aggregation inhibitor Substances 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 2
- YZXBAPSDXZZRGB-DOFZRALJSA-N arachidonic acid Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(O)=O YZXBAPSDXZZRGB-DOFZRALJSA-N 0.000 abstract description 6
- 150000001875 compounds Chemical class 0.000 abstract description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 abstract description 4
- 102000008186 Collagen Human genes 0.000 abstract description 3
- 108010035532 Collagen Proteins 0.000 abstract description 3
- 229940114079 arachidonic acid Drugs 0.000 abstract description 3
- 235000021342 arachidonic acid Nutrition 0.000 abstract description 3
- 229920001436 collagen Polymers 0.000 abstract description 3
- 239000000546 pharmaceutical excipient Substances 0.000 abstract description 3
- JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 abstract description 3
- YLBCZNNGPOPTGM-UHFFFAOYSA-N 2-chloro-3,5-diphenylpyrazine Chemical compound ClC1=NC=C(C=2C=CC=CC=2)N=C1C1=CC=CC=C1 YLBCZNNGPOPTGM-UHFFFAOYSA-N 0.000 abstract description 2
- FYIHUZXWJJAIJW-UHFFFAOYSA-N 2-methyl-3,5-diphenylpyrazine Chemical compound CC1=NC=C(C=2C=CC=CC=2)N=C1C1=CC=CC=C1 FYIHUZXWJJAIJW-UHFFFAOYSA-N 0.000 abstract description 2
- 229920000858 Cyclodextrin Polymers 0.000 abstract description 2
- 239000004480 active ingredient Substances 0.000 abstract description 2
- 239000002775 capsule Substances 0.000 abstract description 2
- 239000003795 chemical substances by application Substances 0.000 abstract description 2
- 239000003937 drug carrier Substances 0.000 abstract description 2
- 238000010438 heat treatment Methods 0.000 abstract description 2
- 239000003960 organic solvent Substances 0.000 abstract description 2
- 229910052763 palladium Inorganic materials 0.000 abstract description 2
- 239000000843 powder Substances 0.000 abstract description 2
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 abstract description 2
- 239000000725 suspension Substances 0.000 abstract description 2
- 239000006188 syrup Substances 0.000 abstract description 2
- 235000020357 syrup Nutrition 0.000 abstract description 2
- 239000003826 tablet Substances 0.000 abstract description 2
- 206010008111 Cerebral haemorrhage Diseases 0.000 abstract 1
- 206010061216 Infarction Diseases 0.000 abstract 1
- 230000004520 agglutination Effects 0.000 abstract 1
- 230000000747 cardiac effect Effects 0.000 abstract 1
- 206010008118 cerebral infarction Diseases 0.000 abstract 1
- 208000026106 cerebrovascular disease Diseases 0.000 abstract 1
- 238000007796 conventional method Methods 0.000 abstract 1
- 230000007574 infarction Effects 0.000 abstract 1
- 230000000302 ischemic effect Effects 0.000 abstract 1
- 238000002156 mixing Methods 0.000 abstract 1
- 230000003449 preventive effect Effects 0.000 abstract 1
- 230000000087 stabilizing effect Effects 0.000 abstract 1
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- 230000002401 inhibitory effect Effects 0.000 description 6
- 239000003146 anticoagulant agent Substances 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000004220 aggregation Methods 0.000 description 4
- 230000002776 aggregation Effects 0.000 description 4
- 230000000702 anti-platelet effect Effects 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- 208000007536 Thrombosis Diseases 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 206010008132 Cerebral thrombosis Diseases 0.000 description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- 201000001429 Intracranial Thrombosis Diseases 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 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
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 231100000215 acute (single dose) toxicity testing Toxicity 0.000 description 1
- 231100000403 acute toxicity Toxicity 0.000 description 1
- 230000007059 acute toxicity Effects 0.000 description 1
- 238000011047 acute toxicity test Methods 0.000 description 1
- 229960004676 antithrombotic agent Drugs 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 210000001715 carotid artery Anatomy 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 150000001793 charged compounds Chemical class 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- SPWVRYZQLGQKGK-UHFFFAOYSA-N dichloromethane;hexane Chemical compound ClCCl.CCCCCC SPWVRYZQLGQKGK-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 239000010446 mirabilite Substances 0.000 description 1
- 208000010125 myocardial infarction Diseases 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 210000004623 platelet-rich plasma Anatomy 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 238000010898 silica gel chromatography 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
- RSIJVJUOQBWMIM-UHFFFAOYSA-L sodium sulfate decahydrate Chemical compound O.O.O.O.O.O.O.O.O.O.[Na+].[Na+].[O-]S([O-])(=O)=O RSIJVJUOQBWMIM-UHFFFAOYSA-L 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4155087A JPS63208520A (ja) | 1987-02-26 | 1987-02-26 | ピラジン誘導体を含有する血小板凝集抑制剤 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP4155087A JPS63208520A (ja) | 1987-02-26 | 1987-02-26 | ピラジン誘導体を含有する血小板凝集抑制剤 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS63208520A true JPS63208520A (ja) | 1988-08-30 |
| JPH0575728B2 JPH0575728B2 (de) | 1993-10-21 |
Family
ID=12611534
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP4155087A Granted JPS63208520A (ja) | 1987-02-26 | 1987-02-26 | ピラジン誘導体を含有する血小板凝集抑制剤 |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS63208520A (de) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013526540A (ja) * | 2010-05-12 | 2013-06-24 | バーテックス ファーマシューティカルズ インコーポレイテッド | Ａｔｒキナーゼ阻害剤として有用な化合物 |
| US9365557B2 (en) | 2008-12-19 | 2016-06-14 | Vertex Pharmaceuticals Incorporated | Substituted pyrazin-2-amines as inhibitors of ATR kinase |
| US9630956B2 (en) | 2010-05-12 | 2017-04-25 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of ATR kinase |
| US9791456B2 (en) | 2012-10-04 | 2017-10-17 | Vertex Pharmaceuticals Incorporated | Method for measuring ATR inhibition mediated increases in DNA damage |
| US9862709B2 (en) | 2011-09-30 | 2018-01-09 | Vertex Pharmaceuticals Incorporated | Processes for making compounds useful as inhibitors of ATR kinase |
| US10478430B2 (en) | 2012-04-05 | 2019-11-19 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of ATR kinase and combination therapies thereof |
| US10813929B2 (en) | 2011-09-30 | 2020-10-27 | Vertex Pharmaceuticals Incorporated | Treating cancer with ATR inhibitors |
| US11464774B2 (en) | 2015-09-30 | 2022-10-11 | Vertex Pharmaceuticals Incorporated | Method for treating cancer using a combination of DNA damaging agents and ATR inhibitors |
-
1987
- 1987-02-26 JP JP4155087A patent/JPS63208520A/ja active Granted
Cited By (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9701674B2 (en) | 2008-12-19 | 2017-07-11 | Vertex Pharmaceuticals Incorporated | Substituted pyrazines as ATR kinase inhibitors |
| US10961232B2 (en) | 2008-12-19 | 2021-03-30 | Vertex Pharmaceuticals Incorporated | Substituted pyrazines as ATR kinase inhibitors |
| US9365557B2 (en) | 2008-12-19 | 2016-06-14 | Vertex Pharmaceuticals Incorporated | Substituted pyrazin-2-amines as inhibitors of ATR kinase |
| US10479784B2 (en) | 2008-12-19 | 2019-11-19 | Vertex Pharmaceuticals Incorporated | Substituted pyrazin-2-amines as inhibitors of ATR kinase |
| US9630956B2 (en) | 2010-05-12 | 2017-04-25 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of ATR kinase |
| JP2013526540A (ja) * | 2010-05-12 | 2013-06-24 | バーテックス ファーマシューティカルズ インコーポレイテッド | Ａｔｒキナーゼ阻害剤として有用な化合物 |
| US9334244B2 (en) | 2010-05-12 | 2016-05-10 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of ATR kinase |
| US9862709B2 (en) | 2011-09-30 | 2018-01-09 | Vertex Pharmaceuticals Incorporated | Processes for making compounds useful as inhibitors of ATR kinase |
| US10208027B2 (en) | 2011-09-30 | 2019-02-19 | Vertex Pharmaceuticals Incorporated | Processes for preparing ATR inhibitors |
| US10813929B2 (en) | 2011-09-30 | 2020-10-27 | Vertex Pharmaceuticals Incorporated | Treating cancer with ATR inhibitors |
| US10822331B2 (en) | 2011-09-30 | 2020-11-03 | Vertex Pharmaceuticals Incorporated | Processes for preparing ATR inhibitors |
| US10478430B2 (en) | 2012-04-05 | 2019-11-19 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of ATR kinase and combination therapies thereof |
| US11110086B2 (en) | 2012-04-05 | 2021-09-07 | Vertex Pharmaceuticals Incorporated | Compounds useful as inhibitors of ATR kinase and combination therapies thereof |
| US9791456B2 (en) | 2012-10-04 | 2017-10-17 | Vertex Pharmaceuticals Incorporated | Method for measuring ATR inhibition mediated increases in DNA damage |
| US11464774B2 (en) | 2015-09-30 | 2022-10-11 | Vertex Pharmaceuticals Incorporated | Method for treating cancer using a combination of DNA damaging agents and ATR inhibitors |
Also Published As
| Publication number | Publication date |
|---|---|
| JPH0575728B2 (de) | 1993-10-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US4847265A (en) | 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 | |
| WO2015039577A1 (zh) | 噻吩并哌啶衍生物及其用途 | |
| JPS63208520A (ja) | ピラジン誘導体を含有する血小板凝集抑制剤 | |
| JPS5919956B2 (ja) | 新規ジアゼピン誘導体の製法 | |
| JPS62270564A (ja) | ピラジン誘導体およびこれを含有する血小板凝集抑制剤 | |
| EP1775293A1 (de) | Antithrombozytenmittel und verfahren zu dessen herstellung | |
| JPS62106019A (ja) | 抗高脂血症剤 | |
| JPS6144870A (ja) | 不飽和脂肪酸アミド誘導体およびこれを含有する血小板凝集抑制剤 | |
| US4461891A (en) | 2-β-D-Ribofuranosylthiazole-4-carboxamidine compounds | |
| JPS637558B2 (de) | ||
| EP0204172B1 (de) | Phenylpyrazinderivate, Verfahren zu deren Herstellung, pharmazeutische Zusammensetzung und Verwendung | |
| JPH032183A (ja) | ビスベンジルイソキノリン誘導体 | |
| US4358441A (en) | Nicotinic derivatives of glucosamine and related pharmaceutical compositions | |
| JPS61277617A (ja) | 坑血小板凝集剤 | |
| JPS61293981A (ja) | １２ｂ−置換１−ヒドロキシメチル−オクタヒドロインドロ〔２，３−ａ〕キノリジン誘導体，それらの製造法及びそれらを含む医薬組成物 | |
| JPS62174060A (ja) | ５−フルオロウラシル誘導体およびこれを含有する医薬製剤 | |
| JPH0368578A (ja) | ビスベンジルイソキノリン誘導体 | |
| JPS62167791A (ja) | 血小板凝集抑制剤 | |
| JPH0153849B2 (de) | ||
| JPS61212522A (ja) | 血小板凝集抑制剤 | |
| JPH01128971A (ja) | ピラジン誘導体およびこれを含有する血小板凝集抑制剤 | |
| JP2534902B2 (ja) | 新規なグリセリン誘導体およびその誘導体を含有する血小板凝集抑制剤 | |
| JPS6034947A (ja) | ドコサヘキサエン酸誘導体およびそれを用いた血小板凝集阻止剤 | |
| JPS5967263A (ja) | ペンタエン高級脂肪酸ピリジルアルコ−ルエステルおよびその製法 | |
| JPS6281372A (ja) | 不飽和脂肪酸アミド誘導体およびこれを含有する血小板凝集抑制剤 |