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 (zh) | 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 (zh) |
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 |
|---|---|---|---|---|
| US10479784B2 (en) | 2008-12-19 | 2019-11-19 | Vertex Pharmaceuticals Incorporated | Substituted pyrazin-2-amines as inhibitors of ATR kinase |
| US9365557B2 (en) | 2008-12-19 | 2016-06-14 | Vertex Pharmaceuticals Incorporated | Substituted pyrazin-2-amines as inhibitors of ATR kinase |
| 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 |
| US9334244B2 (en) | 2010-05-12 | 2016-05-10 | Vertex Pharmaceuticals Incorporated | Compounds useful 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 |
| 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 (zh) | 1993-10-21 |
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