CN102711481A - 吡嗪酮凝血酶抑制剂及其中间体的制备方法 - Google Patents
吡嗪酮凝血酶抑制剂及其中间体的制备方法 Download PDFInfo
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- CN102711481A CN102711481A CN2010800499062A CN201080049906A CN102711481A CN 102711481 A CN102711481 A CN 102711481A CN 2010800499062 A CN2010800499062 A CN 2010800499062A CN 201080049906 A CN201080049906 A CN 201080049906A CN 102711481 A CN102711481 A CN 102711481A
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- 239000000284 extract Substances 0.000 description 1
- MNWFXJYAOYHMED-UHFFFAOYSA-M heptanoate Chemical compound CCCCCCC([O-])=O MNWFXJYAOYHMED-UHFFFAOYSA-M 0.000 description 1
- ULLYUYLDAISRDE-SSPAHAAFSA-N heptanoic acid (2R,3S,4R,5R)-2,3,4,5,6-pentahydroxyhexanal Chemical compound C(CCCCCC)(=O)O.O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO ULLYUYLDAISRDE-SSPAHAAFSA-N 0.000 description 1
- FUZZWVXGSFPDMH-UHFFFAOYSA-M hexanoate Chemical compound CCCCCC([O-])=O FUZZWVXGSFPDMH-UHFFFAOYSA-M 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 238000012423 maintenance Methods 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
- PQIOSYKVBBWRRI-UHFFFAOYSA-N methylphosphonyl difluoride Chemical group CP(F)(F)=O PQIOSYKVBBWRRI-UHFFFAOYSA-N 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-M naphthalene-2-sulfonate Chemical compound C1=CC=CC2=CC(S(=O)(=O)[O-])=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-M 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 1
- 229940075930 picrate Drugs 0.000 description 1
- OXNIZHLAWKMVMX-UHFFFAOYSA-M picrate anion Chemical compound [O-]C1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-M 0.000 description 1
- 229950010765 pivalate Drugs 0.000 description 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 1
- 238000012805 post-processing Methods 0.000 description 1
- SSOLNOMRVKKSON-UHFFFAOYSA-N proguanil Chemical compound CC(C)\N=C(/N)N=C(N)NC1=CC=C(Cl)C=C1 SSOLNOMRVKKSON-UHFFFAOYSA-N 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- APSBXTVYXVQYAB-UHFFFAOYSA-M sodium docusate Chemical compound [Na+].CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC APSBXTVYXVQYAB-UHFFFAOYSA-M 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- ZDPHROOEEOARMN-UHFFFAOYSA-M undecanoate Chemical compound CCCCCCCCCCC([O-])=O ZDPHROOEEOARMN-UHFFFAOYSA-M 0.000 description 1
- 238000005292 vacuum distillation Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/4965—Non-condensed pyrazines
- A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B61/00—Other general methods
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Catalysts (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IN2663/CHE/2009 | 2009-11-03 | ||
| IN2663CH2009 | 2009-11-03 | ||
| PCT/US2010/055176 WO2011056806A1 (en) | 2009-11-03 | 2010-11-02 | Process for the preparation of pyrazinone thrombin inhibitor and its intermediates |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN102711481A true CN102711481A (zh) | 2012-10-03 |
Family
ID=43926105
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2010800499062A Pending CN102711481A (zh) | 2009-11-03 | 2010-11-02 | 吡嗪酮凝血酶抑制剂及其中间体的制备方法 |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US8541580B2 (enExample) |
| EP (1) | EP2496087A4 (enExample) |
| JP (1) | JP2013510159A (enExample) |
| KR (1) | KR20120106727A (enExample) |
| CN (1) | CN102711481A (enExample) |
| AU (1) | AU2010315338A1 (enExample) |
| CA (1) | CA2778922A1 (enExample) |
| MX (1) | MX2012005165A (enExample) |
| RU (1) | RU2012118499A (enExample) |
| WO (1) | WO2011056806A1 (enExample) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10016417B2 (en) | 2011-11-07 | 2018-07-10 | Diakron Pharmaceuticals, Inc. | Extended release formulation of a direct thrombin inhibitor |
| CN108430986B (zh) | 2015-10-26 | 2021-08-31 | 拜耳作物科学股份公司 | 作为有害生物控制剂的稠合双环杂环衍生物 |
| PH12021552065A1 (en) | 2019-02-26 | 2022-05-23 | Bayer Ag | Condensed bicyclic heterocyclic derivatives as pest control agents |
| CN113710669A (zh) | 2019-02-26 | 2021-11-26 | 拜耳公司 | 作为农药的稠合双环杂环衍生物 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002046160A2 (en) * | 2000-12-06 | 2002-06-13 | Merck & Co., Inc. | Process for making a thrombin inhibitor |
| EP1422221A1 (en) * | 2002-11-20 | 2004-05-26 | Bayer CropScience SA | Novel process for the preparation of 2-aminomethylpyridine derivative |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6147078A (en) * | 1998-05-19 | 2000-11-14 | Merck & Co., Inc. | Pyrazinone thrombin inhibitors |
| UA58636C2 (uk) * | 1999-06-04 | 2003-08-15 | Мерк Енд Ко., Інк. | Піразинонові інгібітори тромбіну, фармацевтична композиція, спосіб інгібування утворення тромбів у крові, спосіб лікування станів, пов'язаних із тромбоутворенням |
-
2010
- 2010-11-02 MX MX2012005165A patent/MX2012005165A/es active IP Right Grant
- 2010-11-02 EP EP10828989.3A patent/EP2496087A4/en not_active Withdrawn
- 2010-11-02 KR KR1020127010789A patent/KR20120106727A/ko not_active Ceased
- 2010-11-02 US US12/938,297 patent/US8541580B2/en not_active Expired - Fee Related
- 2010-11-02 CN CN2010800499062A patent/CN102711481A/zh active Pending
- 2010-11-02 AU AU2010315338A patent/AU2010315338A1/en not_active Abandoned
- 2010-11-02 RU RU2012118499/04A patent/RU2012118499A/ru not_active Application Discontinuation
- 2010-11-02 WO PCT/US2010/055176 patent/WO2011056806A1/en not_active Ceased
- 2010-11-02 CA CA2778922A patent/CA2778922A1/en not_active Abandoned
- 2010-11-02 JP JP2012537955A patent/JP2013510159A/ja active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002046160A2 (en) * | 2000-12-06 | 2002-06-13 | Merck & Co., Inc. | Process for making a thrombin inhibitor |
| EP1422221A1 (en) * | 2002-11-20 | 2004-05-26 | Bayer CropScience SA | Novel process for the preparation of 2-aminomethylpyridine derivative |
Non-Patent Citations (1)
| Title |
|---|
| CHRISTOPHER S. BURGEY ET AL.: "Metabolism-Directed Optimization of 3-Aminopyrazinone Acetamide Thrombin Inhibitors.Development of an Orally Bioavailable Series Containing P1 and P3 Pyridines", 《JOURNAL OF MEDICINAL CHEMISTRY》 * |
Also Published As
| Publication number | Publication date |
|---|---|
| KR20120106727A (ko) | 2012-09-26 |
| US8541580B2 (en) | 2013-09-24 |
| EP2496087A1 (en) | 2012-09-12 |
| US20110105753A1 (en) | 2011-05-05 |
| AU2010315338A1 (en) | 2012-05-24 |
| CA2778922A1 (en) | 2011-05-12 |
| WO2011056806A1 (en) | 2011-05-12 |
| MX2012005165A (es) | 2012-08-08 |
| EP2496087A4 (en) | 2013-06-19 |
| JP2013510159A (ja) | 2013-03-21 |
| RU2012118499A (ru) | 2013-12-10 |
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Application publication date: 20121003 |