HRP960597A2 - ISOXAZOLINE, ISOTHIAZOLINE AND PYRAZOLINE FACTOR Xa INHIBITORS - Google Patents
ISOXAZOLINE, ISOTHIAZOLINE AND PYRAZOLINE FACTOR Xa INHIBITORS Download PDFInfo
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- HRP960597A2 HRP960597A2 HR60/030,666A HRP960597A HRP960597A2 HR P960597 A2 HRP960597 A2 HR P960597A2 HR P960597 A HRP960597 A HR P960597A HR P960597 A2 HRP960597 A2 HR P960597A2
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- GUUULVAMQJLDSY-UHFFFAOYSA-N 4,5-dihydro-1,2-thiazole Chemical compound C1CC=NS1 GUUULVAMQJLDSY-UHFFFAOYSA-N 0.000 title abstract description 5
- WEQPBCSPRXFQQS-UHFFFAOYSA-N 4,5-dihydro-1,2-oxazole Chemical compound C1CC=NO1 WEQPBCSPRXFQQS-UHFFFAOYSA-N 0.000 title description 11
- 229940123583 Factor Xa inhibitor Drugs 0.000 title description 7
- DNXIASIHZYFFRO-UHFFFAOYSA-N pyrazoline Chemical compound C1CN=NC1 DNXIASIHZYFFRO-UHFFFAOYSA-N 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 123
- 238000000034 method Methods 0.000 claims abstract description 39
- 230000009424 thromboembolic effect Effects 0.000 claims abstract description 7
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 5
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 4
- 239000000203 mixture Substances 0.000 claims description 76
- 150000003839 salts Chemical group 0.000 claims description 27
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 15
- 239000000651 prodrug Chemical group 0.000 claims description 15
- 229940002612 prodrug Drugs 0.000 claims description 15
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 101100516568 Caenorhabditis elegans nhr-7 gene Proteins 0.000 claims description 8
- 241000124008 Mammalia Species 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 7
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 6
- 150000003413 spiro compounds Chemical class 0.000 claims description 6
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 5
- 101100134922 Gallus gallus COR5 gene Proteins 0.000 claims description 4
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 2
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 claims description 2
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 claims description 2
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 2
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- 108010074860 Factor Xa Proteins 0.000 abstract description 16
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- 238000002360 preparation method Methods 0.000 description 41
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- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical group CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 27
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
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- PNHTVNUYGHUOHR-UHFFFAOYSA-N 3-(3-cyanophenyl)-5-methoxycarbonyl-4-methyl-4H-1,2-oxazole-5-carboxylic acid Chemical compound C(#N)C=1C=C(C=CC=1)C1=NOC(C1C)(C(=O)OC)C(=O)O PNHTVNUYGHUOHR-UHFFFAOYSA-N 0.000 description 5
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- TUEIURIZJQRMQE-UHFFFAOYSA-N [2-(tert-butylsulfamoyl)phenyl]boronic acid Chemical compound CC(C)(C)NS(=O)(=O)C1=CC=CC=C1B(O)O TUEIURIZJQRMQE-UHFFFAOYSA-N 0.000 description 5
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- LAAVOASESNVMQA-UHFFFAOYSA-N 2-(4-aminophenyl)-n-tert-butylbenzenesulfonamide Chemical group CC(C)(C)NS(=O)(=O)C1=CC=CC=C1C1=CC=C(N)C=C1 LAAVOASESNVMQA-UHFFFAOYSA-N 0.000 description 4
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
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- MLKXDPUZXIRXEP-MFOYZWKCSA-N sulindac Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)=O)C=C1 MLKXDPUZXIRXEP-MFOYZWKCSA-N 0.000 description 1
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- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 1
- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
- UEUXEKPTXMALOB-UHFFFAOYSA-J tetrasodium;2-[2-[bis(carboxylatomethyl)amino]ethyl-(carboxylatomethyl)amino]acetate Chemical compound [Na+].[Na+].[Na+].[Na+].[O-]C(=O)CN(CC([O-])=O)CCN(CC([O-])=O)CC([O-])=O UEUXEKPTXMALOB-UHFFFAOYSA-J 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000001149 thermolysis Methods 0.000 description 1
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical class NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 1
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- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 1
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 1
- 235000012141 vanillin Nutrition 0.000 description 1
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- PJVWKTKQMONHTI-UHFFFAOYSA-N warfarin Chemical compound OC=1C2=CC=CC=C2OC(=O)C=1C(CC(=O)C)C1=CC=CC=C1 PJVWKTKQMONHTI-UHFFFAOYSA-N 0.000 description 1
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- 229940082509 xanthan gum Drugs 0.000 description 1
- BPICBUSOMSTKRF-UHFFFAOYSA-N xylazine Chemical compound CC1=CC=CC(C)=C1NC1=NCCCS1 BPICBUSOMSTKRF-UHFFFAOYSA-N 0.000 description 1
- 229960001600 xylazine Drugs 0.000 description 1
- 229930195724 β-lactose Natural products 0.000 description 1
- PAPBSGBWRJIAAV-UHFFFAOYSA-N ε-Caprolactone Chemical compound O=C1CCCCCO1 PAPBSGBWRJIAAV-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/04—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Photoreceptors In Electrophotography (AREA)
- Treatments For Attaching Organic Compounds To Fibrous Goods (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US950895P | 1995-12-21 | 1995-12-21 | |
| US64690396A | 1996-05-08 | 1996-05-08 | |
| US3066696P | 1996-11-12 | 1996-11-12 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP960597A2 true HRP960597A2 (en) | 1998-04-30 |
Family
ID=27358875
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HR60/030,666A HRP960597A2 (en) | 1995-12-21 | 1996-12-19 | ISOXAZOLINE, ISOTHIAZOLINE AND PYRAZOLINE FACTOR Xa INHIBITORS |
Country Status (9)
| Country | Link |
|---|---|
| EP (1) | EP0874629B1 (de) |
| JP (1) | JP2001502655A (de) |
| AT (1) | ATE267011T1 (de) |
| AU (1) | AU1335897A (de) |
| CA (1) | CA2240946C (de) |
| DE (1) | DE69632548T2 (de) |
| ES (1) | ES2219706T3 (de) |
| HR (1) | HRP960597A2 (de) |
| WO (1) | WO1997023212A1 (de) |
Families Citing this family (41)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6153754A (en) | 1995-12-21 | 2000-11-28 | Albany Molecular Research, Inc. | Process for production of piperidine derivatives |
| ZA985247B (en) * | 1997-06-19 | 1999-12-17 | Du Pont Merck Pharma | Guanidine mimics as factor Xa inhibitors. |
| CA2293824A1 (en) * | 1997-06-19 | 1998-12-23 | Mimi Lifen Quan | (amidino)6-membered aromatics as factor xa inhibitors |
| US6339099B1 (en) | 1997-06-20 | 2002-01-15 | Dupont Pharmaceuticals Company | Guanidine mimics as factor Xa inhibitors |
| EP1007037A4 (de) | 1997-06-26 | 2004-10-06 | Lilly Co Eli | Antithrombose mittel |
| AU9309898A (en) * | 1997-09-09 | 1999-03-29 | Du Pont Pharmaceuticals Company | Benzimidazolinones, benzoxazolinones, benzopiperazinones, indanones, and derivatives thereof as inhibitors of factor xa |
| DE19755268A1 (de) * | 1997-12-12 | 1999-06-17 | Merck Patent Gmbh | Benzamidinderivate |
| KR20010082515A (ko) * | 1998-02-17 | 2001-08-30 | 우에노 도시오 | 아미디노 유도체 및 그 유도체를 유효 성분으로서함유하는 약제 |
| CA2321538A1 (en) | 1998-03-27 | 1999-10-07 | Dupont Pharmaceuticals Company | Disubstituted pyrazolines and triazolines as factor xa inhibitors |
| DE69921994T2 (de) | 1998-05-02 | 2005-12-01 | Astrazeneca Ab | Heterozyklische verbindungen mit faktor xa hemmender wirkung |
| GB9809349D0 (en) * | 1998-05-02 | 1998-07-01 | Zeneca Ltd | Heterocyclic derivatives |
| CA2346396C (en) * | 1998-10-09 | 2009-04-28 | Janssen Pharmaceutica N.V. | 4,5-dihydro-isoxazole derivatives and their pharmaceutical use |
| US6319937B1 (en) * | 1998-11-18 | 2001-11-20 | Dupont Pharmaceuticals Company | Isoxazoline fibrinogen receptor antagonists |
| CA2348740A1 (en) | 1998-12-23 | 2000-07-06 | Ruth R. Wexler | Thrombin or factor xa inhibitors |
| JP2003502314A (ja) | 1999-06-14 | 2003-01-21 | イーライ・リリー・アンド・カンパニー | 化合物 |
| KR20030011268A (ko) | 1999-07-16 | 2003-02-07 | 브리스톨-마이어스 스퀴브 파마 컴퍼니 | Ｘａ 인자 억제제로서의 질소 함유 헤테로바이사이클 |
| GB9928568D0 (en) * | 1999-12-03 | 2000-02-02 | Zeneca Ltd | Chemical compounds |
| GB0009803D0 (en) | 2000-04-25 | 2000-06-07 | Astrazeneca Ab | Chemical compounds |
| CN1439008A (zh) * | 2000-06-23 | 2003-08-27 | 布里斯托尔-迈尔斯斯奎布药品公司 | 作为因子xa抑制剂的1－(杂芳环基－苯基)－稠合吡唑衍生物 |
| WO2002000647A1 (en) | 2000-06-23 | 2002-01-03 | Bristol-Myers Squibb Pharma Company | Heteroaryl-phenyl substituted factor xa inhibitors |
| AU2001273040A1 (en) * | 2000-06-27 | 2002-01-08 | Du Pont Pharmaceuticals Company | Factor xa inhibitors |
| AU2001275857A1 (en) | 2000-06-29 | 2002-01-14 | Bristol-Myers Squibb Pharma Company | Thrombin or factor xa inhibitors |
| DE10129725A1 (de) | 2001-06-20 | 2003-01-02 | Bayer Ag | Kombinationstherapie substituierter Oxazolidinone |
| EP1443930A1 (de) | 2001-10-25 | 2004-08-11 | AstraZeneca AB | Isoxazolinderivative verwendbar als antimikrobielle agenzien |
| PA8557501A1 (es) | 2001-11-12 | 2003-06-30 | Pfizer Prod Inc | Benzamida, heteroarilamida y amidas inversas |
| WO2003042190A1 (en) | 2001-11-12 | 2003-05-22 | Pfizer Products Inc. | N-alkyl-adamantyl derivatives as p2x7-receptor antagonists |
| AU2003302238A1 (en) | 2002-12-03 | 2004-06-23 | Axys Pharmaceuticals, Inc. | 2-(2-hydroxybiphenyl-3-yl)-1h-benzoimidazole-5-carboxamidine derivatives as factor viia inhibitors |
| PA8591801A1 (es) | 2002-12-31 | 2004-07-26 | Pfizer Prod Inc | Inhibidores benzamidicos del receptor p2x7. |
| AU2005219788B2 (en) | 2004-03-05 | 2010-06-03 | Nissan Chemical Corporation | Isoxazoline-substituted benzamide compound and noxious organism control agent |
| KR20140018997A (ko) | 2005-01-07 | 2014-02-13 | 신타 파마슈티칼스 코프. | 염증 및 면역 관련 용도를 위한 화합물 |
| WO2007026965A1 (ja) | 2005-09-02 | 2007-03-08 | Nissan Chemical Industries, Ltd. | イソキサゾリン置換ベンズアミド化合物及び有害生物防除剤 |
| BRPI0707091B8 (pt) | 2006-03-10 | 2018-02-14 | Nissan Chemical Ind Ltd | composto de isoxalina e benzaldoxima substituído ou um sal do mesmo; pesticida, agroquímico, endo- ou ecto-parasiticidapara mamíferos ou pássaros, inseticida e acaricida contendo como um ou mais ingredientes ativos selecionados a partir do composto de isoxalina substituído e o sal do mesmo |
| CN101583593A (zh) | 2006-11-13 | 2009-11-18 | 辉瑞产品公司 | 二芳基、二吡啶基和芳基-吡啶基衍生物及其用途 |
| WO2013092943A1 (en) | 2011-12-23 | 2013-06-27 | Basf Se | Isothiazoline compounds for combating invertebrate pests |
| JP6285937B2 (ja) * | 2012-09-25 | 2018-02-28 | バイエル・クロップサイエンス・アクチェンゲゼルシャフト | 除草性および殺真菌性の５−オキシ置換３−フェニルイソオキサゾリン−５−カルボキサミドおよび５−オキシ置換３−フェニルイソオキサゾリン−５−チオアミド |
| US20160145222A1 (en) | 2013-06-21 | 2016-05-26 | Basf Se | Methods for Controlling Pests in Soybean |
| CN105473584B (zh) * | 2013-06-24 | 2020-01-31 | 勃林格殷格翰动物保健美国公司 | 噻吩-或呋喃-取代的异噻唑啉化合物 |
| ES2821877T3 (es) | 2016-07-07 | 2021-04-28 | Bristol Myers Squibb Co | Espirolactamas como inhibidores de ROCK |
| WO2018207950A1 (ja) * | 2017-05-12 | 2018-11-15 | 横山 茂之 | クラスａ ｇｐｃｒ結合性化合物改変体 |
| RU2704967C1 (ru) * | 2018-06-19 | 2019-11-01 | Федеральное государственное бюджетное образовательное учреждение высшего образования "Ярославский государственный педагогический университет им. К.Д. Ушинского (ЯГПУ им. К.Д. Ушинского) | Карбоксамидные производные изоксазолина, способ их получения и применения для лечения воспалительных заболеваний |
| WO2021000297A1 (en) | 2019-07-03 | 2021-01-07 | Merck Sharp & Dohme Corp. | Compounds and methods of use thereof as antibacterial agents |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9110858D0 (en) * | 1991-05-20 | 1991-07-10 | Shell Int Research | Herbicidal compounds |
| WO1995014682A1 (en) * | 1993-11-24 | 1995-06-01 | The Du Pont Merck Pharmaceutical Company | Isoxazoline compounds useful as fibrinogen receptor antagonists |
| DK0730590T3 (da) * | 1993-11-24 | 2001-03-19 | Du Pont Pharm Co | Isoxazolin og isozazol fibrinogenreceptorantagonister |
-
1996
- 1996-12-17 WO PCT/US1996/020076 patent/WO1997023212A1/en not_active Ceased
- 1996-12-17 JP JP09523762A patent/JP2001502655A/ja active Pending
- 1996-12-17 ES ES96944844T patent/ES2219706T3/es not_active Expired - Lifetime
- 1996-12-17 EP EP96944844A patent/EP0874629B1/de not_active Expired - Lifetime
- 1996-12-17 AT AT96944844T patent/ATE267011T1/de not_active IP Right Cessation
- 1996-12-17 AU AU13358/97A patent/AU1335897A/en not_active Abandoned
- 1996-12-17 DE DE69632548T patent/DE69632548T2/de not_active Expired - Lifetime
- 1996-12-17 CA CA002240946A patent/CA2240946C/en not_active Expired - Fee Related
- 1996-12-19 HR HR60/030,666A patent/HRP960597A2/hr not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| CA2240946A1 (en) | 1997-07-03 |
| CA2240946C (en) | 2002-09-10 |
| WO1997023212A1 (en) | 1997-07-03 |
| EP0874629A1 (de) | 1998-11-04 |
| AU1335897A (en) | 1997-07-17 |
| DE69632548T2 (de) | 2005-06-02 |
| DE69632548D1 (de) | 2004-06-24 |
| EP0874629B1 (de) | 2004-05-19 |
| JP2001502655A (ja) | 2001-02-27 |
| ES2219706T3 (es) | 2004-12-01 |
| ATE267011T1 (de) | 2004-06-15 |
| EP0874629A4 (de) | 1999-08-04 |
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