CA2296358A1 - Certain benzothiazine dioxide endothelin antagonists and processes for their preparation - Google Patents
Certain benzothiazine dioxide endothelin antagonists and processes for their preparation Download PDFInfo
- Publication number
- CA2296358A1 CA2296358A1 CA002296358A CA2296358A CA2296358A1 CA 2296358 A1 CA2296358 A1 CA 2296358A1 CA 002296358 A CA002296358 A CA 002296358A CA 2296358 A CA2296358 A CA 2296358A CA 2296358 A1 CA2296358 A1 CA 2296358A1
- Authority
- CA
- Canada
- Prior art keywords
- benzo
- phenyl
- dioxo
- dihydro
- carboxylic acid
- 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.)
- Abandoned
Links
- 108050009340 Endothelin Proteins 0.000 title claims abstract description 14
- 102000002045 Endothelin Human genes 0.000 title claims abstract description 14
- ZUBDGKVDJUIMQQ-UBFCDGJISA-N endothelin-1 Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(O)=O)NC(=O)[C@H]1NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@@H](CC=2C=CC(O)=CC=2)NC(=O)[C@H](C(C)C)NC(=O)[C@H]2CSSC[C@@H](C(N[C@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N2)=O)NC(=O)[C@@H](CO)NC(=O)[C@H](N)CSSC1)C1=CNC=N1 ZUBDGKVDJUIMQQ-UBFCDGJISA-N 0.000 title claims abstract description 14
- 238000000034 method Methods 0.000 title claims description 67
- 238000002360 preparation method Methods 0.000 title claims description 42
- 230000008569 process Effects 0.000 title claims description 27
- 239000005557 antagonist Substances 0.000 title abstract description 13
- GHNLJDPNIAIWOQ-UHFFFAOYSA-N 2h-1$l^{6},2-benzothiazine 1,1-dioxide Chemical compound C1=CC=C2S(=O)(=O)NC=CC2=C1 GHNLJDPNIAIWOQ-UHFFFAOYSA-N 0.000 title abstract description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 124
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- 150000003839 salts Chemical class 0.000 claims abstract description 9
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- 201000006474 Brain Ischemia Diseases 0.000 claims abstract description 5
- 206010008120 Cerebral ischaemia Diseases 0.000 claims abstract description 5
- 208000026106 cerebrovascular disease Diseases 0.000 claims abstract description 5
- 206010007559 Cardiac failure congestive Diseases 0.000 claims abstract description 4
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- 230000003211 malignant effect Effects 0.000 claims abstract description 4
- 201000005857 malignant hypertension Diseases 0.000 claims abstract description 4
- 239000000243 solution Substances 0.000 claims description 75
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 65
- 229910052739 hydrogen Inorganic materials 0.000 claims description 50
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 46
- 239000002552 dosage form Substances 0.000 claims description 27
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 26
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 24
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 24
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 23
- 238000010992 reflux Methods 0.000 claims description 22
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 21
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 20
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- -1 aryl zinc bromide Chemical compound 0.000 claims description 19
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- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 14
- 238000005859 coupling reaction Methods 0.000 claims description 13
- YDCHPLOFQATIDS-UHFFFAOYSA-N methyl 2-bromoacetate Chemical compound COC(=O)CBr YDCHPLOFQATIDS-UHFFFAOYSA-N 0.000 claims description 13
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 13
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 12
- 229960000549 4-dimethylaminophenol Drugs 0.000 claims description 11
- 238000006243 chemical reaction Methods 0.000 claims description 11
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- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 229910000104 sodium hydride Inorganic materials 0.000 claims description 10
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- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- 150000004702 methyl esters Chemical class 0.000 claims description 8
- 229940102001 zinc bromide Drugs 0.000 claims description 8
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 7
- CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 claims description 7
- 239000003054 catalyst Substances 0.000 claims description 7
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- 229930194542 Keto Natural products 0.000 claims description 6
- ZADPBFCGQRWHPN-UHFFFAOYSA-N boronic acid Chemical compound OBO ZADPBFCGQRWHPN-UHFFFAOYSA-N 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 238000010791 quenching Methods 0.000 claims description 6
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 claims description 6
- 229910003074 TiCl4 Inorganic materials 0.000 claims description 5
- 150000002085 enols Chemical class 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical group 0.000 claims description 5
- 229910052763 palladium Inorganic materials 0.000 claims description 5
- 230000000171 quenching effect Effects 0.000 claims description 5
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 claims description 5
- LOFRBHZYZCIOJO-UHFFFAOYSA-N 7-methoxy-1,3-benzodioxole-5-carbaldehyde Chemical compound COC1=CC(C=O)=CC2=C1OCO2 LOFRBHZYZCIOJO-UHFFFAOYSA-N 0.000 claims description 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical group C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 4
- 206010040070 Septic Shock Diseases 0.000 claims description 4
- 230000001154 acute effect Effects 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 claims description 4
- 229940124530 sulfonamide Drugs 0.000 claims description 4
- 150000003456 sulfonamides Chemical class 0.000 claims description 4
- WMOVHXAZOJBABW-UHFFFAOYSA-N tert-butyl acetate Chemical compound CC(=O)OC(C)(C)C WMOVHXAZOJBABW-UHFFFAOYSA-N 0.000 claims description 4
- 238000010626 work up procedure Methods 0.000 claims description 4
- YMRUIRRQMVWHTM-UHFFFAOYSA-N 3-bromo-5-(2-hydroxyethyl)phenol Chemical compound OCCC1=CC(O)=CC(Br)=C1 YMRUIRRQMVWHTM-UHFFFAOYSA-N 0.000 claims description 3
- 239000002841 Lewis acid Substances 0.000 claims description 3
- 229910010068 TiCl2 Inorganic materials 0.000 claims description 3
- 239000012670 alkaline solution Substances 0.000 claims description 3
- 150000001499 aryl bromides Chemical class 0.000 claims description 3
- 125000004122 cyclic group Chemical group 0.000 claims description 3
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- 208000001286 intracranial vasospasm Diseases 0.000 claims description 3
- 150000007517 lewis acids Chemical class 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims description 3
- ZWYDDDAMNQQZHD-UHFFFAOYSA-L titanium(ii) chloride Chemical compound [Cl-].[Cl-].[Ti+2] ZWYDDDAMNQQZHD-UHFFFAOYSA-L 0.000 claims description 3
- 208000009304 Acute Kidney Injury Diseases 0.000 claims description 2
- 206010002383 Angina Pectoris Diseases 0.000 claims description 2
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- 208000033626 Renal failure acute Diseases 0.000 claims description 2
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- 206010049771 Shock haemorrhagic Diseases 0.000 claims description 2
- 201000011040 acute kidney failure Diseases 0.000 claims description 2
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- 230000002152 alkylating effect Effects 0.000 claims description 2
- 206010003119 arrhythmia Diseases 0.000 claims description 2
- 230000006793 arrhythmia Effects 0.000 claims description 2
- 208000006673 asthma Diseases 0.000 claims description 2
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- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
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- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 claims description 2
- 230000036303 septic shock Effects 0.000 claims description 2
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- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
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- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 claims 1
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/36—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids
- C07C303/40—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids by reactions not involving the formation of sulfonamide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D279/02—1,2-Thiazines; Hydrogenated 1,2-thiazines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing aromatic rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Urology & Nephrology (AREA)
- Diabetes (AREA)
- Pulmonology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Hospice & Palliative Care (AREA)
- Endocrinology (AREA)
- Vascular Medicine (AREA)
- Emergency Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US5811197P | 1997-09-05 | 1997-09-05 | |
| US60/058,111 | 1997-09-05 | ||
| US9232698P | 1998-07-09 | 1998-07-09 | |
| US60/092,326 | 1998-07-09 | ||
| PCT/US1998/016856 WO1999012916A1 (en) | 1997-09-05 | 1998-08-13 | Certain benzothiazine dioxide endothelin antagonists and processes for their preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2296358A1 true CA2296358A1 (en) | 1999-03-18 |
Family
ID=26737251
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002296358A Abandoned CA2296358A1 (en) | 1997-09-05 | 1998-08-13 | Certain benzothiazine dioxide endothelin antagonists and processes for their preparation |
Country Status (24)
| Country | Link |
|---|---|
| US (5) | US6265399B1 (https=) |
| EP (1) | EP1009743B1 (https=) |
| JP (1) | JP2001515893A (https=) |
| KR (1) | KR20010023686A (https=) |
| AR (1) | AR017056A1 (https=) |
| AT (1) | ATE270281T1 (https=) |
| AU (1) | AU759169B2 (https=) |
| BR (1) | BR9812431A (https=) |
| CA (1) | CA2296358A1 (https=) |
| CO (1) | CO4970725A1 (https=) |
| DE (1) | DE69824863T2 (https=) |
| ES (1) | ES2221191T3 (https=) |
| HU (1) | HUP0003689A3 (https=) |
| IL (1) | IL134057A0 (https=) |
| IS (1) | IS5356A (https=) |
| MY (1) | MY116277A (https=) |
| NO (1) | NO20001078L (https=) |
| NZ (1) | NZ502670A (https=) |
| PE (1) | PE116699A1 (https=) |
| PL (1) | PL338983A1 (https=) |
| PT (1) | PT1009743E (https=) |
| TW (1) | TW508355B (https=) |
| UY (1) | UY25168A1 (https=) |
| WO (1) | WO1999012916A1 (https=) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU759169B2 (en) | 1997-09-05 | 2003-04-10 | Warner-Lambert Company | Certain benzothiazine dioxide endothelin antagonists and processes for their preparation |
| EP1288199A4 (en) | 2000-04-28 | 2005-10-12 | Shionogi & Co | INHIBITORS OF MMP-12 |
| WO2001091736A2 (en) * | 2000-05-31 | 2001-12-06 | Warner-Lambert Company | Combinations of an endothelin receptor antagonist and an antiepileptic compound having pain alleviating properties or analgesic |
| US20020115661A1 (en) * | 2000-12-07 | 2002-08-22 | Keller Laurence Harvey | Method for treating chronic obstructive pulmonary disease |
| CN1882327A (zh) | 2003-11-19 | 2006-12-20 | 症变治疗公司 | 含磷的新的拟甲状腺素药 |
| FR2874011B1 (fr) * | 2004-08-03 | 2007-06-15 | Sanofi Synthelabo | Derives de sulfonamides, leur preparation et leur application en therapeutique |
| DE102008026894A1 (de) * | 2008-06-05 | 2009-12-10 | Evonik Degussa Gmbh | Ink Jet Tinte |
| CA2969756A1 (en) * | 2014-12-05 | 2016-06-09 | Aquinnah Pharmaceuticals, Inc. | Sulfonamide derivatives, compositions and methods of use in the treatment of neurodegenerative diseases |
| CN108727176B (zh) * | 2018-07-26 | 2021-05-18 | 荆楚理工学院 | 一种制备5-卤-2,3-二羟基苯甲醛的方法 |
| CN113214299A (zh) * | 2021-03-01 | 2021-08-06 | 重庆西南制药二厂有限责任公司 | γ-联苯双酯中间体及合成方法及γ-联苯双酯合成方法 |
Family Cites Families (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3960856A (en) * | 1975-06-20 | 1976-06-01 | Warner-Lambert Company | Process for the preparation of 4-hydroxy-3-(5-methyl-3-isoxazolylcarbamoyl)-2-methyl-2H-1,2-benzothiazine 1,1-dioxide |
| IN159273B (https=) * | 1981-10-05 | 1987-04-25 | Pfizer | |
| JPH0495057A (ja) * | 1990-08-08 | 1992-03-27 | Taisho Pharmaceut Co Ltd | Ｎ―置換スルホンアニリド化合物 |
| AU675870B2 (en) * | 1993-08-18 | 1997-02-20 | Msd K.K. | Endothelin antagonistic heteroaromatic ring-fused cyclopentene derivatives |
| US5389620A (en) | 1993-08-18 | 1995-02-14 | Banyu Pharmaceutical Co., Ltd. | Endothelin antagonistic heteroaromatic ring-fused cyclopentene derivatives |
| CA2156849A1 (en) | 1993-12-24 | 1995-07-06 | Akira Mizuno | Benzothiazine derivative |
| JPH0912562A (ja) | 1995-06-22 | 1997-01-14 | Suntory Ltd | 置換ベンゾチアジン誘導体 |
| US5482960A (en) | 1994-11-14 | 1996-01-09 | Warner-Lambert Company | Nonpeptide endothelin antagonists |
| US5599811A (en) * | 1995-02-21 | 1997-02-04 | Warner-Lambert Company | Benzothiazine dioxides as endothelin antagonists |
| CA2190708A1 (en) | 1995-12-08 | 1997-06-09 | Johannes Aebi | Aminoalkyl substituted benzo-heterocyclic compounds |
| AU759169B2 (en) | 1997-09-05 | 2003-04-10 | Warner-Lambert Company | Certain benzothiazine dioxide endothelin antagonists and processes for their preparation |
-
1998
- 1998-08-13 AU AU90196/98A patent/AU759169B2/en not_active Ceased
- 1998-08-13 WO PCT/US1998/016856 patent/WO1999012916A1/en not_active Ceased
- 1998-08-13 KR KR1020007002339A patent/KR20010023686A/ko not_active Withdrawn
- 1998-08-13 EP EP98942061A patent/EP1009743B1/en not_active Expired - Lifetime
- 1998-08-13 NZ NZ502670A patent/NZ502670A/xx unknown
- 1998-08-13 ES ES98942061T patent/ES2221191T3/es not_active Expired - Lifetime
- 1998-08-13 JP JP2000510724A patent/JP2001515893A/ja not_active Abandoned
- 1998-08-13 HU HU0003689A patent/HUP0003689A3/hu unknown
- 1998-08-13 AT AT98942061T patent/ATE270281T1/de not_active IP Right Cessation
- 1998-08-13 CA CA002296358A patent/CA2296358A1/en not_active Abandoned
- 1998-08-13 PT PT98942061T patent/PT1009743E/pt unknown
- 1998-08-13 PL PL98338983A patent/PL338983A1/xx unknown
- 1998-08-13 IL IL13405798A patent/IL134057A0/xx unknown
- 1998-08-13 BR BR9812431-5A patent/BR9812431A/pt not_active Application Discontinuation
- 1998-08-13 US US09/445,504 patent/US6265399B1/en not_active Expired - Fee Related
- 1998-08-13 DE DE69824863T patent/DE69824863T2/de not_active Expired - Fee Related
- 1998-09-03 MY MYPI98004024A patent/MY116277A/en unknown
- 1998-09-04 PE PE1998000822A patent/PE116699A1/es not_active Application Discontinuation
- 1998-09-04 UY UY25168A patent/UY25168A1/es not_active IP Right Cessation
- 1998-09-04 AR ARP980104414A patent/AR017056A1/es unknown
- 1998-09-04 CO CO98050781A patent/CO4970725A1/es unknown
- 1998-10-28 TW TW087114760A patent/TW508355B/zh not_active IP Right Cessation
-
2000
- 2000-01-21 IS IS5356A patent/IS5356A/is unknown
- 2000-03-02 NO NO20001078A patent/NO20001078L/no unknown
- 2000-08-07 US US09/633,720 patent/US6252070B1/en not_active Expired - Fee Related
-
2001
- 2001-03-27 US US09/818,394 patent/US6440962B2/en not_active Expired - Fee Related
- 2001-12-05 US US10/006,589 patent/US6545150B2/en not_active Expired - Fee Related
-
2002
- 2002-06-03 US US10/161,569 patent/US20030073684A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| AR017056A1 (es) | 2001-08-22 |
| PE116699A1 (es) | 1999-12-19 |
| HUP0003689A2 (hu) | 2001-09-28 |
| US20030073684A1 (en) | 2003-04-17 |
| DE69824863T2 (de) | 2005-06-30 |
| BR9812431A (pt) | 2000-09-19 |
| JP2001515893A (ja) | 2001-09-25 |
| NO20001078D0 (no) | 2000-03-02 |
| US6440962B2 (en) | 2002-08-27 |
| US6265399B1 (en) | 2001-07-24 |
| UY25168A1 (es) | 1999-05-14 |
| MY116277A (en) | 2003-12-31 |
| US6252070B1 (en) | 2001-06-26 |
| ES2221191T3 (es) | 2004-12-16 |
| PL338983A1 (en) | 2000-12-04 |
| AU759169B2 (en) | 2003-04-10 |
| HUP0003689A3 (en) | 2003-05-28 |
| WO1999012916A1 (en) | 1999-03-18 |
| IS5356A (is) | 2000-01-21 |
| EP1009743A1 (en) | 2000-06-21 |
| IL134057A0 (en) | 2001-04-30 |
| US20020094980A1 (en) | 2002-07-18 |
| EP1009743B1 (en) | 2004-06-30 |
| DE69824863D1 (de) | 2004-08-05 |
| US6545150B2 (en) | 2003-04-08 |
| KR20010023686A (ko) | 2001-03-26 |
| NO20001078L (no) | 2000-03-02 |
| AU9019698A (en) | 1999-03-29 |
| US20010036944A1 (en) | 2001-11-01 |
| PT1009743E (pt) | 2004-09-30 |
| TW508355B (en) | 2002-11-01 |
| CO4970725A1 (es) | 2000-11-07 |
| NZ502670A (en) | 2003-01-31 |
| ATE270281T1 (de) | 2004-07-15 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| FZDE | Discontinued |