DE69803750T2 - Thiazolidinedione- und oxazolidinedione-derivate mit antidiabetischen, hypolipidämischen und anti hypertensiven eigenschaften - Google Patents
Thiazolidinedione- und oxazolidinedione-derivate mit antidiabetischen, hypolipidämischen und anti hypertensiven eigenschaftenInfo
- Publication number
- DE69803750T2 DE69803750T2 DE69803750T DE69803750T DE69803750T2 DE 69803750 T2 DE69803750 T2 DE 69803750T2 DE 69803750 T DE69803750 T DE 69803750T DE 69803750 T DE69803750 T DE 69803750T DE 69803750 T2 DE69803750 T2 DE 69803750T2
- Authority
- DE
- Germany
- Prior art keywords
- compound
- group
- formula
- salts
- oxo
- 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.)
- Expired - Fee Related
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- ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 title claims description 21
- 230000003178 anti-diabetic effect Effects 0.000 title abstract description 6
- 239000003472 antidiabetic agent Substances 0.000 title abstract description 6
- 229940123464 Thiazolidinedione Drugs 0.000 title 1
- 230000003276 anti-hypertensive effect Effects 0.000 title 1
- 230000000055 hyoplipidemic effect Effects 0.000 title 1
- 150000001475 oxazolidinediones Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 148
- 150000003839 salts Chemical class 0.000 claims abstract description 59
- 239000012453 solvate Substances 0.000 claims abstract description 21
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 12
- 238000006243 chemical reaction Methods 0.000 claims description 51
- -1 aralkoxycarbonyl Chemical group 0.000 claims description 47
- 238000000034 method Methods 0.000 claims description 36
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 33
- 125000000217 alkyl group Chemical group 0.000 claims description 32
- 150000001408 amides Chemical class 0.000 claims description 28
- 239000001257 hydrogen Substances 0.000 claims description 28
- 229910052739 hydrogen Inorganic materials 0.000 claims description 28
- 125000003118 aryl group Chemical group 0.000 claims description 27
- 125000002252 acyl group Chemical group 0.000 claims description 25
- 239000002904 solvent Substances 0.000 claims description 25
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 24
- 229910052721 tungsten Inorganic materials 0.000 claims description 23
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 22
- 229910052736 halogen Inorganic materials 0.000 claims description 20
- 125000000623 heterocyclic group Chemical group 0.000 claims description 20
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 20
- 206010022489 Insulin Resistance Diseases 0.000 claims description 19
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 19
- 125000001072 heteroaryl group Chemical group 0.000 claims description 19
- 125000001424 substituent group Chemical group 0.000 claims description 19
- 125000004423 acyloxy group Chemical group 0.000 claims description 18
- 150000002367 halogens Chemical class 0.000 claims description 18
- 238000011282 treatment Methods 0.000 claims description 18
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 17
- 125000004104 aryloxy group Chemical group 0.000 claims description 17
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 16
- 206010012601 diabetes mellitus Diseases 0.000 claims description 16
- 125000005843 halogen group Chemical group 0.000 claims description 16
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
- 125000004442 acylamino group Chemical group 0.000 claims description 15
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 14
- 125000004076 pyridyl group Chemical group 0.000 claims description 14
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 13
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 13
- 125000004475 heteroaralkyl group Chemical group 0.000 claims description 13
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 13
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- 125000002971 oxazolyl group Chemical group 0.000 claims description 11
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- 125000005162 aryl oxy carbonyl amino group Chemical group 0.000 claims description 10
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- 125000002541 furyl group Chemical group 0.000 claims description 10
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- 206010020772 Hypertension Diseases 0.000 claims description 8
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- 125000004430 oxygen atom Chemical group O* 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
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- 125000001624 naphthyl group Chemical group 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 125000001639 phenylmethylene group Chemical group [H]C(=*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims description 6
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- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 5
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- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 150000003460 sulfonic acids Chemical class 0.000 claims description 5
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 4
- SPTCCMODSMVDGB-UHFFFAOYSA-N 5-[[4-[2-(1-oxophthalazin-2-yl)ethoxy]phenyl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound S1C(=O)NC(=O)C1=CC(C=C1)=CC=C1OCCN1C(=O)C2=CC=CC=C2C=N1 SPTCCMODSMVDGB-UHFFFAOYSA-N 0.000 claims description 4
- PKHWZBBQBGJNOI-UHFFFAOYSA-N 5-[[4-[2-(4-ethyl-1-oxophthalazin-2-yl)ethoxy]phenyl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound O=C1C2=CC=CC=C2C(CC)=NN1CCOC(C=C1)=CC=C1C=C1SC(=O)NC1=O PKHWZBBQBGJNOI-UHFFFAOYSA-N 0.000 claims description 4
- HWTVWYSIMDNUEI-UHFFFAOYSA-N 5-[[4-[2-(4-methyl-1-oxophthalazin-2-yl)ethoxy]phenyl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound O=C1C2=CC=CC=C2C(C)=NN1CCOC(C=C1)=CC=C1C=C1SC(=O)NC1=O HWTVWYSIMDNUEI-UHFFFAOYSA-N 0.000 claims description 4
- 201000001320 Atherosclerosis Diseases 0.000 claims description 4
- 201000004681 Psoriasis Diseases 0.000 claims description 4
- 150000007513 acids Chemical class 0.000 claims description 4
- 125000005334 azaindolyl group Chemical group N1N=C(C2=CC=CC=C12)* 0.000 claims description 4
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 4
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 4
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 4
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 4
- 125000001041 indolyl group Chemical group 0.000 claims description 4
- COWNFYYYZFRNOY-UHFFFAOYSA-N oxazolidinedione Chemical compound O=C1COC(=O)N1 COWNFYYYZFRNOY-UHFFFAOYSA-N 0.000 claims description 4
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 4
- 125000004434 sulfur atom Chemical group 0.000 claims description 4
- ZOEGSOBAHONJKF-UHFFFAOYSA-N 5-[[4-[2-(1-oxo-4-phenylphthalazin-2-yl)ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound S1C(=O)NC(=O)C1CC(C=C1)=CC=C1OCCN1C(=O)C2=CC=CC=C2C(C=2C=CC=CC=2)=N1 ZOEGSOBAHONJKF-UHFFFAOYSA-N 0.000 claims description 3
- SSOWJXNHFJYAIY-UHFFFAOYSA-N 5-[[4-[2-(1-oxo-4-phenylphthalazin-2-yl)ethoxy]phenyl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound S1C(=O)NC(=O)C1=CC(C=C1)=CC=C1OCCN1C(=O)C2=CC=CC=C2C(C=2C=CC=CC=2)=N1 SSOWJXNHFJYAIY-UHFFFAOYSA-N 0.000 claims description 3
- LKZCTOQTOWSTJJ-UHFFFAOYSA-N 5-[[4-[2-(4-methyl-1-oxophthalazin-2-yl)ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound O=C1C2=CC=CC=C2C(C)=NN1CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O LKZCTOQTOWSTJJ-UHFFFAOYSA-N 0.000 claims description 3
- GMLMDFUMTKVQKN-UHFFFAOYSA-N 5-[[4-[2-(4-oxo-1h-2,3-benzoxazin-3-yl)ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound S1C(=O)NC(=O)C1CC(C=C1)=CC=C1OCCN1C(=O)C2=CC=CC=C2CO1 GMLMDFUMTKVQKN-UHFFFAOYSA-N 0.000 claims description 3
- OZLRYDFIKRDDCP-UHFFFAOYSA-N 5-[[4-[2-(4-oxo-1h-2,3-benzoxazin-3-yl)ethoxy]phenyl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound S1C(=O)NC(=O)C1=CC(C=C1)=CC=C1OCCN1C(=O)C2=CC=CC=C2CO1 OZLRYDFIKRDDCP-UHFFFAOYSA-N 0.000 claims description 3
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- 125000004598 dihydrobenzofuryl group Chemical group O1C(CC2=C1C=CC=C2)* 0.000 claims description 3
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- PBXMWFFJGIWFGT-UHFFFAOYSA-N 5-[[4-[2-(1-oxophthalazin-2-yl)ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound S1C(=O)NC(=O)C1CC(C=C1)=CC=C1OCCN1C(=O)C2=CC=CC=C2C=N1 PBXMWFFJGIWFGT-UHFFFAOYSA-N 0.000 claims description 2
- QLCAPHLBEJZXLY-UHFFFAOYSA-N 5-[[4-[2-(4-ethyl-1-oxophthalazin-2-yl)ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound O=C1C2=CC=CC=C2C(CC)=NN1CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O QLCAPHLBEJZXLY-UHFFFAOYSA-N 0.000 claims description 2
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Classifications
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- 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
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/26—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings condensed with carbocyclic rings or ring systems
- C07D237/30—Phthalazines
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
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- 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
- C07D417/12—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 chain containing hetero atoms as chain links
Landscapes
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- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Diabetes (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Physical Education & Sports Medicine (AREA)
- Cardiology (AREA)
- Endocrinology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Heart & Thoracic Surgery (AREA)
- Rheumatology (AREA)
- Emergency Medicine (AREA)
- Vascular Medicine (AREA)
- Child & Adolescent Psychology (AREA)
- Nutrition Science (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/982,962 US6011036A (en) | 1997-04-15 | 1997-12-02 | Heterocyclic compounds having antidiabetic hypolipidemic antihypertensive properties process for their preparation and pharmaceutical compositions containing them |
| PCT/US1998/007285 WO1998045292A1 (en) | 1997-12-02 | 1998-04-10 | Thiazolidinedione and oxazolidinedione derivatives having antidiabetic, hypolipidaemic and antihypertensive properties |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE69803750D1 DE69803750D1 (de) | 2002-03-21 |
| DE69803750T2 true DE69803750T2 (de) | 2002-09-12 |
Family
ID=25529696
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE69803750T Expired - Fee Related DE69803750T2 (de) | 1997-12-02 | 1998-04-10 | Thiazolidinedione- und oxazolidinedione-derivate mit antidiabetischen, hypolipidämischen und anti hypertensiven eigenschaften |
Country Status (6)
| Country | Link |
|---|---|
| EP (1) | EP0971917B1 (cg-RX-API-DMAC7.html) |
| JP (1) | JP4391597B2 (cg-RX-API-DMAC7.html) |
| AT (1) | ATE212991T1 (cg-RX-API-DMAC7.html) |
| AU (1) | AU6966498A (cg-RX-API-DMAC7.html) |
| DE (1) | DE69803750T2 (cg-RX-API-DMAC7.html) |
| WO (1) | WO1998045292A1 (cg-RX-API-DMAC7.html) |
Families Citing this family (33)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19921567A1 (de) * | 1999-05-11 | 2000-11-16 | Basf Ag | Verwendung von Phthalazine-Derivaten |
| EP1634605A3 (en) | 2000-03-08 | 2006-10-11 | Novo Nordisk A/S | treatment of dyslipidemia in a patient having type 2 diabetes |
| EP1444219A1 (en) | 2001-10-12 | 2004-08-11 | Novo Nordisk A/S | Substituted piperidines and their use for the treatment of diseases related to the histamine h3 receptor |
| IL162620A0 (en) | 2001-12-21 | 2005-11-20 | Novo Nordisk As | Amide derivatives as gk activators |
| DE60335359D1 (de) * | 2002-04-30 | 2011-01-27 | Kudos Pharm Ltd | Phthalazinonderivate |
| PL215132B1 (pl) | 2002-06-27 | 2013-10-31 | Novo Nordisk As | Pochodna arylokarbonylowa jako srodek terapeutyczny, jej zastosowanie i kompozycja farmaceutyczna ja zawierajaca |
| WO2005030797A2 (en) | 2003-09-30 | 2005-04-07 | Novo Nordisk A/S | Melanocortin receptor agonists |
| EP2298337B1 (en) | 2003-12-09 | 2017-02-22 | Novo Nordisk A/S | Regulation of food preference using GLP-1 agonists |
| PT1723128E (pt) | 2004-01-06 | 2013-02-27 | Novo Nordisk As | Heteroaril-ureias e o seu uso como activadores da glicoquinase |
| US20080113944A1 (en) | 2004-05-04 | 2008-05-15 | Novo Nordisk A/S | Novel Indole Derivatives |
| EP1758575A1 (en) | 2004-06-11 | 2007-03-07 | Novo Nordisk A/S | Counteracting drug-induced obesity using glp-1 agonists |
| US8263551B2 (en) | 2004-11-22 | 2012-09-11 | Novo Nordisk A/S | Soluble, stable insulin-containing formulations with a protamine salt |
| CN101137631A (zh) | 2004-12-03 | 2008-03-05 | 转化技术制药公司 | 杂芳族葡糖激酶激活剂 |
| CA2614116A1 (en) | 2005-07-04 | 2007-01-11 | Novo Nordisk A/S | Novel medicaments |
| KR101446973B1 (ko) | 2005-07-14 | 2014-10-07 | 트랜스테크 파르마 엘엘씨 | 우레아 글루코키나제 활성제 |
| EP1910317B1 (en) | 2005-07-20 | 2013-07-03 | Eli Lilly And Company | 1-amino linked compounds |
| SI1951658T1 (sl) | 2005-11-17 | 2012-11-30 | Lilly Co Eli | Antagonisti glukagonskega receptorja priprava interapevtska uporaba |
| NZ570524A (en) | 2006-03-28 | 2011-08-26 | High Point Pharmaceuticals Llc | Benzothiazoles having histamine H3 receptor activity |
| PT2079732E (pt) | 2006-05-29 | 2012-02-02 | High Point Pharmaceuticals Llc | 3-(1,3-benzodioxol-5-il)-6-(4-ciclopropilpiperazin-1-il)- piridazina, os seus sais e solvatos e a sua utilização a título de antagonista do receptor h3 de histamina |
| EP2086951B1 (en) | 2006-11-15 | 2011-12-21 | High Point Pharmaceuticals, LLC | Novel 2-(2-hydroxyphenyl) benzothiadiazines useful for treating obesity and diabetes |
| CA2669884A1 (en) | 2006-11-15 | 2008-05-22 | High Point Pharmaceuticals, Llc | Novel 2-(2-hydroxyphenyl)benzimidazoles useful for treating obesity and diabetes |
| EP2099777B1 (en) | 2007-01-11 | 2015-08-12 | Novo Nordisk A/S | Urea glucokinase activators |
| EP2539364A1 (en) | 2010-02-26 | 2013-01-02 | Novo Nordisk A/S | Peptides for treatment of obesity |
| BR112012021231A2 (pt) | 2010-02-26 | 2015-09-08 | Basf Plant Science Co Gmbh | método para acentuar o rendimento em plantas, planta, construto, uso de um construto, método para a produção de uma planta transgênica, partes coletáveis de uma planta, produtos derivados de uma planta, uso de um ácido nucleíco e método para a produção de um produto |
| WO2011117415A1 (en) | 2010-03-26 | 2011-09-29 | Novo Nordisk A/S | Novel glucagon analogues |
| US10130684B2 (en) | 2011-02-03 | 2018-11-20 | Pharmedica Ltd. | Oral dissolving films for insulin administration, for treating diabetes |
| JP2014510739A (ja) | 2011-03-28 | 2014-05-01 | ノヴォ ノルディスク アー／エス | 新規のグルカゴン類似体 |
| CA2849673A1 (en) | 2011-09-23 | 2013-03-28 | Novo Nordisk A/S | Novel glucagon analogues |
| WO2014170496A1 (en) | 2013-04-18 | 2014-10-23 | Novo Nordisk A/S | Stable, protracted glp-1/glucagon receptor co-agonists for medical use |
| JP2017525656A (ja) | 2014-06-04 | 2017-09-07 | ノヴォ ノルディスク アー／エス | 医療用のｇｌｐ−１／グルカゴン受容体コアゴニスト |
| CN111032680A (zh) | 2017-03-15 | 2020-04-17 | 诺和诺德股份有限公司 | 能够与黑皮质素4受体结合的双环化合物 |
| US20210221867A1 (en) | 2018-05-15 | 2021-07-22 | Novo Nordisk A/S | Compounds Capable of Binding to Melanocortin 4 Receptor |
| WO2020053414A1 (en) | 2018-09-14 | 2020-03-19 | Novo Nordisk A/S | Bicyclic compounds capable of acting as melanocortin 4 receptor agonists |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10199003I1 (de) * | 1987-09-04 | 2003-06-12 | Beecham Group Plc | Substituierte Thiazolidinionderivate |
| GB8820389D0 (en) * | 1988-08-26 | 1988-09-28 | Beecham Group Plc | Novel compounds |
| GB8919417D0 (en) * | 1989-08-25 | 1989-10-11 | Beecham Group Plc | Novel compounds |
| GB9023585D0 (en) * | 1990-10-30 | 1990-12-12 | Beecham Group Plc | Novel compounds |
| GB9023583D0 (en) * | 1990-10-30 | 1990-12-12 | Beecham Group Plc | Novel compounds |
-
1998
- 1998-04-10 AU AU69664/98A patent/AU6966498A/en not_active Abandoned
- 1998-04-10 AT AT98915492T patent/ATE212991T1/de active
- 1998-04-10 JP JP54317398A patent/JP4391597B2/ja not_active Expired - Fee Related
- 1998-04-10 DE DE69803750T patent/DE69803750T2/de not_active Expired - Fee Related
- 1998-04-10 WO PCT/US1998/007285 patent/WO1998045292A1/en not_active Ceased
- 1998-04-10 EP EP98915492A patent/EP0971917B1/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| JP4391597B2 (ja) | 2009-12-24 |
| DE69803750D1 (de) | 2002-03-21 |
| EP0971917A1 (en) | 2000-01-19 |
| WO1998045292A1 (en) | 1998-10-15 |
| EP0971917B1 (en) | 2002-02-06 |
| AU6966498A (en) | 1998-10-30 |
| JP2002508745A (ja) | 2002-03-19 |
| ATE212991T1 (de) | 2002-02-15 |
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| 8339 | Ceased/non-payment of the annual fee | ||
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| 8339 | Ceased/non-payment of the annual fee | ||
| 8370 | Indication related to discontinuation of the patent is to be deleted | ||
| 8339 | Ceased/non-payment of the annual fee |