JP2002513422A - 新規甲状腺レセプターリガンドおよび方法 - Google Patents
新規甲状腺レセプターリガンドおよび方法Info
- Publication number
- JP2002513422A JP2002513422A JP50530199A JP50530199A JP2002513422A JP 2002513422 A JP2002513422 A JP 2002513422A JP 50530199 A JP50530199 A JP 50530199A JP 50530199 A JP50530199 A JP 50530199A JP 2002513422 A JP2002513422 A JP 2002513422A
- Authority
- JP
- Japan
- Prior art keywords
- hydroxy
- isopropylphenoxy
- acid
- compound
- dibromo
- 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.)
- Ceased
Links
- 238000000034 method Methods 0.000 title claims abstract description 41
- 239000003446 ligand Substances 0.000 title claims abstract description 15
- 108090000721 thyroid hormone receptors Proteins 0.000 title claims abstract description 15
- 102000004217 thyroid hormone receptors Human genes 0.000 title claims abstract description 15
- -1 alkenyl carboxylic acid Chemical class 0.000 claims abstract description 97
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 24
- 150000002367 halogens Chemical class 0.000 claims abstract description 24
- 150000002148 esters Chemical class 0.000 claims abstract description 23
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 22
- 150000003839 salts Chemical class 0.000 claims abstract description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 17
- 201000010099 disease Diseases 0.000 claims abstract description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 11
- 239000001257 hydrogen Substances 0.000 claims abstract description 11
- 208000003532 hypothyroidism Diseases 0.000 claims abstract description 11
- 230000002989 hypothyroidism Effects 0.000 claims abstract description 11
- 108090000623 proteins and genes Proteins 0.000 claims abstract description 10
- 230000001105 regulatory effect Effects 0.000 claims abstract description 9
- 208000035150 Hypercholesterolemia Diseases 0.000 claims abstract description 8
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical compound OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 claims abstract description 8
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims abstract description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 8
- 208000008589 Obesity Diseases 0.000 claims abstract description 7
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 6
- 230000014509 gene expression Effects 0.000 claims abstract description 6
- 235000020824 obesity Nutrition 0.000 claims abstract description 6
- 208000001132 Osteoporosis Diseases 0.000 claims abstract description 5
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 claims abstract description 5
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- 230000001419 dependent effect Effects 0.000 claims abstract description 5
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- 206010018498 Goitre Diseases 0.000 claims abstract description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 3
- 201000003872 goiter Diseases 0.000 claims abstract description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 4
- 150000001875 compounds Chemical class 0.000 claims description 55
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 31
- 239000002253 acid Substances 0.000 claims description 30
- 238000011282 treatment Methods 0.000 claims description 21
- 229960000583 acetic acid Drugs 0.000 claims description 20
- 239000005495 thyroid hormone Substances 0.000 claims description 17
- 229940036555 thyroid hormone Drugs 0.000 claims description 17
- 239000000460 chlorine Substances 0.000 claims description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
- WVDDGKGOMKODPV-UHFFFAOYSA-N hydroxymethyl benzene Natural products OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 claims description 13
- AUYYCJSJGJYCDS-LBPRGKRZSA-N Thyrolar Chemical class IC1=CC(C[C@H](N)C(O)=O)=CC(I)=C1OC1=CC=C(O)C(I)=C1 AUYYCJSJGJYCDS-LBPRGKRZSA-N 0.000 claims description 12
- 229910052794 bromium Inorganic materials 0.000 claims description 10
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 8
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 7
- 206010019280 Heart failures Diseases 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 6
- 208000010412 Glaucoma Diseases 0.000 claims description 5
- 235000019445 benzyl alcohol Nutrition 0.000 claims description 5
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 claims description 4
- 206010007559 Cardiac failure congestive Diseases 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- 230000005856 abnormality Effects 0.000 claims description 4
- 125000003342 alkenyl group Chemical group 0.000 claims description 4
- 206010003119 arrhythmia Diseases 0.000 claims description 4
- QEIMLVPITPFUIG-UHFFFAOYSA-N 2-[3,5-dibromo-4-(4-hydroxy-3-propan-2-ylphenoxy)phenyl]acetonitrile Chemical compound C1=C(O)C(C(C)C)=CC(OC=2C(=CC(CC#N)=CC=2Br)Br)=C1 QEIMLVPITPFUIG-UHFFFAOYSA-N 0.000 claims description 3
- RMULTKUVQIIBQQ-UHFFFAOYSA-N 2-[3-chloro-4-(4-hydroxy-3-propan-2-ylphenoxy)phenyl]acetic acid Chemical compound C1=C(O)C(C(C)C)=CC(OC=2C(=CC(CC(O)=O)=CC=2)Cl)=C1 RMULTKUVQIIBQQ-UHFFFAOYSA-N 0.000 claims description 3
- CWCHTDVUZXHTLC-UHFFFAOYSA-N 2-[4-(4-hydroxy-3-propan-2-ylphenoxy)-3,5-dimethylphenyl]acetic acid Chemical compound C1=C(O)C(C(C)C)=CC(OC=2C(=CC(CC(O)=O)=CC=2C)C)=C1 CWCHTDVUZXHTLC-UHFFFAOYSA-N 0.000 claims description 3
- SSQJHTBDVVULTC-UHFFFAOYSA-N 4-[2,6-dibromo-4-(hydroxymethyl)phenoxy]-2-propan-2-ylphenol Chemical compound C1=C(O)C(C(C)C)=CC(OC=2C(=CC(CO)=CC=2Br)Br)=C1 SSQJHTBDVVULTC-UHFFFAOYSA-N 0.000 claims description 3
- 201000001320 Atherosclerosis Diseases 0.000 claims description 3
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 claims description 3
- 208000006981 Skin Abnormalities Diseases 0.000 claims description 3
- 229930016911 cinnamic acid Natural products 0.000 claims description 3
- 235000013985 cinnamic acid Nutrition 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 claims description 3
- FDLOBNTWQDSHPF-UHFFFAOYSA-N 2-[3,5-dibromo-4-(4-hydroxy-3-propan-2-ylphenoxy)phenyl]acetic acid Chemical compound C1=C(O)C(C(C)C)=CC(OC=2C(=CC(CC(O)=O)=CC=2Br)Br)=C1 FDLOBNTWQDSHPF-UHFFFAOYSA-N 0.000 claims description 2
- OZYQIQVPUZANTM-UHFFFAOYSA-N 2-[3,5-dichloro-4-(4-hydroxy-3-propan-2-ylphenoxy)phenyl]acetic acid Chemical compound C1=C(O)C(C(C)C)=CC(OC=2C(=CC(CC(O)=O)=CC=2Cl)Cl)=C1 OZYQIQVPUZANTM-UHFFFAOYSA-N 0.000 claims description 2
- QJSZKQGOEKSPPI-UHFFFAOYSA-N 3,5-dibromo-4-(4-hydroxy-3-propan-2-ylphenoxy)benzoic acid Chemical compound C1=C(O)C(C(C)C)=CC(OC=2C(=CC(=CC=2Br)C(O)=O)Br)=C1 QJSZKQGOEKSPPI-UHFFFAOYSA-N 0.000 claims description 2
- TVQYCFFCYRSFQF-UHFFFAOYSA-N 3,5-dichloro-4-(4-hydroxy-3-propan-2-ylphenoxy)benzoic acid Chemical compound C1=C(O)C(C(C)C)=CC(OC=2C(=CC(=CC=2Cl)C(O)=O)Cl)=C1 TVQYCFFCYRSFQF-UHFFFAOYSA-N 0.000 claims description 2
- UGEBMEYZKKASGB-UHFFFAOYSA-N 4-(4-hydroxy-3-propan-2-ylphenoxy)-3,5-dimethylbenzoic acid Chemical compound C1=C(O)C(C(C)C)=CC(OC=2C(=CC(=CC=2C)C(O)=O)C)=C1 UGEBMEYZKKASGB-UHFFFAOYSA-N 0.000 claims description 2
- KOEJGQKJIIRANK-UHFFFAOYSA-N 4-[2,6-dibromo-4-(iodomethyl)phenoxy]-2-propan-2-ylphenol Chemical compound C1=C(O)C(C(C)C)=CC(OC=2C(=CC(CI)=CC=2Br)Br)=C1 KOEJGQKJIIRANK-UHFFFAOYSA-N 0.000 claims description 2
- NLVPRWUCENXJCF-UHFFFAOYSA-N 4-[2,6-dichloro-4-(iodomethyl)phenoxy]-2-propan-2-ylphenol Chemical compound C1=C(O)C(C(C)C)=CC(OC=2C(=CC(CI)=CC=2Cl)Cl)=C1 NLVPRWUCENXJCF-UHFFFAOYSA-N 0.000 claims description 2
- PWSMKMSJUYSIGD-UHFFFAOYSA-N 4-[4-(hydroxymethyl)-2,6-dimethylphenoxy]-2-propan-2-ylphenol Chemical compound C1=C(O)C(C(C)C)=CC(OC=2C(=CC(CO)=CC=2C)C)=C1 PWSMKMSJUYSIGD-UHFFFAOYSA-N 0.000 claims description 2
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 2
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- 208000024172 Cardiovascular disease Diseases 0.000 claims 2
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- 230000006793 arrhythmia Effects 0.000 claims 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 1
- 150000001735 carboxylic acids Chemical class 0.000 claims 1
- 230000001335 demethylating effect Effects 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 230000005861 gene abnormality Effects 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- JWHOQZUREKYPBY-UHFFFAOYSA-N rubonic acid Natural products CC1(C)CCC2(CCC3(C)C(=CCC4C5(C)CCC(=O)C(C)(C)C5CC(=O)C34C)C2C1)C(=O)O JWHOQZUREKYPBY-UHFFFAOYSA-N 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 115
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 60
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 57
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Classifications
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
- C07F9/3882—Arylalkanephosphonic acids
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
- C07C255/32—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring
- C07C255/37—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by etherified hydroxy groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C43/00—Ethers; Compounds having groups, groups or groups
- C07C43/02—Ethers
- C07C43/257—Ethers having an ether-oxygen atom bound to carbon atoms both belonging to six-membered aromatic rings
- C07C43/295—Ethers having an ether-oxygen atom bound to carbon atoms both belonging to six-membered aromatic rings containing hydroxy or O-metal groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C59/00—Compounds having carboxyl groups bound to acyclic carbon atoms and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C59/40—Unsaturated compounds
- C07C59/58—Unsaturated compounds containing ether groups, groups, groups, or groups
- C07C59/64—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings
- C07C59/66—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings the non-carboxylic part of the ether containing six-membered aromatic rings
- C07C59/68—Unsaturated compounds containing ether groups, groups, groups, or groups containing six-membered aromatic rings the non-carboxylic part of the ether containing six-membered aromatic rings the oxygen atom of the ether group being bound to a non-condensed six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C65/00—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C65/21—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing ether groups, groups, groups, or groups
- C07C65/24—Compounds having carboxyl groups bound to carbon atoms of six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups containing ether groups, groups, groups, or groups polycyclic
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
- C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4056—Esters of arylalkanephosphonic acids
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
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- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
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- Molecular Biology (AREA)
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- Neurology (AREA)
- Child & Adolescent Psychology (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9713739.2 | 1997-06-27 | ||
| GBGB9713739.2A GB9713739D0 (en) | 1997-06-27 | 1997-06-27 | Thyroid receptor ligands |
| PCT/EP1998/004039 WO1999000353A1 (en) | 1997-06-27 | 1998-06-26 | Novel thyroid receptor ligands and method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2002513422A true JP2002513422A (ja) | 2002-05-08 |
| JP2002513422A5 JP2002513422A5 (https=) | 2005-12-02 |
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| Application Number | Title | Priority Date | Filing Date |
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| JP50530199A Ceased JP2002513422A (ja) | 1997-06-27 | 1998-06-26 | 新規甲状腺レセプターリガンドおよび方法 |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US6465687B1 (https=) |
| EP (1) | EP1000008B1 (https=) |
| JP (1) | JP2002513422A (https=) |
| KR (1) | KR20010020472A (https=) |
| AT (1) | ATE243672T1 (https=) |
| AU (1) | AU735525C (https=) |
| CA (1) | CA2294098C (https=) |
| DE (1) | DE69815852T2 (https=) |
| DK (1) | DK1000008T3 (https=) |
| ES (1) | ES2197486T3 (https=) |
| GB (1) | GB9713739D0 (https=) |
| PT (1) | PT1000008E (https=) |
| WO (1) | WO1999000353A1 (https=) |
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006038719A1 (ja) * | 2004-10-08 | 2006-04-13 | Kotobuki Pharmaceutical Co., Ltd. | ホスホン酸誘導体及び血中の高リン酸が関与する疾患の治療剤 |
| JP2007512359A (ja) * | 2003-11-19 | 2007-05-17 | メタバシス・セラピューティクス・インコーポレイテッド | 新規なリン含有甲状腺ホルモン様物質 |
| JP2008545711A (ja) * | 2005-05-26 | 2008-12-18 | メタバシス・セラピューティクス・インコーポレイテッド | 新規ホスフィン酸含有甲状腺ホルモン様剤 |
| JP2019516739A (ja) * | 2016-05-18 | 2019-06-20 | オレゴン ヘルス アンド サイエンス ユニバーシティ | ソベチロム誘導体 |
| JP2022513449A (ja) * | 2018-12-12 | 2022-02-08 | オートバーン セラピューティクス，インク． | 新規な甲状腺模倣物 |
| US11667606B2 (en) | 2019-03-01 | 2023-06-06 | Autobahn Therapeutics, Inc. | Thyromimetics |
Families Citing this family (131)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6380255B1 (en) * | 1995-06-07 | 2002-04-30 | Karo Bio Ab | Treatment for dermal skin atrophy using thyroid hormone compounds or thyroid hormone-like compounds |
| EP1127882A1 (en) * | 2000-01-25 | 2001-08-29 | Pfizer Products Inc. | Tetrazole compounds as thyroid receptor ligands |
| CZ20022771A3 (cs) | 2000-02-17 | 2003-09-17 | Bristol-Myers Squibb Company | Ligandy thyreoidního receptoru odvozené od anilinu |
| US6395767B2 (en) | 2000-03-10 | 2002-05-28 | Bristol-Myers Squibb Company | Cyclopropyl-fused pyrrolidine-based inhibitors of dipeptidyl peptidase IV and method |
| US6620830B2 (en) | 2000-04-21 | 2003-09-16 | Pfizer, Inc. | Thyroid receptor ligands |
| ATE310733T1 (de) * | 2000-04-21 | 2005-12-15 | Pfizer Prod Inc | Thyroid-rezeptorliganden |
| US6395784B1 (en) | 2000-06-07 | 2002-05-28 | Bristol-Myers Squibb Company | Benzamide ligands for the thyroid receptor |
| DE10038007A1 (de) | 2000-08-04 | 2002-02-14 | Bayer Ag | Neue Amino-und Amido-Diphenylether für Arzneimittel |
| EP1358175A2 (en) | 2001-02-08 | 2003-11-05 | Karo Bio Ab | Phenoxy substituted benzocondensed heteroaryl derivatives as thyroid receptor ligands |
| US6777442B2 (en) | 2001-03-12 | 2004-08-17 | Bayer Aktiengesellschaft | Diphenyl derivatives |
| US6423549B1 (en) * | 2001-03-14 | 2002-07-23 | Bio-Rad Laboratories, Inc. | Phycoerythrin labeled thyronine analogues and assays using labeled analogues |
| WO2002083066A2 (en) | 2001-04-11 | 2002-10-24 | Bristol-Myers Squibb Company | Amino acid complexes of c-aryl glucosides for treatment of diabetes and method |
| GB0111861D0 (en) | 2001-05-15 | 2001-07-04 | Karobio Ab | Novel compounds |
| EP1499578A2 (en) * | 2001-08-24 | 2005-01-26 | Karo Bio Ab | Prime ring substituted thyroid receptor antagonists for the treatment of cardiac and metabolic disorders |
| US7238671B2 (en) | 2001-10-18 | 2007-07-03 | Bristol-Myers Squibb Company | Human glucagon-like-peptide-1 mimics and their use in the treatment of diabetes and related conditions |
| CA2463908A1 (en) | 2001-10-18 | 2003-04-24 | Bristol-Myers Squibb Company | Human glucagon-like-peptide-1 mimics and their use in the treatment of diabetes and related conditions |
| EP1443919A4 (en) | 2001-11-16 | 2006-03-22 | Bristol Myers Squibb Co | DOUBLE INHIBITORS OF THE FATTY ACID BINDING PROTEIN OF THE ADIPOCYTES AND THE FATTY ACID BINDING PROTEIN OF KERATINOCYTES |
| US6831102B2 (en) | 2001-12-07 | 2004-12-14 | Bristol-Myers Squibb Company | Phenyl naphthol ligands for thyroid hormone receptor |
| GB0208384D0 (en) * | 2002-04-11 | 2002-05-22 | Karobio Ab | Novel compounds |
| WO2003094845A2 (en) | 2002-05-08 | 2003-11-20 | Bristol-Myers Squibb Company | Pyridine-based thyroid receptor ligands |
| US7405234B2 (en) | 2002-05-17 | 2008-07-29 | Bristol-Myers Squibb Company | Bicyclic modulators of androgen receptor function |
| US7057046B2 (en) | 2002-05-20 | 2006-06-06 | Bristol-Myers Squibb Company | Lactam glycogen phosphorylase inhibitors and method of use |
| DE60332856D1 (de) | 2002-10-23 | 2010-07-15 | Bristol Myers Squibb Co | Auf glycinnitril basierende hemmer der dipeptidylpeptidase iv |
| US7098235B2 (en) | 2002-11-14 | 2006-08-29 | Bristol-Myers Squibb Co. | Triglyceride and triglyceride-like prodrugs of glycogen phosphorylase inhibiting compounds |
| US7632858B2 (en) | 2002-11-15 | 2009-12-15 | Bristol-Myers Squibb Company | Open chain prolyl urea-related modulators of androgen receptor function |
| WO2004066929A2 (en) * | 2003-01-24 | 2004-08-12 | Bristol-Myers Squibb Company | Cycloalkyl containing anilide ligands for the thyroid receptor |
| TW200504021A (en) | 2003-01-24 | 2005-02-01 | Bristol Myers Squibb Co | Substituted anilide ligands for the thyroid receptor |
| US7557143B2 (en) | 2003-04-18 | 2009-07-07 | Bristol-Myers Squibb Company | Thyroid receptor ligands |
| US7459474B2 (en) | 2003-06-11 | 2008-12-02 | Bristol-Myers Squibb Company | Modulators of the glucocorticoid receptor and method |
| US6995183B2 (en) | 2003-08-01 | 2006-02-07 | Bristol Myers Squibb Company | Adamantylglycine-based inhibitors of dipeptidyl peptidase IV and methods |
| US7371759B2 (en) | 2003-09-25 | 2008-05-13 | Bristol-Myers Squibb Company | HMG-CoA reductase inhibitors and method |
| US7576121B2 (en) | 2003-11-12 | 2009-08-18 | Phenomix Corporation | Pyrrolidine compounds and methods for selective inhibition of dipeptidyl peptidase-IV |
| US7767828B2 (en) | 2003-11-12 | 2010-08-03 | Phenomix Corporation | Methyl and ethyl substituted pyrrolidine compounds and methods for selective inhibition of dipeptidyl peptidase-IV |
| US7317109B2 (en) | 2003-11-12 | 2008-01-08 | Phenomix Corporation | Pyrrolidine compounds and methods for selective inhibition of dipeptidyl peptidase-IV |
| NZ547752A (en) | 2003-11-12 | 2009-12-24 | Phenomix Corp | Heterocyclic boronic acid compounds for inhibiting dipeptidyl peptidase-IV |
| WO2006128058A2 (en) * | 2005-05-26 | 2006-11-30 | Metabasis Therapeutics, Inc. | Thyromimetics for the treatment of fatty liver diseases |
| US7420059B2 (en) | 2003-11-20 | 2008-09-02 | Bristol-Myers Squibb Company | HMG-CoA reductase inhibitors and method |
| US7820702B2 (en) | 2004-02-04 | 2010-10-26 | Bristol-Myers Squibb Company | Sulfonylpyrrolidine modulators of androgen receptor function and method |
| US7378426B2 (en) | 2004-03-01 | 2008-05-27 | Bristol-Myers Squibb Company | Fused heterotricyclic compounds as inhibitors of 17β-hydroxysteroid dehydrogenase 3 |
| US7625923B2 (en) | 2004-03-04 | 2009-12-01 | Bristol-Myers Squibb Company | Bicyclic modulators of androgen receptor function |
| US7696241B2 (en) | 2004-03-04 | 2010-04-13 | Bristol-Myers Squibb Company | Bicyclic compounds as modulators of androgen receptor function and method |
| US7534763B2 (en) | 2004-07-02 | 2009-05-19 | Bristol-Myers Squibb Company | Sustained release GLP-1 receptor modulators |
| TW200611704A (en) | 2004-07-02 | 2006-04-16 | Bristol Myers Squibb Co | Human glucagon-like-peptide-1 modulators and their use in the treatment of diabetes and related conditions |
| US7145040B2 (en) | 2004-07-02 | 2006-12-05 | Bristol-Myers Squibb Co. | Process for the preparation of amino acids useful in the preparation of peptide receptor modulators |
| CA2573848A1 (en) | 2004-07-12 | 2006-02-16 | Phenomix Corporation | Constrained cyano compounds |
| US7572805B2 (en) | 2004-07-14 | 2009-08-11 | Bristol-Myers Squibb Company | Pyrrolo(oxo)isoquinolines as 5HT ligands |
| AR051446A1 (es) | 2004-09-23 | 2007-01-17 | Bristol Myers Squibb Co | Glucosidos de c-arilo como inhibidores selectivos de transportadores de glucosa (sglt2) |
| US7517991B2 (en) | 2004-10-12 | 2009-04-14 | Bristol-Myers Squibb Company | N-sulfonylpiperidine cannabinoid receptor 1 antagonists |
| US7635699B2 (en) | 2004-12-29 | 2009-12-22 | Bristol-Myers Squibb Company | Azolopyrimidine-based inhibitors of dipeptidyl peptidase IV and methods |
| US7589088B2 (en) | 2004-12-29 | 2009-09-15 | Bristol-Myers Squibb Company | Pyrimidine-based inhibitors of dipeptidyl peptidase IV and methods |
| WO2006076568A2 (en) | 2005-01-12 | 2006-07-20 | Bristol-Myers Squibb Company | Thiazolopyridines as cannabinoid receptor modulators |
| US7368458B2 (en) | 2005-01-12 | 2008-05-06 | Bristol-Myers Squibb Company | Bicyclic heterocycles as cannabinoid receptor modulators |
| WO2006076598A2 (en) | 2005-01-12 | 2006-07-20 | Bristol-Myers Squibb Company | Bicyclic heterocycles as cannabinoid receptor modulators |
| US7317024B2 (en) | 2005-01-13 | 2008-01-08 | Bristol-Myers Squibb Co. | Heterocyclic modulators of the glucocorticoid receptor, AP-1, and/or NF-κB activity and use thereof |
| WO2006078697A1 (en) | 2005-01-18 | 2006-07-27 | Bristol-Myers Squibb Company | Bicyclic heterocycles as cannabinoid receptor modulators |
| WO2006086464A2 (en) | 2005-02-10 | 2006-08-17 | Bristol-Myers Squibb Company | Dihydroquinazolinones as 5ht modulators |
| EP2527337A1 (en) | 2005-04-14 | 2012-11-28 | Bristol-Myers Squibb Company | Inhibitors of 11-beta hydroxysteroid dehydrogenase type I |
| US7521557B2 (en) | 2005-05-20 | 2009-04-21 | Bristol-Myers Squibb Company | Pyrrolopyridine-based inhibitors of dipeptidyl peptidase IV and methods |
| US7825139B2 (en) | 2005-05-25 | 2010-11-02 | Forest Laboratories Holdings Limited (BM) | Compounds and methods for selective inhibition of dipeptidyl peptidase-IV |
| AU2006249347A1 (en) * | 2005-05-26 | 2006-11-30 | Metabasis Therapeutics, Inc. | Novel phosphorus-containing thyromimetics |
| US7888381B2 (en) | 2005-06-14 | 2011-02-15 | Bristol-Myers Squibb Company | Modulators of glucocorticoid receptor, AP-1, and/or NF-κB activity, and use thereof |
| US7317012B2 (en) | 2005-06-17 | 2008-01-08 | Bristol-Myers Squibb Company | Bicyclic heterocycles as cannabinoind-1 receptor modulators |
| US7632837B2 (en) | 2005-06-17 | 2009-12-15 | Bristol-Myers Squibb Company | Bicyclic heterocycles as cannabinoid-1 receptor modulators |
| US7452892B2 (en) | 2005-06-17 | 2008-11-18 | Bristol-Myers Squibb Company | Triazolopyrimidine cannabinoid receptor 1 antagonists |
| TW200726765A (en) | 2005-06-17 | 2007-07-16 | Bristol Myers Squibb Co | Triazolopyridine cannabinoid receptor 1 antagonists |
| US7629342B2 (en) | 2005-06-17 | 2009-12-08 | Bristol-Myers Squibb Company | Azabicyclic heterocycles as cannabinoid receptor modulators |
| PL1919878T3 (pl) | 2005-07-21 | 2011-03-31 | Hoffmann La Roche | Pochodne pirydazynonu jako agoniści receptora hormonu tarczycy |
| US7795436B2 (en) | 2005-08-24 | 2010-09-14 | Bristol-Myers Squibb Company | Substituted tricyclic heterocycles as serotonin receptor agonists and antagonists |
| US8618115B2 (en) | 2005-10-26 | 2013-12-31 | Bristol-Myers Squibb Company | Substituted thieno[3,2-d]pyrimidinones as MCHR1 antagonists and methods for using them |
| EP1943215A2 (en) | 2005-10-31 | 2008-07-16 | Brystol-Myers Squibb Company | Pyrrolidinyl beta-amino amide-based inhibitors of dipeptidyl peptidase iv and methods |
| US7592461B2 (en) | 2005-12-21 | 2009-09-22 | Bristol-Myers Squibb Company | Indane modulators of glucocorticoid receptor, AP-1, and/or NF-κB activity and use thereof |
| US7553836B2 (en) | 2006-02-06 | 2009-06-30 | Bristol-Myers Squibb Company | Melanin concentrating hormone receptor-1 antagonists |
| US20100022457A1 (en) | 2006-05-26 | 2010-01-28 | Bristol-Myers Squibb Company | Sustained release glp-1 receptor modulators |
| US7919598B2 (en) | 2006-06-28 | 2011-04-05 | Bristol-Myers Squibb Company | Crystal structures of SGLT2 inhibitors and processes for preparing same |
| ES2558517T3 (es) | 2006-08-02 | 2016-02-04 | Cytokinetics, Inc. | Ciertas entidades químicas, composiciones y métodos que comprenden imidazopirimidinas |
| US8299248B2 (en) | 2006-08-02 | 2012-10-30 | Cytokinetics, Incorporated | Certain 1H-imidazo[4,5-b]pyrazin-2(3H)-ones and 1H-imidazo[4,5-b]pyrazin-2-ols and methods for their use |
| US7727978B2 (en) | 2006-08-24 | 2010-06-01 | Bristol-Myers Squibb Company | Cyclic 11-beta hydroxysteroid dehydrogenase type I inhibitors |
| US8198311B2 (en) | 2006-11-01 | 2012-06-12 | Bristol-Myers Squibb Company | Modulators of glucocorticoid receptor, AP-1, and/or NF-κB activity and use thereof |
| EP2089355A2 (en) | 2006-11-01 | 2009-08-19 | Brystol-Myers Squibb Company | Modulators of glucocorticoid receptor, ap-1, and/or nf- kappa b activity and use thereof |
| AR065809A1 (es) | 2007-03-22 | 2009-07-01 | Bristol Myers Squibb Co | Formulaciones farmaceuticas que contienen un inhibidor sglt2 |
| US8546394B2 (en) | 2007-04-17 | 2013-10-01 | Bristol-Myers Squibb Company | Substituted [1,2,4]triazolo[4,3-A]pyrazine 11-beta-hydroxysteroid dehydrogenase inhibitors |
| PE20090696A1 (es) | 2007-04-20 | 2009-06-20 | Bristol Myers Squibb Co | Formas cristalinas de saxagliptina y procesos para preparar las mismas |
| US8969514B2 (en) | 2007-06-04 | 2015-03-03 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
| EP2527360B1 (en) | 2007-06-04 | 2015-10-28 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| US20090011994A1 (en) | 2007-07-06 | 2009-01-08 | Bristol-Myers Squibb Company | Non-basic melanin concentrating hormone receptor-1 antagonists and methods |
| CN101808995A (zh) | 2007-07-27 | 2010-08-18 | 百时美施贵宝公司 | 新颖的葡糖激酶激活剂及其使用方法 |
| RU2443699C2 (ru) | 2007-09-20 | 2012-02-27 | Айрм Ллк | Соединения и композиции в качестве модуляторов активности gpr119 |
| US8076334B2 (en) | 2007-09-20 | 2011-12-13 | Hoffmann-La Roche Inc. | Prodrugs of thyroid hormone analogs |
| ES2448839T3 (es) | 2007-11-01 | 2014-03-17 | Bristol-Myers Squibb Company | Compuestos no esteroideos útiles como moderadores de la actividad del receptor de glucocorticoides AP-1 y/o NF-kappa b y uso de los mismos |
| PE20091928A1 (es) | 2008-05-29 | 2009-12-31 | Bristol Myers Squibb Co | Tienopirimidinas hidroxisustituidas como antagonistas de receptor-1 de hormona concentradora de melanina no basicos |
| EP2810951B1 (en) | 2008-06-04 | 2017-03-15 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| EP3241839B1 (en) | 2008-07-16 | 2019-09-04 | Bausch Health Ireland Limited | Agonists of guanylate cyclase useful for the treatment of gastrointestinal, inflammation, cancer and other disorders |
| SG174504A1 (en) | 2009-03-27 | 2011-10-28 | Bristol Myers Squibb Co | Methods for preventing major adverse cardiovascular events with dpp-iv inhibitors |
| WO2011014520A2 (en) | 2009-07-29 | 2011-02-03 | Irm Llc | Compounds and compositions as modulators of gpr119 activity |
| WO2011038207A1 (en) * | 2009-09-25 | 2011-03-31 | Metabasis Therapeutics, Inc. | Phosphorus-containing thyroid hormone receptor agonists and methods of use |
| CN102686579A (zh) | 2009-10-09 | 2012-09-19 | Irm责任有限公司 | 作为gpr119活性调节剂的化合物和组合物 |
| EP3315124B1 (en) | 2009-11-13 | 2021-01-06 | Astrazeneca AB | Bilayer tablet formulations |
| CN102711738A (zh) | 2009-11-13 | 2012-10-03 | 百时美施贵宝公司 | 质量得以减小的二甲双胍制剂 |
| JP5784623B2 (ja) | 2009-11-13 | 2015-09-24 | アストラゼネカ・アクチエボラーグＡｓｔｒａｚｅｎｅｃａ Ａｋｔｉｅｂｏｌａｇ | 速放性錠剤製剤 |
| US8394858B2 (en) | 2009-12-03 | 2013-03-12 | Novartis Ag | Cyclohexane derivatives and uses thereof |
| TWI562775B (en) | 2010-03-02 | 2016-12-21 | Lexicon Pharmaceuticals Inc | Methods of using inhibitors of sodium-glucose cotransporters 1 and 2 |
| US8592396B2 (en) | 2010-04-14 | 2013-11-26 | Bristol-Myers Squibb Company | Glucokinase activators and methods of using same |
| AR081626A1 (es) | 2010-04-23 | 2012-10-10 | Cytokinetics Inc | Compuestos amino-piridazinicos, composiciones farmaceuticas que los contienen y uso de los mismos para tratar trastornos musculares cardiacos y esqueleticos |
| US9133123B2 (en) | 2010-04-23 | 2015-09-15 | Cytokinetics, Inc. | Certain amino-pyridines and amino-triazines, compositions thereof, and methods for their use |
| AR081331A1 (es) | 2010-04-23 | 2012-08-08 | Cytokinetics Inc | Amino- pirimidinas composiciones de las mismas y metodos para el uso de los mismos |
| US8697739B2 (en) | 2010-07-29 | 2014-04-15 | Novartis Ag | Bicyclic acetyl-CoA carboxylase inhibitors and uses thereof |
| US20130156720A1 (en) | 2010-08-27 | 2013-06-20 | Ironwood Pharmaceuticals, Inc. | Compositions and methods for treating or preventing metabolic syndrome and related diseases and disorders |
| US9616097B2 (en) | 2010-09-15 | 2017-04-11 | Synergy Pharmaceuticals, Inc. | Formulations of guanylate cyclase C agonists and methods of use |
| TWI631963B (zh) | 2011-01-05 | 2018-08-11 | 雷西肯製藥股份有限公司 | 包含鈉－葡萄糖共同輸送體１與２之抑制劑的組合物與應用方法 |
| EP2892897A1 (en) | 2012-09-05 | 2015-07-15 | Bristol-Myers Squibb Company | Pyrrolone or pyrrolidinone melanin concentrating hormone receptor-1 antagonists |
| EP2892896B1 (en) | 2012-09-05 | 2016-06-29 | Bristol-Myers Squibb Company | Pyrrolone or pyrrolidinone melanin concentrating hormore receptor-1 antagonists |
| WO2014052619A1 (en) | 2012-09-27 | 2014-04-03 | Irm Llc | Piperidine derivatives and compositions as modulators of gpr119 activity |
| PL3489226T3 (pl) | 2012-11-20 | 2021-08-02 | Lexicon Pharmaceuticals, Inc. | Inhibitory kotransportera glukozowo-sodowego 1 |
| CA2905435A1 (en) | 2013-03-15 | 2014-09-25 | Synergy Pharmaceuticals Inc. | Compositions useful for the treatment of gastrointestinal disorders |
| CA2905438A1 (en) | 2013-03-15 | 2014-09-25 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase and their uses |
| EP2983694B1 (en) | 2013-04-08 | 2022-06-22 | President and Fellows of Harvard College | Compositions for rejuvenating skeletal muscle stem cells |
| SI3004138T1 (sl) | 2013-06-05 | 2024-07-31 | Bausch Health Ireland Limited | Ultra čisti agonisti gvanilat ciklaze C, postopek za njihovo pripravo in uporabo |
| US9593113B2 (en) | 2013-08-22 | 2017-03-14 | Bristol-Myers Squibb Company | Imide and acylurea derivatives as modulators of the glucocorticoid receptor |
| WO2017180988A2 (en) | 2016-04-15 | 2017-10-19 | Indiana University Research And Technology Corporation | Fgf21 c-terminal peptide optimization |
| CA3044059A1 (en) | 2016-11-21 | 2018-05-24 | Viking Therapeutics, Inc. | Method of treating glycogen storage disease |
| US11707472B2 (en) | 2017-06-05 | 2023-07-25 | Viking Therapeutics, Inc. | Compositions for the treatment of fibrosis |
| CN109929806B (zh) | 2017-12-19 | 2020-05-08 | 北京吉源生物科技有限公司 | 一种表达glp1和fgf21的干细胞及其用途 |
| ES3053674T3 (en) | 2018-03-22 | 2026-01-23 | Viking Therapeutics Inc | Crystalline forms and methods of producing crystalline forms of a compound |
| BR112021000139A2 (pt) | 2018-07-19 | 2021-04-06 | Astrazeneca Ab | Métodos de tratamento da hfpef empregando dapagliflozina e composições compreendendo a mesma |
| WO2020038464A1 (zh) | 2018-08-23 | 2020-02-27 | 北京厚燊药德科技有限责任公司 | 苯氧酸类化合物及其医药用途 |
| US10968192B2 (en) | 2018-09-26 | 2021-04-06 | Lexicon Pharmaceuticals, Inc. | Crystalline solid forms of N-(1-((2-(dimethylamino)ethyl)amino)-2-methyl-1-oxopropan-2-yl)-4-(4-(2-methyl-5-((2S,3R,4R,5S,6R)-3,4,5-trihydroxy-6-(methylthio)tetrahydro-2H-pyran-2-yl)benzyl)phenyl)butanamide and methods of their synthesis |
| WO2020117962A1 (en) | 2018-12-05 | 2020-06-11 | Viking Therapeutics, Inc. | Compositions for the treatment of fibrosis and inflammation |
| JP2022538119A (ja) | 2019-06-27 | 2022-08-31 | サイトキネティックス， インコーポレイテッド | １－（２－（（（（ｔｒａｎｓ）－３－フルオロ－１－（３－フルオロピリジン－２－イル）シクロブチル）メチル）アミノ）ピリミジン－５－イル）－１Ｈ－ピロール－３－カルボキサミドの多形 |
| KR20220121239A (ko) | 2019-11-29 | 2022-08-31 | 아우토반 쎄라퓨틱스, 인크. | 신규한 갑상선 호르몬 모방제 |
| WO2021257851A1 (en) | 2020-06-17 | 2021-12-23 | Autobahn Therapeutics, Inc. | Thyromimetics |
| JP7813730B2 (ja) | 2020-06-17 | 2026-02-13 | オートバーン セラピューティクス，インク． | 甲状腺様作用剤 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1072998B (de) | 1957-08-21 | 1960-01-14 | Farbwerke Hoechst Aktiengesellschaft vormals Meister Lucius &. Brüning, Frankfurt/M | Verfahren zur Herstellung von substituierten Diphenyläthern |
| DE1078582B (de) | 1958-10-29 | 1960-03-31 | Hoechst Ag | Verfahren zur Herstellung substituierter Thyropropionsaeuren |
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- 1998-06-26 DE DE69815852T patent/DE69815852T2/de not_active Expired - Fee Related
- 1998-06-26 ES ES98935008T patent/ES2197486T3/es not_active Expired - Lifetime
- 1998-06-26 JP JP50530199A patent/JP2002513422A/ja not_active Ceased
- 1998-06-26 AT AT98935008T patent/ATE243672T1/de not_active IP Right Cessation
Cited By (8)
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|---|---|---|---|---|
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| JP2022513449A (ja) * | 2018-12-12 | 2022-02-08 | オートバーン セラピューティクス，インク． | 新規な甲状腺模倣物 |
| US11667606B2 (en) | 2019-03-01 | 2023-06-06 | Autobahn Therapeutics, Inc. | Thyromimetics |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2294098A1 (en) | 1999-01-07 |
| EP1000008A1 (en) | 2000-05-17 |
| US6465687B1 (en) | 2002-10-15 |
| AU735525B2 (en) | 2001-07-12 |
| DE69815852T2 (de) | 2004-05-19 |
| CA2294098C (en) | 2009-02-10 |
| DE69815852D1 (de) | 2003-07-31 |
| EP1000008B1 (en) | 2003-06-25 |
| ES2197486T3 (es) | 2004-01-01 |
| AU8440598A (en) | 1999-01-19 |
| GB9713739D0 (en) | 1997-09-03 |
| ATE243672T1 (de) | 2003-07-15 |
| PT1000008E (pt) | 2003-10-31 |
| WO1999000353A1 (en) | 1999-01-07 |
| DK1000008T3 (da) | 2003-10-20 |
| KR20010020472A (ko) | 2001-03-15 |
| AU735525C (en) | 2002-02-21 |
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