CZ20031737A3 - Thiazolové deriváty - Google Patents
Thiazolové deriváty Download PDFInfo
- Publication number
- CZ20031737A3 CZ20031737A3 CZ20031737A CZ20031737A CZ20031737A3 CZ 20031737 A3 CZ20031737 A3 CZ 20031737A3 CZ 20031737 A CZ20031737 A CZ 20031737A CZ 20031737 A CZ20031737 A CZ 20031737A CZ 20031737 A3 CZ20031737 A3 CZ 20031737A3
- Authority
- CZ
- Czechia
- Prior art keywords
- methyl
- thiazol
- phenoxy
- propionic acid
- trifluoromethylphenyl
- Prior art date
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- 150000007979 thiazole derivatives Chemical class 0.000 title claims description 20
- 150000001875 compounds Chemical class 0.000 claims abstract description 127
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 15
- 201000010099 disease Diseases 0.000 claims abstract description 13
- 238000011282 treatment Methods 0.000 claims abstract description 8
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 61
- -1 3-Fluoro-4-trifluoromethyl-phenyl Chemical group 0.000 claims description 34
- 235000019260 propionic acid Nutrition 0.000 claims description 25
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 25
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 24
- 239000008194 pharmaceutical composition Substances 0.000 claims description 21
- 150000003839 salts Chemical class 0.000 claims description 19
- 239000004480 active ingredient Substances 0.000 claims description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims description 16
- 102100038831 Peroxisome proliferator-activated receptor alpha Human genes 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 14
- 150000002148 esters Chemical class 0.000 claims description 13
- 125000004494 ethyl ester group Chemical group 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 239000000556 agonist Substances 0.000 claims description 12
- 239000001257 hydrogen Substances 0.000 claims description 12
- 101000741788 Homo sapiens Peroxisome proliferator-activated receptor alpha Proteins 0.000 claims description 11
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 10
- 239000012453 solvate Substances 0.000 claims description 10
- 229910052717 sulfur Inorganic materials 0.000 claims description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 230000000694 effects Effects 0.000 claims description 8
- 230000001404 mediated effect Effects 0.000 claims description 8
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 125000004496 thiazol-5-yl group Chemical group S1C=NC=C1* 0.000 claims description 6
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 6
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 5
- 208000032928 Dyslipidaemia Diseases 0.000 claims description 5
- 208000017170 Lipid metabolism disease Diseases 0.000 claims description 5
- 150000001721 carbon Chemical group 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 5
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 5
- RRDUKUBKIRKLQP-OAHLLOKOSA-N 2-methyl-2-[2-methyl-4-[(1r)-1-[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]ethoxy]phenoxy]propanoic acid Chemical compound O([C@H](C)C1=C(N=C(S1)C=1C=CC(=CC=1)C(F)(F)F)C)C1=CC=C(OC(C)(C)C(O)=O)C(C)=C1 RRDUKUBKIRKLQP-OAHLLOKOSA-N 0.000 claims description 4
- TUXGYOGLJLNSLC-UHFFFAOYSA-N 2-methyl-2-[2-methyl-4-[1-[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]-2-phenylethoxy]phenoxy]propanoic acid Chemical compound CC=1N=C(C=2C=CC(=CC=2)C(F)(F)F)SC=1C(OC=1C=C(C)C(OC(C)(C)C(O)=O)=CC=1)CC1=CC=CC=C1 TUXGYOGLJLNSLC-UHFFFAOYSA-N 0.000 claims description 4
- DOYOGUXJFXYZPD-UHFFFAOYSA-N 2-methyl-2-[2-methyl-4-[1-[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]butoxy]phenoxy]propanoic acid Chemical compound S1C(C=2C=CC(=CC=2)C(F)(F)F)=NC(C)=C1C(CCC)OC1=CC=C(OC(C)(C)C(O)=O)C(C)=C1 DOYOGUXJFXYZPD-UHFFFAOYSA-N 0.000 claims description 4
- 208000008589 Obesity Diseases 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 150000002431 hydrogen Chemical class 0.000 claims description 4
- 235000020824 obesity Nutrition 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 208000011580 syndromic disease Diseases 0.000 claims description 4
- ACNJQJVNIHENMJ-UHFFFAOYSA-N 2-[4-[1-[2-(3,4-dichlorophenyl)-4-methyl-1,3-thiazol-5-yl]ethoxy]-2-methylphenoxy]-2-methylpropanoic acid Chemical compound S1C(C=2C=C(Cl)C(Cl)=CC=2)=NC(C)=C1C(C)OC1=CC=C(OC(C)(C)C(O)=O)C(C)=C1 ACNJQJVNIHENMJ-UHFFFAOYSA-N 0.000 claims description 3
- JDJCZGMWUDTZHP-UHFFFAOYSA-N 2-[4-[1-[2-(4-chlorophenyl)-4-methyl-1,3-thiazol-5-yl]ethoxy]-2-methylphenoxy]-2-methylpropanoic acid Chemical compound S1C(C=2C=CC(Cl)=CC=2)=NC(C)=C1C(C)OC1=CC=C(OC(C)(C)C(O)=O)C(C)=C1 JDJCZGMWUDTZHP-UHFFFAOYSA-N 0.000 claims description 3
- LQAGUDSBCGFOHU-UHFFFAOYSA-N 2-[4-[1-[2-[2-fluoro-4-(trifluoromethyl)phenyl]-4-methyl-1,3-thiazol-5-yl]ethoxy]-2-methylphenoxy]-2-methylpropanoic acid Chemical compound S1C(C=2C(=CC(=CC=2)C(F)(F)F)F)=NC(C)=C1C(C)OC1=CC=C(OC(C)(C)C(O)=O)C(C)=C1 LQAGUDSBCGFOHU-UHFFFAOYSA-N 0.000 claims description 3
- RRDUKUBKIRKLQP-HNNXBMFYSA-N 2-methyl-2-[2-methyl-4-[(1s)-1-[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]ethoxy]phenoxy]propanoic acid Chemical compound O([C@@H](C)C1=C(N=C(S1)C=1C=CC(=CC=1)C(F)(F)F)C)C1=CC=C(OC(C)(C)C(O)=O)C(C)=C1 RRDUKUBKIRKLQP-HNNXBMFYSA-N 0.000 claims description 3
- ACLIMENRFRVCSU-UHFFFAOYSA-N 2-methyl-2-[2-methyl-4-[1-[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]but-3-enoxy]phenoxy]propanoic acid Chemical compound CC=1N=C(C=2C=CC(=CC=2)C(F)(F)F)SC=1C(CC=C)OC1=CC=C(OC(C)(C)C(O)=O)C(C)=C1 ACLIMENRFRVCSU-UHFFFAOYSA-N 0.000 claims description 3
- MEAQHQOZORFODX-UHFFFAOYSA-N 2-methyl-2-[2-methyl-4-[1-[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]ethylsulfanyl]phenoxy]propanoic acid Chemical compound S1C(C=2C=CC(=CC=2)C(F)(F)F)=NC(C)=C1C(C)SC1=CC=C(OC(C)(C)C(O)=O)C(C)=C1 MEAQHQOZORFODX-UHFFFAOYSA-N 0.000 claims description 3
- YIJZPRXQAKJHNE-UHFFFAOYSA-N 2-methyl-2-[2-methyl-4-[2-[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]propan-2-yloxy]phenoxy]propanoic acid Chemical compound CC=1N=C(C=2C=CC(=CC=2)C(F)(F)F)SC=1C(C)(C)OC1=CC=C(OC(C)(C)C(O)=O)C(C)=C1 YIJZPRXQAKJHNE-UHFFFAOYSA-N 0.000 claims description 3
- 208000000103 Anorexia Nervosa Diseases 0.000 claims description 3
- 206010006550 Bulimia nervosa Diseases 0.000 claims description 3
- 206010019280 Heart failures Diseases 0.000 claims description 3
- 208000035150 Hypercholesterolemia Diseases 0.000 claims description 3
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 3
- 208000022531 anorexia Diseases 0.000 claims description 3
- 230000000747 cardiac effect Effects 0.000 claims description 3
- 206010061428 decreased appetite Diseases 0.000 claims description 3
- 208000019622 heart disease Diseases 0.000 claims description 3
- 125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 3
- 208000019553 vascular disease Diseases 0.000 claims description 3
- GALPDOKVVGMRBH-UHFFFAOYSA-N 2-[4-[1-[2-(4-ethylphenyl)-4-methyl-1,3-thiazol-5-yl]ethoxy]-2-methylphenoxy]-2-methylpropanoic acid Chemical compound C1=CC(CC)=CC=C1C1=NC(C)=C(C(C)OC=2C=C(C)C(OC(C)(C)C(O)=O)=CC=2)S1 GALPDOKVVGMRBH-UHFFFAOYSA-N 0.000 claims description 2
- ZUGQWAYOWCBWGM-UHFFFAOYSA-N 2-[4-[[2-[2-fluoro-4-(trifluoromethyl)phenyl]-4-methyl-1,3-thiazol-5-yl]methylsulfanyl]-2-methylphenoxy]-2-methylpropanoic acid Chemical compound CC=1N=C(C=2C(=CC(=CC=2)C(F)(F)F)F)SC=1CSC1=CC=C(OC(C)(C)C(O)=O)C(C)=C1 ZUGQWAYOWCBWGM-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- 125000000217 alkyl group Chemical group 0.000 claims description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- DBURNDRLWVLANW-UHFFFAOYSA-N ethyl 2-[4-[1-[2-(3,4-dichlorophenyl)-4-methyl-1,3-thiazol-5-yl]ethoxy]-2-methylphenoxy]-2-methylpropanoate Chemical compound C1=C(C)C(OC(C)(C)C(=O)OCC)=CC=C1OC(C)C1=C(C)N=C(C=2C=C(Cl)C(Cl)=CC=2)S1 DBURNDRLWVLANW-UHFFFAOYSA-N 0.000 claims description 2
- LWZJOPATGVBMKD-UHFFFAOYSA-N ethyl 2-[4-[1-[2-(4-ethylphenyl)-4-methyl-1,3-thiazol-5-yl]ethoxy]-2-methylphenoxy]-2-methylpropanoate Chemical compound C1=C(C)C(OC(C)(C)C(=O)OCC)=CC=C1OC(C)C1=C(C)N=C(C=2C=CC(CC)=CC=2)S1 LWZJOPATGVBMKD-UHFFFAOYSA-N 0.000 claims description 2
- VVSDRJWDUWKJEQ-QGZVFWFLSA-N ethyl 2-methyl-2-[2-methyl-4-[(1r)-1-[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]ethoxy]phenoxy]propanoate Chemical compound C1=C(C)C(OC(C)(C)C(=O)OCC)=CC=C1O[C@H](C)C1=C(C)N=C(C=2C=CC(=CC=2)C(F)(F)F)S1 VVSDRJWDUWKJEQ-QGZVFWFLSA-N 0.000 claims description 2
- DUHMSMHVKCZPHW-NRFANRHFSA-N ethyl 2-methyl-2-[2-methyl-4-[(1s)-1-[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]propoxy]phenoxy]propanoate Chemical compound C1=C(C)C(OC(C)(C)C(=O)OCC)=CC=C1O[C@@H](CC)C1=C(C)N=C(C=2C=CC(=CC=2)C(F)(F)F)S1 DUHMSMHVKCZPHW-NRFANRHFSA-N 0.000 claims description 2
- WBMZDAQGXFDTBQ-UHFFFAOYSA-N ethyl 2-methyl-2-[2-methyl-4-[1-[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]butoxy]phenoxy]propanoate Chemical compound S1C(C=2C=CC(=CC=2)C(F)(F)F)=NC(C)=C1C(CCC)OC1=CC=C(OC(C)(C)C(=O)OCC)C(C)=C1 WBMZDAQGXFDTBQ-UHFFFAOYSA-N 0.000 claims description 2
- FIZDTPYPDHOYMY-UHFFFAOYSA-N ethyl 2-methyl-2-[2-methyl-4-[2-[2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]propan-2-ylsulfanyl]phenoxy]propanoate Chemical compound C1=C(C)C(OC(C)(C)C(=O)OCC)=CC=C1SC(C)(C)C1=CN=C(C=2C=CC(=CC=2)C(F)(F)F)S1 FIZDTPYPDHOYMY-UHFFFAOYSA-N 0.000 claims description 2
- NCNIULXXTBGJFD-UHFFFAOYSA-N ethyl 2-methyl-2-[2-methyl-4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methoxy]phenoxy]propanoate Chemical compound C1=C(C)C(OC(C)(C)C(=O)OCC)=CC=C1OCC1=C(C)N=C(C=2C=CC(=CC=2)C(F)(F)F)S1 NCNIULXXTBGJFD-UHFFFAOYSA-N 0.000 claims description 2
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- FTYMJPNQPCWPAL-UHFFFAOYSA-N 2-methyl-2-(2-methylphenoxy)propanoic acid Chemical compound CC1=CC=CC=C1OC(C)(C)C(O)=O FTYMJPNQPCWPAL-UHFFFAOYSA-N 0.000 claims 1
- PMIZOBUIWOYRRZ-UHFFFAOYSA-N 2-methyl-2-[2-methyl-4-[1-[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]propoxy]phenoxy]pentanoic acid Chemical compound C(C)CC(C(=O)O)(OC1=C(C=C(C=C1)OC(CC)C1=C(N=C(S1)C1=CC=C(C=C1)C(F)(F)F)C)C)C PMIZOBUIWOYRRZ-UHFFFAOYSA-N 0.000 claims 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D277/24—Radicals substituted by oxygen atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D277/26—Radicals substituted by sulfur atoms
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Life Sciences & Earth Sciences (AREA)
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- Diabetes (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Neurology (AREA)
- Vascular Medicine (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Neurosurgery (AREA)
- Child & Adolescent Psychology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0031107.6A GB0031107D0 (en) | 2000-12-20 | 2000-12-20 | Chemical compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CZ20031737A3 true CZ20031737A3 (cs) | 2003-10-15 |
Family
ID=9905492
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CZ20031737A CZ20031737A3 (cs) | 2000-12-20 | 2001-12-19 | Thiazolové deriváty |
Country Status (27)
| Country | Link |
|---|---|
| EP (1) | EP1343773B1 (enExample) |
| JP (1) | JP4209681B2 (enExample) |
| KR (1) | KR100815022B1 (enExample) |
| CN (1) | CN1252057C (enExample) |
| AR (1) | AR035522A1 (enExample) |
| AT (1) | ATE344253T1 (enExample) |
| AU (1) | AU2002246713B2 (enExample) |
| BR (1) | BR0116370A (enExample) |
| CA (1) | CA2432188A1 (enExample) |
| CY (1) | CY1105915T1 (enExample) |
| CZ (1) | CZ20031737A3 (enExample) |
| DE (1) | DE60124302T2 (enExample) |
| DK (1) | DK1343773T3 (enExample) |
| ES (1) | ES2274914T3 (enExample) |
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Families Citing this family (46)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7041691B1 (en) | 1999-06-30 | 2006-05-09 | Amgen Inc. | Compounds for the modulation of PPARγ activity |
| AU2001258841B2 (en) * | 2000-05-26 | 2005-06-23 | Nippon Shinyaku Co., Ltd. | Heterocyclic compounds |
| US20030171399A1 (en) | 2000-06-28 | 2003-09-11 | Tularik Inc. | Quinolinyl and benzothiazolyl modulators |
| GB0031109D0 (en) | 2000-12-20 | 2001-01-31 | Glaxo Group Ltd | Chemical compounds |
| US20040072838A1 (en) | 2000-12-20 | 2004-04-15 | Pierette Banker | Thiazole and oxazole derivatives as activators of human peroxisome proliferator activated receptors |
| WO2003015776A1 (en) * | 2001-08-13 | 2003-02-27 | Janssen Pharmaceutica N.V. | 2,4,5-trisubstituted thiazolyl derivatives and their antiinflammatory activity |
| DE60324898D1 (de) | 2002-02-25 | 2009-01-08 | Lilly Co Eli | Modulatoren von peroxisome proliferator-aktivierten rezeptoren |
| JP2005529077A (ja) | 2002-02-25 | 2005-09-29 | イーライ・リリー・アンド・カンパニー | ペルオキシソーム増殖因子活性化受容体調節物質 |
| US6833380B2 (en) | 2002-03-07 | 2004-12-21 | Warner-Lambert Company, Llc | Compounds that modulate PPAR activity and methods of preparation |
| US20030207924A1 (en) * | 2002-03-07 | 2003-11-06 | Xue-Min Cheng | Compounds that modulate PPAR activity and methods of preparation |
| US6875780B2 (en) | 2002-04-05 | 2005-04-05 | Warner-Lambert Company | Compounds that modulate PPAR activity and methods for their preparation |
| US7244763B2 (en) | 2003-04-17 | 2007-07-17 | Warner Lambert Company Llc | Compounds that modulate PPAR activity and methods of preparation |
| US6987118B2 (en) * | 2003-05-21 | 2006-01-17 | Pfizer Inc. | Tetrahydroisoquinoline derivatives as PPAR-alpha activators |
| AU2004247355A1 (en) * | 2003-06-06 | 2004-12-23 | F. Hoffmann-La Roche Ag | Aniline derivatives |
| BRPI0412236A (pt) | 2003-07-02 | 2006-09-12 | Hoffmann La Roche | compostos, processo para a sua manufatura, composições farmacêuticas que compreendem os mesmos, método para o tratamento e/ou prevenção de enfermidades que são moduladas por agonistas ppar(delta) e/ou ppar(alfa), e utilização desses compostos |
| EP2100877B1 (en) | 2003-09-19 | 2012-01-25 | Janssen Pharmaceutica N.V. | 4-((Phenoxyalkyl)thio)-phenoxyacetic acids and analogs |
| US7223761B2 (en) | 2003-10-03 | 2007-05-29 | Amgen Inc. | Salts and polymorphs of a potent antidiabetic compound |
| EA011010B1 (ru) | 2004-02-27 | 2008-12-30 | Эмджен, Инк. | Соединения, модулирующие рецептор gpr40, фармацевтическая композиция, способ лечения заболеваний, чувствительных к модулированию рецептора gpr40 (варианты), способ модулирования функции gpr40 (варианты) и способ модулирования циркулирующей концентрации инсулина |
| EP1745014B1 (en) | 2004-05-05 | 2011-07-06 | High Point Pharmaceuticals, LLC | Novel compounds, their preparation and use |
| JP2007536343A (ja) | 2004-05-05 | 2007-12-13 | ノボ ノルディスク アクティーゼルスカブ | Ｐｐａｒアゴニストとしてのフェノキシ酢酸誘導体 |
| MY145712A (en) | 2004-09-15 | 2012-03-30 | Janssen Pharmaceutica Nv | 4-((phenoxyalkyl)thio)-phenoxyacetic acids and analogs |
| MY147518A (en) | 2004-09-15 | 2012-12-31 | Janssen Pharmaceutica Nv | 4-((phenoxyalkyl)thio)-phenoxyacetic acids and analogs |
| RU2371437C2 (ru) * | 2004-12-31 | 2009-10-27 | Сеул Нэшнл Юниверсити Индастри Фаундейшн | Селенорганические соединения и их применение |
| EP1856072A4 (en) * | 2005-02-25 | 2009-10-21 | Seoul Nat Univ Ind Foundation | THIAZOLE DERIVATIVES AS PPAR DELTA LIGANDS AND PROCESSES FOR THE PRODUCTION THEREOF |
| RU2392274C2 (ru) * | 2005-02-25 | 2010-06-20 | Сеул Нэшнл Юниверсити Индастри Фаундейшн | Тиазольные производные в качестве лигандов ppar-дельта и способ их получения |
| US7465804B2 (en) | 2005-05-20 | 2008-12-16 | Amgen Inc. | Compounds, pharmaceutical compositions and methods for their use in treating metabolic disorders |
| US7943669B2 (en) | 2005-06-30 | 2011-05-17 | High Point Pharmaceuticals, Llc | Phenoxy acetic acids as PPAR delta activators |
| EP1924546A1 (en) | 2005-09-14 | 2008-05-28 | Amgen, Inc | Conformationally constrained 3- (4-hydroxy-phenyl) - substituted-propanoic acids useful for treating metabolic disorders |
| JO3006B1 (ar) | 2005-09-14 | 2016-09-05 | Janssen Pharmaceutica Nv | املاح ليسين مبتكرة من مشتقات حامض 4-((فينوكسي الكيل)ثيو) فينوكسي الخليك |
| EA201101084A1 (ru) | 2005-12-22 | 2012-04-30 | ХАЙ ПОЙНТ ФАРМАСЬЮТИКАЛЗ, ЭлЭлСи | Феноксиуксусные кислоты в качестве активаторов ppar дельта |
| CN101007790B (zh) * | 2006-01-27 | 2011-03-30 | 北京摩力克科技有限公司 | 草氨酸衍生物、其制备方法和医药用途 |
| JP2009529512A (ja) | 2006-03-09 | 2009-08-20 | ハイ ポイント ファーマシューティカルズ，リミティド ライアビリティ カンパニー | 新規な化合物、それらの製造法、及び使用法 |
| UY30288A1 (es) | 2006-04-18 | 2007-08-31 | Janssen Pharmaceutica Nv | Derivados del ácido benzoazepin-oxi-acético como agonistas de ppar-delta usados para aumentar hdl-c. reducir ldl-c y reducir colesterol |
| AU2007293028B2 (en) | 2006-09-07 | 2012-05-31 | Amgen Inc. | Heterocyclic GPR40 modulators |
| US7687526B2 (en) | 2006-09-07 | 2010-03-30 | Amgen Inc. | Benzo-fused compounds for use in treating metabolic disorders |
| JP5455636B2 (ja) * | 2006-12-02 | 2014-03-26 | ソウル ナショナル ユニバーシティー インダストリー ファンデーション | アリール化合物、その水和物、その溶媒化物、その立体異性体、または、その薬学的に許容される塩、アリール化合物の製造方法、及び、アリール化合物等の用途 |
| RU2444518C2 (ru) | 2007-01-08 | 2012-03-10 | Сеул Нэшнл Юниверсити Индастри Фаундейшн | ПРОИЗВОДНОЕ ТИАЗОЛА КАК PPARδ ЛИГАНД И ФАРМАЦЕВТИЧЕСКИЙ, КОСМЕТИЧЕСКИЙ И ДИЕТИЧЕСКИЙ ПИЩЕВОЙ ПРОДУКТ, СОДЕРЖАЩИЙ ЕГО |
| PE20090159A1 (es) | 2007-03-08 | 2009-02-21 | Plexxikon Inc | COMPUESTOS DERIVADOS DE ACIDO INDOL-PROPIONICO COMO MODULADORES PPARs |
| CA2683751C (en) | 2007-04-16 | 2013-01-08 | Amgen Inc. | Substituted biphenyl phenoxy-, thiophenyl- and aminophenylpropanoic acid gpr40 modulators |
| KR20100090249A (ko) | 2007-10-10 | 2010-08-13 | 암젠 인크 | 치환된 비페닐 ｇｒｐ４０ 조절제 |
| US8450522B2 (en) | 2008-03-06 | 2013-05-28 | Amgen Inc. | Conformationally constrained carboxylic acid derivatives useful for treating metabolic disorders |
| US8748462B2 (en) | 2008-10-15 | 2014-06-10 | Amgen Inc. | Spirocyclic GPR40 modulators |
| EP2540711A4 (en) * | 2010-02-25 | 2014-01-22 | Snu R&Db Foundation | Selenium-Zolderivate with ligand for the activation of the peroxisome-proliferator-activated receptor (PPAR), preparation method therefor and use of the chemical compounds |
| US20120094959A1 (en) | 2010-10-19 | 2012-04-19 | Bonnie Blazer-Yost | Treatment of cystic diseases |
| ES2811087T3 (es) | 2013-09-09 | 2021-03-10 | Vtv Therapeutics Llc | Uso de agonistas de PPAR-delta para tratar la atrofia muscular |
| WO2023147309A1 (en) | 2022-01-25 | 2023-08-03 | Reneo Pharmaceuticals, Inc. | Use of ppar-delta agonists in the treatment of disease |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4434164A (en) * | 1981-06-01 | 1984-02-28 | Pfizer Inc. | Crystalline benzothiazine dioxide salts |
| US4623486A (en) * | 1985-05-29 | 1986-11-18 | Pfizer Inc. | [4-substituted benzoyloxy]-N-substituted-2H-1,2-benzothiazine-3-carboxamide 1,1-dioxides having anti-arthritic activity |
| GB9914977D0 (en) * | 1999-06-25 | 1999-08-25 | Glaxo Group Ltd | Chemical compounds |
| PE20011010A1 (es) * | 1999-12-02 | 2001-10-18 | Glaxo Group Ltd | Oxazoles y tiazoles sustituidos como agonista del receptor activado por el proliferador de peroxisomas humano |
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2000
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- 2001-12-18 AR ARP010105863A patent/AR035522A1/es not_active Application Discontinuation
- 2001-12-19 EP EP01994305A patent/EP1343773B1/en not_active Expired - Lifetime
- 2001-12-19 WO PCT/US2001/049230 patent/WO2002062774A1/en not_active Ceased
- 2001-12-19 MX MXPA03005699A patent/MXPA03005699A/es active IP Right Grant
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- 2001-12-19 DK DK01994305T patent/DK1343773T3/da active
- 2001-12-19 HU HU0400837A patent/HUP0400837A3/hu unknown
- 2001-12-19 PT PT01994305T patent/PT1343773E/pt unknown
- 2001-12-19 AT AT01994305T patent/ATE344253T1/de not_active IP Right Cessation
- 2001-12-19 PL PL01365797A patent/PL365797A1/xx not_active Application Discontinuation
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- 2001-12-19 DE DE60124302T patent/DE60124302T2/de not_active Expired - Fee Related
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