ES2310650T3 - Derivados de tiazol y oxazol que modulan la actividad de los ppar. - Google Patents
Derivados de tiazol y oxazol que modulan la actividad de los ppar. Download PDFInfo
- Publication number
- ES2310650T3 ES2310650T3 ES03702943T ES03702943T ES2310650T3 ES 2310650 T3 ES2310650 T3 ES 2310650T3 ES 03702943 T ES03702943 T ES 03702943T ES 03702943 T ES03702943 T ES 03702943T ES 2310650 T3 ES2310650 T3 ES 2310650T3
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- Spain
- Prior art keywords
- alkyl
- compound
- methyl
- baselineskip
- phenyl
- 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 - Lifetime
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- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 title description 18
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 title description 18
- 230000000694 effects Effects 0.000 title description 12
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 545
- 125000003118 aryl group Chemical group 0.000 claims abstract description 61
- 239000001257 hydrogen Substances 0.000 claims abstract description 43
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 43
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 31
- 150000002367 halogens Chemical class 0.000 claims abstract description 31
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 22
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 22
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 17
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 17
- 125000005309 thioalkoxy group Chemical group 0.000 claims abstract description 16
- 150000003839 salts Chemical class 0.000 claims abstract description 15
- 125000001424 substituent group Chemical group 0.000 claims abstract description 15
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 14
- 125000006710 (C2-C12) alkenyl group Chemical group 0.000 claims abstract description 12
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 12
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 9
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims abstract description 7
- 125000000392 cycloalkenyl group Chemical group 0.000 claims abstract description 7
- 125000005843 halogen group Chemical group 0.000 claims abstract description 5
- 239000002253 acid Substances 0.000 claims description 176
- -1 methoxy, ethoxy, isopropoxy, n-propoxy, t-butoxy Chemical group 0.000 claims description 171
- 238000002360 preparation method Methods 0.000 claims description 167
- 125000000217 alkyl group Chemical group 0.000 claims description 117
- 125000004199 4-trifluoromethylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C(F)(F)F 0.000 claims description 48
- 150000002431 hydrogen Chemical class 0.000 claims description 31
- 125000003545 alkoxy group Chemical group 0.000 claims description 27
- 125000000304 alkynyl group Chemical group 0.000 claims description 25
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 23
- 238000000034 method Methods 0.000 claims description 21
- 125000003342 alkenyl group Chemical group 0.000 claims description 17
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 14
- 208000035150 Hypercholesterolemia Diseases 0.000 claims description 12
- 125000002993 cycloalkylene group Chemical group 0.000 claims description 12
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- DDIWEYHLKGCWLH-UHFFFAOYSA-N 1-[4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]phenyl]cyclopropane-1-carboxylic acid Chemical compound CC=1N=C(C=2C=CC(=CC=2)C(F)(F)F)SC=1CSC(C=C1)=CC=C1C1(C(O)=O)CC1 DDIWEYHLKGCWLH-UHFFFAOYSA-N 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 241000124008 Mammalia Species 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
- OYDWHPGDTLGSKX-UHFFFAOYSA-N 1-[4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]phenyl]cyclopentane-1-carboxylic acid Chemical compound CC=1N=C(C=2C=CC(=CC=2)C(F)(F)F)SC=1CSC(C=C1)=CC=C1C1(C(O)=O)CCCC1 OYDWHPGDTLGSKX-UHFFFAOYSA-N 0.000 claims description 7
- 201000001320 Atherosclerosis Diseases 0.000 claims description 7
- 125000001188 haloalkyl group Chemical group 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 5
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 5
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- JFOBZYWLCOLFPS-UHFFFAOYSA-N 2-[4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]phenyl]cyclopropane-1-carboxylic acid Chemical compound CC=1N=C(C=2C=CC(=CC=2)C(F)(F)F)SC=1CSC(C=C1)=CC=C1C1CC1C(O)=O JFOBZYWLCOLFPS-UHFFFAOYSA-N 0.000 claims description 3
- URHSUAIFIXFSFV-UHFFFAOYSA-N 2-[4-[4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]phenyl]cyclohexyl]acetic acid Chemical compound CC=1N=C(C=2C=CC(=CC=2)C(F)(F)F)SC=1CSC(C=C1)=CC=C1C1CCC(CC(O)=O)CC1 URHSUAIFIXFSFV-UHFFFAOYSA-N 0.000 claims description 2
- 125000002510 isobutoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])O* 0.000 claims description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 abstract description 8
- 125000006588 heterocycloalkylene group Chemical group 0.000 abstract description 7
- 125000004406 C3-C8 cycloalkylene group Chemical group 0.000 abstract description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract description 4
- 125000006711 (C2-C12) alkynyl group Chemical group 0.000 abstract 4
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract 3
- 229910006074 SO2NH2 Inorganic materials 0.000 abstract 2
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 119
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 110
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 96
- 150000004702 methyl esters Chemical class 0.000 description 76
- 239000000203 mixture Substances 0.000 description 58
- 235000019439 ethyl acetate Nutrition 0.000 description 55
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 45
- 239000000243 solution Substances 0.000 description 44
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 43
- 239000000047 product Substances 0.000 description 43
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 42
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 40
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 35
- 230000015572 biosynthetic process Effects 0.000 description 35
- 238000003786 synthesis reaction Methods 0.000 description 34
- 239000007787 solid Substances 0.000 description 32
- 150000002148 esters Chemical class 0.000 description 30
- 239000011541 reaction mixture Substances 0.000 description 25
- 238000000746 purification Methods 0.000 description 24
- JQVJAQPUFIIRJP-UHFFFAOYSA-N 5-(chloromethyl)-4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazole Chemical compound S1C(CCl)=C(C)N=C1C1=CC=C(C(F)(F)F)C=C1 JQVJAQPUFIIRJP-UHFFFAOYSA-N 0.000 description 22
- 239000003921 oil Substances 0.000 description 22
- 235000019198 oils Nutrition 0.000 description 22
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
- 239000012267 brine Substances 0.000 description 20
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 20
- 239000002904 solvent Substances 0.000 description 20
- 229960000583 acetic acid Drugs 0.000 description 19
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 238000004587 chromatography analysis Methods 0.000 description 17
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 17
- 235000019341 magnesium sulphate Nutrition 0.000 description 17
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 16
- 239000012043 crude product Substances 0.000 description 16
- 238000003818 flash chromatography Methods 0.000 description 16
- 239000010409 thin film Substances 0.000 description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 15
- 238000010992 reflux Methods 0.000 description 15
- 229910000024 caesium carbonate Inorganic materials 0.000 description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 13
- 238000010828 elution Methods 0.000 description 13
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 12
- 238000001953 recrystallisation Methods 0.000 description 12
- 125000004432 carbon atom Chemical group C* 0.000 description 11
- 239000010410 layer Substances 0.000 description 11
- 239000012071 phase Substances 0.000 description 11
- GHYOCDFICYLMRF-UTIIJYGPSA-N (2S,3R)-N-[(2S)-3-(cyclopenten-1-yl)-1-[(2R)-2-methyloxiran-2-yl]-1-oxopropan-2-yl]-3-hydroxy-3-(4-methoxyphenyl)-2-[[(2S)-2-[(2-morpholin-4-ylacetyl)amino]propanoyl]amino]propanamide Chemical compound C1(=CCCC1)C[C@@H](C(=O)[C@@]1(OC1)C)NC([C@H]([C@@H](C1=CC=C(C=C1)OC)O)NC([C@H](C)NC(CN1CCOCC1)=O)=O)=O GHYOCDFICYLMRF-UTIIJYGPSA-N 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 10
- 210000004027 cell Anatomy 0.000 description 10
- 229940125797 compound 12 Drugs 0.000 description 10
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 10
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 9
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 9
- 229910052794 bromium Inorganic materials 0.000 description 9
- 238000009472 formulation Methods 0.000 description 9
- 239000000741 silica gel Substances 0.000 description 9
- 229910002027 silica gel Inorganic materials 0.000 description 9
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 8
- 239000008346 aqueous phase Substances 0.000 description 8
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 8
- 239000000284 extract Substances 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 8
- GLXDVVHUTZTUQK-UHFFFAOYSA-M lithium hydroxide monohydrate Substances [Li+].O.[OH-] GLXDVVHUTZTUQK-UHFFFAOYSA-M 0.000 description 8
- 239000011734 sodium Substances 0.000 description 8
- 239000003981 vehicle Substances 0.000 description 8
- 108010010234 HDL Lipoproteins Proteins 0.000 description 7
- 102000015779 HDL Lipoproteins Human genes 0.000 description 7
- 235000019441 ethanol Nutrition 0.000 description 7
- 150000002430 hydrocarbons Chemical class 0.000 description 7
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 7
- 229960003010 sodium sulfate Drugs 0.000 description 7
- 229910052938 sodium sulfate Inorganic materials 0.000 description 7
- 235000011152 sodium sulphate Nutrition 0.000 description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- BTHTYPIDOTXIMQ-UHFFFAOYSA-N 2-[2,6-dimethyl-4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]phenoxy]acetic acid Chemical compound CC=1N=C(C=2C=CC(=CC=2)C(F)(F)F)SC=1CSC1=CC(C)=C(OCC(O)=O)C(C)=C1 BTHTYPIDOTXIMQ-UHFFFAOYSA-N 0.000 description 6
- UEOKXESYLLOOPO-UHFFFAOYSA-N 2-[3,5-dimethyl-4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]phenoxy]acetic acid Chemical compound CC=1N=C(C=2C=CC(=CC=2)C(F)(F)F)SC=1CSC1=C(C)C=C(OCC(O)=O)C=C1C UEOKXESYLLOOPO-UHFFFAOYSA-N 0.000 description 6
- IFNDEOYXGHGERA-UHFFFAOYSA-N 2-methoxy-5-methylphenol Chemical compound COC1=CC=C(C)C=C1O IFNDEOYXGHGERA-UHFFFAOYSA-N 0.000 description 6
- AHDDRJBFJBDEPW-UHFFFAOYSA-N 2-phenylcyclopropane-1-carboxylic acid Chemical compound OC(=O)C1CC1C1=CC=CC=C1 AHDDRJBFJBDEPW-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 230000004913 activation Effects 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- PQVSTLUFSYVLTO-UHFFFAOYSA-N ethyl n-ethoxycarbonylcarbamate Chemical compound CCOC(=O)NC(=O)OCC PQVSTLUFSYVLTO-UHFFFAOYSA-N 0.000 description 6
- 229940040692 lithium hydroxide monohydrate Drugs 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- BGHCVCJVXZWKCC-UHFFFAOYSA-N tetradecane Chemical compound CCCCCCCCCCCCCC BGHCVCJVXZWKCC-UHFFFAOYSA-N 0.000 description 6
- IWWCCNVRNHTGLV-UHFFFAOYSA-N 1-phenylcyclopropane-1-carboxylic acid Chemical compound C=1C=CC=CC=1C1(C(=O)O)CC1 IWWCCNVRNHTGLV-UHFFFAOYSA-N 0.000 description 5
- LKSOUOBHAZNKFE-UHFFFAOYSA-N 2-[4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]-2,6-di(propan-2-yl)phenoxy]acetic acid Chemical compound CC(C)C1=C(OCC(O)=O)C(C(C)C)=CC(SCC2=C(N=C(S2)C=2C=CC(=CC=2)C(F)(F)F)C)=C1 LKSOUOBHAZNKFE-UHFFFAOYSA-N 0.000 description 5
- XOOSHDNHFWJPFP-UHFFFAOYSA-N 2-[5-ethyl-2-methyl-4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]phenoxy]acetic acid Chemical compound CCC1=CC(OCC(O)=O)=C(C)C=C1SCC1=C(C)N=C(C=2C=CC(=CC=2)C(F)(F)F)S1 XOOSHDNHFWJPFP-UHFFFAOYSA-N 0.000 description 5
- AUFCIMVSEPPGHN-UHFFFAOYSA-N 4-methyl-4-[4-[[4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl]methylsulfanyl]phenyl]pentanoic acid Chemical compound CC=1N=C(C=2C=CC(=CC=2)C(F)(F)F)SC=1CSC1=CC=C(C(C)(C)CCC(O)=O)C=C1 AUFCIMVSEPPGHN-UHFFFAOYSA-N 0.000 description 5
- BPJUJQWNAUSZJS-UHFFFAOYSA-N CC1=CC(S)=CC(C)=C1OCC(O)=O Chemical compound CC1=CC(S)=CC(C)=C1OCC(O)=O BPJUJQWNAUSZJS-UHFFFAOYSA-N 0.000 description 5
- 239000004215 Carbon black (E152) Substances 0.000 description 5
- 108020004414 DNA Proteins 0.000 description 5
- 108010007622 LDL Lipoproteins Proteins 0.000 description 5
- 102000007330 LDL Lipoproteins Human genes 0.000 description 5
- 108060001084 Luciferase Proteins 0.000 description 5
- 239000005089 Luciferase Substances 0.000 description 5
- 125000002947 alkylene group Chemical group 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 229940125904 compound 1 Drugs 0.000 description 5
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 5
- 229930195733 hydrocarbon Natural products 0.000 description 5
- 239000012299 nitrogen atmosphere Substances 0.000 description 5
- 239000012074 organic phase Substances 0.000 description 5
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 5
- 229920001223 polyethylene glycol Polymers 0.000 description 5
- 102000005962 receptors Human genes 0.000 description 5
- 108020003175 receptors Proteins 0.000 description 5
- VGTPCRGMBIAPIM-UHFFFAOYSA-M sodium thiocyanate Chemical compound [Na+].[S-]C#N VGTPCRGMBIAPIM-UHFFFAOYSA-M 0.000 description 5
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Classifications
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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
-
- 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
- A61P9/10—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
- C07D277/24—Radicals substituted by oxygen atoms
-
- 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
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- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Child & Adolescent Psychology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicinal Preparation (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US36240202P | 2002-03-07 | 2002-03-07 | |
| US362402P | 2002-03-07 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2310650T3 true ES2310650T3 (es) | 2009-01-16 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES03702943T Expired - Lifetime ES2310650T3 (es) | 2002-03-07 | 2003-02-24 | Derivados de tiazol y oxazol que modulan la actividad de los ppar. |
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| US (1) | US20030207924A1 (https=) |
| EP (1) | EP1482935B1 (https=) |
| JP (1) | JP2005528348A (https=) |
| KR (1) | KR20040091693A (https=) |
| AP (1) | AP2004003124A0 (https=) |
| AR (1) | AR038881A1 (https=) |
| AT (1) | ATE405260T1 (https=) |
| AU (1) | AU2003206059A1 (https=) |
| BR (1) | BR0308277A (https=) |
| CA (1) | CA2478520A1 (https=) |
| CO (1) | CO5601012A2 (https=) |
| DE (1) | DE60323060D1 (https=) |
| EA (1) | EA200400943A1 (https=) |
| EC (1) | ECSP045285A (https=) |
| ES (1) | ES2310650T3 (https=) |
| HN (1) | HN2003000090A (https=) |
| IS (1) | IS7377A (https=) |
| MA (1) | MA27181A1 (https=) |
| MX (1) | MXPA04007564A (https=) |
| NO (1) | NO20044242L (https=) |
| OA (1) | OA12780A (https=) |
| PA (1) | PA8567801A1 (https=) |
| PE (1) | PE20030989A1 (https=) |
| PL (1) | PL372969A1 (https=) |
| TN (1) | TNSN04168A1 (https=) |
| TW (1) | TW200305403A (https=) |
| UY (1) | UY27695A1 (https=) |
| WO (1) | WO2003074050A1 (https=) |
| ZA (1) | ZA200406068B (https=) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US6833380B2 (en) | 2002-03-07 | 2004-12-21 | Warner-Lambert Company, Llc | 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 |
| MXPA05012459A (es) * | 2003-05-19 | 2006-02-22 | Irm Llc | Compuestos y composiciones inmunosupresoras. |
| MY150088A (en) | 2003-05-19 | 2013-11-29 | Irm Llc | Immunosuppressant compounds and compositions |
| CA2558585C (en) | 2004-02-27 | 2010-10-12 | Amgen Inc. | Compounds, pharmaceutical compositions and methods for use in treating metabolic disorders |
| ES2352085T3 (es) | 2004-05-05 | 2011-02-15 | High Point Pharmaceuticals, Llc | Nuevos compuestos, su preparación y uso. |
| WO2005105736A1 (en) | 2004-05-05 | 2005-11-10 | Novo Nordisk A/S | Novel compounds, their preparation and use |
| US7456164B2 (en) | 2004-05-07 | 2008-11-25 | Pfizer, Inc | 3- or 4-monosubtituted phenol and thiophenol derivatives useful as H3 ligands |
| AU2012200214B2 (en) * | 2004-05-14 | 2013-10-24 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| WO2005115384A2 (en) * | 2004-05-25 | 2005-12-08 | Metabolex, Inc. | Bicyclic, substituted triazoles as modulators of ppar and methods of their preparation |
| CN1997633A (zh) * | 2004-05-25 | 2007-07-11 | 麦它波莱克斯股份有限公司 | 作为ppar调节剂的取代的三唑及其制备方法 |
| US20090054493A1 (en) * | 2005-02-25 | 2009-02-26 | Heonjoong Kang Kang | Thiazole derivatives as ppar delta ligands and their manufacturing process |
| CN101193876B (zh) * | 2005-05-07 | 2011-05-11 | 财团法人首尔大学校产学协力财团 | 制备PPARδ的配体的方法和用于制备该配体的中间化合物 |
| US7465804B2 (en) | 2005-05-20 | 2008-12-16 | Amgen Inc. | Compounds, pharmaceutical compositions and methods for their use in treating metabolic disorders |
| ATE529404T1 (de) | 2005-06-30 | 2011-11-15 | High Point Pharmaceuticals Llc | Phenoxyessigsäuren als ppar-delta-aktivatoren |
| EP1916234B1 (en) * | 2005-07-29 | 2014-11-12 | Takeda Pharmaceutical Company Limited | Cyclopropanecarboxylic acid compound |
| EP1924546A1 (en) | 2005-09-14 | 2008-05-28 | Amgen, Inc | Conformationally constrained 3- (4-hydroxy-phenyl) - substituted-propanoic acids useful for treating metabolic disorders |
| BRPI0620468A2 (pt) | 2005-12-22 | 2011-11-08 | Transtech Pharma, Inc. | ácidos fenóxi acéticos como ativadores de ppar delta |
| JP2009132620A (ja) * | 2006-03-07 | 2009-06-18 | Astellas Pharma Inc | フェニルチアゾール誘導体 |
| WO2007101864A2 (en) | 2006-03-09 | 2007-09-13 | High Point Pharmaceuticals, Llc | Compounds that modulate ppar activity, their preparation and use |
| EP2064193A1 (en) | 2006-09-07 | 2009-06-03 | Amgen, Inc | Heterocyclic gpr40 modulators |
| CA2662242C (en) | 2006-09-07 | 2012-06-12 | Amgen Inc. | Benzo-fused compounds for use in treating metabolic disorders |
| AU2008241490B2 (en) | 2007-04-16 | 2011-07-21 | Amgen Inc. | Substituted biphenyl phenoxy-, thiophenyl- and aminophenylpropanoic acid GPR40 modulators |
| US8030354B2 (en) | 2007-10-10 | 2011-10-04 | Amgen Inc. | Substituted biphenyl GPR40 modulators |
| AU2008338963A1 (en) * | 2007-12-13 | 2009-06-25 | Sri International | PPAR-delta ligands and methods of their use |
| WO2009086277A1 (en) | 2007-12-20 | 2009-07-09 | Envivo Pharmaceuticals, Inc. | Tetrasubstituted benzenes |
| WO2009111056A1 (en) | 2008-03-06 | 2009-09-11 | Amgen Inc. | Conformationally constrained carboxylic acid derivatives useful for treating metabolic disorders |
| AU2009303475B2 (en) | 2008-10-15 | 2012-09-13 | 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 |
| WO2015035171A1 (en) | 2013-09-09 | 2015-03-12 | High Point Pharmaceuticals, Llc | Use of a ppar-delta agonist for treating muscle atrophy |
| WO2023147309A1 (en) | 2022-01-25 | 2023-08-03 | Reneo Pharmaceuticals, Inc. | Use of ppar-delta agonists in the treatment of disease |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5859051A (en) * | 1996-02-02 | 1999-01-12 | Merck & Co., Inc. | Antidiabetic agents |
| CN1233241A (zh) * | 1996-08-19 | 1999-10-27 | 日本烟草产业株式会社 | 丙酸衍生物及其用途 |
| GB9914977D0 (en) * | 1999-06-25 | 1999-08-25 | Glaxo Group Ltd | Chemical compounds |
| GB0031107D0 (en) * | 2000-12-20 | 2001-01-31 | Glaxo Group Ltd | Chemical compounds |
| AU2002233271A1 (en) * | 2000-12-20 | 2002-07-01 | Glaxo Group Limited | Substitued oxazoles and thiazoles as hppar alpha agonists |
| GB0111523D0 (en) * | 2001-05-11 | 2001-07-04 | Glaxo Group Ltd | Chemical compounds |
| HRP20031002A2 (en) * | 2001-06-07 | 2004-06-30 | Lilly Co Eli | Modulators of peroxisome proliferator activated receptors (ppar) |
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2002
- 2002-12-20 US US10/324,148 patent/US20030207924A1/en not_active Abandoned
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2003
- 2003-02-24 AU AU2003206059A patent/AU2003206059A1/en not_active Abandoned
- 2003-02-24 PL PL03372969A patent/PL372969A1/xx not_active Application Discontinuation
- 2003-02-24 DE DE60323060T patent/DE60323060D1/de not_active Expired - Fee Related
- 2003-02-24 AP APAP/P/2004/003124A patent/AP2004003124A0/en unknown
- 2003-02-24 OA OA1200400232A patent/OA12780A/en unknown
- 2003-02-24 BR BR0308277-6A patent/BR0308277A/pt not_active IP Right Cessation
- 2003-02-24 WO PCT/IB2003/000708 patent/WO2003074050A1/en not_active Ceased
- 2003-02-24 JP JP2003572567A patent/JP2005528348A/ja not_active Abandoned
- 2003-02-24 MX MXPA04007564A patent/MXPA04007564A/es active IP Right Grant
- 2003-02-24 ES ES03702943T patent/ES2310650T3/es not_active Expired - Lifetime
- 2003-02-24 AT AT03702943T patent/ATE405260T1/de not_active IP Right Cessation
- 2003-02-24 EA EA200400943A patent/EA200400943A1/ru unknown
- 2003-02-24 EP EP03702943A patent/EP1482935B1/en not_active Expired - Lifetime
- 2003-02-24 CA CA002478520A patent/CA2478520A1/en not_active Abandoned
- 2003-02-24 KR KR10-2004-7013951A patent/KR20040091693A/ko not_active Ceased
- 2003-02-27 PA PA20038567801A patent/PA8567801A1/es unknown
- 2003-03-04 PE PE2003000210A patent/PE20030989A1/es not_active Application Discontinuation
- 2003-03-05 AR ARP030100737A patent/AR038881A1/es unknown
- 2003-03-06 TW TW092104790A patent/TW200305403A/zh unknown
- 2003-03-06 UY UY27695A patent/UY27695A1/es not_active Application Discontinuation
- 2003-03-06 HN HN2003000090A patent/HN2003000090A/es unknown
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2004
- 2004-07-29 IS IS7377A patent/IS7377A/is unknown
- 2004-07-29 ZA ZA200406068A patent/ZA200406068B/en unknown
- 2004-08-24 CO CO04082302A patent/CO5601012A2/es not_active Application Discontinuation
- 2004-08-30 MA MA27839A patent/MA27181A1/fr unknown
- 2004-09-03 TN TNP2004000168A patent/TNSN04168A1/fr unknown
- 2004-09-07 EC EC2004005285A patent/ECSP045285A/es unknown
- 2004-10-06 NO NO20044242A patent/NO20044242L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| EP1482935B1 (en) | 2008-08-20 |
| UY27695A1 (es) | 2003-10-31 |
| AP2004003124A0 (en) | 2004-09-30 |
| NO20044242L (no) | 2004-10-06 |
| EP1482935A1 (en) | 2004-12-08 |
| ECSP045285A (es) | 2004-10-26 |
| MA27181A1 (fr) | 2005-01-03 |
| ATE405260T1 (de) | 2008-09-15 |
| TW200305403A (en) | 2003-11-01 |
| DE60323060D1 (de) | 2008-10-02 |
| US20030207924A1 (en) | 2003-11-06 |
| AU2003206059A1 (en) | 2003-09-16 |
| CA2478520A1 (en) | 2003-09-12 |
| WO2003074050A1 (en) | 2003-09-12 |
| PA8567801A1 (es) | 2003-11-12 |
| IS7377A (is) | 2004-07-29 |
| HN2003000090A (es) | 2004-05-05 |
| PL372969A1 (en) | 2005-08-08 |
| CO5601012A2 (es) | 2006-01-31 |
| JP2005528348A (ja) | 2005-09-22 |
| OA12780A (en) | 2006-07-07 |
| PE20030989A1 (es) | 2003-11-29 |
| BR0308277A (pt) | 2004-12-28 |
| TNSN04168A1 (fr) | 2007-03-12 |
| MXPA04007564A (es) | 2004-11-10 |
| KR20040091693A (ko) | 2004-10-28 |
| EA200400943A1 (ru) | 2005-02-24 |
| AR038881A1 (es) | 2005-02-02 |
| ZA200406068B (en) | 2005-09-06 |
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