CN1479716A - 具有活化过氧化物酶体-增殖因子激活的受体α性质的丙酸衍生物 - Google Patents
具有活化过氧化物酶体-增殖因子激活的受体α性质的丙酸衍生物 Download PDFInfo
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- CN1479716A CN1479716A CNA018200885A CN01820088A CN1479716A CN 1479716 A CN1479716 A CN 1479716A CN A018200885 A CNA018200885 A CN A018200885A CN 01820088 A CN01820088 A CN 01820088A CN 1479716 A CN1479716 A CN 1479716A
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- Prior art keywords
- methyl
- amino
- compound
- group
- phenyl
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- 102000023984 PPAR alpha Human genes 0.000 title abstract description 4
- 230000003213 activating effect Effects 0.000 title abstract 2
- 108091008725 peroxisome proliferator-activated receptors alpha Proteins 0.000 title abstract 2
- 229940111131 antiinflammatory and antirheumatic product propionic acid derivative Drugs 0.000 title 1
- 150000005599 propionic acid derivatives Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 159
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 299
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 215
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 102
- -1 methoxyl group Chemical group 0.000 claims description 76
- 239000001257 hydrogen Substances 0.000 claims description 69
- 229910052739 hydrogen Inorganic materials 0.000 claims description 69
- 238000000034 method Methods 0.000 claims description 68
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 57
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 56
- 239000002904 solvent Substances 0.000 claims description 50
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 39
- 239000002253 acid Substances 0.000 claims description 35
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 35
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 34
- 125000004432 carbon atom Chemical group C* 0.000 claims description 34
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 31
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 27
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 27
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 22
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 22
- 229910052736 halogen Inorganic materials 0.000 claims description 21
- 150000002367 halogens Chemical class 0.000 claims description 21
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 19
- 239000002585 base Substances 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 17
- 229910052799 carbon Inorganic materials 0.000 claims description 16
- 125000001424 substituent group Chemical group 0.000 claims description 16
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 14
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 14
- 239000003513 alkali Substances 0.000 claims description 14
- 125000003118 aryl group Chemical group 0.000 claims description 14
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 14
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 13
- 125000000217 alkyl group Chemical group 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 13
- 150000002431 hydrogen Chemical class 0.000 claims description 13
- 239000011737 fluorine Substances 0.000 claims description 12
- 229910052731 fluorine Inorganic materials 0.000 claims description 12
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 11
- YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 claims description 11
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 11
- 125000001072 heteroaryl group Chemical group 0.000 claims description 11
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 11
- 229910052717 sulfur Inorganic materials 0.000 claims description 11
- 229910052760 oxygen Inorganic materials 0.000 claims description 10
- 239000012453 solvate Substances 0.000 claims description 9
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 8
- 239000000460 chlorine Substances 0.000 claims description 8
- 229910052801 chlorine Inorganic materials 0.000 claims description 8
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 8
- 238000011282 treatment Methods 0.000 claims description 8
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 7
- 230000015572 biosynthetic process Effects 0.000 claims description 7
- 125000004122 cyclic group Chemical group 0.000 claims description 7
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 7
- 239000007787 solid Substances 0.000 claims description 7
- 238000003786 synthesis reaction Methods 0.000 claims description 7
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 6
- 238000006467 substitution reaction Methods 0.000 claims description 6
- 150000001408 amides Chemical class 0.000 claims description 5
- 239000012752 auxiliary agent Substances 0.000 claims description 5
- 201000010099 disease Diseases 0.000 claims description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 5
- 229940079593 drug Drugs 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- 125000005301 thienylmethyl group Chemical group [H]C1=C([H])C([H])=C(S1)C([H])([H])* 0.000 claims description 5
- 208000034189 Sclerosis Diseases 0.000 claims description 4
- 210000001367 artery Anatomy 0.000 claims description 4
- RLMUBIZOFHUHBI-UHFFFAOYSA-N trifluoromethyl hypochlorite Chemical compound FC(F)(F)OCl RLMUBIZOFHUHBI-UHFFFAOYSA-N 0.000 claims description 4
- 125000004750 (C1-C6) alkylaminosulfonyl group Chemical group 0.000 claims description 3
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 3
- 239000000654 additive Substances 0.000 claims description 3
- 239000002270 dispersing agent Substances 0.000 claims description 3
- 239000003995 emulsifying agent Substances 0.000 claims description 3
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 231100000252 nontoxic Toxicity 0.000 claims description 3
- 230000003000 nontoxic effect Effects 0.000 claims description 3
- 230000009467 reduction Effects 0.000 claims description 3
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 2
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 2
- 206010014486 Elevated triglycerides Diseases 0.000 claims description 2
- 208000035150 Hypercholesterolemia Diseases 0.000 claims description 2
- 239000012190 activator Substances 0.000 claims description 2
- 230000029936 alkylation Effects 0.000 claims description 2
- 238000005804 alkylation reaction Methods 0.000 claims description 2
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- 238000005886 esterification reaction Methods 0.000 claims description 2
- 230000004927 fusion Effects 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims 2
- 230000002508 compound effect Effects 0.000 claims 1
- 230000001575 pathological effect Effects 0.000 claims 1
- 208000029078 coronary artery disease Diseases 0.000 abstract description 5
- 238000004519 manufacturing process Methods 0.000 abstract 1
- 230000003389 potentiating effect Effects 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 268
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 242
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 211
- 238000005160 1H NMR spectroscopy Methods 0.000 description 145
- 239000000203 mixture Substances 0.000 description 109
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 100
- 125000004646 sulfenyl group Chemical group S(*)* 0.000 description 94
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 92
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 79
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 70
- 239000000243 solution Substances 0.000 description 68
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 64
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 62
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 59
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 55
- 239000007864 aqueous solution Substances 0.000 description 55
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 51
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 46
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 44
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 44
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 43
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 42
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 36
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 36
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 36
- 239000012074 organic phase Substances 0.000 description 34
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 26
- 235000019441 ethanol Nutrition 0.000 description 26
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 26
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 25
- 238000000746 purification Methods 0.000 description 23
- 235000011121 sodium hydroxide Nutrition 0.000 description 23
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 22
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 22
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 22
- 239000000741 silica gel Substances 0.000 description 22
- 229910002027 silica gel Inorganic materials 0.000 description 22
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 21
- 235000019341 magnesium sulphate Nutrition 0.000 description 21
- 229910052796 boron Inorganic materials 0.000 description 20
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 20
- 239000003921 oil Substances 0.000 description 20
- 235000019198 oils Nutrition 0.000 description 20
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 19
- 239000011780 sodium chloride Substances 0.000 description 19
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 18
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 17
- 125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- WLYPBMBWKYALCG-UHFFFAOYSA-N [2,4-bis(trifluoromethyl)phenyl]boronic acid Chemical group OB(O)C1=CC=C(C(F)(F)F)C=C1C(F)(F)F WLYPBMBWKYALCG-UHFFFAOYSA-N 0.000 description 15
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 14
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 14
- 239000011347 resin Substances 0.000 description 14
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- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 13
- 239000000463 material Substances 0.000 description 13
- 239000000376 reactant Substances 0.000 description 13
- 229910052938 sodium sulfate Inorganic materials 0.000 description 13
- 235000011152 sodium sulphate Nutrition 0.000 description 13
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 13
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- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 12
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- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
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- 239000004471 Glycine Substances 0.000 description 9
- 229960000583 acetic acid Drugs 0.000 description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 9
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 9
- 150000002148 esters Chemical class 0.000 description 9
- 229910052708 sodium Inorganic materials 0.000 description 9
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 8
- 229910000029 sodium carbonate Inorganic materials 0.000 description 8
- DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 8
- 238000005406 washing Methods 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
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- OFJBYLCQNJHFMI-UHFFFAOYSA-N 2,5-dihydro-1,2-oxazole Chemical compound C1ONC=C1 OFJBYLCQNJHFMI-UHFFFAOYSA-N 0.000 description 7
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- 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 7
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- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical class CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 6
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- PNWSHHILERSSLF-UHFFFAOYSA-N 4-methylbenzene-1,3-dicarboxylic acid Chemical class CC1=CC=C(C(O)=O)C=C1C(O)=O PNWSHHILERSSLF-UHFFFAOYSA-N 0.000 description 6
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- 238000007445 Chromatographic isolation Methods 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- 108010049003 Fibrinogen Proteins 0.000 description 4
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- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
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- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 4
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/32—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
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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
- A61P3/04—Anorexiants; Antiobesity agents
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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
- A61P3/06—Antihyperlipidemics
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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
- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/04—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C229/06—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton
- C07C229/18—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having only one amino and one carboxyl group bound to the carbon skeleton the nitrogen atom of the amino group being further bound to carbon atoms of six-membered aromatic rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/34—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
- C07C237/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C317/00—Sulfones; Sulfoxides
- C07C317/26—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
- C07C317/28—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to acyclic carbon atoms of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/51—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton
- C07C323/52—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atoms of the thio groups bound to acyclic carbon atoms of the carbon skeleton the carbon skeleton being acyclic and saturated
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/52—Radicals substituted by nitrogen atoms not forming part of a nitro radical
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
- C07D333/20—Radicals substituted by singly bound hetero atoms other than halogen by nitrogen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
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Applications Claiming Priority (4)
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| DE10049208.8 | 2000-10-05 | ||
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| DE10124905A DE10124905A1 (de) | 2000-10-05 | 2001-05-22 | Propionsäurederivate |
| DE10124905.5 | 2001-05-22 |
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| CN1479716A true CN1479716A (zh) | 2004-03-03 |
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| EP (1) | EP1328508A2 (de) |
| JP (1) | JP2004510757A (de) |
| CN (1) | CN1479716A (de) |
| AU (1) | AU2001293838A1 (de) |
| BG (1) | BG107684A (de) |
| BR (1) | BR0114437A (de) |
| CA (1) | CA2424540A1 (de) |
| CZ (1) | CZ2003964A3 (de) |
| EE (1) | EE200300140A (de) |
| HN (1) | HN2001000223A (de) |
| HR (1) | HRP20030346A2 (de) |
| HU (1) | HUP0302306A3 (de) |
| IL (1) | IL155125A0 (de) |
| MA (1) | MA25917A1 (de) |
| MX (1) | MXPA03002901A (de) |
| NO (1) | NO20031517L (de) |
| NZ (1) | NZ525119A (de) |
| PL (1) | PL361162A1 (de) |
| RU (1) | RU2003112968A (de) |
| SK (1) | SK4132003A3 (de) |
| UY (1) | UY26951A1 (de) |
| WO (1) | WO2002028821A2 (de) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101054372B (zh) * | 2006-04-11 | 2010-10-13 | 中国科学院上海药物研究所 | 嘧啶取代苯丙酸衍生化合物、其制法和在治疗多囊肾疾病中的用途 |
| CN107406484A (zh) * | 2014-12-11 | 2017-11-28 | 中化帝斯曼制药有限公司荷兰公司 | 酰化环状肽的方法 |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10151390A1 (de) * | 2001-10-18 | 2003-05-08 | Bayer Ag | Essigsäurederivate |
| GB0214254D0 (en) | 2002-06-20 | 2002-07-31 | Glaxo Group Ltd | Chemical compounds |
| BR0315596A (pt) * | 2002-10-21 | 2005-09-06 | Janssen Pharmaceutica Nv | Tetralinas e indanos substituìdos |
| CN100354259C (zh) | 2002-10-21 | 2007-12-12 | 詹森药业有限公司 | 取代的四氢化萘和茚满及其用途 |
| MXPA05004296A (es) * | 2002-10-21 | 2005-11-23 | Johnson & Johnson | Tratamiento del sindrome x con tetralinas e indanos sustituidos. |
| EP1583754A1 (de) | 2003-01-06 | 2005-10-12 | Eli Lilly And Company | Thiophenderivate ppar modulatoren |
| JP4947406B2 (ja) | 2003-08-29 | 2012-06-06 | 小野薬品工業株式会社 | Ｓ１ｐ受容体結合能を有する化合物およびその医薬用途 |
| AR048931A1 (es) | 2004-04-21 | 2006-06-14 | Janssen Pharmaceutica Nv | Proceso para la preparacion de derivados de tetralina sustituida e indano sustituido y preparacion de intermediarios de sintesis |
| CN100344618C (zh) * | 2004-05-24 | 2007-10-24 | 北京摩力克科技有限公司 | 作为hPPARα和hPPARγ激动剂的N－芳丙烯酰基取代的酪氨酸衍生物 |
| KR100699928B1 (ko) | 2004-10-05 | 2007-03-26 | 재단법인서울대학교산학협력재단 | 퍼록시솜 증식자 활성화 수용체 알파 리간드를 제조하기위한 중간체의 제조방법 |
| AU2005314938B2 (en) | 2004-12-13 | 2011-06-09 | Ono Pharmaceutical Co., Ltd. | Aminocarboxylic acid derivative and medicinal use thereof |
| TW201022221A (en) | 2008-12-01 | 2010-06-16 | Mitsubishi Tanabe Pharma Corp | Carboxylic acid derivatives containing thiazole ring and pharmaceutical use thereof |
| JP5436941B2 (ja) * | 2009-06-03 | 2014-03-05 | あすか製薬株式会社 | ラクタム化合物又はその塩及びｐｐａｒ活性化剤 |
| UY34200A (es) | 2011-07-21 | 2013-02-28 | Bayer Ip Gmbh | 3-(fluorovinil)pirazoles y su uso |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2320387A1 (de) * | 1973-04-21 | 1974-10-31 | Boehringer Mannheim Gmbh | Phenoxyalkylcarbonsaeurederivate und verfahren zur herstellung derselben |
| GB9822473D0 (en) * | 1998-10-16 | 1998-12-09 | Glaxo Group Ltd | Chemical compounds |
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2001
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- 2001-09-24 CA CA002424540A patent/CA2424540A1/en not_active Abandoned
- 2001-09-24 HU HU0302306A patent/HUP0302306A3/hu unknown
- 2001-09-24 EP EP01974287A patent/EP1328508A2/de not_active Withdrawn
- 2001-09-24 WO PCT/EP2001/011005 patent/WO2002028821A2/de active IP Right Grant
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- 2001-09-24 AU AU2001293838A patent/AU2001293838A1/en not_active Abandoned
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101054372B (zh) * | 2006-04-11 | 2010-10-13 | 中国科学院上海药物研究所 | 嘧啶取代苯丙酸衍生化合物、其制法和在治疗多囊肾疾病中的用途 |
| CN107406484A (zh) * | 2014-12-11 | 2017-11-28 | 中化帝斯曼制药有限公司荷兰公司 | 酰化环状肽的方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| NZ525119A (en) | 2005-04-29 |
| HUP0302306A2 (hu) | 2003-10-28 |
| IL155125A0 (en) | 2003-10-31 |
| WO2002028821A2 (de) | 2002-04-11 |
| BG107684A (bg) | 2003-10-31 |
| HRP20030346A2 (en) | 2005-04-30 |
| WO2002028821A3 (de) | 2002-08-15 |
| NO20031517D0 (no) | 2003-04-03 |
| AU2001293838A1 (en) | 2002-04-15 |
| MA25917A1 (fr) | 2003-10-01 |
| CZ2003964A3 (cs) | 2003-08-13 |
| UY26951A1 (es) | 2002-06-20 |
| HUP0302306A3 (en) | 2005-02-28 |
| SK4132003A3 (en) | 2004-02-03 |
| NO20031517L (no) | 2003-05-28 |
| CA2424540A1 (en) | 2003-04-02 |
| BR0114437A (pt) | 2003-07-01 |
| RU2003112968A (ru) | 2004-09-20 |
| MXPA03002901A (es) | 2003-10-15 |
| HN2001000223A (es) | 2001-10-25 |
| EE200300140A (et) | 2003-08-15 |
| JP2004510757A (ja) | 2004-04-08 |
| EP1328508A2 (de) | 2003-07-23 |
| PL361162A1 (en) | 2004-09-20 |
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