FI81097C - Foerfarande foer framstaellning av nya terapeutiskt verksamma tiazolidindionderivat. - Google Patents
Foerfarande foer framstaellning av nya terapeutiskt verksamma tiazolidindionderivat. Download PDFInfo
- Publication number
- FI81097C FI81097C FI853796A FI853796A FI81097C FI 81097 C FI81097 C FI 81097C FI 853796 A FI853796 A FI 853796A FI 853796 A FI853796 A FI 853796A FI 81097 C FI81097 C FI 81097C
- Authority
- FI
- Finland
- Prior art keywords
- compound
- methyl
- general formula
- oxazolyl
- phenyl
- Prior art date
Links
- 230000001225 therapeutic effect Effects 0.000 title description 3
- 238000012795 verification Methods 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 186
- 150000003839 salts Chemical class 0.000 claims abstract description 42
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000001257 hydrogen Substances 0.000 claims abstract description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 5
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 4
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 3
- 239000001301 oxygen Substances 0.000 claims abstract description 3
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 3
- 229910052717 sulfur Chemical group 0.000 claims abstract description 3
- 125000004434 sulfur atom Chemical group 0.000 claims abstract description 3
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims abstract 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 54
- 238000000034 method Methods 0.000 claims description 41
- 238000002360 preparation method Methods 0.000 claims description 16
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- GUTCYOKMCPFRGH-UHFFFAOYSA-N 5-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O GUTCYOKMCPFRGH-UHFFFAOYSA-N 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- XSODVQRJECSHDL-UHFFFAOYSA-N 5-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC(C=C1)=CC=C1C=C1SC(=O)NC1=O XSODVQRJECSHDL-UHFFFAOYSA-N 0.000 claims description 4
- 239000007795 chemical reaction product Substances 0.000 claims description 3
- 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 3
- 125000002541 furyl group Chemical group 0.000 claims description 3
- 125000004076 pyridyl group Chemical group 0.000 claims description 3
- 125000001544 thienyl group Chemical group 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 1
- YVQKIDLSVHRBGZ-UHFFFAOYSA-N 5-[[4-[2-hydroxy-2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1C(O)COC(C=C1)=CC=C1CC1SC(=O)NC1=O YVQKIDLSVHRBGZ-UHFFFAOYSA-N 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 abstract description 12
- 150000001467 thiazolidinediones Chemical class 0.000 abstract description 9
- 206010012601 diabetes mellitus Diseases 0.000 abstract description 7
- 239000003814 drug Substances 0.000 abstract description 5
- 239000008103 glucose Substances 0.000 abstract description 5
- 229940124597 therapeutic agent Drugs 0.000 abstract description 5
- 201000005577 familial hyperlipidemia Diseases 0.000 abstract description 3
- 125000000623 heterocyclic group Chemical group 0.000 abstract description 3
- 241000124008 Mammalia Species 0.000 abstract description 2
- 125000001183 hydrocarbyl group Chemical group 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 144
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 130
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 109
- 239000000203 mixture Substances 0.000 description 62
- 239000000243 solution Substances 0.000 description 62
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 59
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 58
- 238000006243 chemical reaction Methods 0.000 description 49
- 238000001953 recrystallisation Methods 0.000 description 41
- 239000002904 solvent Substances 0.000 description 40
- -1 cyclohexyl 1-cyclohexenyl Chemical group 0.000 description 37
- 238000000921 elemental analysis Methods 0.000 description 34
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 33
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 28
- 239000013078 crystal Substances 0.000 description 28
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 27
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 25
- 239000000126 substance Substances 0.000 description 24
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 22
- 238000003756 stirring Methods 0.000 description 22
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 20
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 20
- 238000001914 filtration Methods 0.000 description 19
- 238000010992 reflux Methods 0.000 description 17
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 14
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 12
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 12
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 12
- 239000002585 base Substances 0.000 description 11
- 238000001816 cooling Methods 0.000 description 11
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 11
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 11
- 229910000104 sodium hydride Inorganic materials 0.000 description 11
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 10
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 10
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 10
- 239000004615 ingredient Substances 0.000 description 10
- 239000012312 sodium hydride Substances 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 9
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- 238000006722 reduction reaction Methods 0.000 description 9
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 8
- 239000003054 catalyst Substances 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- KDCIHNCMPUBDKT-UHFFFAOYSA-N hexane;propan-2-one Chemical compound CC(C)=O.CCCCCC KDCIHNCMPUBDKT-UHFFFAOYSA-N 0.000 description 8
- 238000006460 hydrolysis reaction Methods 0.000 description 8
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 8
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
- 235000017557 sodium bicarbonate Nutrition 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 230000002218 hypoglycaemic effect Effects 0.000 description 7
- 238000007254 oxidation reaction Methods 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- 230000035484 reaction time Effects 0.000 description 7
- 239000012279 sodium borohydride Substances 0.000 description 7
- 229910000033 sodium borohydride Inorganic materials 0.000 description 7
- 239000007858 starting material Substances 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 6
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 6
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 239000008280 blood Substances 0.000 description 6
- 210000004369 blood Anatomy 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 238000010438 heat treatment Methods 0.000 description 6
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 6
- 230000003647 oxidation Effects 0.000 description 6
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- 239000001632 sodium acetate Substances 0.000 description 6
- 235000017281 sodium acetate Nutrition 0.000 description 6
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 6
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 5
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 5
- 229940123464 Thiazolidinedione Drugs 0.000 description 5
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- 238000007796 conventional method Methods 0.000 description 5
- 238000000354 decomposition reaction Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 230000007062 hydrolysis Effects 0.000 description 5
- 229910052500 inorganic mineral Inorganic materials 0.000 description 5
- 239000011707 mineral Substances 0.000 description 5
- 235000010755 mineral Nutrition 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 4
- RSBWHTQEZHZARK-UHFFFAOYSA-N 2-bromo-1-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethanone Chemical compound BrCC(=O)C1=C(C)OC(C=2C=CC=CC=2)=N1 RSBWHTQEZHZARK-UHFFFAOYSA-N 0.000 description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 4
- 241000699670 Mus sp. Species 0.000 description 4
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 235000011114 ammonium hydroxide Nutrition 0.000 description 4
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 4
- UXTMROKLAAOEQO-UHFFFAOYSA-N chloroform;ethanol Chemical compound CCO.ClC(Cl)Cl UXTMROKLAAOEQO-UHFFFAOYSA-N 0.000 description 4
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 4
- 238000006482 condensation reaction Methods 0.000 description 4
- 229910052802 copper Inorganic materials 0.000 description 4
- 239000010949 copper Substances 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 238000002955 isolation Methods 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 238000002844 melting Methods 0.000 description 4
- 230000008018 melting Effects 0.000 description 4
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 3
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 3
- REGFWZVTTFGQOJ-UHFFFAOYSA-N 4,5-dihydro-1,3-thiazol-2-amine Chemical class NC1=NCCS1 REGFWZVTTFGQOJ-UHFFFAOYSA-N 0.000 description 3
- VCTKYTBWZTZPHF-UHFFFAOYSA-N 4-(chloromethyl)-5-methyl-2-phenyl-1,3-oxazole Chemical compound ClCC1=C(C)OC(C=2C=CC=CC=2)=N1 VCTKYTBWZTZPHF-UHFFFAOYSA-N 0.000 description 3
- 101100132433 Arabidopsis thaliana VIII-1 gene Proteins 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 3
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000001338 aliphatic hydrocarbons Chemical group 0.000 description 3
- 150000001412 amines Chemical class 0.000 description 3
- 125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 238000004587 chromatography analysis Methods 0.000 description 3
- LBJNMUFDOHXDFG-UHFFFAOYSA-N copper;hydrate Chemical compound O.[Cu].[Cu] LBJNMUFDOHXDFG-UHFFFAOYSA-N 0.000 description 3
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 3
- 229910001873 dinitrogen Inorganic materials 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 239000008187 granular material Substances 0.000 description 3
- 230000026030 halogenation Effects 0.000 description 3
- 238000005658 halogenation reaction Methods 0.000 description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 3
- 150000002632 lipids Chemical class 0.000 description 3
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 3
- 150000002828 nitro derivatives Chemical class 0.000 description 3
- 230000001603 reducing effect Effects 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 159000000000 sodium salts Chemical class 0.000 description 3
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 3
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 3
- SUNMBRGCANLOEG-UHFFFAOYSA-N 1,3-dichloroacetone Chemical compound ClCC(=O)CCl SUNMBRGCANLOEG-UHFFFAOYSA-N 0.000 description 2
- ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 description 2
- SSXRWNJPVNCZEH-UHFFFAOYSA-N 2-(4-aminophenoxy)-1-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethanol Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1C(O)COC1=CC=C(N)C=C1 SSXRWNJPVNCZEH-UHFFFAOYSA-N 0.000 description 2
- JYWHQBLLIBQGCU-UHFFFAOYSA-N 2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethanol Chemical compound OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 JYWHQBLLIBQGCU-UHFFFAOYSA-N 0.000 description 2
- GWLQSOUYFNEYTE-UHFFFAOYSA-N 2-amino-5-[[4-[(5-methyl-2-phenyl-1,3-oxazol-4-yl)methoxy]phenyl]methyl]-1,3-thiazol-4-one Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1COC(C=C1)=CC=C1CC1SC(=N)NC1=O GWLQSOUYFNEYTE-UHFFFAOYSA-N 0.000 description 2
- QMUMFAQJNIKPCR-UHFFFAOYSA-N 2-amino-5-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]-1,3-thiazol-4-one Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC(C=C1)=CC=C1CC1SC(N)=NC1=O QMUMFAQJNIKPCR-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 2
- JITCQDSQQJETLN-UHFFFAOYSA-N 4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)-2-oxoethoxy]benzonitrile Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1C(=O)COC1=CC=C(C#N)C=C1 JITCQDSQQJETLN-UHFFFAOYSA-N 0.000 description 2
- IPWZPTYWJHXUHD-UHFFFAOYSA-N 4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]benzaldehyde Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC1=CC=C(C=O)C=C1 IPWZPTYWJHXUHD-UHFFFAOYSA-N 0.000 description 2
- SHVZZBNLABQDQJ-UHFFFAOYSA-N 4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]benzonitrile Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC1=CC=C(C#N)C=C1 SHVZZBNLABQDQJ-UHFFFAOYSA-N 0.000 description 2
- RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 description 2
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- NKOHRVBBQISBSB-UHFFFAOYSA-N 5-[(4-hydroxyphenyl)methyl]-1,3-thiazolidine-2,4-dione Chemical compound C1=CC(O)=CC=C1CC1C(=O)NC(=O)S1 NKOHRVBBQISBSB-UHFFFAOYSA-N 0.000 description 2
- ARHIHDVVUHVQCP-UHFFFAOYSA-N 5-[(4-hydroxyphenyl)methylidene]-1,3-thiazolidine-2,4-dione Chemical compound C1=CC(O)=CC=C1C=C1C(=O)NC(=O)S1 ARHIHDVVUHVQCP-UHFFFAOYSA-N 0.000 description 2
- AIYMQIHPXLABBR-UHFFFAOYSA-N 5-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)-2-oxoethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1C(=O)COC(C=C1)=CC=C1CC1SC(=O)NC1=O AIYMQIHPXLABBR-UHFFFAOYSA-N 0.000 description 2
- IBVBAEAQAFKYMI-UHFFFAOYSA-N 5-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)-2-oxoethoxy]phenyl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1C(=O)COC(C=C1)=CC=C1C=C1SC(=O)NC1=O IBVBAEAQAFKYMI-UHFFFAOYSA-N 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- 239000007868 Raney catalyst Substances 0.000 description 2
- 229910000564 Raney nickel Inorganic materials 0.000 description 2
- 229910045601 alloy Inorganic materials 0.000 description 2
- 239000000956 alloy Substances 0.000 description 2
- 150000004945 aromatic hydrocarbons Chemical group 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- OYPRJOBELJOOCE-RNFDNDRNSA-N calcium-44 Chemical compound [44Ca] OYPRJOBELJOOCE-RNFDNDRNSA-N 0.000 description 2
- 229940084030 carboxymethylcellulose calcium Drugs 0.000 description 2
- 238000010531 catalytic reduction reaction Methods 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 description 2
- 229940117975 chromium trioxide Drugs 0.000 description 2
- WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 2
- GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- BERDEBHAJNAUOM-UHFFFAOYSA-N copper(i) oxide Chemical compound [Cu]O[Cu] BERDEBHAJNAUOM-UHFFFAOYSA-N 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- 230000008025 crystallization Effects 0.000 description 2
- FHHZOYXKOICLGH-UHFFFAOYSA-N dichloromethane;ethanol Chemical compound CCO.ClCCl FHHZOYXKOICLGH-UHFFFAOYSA-N 0.000 description 2
- YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- OHLRLMWUFVDREV-UHFFFAOYSA-N ethyl 4-chloro-3-oxobutanoate Chemical compound CCOC(=O)CC(=O)CCl OHLRLMWUFVDREV-UHFFFAOYSA-N 0.000 description 2
- UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- AWJWCTOOIBYHON-UHFFFAOYSA-N furo[3,4-b]pyrazine-5,7-dione Chemical compound C1=CN=C2C(=O)OC(=O)C2=N1 AWJWCTOOIBYHON-UHFFFAOYSA-N 0.000 description 2
- 150000002430 hydrocarbons Chemical group 0.000 description 2
- 239000003999 initiator Substances 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 2
- FCFAZTVQKDLAOR-UHFFFAOYSA-N n-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)-2-oxoethoxy]phenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1OCC(=O)C1=C(C)OC(C=2C=CC=CC=2)=N1 FCFAZTVQKDLAOR-UHFFFAOYSA-N 0.000 description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 2
- DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 2
- 235000011056 potassium acetate Nutrition 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- XSODVQRJECSHDL-UYRXBGFRSA-N (5z)-5-[[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC(C=C1)=CC=C1\C=C1/SC(=O)NC1=O XSODVQRJECSHDL-UYRXBGFRSA-N 0.000 description 1
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 1
- NMSUUNOVNFUBPW-UHFFFAOYSA-N 1-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethanone Chemical compound O1C(C)=C(C(=O)C)N=C1C1=CC=CC=C1 NMSUUNOVNFUBPW-UHFFFAOYSA-N 0.000 description 1
- ULHFFAFDSSHFDA-UHFFFAOYSA-N 1-amino-2-ethoxybenzene Chemical compound CCOC1=CC=CC=C1N ULHFFAFDSSHFDA-UHFFFAOYSA-N 0.000 description 1
- WFQDTOYDVUWQMS-UHFFFAOYSA-N 1-fluoro-4-nitrobenzene Chemical compound [O-][N+](=O)C1=CC=C(F)C=C1 WFQDTOYDVUWQMS-UHFFFAOYSA-N 0.000 description 1
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 description 1
- 125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 description 1
- MVCMYVMDPKKJSG-UHFFFAOYSA-N 2,5-dimethyl-4-[2-(4-nitrophenoxy)ethyl]-1,3-oxazole Chemical compound O1C(C)=NC(CCOC=2C=CC(=CC=2)[N+]([O-])=O)=C1C MVCMYVMDPKKJSG-UHFFFAOYSA-N 0.000 description 1
- KPEQEVVZYHFYKV-UHFFFAOYSA-N 2-(2,5-dimethyl-1,3-oxazol-4-yl)ethanol Chemical compound CC1=NC(CCO)=C(C)O1 KPEQEVVZYHFYKV-UHFFFAOYSA-N 0.000 description 1
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- OJYWYVRHZKTZSC-UHFFFAOYSA-N 2-(4-aminophenoxy)-1-(2,5-dimethyl-1,3-oxazol-4-yl)ethanol Chemical compound O1C(C)=NC(C(O)COC=2C=CC(N)=CC=2)=C1C OJYWYVRHZKTZSC-UHFFFAOYSA-N 0.000 description 1
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- WWSJZGAPAVMETJ-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-3-ethoxypyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C(=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2)OCC WWSJZGAPAVMETJ-UHFFFAOYSA-N 0.000 description 1
- FYELSNVLZVIGTI-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-5-ethylpyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C=NN(C=1CC)CC(=O)N1CC2=C(CC1)NN=N2 FYELSNVLZVIGTI-UHFFFAOYSA-N 0.000 description 1
- ZRPAUEVGEGEPFQ-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]pyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2 ZRPAUEVGEGEPFQ-UHFFFAOYSA-N 0.000 description 1
- VXZBYIWNGKSFOJ-UHFFFAOYSA-N 2-[4-[5-(2,3-dihydro-1H-inden-2-ylamino)pyrazin-2-yl]pyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC=1N=CC(=NC=1)C=1C=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2 VXZBYIWNGKSFOJ-UHFFFAOYSA-N 0.000 description 1
- YJLUBHOZZTYQIP-UHFFFAOYSA-N 2-[5-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-1,3,4-oxadiazol-2-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C1=NN=C(O1)CC(=O)N1CC2=C(CC1)NN=N2 YJLUBHOZZTYQIP-UHFFFAOYSA-N 0.000 description 1
- RQIDJIKSAUETPW-UHFFFAOYSA-N 2-amino-5-[[4-[2-(2-cyclohexyl-5-methyl-1,3-oxazol-4-yl)-2-hydroxyethoxy]phenyl]methyl]-1,3-thiazol-4-one Chemical compound CC=1OC(C2CCCCC2)=NC=1C(O)COC(C=C1)=CC=C1CC1SC(=N)NC1=O RQIDJIKSAUETPW-UHFFFAOYSA-N 0.000 description 1
- PSQNBDPTWMPLRX-UHFFFAOYSA-N 2-amino-5-[[4-[2-hydroxy-2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]methyl]-1,3-thiazol-4-one Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1C(O)COC(C=C1)=CC=C1CC1SC(N)=NC1=O PSQNBDPTWMPLRX-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- FBOHLCOHXIYDSL-UHFFFAOYSA-N 4-(chloromethyl)-2-(1-methylcyclohexyl)-1,3-oxazole Chemical compound N=1C(CCl)=COC=1C1(C)CCCCC1 FBOHLCOHXIYDSL-UHFFFAOYSA-N 0.000 description 1
- ANSKJZIDWXDAJW-UHFFFAOYSA-N 4-(chloromethyl)-2-phenyl-1,3-oxazole Chemical compound ClCC1=COC(C=2C=CC=CC=2)=N1 ANSKJZIDWXDAJW-UHFFFAOYSA-N 0.000 description 1
- VPIIHGYMVIEXOA-UHFFFAOYSA-N 4-(chloromethyl)-2-propyl-1,3-oxazole Chemical compound CCCC1=NC(CCl)=CO1 VPIIHGYMVIEXOA-UHFFFAOYSA-N 0.000 description 1
- QLDYNJIXNZZDJP-UHFFFAOYSA-N 4-[(5-methyl-2-phenyl-1,3-oxazol-4-yl)methoxy]aniline Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1COC1=CC=C(N)C=C1 QLDYNJIXNZZDJP-UHFFFAOYSA-N 0.000 description 1
- DXCFASBQOCZUGV-UHFFFAOYSA-N 4-[(5-methyl-2-phenyl-1,3-oxazol-4-yl)methoxy]benzaldehyde Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1COC1=CC=C(C=O)C=C1 DXCFASBQOCZUGV-UHFFFAOYSA-N 0.000 description 1
- RUYVHBOOZYPIIP-UHFFFAOYSA-N 4-[2-hydroxy-2-[2-(3-methylphenyl)-1,3-oxazol-4-yl]ethoxy]benzonitrile Chemical compound CC1=CC=CC(C=2OC=C(N=2)C(O)COC=2C=CC(=CC=2)C#N)=C1 RUYVHBOOZYPIIP-UHFFFAOYSA-N 0.000 description 1
- CVNOWLNNPYYEOH-UHFFFAOYSA-N 4-cyanophenol Chemical compound OC1=CC=C(C#N)C=C1 CVNOWLNNPYYEOH-UHFFFAOYSA-N 0.000 description 1
- AEKVBBNGWBBYLL-UHFFFAOYSA-N 4-fluorobenzonitrile Chemical compound FC1=CC=C(C#N)C=C1 AEKVBBNGWBBYLL-UHFFFAOYSA-N 0.000 description 1
- IQSACVLDGFTISB-UHFFFAOYSA-N 5-[[4-[(2-phenyl-1,3-oxazol-4-yl)methoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound S1C(=O)NC(=O)C1CC(C=C1)=CC=C1OCC1=COC(C=2C=CC=CC=2)=N1 IQSACVLDGFTISB-UHFFFAOYSA-N 0.000 description 1
- RREZFAPTUNHCBM-UHFFFAOYSA-N 5-[[4-[(5-methyl-2-phenyl-1,3-oxazol-4-yl)methoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1COC(C=C1)=CC=C1CC1SC(=O)NC1=O RREZFAPTUNHCBM-UHFFFAOYSA-N 0.000 description 1
- QORHQHBXIISUES-UHFFFAOYSA-N 5-[[4-[(5-methyl-2-phenyl-1,3-oxazol-4-yl)methoxy]phenyl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1COC(C=C1)=CC=C1C=C1SC(=O)NC1=O QORHQHBXIISUES-UHFFFAOYSA-N 0.000 description 1
- AIVXGMLGIUUFHH-UHFFFAOYSA-N 5-[[4-[2-(2,5-dimethyl-1,3-oxazol-4-yl)-2-hydroxyethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound O1C(C)=NC(C(O)COC=2C=CC(CC3C(NC(=O)S3)=O)=CC=2)=C1C AIVXGMLGIUUFHH-UHFFFAOYSA-N 0.000 description 1
- IXPYYRJTCQCPAL-UHFFFAOYSA-N 5-[[4-[2-(2,5-dimethyl-1,3-oxazol-4-yl)-2-oxoethoxy]phenyl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound O1C(C)=NC(C(=O)COC=2C=CC(C=C3C(NC(=O)S3)=O)=CC=2)=C1C IXPYYRJTCQCPAL-UHFFFAOYSA-N 0.000 description 1
- OIZFSJBBHJMUGN-UHFFFAOYSA-N 5-[[4-[2-[5-(bromomethyl)-2-phenyl-1,3-oxazol-4-yl]ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound BrCC=1OC(C=2C=CC=CC=2)=NC=1CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O OIZFSJBBHJMUGN-UHFFFAOYSA-N 0.000 description 1
- AAZZLIFIDFGXRS-UHFFFAOYSA-N 5-[[4-[[2-(1-methylcyclohexyl)-1,3-oxazol-4-yl]methoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound N=1C(COC=2C=CC(CC3C(NC(=O)S3)=O)=CC=2)=COC=1C1(C)CCCCC1 AAZZLIFIDFGXRS-UHFFFAOYSA-N 0.000 description 1
- SGIZECXZFLAGBW-UHFFFAOYSA-N 5-benzylidene-1,3-thiazolidine-2,4-dione Chemical compound S1C(=O)NC(=O)C1=CC1=CC=CC=C1 SGIZECXZFLAGBW-UHFFFAOYSA-N 0.000 description 1
- QRNNZSBHANAFPS-UHFFFAOYSA-N 5-methyl-4-[2-(4-nitrophenoxy)ethyl]-2-(4-phenylmethoxyphenyl)-1,3-oxazole Chemical compound CC=1OC(C=2C=CC(OCC=3C=CC=CC=3)=CC=2)=NC=1CCOC1=CC=C([N+]([O-])=O)C=C1 QRNNZSBHANAFPS-UHFFFAOYSA-N 0.000 description 1
- WKPPRZSPZCFKOL-UHFFFAOYSA-N 5-methyl-4-[2-(4-nitrophenoxy)ethyl]-2-phenyl-1,3-oxazole Chemical compound CC=1OC(C=2C=CC=CC=2)=NC=1CCOC1=CC=C([N+]([O-])=O)C=C1 WKPPRZSPZCFKOL-UHFFFAOYSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- 241001135931 Anolis Species 0.000 description 1
- 239000004342 Benzoyl peroxide Substances 0.000 description 1
- OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
- XNCOSPRUTUOJCJ-UHFFFAOYSA-N Biguanide Chemical compound NC(N)=NC(N)=N XNCOSPRUTUOJCJ-UHFFFAOYSA-N 0.000 description 1
- 229940123208 Biguanide Drugs 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 101150065749 Churc1 gene Proteins 0.000 description 1
- 241000725101 Clea Species 0.000 description 1
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 1
- 241000283073 Equus caballus Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 239000004366 Glucose oxidase Substances 0.000 description 1
- 108010015776 Glucose oxidase Proteins 0.000 description 1
- 241000282414 Homo sapiens Species 0.000 description 1
- 208000013016 Hypoglycemia Diseases 0.000 description 1
- 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 1
- 239000003810 Jones reagent Substances 0.000 description 1
- 238000006458 Meerwein arylation reaction Methods 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 102100038239 Protein Churchill Human genes 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 101100137598 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) PRM6 gene Proteins 0.000 description 1
- 229940100389 Sulfonylurea Drugs 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- DSHGXKLQVRINHX-UHFFFAOYSA-N [O-2].[O-2].[O-2].[Cr+6].CC(C)=O.OS(O)(=O)=O Chemical compound [O-2].[O-2].[O-2].[Cr+6].CC(C)=O.OS(O)(=O)=O DSHGXKLQVRINHX-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000002723 alicyclic group Chemical group 0.000 description 1
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 150000003931 anilides Chemical class 0.000 description 1
- 230000003178 anti-diabetic effect Effects 0.000 description 1
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- TXHIDIHEXDFONW-UHFFFAOYSA-N benzene;propan-2-one Chemical compound CC(C)=O.C1=CC=CC=C1 TXHIDIHEXDFONW-UHFFFAOYSA-N 0.000 description 1
- 235000019400 benzoyl peroxide Nutrition 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 150000004283 biguanides Chemical class 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- DNSISZSEWVHGLH-UHFFFAOYSA-N butanamide Chemical compound CCCC(N)=O DNSISZSEWVHGLH-UHFFFAOYSA-N 0.000 description 1
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- OQNGCCWBHLEQFN-UHFFFAOYSA-N chloroform;hexane Chemical compound ClC(Cl)Cl.CCCCCC OQNGCCWBHLEQFN-UHFFFAOYSA-N 0.000 description 1
- JOPOVCBBYLSVDA-UHFFFAOYSA-N chromium(6+) Chemical compound [Cr+6] JOPOVCBBYLSVDA-UHFFFAOYSA-N 0.000 description 1
- VTHIKKVKIVQWHV-UHFFFAOYSA-N chromium(6+) oxygen(2-) pyridine Chemical compound [O-2].[O-2].[O-2].[Cr+6].C1=CC=NC=C1 VTHIKKVKIVQWHV-UHFFFAOYSA-N 0.000 description 1
- YZFWTZACSRHJQD-UHFFFAOYSA-N ciglitazone Chemical compound C=1C=C(CC2C(NC(=O)S2)=O)C=CC=1OCC1(C)CCCCC1 YZFWTZACSRHJQD-UHFFFAOYSA-N 0.000 description 1
- 229950009226 ciglitazone Drugs 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 1
- JMMKXVYQBRGGJF-UHFFFAOYSA-N cyclohexanecarbothioamide Chemical compound NC(=S)C1CCCCC1 JMMKXVYQBRGGJF-UHFFFAOYSA-N 0.000 description 1
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 238000006193 diazotization reaction Methods 0.000 description 1
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- MDKXBBPLEGPIRI-UHFFFAOYSA-N ethoxyethane;methanol Chemical compound OC.CCOCC MDKXBBPLEGPIRI-UHFFFAOYSA-N 0.000 description 1
- YPUXRZZXYYYTNZ-UHFFFAOYSA-N ethyl 2-(2-cyclohexyl-1,3-thiazol-4-yl)acetate Chemical compound CCOC(=O)CC1=CSC(C2CCCCC2)=N1 YPUXRZZXYYYTNZ-UHFFFAOYSA-N 0.000 description 1
- WDASBQYNHGLIKJ-UHFFFAOYSA-N ethyl 2-(2-phenyl-1,3-oxazol-4-yl)acetate Chemical compound CCOC(=O)CC1=COC(C=2C=CC=CC=2)=N1 WDASBQYNHGLIKJ-UHFFFAOYSA-N 0.000 description 1
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 229940116332 glucose oxidase Drugs 0.000 description 1
- 235000019420 glucose oxidase Nutrition 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 239000012433 hydrogen halide Substances 0.000 description 1
- 229910000039 hydrogen halide Inorganic materials 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 208000006443 lactic acidosis Diseases 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
- UDWQWRFEUXUBHR-UHFFFAOYSA-N methyl 2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)acetate Chemical compound O1C(C)=C(CC(=O)OC)N=C1C1=CC=CC=C1 UDWQWRFEUXUBHR-UHFFFAOYSA-N 0.000 description 1
- IKSGKNUQXAHKQT-UHFFFAOYSA-N methyl 2-bromo-3-[4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]propanoate Chemical compound C1=CC(CC(Br)C(=O)OC)=CC=C1OCCC1=C(C)OC(C=2C=CC=CC=2)=N1 IKSGKNUQXAHKQT-UHFFFAOYSA-N 0.000 description 1
- WKQUARCAWWQJCN-UHFFFAOYSA-N methyl 2-bromo-3-[4-[2-hydroxy-2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl]propanoate Chemical compound C1=CC(CC(Br)C(=O)OC)=CC=C1OCC(O)C1=C(C)OC(C=2C=CC=CC=2)=N1 WKQUARCAWWQJCN-UHFFFAOYSA-N 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- WHQSYGRFZMUQGQ-UHFFFAOYSA-N n,n-dimethylformamide;hydrate Chemical compound O.CN(C)C=O WHQSYGRFZMUQGQ-UHFFFAOYSA-N 0.000 description 1
- ZFXVPJOOBTUVCB-UHFFFAOYSA-N n-[4-[2-(2,5-dimethyl-1,3-oxazol-4-yl)-2-oxoethoxy]phenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1OCC(=O)C1=C(C)OC(C)=N1 ZFXVPJOOBTUVCB-UHFFFAOYSA-N 0.000 description 1
- UUUZDXCXUWXGHJ-UHFFFAOYSA-N n-[4-[2-(2-cyclohexyl-5-methyl-1,3-oxazol-4-yl)-2-oxoethoxy]phenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1OCC(=O)C1=C(C)OC(C2CCCCC2)=N1 UUUZDXCXUWXGHJ-UHFFFAOYSA-N 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 125000003884 phenylalkyl group Chemical group 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000010453 quartz Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- VYPDUQYOLCLEGS-UHFFFAOYSA-M sodium;2-ethylhexanoate Chemical compound [Na+].CCCCC(CC)C([O-])=O VYPDUQYOLCLEGS-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- YROXIXLRRCOBKF-UHFFFAOYSA-N sulfonylurea Chemical class OC(=N)N=S(=O)=O YROXIXLRRCOBKF-UHFFFAOYSA-N 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
-
- 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
- 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
-
- 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
-
- 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
- C07D277/30—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- 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
- C07D277/32—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 hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/34—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
-
- 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
- C07D417/14—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 three or more hetero rings
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Liquid Developers In Electrophotography (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Saccharide Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/JP1984/000466 WO1986002073A1 (fr) | 1984-10-03 | 1984-10-03 | Derives de thiazolidinedione, procede de preparation et composition pharmaceutique les contenant |
| JP8400466 | 1984-10-03 | ||
| PCT/JP1985/000179 WO1986006069A1 (fr) | 1985-04-09 | 1985-04-09 | Derives de thiazolidinedione, leur procede de preparation et composition medicinale les contenant |
| JP8500179 | 1985-04-09 |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| FI853796A0 FI853796A0 (fi) | 1985-10-01 |
| FI853796L FI853796L (fi) | 1986-04-04 |
| FI81097B FI81097B (fi) | 1990-05-31 |
| FI81097C true FI81097C (fi) | 1990-09-10 |
Family
ID=26425066
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI853796A FI81097C (fi) | 1984-10-03 | 1985-10-01 | Foerfarande foer framstaellning av nya terapeutiskt verksamma tiazolidindionderivat. |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US4725610A (OSRAM) |
| EP (1) | EP0177353B1 (OSRAM) |
| JP (1) | JPS6185372A (OSRAM) |
| KR (1) | KR920002131B1 (OSRAM) |
| CN (1) | CN1003445B (OSRAM) |
| AT (1) | ATE51869T1 (OSRAM) |
| AU (1) | AU583537B2 (OSRAM) |
| CA (1) | CA1263655A (OSRAM) |
| DE (1) | DE3577092D1 (OSRAM) |
| DK (1) | DK444685A (OSRAM) |
| ES (2) | ES8706150A1 (OSRAM) |
| FI (1) | FI81097C (OSRAM) |
| GR (1) | GR852389B (OSRAM) |
| NO (1) | NO157896C (OSRAM) |
| PT (1) | PT81235B (OSRAM) |
Families Citing this family (126)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR240698A1 (es) * | 1985-01-19 | 1990-09-28 | Takeda Chemical Industries Ltd | Procedimiento para preparar compuestos de 5-(4-(2-(5-etil-2-piridil)-etoxi)benzil)-2,4-tiazolidindiona y sus sales |
| JPH06779B2 (ja) * | 1985-06-10 | 1994-01-05 | 武田薬品工業株式会社 | チアゾリジオン誘導体およびそれを含んでなる医薬組成物 |
| GB8528633D0 (en) * | 1985-11-21 | 1985-12-24 | Beecham Group Plc | Compounds |
| US4812570A (en) * | 1986-07-24 | 1989-03-14 | Takeda Chemical Industries, Ltd. | Method for producing thiazolidinedione derivatives |
| US4873255A (en) * | 1987-02-04 | 1989-10-10 | Sankyo Company Limited | Thiazolidinone derivatives, their preparation and their use |
| JPS63230689A (ja) * | 1987-03-18 | 1988-09-27 | Tanabe Seiyaku Co Ltd | ベンゾオキサジン誘導体 |
| FI91869C (fi) * | 1987-03-18 | 1994-08-25 | Tanabe Seiyaku Co | Menetelmä antidiabeettisena aineena käytettävien bensoksatsolijohdannaisten valmistamiseksi |
| GB8713861D0 (en) * | 1987-06-13 | 1987-07-15 | Beecham Group Plc | Compounds |
| EP0295828A1 (en) * | 1987-06-13 | 1988-12-21 | Beecham Group Plc | Novel compounds |
| US5260445A (en) * | 1987-09-04 | 1993-11-09 | Beecham Group P.L.C. | 2,4-thiazolidinediones |
| US5223522A (en) * | 1988-03-08 | 1993-06-29 | Pfizer Inc. | Thiazolidinedione hypoglycemic agents |
| MX15171A (es) * | 1988-03-08 | 1993-05-01 | Pfizer | Derivados de tiazolidinodiona hipoglicemicos |
| WO1989008652A1 (en) * | 1988-03-08 | 1989-09-21 | Pfizer Inc. | Thiazolidinedione derivatives as hypoglycemic agents |
| US5120754A (en) * | 1988-03-08 | 1992-06-09 | Pfizer Inc. | Thiazolidinedione hypoglycemic agents |
| US5130379A (en) * | 1988-03-08 | 1992-07-14 | Pfizer Inc. | Hypoglycemic thiazolidinedione derivatives |
| FI904414A0 (fi) * | 1988-03-08 | 1990-09-07 | Pfizer | Tiazolidindion-hypoglykemiskt verkande aemnen. |
| US5330998A (en) * | 1988-03-08 | 1994-07-19 | Pfizer Inc. | Thiazolidinedione derivatives as hypoglycemic agents |
| GB8910639D0 (en) * | 1989-05-09 | 1989-06-21 | Beecham Group Plc | Novel compounds |
| GB8919417D0 (en) | 1989-08-25 | 1989-10-11 | Beecham Group Plc | Novel compounds |
| US5053420A (en) * | 1989-10-13 | 1991-10-01 | Pershadsingh Harrihar A | Thiazolidine derivatives for the treatment of hypertension |
| WO1991007107A1 (en) * | 1989-11-13 | 1991-05-30 | Pfizer Inc. | Oxazolidinedione hypoglycemic agents |
| US5036079A (en) * | 1989-12-07 | 1991-07-30 | Pfizer Inc. | Hypoglycemic thiazolidinedione derivatives |
| EP0454501B1 (en) * | 1990-04-27 | 2001-09-05 | Sankyo Company Limited | Benzylidenethiazolidine derivatives, their preparation and their use for the inhibition of lipid peroxides |
| US5037842A (en) * | 1990-06-05 | 1991-08-06 | Pfizer Inc. | Oxa- and thiazolidinedione hypoglycemic and hypocholesterolemic agents |
| US5089514A (en) * | 1990-06-14 | 1992-02-18 | Pfizer Inc. | 3-coxazolyl [phenyl, chromanyl or benzofuranyl]-2-hydroxypropionic acid derivatives and analogs as hypoglycemic agents |
| EP0544696B1 (en) * | 1990-08-23 | 1995-01-11 | Pfizer Inc. | Hypoglycemic hydroxyurea derivatives |
| GB9023584D0 (en) * | 1990-10-30 | 1990-12-12 | Beecham Group Plc | Novel compounds |
| JPH04210683A (ja) * | 1990-12-06 | 1992-07-31 | Terumo Corp | チアゾリジン−２，４−ジオン誘導体およびこれを含有する糖尿病合併症治療薬 |
| TW222626B (OSRAM) | 1991-07-22 | 1994-04-21 | Pfizer | |
| US5498621A (en) * | 1992-05-01 | 1996-03-12 | Pfizer Inc. | Oxazolidinedione hypoglycemic agents |
| US5236941A (en) * | 1992-06-30 | 1993-08-17 | American Home Products Corporation | 5-(2-hydroxy-1-arylethylidene)- and 5-(2-oxo-1-arylethylidene)-2,4-thiazolidinediones and derivatives thereof |
| WO1994001433A1 (fr) * | 1992-07-13 | 1994-01-20 | Japan Tobacco Inc. | Nouveau compose de thiazolidinedione et son utilisation |
| TW245716B (OSRAM) * | 1992-12-28 | 1995-04-21 | Takeda Pharm Industry Co | |
| DE4317320A1 (de) * | 1993-05-25 | 1994-12-01 | Boehringer Mannheim Gmbh | Neue Thiazolidindione und diese enthaltende Arzneimittel |
| US5591862A (en) * | 1993-06-11 | 1997-01-07 | Takeda Chemical Industries, Ltd. | Tetrazole derivatives, their production and use |
| USRE39384E1 (en) | 1993-09-01 | 2006-11-07 | Smithkline Beecham P.L.C. | Substituted thiazolidinedione derivatives |
| US5478852C1 (en) * | 1993-09-15 | 2001-03-13 | Sankyo Co | Use of thiazolidinedione derivatives and related antihyperglycemic agents in the treatment of impaired glucose tolerance in order to prevent or delay the onset of noninsulin-dependent diabetes mellitus |
| US6046222A (en) * | 1993-09-15 | 2000-04-04 | Warner-Lambert Company | Use of thiazolidinedione derivatives in the treatment of polycystic ovary syndrome, gestational diabetes and disease states at risk for progressing to noninsulin-dependent diabetes mellitus |
| US5401761A (en) * | 1993-12-09 | 1995-03-28 | Pfizer, Inc. | Thiazolidinedione hypoglycemic agents |
| US5728720A (en) * | 1993-12-27 | 1998-03-17 | Japan Tobacco Inc. | Isoxazolidinedione compounds and use thereof |
| CA2146701A1 (en) * | 1994-04-11 | 1995-10-12 | Takashi Fujita | Heterocyclic compounds having anti-diabetic activity, their preparation and their use |
| US5468762A (en) * | 1994-05-18 | 1995-11-21 | American Home Products Corporation | Azolidinediones as antihyperglycemic agents |
| US5532256A (en) * | 1994-05-18 | 1996-07-02 | American Home Products Corporation | New azolidinediones and thiadiazolidinediones as antihyperglycemic agents |
| US5594015A (en) * | 1994-06-22 | 1997-01-14 | Regents Of The University Of California | Thiazolidine derivatives for the treatment of psoriasis |
| WO1996005186A1 (en) * | 1994-08-10 | 1996-02-22 | Takeda Chemical Industries, Ltd. | Thiazolidinedione derivatives, their production and use |
| JPH08157473A (ja) * | 1994-10-06 | 1996-06-18 | Nissan Chem Ind Ltd | ピラゾール系チアゾリジン類 |
| CZ261095A3 (en) * | 1994-10-07 | 1996-04-17 | Sankyo Co | Oxime derivatives, process of their preparation, pharmaceutical composition containing thereof and their use |
| US5641796A (en) * | 1994-11-01 | 1997-06-24 | Eli Lilly And Company | Oral hypoglycemic agents |
| TW403748B (en) * | 1994-11-02 | 2000-09-01 | Takeda Chemical Industries Ltd | An oxazolidinedione derivative, its production and a pharmaceutical composition for lowering blood sugar and lipid in blood comprising the same |
| US5925656A (en) * | 1995-04-10 | 1999-07-20 | Dr. Reddy's Research Foundation | Compounds having antidiabetic, hypolipidemic, antihypertensive properties, process for their preparation and pharmaceutical compositions containing them |
| US5708012A (en) * | 1995-04-28 | 1998-01-13 | Sankyo Company, Limited | Use of thiazolidinedione derivatives and related antihyperglycemic agents in the treatment of insulin resistant subjects with normal glucose tolerance in order to prevent or delay the onset of noninsulin-dependent mellitus |
| CZ293016B6 (cs) * | 1995-06-01 | 2004-01-14 | Sankyo Company Limited | Benzimidazolové deriváty a farmaceutické prostředky s jejich obsahem |
| TW474809B (en) * | 1995-07-03 | 2002-02-01 | Sankyo Co | A pharmaceutical composition for arteriosclerosis or xanthoma consisting of HMG-CoA reductase inhibitors and insulin sensitizers |
| NZ314406A (en) * | 1996-03-18 | 2000-12-22 | Sankyo Co | Treatment or prophylaxis of pancreatitis with a medicament containing an insulin sensitiser including oxazoles and thiazoles |
| US6294559B1 (en) | 1996-05-02 | 2001-09-25 | Merck & Co., Inc. | Antiproliferative agents associated with peroxisome proliferator activated receptors gamma1 and gamma2 |
| US5801173A (en) * | 1996-05-06 | 1998-09-01 | Dr. Reddy's Research Foundation | Heterocyclic compounds having antidiabetic, hypolipidaemic, antihypertensive properties, process for their preparation and pharmaceutical compositions containing them |
| US5889032A (en) * | 1996-05-06 | 1999-03-30 | Dr. Reddy's Research Foundation | Heterocyclic compounds having antidiabetic, hypolipidaemic, antihypertensive properties, process for their preparation and pharmaceutical compositions containing them |
| US5919782A (en) * | 1996-05-06 | 1999-07-06 | Dr. Reddy's Research Foundation | Heterocyclic compounds having antidiabetic, hypolipidaemic, antihypertensive properties, process for their preparation and pharmaceutical compositions containing them |
| US5889025A (en) * | 1996-05-06 | 1999-03-30 | Reddy's Research Foundation | Antidiabetic compounds having hypolipidaemic, antihypertensive properties, process for their preparation and pharmaceutical compositions containing them |
| CA2257284C (en) * | 1996-05-31 | 2005-10-04 | Sankyo Company Limited | Remedy for autoimmune diseases |
| US6372750B2 (en) * | 1996-07-01 | 2002-04-16 | Dr. Reddy's Research Foundation | Heterocyclic compounds, process for their preparation and pharmaceutical compounds containing them and their use in the treatment of diabetes and related diseases |
| USRE39266E1 (en) * | 1996-07-01 | 2006-09-05 | Dr. Reddy's Laboratories, Limited | Heterocyclic compounds, process for their preparation and pharmaceutical compositions containing them and their use in the treatment of diabetes and related diseases |
| US5985884A (en) | 1996-07-01 | 1999-11-16 | Dr. Reddy's Research Foundation | Heterocyclic compounds, process for their preparation and pharmaceutical compositions containing them and their use in the treatment of diabetes and related diseases |
| US5885997A (en) * | 1996-07-01 | 1999-03-23 | Dr. Reddy's Research Foundation | Heterocyclic compounds, process for their preparation and pharmaceutical compositions containing them and their use in the treatment of diabetes and related diseases |
| US6114526A (en) * | 1996-07-01 | 2000-09-05 | Dr. Reddy's Research Foundation | Heterocyclic compounds, process for their preparation and pharmaceutical compositions containing them and their use in the treatment of diabetes and related diseases |
| IL128600A0 (en) | 1996-08-19 | 2000-01-31 | Japan Tobacco Inc | Propionic acid derivatives and pharmaceutical compositions containing them |
| US7235627B2 (en) * | 1996-08-30 | 2007-06-26 | Novo Nordisk A/S | Derivatives of GLP-1 analogs |
| UY24886A1 (es) * | 1997-02-18 | 2001-08-27 | Smithkline Beecham Plc | Tiazolidindiona |
| DE69838789T2 (de) * | 1997-03-12 | 2008-10-30 | Suzanne Cambridge de la Monte | Verfahren zur behandlung oder prävention der alzheimerischen krankheit |
| DE19711616A1 (de) | 1997-03-20 | 1998-09-24 | Boehringer Mannheim Gmbh | Verbessertes Verfahren zur Herstellung von Thiazolidindionen |
| IL133142A0 (en) * | 1997-06-18 | 2001-03-19 | Smithkline Beecham Plc | Treatment of diabetes with thiazolidinedione and metformin |
| CA2294385C (en) | 1997-06-18 | 2007-06-05 | Smithkline Beecham P.L.C. | Treatment of diabetes with thiazolidinedione and sulphonylurea |
| GB9715306D0 (en) * | 1997-07-18 | 1997-09-24 | Smithkline Beecham Plc | Novel method of treatment |
| GB9715295D0 (en) * | 1997-07-18 | 1997-09-24 | Smithkline Beecham Plc | Novel method of treatment |
| US5908859A (en) * | 1997-08-11 | 1999-06-01 | Eli Lilly And Company | Benzothiophenes for inhibiting hyperlipidemia |
| DE19738942A1 (de) | 1997-09-05 | 1999-03-25 | Pulsion Verwaltungs Gmbh & Co | Verfahren und Vorrichtung zur Injektionszeitpunkt- und Injektionsdauerbestimmung bei Thermodilutionsmessungen |
| GB9723295D0 (en) * | 1997-11-04 | 1998-01-07 | Smithkline Beecham Plc | Novel process |
| US7091359B2 (en) * | 1997-11-04 | 2006-08-15 | Smithkline Beecham Plc | Process for the preparation of thiazolidinedione derivatives |
| HUP9902721A2 (hu) | 1997-11-25 | 1999-12-28 | The Procter & Gamble Co. | Tömény textillágyító készítmény és ehhez alkalmazható magas telítetlenségű textillágyító vegyület |
| US20040058873A1 (en) * | 1998-03-12 | 2004-03-25 | Esmond Robert W. | Method for treating or preventing Alzheimer's disease |
| BR9906312A (pt) | 1998-03-30 | 2000-07-11 | Japan Tobacco Inc | Método de produção de composto de isoxazolidinadiona |
| EP1992337A1 (en) | 1998-11-12 | 2008-11-19 | Smithkline Beecham Plc | Novel modified release composition and use |
| AR023700A1 (es) | 1998-11-12 | 2002-09-04 | Smithkline Beecham Plc | Un procedimiento para preparar una composicion farmaceutica que comprende un sensibilizador de insulina |
| GB9824893D0 (en) * | 1998-11-12 | 1999-01-06 | Smithkline Beckman Corp | Novel method of treatment |
| WO2000030628A2 (en) * | 1998-11-20 | 2000-06-02 | Genentech, Inc. | Method of inhibiting angiogenesis |
| US6191154B1 (en) | 1998-11-27 | 2001-02-20 | Case Western Reserve University | Compositions and methods for the treatment of Alzheimer's disease, central nervous system injury, and inflammatory diseases |
| US6756360B1 (en) | 1998-12-24 | 2004-06-29 | Metabasis Therapeutics, Inc. | Combination of FBPase inhibitors and insulin sensitizers for the treatment of diabetes |
| JP2001072592A (ja) | 1999-07-01 | 2001-03-21 | Kyowa Hakko Kogyo Co Ltd | テロメラーゼ阻害剤 |
| ID29875A (id) * | 1999-07-01 | 2001-10-18 | Geron Corp Cs | Penghambat-penghambat telomerase dan metode penggunaannya |
| US6531609B2 (en) | 2000-04-14 | 2003-03-11 | Hoffmann-La Roche Inc. | Process for the preparation of thiazolidinedione derivatives |
| US6958355B2 (en) * | 2000-04-24 | 2005-10-25 | Aryx Therapeutics, Inc. | Materials and methods for the treatment of diabetes, hyperlipidemia, hypercholesterolemia, and atherosclerosis |
| US6680387B2 (en) * | 2000-04-24 | 2004-01-20 | Aryx Therapeutics | Materials and methods for the treatment of diabetes, hyperlipidemia, hypercholesterolemia, and atherosclerosis |
| BR0110258A (pt) * | 2000-04-25 | 2003-01-07 | Kyorin Seiyaku Kk | Cristal estável de derivado de tiazolidinadiona e processo para sua produção |
| DE10029077A1 (de) * | 2000-06-13 | 2001-12-20 | Bayer Ag | Thiazolylsubstituierte Heterocyclen |
| GB0014969D0 (en) | 2000-06-19 | 2000-08-09 | Smithkline Beecham Plc | Novel method of treatment |
| US7563774B2 (en) | 2000-06-29 | 2009-07-21 | Metabasis Therapeutics, Inc. | Combination of FBPase inhibitors and antidiabetic agents useful for the treatment of diabetes |
| AU2001294673A1 (en) * | 2000-09-21 | 2002-04-02 | Aryx Therapeutics | Isoxazolidine compounds useful in the treatment of diabetes, hyperlipidemia, andatherosclerosis |
| US6452014B1 (en) | 2000-12-22 | 2002-09-17 | Geron Corporation | Telomerase inhibitors and methods of their use |
| DE10118310A1 (de) * | 2001-04-12 | 2002-10-17 | Bayer Ag | Hetarylsubstituierte carbocyclische 1,3-Dione |
| US20060047000A1 (en) * | 2001-04-24 | 2006-03-02 | Aryx Therapeutics, Inc. | Materials and methods for the treatment of diabetes, hyperlipidemia, hypercholesterolemia, and atherosclerosis |
| US20030092736A1 (en) * | 2001-05-30 | 2003-05-15 | Cheng Peter T. | Substituted azole acid derivatives useful as antidiabetic and antiobesity agents and method |
| JP2003040877A (ja) * | 2001-07-24 | 2003-02-13 | Sumika Fine Chemicals Co Ltd | ５−［６−（２−フルオロベンジルオキシ）−２−ナフチル］メチル−２，４−チアゾリジンジオンの製造方法及びその精製方法 |
| KR100450700B1 (ko) * | 2002-03-22 | 2004-10-01 | 주식회사종근당 | 티아졸리딘디온 유도체 화합물 및 이를 함유하는 약제학적조성물 |
| US8216609B2 (en) * | 2002-08-05 | 2012-07-10 | Torrent Pharmaceuticals Limited | Modified release composition of highly soluble drugs |
| US8268352B2 (en) * | 2002-08-05 | 2012-09-18 | Torrent Pharmaceuticals Limited | Modified release composition for highly soluble drugs |
| DE10331675A1 (de) | 2003-07-14 | 2005-02-10 | Bayer Cropscience Ag | Hetarylsubstituierte Pyrazolidindion-Derivate |
| US7833513B2 (en) | 2004-12-03 | 2010-11-16 | Rhode Island Hospital | Treatment of Alzheimer's Disease |
| PL2001469T3 (pl) * | 2006-03-16 | 2012-10-31 | Metabolic Solutions Dev Co Llc | Analogi tiazolidynodionu |
| EP2001468B1 (en) | 2006-03-16 | 2012-10-31 | Metabolic Solutions Development Company LLC | Thiazolidinedione analogues |
| EP2001470A2 (en) * | 2006-03-16 | 2008-12-17 | Metabolic Solutions Development Company | Combination therapies of thiazolidinedione analogues |
| US20080009534A1 (en) * | 2006-07-07 | 2008-01-10 | Bristol-Myers Squibb Company | Substituted acid derivatives useful as antidiabetic and antiobesity agents and method |
| US11241420B2 (en) | 2007-04-11 | 2022-02-08 | Omeros Corporation | Compositions and methods for prophylaxis and treatment of addictions |
| RU2492858C2 (ru) | 2007-04-11 | 2013-09-20 | Омерос Корпорейшн | Композиции и способы профилактики и лечения зависимостей |
| US20160331729A9 (en) * | 2007-04-11 | 2016-11-17 | Omeros Corporation | Compositions and methods for prophylaxis and treatment of addictions |
| US8304441B2 (en) | 2007-09-14 | 2012-11-06 | Metabolic Solutions Development Company, Llc | Thiazolidinedione analogues for the treatment of metabolic diseases |
| BRPI0817096B8 (pt) | 2007-09-14 | 2021-05-25 | Cirius Therapeutics Inc | análogo de tiazolidinodiona e composição farmacêutica que o compreende |
| MX2011009384A (es) | 2009-03-11 | 2011-10-11 | Omeros Corp | Composiciones y metodos para profilaxis y tratamiento de adicciones. |
| KR20120107493A (ko) | 2009-12-15 | 2012-10-02 | 메타볼릭 솔루션스 디벨롭먼트 컴퍼니, 엘엘씨 | 대사성 질환의 치료를 위한 ｐｐａｒ 절약형 티아졸리딘디온염 |
| AR079451A1 (es) | 2009-12-18 | 2012-01-25 | Nycomed Gmbh | Compuestos 3,4,4a,10b-tetrahidro-1h-tiopirano[4,3-c]isoquinolina |
| WO2011091134A2 (en) | 2010-01-22 | 2011-07-28 | Dana-Farber Cancer Institute, Inc. | Compositions,kits, and methods for identification, assessment, prevention, and therapy of metabolic disorders |
| US8937182B2 (en) | 2010-04-19 | 2015-01-20 | Metabolic Solutions Development Company, Llc | Synthesis for thiazolidinedione compounds |
| JP5927190B2 (ja) | 2010-08-10 | 2016-06-01 | メタボリック ソリューションズ ディベロップメント カンパニー， エルエルシー | チアゾリジンジオン化合物のための新規合成 |
| CA2807815C (en) | 2010-08-10 | 2018-10-02 | Metabolic Solutions Development Company, Llc | Novel synthesis for thiazolidinedione compounds |
| US20120094959A1 (en) | 2010-10-19 | 2012-04-19 | Bonnie Blazer-Yost | Treatment of cystic diseases |
| ES2668310T3 (es) | 2012-11-05 | 2018-05-17 | Commissariat à l'énergie atomique et aux énergies alternatives | Combinación de un agente anticanceroso tal como un inhibidor de la tirosina cinasa y un antagonista STAT5, preferiblemente una tiazolidindiona, para eliminar las células madre de cáncer hematológico in vivo y para prevenir la recidiva de cáncer hematológico |
| WO2016071727A1 (en) | 2014-11-04 | 2016-05-12 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for the prevention and the treatment of rapidly progressive glomerulonephritis |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5522636A (en) * | 1978-08-04 | 1980-02-18 | Takeda Chem Ind Ltd | Thiazoliding derivative |
| JPS58118577A (ja) * | 1982-01-07 | 1983-07-14 | Takeda Chem Ind Ltd | チアゾリジン誘導体 |
| JPS6051189A (ja) * | 1983-08-30 | 1985-03-22 | Sankyo Co Ltd | チアゾリジン誘導体およびその製造法 |
| AR240698A1 (es) * | 1985-01-19 | 1990-09-28 | Takeda Chemical Industries Ltd | Procedimiento para preparar compuestos de 5-(4-(2-(5-etil-2-piridil)-etoxi)benzil)-2,4-tiazolidindiona y sus sales |
-
1985
- 1985-09-26 CN CN85107870.2A patent/CN1003445B/zh not_active Expired
- 1985-09-27 KR KR1019850007158A patent/KR920002131B1/ko not_active Expired
- 1985-09-27 JP JP60216050A patent/JPS6185372A/ja active Granted
- 1985-10-01 FI FI853796A patent/FI81097C/fi not_active IP Right Cessation
- 1985-10-01 AU AU48176/85A patent/AU583537B2/en not_active Ceased
- 1985-10-01 DK DK444685A patent/DK444685A/da unknown
- 1985-10-02 PT PT81235A patent/PT81235B/pt not_active IP Right Cessation
- 1985-10-02 GR GR852389A patent/GR852389B/el unknown
- 1985-10-02 ES ES547507A patent/ES8706150A1/es not_active Expired
- 1985-10-02 CA CA000492072A patent/CA1263655A/en not_active Expired
- 1985-10-02 NO NO853902A patent/NO157896C/no unknown
- 1985-10-03 AT AT85307084T patent/ATE51869T1/de not_active IP Right Cessation
- 1985-10-03 DE DE8585307084T patent/DE3577092D1/de not_active Expired - Fee Related
- 1985-10-03 US US06/783,628 patent/US4725610A/en not_active Expired - Lifetime
- 1985-10-03 EP EP85307084A patent/EP0177353B1/en not_active Expired - Lifetime
-
1986
- 1986-04-30 ES ES554559A patent/ES8801256A1/es not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| NO157896C (no) | 1988-06-08 |
| EP0177353A2 (en) | 1986-04-09 |
| CA1263655A (en) | 1989-12-05 |
| EP0177353B1 (en) | 1990-04-11 |
| NO157896B (no) | 1988-02-29 |
| AU583537B2 (en) | 1989-05-04 |
| KR860003243A (ko) | 1986-05-21 |
| DE3577092D1 (de) | 1990-05-17 |
| CN85107870A (zh) | 1986-07-16 |
| DK444685A (da) | 1986-04-04 |
| ES8706150A1 (es) | 1987-06-01 |
| AU4817685A (en) | 1986-04-10 |
| ES8801256A1 (es) | 1987-12-16 |
| DK444685D0 (da) | 1985-10-01 |
| ES547507A0 (es) | 1987-06-01 |
| KR920002131B1 (ko) | 1992-03-12 |
| CN1003445B (zh) | 1989-03-01 |
| NO853902L (no) | 1986-04-04 |
| PT81235B (pt) | 1987-11-30 |
| ATE51869T1 (de) | 1990-04-15 |
| GR852389B (OSRAM) | 1986-02-04 |
| ES554559A0 (es) | 1987-12-16 |
| FI853796L (fi) | 1986-04-04 |
| US4725610A (en) | 1988-02-16 |
| JPH0570626B2 (OSRAM) | 1993-10-05 |
| PT81235A (en) | 1985-11-01 |
| JPS6185372A (ja) | 1986-04-30 |
| FI81097B (fi) | 1990-05-31 |
| FI853796A0 (fi) | 1985-10-01 |
| EP0177353A3 (en) | 1986-12-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| FI81097C (fi) | Foerfarande foer framstaellning av nya terapeutiskt verksamma tiazolidindionderivat. | |
| Sohda et al. | Studies on antidiabetic agents. I. Synthesis of 5-[4-(2-methyl-2-phenylpropoxy)-benzyl] thiazolidine-2, 4-dione (AL-321) and related compounds | |
| KR930011303B1 (ko) | 아실 조효소 a : 콜레스테롤 아실 전이효소(acat)의 억제제로서 신규한 n-아릴 및 n-헤테로아릴아미드 및 우레아 유도체 | |
| US5952509A (en) | Production of benzaldehyde compounds | |
| SK109993A3 (en) | Thiazolidinedione derivatives producing and use thereof | |
| JPH06779B2 (ja) | チアゾリジオン誘導体およびそれを含んでなる医薬組成物 | |
| CZ287473B6 (en) | Salt of maleic acid and a 5-[4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl]thiazolidine-2,4-dione, process of its preparation, pharmaceutical preparation in which this compound is comprised as well as use thereof | |
| SI9300337A (en) | Alkylamino thiazole branched, a process for the production thereof and pharmaceutical composition containing same | |
| LU85442A1 (fr) | Agents antidepression a base de 1,2,4-triazol-3-one | |
| CA2195559A1 (en) | Thiazolidinedione derivatives, their production and use | |
| JPS6157587A (ja) | 縮合複素環誘導体および抗潰瘍剤 | |
| SK164598A3 (en) | 5-phenoxyalkyl-2,4-thiazolidinedione derivative, method for the preparaton thereof, intermediate products for its preparation and pharmaceutical composition containing same | |
| EP0748317A1 (en) | Novel thiazolidin-4-one derivatives | |
| PL179580B1 (pl) | Srodek farmaceutyczny zawierajacy pochodne kwasów karboksylowych PL PL PL PL PL PL PL | |
| FI66177C (fi) | Foerfarande foer framstaellning av terapeutiskt anvaendbara ,5-diaryl-2-(substituerad-tio)imidazoler | |
| JPH0733376B2 (ja) | ２―イミノベンゾチアゾリン誘導体、その製造およびそれを含有している薬学的組成物 | |
| CN100497323C (zh) | 新的杂环肟化合物、它们的制备方法和含有它们的药物组合物 | |
| KR100199356B1 (ko) | 피리딘유도체, 이의 제조방법 및 용도 | |
| Mulwad et al. | Synthesis of some antibacterial compounds from 4-hydroxycoumarin | |
| HU194199B (en) | Process for producing new thiazolidinedione derivatives and pharmaceutical compositions containing them as active agents | |
| JPH02306965A (ja) | 喘息、関節炎および関連する病気の処置における置換１―［３―（ヘテロアリールメトキシ）フェニル］アルカノールおよび関連化合物 | |
| JPS61502959A (ja) | ４↓−（イソキサゾリル）↓−チアゾ−ル↓−２↓−オキサミド酸誘導体 | |
| KR890002291B1 (ko) | 2-알킬벤즈이미다졸 유도체의 제조방법 | |
| JPH01156966A (ja) | リポキシゲナーゼ抑制作用を有するピリダジノン、トリアジノンおよびオキサピリダジノン化合物 | |
| US5340824A (en) | Benzothiazole derivatives and medicinal products containing them |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM | Patent lapsed | ||
| MM | Patent lapsed |
Owner name: TAKEDA CHEMICAL INDUSTRIES, LTD. |