CA1328452C - Compounds - Google Patents
CompoundsInfo
- Publication number
- CA1328452C CA1328452C CA000576452A CA576452A CA1328452C CA 1328452 C CA1328452 C CA 1328452C CA 000576452 A CA000576452 A CA 000576452A CA 576452 A CA576452 A CA 576452A CA 1328452 C CA1328452 C CA 1328452C
- Authority
- CA
- Canada
- Prior art keywords
- pharmaceutically acceptable
- amino
- thiazolidinedione
- methyl
- ethoxy
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 218
- 150000003839 salts Chemical class 0.000 claims abstract description 72
- 239000012453 solvate Substances 0.000 claims abstract description 60
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 46
- -1 COMPOUNDS Compounds Chemical class 0.000 claims abstract description 44
- 239000001257 hydrogen Substances 0.000 claims abstract description 43
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 43
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 32
- 125000003118 aryl group Chemical group 0.000 claims abstract description 24
- 125000001424 substituent group Chemical group 0.000 claims abstract description 24
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 14
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 14
- 125000002252 acyl group Chemical group 0.000 claims abstract description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 58
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 39
- 125000003545 alkoxy group Chemical group 0.000 claims description 26
- 229910052736 halogen Chemical group 0.000 claims description 24
- 150000002367 halogens Chemical group 0.000 claims description 24
- 125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 22
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 22
- ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 claims description 21
- 238000011282 treatment Methods 0.000 claims description 21
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 20
- 125000004432 carbon atom Chemical group C* 0.000 claims description 15
- 239000003153 chemical reaction reagent Substances 0.000 claims description 15
- 125000001624 naphthyl group Chemical group 0.000 claims description 14
- 238000011321 prophylaxis Methods 0.000 claims description 13
- 229910052757 nitrogen Inorganic materials 0.000 claims description 11
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 10
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 10
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 10
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
- 208000031226 Hyperlipidaemia Diseases 0.000 claims description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
- 239000001301 oxygen Substances 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
- 239000005864 Sulphur Substances 0.000 claims description 6
- 201000001421 hyperglycemia Diseases 0.000 claims description 6
- 231100000252 nontoxic Toxicity 0.000 claims description 6
- 230000003000 nontoxic effect Effects 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 125000006413 ring segment Chemical group 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000004642 (C1-C12) alkoxy group Chemical group 0.000 claims 16
- BZYJVHSYHURRND-UHFFFAOYSA-N 5-[[4-[2-(pyrimidin-2-ylamino)ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound S1C(=O)NC(=O)C1CC(C=C1)=CC=C1OCCNC1=NC=CC=N1 BZYJVHSYHURRND-UHFFFAOYSA-N 0.000 claims 2
- SUDPMGHHEBDIQG-UHFFFAOYSA-N 5-[[4-[2-(pyrimidin-2-ylamino)ethoxy]phenyl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound S1C(=O)NC(=O)C1=CC(C=C1)=CC=C1OCCNC1=NC=CC=N1 SUDPMGHHEBDIQG-UHFFFAOYSA-N 0.000 claims 2
- PGYRMYURHJSMQI-UHFFFAOYSA-N 5-[[4-[2-[1,3-benzothiazol-2-yl(benzyl)amino]ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound S1C(=O)NC(=O)C1CC(C=C1)=CC=C1OCCN(C=1SC2=CC=CC=C2N=1)CC1=CC=CC=C1 PGYRMYURHJSMQI-UHFFFAOYSA-N 0.000 claims 2
- NVBNRRNFSLWBAN-UHFFFAOYSA-N 5-[[4-[2-[1,3-benzothiazol-2-yl(benzyl)amino]ethoxy]phenyl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound S1C(=O)NC(=O)C1=CC(C=C1)=CC=C1OCCN(C=1SC2=CC=CC=C2N=1)CC1=CC=CC=C1 NVBNRRNFSLWBAN-UHFFFAOYSA-N 0.000 claims 2
- MVAJTSXLFIXXAM-UHFFFAOYSA-N 5-[[4-[2-[1,3-benzothiazol-2-yl(methyl)amino]ethoxy]phenyl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound N=1C2=CC=CC=C2SC=1N(C)CCOC(C=C1)=CC=C1C=C1SC(=O)NC1=O MVAJTSXLFIXXAM-UHFFFAOYSA-N 0.000 claims 2
- ZYKPNHFCNSVFNF-UHFFFAOYSA-N 5-[[4-[2-[1,3-benzoxazol-2-yl(methyl)amino]ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound N=1C2=CC=CC=C2OC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O ZYKPNHFCNSVFNF-UHFFFAOYSA-N 0.000 claims 2
- WUKJUHJWWJVUFY-UHFFFAOYSA-N 5-[[4-[2-[1,3-benzoxazol-2-yl(methyl)amino]ethoxy]phenyl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound N=1C2=CC=CC=C2OC=1N(C)CCOC(C=C1)=CC=C1C=C1SC(=O)NC1=O WUKJUHJWWJVUFY-UHFFFAOYSA-N 0.000 claims 2
- NACAADVHQHZGOW-UHFFFAOYSA-N 5-[[4-[2-[methyl(1,3-thiazol-2-yl)amino]ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound N=1C=CSC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O NACAADVHQHZGOW-UHFFFAOYSA-N 0.000 claims 2
- LAXVHMVQGDVLCV-UHFFFAOYSA-N 5-[[4-[2-[methyl(pyrimidin-2-yl)amino]ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound N=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O LAXVHMVQGDVLCV-UHFFFAOYSA-N 0.000 claims 2
- QGWOCKYGZZYXIY-UHFFFAOYSA-N 5-[[4-[2-[methyl(pyrimidin-2-yl)amino]ethoxy]phenyl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound N=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1C=C1SC(=O)NC1=O QGWOCKYGZZYXIY-UHFFFAOYSA-N 0.000 claims 2
- DWPTVWXVZBYAIW-UHFFFAOYSA-N 5-[[4-[3-[1,3-benzoxazol-2-yl(methyl)amino]propoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound N=1C2=CC=CC=C2OC=1N(C)CCCOC(C=C1)=CC=C1CC1SC(=O)NC1=O DWPTVWXVZBYAIW-UHFFFAOYSA-N 0.000 claims 2
- NIJYKWLZVCLBDJ-UHFFFAOYSA-N 5-[[4-[3-[1,3-benzoxazol-2-yl(methyl)amino]propoxy]phenyl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound N=1C2=CC=CC=C2OC=1N(C)CCCOC(C=C1)=CC=C1C=C1SC(=O)NC1=O NIJYKWLZVCLBDJ-UHFFFAOYSA-N 0.000 claims 2
- YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 claims 2
- VBYNVJUPQIUGCH-UHFFFAOYSA-N n-[2-[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenoxy]ethyl]-n-pyrimidin-2-ylacetamide Chemical compound N=1C=CC=NC=1N(C(=O)C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O VBYNVJUPQIUGCH-UHFFFAOYSA-N 0.000 claims 2
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims 1
- ZOSMLZOMKXVTCW-UHFFFAOYSA-N 5-[[4-[2-[1,3-benzothiazol-2-yl(methyl)amino]ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound N=1C2=CC=CC=C2SC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O ZOSMLZOMKXVTCW-UHFFFAOYSA-N 0.000 claims 1
- GRFGENPMKNLCRJ-UHFFFAOYSA-N 5-[[4-[2-[methyl(1,3-thiazol-2-yl)amino]ethoxy]phenyl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound N=1C=CSC=1N(C)CCOC(C=C1)=CC=C1C=C1SC(=O)NC1=O GRFGENPMKNLCRJ-UHFFFAOYSA-N 0.000 claims 1
- HCDYSWMAMRPMST-UHFFFAOYSA-N 5-[[4-[2-[methyl(pyridin-2-yl)amino]ethoxy]phenyl]methylidene]-1,3-thiazolidine-2,4-dione Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1C=C1SC(=O)NC1=O HCDYSWMAMRPMST-UHFFFAOYSA-N 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 29
- 239000003814 drug Substances 0.000 abstract description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 62
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 59
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 57
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 51
- 238000000034 method Methods 0.000 description 48
- 238000002360 preparation method Methods 0.000 description 42
- 238000006243 chemical reaction Methods 0.000 description 33
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 32
- 239000000243 solution Substances 0.000 description 29
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 26
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- 229940123464 Thiazolidinedione Drugs 0.000 description 21
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 20
- OPKOKAMJFNKNAS-UHFFFAOYSA-N N-methylethanolamine Chemical compound CNCCO OPKOKAMJFNKNAS-UHFFFAOYSA-N 0.000 description 20
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 17
- 239000002904 solvent Substances 0.000 description 17
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- UOQXIWFBQSVDPP-UHFFFAOYSA-N 4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1 UOQXIWFBQSVDPP-UHFFFAOYSA-N 0.000 description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
- 239000000284 extract Substances 0.000 description 13
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 13
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 13
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
- 150000002431 hydrogen Chemical class 0.000 description 12
- 238000004587 chromatography analysis Methods 0.000 description 11
- 238000001816 cooling Methods 0.000 description 11
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 10
- 101150041968 CDC13 gene Proteins 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- 239000012267 brine Substances 0.000 description 10
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 10
- 238000010992 reflux Methods 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 7
- 229910002027 silica gel Inorganic materials 0.000 description 7
- 229960001866 silicon dioxide Drugs 0.000 description 7
- RGHHSNMVTDWUBI-UHFFFAOYSA-N 4-hydroxybenzaldehyde Chemical compound OC1=CC=C(C=O)C=C1 RGHHSNMVTDWUBI-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 239000005909 Kieselgur Substances 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000000499 gel Substances 0.000 description 6
- 239000008103 glucose Substances 0.000 description 6
- 235000019341 magnesium sulphate Nutrition 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 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 5
- 239000003054 catalyst Substances 0.000 description 5
- 230000037213 diet Effects 0.000 description 5
- 235000005911 diet Nutrition 0.000 description 5
- 239000006260 foam Substances 0.000 description 5
- 238000000746 purification Methods 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 4
- 208000024172 Cardiovascular disease Diseases 0.000 description 4
- 208000030814 Eating disease Diseases 0.000 description 4
- 208000019454 Feeding and Eating disease Diseases 0.000 description 4
- 206010020772 Hypertension Diseases 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 235000014632 disordered eating Nutrition 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- 238000006722 reduction reaction Methods 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 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 3
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 3
- 241000699670 Mus sp. Species 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 229910052782 aluminium Inorganic materials 0.000 description 3
- 239000000010 aprotic solvent Substances 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- 239000007822 coupling agent Substances 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 150000004678 hydrides Chemical class 0.000 description 3
- 230000003345 hyperglycaemic effect Effects 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 3
- RAIYODFGMLZUDF-UHFFFAOYSA-N piperidin-1-ium;acetate Chemical compound CC([O-])=O.C1CC[NH2+]CC1 RAIYODFGMLZUDF-UHFFFAOYSA-N 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 2
- LITDWGSWBCBPDI-UHFFFAOYSA-N 2-[1,3-benzoxazol-2-yl(methyl)amino]ethanol Chemical compound C1=CC=C2OC(N(CCO)C)=NC2=C1 LITDWGSWBCBPDI-UHFFFAOYSA-N 0.000 description 2
- BSQLQMLFTHJVKS-UHFFFAOYSA-N 2-chloro-1,3-benzothiazole Chemical compound C1=CC=C2SC(Cl)=NC2=C1 BSQLQMLFTHJVKS-UHFFFAOYSA-N 0.000 description 2
- SLRMQYXOBQWXCR-UHFFFAOYSA-N 2154-56-5 Chemical class [CH2]C1=CC=CC=C1 SLRMQYXOBQWXCR-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical group CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
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- 238000001953 recrystallisation Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
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- KEAYESYHFKHZAL-BJUDXGSMSA-N sodium-22 Chemical compound [22Na] KEAYESYHFKHZAL-BJUDXGSMSA-N 0.000 description 1
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- GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
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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
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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
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- 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
-
- 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
- C07D277/38—Nitrogen atoms
- C07D277/42—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
- C07D277/62—Benzothiazoles
- C07D277/68—Benzothiazoles 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 in position 2
- C07D277/82—Nitrogen atoms
-
- 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Diabetes (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Emergency Medicine (AREA)
- Endocrinology (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Pyridine Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Peptides Or Proteins (AREA)
- Steroid Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA000616769A CA1339902C (en) | 1987-09-04 | 1993-11-15 | Novel intermediates for preparing substitudes thiazolidinedione derivatives |
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB878720825A GB8720825D0 (en) | 1987-09-04 | 1987-09-04 | Compounds |
| GB878727987A GB8727987D0 (en) | 1987-11-30 | 1987-11-30 | Novel compounds |
| GB8727987 | 1988-02-04 | ||
| GB888802454A GB8802454D0 (en) | 1988-02-04 | 1988-02-04 | Compounds |
| GB8720825 | 1988-02-04 | ||
| GB8802454 | 1988-02-04 |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000616769A Division CA1339902C (en) | 1987-09-04 | 1993-11-15 | Novel intermediates for preparing substitudes thiazolidinedione derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1328452C true CA1328452C (en) | 1994-04-12 |
Family
ID=27263577
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000576452A Expired - Lifetime CA1328452C (en) | 1987-09-04 | 1988-09-02 | Compounds |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US5002953A (OSRAM) |
| EP (2) | EP0306228B1 (OSRAM) |
| JP (6) | JP2614497B2 (OSRAM) |
| KR (1) | KR0164207B1 (OSRAM) |
| AT (1) | ATE186724T1 (OSRAM) |
| AU (1) | AU611938B2 (OSRAM) |
| CA (1) | CA1328452C (OSRAM) |
| CZ (1) | CZ391691A3 (OSRAM) |
| DE (2) | DE3856378T2 (OSRAM) |
| DK (2) | DK175176B1 (OSRAM) |
| ES (1) | ES2137915T3 (OSRAM) |
| GR (1) | GR3031873T3 (OSRAM) |
| IE (1) | IE20000683A1 (OSRAM) |
| LU (1) | LU90711I2 (OSRAM) |
| NL (1) | NL300034I2 (OSRAM) |
| NZ (1) | NZ226027A (OSRAM) |
| PT (1) | PT88410B (OSRAM) |
| SG (1) | SG59988A1 (OSRAM) |
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| US10034868B2 (en) | 2014-11-04 | 2018-07-31 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for the prevention and the treatment of rapidly progressive glomerulonephritis |
| WO2018130679A1 (en) | 2017-01-16 | 2018-07-19 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods and pharmaceutical compositions for reducing cd95- mediated cell motility |
| GR1010570B (el) * | 2022-12-22 | 2023-11-17 | Uni-Pharma Κλεων Τσετης Φαρμακευτικα Εργαστηρια Α.Β.Ε.Ε., | 4-(2-(4-((2,4-διοξοθειαζολιδιν-5-υλ)μεθυλ)φαινοξυ) παραγωγα με δραση αναστολης της αυτοταξινης |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5522636A (en) * | 1978-08-04 | 1980-02-18 | Takeda Chem Ind Ltd | Thiazoliding derivative |
| SG59988A1 (en) * | 1987-09-04 | 1999-02-22 | Beecham Group Plc | Substituted thiazolidinedione derivatives |
-
1988
- 1988-08-26 SG SG1996009246A patent/SG59988A1/en unknown
- 1988-08-26 ES ES88307910T patent/ES2137915T3/es not_active Expired - Lifetime
- 1988-08-26 AT AT88307910T patent/ATE186724T1/de active
- 1988-08-26 EP EP88307910A patent/EP0306228B1/en not_active Expired - Lifetime
- 1988-08-26 DE DE3856378T patent/DE3856378T2/de not_active Expired - Lifetime
- 1988-08-26 EP EP98102500A patent/EP0842925A1/en not_active Withdrawn
- 1988-08-26 DE DE2001199003 patent/DE10199003I1/de active Granted
- 1988-09-02 IE IE20000683A patent/IE20000683A1/en not_active IP Right Cessation
- 1988-09-02 CA CA000576452A patent/CA1328452C/en not_active Expired - Lifetime
- 1988-09-02 AU AU21738/88A patent/AU611938B2/en not_active Expired
- 1988-09-02 NZ NZ226027A patent/NZ226027A/en unknown
- 1988-09-02 DK DK198804902A patent/DK175176B1/da not_active IP Right Cessation
- 1988-09-02 PT PT88410A patent/PT88410B/pt not_active IP Right Cessation
- 1988-09-03 KR KR1019880011399A patent/KR0164207B1/ko not_active Expired - Lifetime
- 1988-09-03 JP JP63221206A patent/JP2614497B2/ja not_active Expired - Lifetime
-
1989
- 1989-12-27 US US07/457,272 patent/US5002953A/en not_active Expired - Lifetime
-
1991
- 1991-12-19 CZ CS913916A patent/CZ391691A3/cs unknown
-
1996
- 1996-10-02 JP JP8279897A patent/JP2817840B2/ja not_active Expired - Lifetime
- 1996-10-02 JP JP8279899A patent/JPH09183772A/ja active Pending
- 1996-10-02 JP JP8279898A patent/JP2837139B2/ja not_active Expired - Lifetime
-
1998
- 1998-01-28 JP JP10029076A patent/JPH10194971A/ja active Pending
- 1998-01-28 JP JP10029075A patent/JPH10194970A/ja active Pending
-
1999
- 1999-11-18 GR GR990402958T patent/GR3031873T3/el unknown
-
2000
- 2000-10-18 DK DK200001556A patent/DK200001556A/da not_active Application Discontinuation
-
2001
- 2001-01-03 LU LU90711C patent/LU90711I2/fr unknown
- 2001-01-04 NL NL300034C patent/NL300034I2/nl unknown
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