FI80693C - Foerfarande foer framstaellning av derivat av 5-/4-(kromanalkoxi)bensyl/-tiazolidin. - Google Patents
Foerfarande foer framstaellning av derivat av 5-/4-(kromanalkoxi)bensyl/-tiazolidin. Download PDFInfo
- Publication number
- FI80693C FI80693C FI843422A FI843422A FI80693C FI 80693 C FI80693 C FI 80693C FI 843422 A FI843422 A FI 843422A FI 843422 A FI843422 A FI 843422A FI 80693 C FI80693 C FI 80693C
- Authority
- FI
- Finland
- Prior art keywords
- benzyl
- ylmethoxy
- hydroxy
- dione
- thiazolidine
- Prior art date
Links
- 229950001139 timonacic Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 188
- 238000000034 method Methods 0.000 claims abstract description 42
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 34
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims abstract description 34
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 25
- 150000003839 salts Chemical class 0.000 claims abstract description 23
- 239000002253 acid Substances 0.000 claims abstract description 19
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims abstract description 17
- 125000001841 imino group Chemical group [H]N=* 0.000 claims abstract description 13
- 239000001257 hydrogen Substances 0.000 claims abstract description 9
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 7
- 125000004429 atom Chemical group 0.000 claims abstract description 4
- -1 6-hydroxy-2,5,7,8-tetramethylchroman-2-ylmethoxy Chemical group 0.000 claims description 175
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 119
- 238000006243 chemical reaction Methods 0.000 claims description 94
- 238000002360 preparation method Methods 0.000 claims description 88
- ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 claims description 57
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 54
- 239000007858 starting material Substances 0.000 claims description 25
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 17
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 14
- 150000001768 cations Chemical group 0.000 claims description 10
- 238000006460 hydrolysis reaction Methods 0.000 claims description 10
- 229910052727 yttrium Inorganic materials 0.000 claims description 10
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 9
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
- 239000000126 substance Substances 0.000 claims description 8
- 230000007062 hydrolysis Effects 0.000 claims description 7
- 229910052721 tungsten Inorganic materials 0.000 claims description 6
- FSRRLWAYZNCQQH-UHFFFAOYSA-N 3-benzyl-2-imino-1,3-thiazolidin-4-one Chemical compound N=C1SCC(=O)N1CC1=CC=CC=C1 FSRRLWAYZNCQQH-UHFFFAOYSA-N 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- CAEMWTIZSYCXJB-UHFFFAOYSA-N 2-amino-5-[[4-[(6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydrochromen-2-yl)methoxy]phenyl]methyl]-1,3-thiazol-4-one Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=N)NC1=O CAEMWTIZSYCXJB-UHFFFAOYSA-N 0.000 claims description 3
- GHVMCVHCRDMSIU-UHFFFAOYSA-N 5-[[4-[(6-hydroxy-5,7,8-trimethyl-3,4-dihydro-2h-chromen-2-yl)methoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1COC(C=C1)=CC=C1CC1SC(=O)NC1=O GHVMCVHCRDMSIU-UHFFFAOYSA-N 0.000 claims description 3
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 3
- 125000005400 pyridylcarbonyl group Chemical group N1=C(C=CC=C1)C(=O)* 0.000 claims description 3
- WCQNOKTYTUUQHU-UHFFFAOYSA-N 2-amino-5-[[4-[(7-tert-butyl-6-hydroxy-2-methyl-4-oxo-3h-chromen-2-yl)methoxy]phenyl]methyl]-1,3-thiazol-4-one Chemical compound C1C(=O)C=2C=C(O)C(C(C)(C)C)=CC=2OC1(C)COC(C=C1)=CC=C1CC1SC(=N)NC1=O WCQNOKTYTUUQHU-UHFFFAOYSA-N 0.000 claims description 2
- GYQXZPFPKJFLAI-UHFFFAOYSA-N 5-[[4-[2-(6-hydroxy-7,8-dimethoxy-2,5-dimethyl-3,4-dihydrochromen-2-yl)ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound O1C2=C(OC)C(OC)=C(O)C(C)=C2CCC1(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O GYQXZPFPKJFLAI-UHFFFAOYSA-N 0.000 claims 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 claims 1
- XKCFRYBMDXGIIA-UHFFFAOYSA-N [2-[2-[4-[(2-amino-4-oxo-1,3-thiazol-5-yl)methyl]phenoxy]ethyl]-7,8-dimethoxy-2,5-dimethyl-3,4-dihydrochromen-6-yl] acetate Chemical compound C1CC=2C(C)=C(OC(C)=O)C(OC)=C(OC)C=2OC1(C)CCOC(C=C1)=CC=C1CC1SC(=N)NC1=O XKCFRYBMDXGIIA-UHFFFAOYSA-N 0.000 claims 1
- 159000000000 sodium salts Chemical group 0.000 claims 1
- 239000008280 blood Substances 0.000 abstract description 16
- 210000004369 blood Anatomy 0.000 abstract description 16
- 125000002252 acyl group Chemical group 0.000 abstract description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 7
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 abstract description 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 abstract description 2
- 230000001225 therapeutic effect Effects 0.000 abstract description 2
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 abstract 2
- 125000005530 alkylenedioxy group Chemical group 0.000 abstract 1
- 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 abstract 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract 1
- 239000001301 oxygen Substances 0.000 abstract 1
- 229910052760 oxygen Inorganic materials 0.000 abstract 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 318
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 279
- 239000000203 mixture Substances 0.000 description 137
- 239000002904 solvent Substances 0.000 description 120
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 78
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 74
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 59
- 239000000741 silica gel Substances 0.000 description 59
- 229910002027 silica gel Inorganic materials 0.000 description 59
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 55
- 238000004809 thin layer chromatography Methods 0.000 description 52
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 51
- 238000001819 mass spectrum Methods 0.000 description 49
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 47
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 44
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 36
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 33
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 32
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 30
- 239000011541 reaction mixture Substances 0.000 description 30
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 29
- 239000000243 solution Substances 0.000 description 25
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 20
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 20
- 239000012043 crude product Substances 0.000 description 20
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 18
- 229910052757 nitrogen Inorganic materials 0.000 description 18
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 17
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
- 239000000284 extract Substances 0.000 description 16
- 238000002844 melting Methods 0.000 description 16
- 230000008018 melting Effects 0.000 description 16
- 239000000047 product Substances 0.000 description 16
- 238000010898 silica gel chromatography Methods 0.000 description 16
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 15
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 15
- 239000003921 oil Substances 0.000 description 15
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 14
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 14
- 238000004440 column chromatography Methods 0.000 description 13
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 12
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 12
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 12
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 12
- VZWXIQHBIQLMPN-UHFFFAOYSA-N chromane Chemical group C1=CC=C2CCCOC2=C1 VZWXIQHBIQLMPN-UHFFFAOYSA-N 0.000 description 12
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 12
- 239000003638 chemical reducing agent Substances 0.000 description 11
- 239000003795 chemical substances by application Substances 0.000 description 11
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical class [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 10
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 10
- 239000002585 base Substances 0.000 description 10
- 239000011734 sodium Substances 0.000 description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 229910052783 alkali metal Inorganic materials 0.000 description 9
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- HIMXGTXNXJYFGB-UHFFFAOYSA-N alloxan Chemical compound O=C1NC(=O)C(=O)C(=O)N1 HIMXGTXNXJYFGB-UHFFFAOYSA-N 0.000 description 8
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 8
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 8
- JIMXJAFZPUUCAD-UHFFFAOYSA-N 3-benzyl-1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1CC1=CC=CC=C1 JIMXJAFZPUUCAD-UHFFFAOYSA-N 0.000 description 7
- 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 7
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 7
- 150000001298 alcohols Chemical class 0.000 description 7
- 125000000217 alkyl group Chemical group 0.000 description 7
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 7
- 125000004432 carbon atom Chemical group C* 0.000 description 7
- 239000013078 crystal Substances 0.000 description 7
- 150000002170 ethers Chemical class 0.000 description 7
- 229910052751 metal Inorganic materials 0.000 description 7
- 239000002184 metal Substances 0.000 description 7
- 231100000989 no adverse effect Toxicity 0.000 description 7
- 150000007524 organic acids Chemical class 0.000 description 7
- 229910052708 sodium Inorganic materials 0.000 description 7
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 6
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 6
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 6
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- BERDEBHAJNAUOM-UHFFFAOYSA-N copper(i) oxide Chemical compound [Cu]O[Cu] BERDEBHAJNAUOM-UHFFFAOYSA-N 0.000 description 6
- 238000001704 evaporation Methods 0.000 description 6
- 150000002576 ketones Chemical class 0.000 description 6
- 229910052700 potassium Inorganic materials 0.000 description 6
- 239000011591 potassium Substances 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 235000019260 propionic acid Nutrition 0.000 description 6
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 6
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 6
- 230000035484 reaction time Effects 0.000 description 6
- 229910000029 sodium carbonate Inorganic materials 0.000 description 6
- 229940126062 Compound A Drugs 0.000 description 5
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
- 229910052782 aluminium Inorganic materials 0.000 description 5
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 5
- 150000001408 amides Chemical class 0.000 description 5
- 230000008020 evaporation Effects 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 239000000499 gel Substances 0.000 description 5
- 239000005457 ice water Substances 0.000 description 5
- 238000002955 isolation Methods 0.000 description 5
- 239000010410 layer Substances 0.000 description 5
- 125000006239 protecting group Chemical group 0.000 description 5
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 5
- 238000006722 reduction reaction Methods 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 150000003548 thiazolidines Chemical class 0.000 description 5
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 4
- JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 4
- 238000005917 acylation reaction Methods 0.000 description 4
- 238000010171 animal model Methods 0.000 description 4
- 239000011575 calcium Substances 0.000 description 4
- 229910052791 calcium Inorganic materials 0.000 description 4
- 235000012000 cholesterol Nutrition 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- IIEWJVIFRVWJOD-UHFFFAOYSA-N ethylcyclohexane Chemical compound CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 150000007529 inorganic bases Chemical class 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- 150000002632 lipids Chemical class 0.000 description 4
- PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
- 150000003335 secondary amines Chemical class 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 239000012279 sodium borohydride Substances 0.000 description 4
- 229910000033 sodium borohydride Inorganic materials 0.000 description 4
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- 235000010288 sodium nitrite Nutrition 0.000 description 4
- 150000003462 sulfoxides Chemical class 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 description 4
- 239000008096 xylene Substances 0.000 description 4
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- DSNYFFJTZPIKFZ-UHFFFAOYSA-N propoxybenzene Chemical group CCCOC1=CC=CC=C1 DSNYFFJTZPIKFZ-UHFFFAOYSA-N 0.000 description 1
- 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
- QGKLPGKXAVVPOJ-UHFFFAOYSA-N pyrrolidin-3-one Chemical compound O=C1CCNC1 QGKLPGKXAVVPOJ-UHFFFAOYSA-N 0.000 description 1
- DOQJUNNMZNNQAD-UHFFFAOYSA-N pyrrolidine-2,4-dione Chemical compound O=C1CNC(=O)C1 DOQJUNNMZNNQAD-UHFFFAOYSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000011946 reduction process Methods 0.000 description 1
- 239000012419 sodium bis(2-methoxyethoxy)aluminum hydride Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000003797 solvolysis reaction Methods 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000003419 tautomerization reaction Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
- C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
- C07D311/58—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring other than with oxygen or sulphur atoms in position 2 or 4
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D407/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00
- C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
- C07D407/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 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)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Obesity (AREA)
- Diabetes (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)
- Hematology (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Medicinal Preparation (AREA)
- Pyrane Compounds (AREA)
- Cosmetics (AREA)
- Peptides Or Proteins (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pyrrole Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP58158375A JPS6051189A (ja) | 1983-08-30 | 1983-08-30 | チアゾリジン誘導体およびその製造法 |
| JP15837583 | 1983-08-30 |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| FI843422A0 FI843422A0 (fi) | 1984-08-30 |
| FI843422A7 FI843422A7 (fi) | 1985-03-01 |
| FI80693B FI80693B (fi) | 1990-03-30 |
| FI80693C true FI80693C (fi) | 1990-07-10 |
Family
ID=15670325
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI843422A FI80693C (fi) | 1983-08-30 | 1984-08-30 | Foerfarande foer framstaellning av derivat av 5-/4-(kromanalkoxi)bensyl/-tiazolidin. |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US4572912A (OSRAM) |
| EP (1) | EP0139421B1 (OSRAM) |
| JP (1) | JPS6051189A (OSRAM) |
| KR (1) | KR890000370B1 (OSRAM) |
| AT (1) | ATE33838T1 (OSRAM) |
| AU (1) | AU570067B2 (OSRAM) |
| CA (1) | CA1263395A (OSRAM) |
| DE (1) | DE3470742D1 (OSRAM) |
| DK (1) | DK164701C (OSRAM) |
| ES (1) | ES8607297A1 (OSRAM) |
| FI (1) | FI80693C (OSRAM) |
| IE (1) | IE58036B1 (OSRAM) |
Families Citing this family (206)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6051189B2 (ja) * | 1980-07-21 | 1985-11-12 | 株式会社日立製作所 | 磁気バブル駆動回路 |
| JPS60226873A (ja) * | 1984-03-28 | 1985-11-12 | Sankyo Co Ltd | １，３−ベンゾオキサチオ−ル誘導体及びその製法 |
| CN1003445B (zh) * | 1984-10-03 | 1989-03-01 | 武田药品工业株式会社 | 噻唑烷二酮衍生物，其制备方法和用途 |
| JPH0653738B2 (ja) * | 1985-02-26 | 1994-07-20 | 三共株式会社 | チアゾリジン誘導体 |
| DK173350B1 (da) | 1985-02-26 | 2000-08-07 | Sankyo Co | Thiazolidinderivater, deres fremstilling og farmaceutisk paæparat indeholdende dem |
| HU210339B (en) * | 1985-05-21 | 1995-03-28 | Pfizer | Process for preparing thiazolidinediones and their pharmaceutical compositions haring hypoglycemic effect |
| US4738972A (en) * | 1985-05-21 | 1988-04-19 | Pfizer Inc. | Hypoglycemic thiazolidinediones |
| 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 |
| JPS62234085A (ja) * | 1985-12-18 | 1987-10-14 | Sankyo Co Ltd | チアゾリジン誘導体を有効成分とする糖尿病性合併症治療剤 |
| US4873255A (en) * | 1987-02-04 | 1989-10-10 | Sankyo Company Limited | Thiazolidinone derivatives, their preparation and their use |
| JP2574845B2 (ja) * | 1987-02-04 | 1997-01-22 | 三共株式会社 | チアゾリジン化合物 |
| US4791125A (en) * | 1987-12-02 | 1988-12-13 | Pfizer Inc. | Thiazolidinediones as hypoglycemic and anti-atherosclerosis agents |
| US4798835A (en) * | 1987-12-02 | 1989-01-17 | Pfizer Inc. | dl-5-[(2-benzyl-3,4-dihydro-2H-benzopyran-6-yl)methyl]thiazolidine-2,4-dione as an anti-atherosclerosis agent |
| US5132310A (en) * | 1988-08-09 | 1992-07-21 | Hoffmann-La Roche Inc. | Pharmacologically active chromanes |
| US5260294A (en) * | 1988-08-09 | 1993-11-09 | Hoffman-La Roche Inc. | Chromanes and their pharmaceutical compositions and methods |
| US5015661A (en) * | 1988-08-09 | 1991-05-14 | Hoffmann-La Roche Inc. | Chromanes and their pharmaceutical compositions and methods |
| 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 |
| JP2826379B2 (ja) * | 1990-01-22 | 1998-11-18 | 三共株式会社 | チアゾリジン誘導体を有効成分とする肥満性高血圧症治療剤 |
| US5143930A (en) * | 1990-02-07 | 1992-09-01 | Sankyo Company, Limited | Thiazolidine derivatives with anti-diabetic activity, their preparation and their use |
| WO1991012003A1 (en) * | 1990-02-09 | 1991-08-22 | The Upjohn Company | Use of insulin sensitizing agents to treat hypertension |
| US5356913A (en) * | 1990-02-09 | 1994-10-18 | The Upjohn Company | Use of insulin sensitizing agents to treat hypertension |
| DE69132713D1 (de) * | 1990-04-27 | 2001-10-11 | Sankyo Co | Benzylidenthiazolidinderivate, ihre Herstellung und ihre Anwendung als Lipidperoxid-Inhibitoren |
| GB9023584D0 (en) * | 1990-10-30 | 1990-12-12 | Beecham Group Plc | Novel compounds |
| CA2082003A1 (en) * | 1991-11-20 | 1993-05-21 | David Laffan | Process for the preparation of substituted pentaalkylchromenes |
| ES2109377T3 (es) * | 1991-12-18 | 1998-01-16 | Warner Lambert Co | Proceso para la preparacion de una dispersion solida. |
| NO302519B1 (no) * | 1991-12-26 | 1998-03-16 | Sankyo Co | Tiazolidinforbindelser som inneholder en kinongruppe, og farmasöytisk preparat |
| NO302471B1 (no) * | 1991-12-26 | 1998-03-09 | Sankyo Co | Tiazolidinforbindelser og farmasöytisk preparat |
| CA2089013A1 (en) * | 1992-02-21 | 1993-08-22 | Josef Heveling | Process for the preparation of 6-hydroxy-2, 5, 7, 8- tetraalkyl-2-(4-aminophenoxymethyl) chromans |
| CA2089012A1 (en) * | 1992-02-21 | 1993-08-22 | Josef Heveling | Process for the preparation of 6-hydroxy-2,5,7,8-tetra- alkyl-2-(4-aminophenoxymethyl) chromans |
| DK0590793T3 (da) * | 1992-08-31 | 2000-01-31 | Sankyo Co | Oxazolidin-derivater med anti-diabetiske og anti-obesitas-egenskaber, fremstilling deraf samt deres terapeutiske anvendelse |
| JPH0631079U (ja) * | 1992-09-22 | 1994-04-22 | 沖電線株式会社 | シート付き小型ｓｍｔコネクタ |
| US5594016A (en) * | 1992-12-28 | 1997-01-14 | Mitsubishi Chemical Corporation | Naphthalene derivatives |
| AU6114794A (en) * | 1993-02-24 | 1994-09-14 | Sankyo Company Limited | Arteriosclerosis remedy |
| USRE39384E1 (en) | 1993-09-01 | 2006-11-07 | Smithkline Beecham P.L.C. | Substituted thiazolidinedione derivatives |
| US5874454A (en) * | 1993-09-15 | 1999-02-23 | 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 |
| 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 |
| AU749416B2 (en) * | 1993-09-15 | 2002-06-27 | Daiichi Sankyo Company, Limited | Use of thiazolidinediones to prevent or delay onset of NIDDM |
| CA2171827C (en) * | 1993-09-15 | 2004-06-29 | Jerrold Olefsky | Use of thiazolidinediones to prevent or delay onset of niddm |
| 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 |
| ATE179709T1 (de) * | 1993-12-27 | 1999-05-15 | Japan Tobacco Inc | Isoxazolidindionderivate und deren verwendung |
| CA2146701A1 (en) * | 1994-04-11 | 1995-10-12 | Takashi Fujita | Heterocyclic compounds having anti-diabetic activity, their preparation and their use |
| US5594015A (en) * | 1994-06-22 | 1997-01-14 | Regents Of The University Of California | Thiazolidine derivatives for the treatment of psoriasis |
| US5703096A (en) * | 1994-10-07 | 1997-12-30 | Sankyo Company, Limited | Oxime derivatives, their preparation and their therapeutic use |
| 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 |
| AU706628B2 (en) * | 1995-07-03 | 1999-06-17 | Sankyo Company Limited | Treatment of arteriosclerosis and xanthoma |
| HUP9802543A2 (hu) * | 1995-08-10 | 1999-07-28 | Warner-Lambert Company | Eljárás nem inzulinfüggő diabetes mellitusban szenvedő betegek esetében az adagolt exogén inzulin mennyiségének csökkentésére alkalmas tiazolindion-származékokat tartalmazó gyógyszerkészítmények előállítására |
| AU7604596A (en) * | 1995-11-17 | 1997-06-11 | Warner-Lambert Company | A method of treating myotonic dystrophy |
| EP0783888A1 (en) * | 1995-12-26 | 1997-07-16 | Sankyo Company Limited | Use of troglitazone and related thiazolidinediones in the manufacture of a medicament for the treatment and prophylaxis of osteoporosis |
| IN182496B (OSRAM) * | 1996-02-20 | 1999-04-17 | Reddy Research Foundation | |
| IL120443A (en) * | 1996-03-18 | 2000-07-16 | Sankyo Co | Use of an insulin sensitizer for the manufacture of a medicament for the treatment or prophylaxis of pancreatitis |
| ATE252074T1 (de) * | 1996-04-04 | 2003-11-15 | Sankyo Co | Phenylalkylcarbonsäure-derivate |
| DE69625795T2 (de) * | 1996-04-09 | 2003-08-14 | Dr. Reddy's Laboratories Ltd., Hyderabad | Thiazolidinedionderivate mit antidiabetischen, hypolipidämischen und antihypertensiven Eigenschaften, Verfahren zu deren Herstellung und pharmazeutischen Zusammenstellungen, die sie enthalten |
| 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 |
| ZA973848B (en) * | 1996-05-06 | 1997-12-02 | Reddy Research Foundation | Novel heterocyclic compounds having antidiabetic, hypolipidaemic, antihypertensive properties, process for their preparation and pharmaceutical compositions containing them. |
| ZA973850B (en) * | 1996-05-06 | 1997-12-02 | Reddy Research Foundation | Novel antidiabetic compounds having hypolipidaemic, anti-hypertensive properties, process for their preparation and pharmaceutical compositions containing them. |
| 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 |
| DE19619819A1 (de) * | 1996-05-16 | 1997-11-20 | Boehringer Mannheim Gmbh | Neue Thiazolidindione, Verfahren zu ihrer Herstellung und diese enthaltenden Arzneimittel |
| WO1997043283A1 (de) * | 1996-05-16 | 1997-11-20 | Boehringer Mannheim Gmbh | Neues verfahren zur herstellung von troglitazone |
| CA2257284C (en) * | 1996-05-31 | 2005-10-04 | Sankyo Company Limited | Remedy for autoimmune diseases |
| GB9611947D0 (en) * | 1996-06-07 | 1996-08-07 | Glaxo Group Ltd | Medicaments |
| CN1196730A (zh) * | 1996-06-19 | 1998-10-21 | 雷迪博士研究基金会 | 具有增强的抗糖尿病活性的穴糖酮的新的多晶型形式及其制备方法 |
| 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 |
| 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 |
| KR100579765B1 (ko) * | 1996-07-01 | 2006-12-28 | 닥터 레디스 레보러터리즈 리미티드 | 신규헤테로고리형화합물의제조방법,이를함유하는약제조성물및당뇨병및이와관련된질병의치료에있어서그의용도 |
| 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 |
| 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 |
| JP2000514807A (ja) * | 1996-07-12 | 2000-11-07 | スミスクライン・ビーチャム・パブリック・リミテッド・カンパニー | レプチン耐性の新規な治療 |
| AU723354B2 (en) * | 1996-09-12 | 2000-08-24 | Sankyo Company Limited | Glutathione reductase activity potentiator containing troglitazone |
| DE69738809D1 (de) * | 1996-11-08 | 2008-08-14 | Nippon Chemiphar Co | Mittel zur verringerung der eigeweidefette |
| EP1006794B1 (en) * | 1997-03-12 | 2007-11-28 | Robert W. Esmond | A method for treating or preventing alzheimer's disease |
| US6011036A (en) * | 1997-04-15 | 2000-01-04 | Dr. Reddy's Research Foundation | Heterocyclic compounds having antidiabetic hypolipidemic antihypertensive properties process for their preparation and pharmaceutical compositions containing them |
| US6011031A (en) * | 1997-05-30 | 2000-01-04 | Dr. Reddy's Research Foundation | Azolidinediones useful for the treatment of diabetes, dyslipidemia and hypertension: process for their preparation and pharmaceutical compositions containing them |
| SE9702305D0 (sv) * | 1997-06-17 | 1997-06-17 | Astra Ab | New thiazolidinedione, oxazolidinedione and oxadiazolidinedione derivatives |
| EP1787646A3 (en) * | 1997-06-18 | 2007-10-03 | Smithkline Beecham Plc | Novel method of treatment |
| KR20010013840A (ko) | 1997-06-18 | 2001-02-26 | 피터 기딩스 | 티아졸리딘디온 및 술포닐우레아를 사용한 당뇨병의 치료 |
| 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 |
| US6171856B1 (en) | 1997-07-30 | 2001-01-09 | Board Of Regents, The University Of Texas System | Methods and compositions relating to no-mediated cytotoxicity |
| FR2766820B1 (fr) * | 1997-07-31 | 1999-10-22 | Rhodia Chimie Sa | Procede de preparation de 2h-1-benzopyranes et intermediaires de synthese utiles dans la mise en oeuvre du procede |
| BR9813019A (pt) * | 1997-10-02 | 2000-09-05 | Sankyo Co | Derivados do ácido amidocarboxìlico, agentes para diminuir a glicose do sangue, redutor de lipìdio, para melhorar a resistência à insulina, anti-inflamatório, para imuno regulagem, para inibir a aldose reductase, para inibir a 5-lipoxigenase, para a geração de supressor de peróxido de lipìdio, para ativar a ppar, para minorar a osteoporose, e, composições para a terapia ou prevenção da diabete melito, da hiperlipemia, da obesidade, da tolerância à glicose prejudicada, da resistência à insulina que não a igt, do fìgado gorduroso, de complicações diabéticas, da arterioesclerose, da diabete melito gestacional, da sìndrome do ovário policìstico, da artroesteìte, da artrite reumática, de doenças alérgicas, da asma, do câncer, de doenças auto imunes, da pancreatite, e de cataratas |
| EP0916665A1 (de) * | 1997-11-11 | 1999-05-19 | Lonza A.G. | Verfahren zur Herstellung von Chromanderivaten |
| KR100567183B1 (ko) * | 1997-11-14 | 2006-06-13 | 론자 아게 | 포르밀이미다졸의제조방법 |
| HUP9902721A2 (hu) * | 1997-11-25 | 1999-12-28 | The Procter & Gamble Co. | Tömény textillágyító készítmény és ehhez alkalmazható magas telítetlenségű textillágyító vegyület |
| AU1507799A (en) * | 1997-12-16 | 1999-07-05 | Sankyo Company Limited | Leukemia remedy |
| US20040058873A1 (en) * | 1998-03-12 | 2004-03-25 | Esmond Robert W. | Method for treating or preventing Alzheimer's disease |
| CN1203846C (zh) | 1998-03-19 | 2005-06-01 | 布里斯托尔-迈尔斯斯奎布公司 | 高溶解性药物的双相控释递送系统和方法 |
| RU2243214C2 (ru) * | 1998-06-04 | 2004-12-27 | Астразенека Аб | Новые производные и аналоги 3-арилпропионовой кислоты |
| WO2000007582A2 (en) * | 1998-08-06 | 2000-02-17 | Warner-Lambert Company | Use of thiazolidinedione derivatives for the treatment or prevention of cataracts |
| AU5514199A (en) * | 1998-08-19 | 2000-03-14 | Sankyo Company Limited | Process for the preparation of 2-(aryloxymethyl)-2,5,7,8-tetramethylchroman-6-ols |
| KR20010079842A (ko) | 1998-09-17 | 2001-08-22 | 스티븐 비. 데이비스 | ａＰ2 억제제 또는 조합을 사용한 아테롬성동맥경화증의치료 방법 |
| US6028088A (en) * | 1998-10-30 | 2000-02-22 | The University Of Mississippi | Flavonoid derivatives |
| GB9824893D0 (en) * | 1998-11-12 | 1999-01-06 | Smithkline Beckman Corp | Novel method of treatment |
| AR023700A1 (es) * | 1998-11-12 | 2002-09-04 | Smithkline Beecham Plc | Un procedimiento para preparar una composicion farmaceutica que comprende un sensibilizador de insulina |
| TR200101333T2 (tr) | 1998-11-12 | 2001-10-22 | Smithkline Beecham P.L.C. | Bir ensülin sensitizörü ve başka bir anti-diyabetik maddenin değiştirilmiş salımı için farmasötik terkip. |
| 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 |
| US5968960A (en) * | 1999-01-14 | 1999-10-19 | The Regents Of The University Of California | Use of thiazolidinediones to ameliorate the adverse consequences of myocardial ischemia on myocardial function and metabolism |
| US6204288B1 (en) | 1999-03-08 | 2001-03-20 | The University Of Mississippi | 1,2-dithiolane derivatives |
| US6127394A (en) * | 1999-03-08 | 2000-10-03 | The University Of Mississippi | 1,2-Dithiolane derivatives |
| US6548529B1 (en) | 1999-04-05 | 2003-04-15 | Bristol-Myers Squibb Company | Heterocyclic containing biphenyl aP2 inhibitors and method |
| US7041691B1 (en) * | 1999-06-30 | 2006-05-09 | Amgen Inc. | Compounds for the modulation of PPARγ activity |
| JP2001072592A (ja) | 1999-07-01 | 2001-03-21 | Kyowa Hakko Kogyo Co Ltd | テロメラーゼ阻害剤 |
| US6559188B1 (en) | 1999-09-17 | 2003-05-06 | Novartis Ag | Method of treating metabolic disorders especially diabetes, or a disease or condition associated with diabetes |
| US6878749B2 (en) | 1999-09-17 | 2005-04-12 | Novartis Ag | Method of treating metabolic disorders, especially diabetes, or a disease or condition associated with diabetes |
| CO5200844A1 (es) | 1999-09-17 | 2002-09-27 | Novartis Ag | Una combinacion que comprende nateglinida y cuando por menos otro compuesto antidiabetico usada para el tratamiento de desordenes metabolicos, especialmente diabetes, o de una enfermedad o condicion asociada con dibetes |
| US6586438B2 (en) | 1999-11-03 | 2003-07-01 | Bristol-Myers Squibb Co. | Antidiabetic formulation and method |
| CZ20021911A3 (cs) | 1999-12-03 | 2002-10-16 | Kyoto Pharmaceutical Industries, Ltd. | Nové heterocyklické sloučeniny a jejich soli a jejich vyuľití v lékařství |
| CA2673615C (en) | 2000-01-21 | 2013-07-16 | Novartis Ag | Combinations comprising dipeptidylpeptidase-iv inhibitors and antidiabetic agents |
| US6395767B2 (en) | 2000-03-10 | 2002-05-28 | Bristol-Myers Squibb Company | Cyclopropyl-fused pyrrolidine-based inhibitors of dipeptidyl peptidase IV and method |
| US6680387B2 (en) * | 2000-04-24 | 2004-01-20 | Aryx Therapeutics | Materials and methods for the treatment of diabetes, hyperlipidemia, hypercholesterolemia, and atherosclerosis |
| US6958355B2 (en) * | 2000-04-24 | 2005-10-25 | Aryx Therapeutics, Inc. | Materials and methods for the treatment of diabetes, hyperlipidemia, hypercholesterolemia, and atherosclerosis |
| WO2001082916A2 (en) * | 2000-05-03 | 2001-11-08 | Tularik Inc. | Combination therapeutic compositions and methods of use |
| GB0014969D0 (en) | 2000-06-19 | 2000-08-09 | Smithkline Beecham Plc | Novel method of treatment |
| US20030171399A1 (en) * | 2000-06-28 | 2003-09-11 | Tularik Inc. | Quinolinyl and benzothiazolyl modulators |
| NZ524519A (en) * | 2000-08-07 | 2004-09-24 | Ranbaxy Signature Llc | Liquid formulation of metformin |
| WO2003079972A2 (en) | 2002-02-22 | 2003-10-02 | New River Parmaceuticals Inc. | Active agent delivery systems and methods for protecting and administering active agents |
| AU2001294673A1 (en) * | 2000-09-21 | 2002-04-02 | Aryx Therapeutics | Isoxazolidine compounds useful in the treatment of diabetes, hyperlipidemia, andatherosclerosis |
| FR2816840B1 (fr) * | 2000-11-17 | 2004-04-09 | Flamel Tech Sa | Medicament a base de microcapsules d'anti-hyperclycemiant a liberation prolongee et son procede de preparation |
| US6452014B1 (en) | 2000-12-22 | 2002-09-17 | Geron Corporation | Telomerase inhibitors and methods of their use |
| CA2444481A1 (en) | 2001-04-11 | 2002-10-24 | Bristol-Myers Squibb Company | Amino acid complexes of c-aryl glucosides for treatment of diabetes and method |
| US20060047000A1 (en) * | 2001-04-24 | 2006-03-02 | Aryx Therapeutics, Inc. | Materials and methods for the treatment of diabetes, hyperlipidemia, hypercholesterolemia, and atherosclerosis |
| CZ20033450A3 (cs) * | 2001-05-29 | 2004-05-12 | Kyotoápharmaceuticaláindustriesźáltd | Heterocyklická sloučenina a její lékařské použití |
| RU2287529C2 (ru) * | 2001-05-29 | 2006-11-20 | Киото Фармасьютикал Индастриз, Лтд. | Новые гетероциклические производные и их медицинское использование |
| JP4152641B2 (ja) * | 2001-08-07 | 2008-09-17 | クラシエ製薬株式会社 | チアゾリジン誘導体の副作用軽減剤 |
| US8101209B2 (en) * | 2001-10-09 | 2012-01-24 | Flamel Technologies | Microparticulate oral galenical form for the delayed and controlled release of pharmaceutical active principles |
| FR2830447B1 (fr) * | 2001-10-09 | 2004-04-16 | Flamel Tech Sa | Forme galenique orale microparticulaire pour la liberation retardee et controlee de principes actifs pharmaceutiques |
| US6806381B2 (en) * | 2001-11-02 | 2004-10-19 | Bristol-Myers Squibb Company | Process for the preparation of aniline-derived thyroid receptor ligands |
| AU2002348276A1 (en) * | 2001-11-16 | 2003-06-10 | Bristol-Myers Squibb Company | Dual inhibitors of adipocyte fatty acid binding protein and keratinocyte fatty acid binding protein |
| US7015345B2 (en) * | 2002-02-21 | 2006-03-21 | Asahi Kasei Pharma Corporation | Propionic acid derivatives |
| PT1492511E (pt) | 2002-04-09 | 2009-04-09 | Flamel Tech Sa | Formulação farmacêutica oral na forma de suspensão aquosa de microcápsulas para libertação modificada de princípio(s) activo(s) |
| AU2003246791A1 (en) * | 2002-04-09 | 2003-10-20 | Flamel Technologies | Oral suspension of amoxicillin capsules |
| AU2003245832A1 (en) * | 2002-05-14 | 2003-11-11 | Siemens Aktiengesellschaft | Method for producing a transmission signal |
| US8268352B2 (en) * | 2002-08-05 | 2012-09-18 | Torrent Pharmaceuticals Limited | Modified release composition for highly soluble drugs |
| US8216609B2 (en) * | 2002-08-05 | 2012-07-10 | Torrent Pharmaceuticals Limited | Modified release composition of highly soluble drugs |
| TW200504021A (en) * | 2003-01-24 | 2005-02-01 | Bristol Myers Squibb Co | Substituted anilide ligands for the thyroid receptor |
| WO2004066929A2 (en) * | 2003-01-24 | 2004-08-12 | Bristol-Myers Squibb Company | Cycloalkyl containing anilide ligands for the thyroid receptor |
| US7851615B2 (en) * | 2003-04-17 | 2010-12-14 | Alnylam Pharmaceuticals, Inc. | Lipophilic conjugated iRNA agents |
| AU2004233092C9 (en) * | 2003-04-17 | 2010-10-28 | Alnylam Pharmaceuticals, Inc. | Modified iRNA agents |
| US8017762B2 (en) * | 2003-04-17 | 2011-09-13 | Alnylam Pharmaceuticals, Inc. | Modified iRNA agents |
| US8796436B2 (en) | 2003-04-17 | 2014-08-05 | Alnylam Pharmaceuticals, Inc. | Modified iRNA agents |
| US7723509B2 (en) * | 2003-04-17 | 2010-05-25 | Alnylam Pharmaceuticals | IRNA agents with biocleavable tethers |
| US20050004179A1 (en) * | 2003-05-22 | 2005-01-06 | Pedersen Ward A. | Methods and materials for treating, detecting, and reducing the risk of developing Alzheimer's Disease |
| US7459474B2 (en) * | 2003-06-11 | 2008-12-02 | Bristol-Myers Squibb Company | Modulators of the glucocorticoid receptor and method |
| US7371759B2 (en) * | 2003-09-25 | 2008-05-13 | Bristol-Myers Squibb Company | HMG-CoA reductase inhibitors and method |
| US7223761B2 (en) * | 2003-10-03 | 2007-05-29 | Amgen Inc. | Salts and polymorphs of a potent antidiabetic compound |
| US7317109B2 (en) * | 2003-11-12 | 2008-01-08 | Phenomix Corporation | Pyrrolidine compounds and methods for selective inhibition of dipeptidyl peptidase-IV |
| US7767828B2 (en) * | 2003-11-12 | 2010-08-03 | Phenomix Corporation | Methyl and ethyl substituted pyrrolidine compounds and methods for selective inhibition of dipeptidyl peptidase-IV |
| US7576121B2 (en) * | 2003-11-12 | 2009-08-18 | Phenomix Corporation | Pyrrolidine compounds and methods for selective inhibition of dipeptidyl peptidase-IV |
| US7674913B2 (en) * | 2003-11-12 | 2010-03-09 | Phenomix Corporation | Heterocyclic boronic acid compounds |
| US7420059B2 (en) * | 2003-11-20 | 2008-09-02 | Bristol-Myers Squibb Company | HMG-CoA reductase inhibitors and method |
| EP1778220A1 (en) * | 2004-07-12 | 2007-05-02 | Phenomix Corporation | Constrained cyano compounds |
| US7572805B2 (en) | 2004-07-14 | 2009-08-11 | Bristol-Myers Squibb Company | Pyrrolo(oxo)isoquinolines as 5HT ligands |
| WO2006064744A1 (ja) * | 2004-12-13 | 2006-06-22 | Daiichi Sankyo Company, Limited | 糖尿病の治療のための医薬組成物 |
| US7317024B2 (en) | 2005-01-13 | 2008-01-08 | Bristol-Myers Squibb Co. | Heterocyclic modulators of the glucocorticoid receptor, AP-1, and/or NF-κB activity and use thereof |
| EP1846410B1 (en) * | 2005-02-10 | 2009-01-21 | Bristol-Myers Squibb Company | Dihydroquinazolinones as 5ht modulators |
| US20070269486A1 (en) * | 2005-03-14 | 2007-11-22 | Conor Medsystems, Llc. | Methods and Devices for Reducing Tissue Damage After Ischemic Injury |
| US20080319031A1 (en) * | 2005-03-18 | 2008-12-25 | Orchid Chemicals & Pharmaceuticals Limited | Novel Tyrosine Derivatives |
| US7825139B2 (en) * | 2005-05-25 | 2010-11-02 | Forest Laboratories Holdings Limited (BM) | Compounds and methods for selective inhibition of dipeptidyl peptidase-IV |
| US7888381B2 (en) | 2005-06-14 | 2011-02-15 | Bristol-Myers Squibb Company | Modulators of glucocorticoid receptor, AP-1, and/or NF-κB activity, and use thereof |
| CA2617102A1 (en) * | 2005-07-28 | 2007-02-08 | Bristol-Myers Squibb Company | Substituted tetrahydro-1h-pyrido[4,3,b]indoles as serotonin receptor agonists and antagonists |
| US7795436B2 (en) * | 2005-08-24 | 2010-09-14 | Bristol-Myers Squibb Company | Substituted tricyclic heterocycles as serotonin receptor agonists and antagonists |
| US7592461B2 (en) | 2005-12-21 | 2009-09-22 | Bristol-Myers Squibb Company | Indane modulators of glucocorticoid receptor, AP-1, and/or NF-κB activity and use thereof |
| US20070238770A1 (en) * | 2006-04-05 | 2007-10-11 | Bristol-Myers Squibb Company | Process for preparing novel crystalline forms of peliglitazar, novel stable forms produced therein and formulations |
| US20080064884A1 (en) * | 2006-05-10 | 2008-03-13 | Astrazeneca Ab | Novel Process 1 |
| WO2008057857A1 (en) | 2006-11-01 | 2008-05-15 | Bristol-Myers Squibb Company | MODULATORS OF GLUCOCORTICOID RECEPTOR, AP-1, AND/OR NF-ϰB ACTIVITY AND USE THEREOF |
| US7968577B2 (en) | 2006-11-01 | 2011-06-28 | Bristol-Myers Squibb Company | Modulators of glucocorticoid receptor, AP-1, and/or NF-κB activity and use thereof |
| WO2008057855A2 (en) | 2006-11-01 | 2008-05-15 | Bristol-Myers Squibb Company | Heterocyclic compounds as modulators of glucocorticoid receptor, ap-i, and/or np-kappa-b activity |
| KR20140012199A (ko) | 2007-03-30 | 2014-01-29 | 암브룩스, 인코포레이티드 | 변형된 ｆｇｆ-21 폴리펩티드 및 그 용도 |
| US20160331729A9 (en) * | 2007-04-11 | 2016-11-17 | Omeros Corporation | Compositions and methods for prophylaxis and treatment of addictions |
| EP3053440B1 (en) | 2007-04-11 | 2020-08-12 | Omeros Corporation | Compositions and methods for prophylaxis and treatment of addictions |
| US11241420B2 (en) | 2007-04-11 | 2022-02-08 | Omeros Corporation | Compositions and methods for prophylaxis and treatment of addictions |
| ES2393885T7 (es) | 2007-06-04 | 2014-01-30 | Synergy Pharmaceuticals Inc. | Agonistas de la guanilato ciclasa útiles para el tratamiento de trastornos gastrointestinales, inflamación, cáncer y otros trastornos |
| US8969514B2 (en) | 2007-06-04 | 2015-03-03 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
| EP2209780B1 (en) | 2007-11-01 | 2014-01-01 | Bristol-Myers Squibb Company | Nonsteroidal compounds useful as modulators of glucocorticoid receptor ap-1 and/or nf- kappa b activity and use thereof |
| WO2009149279A2 (en) | 2008-06-04 | 2009-12-10 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| US8173621B2 (en) | 2008-06-11 | 2012-05-08 | Gilead Pharmasset Llc | Nucleoside cyclicphosphates |
| AU2009270833B2 (en) | 2008-07-16 | 2015-02-19 | Bausch Health Ireland Limited | Agonists of guanylate cyclase useful for the treatment of gastrointestinal, inflammation, cancer and other disorders |
| CN102695513A (zh) | 2008-12-23 | 2012-09-26 | 吉利德制药有限责任公司 | 核苷氨基磷酸酯 |
| AU2009329917B2 (en) * | 2008-12-23 | 2016-03-31 | Gilead Pharmasset Llc | Nucleoside analogs |
| BRPI0923815A2 (pt) | 2008-12-23 | 2015-07-14 | Pharmasset Inc | Síntese de nucleosídeos de purina |
| CA2754901A1 (en) | 2009-03-11 | 2010-09-16 | Omeros Corporation | Compositions and methods for prophylaxis and treatment of addictions |
| AU2011207210A1 (en) | 2010-01-22 | 2012-08-16 | Dana-Farber Cancer Institute, Inc. | Compositions,kits, and methods for identification, assessment, prevention, and therapy of metabolic disorders |
| SMT201700412T1 (it) | 2010-03-31 | 2017-11-15 | Gilead Pharmasset Llc | Procedimento per la cristallizzazione di (s)-isopropil 2-(((s)-(perfluorofenossi)(fenossi)fosforil)ammino)propanoato |
| ES2575860T3 (es) | 2010-07-09 | 2016-07-01 | Bhv Pharma, Inc. | Sistema de administración de liberación inmediata/retardada de combinación para productos farmacéuticos de semivida corta que incluyen remogliflozina |
| US20130156720A1 (en) | 2010-08-27 | 2013-06-20 | Ironwood Pharmaceuticals, Inc. | Compositions and methods for treating or preventing metabolic syndrome and related diseases and disorders |
| US9616097B2 (en) | 2010-09-15 | 2017-04-11 | Synergy Pharmaceuticals, Inc. | Formulations of guanylate cyclase C agonists and methods of use |
| US20120094959A1 (en) | 2010-10-19 | 2012-04-19 | Bonnie Blazer-Yost | Treatment of cystic diseases |
| US9486433B2 (en) | 2012-10-12 | 2016-11-08 | Mochida Pharmaceuticals Co. Ltd. | Compositions and methods for treating non-alcoholic steatohepatitis |
| US9623015B2 (en) | 2012-11-05 | 2017-04-18 | Commissariat À L'energie Atomique Et Aux Energies Alternatives (Cea) | Combination of an anti-cancer agent such as a tyrosinekinase inhibitor and a STAT5 antagonist, preferably a thiazolidinedione, for eliminating hematologic cancer stem cells in vivo and for preventing hematologic cancer relapse |
| US9486494B2 (en) | 2013-03-15 | 2016-11-08 | Synergy Pharmaceuticals, Inc. | Compositions useful for the treatment of gastrointestinal disorders |
| US10441560B2 (en) | 2013-03-15 | 2019-10-15 | Mochida Pharmaceutical Co., Ltd. | Compositions and methods for treating non-alcoholic steatohepatitis |
| SG11201507288UA (en) | 2013-03-15 | 2015-10-29 | Mochida Pharm Co Ltd | Compositions and methods for treating non-alcoholic steatohepatitis |
| WO2014151206A1 (en) | 2013-03-15 | 2014-09-25 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase and their uses |
| EP3004138B1 (en) | 2013-06-05 | 2024-03-13 | Bausch Health Ireland Limited | Ultra-pure agonists of guanylate cyclase c, method of making and using same |
| US9593113B2 (en) | 2013-08-22 | 2017-03-14 | Bristol-Myers Squibb Company | Imide and acylurea derivatives as modulators of the glucocorticoid receptor |
| JP2016534043A (ja) | 2013-10-09 | 2016-11-04 | シナジー ファーマシューティカルズ インコーポレイテッド | 炎症促進性サイトカインのダウンレギュレーションに有用なグアニル酸シクラーゼのアゴニスト |
| CN107108710B (zh) | 2014-10-24 | 2022-02-15 | 百时美施贵宝公司 | 修饰的fgf-21多肽及其用途 |
| 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 |
| US12310967B2 (en) | 2017-12-21 | 2025-05-27 | Gliapharm Sa | Compositions and methods of treatment for neurological disorders comprising motor neuron diseases |
| US12274703B2 (en) | 2017-12-21 | 2025-04-15 | Gliapharm Sa | Compositions and methods of treatment for neurological disorders comprising a dementia |
| MY210508A (en) | 2018-07-19 | 2025-09-28 | Astrazeneca Ab | Methods of treating hfpef employing dapagliflozin and compositions comprising the same |
| WO2020132378A2 (en) | 2018-12-22 | 2020-06-25 | Gliapharm Sa | Compositions and methods of treatment for neurological disorders comprising depression |
| TW202220672A (zh) | 2020-07-27 | 2022-06-01 | 瑞典商阿斯特捷利康公司 | 用達格列淨治療慢性腎臟病之方法 |
| WO2023144722A1 (en) | 2022-01-26 | 2023-08-03 | Astrazeneca Ab | Dapagliflozin for use in the treatment of prediabetes or reducing the risk of developing type 2 diabetes |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1432660A (en) * | 1973-10-30 | 1976-04-22 | Science Union & Cie | Piperazine derivatives processes for their preparation and and pharamacueitcal compositions containing them |
| JPS5522636A (en) * | 1978-08-04 | 1980-02-18 | Takeda Chem Ind Ltd | Thiazoliding derivative |
| DE3115152A1 (de) * | 1981-04-15 | 1982-12-02 | Hoechst Ag, 6000 Frankfurt | "heterocyclische phenylether und diese enthaltende herbizide mittel" |
| JPS58118577A (ja) * | 1982-01-07 | 1983-07-14 | Takeda Chem Ind Ltd | チアゾリジン誘導体 |
| HU194214B (en) * | 1983-02-15 | 1988-01-28 | Alkaloida Vegyeszeti Gyar | Process for producing 7-alkoxy-2h-chromene derivatives and insecticide and nematocide compositions containing them as active components |
-
1983
- 1983-08-30 JP JP58158375A patent/JPS6051189A/ja active Granted
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1984
- 1984-08-28 US US06/644,996 patent/US4572912A/en not_active Expired - Lifetime
- 1984-08-30 KR KR1019840005314A patent/KR890000370B1/ko not_active Expired
- 1984-08-30 ES ES535552A patent/ES8607297A1/es not_active Expired
- 1984-08-30 EP EP84305922A patent/EP0139421B1/en not_active Expired
- 1984-08-30 AU AU32559/84A patent/AU570067B2/en not_active Expired
- 1984-08-30 FI FI843422A patent/FI80693C/fi not_active IP Right Cessation
- 1984-08-30 DE DE8484305922T patent/DE3470742D1/de not_active Expired
- 1984-08-30 IE IE221784A patent/IE58036B1/en not_active IP Right Cessation
- 1984-08-30 CA CA000462173A patent/CA1263395A/en not_active Expired
- 1984-08-30 AT AT84305922T patent/ATE33838T1/de not_active IP Right Cessation
- 1984-08-30 DK DK415184A patent/DK164701C/da active
Also Published As
| Publication number | Publication date |
|---|---|
| EP0139421A1 (en) | 1985-05-02 |
| DK415184A (da) | 1985-03-01 |
| US4572912A (en) | 1986-02-25 |
| KR850001739A (ko) | 1985-04-01 |
| DE3470742D1 (en) | 1988-06-01 |
| FI843422A7 (fi) | 1985-03-01 |
| AU570067B2 (en) | 1988-03-03 |
| FI80693B (fi) | 1990-03-30 |
| JPH0231079B2 (OSRAM) | 1990-07-11 |
| DK164701B (da) | 1992-08-03 |
| IE842217L (en) | 1985-02-28 |
| IE58036B1 (en) | 1993-06-16 |
| ATE33838T1 (de) | 1988-05-15 |
| JPS6051189A (ja) | 1985-03-22 |
| DK164701C (da) | 1992-12-21 |
| EP0139421B1 (en) | 1988-04-27 |
| FI843422A0 (fi) | 1984-08-30 |
| KR890000370B1 (ko) | 1989-03-15 |
| CA1263395A (en) | 1989-11-28 |
| ES535552A0 (es) | 1986-05-16 |
| DK415184D0 (da) | 1984-08-30 |
| AU3255984A (en) | 1985-03-07 |
| ES8607297A1 (es) | 1986-05-16 |
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