CA1263395A - ¬5-(4-chroman-2-ylalkoxy)benzyl|-thiazolidine compounds - Google Patents
¬5-(4-chroman-2-ylalkoxy)benzyl|-thiazolidine compoundsInfo
- Publication number
- CA1263395A CA1263395A CA000462173A CA462173A CA1263395A CA 1263395 A CA1263395 A CA 1263395A CA 000462173 A CA000462173 A CA 000462173A CA 462173 A CA462173 A CA 462173A CA 1263395 A CA1263395 A CA 1263395A
- Authority
- CA
- Canada
- Prior art keywords
- group
- benzyl
- hydroxy
- ylmethoxy
- dione
- 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
Links
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 title description 109
- 150000001875 compounds Chemical class 0.000 claims abstract description 216
- 150000003839 salts Chemical class 0.000 claims abstract description 58
- 125000002252 acyl group Chemical group 0.000 claims abstract description 50
- 238000000034 method Methods 0.000 claims abstract description 46
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 42
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims abstract description 38
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 34
- 239000001257 hydrogen Substances 0.000 claims abstract description 30
- 239000002253 acid Substances 0.000 claims abstract description 22
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims abstract description 19
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 16
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims abstract description 15
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 15
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 15
- 125000001841 imino group Chemical group [H]N=* 0.000 claims abstract description 15
- 125000004429 atom Chemical group 0.000 claims abstract description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 6
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 6
- 239000001301 oxygen Substances 0.000 claims abstract description 6
- 125000005530 alkylenedioxy group Chemical group 0.000 claims abstract description 5
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract 3
- -1 nitro, amino Chemical group 0.000 claims description 80
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 36
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 33
- 229910052757 nitrogen Inorganic materials 0.000 claims description 23
- 125000001931 aliphatic group Chemical group 0.000 claims description 22
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 19
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 15
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 15
- 238000006460 hydrolysis reaction Methods 0.000 claims description 12
- 229910052727 yttrium Inorganic materials 0.000 claims description 11
- 150000001768 cations Chemical class 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 10
- 230000007062 hydrolysis Effects 0.000 claims description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 8
- 125000005843 halogen group Chemical group 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 229910052721 tungsten Inorganic materials 0.000 claims description 5
- WBOOERRGGVUMFH-UHFFFAOYSA-N [2-[[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenoxy]methyl]-2,5,7,8-tetramethyl-3,4-dihydrochromen-6-yl] acetate Chemical compound C1CC2=C(C)C(OC(=O)C)=C(C)C(C)=C2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O WBOOERRGGVUMFH-UHFFFAOYSA-N 0.000 claims description 4
- MKRQOYXCBGLHSP-UHFFFAOYSA-N [2-[[4-[(2-amino-4-oxo-1,3-thiazol-5-yl)methyl]phenoxy]methyl]-5,7,8-trimethyl-3,4-dihydro-2h-chromen-6-yl] acetate Chemical compound C1CC2=C(C)C(OC(=O)C)=C(C)C(C)=C2OC1COC(C=C1)=CC=C1CC1SC(=N)NC1=O MKRQOYXCBGLHSP-UHFFFAOYSA-N 0.000 claims description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 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 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
- PBDGWGCGORSKMS-UHFFFAOYSA-N 5-[[4-[(2-ethyl-6-hydroxy-5,7,8-trimethyl-3,4-dihydrochromen-2-yl)methoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound C1CC2=C(C)C(O)=C(C)C(C)=C2OC1(CC)COC(C=C1)=CC=C1CC1SC(=O)NC1=O PBDGWGCGORSKMS-UHFFFAOYSA-N 0.000 claims description 3
- XVHGGUYOMWMLEZ-UHFFFAOYSA-N 5-[[4-[(6-hydroxy-2,5,7,8-tetramethyl-4-oxo-3h-chromen-2-yl)methoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound C1C(=O)C=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O XVHGGUYOMWMLEZ-UHFFFAOYSA-N 0.000 claims description 3
- JIFNMLAISKSHGU-UHFFFAOYSA-N 5-[[4-[2-(6-hydroxy-2,5,7,8-tetramethyl-3,4-dihydrochromen-2-yl)ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O JIFNMLAISKSHGU-UHFFFAOYSA-N 0.000 claims description 3
- PJMZZASXTKZGFG-UHFFFAOYSA-N 5-[[4-[2-(7-tert-butyl-6-hydroxy-2-methyl-3,4-dihydrochromen-2-yl)ethoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound C1CC=2C=C(O)C(C(C)(C)C)=CC=2OC1(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O PJMZZASXTKZGFG-UHFFFAOYSA-N 0.000 claims description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 3
- 239000005864 Sulphur Substances 0.000 claims description 3
- ZFRCSMMBLAERFG-UHFFFAOYSA-N [2-[[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenoxy]methyl]-2,5,7,8-tetramethyl-3,4-dihydrochromen-6-yl] butanoate Chemical compound C1CC2=C(C)C(OC(=O)CCC)=C(C)C(C)=C2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O ZFRCSMMBLAERFG-UHFFFAOYSA-N 0.000 claims description 3
- JDHLLPHSCPFSRN-UHFFFAOYSA-N 2-amino-5-[[4-[(6-hydroxy-2,7-dimethyl-3,4-dihydrochromen-2-yl)methoxy]phenyl]methyl]-1,3-thiazol-4-one Chemical compound C1CC=2C=C(O)C(C)=CC=2OC1(C)COC(C=C1)=CC=C1CC1SC(=N)NC1=O JDHLLPHSCPFSRN-UHFFFAOYSA-N 0.000 claims description 2
- NADGGYNLWBHMFK-UHFFFAOYSA-N 2-amino-5-[[4-[(7-tert-butyl-6-hydroxy-2-methyl-3,4-dihydrochromen-2-yl)methoxy]phenyl]methyl]-1,3-thiazol-4-one Chemical compound C1CC=2C=C(O)C(C(C)(C)C)=CC=2OC1(C)COC(C=C1)=CC=C1CC1SC(N)=NC1=O NADGGYNLWBHMFK-UHFFFAOYSA-N 0.000 claims description 2
- AYHOXONMNWCGII-UHFFFAOYSA-N 2-amino-5-[[4-[[6-hydroxy-5,7,8-trimethyl-2-(2-methylpropyl)-4-oxo-3h-chromen-2-yl]methoxy]phenyl]methyl]-1,3-thiazol-4-one Chemical compound C1C(=O)C2=C(C)C(O)=C(C)C(C)=C2OC1(CC(C)C)COC(C=C1)=CC=C1CC1SC(=N)NC1=O AYHOXONMNWCGII-UHFFFAOYSA-N 0.000 claims description 2
- SRWRQPQMXBCFIH-UHFFFAOYSA-N 5-[[4-[(6-hydroxy-2,7-dimethyl-3,4-dihydrochromen-2-yl)methoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound C1CC=2C=C(O)C(C)=CC=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O SRWRQPQMXBCFIH-UHFFFAOYSA-N 0.000 claims description 2
- 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 2
- 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 description 2
- CPUZQNCYTMEBRA-UHFFFAOYSA-N [2-[[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenoxy]methyl]-2,5,7,8-tetramethyl-3,4-dihydrochromen-6-yl] benzoate Chemical compound C1CC=2C(C)=C(OC(=O)C=3C=CC=CC=3)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O CPUZQNCYTMEBRA-UHFFFAOYSA-N 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 24
- 150000002431 hydrogen Chemical group 0.000 claims 10
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 8
- 229910052736 halogen Inorganic materials 0.000 claims 8
- 150000002367 halogens Chemical class 0.000 claims 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 7
- 125000001038 naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 claims 6
- IDAAHCHPOHQGHC-UHFFFAOYSA-N 5-[[4-[(7-tert-butyl-6-hydroxy-2-methyl-4-oxo-3h-chromen-2-yl)methoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound C1C(=O)C=2C=C(O)C(C(C)(C)C)=CC=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O IDAAHCHPOHQGHC-UHFFFAOYSA-N 0.000 claims 2
- HIKRPVCYHOKTNQ-UHFFFAOYSA-N 5-[[4-[[6-hydroxy-5,7,8-trimethyl-2-(2-methylpropyl)-3,4-dihydrochromen-2-yl]methoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound C1CC2=C(C)C(O)=C(C)C(C)=C2OC1(CC(C)C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O HIKRPVCYHOKTNQ-UHFFFAOYSA-N 0.000 claims 2
- XOCUXOWLYLLJLV-UHFFFAOYSA-N [O].[S] Chemical compound [O].[S] XOCUXOWLYLLJLV-UHFFFAOYSA-N 0.000 claims 2
- AWOOSJDSQSEOEE-UHFFFAOYSA-N 2-amino-5-[[4-[(2-ethyl-6-hydroxy-5,7,8-trimethyl-3,4-dihydrochromen-2-yl)methoxy]phenyl]methyl]-1,3-thiazol-4-one Chemical compound C1CC2=C(C)C(O)=C(C)C(C)=C2OC1(CC)COC(C=C1)=CC=C1CC1SC(=N)NC1=O AWOOSJDSQSEOEE-UHFFFAOYSA-N 0.000 claims 1
- MBKXRJQMLWSSTQ-UHFFFAOYSA-N 2-amino-5-[[4-[(6-hydroxy-2,5,7,8-tetramethyl-4-oxo-3h-chromen-2-yl)methoxy]phenyl]methyl]-1,3-thiazol-4-one Chemical compound C1C(=O)C=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(N)=NC1=O MBKXRJQMLWSSTQ-UHFFFAOYSA-N 0.000 claims 1
- RNNLMVCUVMLZFX-UHFFFAOYSA-N 2-amino-5-[[4-[(6-hydroxy-5,7,8-trimethyl-3,4-dihydro-2h-chromen-2-yl)methoxy]phenyl]methyl]-1,3-thiazol-4-one Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1COC(C=C1)=CC=C1CC1SC(=N)NC1=O RNNLMVCUVMLZFX-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- 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
- QFNLYWYLRFIOKH-UHFFFAOYSA-N 5-[[4-[[6-hydroxy-5,7,8-trimethyl-2-(2-methylpropyl)-4-oxo-3h-chromen-2-yl]methoxy]phenyl]methyl]-1,3-thiazolidine-2,4-dione Chemical compound C1C(=O)C2=C(C)C(O)=C(C)C(C)=C2OC1(CC(C)C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O QFNLYWYLRFIOKH-UHFFFAOYSA-N 0.000 claims 1
- NPWAZFOGEUJYOS-UHFFFAOYSA-N [2-[2-[4-[(2-amino-4-oxo-1,3-thiazol-5-yl)methyl]phenoxy]ethyl]-7-tert-butyl-2-methyl-3,4-dihydrochromen-6-yl] acetate Chemical compound O1C=2C=C(C(C)(C)C)C(OC(=O)C)=CC=2CCC1(C)CCOC(C=C1)=CC=C1CC1SC(N)=NC1=O NPWAZFOGEUJYOS-UHFFFAOYSA-N 0.000 claims 1
- NLYKYOJFKOSQBY-UHFFFAOYSA-N [2-[[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenoxy]methyl]-2,5,7,8-tetramethyl-3,4-dihydrochromen-6-yl] pyridine-3-carboxylate Chemical compound C1CC=2C(C)=C(OC(=O)C=3C=NC=CC=3)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O NLYKYOJFKOSQBY-UHFFFAOYSA-N 0.000 claims 1
- VXEJOWPCTWGRDC-UHFFFAOYSA-N [2-[[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenoxy]methyl]-2,5,7,8-tetramethyl-4-oxo-3h-chromen-6-yl] acetate Chemical compound C1C(=O)C2=C(C)C(OC(=O)C)=C(C)C(C)=C2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O VXEJOWPCTWGRDC-UHFFFAOYSA-N 0.000 claims 1
- 159000000000 sodium salts Chemical class 0.000 claims 1
- 239000008280 blood Substances 0.000 abstract description 20
- 210000004369 blood Anatomy 0.000 abstract description 20
- 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 abstract description 3
- 230000001225 therapeutic effect Effects 0.000 abstract description 3
- 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 264
- 239000000203 mixture Substances 0.000 description 144
- 239000002904 solvent Substances 0.000 description 118
- 238000006243 chemical reaction Methods 0.000 description 97
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 74
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 69
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 66
- 239000000741 silica gel Substances 0.000 description 64
- 229910002027 silica gel Inorganic materials 0.000 description 64
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 57
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 56
- 101150041968 CDC13 gene Proteins 0.000 description 51
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 51
- 238000001819 mass spectrum Methods 0.000 description 50
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 50
- 238000002360 preparation method Methods 0.000 description 49
- 238000004809 thin layer chromatography Methods 0.000 description 48
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 45
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 41
- ZOBPZXTWZATXDG-UHFFFAOYSA-N 1,3-thiazolidine-2,4-dione Chemical compound O=C1CSC(=O)N1 ZOBPZXTWZATXDG-UHFFFAOYSA-N 0.000 description 40
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 40
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 35
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 33
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 30
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 30
- 239000011541 reaction mixture Substances 0.000 description 29
- 238000002844 melting Methods 0.000 description 27
- 230000008018 melting Effects 0.000 description 27
- 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 24
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 22
- VZWXIQHBIQLMPN-UHFFFAOYSA-N chromane Chemical group C1=CC=C2CCCOC2=C1 VZWXIQHBIQLMPN-UHFFFAOYSA-N 0.000 description 22
- 239000007858 starting material Substances 0.000 description 22
- 125000000217 alkyl group Chemical group 0.000 description 20
- 229910052938 sodium sulfate Inorganic materials 0.000 description 20
- 235000011152 sodium sulphate Nutrition 0.000 description 20
- 239000012043 crude product Substances 0.000 description 19
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 18
- 239000003795 chemical substances by application Substances 0.000 description 17
- 239000003921 oil Substances 0.000 description 17
- 239000000243 solution Substances 0.000 description 17
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 16
- 239000000284 extract Substances 0.000 description 16
- 238000010898 silica gel chromatography Methods 0.000 description 16
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 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
- 239000000047 product Substances 0.000 description 15
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 14
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- 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
- 238000004440 column chromatography Methods 0.000 description 13
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- XULZDUJMHUYSIN-UHFFFAOYSA-N [2-[[4-(2-chloro-3-ethoxy-3-oxopropyl)phenoxy]methyl]-2,5,7,8-tetramethyl-3,4-dihydrochromen-6-yl] benzoate Chemical compound C1=CC(CC(Cl)C(=O)OCC)=CC=C1OCC1(C)OC2=C(C)C(C)=C(OC(=O)C=3C=CC=CC=3)C(C)=C2CC1 XULZDUJMHUYSIN-UHFFFAOYSA-N 0.000 description 1
- KIEXEJMNEKHHMI-UHFFFAOYSA-N [2-[[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenoxy]methyl]-2,5,7,8-tetramethyl-6-(pyridine-3-carbonyloxy)-3,4-dihydrochromen-4-yl] pyridine-3-carboxylate Chemical compound C1C(OC(=O)C=2C=NC=CC=2)C=2C(C)=C(OC(=O)C=3C=NC=CC=3)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O KIEXEJMNEKHHMI-UHFFFAOYSA-N 0.000 description 1
- OERHJMLCXTYNRU-UHFFFAOYSA-N [2-[[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenoxy]methyl]-2,7-dimethyl-3,4-dihydrochromen-6-yl] acetate Chemical compound O1C=2C=C(C)C(OC(=O)C)=CC=2CCC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O OERHJMLCXTYNRU-UHFFFAOYSA-N 0.000 description 1
- QXWXLXPNUURLPI-UHFFFAOYSA-N [2-[[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenoxy]methyl]-2-ethyl-5,7,8-trimethyl-3,4-dihydrochromen-6-yl] 2-methylpropanoate Chemical compound C1CC2=C(C)C(OC(=O)C(C)C)=C(C)C(C)=C2OC1(CC)COC(C=C1)=CC=C1CC1SC(=O)NC1=O QXWXLXPNUURLPI-UHFFFAOYSA-N 0.000 description 1
- GXYNQYNZZSEZTP-UHFFFAOYSA-N [2-[[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenoxy]methyl]-2-ethyl-7,8-dimethoxy-5-methyl-3,4-dihydrochromen-6-yl] pentanoate Chemical compound O1C=2C(OC)=C(OC)C(OC(=O)CCCC)=C(C)C=2CCC1(CC)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXYNQYNZZSEZTP-UHFFFAOYSA-N 0.000 description 1
- ALKWCXJQCFRQNZ-UHFFFAOYSA-N [2-[[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenoxy]methyl]-2-methyl-3,4-dihydrochromen-6-yl] acetate Chemical compound C1CC2=CC(OC(=O)C)=CC=C2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O ALKWCXJQCFRQNZ-UHFFFAOYSA-N 0.000 description 1
- HXFGCRHHSCJLLW-UHFFFAOYSA-N [2-[[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenoxy]methyl]-4-hydroxy-2,5,7,8-tetramethyl-3,4-dihydrochromen-6-yl] acetate Chemical compound C1C(O)C2=C(C)C(OC(=O)C)=C(C)C(C)=C2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O HXFGCRHHSCJLLW-UHFFFAOYSA-N 0.000 description 1
- POEDKGMTTJWUCC-UHFFFAOYSA-N [2-[[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenoxy]methyl]-7,8-dimethoxy-2,5-dimethyl-4-oxo-3H-chromen-6-yl] 3-phenylprop-2-enoate Chemical compound C(C=CC1=CC=CC=C1)(=O)OC=1C(=C2C(CC(OC2=C(C=1OC)OC)(C)COC1=CC=C(CC2C(NC(S2)=O)=O)C=C1)=O)C POEDKGMTTJWUCC-UHFFFAOYSA-N 0.000 description 1
- HKJWVVFXPNSIQN-UHFFFAOYSA-N [2-[[4-[(2-amino-4-oxo-1,3-thiazol-5-yl)methyl]phenoxy]methyl]-2,5,7,8-tetramethyl-3,4-dihydrochromen-6-yl] acetate Chemical compound C1CC2=C(C)C(OC(=O)C)=C(C)C(C)=C2OC1(C)COC(C=C1)=CC=C1CC1SC(N)=NC1=O HKJWVVFXPNSIQN-UHFFFAOYSA-N 0.000 description 1
- PGGUTEVKGPGTDF-UHFFFAOYSA-N [2-[[4-[(2-amino-4-oxo-1,3-thiazol-5-yl)methyl]phenoxy]methyl]-2,5,7,8-tetramethyl-4-oxo-3h-chromen-6-yl] acetate Chemical compound C1C(=O)C2=C(C)C(OC(=O)C)=C(C)C(C)=C2OC1(C)COC(C=C1)=CC=C1CC1SC(N)=NC1=O PGGUTEVKGPGTDF-UHFFFAOYSA-N 0.000 description 1
- KSJXUAQYPZFHNB-UHFFFAOYSA-N [2-[[4-[(2-amino-4-oxo-1,3-thiazol-5-yl)methyl]phenoxy]methyl]-2,7-dimethyl-3,4-dihydrochromen-6-yl] acetate Chemical compound O1C=2C=C(C)C(OC(=O)C)=CC=2CCC1(C)COC(C=C1)=CC=C1CC1SC(=N)NC1=O KSJXUAQYPZFHNB-UHFFFAOYSA-N 0.000 description 1
- OUVBUCVJPOSKMX-UHFFFAOYSA-N [2-[[4-[(2-amino-4-oxo-1,3-thiazol-5-yl)methyl]phenoxy]methyl]-2-ethyl-5,7,8-trimethyl-3,4-dihydrochromen-6-yl] 2-phenylacetate Chemical compound C1CC2=C(C)C(OC(=O)CC=3C=CC=CC=3)=C(C)C(C)=C2OC1(CC)COC(C=C1)=CC=C1CC1SC(=N)NC1=O OUVBUCVJPOSKMX-UHFFFAOYSA-N 0.000 description 1
- YUMIXJDAPVOXFK-UHFFFAOYSA-N [2-[[4-[(2-amino-4-oxo-1,3-thiazol-5-yl)methyl]phenoxy]methyl]-2-ethyl-7,8-dimethoxy-5-methyl-3,4-dihydrochromen-6-yl] pentanoate Chemical compound O1C=2C(OC)=C(OC)C(OC(=O)CCCC)=C(C)C=2CCC1(CC)COC(C=C1)=CC=C1CC1SC(=N)NC1=O YUMIXJDAPVOXFK-UHFFFAOYSA-N 0.000 description 1
- WRZAXUSXBKLBMO-UHFFFAOYSA-N [2-[[4-[(2-amino-4-oxo-1,3-thiazol-5-yl)methyl]phenoxy]methyl]-2-methyl-3,4-dihydrochromen-6-yl] acetate Chemical compound C1CC2=CC(OC(=O)C)=CC=C2OC1(C)COC(C=C1)=CC=C1CC1SC(N)=NC1=O WRZAXUSXBKLBMO-UHFFFAOYSA-N 0.000 description 1
- KPJWYTQJLIYNAA-UHFFFAOYSA-N [2-[[4-[(2-amino-4-oxo-1,3-thiazol-5-yl)methyl]phenoxy]methyl]-2-methyl-5,7-di(propan-2-yl)-3,4-dihydrochromen-6-yl] acetate Chemical compound C1CC=2C(C(C)C)=C(OC(C)=O)C(C(C)C)=CC=2OC1(C)COC(C=C1)=CC=C1CC1SC(N)=NC1=O KPJWYTQJLIYNAA-UHFFFAOYSA-N 0.000 description 1
- LWXFFYBAPHOPNS-UHFFFAOYSA-N [2-[[4-[(2-amino-4-oxo-1,3-thiazol-5-yl)methyl]phenoxy]methyl]-7,8-dimethoxy-2,5-dimethyl-3,4-dihydrochromen-6-yl] 3-phenylprop-2-enoate Chemical compound CC1=C2CCC(C)(COC=3C=CC(CC4C(N=C(N)S4)=O)=CC=3)OC2=C(OC)C(OC)=C1OC(=O)C=CC1=CC=CC=C1 LWXFFYBAPHOPNS-UHFFFAOYSA-N 0.000 description 1
- RSACYUIGOJHQMS-UHFFFAOYSA-N [2-[[4-[(2-amino-4-oxo-1,3-thiazol-5-yl)methyl]phenoxy]methyl]-7,8-dimethoxy-5-methyl-3,4-dihydro-2h-chromen-6-yl] 3-chlorobenzoate Chemical compound CC1=C2CCC(COC=3C=CC(CC4C(NC(=N)S4)=O)=CC=3)OC2=C(OC)C(OC)=C1OC(=O)C1=CC=CC(Cl)=C1 RSACYUIGOJHQMS-UHFFFAOYSA-N 0.000 description 1
- HSBCYHGEDCAPTE-UHFFFAOYSA-N [2-[[4-[(2-amino-4-oxo-1,3-thiazol-5-yl)methyl]phenoxy]methyl]-7-tert-butyl-2-methyl-3,4-dihydrochromen-6-yl] 3,5-ditert-butyl-4-hydroxybenzoate Chemical compound CC(C)(C)C1=C(O)C(C(C)(C)C)=CC(C(=O)OC=2C(=CC=3OC(C)(COC=4C=CC(CC5C(NC(=N)S5)=O)=CC=4)CCC=3C=2)C(C)(C)C)=C1 HSBCYHGEDCAPTE-UHFFFAOYSA-N 0.000 description 1
- BEGOQIHJNDOLIF-UHFFFAOYSA-N [2-[[4-[(4-amino-2-imino-5h-1,3-thiazol-5-yl)methyl]phenoxy]methyl]-2,5,7,8-tetramethyl-3,4-dihydrochromen-6-yl] benzoate Chemical compound C1CC=2C(C)=C(OC(=O)C=3C=CC=CC=3)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=N)N=C1N BEGOQIHJNDOLIF-UHFFFAOYSA-N 0.000 description 1
- YQQTZEPOVBHUCF-UHFFFAOYSA-N [2-[[4-[(4-amino-2-imino-5h-1,3-thiazol-5-yl)methyl]phenoxy]methyl]-2,5,7,8-tetramethyl-4-oxo-3h-chromen-6-yl] cyclohexanecarboxylate Chemical compound C1C(=O)C=2C(C)=C(OC(=O)C3CCCCC3)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=N)NC1=N YQQTZEPOVBHUCF-UHFFFAOYSA-N 0.000 description 1
- KGELBEPUCNLAFD-UHFFFAOYSA-N [2-[[4-[(4-amino-2-imino-5h-1,3-thiazol-5-yl)methyl]phenoxy]methyl]-2,5,7-trimethyl-3,4-dihydrochromen-6-yl] cyclohexanecarboxylate Chemical compound C1CC=2C(C)=C(OC(=O)C3CCCCC3)C(C)=CC=2OC1(C)COC(C=C1)=CC=C1CC1SC(=N)NC1=N KGELBEPUCNLAFD-UHFFFAOYSA-N 0.000 description 1
- YQZSHJGCFOPIPZ-UHFFFAOYSA-N [2-[[4-[(4-amino-2-imino-5h-1,3-thiazol-5-yl)methyl]phenoxy]methyl]-2-ethyl-7,8-dimethoxy-5-methyl-3,4-dihydrochromen-6-yl] acetate Chemical compound C1CC2=C(C)C(OC(C)=O)=C(OC)C(OC)=C2OC1(CC)COC(C=C1)=CC=C1CC1SC(=N)NC1=N YQZSHJGCFOPIPZ-UHFFFAOYSA-N 0.000 description 1
- JFVVWUZUBPYGNG-UHFFFAOYSA-N [2-[[4-[(4-amino-2-imino-5h-1,3-thiazol-5-yl)methyl]phenoxy]methyl]-7-tert-butyl-2-methyl-3,4-dihydrochromen-6-yl] acetate Chemical compound O1C=2C=C(C(C)(C)C)C(OC(=O)C)=CC=2CCC1(C)COC(C=C1)=CC=C1CC1SC(=N)N=C1N JFVVWUZUBPYGNG-UHFFFAOYSA-N 0.000 description 1
- HWHNTGSMMNCAKN-UHFFFAOYSA-N [2-[[4-[(4-amino-2-imino-5h-1,3-thiazol-5-yl)methyl]phenoxy]methyl]-7-tert-butyl-3,4-dihydro-2h-chromen-6-yl] acetate Chemical compound O1C=2C=C(C(C)(C)C)C(OC(=O)C)=CC=2CCC1COC(C=C1)=CC=C1CC1SC(=N)N=C1N HWHNTGSMMNCAKN-UHFFFAOYSA-N 0.000 description 1
- KHZAIDOCEPSBAM-UHFFFAOYSA-N [4-acetyloxy-2-[[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenoxy]methyl]-2,5,7,8-tetramethyl-3,4-dihydrochromen-6-yl] benzoate Chemical compound O1C2=C(C)C(C)=C(OC(=O)C=3C=CC=CC=3)C(C)=C2C(OC(=O)C)CC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O KHZAIDOCEPSBAM-UHFFFAOYSA-N 0.000 description 1
- YUCGRXIZSXMNQZ-UHFFFAOYSA-N [6-(3,5-dichlorobenzoyl)oxy-2-[[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenoxy]methyl]-7,8-dimethoxy-5-methyl-3,4-dihydro-2h-chromen-4-yl] 3,5-dichlorobenzoate Chemical compound C1C(OC(=O)C=2C=C(Cl)C=C(Cl)C=2)C=2C(C)=C(OC(=O)C=3C=C(Cl)C=C(Cl)C=3)C(OC)=C(OC)C=2OC1COC(C=C1)=CC=C1CC1SC(=O)NC1=O YUCGRXIZSXMNQZ-UHFFFAOYSA-N 0.000 description 1
- JQGLXFODQGLGTH-UHFFFAOYSA-N [6-(methoxymethoxy)-2,5,7,8-tetramethyl-3,4-dihydrochromen-2-yl]methanol Chemical compound O1C(C)(CO)CCC2=C(C)C(OCOC)=C(C)C(C)=C21 JQGLXFODQGLGTH-UHFFFAOYSA-N 0.000 description 1
- ICBFXRNRZFRFLA-UHFFFAOYSA-N [6-benzoyloxy-2-[[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenoxy]methyl]-2,5,7,8-tetramethyl-3,4-dihydrochromen-4-yl] benzoate Chemical compound C1C(OC(=O)C=2C=CC=CC=2)C=2C(C)=C(OC(=O)C=3C=CC=CC=3)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O ICBFXRNRZFRFLA-UHFFFAOYSA-N 0.000 description 1
- AOEOUJHWIFMXCQ-UHFFFAOYSA-N [6-butanoyloxy-2-[[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenoxy]methyl]-2,5,7,8-tetramethyl-3,4-dihydrochromen-4-yl] butanoate Chemical compound O1C2=C(C)C(C)=C(OC(=O)CCC)C(C)=C2C(OC(=O)CCC)CC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O AOEOUJHWIFMXCQ-UHFFFAOYSA-N 0.000 description 1
- QFOFKZGKZMZBRU-UHFFFAOYSA-N [7-tert-butyl-2-[2-[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenoxy]ethyl]-2-methyl-3,4-dihydrochromen-6-yl] prop-2-enoate Chemical compound C1CC=2C=C(OC(=O)C=C)C(C(C)(C)C)=CC=2OC1(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O QFOFKZGKZMZBRU-UHFFFAOYSA-N 0.000 description 1
- CNEHQGYOKKTJBM-UHFFFAOYSA-N [7-tert-butyl-2-methyl-2-[2-(4-nitrophenoxy)ethyl]-3,4-dihydrochromen-6-yl] acetate Chemical compound O1C=2C=C(C(C)(C)C)C(OC(=O)C)=CC=2CCC1(C)CCOC1=CC=C([N+]([O-])=O)C=C1 CNEHQGYOKKTJBM-UHFFFAOYSA-N 0.000 description 1
- NQBWCYBRNVDLGV-UHFFFAOYSA-N [[4-[(2,4-dioxo-1,3-thiazolidin-5-yl)methyl]phenoxy]-(5,7,8-trimethyl-4-oxo-6-phenyl-2,3-dihydrochromen-2-yl)methyl] butanoate Chemical compound C1C(=O)C2=C(C)C(C=3C=CC=CC=3)=C(C)C(C)=C2OC1C(OC(=O)CCC)OC(C=C1)=CC=C1CC1SC(=O)NC1=O NQBWCYBRNVDLGV-UHFFFAOYSA-N 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 150000008062 acetophenones Chemical class 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 150000001252 acrylic acid derivatives Chemical class 0.000 description 1
- 125000003647 acryloyl group Chemical group O=C([*])C([H])=C([H])[H] 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 150000007933 aliphatic carboxylic acids Chemical class 0.000 description 1
- 150000004703 alkoxides Chemical class 0.000 description 1
- 159000000013 aluminium salts Chemical class 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O ammonium group Chemical group [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000001315 anti-hyperlipaemic effect Effects 0.000 description 1
- 230000036528 appetite Effects 0.000 description 1
- 235000019789 appetite Nutrition 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 1
- 229940073608 benzyl chloride Drugs 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 244000309464 bull Species 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
- 125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
- DVECBJCOGJRVPX-UHFFFAOYSA-N butyryl chloride Chemical compound CCCC(Cl)=O DVECBJCOGJRVPX-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
- 239000010779 crude oil Substances 0.000 description 1
- 229940045803 cuprous chloride Drugs 0.000 description 1
- NKLCHDQGUHMCGL-UHFFFAOYSA-N cyclohexylidenemethanone Chemical group O=C=C1CCCCC1 NKLCHDQGUHMCGL-UHFFFAOYSA-N 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 239000012024 dehydrating agents Substances 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 150000001989 diazonium salts Chemical class 0.000 description 1
- 238000006193 diazotization reaction Methods 0.000 description 1
- 229940117389 dichlorobenzene Drugs 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 229940088598 enzyme Drugs 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- RDEGOZZHIBWTOB-UHFFFAOYSA-N ethyl 2-bromo-3-[4-[(2-ethyl-6-hydroxy-7,8-dimethoxy-5-methyl-4-oxo-3h-chromen-2-yl)methoxy]phenyl]propanoate Chemical compound C1=CC(CC(Br)C(=O)OCC)=CC=C1OCC1(CC)OC2=C(OC)C(OC)=C(O)C(C)=C2C(=O)C1 RDEGOZZHIBWTOB-UHFFFAOYSA-N 0.000 description 1
- VCDUZWFBQGVYPM-UHFFFAOYSA-N ethyl 2-chloro-3-[4-[(6-hydroxy-2,7-dimethyl-4-oxo-3h-chromen-2-yl)methoxy]phenyl]propanoate Chemical compound C1=CC(CC(Cl)C(=O)OCC)=CC=C1OCC1(C)OC2=CC(C)=C(O)C=C2C(=O)C1 VCDUZWFBQGVYPM-UHFFFAOYSA-N 0.000 description 1
- FCZCIXQGZOUIDN-UHFFFAOYSA-N ethyl 2-diethoxyphosphinothioyloxyacetate Chemical compound CCOC(=O)COP(=S)(OCC)OCC FCZCIXQGZOUIDN-UHFFFAOYSA-N 0.000 description 1
- BJZLJBWZSYDNBG-UHFFFAOYSA-N ethyl 3-[4-[(6-acetyloxy-2,7-dimethyl-4-oxo-3h-chromen-2-yl)methoxy]phenyl]-2-chloropropanoate Chemical compound C1=CC(CC(Cl)C(=O)OCC)=CC=C1OCC1(C)OC2=CC(C)=C(OC(C)=O)C=C2C(=O)C1 BJZLJBWZSYDNBG-UHFFFAOYSA-N 0.000 description 1
- VNJIXVMEVJUOMU-UHFFFAOYSA-N ethyl 3-[4-[(6-acetyloxy-2-ethyl-5,7,8-trimethyl-3,4-dihydrochromen-2-yl)methoxy]phenyl]-2-chloropropanoate Chemical compound C1=CC(CC(Cl)C(=O)OCC)=CC=C1OCC1(CC)OC2=C(C)C(C)=C(OC(C)=O)C(C)=C2CC1 VNJIXVMEVJUOMU-UHFFFAOYSA-N 0.000 description 1
- LGVWTYMOYHUQEO-UHFFFAOYSA-N ethyl 3-[4-[(6-acetyloxy-5,7,8-trimethyl-3,4-dihydro-2h-chromen-2-yl)methoxy]phenyl]-2-chloropropanoate Chemical compound C1=CC(CC(Cl)C(=O)OCC)=CC=C1OCC1OC2=C(C)C(C)=C(OC(C)=O)C(C)=C2CC1 LGVWTYMOYHUQEO-UHFFFAOYSA-N 0.000 description 1
- XTUDJVATAVBGJE-UHFFFAOYSA-N ethyl 3-[4-[(6-acetyloxy-7-tert-butyl-2-methyl-3,4-dihydrochromen-2-yl)methoxy]phenyl]-2-chloropropanoate Chemical compound C1=CC(CC(Cl)C(=O)OCC)=CC=C1OCC1(C)OC2=CC(C(C)(C)C)=C(OC(C)=O)C=C2CC1 XTUDJVATAVBGJE-UHFFFAOYSA-N 0.000 description 1
- XMBVJWWQZIUBEF-UHFFFAOYSA-N ethyl 3-[4-[2-(6-acetyloxy-2,5,7,8-tetramethyl-3,4-dihydrochromen-2-yl)ethoxy]phenyl]-2-chloropropanoate Chemical compound C1=CC(CC(Cl)C(=O)OCC)=CC=C1OCCC1(C)OC2=C(C)C(C)=C(OC(C)=O)C(C)=C2CC1 XMBVJWWQZIUBEF-UHFFFAOYSA-N 0.000 description 1
- NPZYGABDUFTKKN-UHFFFAOYSA-N ethyl 3-[4-[2-(6-acetyloxy-7,8-dimethoxy-2,5-dimethyl-3,4-dihydrochromen-2-yl)ethoxy]phenyl]-2-chloropropanoate Chemical compound C1=CC(CC(Cl)C(=O)OCC)=CC=C1OCCC1(C)OC2=C(OC)C(OC)=C(OC(C)=O)C(C)=C2CC1 NPZYGABDUFTKKN-UHFFFAOYSA-N 0.000 description 1
- PCJKLNUDPHSYRB-UHFFFAOYSA-N ethyl 3-[4-[2-(6-acetyloxy-7-tert-butyl-2-methyl-3,4-dihydrochromen-2-yl)ethoxy]phenyl]-2-chloropropanoate Chemical compound C1=CC(CC(Cl)C(=O)OCC)=CC=C1OCCC1(C)OC2=CC(C(C)(C)C)=C(OC(C)=O)C=C2CC1 PCJKLNUDPHSYRB-UHFFFAOYSA-N 0.000 description 1
- MIAYJKISFQIYJL-UHFFFAOYSA-N ethyl 3-[4-[[6-acetyloxy-5,7,8-trimethyl-2-(2-methylpropyl)-3,4-dihydrochromen-2-yl]methoxy]phenyl]-2-chloropropanoate Chemical compound C1=CC(CC(Cl)C(=O)OCC)=CC=C1OCC1(CC(C)C)OC2=C(C)C(C)=C(OC(C)=O)C(C)=C2CC1 MIAYJKISFQIYJL-UHFFFAOYSA-N 0.000 description 1
- 239000002024 ethyl acetate extract Substances 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 229940116332 glucose oxidase Drugs 0.000 description 1
- 235000019420 glucose oxidase Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004464 hydroxyphenyl group Chemical group 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 230000037356 lipid metabolism Effects 0.000 description 1
- 230000003859 lipid peroxidation Effects 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical class [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
- VCCPBPXMXHHRLN-UHFFFAOYSA-N methylsulfinylmethane;propan-2-one Chemical compound CC(C)=O.CS(C)=O VCCPBPXMXHHRLN-UHFFFAOYSA-N 0.000 description 1
- 230000003228 microsomal effect Effects 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 125000003232 p-nitrobenzoyl group Chemical group [N+](=O)([O-])C1=CC=C(C(=O)*)C=C1 0.000 description 1
- KDLHZDBZIXYQEI-VENIDDJXSA-N palladium-100 Chemical compound [100Pd] KDLHZDBZIXYQEI-VENIDDJXSA-N 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- HPQWFBQEBOJJDP-UHFFFAOYSA-M potassium;2-chloro-3-[4-[2-[5,7-dibutyl-6-(cyclohexanecarbonyloxy)-4-oxo-2-propan-2-yl-8-propyl-3h-chromen-2-yl]ethoxy]phenyl]propanoate Chemical compound [K+].C1C(=O)C=2C(CCCC)=C(OC(=O)C3CCCCC3)C(CCCC)=C(CCC)C=2OC1(C(C)C)CCOC1=CC=C(CC(Cl)C([O-])=O)C=C1 HPQWFBQEBOJJDP-UHFFFAOYSA-M 0.000 description 1
- 229940080818 propionamide Drugs 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004742 propyloxycarbonyl group Chemical group 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000012419 sodium bis(2-methoxyethoxy)aluminum hydride Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- CMXPERZAMAQXSF-UHFFFAOYSA-M sodium;1,4-bis(2-ethylhexoxy)-1,4-dioxobutane-2-sulfonate;1,8-dihydroxyanthracene-9,10-dione Chemical compound [Na+].O=C1C2=CC=CC(O)=C2C(=O)C2=C1C=CC=C2O.CCCCC(CC)COC(=O)CC(S([O-])(=O)=O)C(=O)OCC(CC)CCCC CMXPERZAMAQXSF-UHFFFAOYSA-M 0.000 description 1
- CGDPGFZDOYUWJU-UHFFFAOYSA-M sodium;2-chloro-3-[4-[3-[8-ethyl-6-(4-methylbenzoyl)oxy-5,7-bis(3-methylbutyl)-2-propyl-3,4-dihydrochromen-2-yl]propoxy]phenyl]propanoate Chemical compound [Na+].C1CC2=C(CCC(C)C)C(OC(=O)C=3C=CC(C)=CC=3)=C(CCC(C)C)C(CC)=C2OC1(CCC)CCCOC1=CC=C(CC(Cl)C([O-])=O)C=C1 CGDPGFZDOYUWJU-UHFFFAOYSA-M 0.000 description 1
- GQONGOSCIGPXEL-UHFFFAOYSA-M sodium;2-chloro-3-[4-[3-[8-ethyl-6-(4-methylbenzoyl)oxy-5,7-bis(3-methylbutyl)-4-oxo-2-propyl-3h-chromen-2-yl]propoxy]phenyl]propanoate Chemical compound [Na+].C1C(=O)C2=C(CCC(C)C)C(OC(=O)C=3C=CC(C)=CC=3)=C(CCC(C)C)C(CC)=C2OC1(CCC)CCCOC1=CC=C(CC(Cl)C([O-])=O)C=C1 GQONGOSCIGPXEL-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000003797 solvolysis reaction Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000829 suppository 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
- 239000002699 waste material Substances 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
- 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)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (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)
- Cosmetics (AREA)
- Pyrane Compounds (AREA)
- Pyrrole Compounds (AREA)
- Thiazole And Isothizaole Compounds (AREA)
- Peptides Or Proteins (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP158375/83 | 1983-08-30 | ||
| 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 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1263395A true CA1263395A (en) | 1989-11-28 |
Family
ID=15670325
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000462173A Expired CA1263395A (en) | 1983-08-30 | 1984-08-30 | ¬5-(4-chroman-2-ylalkoxy)benzyl|-thiazolidine compounds |
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 (207)
| 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 |
| US4738972A (en) * | 1985-05-21 | 1988-04-19 | Pfizer Inc. | Hypoglycemic thiazolidinediones |
| HU210339B (en) * | 1985-05-21 | 1995-03-28 | Pfizer | Process for preparing thiazolidinediones and their pharmaceutical compositions haring hypoglycemic effect |
| 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 |
| JP2574845B2 (ja) * | 1987-02-04 | 1997-01-22 | 三共株式会社 | チアゾリジン化合物 |
| US4873255A (en) * | 1987-02-04 | 1989-10-10 | Sankyo Company Limited | Thiazolidinone derivatives, their preparation and their use |
| 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 |
| US4791125A (en) * | 1987-12-02 | 1988-12-13 | Pfizer Inc. | Thiazolidinediones as hypoglycemic and anti-atherosclerosis agents |
| 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 |
| US5356913A (en) * | 1990-02-09 | 1994-10-18 | The Upjohn Company | Use of insulin sensitizing agents to treat hypertension |
| ES2059121T5 (es) * | 1990-02-09 | 2000-12-01 | Upjohn Co | Uso de agentes sensibilizantes de la insulina para tratar la hipertension. |
| EP0839812A1 (en) * | 1990-04-27 | 1998-05-06 | Sankyo Company Limited | Preparation of benzylthiazolidine derivatives |
| 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 |
| DE69222182T2 (de) * | 1991-12-18 | 1998-02-26 | Warner Lambert Co | Verfahren für die herstellung einer festen dispersion |
| 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 |
| CZ287027B6 (en) * | 1992-08-31 | 2000-08-16 | Sankyo Co | Oxazolidine derivatives, process of their preparation and pharmaceutical preparations containing thereof |
| 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 |
| WO1994019347A1 (fr) * | 1993-02-24 | 1994-09-01 | Sankyo Company, Limited | Remede contre l'arteriosclerose |
| USRE39384E1 (en) | 1993-09-01 | 2006-11-07 | Smithkline Beecham P.L.C. | Substituted thiazolidinedione derivatives |
| AU749416B2 (en) * | 1993-09-15 | 2002-06-27 | Daiichi Sankyo Company, Limited | Use of thiazolidinediones to prevent or delay onset of NIDDM |
| ES2296288T3 (es) * | 1993-09-15 | 2008-04-16 | Daiichi Sankyo Company, Limited | Uso de tiazolidinodionas para evitar o retardar el comienzo de la diabetes mellitus no insulina dependiente (niddm). |
| 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 |
| US5457109A (en) * | 1993-09-15 | 1995-10-10 | Warner-Lambert Company | Use of thiazolidinedione derivatives and related antihyperglycemic agents in the treatment of 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 |
| 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 |
| US5594015A (en) * | 1994-06-22 | 1997-01-14 | Regents Of The University Of California | Thiazolidine derivatives for the treatment of psoriasis |
| CA2159938A1 (en) * | 1994-10-07 | 1996-04-08 | Hiroaki Yanagisawa | 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 |
| IL118474A (en) * | 1995-06-01 | 2001-08-08 | Sankyo Co | Benzimideol derivatives and pharmaceutical preparations containing them |
| 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 |
| KR19990036290A (ko) * | 1995-08-10 | 1999-05-25 | 로즈 암스트롱 | 비인슐린 의존성 진성 당뇨병 환자에 대한 외인성 인슐린 투여량의 감소 방법 |
| WO1997018811A1 (en) * | 1995-11-17 | 1997-05-29 | 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 | |
| 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 |
| 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 |
| 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. |
| 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. |
| 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 |
| 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 |
| AU3091197A (en) * | 1996-05-16 | 1997-12-05 | Boehringer Mannheim Gmbh | New process for preparing troglitazone |
| DE19619819A1 (de) * | 1996-05-16 | 1997-11-20 | Boehringer Mannheim Gmbh | Neue Thiazolidindione, Verfahren zu ihrer Herstellung und diese enthaltenden Arzneimittel |
| CA2257284C (en) * | 1996-05-31 | 2005-10-04 | Sankyo Company Limited | Remedy for autoimmune diseases |
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| JP2023536009A (ja) | 2020-07-27 | 2023-08-23 | アストラゼネカ・アクチエボラーグ | ダパグリフロジンによる慢性腎疾患の処置方法 |
| 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 |
| JP2025503136A (ja) | 2022-01-26 | 2025-01-30 | アストラゼネカ・アクチエボラーグ | 前糖尿病の治療又は2型糖尿病の発症リスクを低減する際に使用するためのダパグリフロジン |
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
-
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 CA CA000462173A patent/CA1263395A/en not_active Expired
- 1984-08-30 FI FI843422A patent/FI80693C/fi not_active IP Right Cessation
- 1984-08-30 AT AT84305922T patent/ATE33838T1/de not_active IP Right Cessation
- 1984-08-30 ES ES535552A patent/ES8607297A1/es not_active Expired
- 1984-08-30 IE IE221784A patent/IE58036B1/en not_active IP Right Cessation
- 1984-08-30 DE DE8484305922T patent/DE3470742D1/de not_active Expired
- 1984-08-30 DK DK415184A patent/DK164701C/da active
- 1984-08-30 EP EP84305922A patent/EP0139421B1/en not_active Expired
- 1984-08-30 AU AU32559/84A patent/AU570067B2/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| IE842217L (en) | 1985-02-28 |
| DK164701C (da) | 1992-12-21 |
| DK164701B (da) | 1992-08-03 |
| FI80693C (fi) | 1990-07-10 |
| ES8607297A1 (es) | 1986-05-16 |
| US4572912A (en) | 1986-02-25 |
| FI843422A0 (fi) | 1984-08-30 |
| FI843422A7 (fi) | 1985-03-01 |
| EP0139421B1 (en) | 1988-04-27 |
| KR890000370B1 (ko) | 1989-03-15 |
| EP0139421A1 (en) | 1985-05-02 |
| DK415184A (da) | 1985-03-01 |
| KR850001739A (ko) | 1985-04-01 |
| FI80693B (fi) | 1990-03-30 |
| DE3470742D1 (en) | 1988-06-01 |
| JPH0231079B2 (OSRAM) | 1990-07-11 |
| AU3255984A (en) | 1985-03-07 |
| DK415184D0 (da) | 1984-08-30 |
| AU570067B2 (en) | 1988-03-03 |
| ATE33838T1 (de) | 1988-05-15 |
| IE58036B1 (en) | 1993-06-16 |
| ES535552A0 (es) | 1986-05-16 |
| JPS6051189A (ja) | 1985-03-22 |
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