DE60107395T2 - 1,5-benzothiazepine und ihre verwendungs als hypolipidämika - Google Patents
1,5-benzothiazepine und ihre verwendungs als hypolipidämika Download PDFInfo
- Publication number
- DE60107395T2 DE60107395T2 DE60107395T DE60107395T DE60107395T2 DE 60107395 T2 DE60107395 T2 DE 60107395T2 DE 60107395 T DE60107395 T DE 60107395T DE 60107395 T DE60107395 T DE 60107395T DE 60107395 T2 DE60107395 T2 DE 60107395T2
- Authority
- DE
- Germany
- Prior art keywords
- solvate
- alkyl
- salt
- formula
- pharmaceutically acceptable
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
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- KJFRSZASZNLCDF-UHFFFAOYSA-N 1,5-benzothiazepine Chemical compound S1C=CC=NC2=CC=CC=C12 KJFRSZASZNLCDF-UHFFFAOYSA-N 0.000 title 1
- 150000003839 salts Chemical class 0.000 claims abstract description 245
- 239000012453 solvate Substances 0.000 claims abstract description 238
- 150000001875 compounds Chemical class 0.000 claims abstract description 157
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 125
- 238000000034 method Methods 0.000 claims abstract description 80
- 238000011282 treatment Methods 0.000 claims abstract description 45
- 239000003613 bile acid Substances 0.000 claims abstract description 44
- HSINOMROUCMIEA-FGVHQWLLSA-N (2s,4r)-4-[(3r,5s,6r,7r,8s,9s,10s,13r,14s,17r)-6-ethyl-3,7-dihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1h-cyclopenta[a]phenanthren-17-yl]-2-methylpentanoic acid Chemical compound C([C@@]12C)C[C@@H](O)C[C@H]1[C@@H](CC)[C@@H](O)[C@@H]1[C@@H]2CC[C@]2(C)[C@@H]([C@H](C)C[C@H](C)C(O)=O)CC[C@H]21 HSINOMROUCMIEA-FGVHQWLLSA-N 0.000 claims abstract description 40
- 238000004519 manufacturing process Methods 0.000 claims abstract description 19
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 13
- 230000008569 process Effects 0.000 claims abstract description 10
- -1 nitro, cyano, hydroxy, amino, carboxy, carbamoyl Chemical group 0.000 claims description 187
- 229910052757 nitrogen Inorganic materials 0.000 claims description 56
- 229910052739 hydrogen Inorganic materials 0.000 claims description 53
- 239000001257 hydrogen Substances 0.000 claims description 53
- 241001465754 Metazoa Species 0.000 claims description 42
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 41
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 30
- 102100021711 Ileal sodium/bile acid cotransporter Human genes 0.000 claims description 30
- 101710156096 Ileal sodium/bile acid cotransporter Proteins 0.000 claims description 30
- 239000011230 binding agent Substances 0.000 claims description 29
- 229940123934 Reductase inhibitor Drugs 0.000 claims description 28
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 26
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 26
- 239000003814 drug Substances 0.000 claims description 26
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 25
- 229910052799 carbon Inorganic materials 0.000 claims description 25
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 24
- 150000002431 hydrogen Chemical class 0.000 claims description 23
- 229910052736 halogen Inorganic materials 0.000 claims description 22
- 150000002367 halogens Chemical class 0.000 claims description 22
- 230000002401 inhibitory effect Effects 0.000 claims description 22
- 125000000623 heterocyclic group Chemical group 0.000 claims description 21
- 239000000203 mixture Substances 0.000 claims description 21
- 125000001424 substituent group Chemical group 0.000 claims description 19
- 241000282412 Homo Species 0.000 claims description 18
- 241000282414 Homo sapiens Species 0.000 claims description 17
- 239000002253 acid Substances 0.000 claims description 15
- 239000003085 diluting agent Substances 0.000 claims description 15
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 14
- 125000004452 carbocyclyl group Chemical group 0.000 claims description 14
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
- 125000006239 protecting group Chemical group 0.000 claims description 14
- 125000003545 alkoxy group Chemical group 0.000 claims description 13
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 13
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 12
- 230000001225 therapeutic effect Effects 0.000 claims description 12
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims description 11
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 11
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 10
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 10
- 229940079593 drug Drugs 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 125000004423 acyloxy group Chemical group 0.000 claims description 9
- 125000004122 cyclic group Chemical group 0.000 claims description 9
- 230000001939 inductive effect Effects 0.000 claims description 9
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 8
- 230000000694 effects Effects 0.000 claims description 8
- 150000001412 amines Chemical class 0.000 claims description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
- 125000000304 alkynyl group Chemical group 0.000 claims description 6
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 6
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 238000002360 preparation method Methods 0.000 claims description 5
- 230000000069 prophylactic effect Effects 0.000 claims description 5
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 5
- XUKUURHRXDUEBC-KAYWLYCHSA-N Atorvastatin Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-KAYWLYCHSA-N 0.000 claims description 4
- XUKUURHRXDUEBC-UHFFFAOYSA-N Atorvastatin Natural products C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CCC(O)CC(O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-UHFFFAOYSA-N 0.000 claims description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 4
- 229960005370 atorvastatin Drugs 0.000 claims description 4
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 4
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 4
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 4
- ZGGHKIMDNBDHJB-NRFPMOEYSA-M (3R,5S)-fluvastatin sodium Chemical compound [Na+].C12=CC=CC=C2N(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)=C1C1=CC=C(F)C=C1 ZGGHKIMDNBDHJB-NRFPMOEYSA-M 0.000 claims description 3
- FHGWEHGZBUBQKL-UHFFFAOYSA-N 1,2-benzothiazepine Chemical compound S1N=CC=CC2=CC=CC=C12 FHGWEHGZBUBQKL-UHFFFAOYSA-N 0.000 claims description 3
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 3
- 229920001268 Cholestyramine Polymers 0.000 claims description 3
- 229920002911 Colestipol Polymers 0.000 claims description 3
- RYMZZMVNJRMUDD-UHFFFAOYSA-N SJ000286063 Natural products C12C(OC(=O)C(C)(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 RYMZZMVNJRMUDD-UHFFFAOYSA-N 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 125000002947 alkylene group Chemical group 0.000 claims description 3
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 claims description 3
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 3
- 229960003765 fluvastatin Drugs 0.000 claims description 3
- 239000011347 resin Substances 0.000 claims description 3
- 229920005989 resin Polymers 0.000 claims description 3
- BPRHUIZQVSMCRT-VEUZHWNKSA-N rosuvastatin Chemical compound CC(C)C1=NC(N(C)S(C)(=O)=O)=NC(C=2C=CC(F)=CC=2)=C1\C=C\[C@@H](O)C[C@@H](O)CC(O)=O BPRHUIZQVSMCRT-VEUZHWNKSA-N 0.000 claims description 3
- 229960002855 simvastatin Drugs 0.000 claims description 3
- RYMZZMVNJRMUDD-HGQWONQESA-N simvastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)C(C)(C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 RYMZZMVNJRMUDD-HGQWONQESA-N 0.000 claims description 3
- VDSBXXDKCUBMQC-HNGSOEQISA-N (4r,6s)-6-[(e)-2-[2-(4-fluoro-3-methylphenyl)-4,4,6,6-tetramethylcyclohexen-1-yl]ethenyl]-4-hydroxyoxan-2-one Chemical compound C1=C(F)C(C)=CC(C=2CC(C)(C)CC(C)(C)C=2\C=C\[C@H]2OC(=O)C[C@H](O)C2)=C1 VDSBXXDKCUBMQC-HNGSOEQISA-N 0.000 claims description 2
- 125000004769 (C1-C4) alkylsulfonyl group Chemical group 0.000 claims description 2
- PCZOHLXUXFIOCF-UHFFFAOYSA-N Monacolin X Natural products C12C(OC(=O)C(C)CC)CC(C)C=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 PCZOHLXUXFIOCF-UHFFFAOYSA-N 0.000 claims description 2
- TUZYXOIXSAXUGO-UHFFFAOYSA-N Pravastatin Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(O)C=C21 TUZYXOIXSAXUGO-UHFFFAOYSA-N 0.000 claims description 2
- AJLFOPYRIVGYMJ-UHFFFAOYSA-N SJ000287055 Natural products C12C(OC(=O)C(C)CC)CCC=C2C=CC(C)C1CCC1CC(O)CC(=O)O1 AJLFOPYRIVGYMJ-UHFFFAOYSA-N 0.000 claims description 2
- FFBHFFJDDLITSX-UHFFFAOYSA-N benzyl N-[2-hydroxy-4-(3-oxomorpholin-4-yl)phenyl]carbamate Chemical compound OC1=C(NC(=O)OCC2=CC=CC=C2)C=CC(=C1)N1CCOCC1=O FFBHFFJDDLITSX-UHFFFAOYSA-N 0.000 claims description 2
- 229950005357 bervastatin Drugs 0.000 claims description 2
- 229960005110 cerivastatin Drugs 0.000 claims description 2
- SEERZIQQUAZTOL-ANMDKAQQSA-N cerivastatin Chemical compound COCC1=C(C(C)C)N=C(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)=C1C1=CC=C(F)C=C1 SEERZIQQUAZTOL-ANMDKAQQSA-N 0.000 claims description 2
- 229950003040 dalvastatin Drugs 0.000 claims description 2
- ZADJRRFMOOACHL-WQICJITCSA-N ethyl (e,3s,5r)-7-[4-(4-fluorophenyl)spiro[chromene-2,1'-cyclopentane]-3-yl]-3,5-dihydroxyhept-6-enoate Chemical compound C12=CC=CC=C2OC2(CCCC2)C(/C=C/[C@H](O)C[C@H](O)CC(=O)OCC)=C1C1=CC=C(F)C=C1 ZADJRRFMOOACHL-WQICJITCSA-N 0.000 claims description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 2
- 229960004844 lovastatin Drugs 0.000 claims description 2
- PCZOHLXUXFIOCF-BXMDZJJMSA-N lovastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=C[C@H](C)C[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 PCZOHLXUXFIOCF-BXMDZJJMSA-N 0.000 claims description 2
- QLJODMDSTUBWDW-UHFFFAOYSA-N lovastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CC(C)C=C21 QLJODMDSTUBWDW-UHFFFAOYSA-N 0.000 claims description 2
- AJLFOPYRIVGYMJ-INTXDZFKSA-N mevastatin Chemical compound C([C@H]1[C@@H](C)C=CC2=CCC[C@@H]([C@H]12)OC(=O)[C@@H](C)CC)C[C@@H]1C[C@@H](O)CC(=O)O1 AJLFOPYRIVGYMJ-INTXDZFKSA-N 0.000 claims description 2
- 229950009116 mevastatin Drugs 0.000 claims description 2
- BOZILQFLQYBIIY-UHFFFAOYSA-N mevastatin hydroxy acid Natural products C1=CC(C)C(CCC(O)CC(O)CC(O)=O)C2C(OC(=O)C(C)CC)CCC=C21 BOZILQFLQYBIIY-UHFFFAOYSA-N 0.000 claims description 2
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 2
- 229960002965 pravastatin Drugs 0.000 claims description 2
- TUZYXOIXSAXUGO-PZAWKZKUSA-N pravastatin Chemical compound C1=C[C@H](C)[C@H](CC[C@@H](O)C[C@@H](O)CC(O)=O)[C@H]2[C@@H](OC(=O)[C@@H](C)CC)C[C@H](O)C=C21 TUZYXOIXSAXUGO-PZAWKZKUSA-N 0.000 claims description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 1
- 125000001475 halogen functional group Chemical group 0.000 claims 1
- 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims 1
- 239000003112 inhibitor Substances 0.000 abstract description 6
- 208000031226 Hyperlipidaemia Diseases 0.000 abstract description 2
- 239000000651 prodrug Substances 0.000 abstract 1
- 229940002612 prodrug Drugs 0.000 abstract 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 60
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- 238000005481 NMR spectroscopy Methods 0.000 description 30
- 230000002829 reductive effect Effects 0.000 description 26
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
- 239000002552 dosage form Substances 0.000 description 21
- 239000002904 solvent Substances 0.000 description 16
- 235000019439 ethyl acetate Nutrition 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- WMFOQBRAJBCJND-UHFFFAOYSA-M lithium hydroxide Inorganic materials [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 13
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-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 11
- 239000000243 solution Substances 0.000 description 11
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 10
- 125000002252 acyl group Chemical group 0.000 description 10
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- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
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- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 10
- 238000010992 reflux Methods 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 8
- 229910052794 bromium Inorganic materials 0.000 description 8
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 8
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 7
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 7
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 150000007657 benzothiazepines Chemical class 0.000 description 7
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 7
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- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 6
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- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 6
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- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 5
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- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
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- PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 5
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- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
- 229910000029 sodium carbonate Inorganic materials 0.000 description 5
- 238000010561 standard procedure Methods 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 239000011593 sulfur Substances 0.000 description 5
- UWCBQDVOBLAYPM-UHFFFAOYSA-N 2-[(7-bromo-3-butyl-3-ethyl-1,1-dioxo-5-phenyl-2,4-dihydro-1$l^{6},5-benzothiazepin-8-yl)oxy]acetic acid Chemical compound C12=CC(Br)=C(OCC(O)=O)C=C2S(=O)(=O)CC(CCCC)(CC)CN1C1=CC=CC=C1 UWCBQDVOBLAYPM-UHFFFAOYSA-N 0.000 description 4
- 125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 description 4
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- 125000003435 aroyl group Chemical group 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
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- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
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- CWBHKBKGKCDGDM-UHFFFAOYSA-N bis[(2,2,2-trifluoroacetyl)oxy]boranyl 2,2,2-trifluoroacetate Chemical compound FC(F)(F)C(=O)OB(OC(=O)C(F)(F)F)OC(=O)C(F)(F)F CWBHKBKGKCDGDM-UHFFFAOYSA-N 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
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- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
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- DEZRYPDIMOWBDS-UHFFFAOYSA-N dcm dichloromethane Chemical compound ClCCl.ClCCl DEZRYPDIMOWBDS-UHFFFAOYSA-N 0.000 description 1
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- 238000011161 development Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 description 1
- IUNMPGNGSSIWFP-UHFFFAOYSA-N dimethylaminopropylamine Chemical compound CN(C)CCCN IUNMPGNGSSIWFP-UHFFFAOYSA-N 0.000 description 1
- UXGNZZKBCMGWAZ-UHFFFAOYSA-N dimethylformamide dmf Chemical compound CN(C)C=O.CN(C)C=O UXGNZZKBCMGWAZ-UHFFFAOYSA-N 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
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- 238000005886 esterification reaction Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- ARFLASKVLJTEJD-UHFFFAOYSA-N ethyl 2-bromopropanoate Chemical compound CCOC(=O)C(C)Br ARFLASKVLJTEJD-UHFFFAOYSA-N 0.000 description 1
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 1
- 125000006260 ethylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000006125 ethylsulfonyl group Chemical group 0.000 description 1
- 125000004705 ethylthio group Chemical group C(C)S* 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 150000004820 halides Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- RCCPEORTSYDPMB-UHFFFAOYSA-N hydroxy benzenecarboximidothioate Chemical compound OSC(=N)C1=CC=CC=C1 RCCPEORTSYDPMB-UHFFFAOYSA-N 0.000 description 1
- 230000000055 hyoplipidemic effect Effects 0.000 description 1
- 230000000871 hypocholesterolemic effect Effects 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000008604 lipoprotein metabolism Effects 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 238000002514 liquid chromatography mass spectrum Methods 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- BCVXHSPFUWZLGQ-UHFFFAOYSA-N mecn acetonitrile Chemical compound CC#N.CC#N BCVXHSPFUWZLGQ-UHFFFAOYSA-N 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 125000005948 methanesulfonyloxy group Chemical group 0.000 description 1
- VSDUZFOSJDMAFZ-VIFPVBQESA-N methyl L-phenylalaninate Chemical compound COC(=O)[C@@H](N)CC1=CC=CC=C1 VSDUZFOSJDMAFZ-VIFPVBQESA-N 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
- WOOWBQQQJXZGIE-UHFFFAOYSA-N n-ethyl-n-propan-2-ylpropan-2-amine Chemical compound CCN(C(C)C)C(C)C.CCN(C(C)C)C(C)C WOOWBQQQJXZGIE-UHFFFAOYSA-N 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- ZRSNZINYAWTAHE-UHFFFAOYSA-N p-methoxybenzaldehyde Chemical compound COC1=CC=C(C=O)C=C1 ZRSNZINYAWTAHE-UHFFFAOYSA-N 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 125000000538 pentafluorophenyl group Chemical group FC1=C(F)C(F)=C(*)C(F)=C1F 0.000 description 1
- 238000005897 peptide coupling reaction Methods 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
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- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- 125000001476 phosphono group Chemical group [H]OP(*)(=O)O[H] 0.000 description 1
- 125000000612 phthaloyl group Chemical group C(C=1C(C(=O)*)=CC=CC1)(=O)* 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 239000011148 porous material Substances 0.000 description 1
- 108010080180 poststatin Proteins 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 230000009103 reabsorption Effects 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 238000011125 single therapy Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 description 1
- RMBAVIFYHOYIFM-UHFFFAOYSA-M sodium methanethiolate Chemical compound [Na+].[S-]C RMBAVIFYHOYIFM-UHFFFAOYSA-M 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229960003080 taurine Drugs 0.000 description 1
- SJMDMGHPMLKLHQ-UHFFFAOYSA-N tert-butyl 2-aminoacetate Chemical compound CC(C)(C)OC(=O)CN SJMDMGHPMLKLHQ-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000005329 tetralinyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000005505 thiomorpholino group Chemical group 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
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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
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D281/00—Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D281/02—Seven-membered rings
- C07D281/04—Seven-membered rings having the hetero atoms in positions 1 and 4
- C07D281/08—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D281/10—Seven-membered rings having the hetero atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems condensed with one six-membered ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6536—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having nitrogen and sulfur atoms with or without oxygen atoms, as the only ring hetero atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Gastroenterology & Hepatology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Steroid Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE0000772A SE0000772D0 (sv) | 2000-03-08 | 2000-03-08 | Chemical compounds |
| SE0000772 | 2000-03-08 | ||
| PCT/GB2001/000909 WO2001066533A1 (en) | 2000-03-08 | 2001-03-05 | 1,5-benzothiazepines and their use as hypolipidaemics |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60107395D1 DE60107395D1 (de) | 2004-12-30 |
| DE60107395T2 true DE60107395T2 (de) | 2005-12-01 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60107395T Expired - Lifetime DE60107395T2 (de) | 2000-03-08 | 2001-03-05 | 1,5-benzothiazepine und ihre verwendungs als hypolipidämika |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US6906058B2 (enExample) |
| EP (1) | EP1263747B1 (enExample) |
| JP (1) | JP5204361B2 (enExample) |
| KR (1) | KR20020079990A (enExample) |
| CN (1) | CN1416425A (enExample) |
| AT (1) | ATE283266T1 (enExample) |
| AU (2) | AU3755601A (enExample) |
| BR (1) | BR0109011A (enExample) |
| CA (1) | CA2401055A1 (enExample) |
| DE (1) | DE60107395T2 (enExample) |
| IL (1) | IL151296A0 (enExample) |
| MX (1) | MXPA02008600A (enExample) |
| NO (1) | NO20024217L (enExample) |
| NZ (1) | NZ520951A (enExample) |
| SE (1) | SE0000772D0 (enExample) |
| WO (1) | WO2001066533A1 (enExample) |
| ZA (1) | ZA200206739B (enExample) |
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| GB0121337D0 (en) * | 2001-09-04 | 2001-10-24 | Astrazeneca Ab | Chemical compounds |
| GB0121622D0 (en) | 2001-09-07 | 2001-10-31 | Astrazeneca Ab | Chemical compounds |
| GB0121621D0 (en) | 2001-09-07 | 2001-10-31 | Astrazeneca Ab | Chemical compounds |
| MXPA04002179A (es) | 2001-09-08 | 2004-06-29 | Astrazeneca Ab | Derivados de benzotiazepina y benzotiadiazepina con actividad inhibidora de transporte del acido ileal biliar (ibat) para tratar hiperlipidemia. |
| SE0104333D0 (sv) | 2001-12-19 | 2001-12-19 | Astrazeneca Ab | Therapeutic agents |
| GB0201850D0 (en) * | 2002-01-26 | 2002-03-13 | Astrazeneca Ab | Therapeutic treatment |
| AU2003203482B2 (en) | 2002-04-09 | 2005-06-02 | Syngenta Participations Ag | Process for the preparation of cyclic diketones |
| GB0209467D0 (en) | 2002-04-25 | 2002-06-05 | Astrazeneca Ab | Chemical compounds |
| GB0213669D0 (en) * | 2002-06-14 | 2002-07-24 | Astrazeneca Ab | Chemical compounds |
| TWI282784B (en) * | 2002-06-20 | 2007-06-21 | Astrazeneca Ab | Therapeutic agents |
| GB0304194D0 (en) | 2003-02-25 | 2003-03-26 | Astrazeneca Ab | Chemical compounds |
| GB0307918D0 (en) | 2003-04-05 | 2003-05-14 | Astrazeneca Ab | Therapeutic use |
| GB0314131D0 (en) * | 2003-06-18 | 2003-07-23 | Astrazeneca Ab | Therapeutic agents |
| JP5145537B2 (ja) | 2004-12-22 | 2013-02-20 | ビーエイチアイ リミテッド パートナーシップ | アミロイド関連疾患を治療するための方法および組成物 |
| AR057828A1 (es) * | 2005-09-29 | 2007-12-19 | Astrazeneca Ab | Compuestos derivados de azetidina, su preparacion y composicion farmaceuutica |
| JP5607930B2 (ja) | 2006-10-12 | 2014-10-15 | ビーエイチアイ リミテッド パートナーシップ | ３−アミノ−１−プロパンスルホン酸を送達するための方法、化合物、組成物および媒体 |
| WO2008108735A1 (en) * | 2007-03-08 | 2008-09-12 | Albireo Ab | 2 -substituted- 3 -phenylpropionic acid derivatives and their use in the treatment of inflammatory bowel disease |
| WO2010062861A2 (en) | 2008-11-26 | 2010-06-03 | Satiogen Pharmaceuticals, Inc. | Bile acid recycling inhibitors for treatment of obesity and diabetes |
| EP4137137A1 (en) | 2010-05-26 | 2023-02-22 | Satiogen Pharmaceuticals, Inc. | Bile acid recycling inhibitors and satiogens for treatment of diabetes, obesity, and inflammatory gastrointestinal conditions |
| JP5889321B2 (ja) | 2010-11-04 | 2016-03-22 | アルビレオ アクチエボラグ | 肝疾患の処置用のｉｂａｔ阻害剤 |
| WO2012064267A1 (en) | 2010-11-08 | 2012-05-18 | Albireo Ab | A pharmaceutical combination comprising an ibat inhibitor and a bile acid binder |
| WO2013063512A1 (en) | 2011-10-28 | 2013-05-02 | Lumena Pharmaceuticals, Inc | Bile acid recycling inhibitors for treatment of pediatric cholestatic liver diseases |
| MX363161B (es) | 2011-10-28 | 2019-03-13 | Lumena Pharmaceuticals Inc | Inhibidores de la recirculación de ácidos biliares para el tratamiento de hipercolemia y enfermedad hepática colestásica. |
| EP2968230A2 (en) | 2013-03-15 | 2016-01-20 | Lumena Pharmaceuticals, Inc. | Bile acid recycling inhibitors for treatment of primary sclerosing cholangitis and inflammatory bowel disease |
| MX2015013196A (es) | 2013-03-15 | 2016-04-15 | Lumena Pharmaceuticals Inc | Inhibidores de reciclaje de acidos biliares para el tratamiento de la enfermedad de reflujo gastroesofagico y esofago de barrett. |
| JO3301B1 (ar) | 2013-04-26 | 2018-09-16 | Albireo Ab | تعديلات بلورية على إيلوبيكسيبات |
| JP6751020B2 (ja) | 2014-06-25 | 2020-09-02 | Ｅａファーマ株式会社 | 固形製剤及びその着色防止又は着色低減方法 |
| KR101674806B1 (ko) * | 2014-10-20 | 2016-11-10 | 씨제이헬스케어 주식회사 | 신규한 아미노알킬벤조티아제핀 유도체 및 이의 용도 |
| EP3012252A1 (en) | 2014-10-24 | 2016-04-27 | Ferring BV | Crystal modifications of elobixibat |
| EP3413878B1 (en) | 2016-02-09 | 2021-04-14 | Albireo AB | Oral cholestyramine formulation and use thereof |
| US10786529B2 (en) | 2016-02-09 | 2020-09-29 | Albireo Ab | Oral cholestyramine formulation and use thereof |
| CN108601744B (zh) | 2016-02-09 | 2022-01-04 | 阿尔比里奥公司 | 口服考来烯胺制剂及其用途 |
| US10441605B2 (en) | 2016-02-09 | 2019-10-15 | Albireo Ab | Oral cholestyramine formulation and use thereof |
| US10441604B2 (en) | 2016-02-09 | 2019-10-15 | Albireo Ab | Cholestyramine pellets and methods for preparation thereof |
| KR101844184B1 (ko) * | 2017-07-21 | 2018-04-02 | 씨제이헬스케어 주식회사 | 아미노알킬벤조티아제핀 유도체의 용도 |
| CN110996915B (zh) | 2017-08-09 | 2023-10-03 | 阿尔比里奥公司 | 考来烯胺丸粒、口服考来烯胺制剂及其用途 |
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| ZA956647B (en) | 1994-08-10 | 1997-02-10 | Wellcome Found | Hypolipidaemic compounds. |
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| GB9704208D0 (en) | 1997-02-28 | 1997-04-16 | Glaxo Group Ltd | Chemical compounds |
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| PT1140190E (pt) | 1998-12-23 | 2003-02-28 | Searle Llc | Combinacoes de inibidores do transporte ileal dos acidos biliares e agentes sequestrantes dos acidos biliares usadas para problemas cardiovasculares |
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| WO2000038725A1 (en) | 1998-12-23 | 2000-07-06 | G.D. Searle Llc | Combinations for cardiovascular indications |
| NZ512536A (en) | 1998-12-23 | 2003-11-28 | G | Combinations of ileal bile acid transport inhibitors and cholesteryl ester transfer protein inhibitors for cardiovascular indications |
| EP1155007A2 (en) | 1999-02-12 | 2001-11-21 | G.D. Searle LLC | 1,2-benzothiazepines for the treatment of hyperlipidemic diseases |
| DE19916108C1 (de) | 1999-04-09 | 2001-01-11 | Aventis Pharma Gmbh | Mit Zuckerresten substituierte 1,4-Benzothiazepin-1,1-dioxidderivate, Verfahren zu deren Herstellung und deren Verwendung |
| SE9901387D0 (sv) | 1999-04-19 | 1999-04-19 | Astra Ab | New pharmaceutical foromaulations |
| CA2400021A1 (en) | 2000-02-18 | 2001-08-23 | Merck & Co., Inc. | Aryloxyacetic acids for diabetes and lipid disorders |
| US6794544B2 (en) | 2000-03-10 | 2004-09-21 | Pharmacia Corporation | Method for the preparation of tetrahydrobenzothiepines |
| US20020061888A1 (en) | 2000-03-10 | 2002-05-23 | Keller Bradley T. | Combination therapy for the prophylaxis and treatment of hyperlipidemic conditions and disorders |
| US20020183307A1 (en) | 2000-07-26 | 2002-12-05 | Tremont Samuel J. | Novel 1,4-benzothiazephine and 1,5-benzothiazepine compounds as inhibitors of apical sodium co-dependent bile acid transport and taurocholate uptake |
| SE0003766D0 (sv) | 2000-10-18 | 2000-10-18 | Astrazeneca Ab | Novel formulation |
| EG26979A (en) | 2000-12-21 | 2015-03-01 | Astrazeneca Ab | Chemical compounds |
| GB0121337D0 (en) | 2001-09-04 | 2001-10-24 | Astrazeneca Ab | Chemical compounds |
| GB0121622D0 (en) | 2001-09-07 | 2001-10-31 | Astrazeneca Ab | Chemical compounds |
| GB0121621D0 (en) | 2001-09-07 | 2001-10-31 | Astrazeneca Ab | Chemical compounds |
| MXPA04002179A (es) | 2001-09-08 | 2004-06-29 | Astrazeneca Ab | Derivados de benzotiazepina y benzotiadiazepina con actividad inhibidora de transporte del acido ileal biliar (ibat) para tratar hiperlipidemia. |
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2000
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2001
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- 2001-03-05 DE DE60107395T patent/DE60107395T2/de not_active Expired - Lifetime
- 2001-03-05 BR BR0109011-9A patent/BR0109011A/pt not_active IP Right Cessation
- 2001-03-05 AU AU3755601A patent/AU3755601A/xx active Pending
- 2001-03-05 IL IL15129601A patent/IL151296A0/xx unknown
- 2001-03-05 MX MXPA02008600A patent/MXPA02008600A/es unknown
- 2001-03-05 CN CN01806160A patent/CN1416425A/zh active Pending
- 2001-03-05 CA CA002401055A patent/CA2401055A1/en not_active Abandoned
- 2001-03-05 JP JP2001565349A patent/JP5204361B2/ja not_active Expired - Fee Related
- 2001-03-05 EP EP01909970A patent/EP1263747B1/en not_active Expired - Lifetime
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- 2001-03-05 AT AT01909970T patent/ATE283266T1/de not_active IP Right Cessation
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- 2001-03-05 NZ NZ520951A patent/NZ520951A/en unknown
- 2001-03-05 WO PCT/GB2001/000909 patent/WO2001066533A1/en not_active Ceased
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2002
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- 2002-09-04 NO NO20024217A patent/NO20024217L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| IL151296A0 (en) | 2003-04-10 |
| DE60107395D1 (de) | 2004-12-30 |
| SE0000772D0 (sv) | 2000-03-08 |
| CN1416425A (zh) | 2003-05-07 |
| AU3755601A (en) | 2001-09-17 |
| CA2401055A1 (en) | 2001-09-13 |
| EP1263747A1 (en) | 2002-12-11 |
| EP1263747B1 (en) | 2004-11-24 |
| JP2003525933A (ja) | 2003-09-02 |
| MXPA02008600A (es) | 2003-02-24 |
| US6906058B2 (en) | 2005-06-14 |
| BR0109011A (pt) | 2003-06-03 |
| NO20024217D0 (no) | 2002-09-04 |
| ZA200206739B (en) | 2003-11-24 |
| KR20020079990A (ko) | 2002-10-21 |
| US20030166927A1 (en) | 2003-09-04 |
| NO20024217L (no) | 2002-10-09 |
| WO2001066533A1 (en) | 2001-09-13 |
| NZ520951A (en) | 2004-05-28 |
| ATE283266T1 (de) | 2004-12-15 |
| AU2001237556B2 (en) | 2004-10-07 |
| JP5204361B2 (ja) | 2013-06-05 |
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