BG105206A - Бензотиепини, притежаващи активност като инхибитори на пренасянето на илеална жлъчна киселина и на поглъщането на таурохолат - Google Patents

Бензотиепини, притежаващи активност като инхибитори на пренасянето на илеална жлъчна киселина и на поглъщането на таурохолат Download PDF

Info

Publication number: BG105206A
Authority: BG; Bulgaria
Prior art keywords: heterocycle; alkyl; group; quaternary; aryl
Prior art date: 1998-07-02

Application number

BG105206A

Other languages

Bulgarian (bg)

English (en)

Inventor

Len LEE

Shyamal BANERJEE

Horng-Chih Huang

Jinglin Li

Raymond Miller

David Reitz

Samuel TREMONT

Original Assignee

G.D. Searle @ Co

Priority date (The priority date 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 date listed.)

1998-07-02

Filing date

2001-01-31

Publication date

2001-09-28

2001-01-31 Application filed by G.D. Searle @ Co filed Critical G.D. Searle @ Co

2001-09-28 Publication of BG105206A publication Critical patent/BG105206A/bg

Links

NIGNBCLEMMGDQP-UHFFFAOYSA-N 1-benzothiepine Chemical class S1C=CC=CC2=CC=CC=C12 NIGNBCLEMMGDQP-UHFFFAOYSA-N 0.000 title abstract 2
239000003613 bile acid Substances 0.000 title description 29
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 title description 21
239000003112 inhibitor Substances 0.000 title description 8
230000000694 effects Effects 0.000 title description 4
WBWWGRHZICKQGZ-HZAMXZRMSA-N taurocholic acid Chemical compound C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC(=O)NCCS(O)(=O)=O)C)[C@@]2(C)[C@@H](O)C1 WBWWGRHZICKQGZ-HZAMXZRMSA-N 0.000 title description 2
150000001875 compounds Chemical class 0.000 claims abstract description 234
238000000034 method Methods 0.000 claims abstract description 83
239000000203 mixture Substances 0.000 claims abstract description 44
238000011282 treatment Methods 0.000 claims abstract description 22
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 16
238000002360 preparation method Methods 0.000 claims abstract description 15
239000003814 drug Substances 0.000 claims abstract description 11
125000000623 heterocyclic group Chemical group 0.000 claims description 495
125000000217 alkyl group Chemical group 0.000 claims description 417
125000003118 aryl group Chemical group 0.000 claims description 306
125000000304 alkynyl group Chemical group 0.000 claims description 284
125000003342 alkenyl group Chemical group 0.000 claims description 279
125000001072 heteroaryl group Chemical group 0.000 claims description 269
125000000753 cycloalkyl group Chemical group 0.000 claims description 262
125000003710 aryl alkyl group Chemical group 0.000 claims description 247
-1 ammoniumalkyl Chemical group 0.000 claims description 197
229910052739 hydrogen Inorganic materials 0.000 claims description 191
239000001257 hydrogen Substances 0.000 claims description 190
108090000765 processed proteins & peptides Proteins 0.000 claims description 137
239000004721 Polyphenylene oxide Substances 0.000 claims description 136
229920000570 polyether Polymers 0.000 claims description 136
125000001188 haloalkyl group Chemical group 0.000 claims description 123
229910052736 halogen Inorganic materials 0.000 claims description 119
150000002367 halogens Chemical class 0.000 claims description 119
150000002431 hydrogen Chemical class 0.000 claims description 115
125000004043 oxo group Chemical group O=* 0.000 claims description 114
125000004446 heteroarylalkyl group Chemical group 0.000 claims description 98
125000001424 substituent group Chemical group 0.000 claims description 97
125000004432 carbon atom Chemical group C* 0.000 claims description 91
125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 88
125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 84
125000004181 carboxyalkyl group Chemical group 0.000 claims description 81
229910052757 nitrogen Inorganic materials 0.000 claims description 81
RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 claims description 81
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 75
150000001413 amino acids Chemical class 0.000 claims description 74
229910052760 oxygen Inorganic materials 0.000 claims description 71
150000001720 carbohydrates Chemical class 0.000 claims description 70
235000014633 carbohydrates Nutrition 0.000 claims description 70
239000001301 oxygen Substances 0.000 claims description 69
229920001184 polypeptide Polymers 0.000 claims description 69
102000004196 processed proteins & peptides Human genes 0.000 claims description 69
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 68
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 66
125000002252 acyl group Chemical group 0.000 claims description 60
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims description 54
125000003545 alkoxy group Chemical group 0.000 claims description 53
229910052799 carbon Inorganic materials 0.000 claims description 52
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 50
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 48
125000002877 alkyl aryl group Chemical group 0.000 claims description 47
239000003795 chemical substances by application Substances 0.000 claims description 45
125000004423 acyloxy group Chemical group 0.000 claims description 41
150000003839 salts Chemical group 0.000 claims description 39
125000004122 cyclic group Chemical group 0.000 claims description 34
125000004433 nitrogen atom Chemical group N* 0.000 claims description 34
125000004663 dialkyl amino group Chemical group 0.000 claims description 33
125000004948 alkyl aryl alkyl group Chemical group 0.000 claims description 31
125000004414 alkyl thio group Chemical group 0.000 claims description 31
150000001450 anions Chemical class 0.000 claims description 29
125000005098 aryl alkoxy carbonyl group Chemical group 0.000 claims description 29
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 28
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 27
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 27
150000001768 cations Chemical class 0.000 claims description 26
UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical group [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 26
238000006243 chemical reaction Methods 0.000 claims description 25
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 25
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 24
201000010099 disease Diseases 0.000 claims description 23
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 23
125000004964 sulfoalkyl group Chemical group 0.000 claims description 22
150000005171 halobenzenes Chemical class 0.000 claims description 20
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 17
239000002585 base Substances 0.000 claims description 17
125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 17
125000004585 polycyclic heterocycle group Chemical group 0.000 claims description 17
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 15
229910052717 sulfur Inorganic materials 0.000 claims description 15
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
239000007800 oxidant agent Substances 0.000 claims description 14
LEHBURLTIWGHEM-UHFFFAOYSA-N pyridinium chlorochromate Chemical compound [O-][Cr](Cl)(=O)=O.C1=CC=[NH+]C=C1 LEHBURLTIWGHEM-UHFFFAOYSA-N 0.000 claims description 14
239000012453 solvate Substances 0.000 claims description 14
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 13
239000002253 acid Substances 0.000 claims description 13
125000004946 alkenylalkyl group Chemical group 0.000 claims description 13
125000005038 alkynylalkyl group Chemical group 0.000 claims description 13
125000004966 cyanoalkyl group Chemical group 0.000 claims description 13
125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 13
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 13
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 claims description 12
230000003301 hydrolyzing effect Effects 0.000 claims description 12
150000003457 sulfones Chemical class 0.000 claims description 12
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 11
239000002552 dosage form Substances 0.000 claims description 11
239000000651 prodrug Substances 0.000 claims description 11
229940002612 prodrug Drugs 0.000 claims description 11
125000005842 heteroatom Chemical group 0.000 claims description 10
230000002265 prevention Effects 0.000 claims description 10
239000000460 chlorine Substances 0.000 claims description 9
230000003647 oxidation Effects 0.000 claims description 9
238000007254 oxidation reaction Methods 0.000 claims description 9
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 8
125000005119 alkyl cycloalkyl group Chemical group 0.000 claims description 7
125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 7
229910000104 sodium hydride Inorganic materials 0.000 claims description 7
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
229910052801 chlorine Inorganic materials 0.000 claims description 6
125000002485 formyl group Chemical class [H]C(*)=O 0.000 claims description 6
125000005843 halogen group Chemical group 0.000 claims description 6
230000008569 process Effects 0.000 claims description 6
239000012312 sodium hydride Substances 0.000 claims description 6
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical group [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 5
UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 claims description 5
239000003937 drug carrier Substances 0.000 claims description 5
229910052500 inorganic mineral Inorganic materials 0.000 claims description 5
LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 claims description 5
239000011707 mineral Substances 0.000 claims description 5
238000007363 ring formation reaction Methods 0.000 claims description 5
125000004429 atom Chemical group 0.000 claims description 4
IBBLRJGOOANPTQ-JKVLGAQCSA-N quinapril hydrochloride Chemical compound Cl.C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CC2=CC=CC=C2C1)C(O)=O)CC1=CC=CC=C1 IBBLRJGOOANPTQ-JKVLGAQCSA-N 0.000 claims description 4
150000004703 alkoxides Chemical class 0.000 claims description 3
125000003282 alkyl amino group Chemical group 0.000 claims description 3
230000008878 coupling Effects 0.000 claims description 3
238000010168 coupling process Methods 0.000 claims description 3
238000005859 coupling reaction Methods 0.000 claims description 3
125000000392 cycloalkenyl group Chemical group 0.000 claims description 3
125000000592 heterocycloalkyl group Chemical group 0.000 claims description 3
229910052976 metal sulfide Inorganic materials 0.000 claims description 3
239000002243 precursor Substances 0.000 claims description 3
229910021653 sulphate ion Inorganic materials 0.000 claims description 3
229910052721 tungsten Inorganic materials 0.000 claims description 3
229910000102 alkali metal hydride Inorganic materials 0.000 claims description 2
150000008046 alkali metal hydrides Chemical group 0.000 claims description 2
125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 2
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 6
125000002102 aryl alkyloxo group Chemical group 0.000 claims 2
230000003143 atherosclerotic effect Effects 0.000 claims 2
230000000260 hypercholesteremic effect Effects 0.000 claims 2
125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims 1
PUAQLLVFLMYYJJ-UHFFFAOYSA-N 2-aminopropiophenone Chemical compound CC(N)C(=O)C1=CC=CC=C1 PUAQLLVFLMYYJJ-UHFFFAOYSA-N 0.000 claims 1
239000003513 alkali Substances 0.000 claims 1
125000005210 alkyl ammonium group Chemical group 0.000 claims 1
230000000879 anti-atherosclerotic effect Effects 0.000 claims 1
230000001315 anti-hyperlipaemic effect Effects 0.000 claims 1
125000006456 halo alkyl cycloalkyl group Chemical group 0.000 claims 1
230000001537 neural effect Effects 0.000 claims 1
230000001590 oxidative effect Effects 0.000 claims 1
201000001320 Atherosclerosis Diseases 0.000 abstract description 9
241000124008 Mammalia Species 0.000 abstract description 6
238000011321 prophylaxis Methods 0.000 abstract description 4
208000035150 Hypercholesterolemia Diseases 0.000 abstract description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 35
235000001014 amino acid Nutrition 0.000 description 31
150000003254 radicals Chemical class 0.000 description 23
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 20
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
150000001721 carbon Chemical group 0.000 description 17
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
239000000243 solution Substances 0.000 description 14
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 12
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
238000012546 transfer Methods 0.000 description 12
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 11
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
230000037396 body weight Effects 0.000 description 10
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 10
239000011593 sulfur Substances 0.000 description 10
239000003921 oil Substances 0.000 description 9
235000019198 oils Nutrition 0.000 description 9
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 8
ZSIAUFGUXNUGDI-UHFFFAOYSA-N hexan-1-ol Chemical compound CCCCCCO ZSIAUFGUXNUGDI-UHFFFAOYSA-N 0.000 description 8
239000000543 intermediate Substances 0.000 description 8
239000000047 product Substances 0.000 description 8
239000011541 reaction mixture Substances 0.000 description 8
239000007858 starting material Substances 0.000 description 8
239000003826 tablet Substances 0.000 description 8
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 7
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 7
150000001299 aldehydes Chemical class 0.000 description 7
238000007796 conventional method Methods 0.000 description 7
238000004949 mass spectrometry Methods 0.000 description 7
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 6
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
235000012000 cholesterol Nutrition 0.000 description 6
JARKCYVAAOWBJS-UHFFFAOYSA-N hexanal Chemical compound CCCCCC=O JARKCYVAAOWBJS-UHFFFAOYSA-N 0.000 description 6
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
229910052943 magnesium sulfate Inorganic materials 0.000 description 6
235000019341 magnesium sulphate Nutrition 0.000 description 6
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
239000003444 phase transfer catalyst Substances 0.000 description 6
239000002904 solvent Substances 0.000 description 6
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 5
125000004390 alkyl sulfonyl group Chemical group 0.000 description 5
239000002775 capsule Substances 0.000 description 5
229910052731 fluorine Inorganic materials 0.000 description 5
230000007062 hydrolysis Effects 0.000 description 5
238000006460 hydrolysis reaction Methods 0.000 description 5
229910052698 phosphorus Inorganic materials 0.000 description 5
239000011574 phosphorus Substances 0.000 description 5
239000000843 powder Substances 0.000 description 5
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
150000003242 quaternary ammonium salts Chemical class 0.000 description 5
239000000126 substance Substances 0.000 description 5
239000000725 suspension Substances 0.000 description 5
HKQWVTWXDVJYOD-UHFFFAOYSA-N 2-[(2-benzoylphenyl)sulfanylmethyl]-2-ethylhexanal Chemical compound CCCCC(CC)(C=O)CSC1=CC=CC=C1C(=O)C1=CC=CC=C1 HKQWVTWXDVJYOD-UHFFFAOYSA-N 0.000 description 4
FKNQCJSGGFJEIZ-UHFFFAOYSA-N 4-methylpyridine Chemical compound CC1=CC=NC=C1 FKNQCJSGGFJEIZ-UHFFFAOYSA-N 0.000 description 4
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 4
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 4
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 4
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 4
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 4
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
XOBKSJJDNFUZPF-UHFFFAOYSA-N Methoxyethane Chemical compound CCOC XOBKSJJDNFUZPF-UHFFFAOYSA-N 0.000 description 4
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
150000001412 amines Chemical class 0.000 description 4
210000004369 blood Anatomy 0.000 description 4
239000008280 blood Substances 0.000 description 4
239000012267 brine Substances 0.000 description 4
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
229910052794 bromium Inorganic materials 0.000 description 4
229940079593 drug Drugs 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
239000011737 fluorine Substances 0.000 description 4
238000004817 gas chromatography Methods 0.000 description 4
239000008187 granular material Substances 0.000 description 4
238000004128 high performance liquid chromatography Methods 0.000 description 4
238000005984 hydrogenation reaction Methods 0.000 description 4
239000003701 inert diluent Substances 0.000 description 4
230000005764 inhibitory process Effects 0.000 description 4
239000007972 injectable composition Substances 0.000 description 4
229910052740 iodine Inorganic materials 0.000 description 4
239000011630 iodine Substances 0.000 description 4
239000007788 liquid Substances 0.000 description 4
OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 4
238000002156 mixing Methods 0.000 description 4
230000035484 reaction time Effects 0.000 description 4
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Chemical group O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 description 4
229930192474 thiophene Natural products 0.000 description 4
GDVUGFJXFFCXMX-UHFFFAOYSA-N (2-ethyl-2-formylhexyl) methanesulfonate Chemical compound CCCCC(CC)(C=O)COS(C)(=O)=O GDVUGFJXFFCXMX-UHFFFAOYSA-N 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
229920001268 Cholestyramine Polymers 0.000 description 3
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
238000005481 NMR spectroscopy Methods 0.000 description 3
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125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
150000003573 thiols Chemical class 0.000 description 1
YONPGGFAJWQGJC-UHFFFAOYSA-K titanium(iii) chloride Chemical compound Cl[Ti](Cl)Cl YONPGGFAJWQGJC-UHFFFAOYSA-K 0.000 description 1
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235000010487 tragacanth Nutrition 0.000 description 1
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125000005208 trialkylammonium group Chemical group 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1
ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 1
125000004385 trihaloalkyl group Chemical group 0.000 description 1
208000019553 vascular disease Diseases 0.000 description 1
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Classifications

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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
- 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
- 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
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D337/00—Heterocyclic compounds containing rings of more than six members having one sulfur atom as the only ring hetero atom
- C07D337/02—Seven-membered rings
- C07D337/06—Seven-membered rings condensed with carbocyclic rings or ring systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D337/00—Heterocyclic compounds containing rings of more than six members having one sulfur atom as the only ring hetero atom
- C07D337/02—Seven-membered rings
- C07D337/06—Seven-membered rings condensed with carbocyclic rings or ring systems
- C07D337/08—Seven-membered rings condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/10—Spiro-condensed systems
- 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
- C07F9/6553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having sulfur atoms, with or without selenium or tellurium atoms, as the only ring hetero atoms
- C07F9/655381—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having sulfur atoms, with or without selenium or tellurium atoms, as the only ring hetero atoms the sulfur atom being part of a seven-(or more) membered ring
- C07F9/65539—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having sulfur atoms, with or without selenium or tellurium atoms, as the only ring hetero atoms the sulfur atom being part of a seven-(or more) membered ring condensed with carbocyclic rings or carbocyclic ring systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/06—Dipeptides
- C07K5/06086—Dipeptides with the first amino acid being basic
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G65/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
- C08G65/32—Polymers modified by chemical after-treatment
- C08G65/329—Polymers modified by chemical after-treatment with organic compounds

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Life Sciences & Earth Sciences (AREA)
Public Health (AREA)
Pharmacology & Pharmacy (AREA)
General Chemical & Material Sciences (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
Veterinary Medicine (AREA)
Bioinformatics & Cheminformatics (AREA)
Biochemistry (AREA)
Engineering & Computer Science (AREA)
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Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Biophysics (AREA)
Epidemiology (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Genetics & Genomics (AREA)
Polymers & Plastics (AREA)
Diabetes (AREA)
Hematology (AREA)
Obesity (AREA)
Cardiology (AREA)
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Urology & Nephrology (AREA)
Heart & Thoracic Surgery (AREA)
Gastroenterology & Hepatology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Steroid Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
Peptides Or Proteins (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

BG105206A 1998-07-02 2001-01-31 Бензотиепини, притежаващи активност като инхибитори на пренасянето на илеална жлъчна киселина и на поглъщането на таурохолат BG105206A (bg)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US09/109,551 US5994391A (en)	1994-09-13	1998-07-02	Benzothiepines having activity as inhibitors of ileal bile acid transport and taurocholate uptake
PCT/US1999/012828 WO2000001687A1 (en)	1998-07-02	1999-06-29	Benzothiepines having activity as inhibitors of ileal bile acid transport and taurocholate uptake

Publications (1)

Publication Number	Publication Date
BG105206A true BG105206A (bg)	2001-09-28

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BG105206A BG105206A (bg)	1998-07-02	2001-01-31	Бензотиепини, притежаващи активност като инхибитори на пренасянето на илеална жлъчна киселина и на поглъщането на таурохолат

Country Status (37)

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US (1)	US5994391A (id)
EP (2)	EP1091953B1 (id)
JP (3)	JP2002519418A (id)
KR (1)	KR20010083084A (id)
CN (1)	CN1312805A (id)
AP (1)	AP2001002062A0 (id)
AR (1)	AR019880A1 (id)
AT (1)	ATE256122T1 (id)
AU (2)	AU766957B2 (id)
BG (1)	BG105206A (id)
BR (1)	BR9911737A (id)
CA (1)	CA2336315A1 (id)
CO (2)	CO4950537A1 (id)
DE (1)	DE69913530T2 (id)
DK (1)	DK1091953T3 (id)
EA (2)	EA200400149A1 (id)
EE (1)	EE200100002A (id)
ES (1)	ES2213373T3 (id)
GE (1)	GEP20032925B (id)
HK (1)	HK1039614A1 (id)
HR (1)	HRP20010004A2 (id)
HU (1)	HUP0102840A2 (id)
ID (1)	ID28221A (id)
IL (1)	IL140576A0 (id)
IS (1)	IS5798A (id)
NO (1)	NO20010016L (id)
NZ (1)	NZ509621A (id)
OA (1)	OA11629A (id)
PL (1)	PL346324A1 (id)
PT (1)	PT1091953E (id)
SG (1)	SG108309A1 (id)
SK (1)	SK20302000A3 (id)
TR (1)	TR200100824T2 (id)
TW (1)	TWI229670B (id)
WO (1)	WO2000001687A1 (id)
YU (1)	YU84400A (id)
ZA (1)	ZA200100028B (id)

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1998
- 1998-07-02 US US09/109,551 patent/US5994391A/en not_active Expired - Fee Related
1999
- 1999-06-29 CN CN99809602A patent/CN1312805A/zh active Pending
- 1999-06-29 IL IL14057699A patent/IL140576A0/xx unknown
- 1999-06-29 HR HR20010004A patent/HRP20010004A2/hr not_active Application Discontinuation
- 1999-06-29 OA OA1200000365A patent/OA11629A/en unknown
- 1999-06-29 AT AT99931769T patent/ATE256122T1/de not_active IP Right Cessation
- 1999-06-29 EA EA200400149A patent/EA200400149A1/ru unknown
- 1999-06-29 GE GEAP19995707A patent/GEP20032925B/en unknown
- 1999-06-29 SG SG200207701A patent/SG108309A1/en unknown
- 1999-06-29 BR BR9911737-1A patent/BR9911737A/pt not_active IP Right Cessation
- 1999-06-29 HK HK02100948.1A patent/HK1039614A1/zh unknown
- 1999-06-29 JP JP2000558091A patent/JP2002519418A/ja active Pending
- 1999-06-29 AU AU48202/99A patent/AU766957B2/en not_active Ceased
- 1999-06-29 EP EP99931769A patent/EP1091953B1/en not_active Expired - Lifetime
- 1999-06-29 ES ES99931769T patent/ES2213373T3/es not_active Expired - Lifetime
- 1999-06-29 TR TR2001/00824T patent/TR200100824T2/xx unknown
- 1999-06-29 EP EP03026649A patent/EP1466911A3/en not_active Withdrawn
- 1999-06-29 EA EA200100002A patent/EA004650B1/ru not_active IP Right Cessation
- 1999-06-29 ID IDW20010002A patent/ID28221A/id unknown
- 1999-06-29 PL PL99346324A patent/PL346324A1/xx unknown
- 1999-06-29 DE DE69913530T patent/DE69913530T2/de not_active Expired - Fee Related
- 1999-06-29 YU YU84400A patent/YU84400A/sh unknown
- 1999-06-29 DK DK99931769T patent/DK1091953T3/da active
- 1999-06-29 EE EEP200100002A patent/EE200100002A/xx unknown
- 1999-06-29 KR KR1020017000027A patent/KR20010083084A/ko not_active Ceased
- 1999-06-29 NZ NZ509621A patent/NZ509621A/en unknown
- 1999-06-29 SK SK2030-2000A patent/SK20302000A3/sk unknown
- 1999-06-29 HU HU0102840A patent/HUP0102840A2/hu unknown
- 1999-06-29 AP APAP/P/2001/002062A patent/AP2001002062A0/en unknown
- 1999-06-29 WO PCT/US1999/012828 patent/WO2000001687A1/en not_active Ceased
- 1999-06-29 CA CA002336315A patent/CA2336315A1/en not_active Abandoned
- 1999-06-29 PT PT99931769T patent/PT1091953E/pt unknown
- 1999-07-02 CO CO99041717A patent/CO4950537A1/es unknown
- 1999-07-02 CO CO99041717D patent/CO5080807A1/es unknown
- 1999-07-02 AR ARP990103234A patent/AR019880A1/es unknown
2000
- 2000-01-07 TW TW088111293A patent/TWI229670B/zh not_active IP Right Cessation
- 2000-12-29 IS IS5798A patent/IS5798A/is unknown
2001
- 2001-01-02 ZA ZA200100028A patent/ZA200100028B/xx unknown
- 2001-01-02 NO NO20010016A patent/NO20010016L/no not_active Application Discontinuation
- 2001-01-31 BG BG105206A patent/BG105206A/bg unknown
2004
- 2004-01-30 AU AU2004200346A patent/AU2004200346A1/en not_active Abandoned
- 2004-02-25 JP JP2004050473A patent/JP2004203891A/ja active Pending
- 2004-08-03 JP JP2004227034A patent/JP2004359694A/ja active Pending

Also Published As

Publication number	Publication date
PL346324A1 (en)	2002-02-11
US5994391A (en)	1999-11-30
CA2336315A1 (en)	2000-01-13
OA11629A (en)	2004-11-10
DE69913530T2 (de)	2004-09-23
EP1091953B1 (en)	2003-12-10
EE200100002A (et)	2002-06-17
NO20010016L (no)	2001-03-02
DK1091953T3 (da)	2004-04-13
IS5798A (is)	2000-12-29
YU84400A (sh)	2002-12-10
ES2213373T3 (es)	2004-08-16
BR9911737A (pt)	2001-12-11
JP2004203891A (ja)	2004-07-22
JP2004359694A (ja)	2004-12-24
WO2000001687A9 (en)	2000-07-20
ZA200100028B (en)	2001-07-25
JP2002519418A (ja)	2002-07-02
EP1466911A3 (en)	2005-09-07
SG108309A1 (en)	2005-01-28
WO2000001687A1 (en)	2000-01-13
AR019880A1 (es)	2002-03-20
AU2004200346A1 (en)	2004-02-26
IL140576A0 (en)	2002-02-10
PT1091953E (pt)	2004-04-30
DE69913530D1 (de)	2004-01-22
TWI229670B (en)	2005-03-21
ID28221A (id)	2001-05-10
AP2001002062A0 (en)	2001-03-31
GEP20032925B (en)	2003-03-25
EA004650B1 (ru)	2004-06-24
EA200100002A1 (ru)	2001-08-27
CO4950537A1 (es)	2000-09-01
TR200100824T2 (tr)	2001-07-23
SK20302000A3 (sk)	2001-11-06
NO20010016D0 (no)	2001-01-02
EA200400149A1 (ru)	2004-10-28
EP1091953A1 (en)	2001-04-18
KR20010083084A (ko)	2001-08-31
AU4820299A (en)	2000-01-24
HK1039614A1 (zh)	2002-05-03
NZ509621A (en)	2003-08-29
HUP0102840A2 (hu)	2002-01-28
ATE256122T1 (de)	2003-12-15
EP1466911A2 (en)	2004-10-13
CO5080807A1 (es)	2001-09-25
AU766957B2 (en)	2003-10-30
HRP20010004A2 (en)	2001-12-31
CN1312805A (zh)	2001-09-12

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US20040077625A1 (en)	2004-04-22	Novel 1,4-benzothiazepine and 1,5-benzothiazepine compounds as inhibitors of apical sodium codependent bile acid transport abd taurocholate uptake
US6420417B1 (en)	2002-07-16	Combination therapy employing ileal bile acid transport inhibiting benzothiepines and HMG Co-A reductase inhibitors
CZ20004937A3 (cs)	2001-06-13	Benzothiepiny, které mají účinek jako inhibitory transportu žlučových kyselin v ileu a vychytávání taurocholátu
MXPA01000208A (en)	2001-09-07	Novel benzothiepines having activity as inhibitors of ileal bile acid transport and taurocholate uptake
EP1440972A1 (en)	2004-07-28	Novel benzothiepines having pharmaceutical activity.
HK1068342A (en)	2005-04-29	Novel benzothiepines having pharmaceutical activity
KR19990087721A (ko)	1999-12-27	회장 담즙산 운반 및 타우로콜레이트 흡수 저해제로서의 활성을 갖는 신규한 벤조티에핀