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 PDFInfo
- Publication number
- BG105206A BG105206A BG105206A BG10520601A BG105206A BG 105206 A BG105206 A BG 105206A BG 105206 A BG105206 A BG 105206A BG 10520601 A BG10520601 A BG 10520601A BG 105206 A BG105206 A BG 105206A
- Authority
- BG
- Bulgaria
- Prior art keywords
- heterocycle
- alkyl
- group
- quaternary
- aryl
- Prior art date
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
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 3
- 229930006000 Sucrose Natural products 0.000 description 3
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 3
- GNVMUORYQLCPJZ-UHFFFAOYSA-M Thiocarbamate Chemical compound NC([S-])=O GNVMUORYQLCPJZ-UHFFFAOYSA-M 0.000 description 3
- 239000000853 adhesive Substances 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- 150000003863 ammonium salts Chemical class 0.000 description 3
- 230000005540 biological transmission Effects 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 239000002702 enteric coating Substances 0.000 description 3
- 238000009505 enteric coating Methods 0.000 description 3
- 238000000605 extraction Methods 0.000 description 3
- 210000001035 gastrointestinal tract Anatomy 0.000 description 3
- 230000000055 hyoplipidemic effect Effects 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 210000004185 liver Anatomy 0.000 description 3
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 3
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 125000005702 oxyalkylene group Chemical group 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 229920000642 polymer Polymers 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 241000894007 species Species 0.000 description 3
- 239000005720 sucrose Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- FMCAFXHLMUOIGG-JTJHWIPRSA-N (2s)-2-[[(2r)-2-[[(2s)-2-[[(2r)-2-formamido-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,5-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoic acid Chemical compound O=CN[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(=O)N[C@@H](CCSC)C(O)=O)CC1=CC(C)=C(O)C=C1C FMCAFXHLMUOIGG-JTJHWIPRSA-N 0.000 description 2
- QPQAFLPWFVOKBJ-INIZCTEOSA-N (5s)-1-methyl-5-pentyl-5-phenyl-1,3-diazinane-2,4,6-trione Chemical compound C=1C=CC=CC=1[C@@]1(CCCCC)C(=O)NC(=O)N(C)C1=O QPQAFLPWFVOKBJ-INIZCTEOSA-N 0.000 description 2
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 description 2
- CKQFWQCSMNUSRI-UHFFFAOYSA-N 1,1-dimethylpiperazin-1-ium Chemical compound C[N+]1(C)CCNCC1 CKQFWQCSMNUSRI-UHFFFAOYSA-N 0.000 description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
- 241000220479 Acacia Species 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 238000008214 LDL Cholesterol Methods 0.000 description 2
- 102000000853 LDL receptors Human genes 0.000 description 2
- 108010001831 LDL receptors Proteins 0.000 description 2
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 2
- 238000003820 Medium-pressure liquid chromatography Methods 0.000 description 2
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 230000001070 adhesive effect Effects 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 2
- 239000003529 anticholesteremic agent Substances 0.000 description 2
- 239000000010 aprotic solvent Substances 0.000 description 2
- 125000000732 arylene group Chemical group 0.000 description 2
- 125000005605 benzo group Chemical group 0.000 description 2
- 235000019445 benzyl alcohol Nutrition 0.000 description 2
- 210000000941 bile Anatomy 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 150000007942 carboxylates Chemical class 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 2
- 150000002009 diols Chemical class 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- 239000008298 dragée Substances 0.000 description 2
- 230000010235 enterohepatic circulation Effects 0.000 description 2
- 230000029142 excretion Effects 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- 150000004676 glycans Chemical class 0.000 description 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 230000000871 hypocholesterolemic effect Effects 0.000 description 2
- 210000003405 ileum Anatomy 0.000 description 2
- 238000000338 in vitro Methods 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
- GLNWILHOFOBOFD-UHFFFAOYSA-N lithium sulfide Chemical compound [Li+].[Li+].[S-2] GLNWILHOFOBOFD-UHFFFAOYSA-N 0.000 description 2
- 239000000314 lubricant Substances 0.000 description 2
- 229910001629 magnesium chloride Inorganic materials 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N methanol Natural products OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 2
- 229960001047 methyl salicylate Drugs 0.000 description 2
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 2
- 235000010755 mineral Nutrition 0.000 description 2
- 238000000465 moulding Methods 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 239000000346 nonvolatile oil Substances 0.000 description 2
- 239000012074 organic phase Substances 0.000 description 2
- 229920001282 polysaccharide Polymers 0.000 description 2
- 239000005017 polysaccharide Substances 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 235000010265 sodium sulphite Nutrition 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 2
- 125000004434 sulfur atom Chemical group 0.000 description 2
- 239000000375 suspending agent Substances 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 238000011269 treatment regimen Methods 0.000 description 2
- AQRLNPVMDITEJU-UHFFFAOYSA-N triethylsilane Chemical compound CC[SiH](CC)CC AQRLNPVMDITEJU-UHFFFAOYSA-N 0.000 description 2
- PGIPTXFXNUVZFZ-UHFFFAOYSA-N (2-chloro-4-nitrophenyl)-phenylmethanone Chemical compound ClC1=CC([N+](=O)[O-])=CC=C1C(=O)C1=CC=CC=C1 PGIPTXFXNUVZFZ-UHFFFAOYSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- OJMJOSRCBAXSAQ-UHFFFAOYSA-N 2,2-dibutylpropane-1,3-diol Chemical compound CCCCC(CO)(CO)CCCC OJMJOSRCBAXSAQ-UHFFFAOYSA-N 0.000 description 1
- UVEFAZXHHJHMGK-UHFFFAOYSA-N 2-ethyl-2-(hydroxymethyl)hexanal Chemical compound CCCCC(CC)(CO)C=O UVEFAZXHHJHMGK-UHFFFAOYSA-N 0.000 description 1
- OIOASXNVXSNIKG-UHFFFAOYSA-N 2-iodoethyl hypoiodite Chemical compound ICCOI OIOASXNVXSNIKG-UHFFFAOYSA-N 0.000 description 1
- SDTMFDGELKWGFT-UHFFFAOYSA-N 2-methylpropan-2-olate Chemical compound CC(C)(C)[O-] SDTMFDGELKWGFT-UHFFFAOYSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- JRLTTZUODKEYDH-UHFFFAOYSA-N 8-methylquinoline Chemical group C1=CN=C2C(C)=CC=CC2=C1 JRLTTZUODKEYDH-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 1
- 229920001661 Chitosan Polymers 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 241000699800 Cricetinae Species 0.000 description 1
- 206010012186 Delayed delivery Diseases 0.000 description 1
- ZNZYKNKBJPZETN-WELNAUFTSA-N Dialdehyde 11678 Chemical compound N1C2=CC=CC=C2C2=C1[C@H](C[C@H](/C(=C/O)C(=O)OC)[C@@H](C=C)C=O)NCC2 ZNZYKNKBJPZETN-WELNAUFTSA-N 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 102000004286 Hydroxymethylglutaryl CoA Reductases Human genes 0.000 description 1
- 108090000895 Hydroxymethylglutaryl CoA Reductases Proteins 0.000 description 1
- 108010028554 LDL Cholesterol Proteins 0.000 description 1
- 108010007622 LDL Lipoproteins Proteins 0.000 description 1
- 102000007330 LDL Lipoproteins Human genes 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 239000004166 Lanolin Substances 0.000 description 1
- 229910018091 Li 2 S Inorganic materials 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 description 1
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical group SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 1
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- KBXILIYZUWEKCM-UHFFFAOYSA-N N-amino-N-ethylsulfanylhydroxylamine Chemical compound CCSN(N)O KBXILIYZUWEKCM-UHFFFAOYSA-N 0.000 description 1
- HMNPNZSYZGFMOE-UHFFFAOYSA-N OI(SC)(OC(C)C)(OCC)OC Chemical compound OI(SC)(OC(C)C)(OCC)OC HMNPNZSYZGFMOE-UHFFFAOYSA-N 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 239000004264 Petrolatum Substances 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical group CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 description 1
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 1
- 108010069201 VLDL Cholesterol Proteins 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 description 1
- DGAXYDCFAIZNGZ-UHFFFAOYSA-N [ethoxy(methoxy)methyl]-dimethyl-propan-2-yloxyazanium Chemical compound COC([N+](C)(C)OC(C)C)OCC DGAXYDCFAIZNGZ-UHFFFAOYSA-N 0.000 description 1
- 230000001133 acceleration Effects 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001345 alkine derivatives Chemical class 0.000 description 1
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 1
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 description 1
- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 125000003705 anilinocarbonyl group Chemical group O=C([*])N([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 229920006318 anionic polymer Polymers 0.000 description 1
- 239000003524 antilipemic agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000005199 aryl carbonyloxy group Chemical group 0.000 description 1
- 150000005840 aryl radicals Chemical class 0.000 description 1
- 125000004104 aryloxy group Chemical group 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000002619 bicyclic group Chemical group 0.000 description 1
- 238000009739 binding Methods 0.000 description 1
- 230000027455 binding Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000035587 bioadhesion Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- SIPUZPBQZHNSDW-UHFFFAOYSA-N bis(2-methylpropyl)aluminum Chemical compound CC(C)C[Al]CC(C)C SIPUZPBQZHNSDW-UHFFFAOYSA-N 0.000 description 1
- BPVYMDMPLCOQPJ-UHFFFAOYSA-L bis(trifluoromethylsulfonyloxy)mercury Chemical compound [Hg+2].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F BPVYMDMPLCOQPJ-UHFFFAOYSA-L 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 230000001364 causal effect Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 1
- 239000007806 chemical reaction intermediate Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 150000001840 cholesterol esters Chemical class 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 230000009850 completed effect Effects 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 239000007891 compressed tablet Substances 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 208000029078 coronary artery disease Diseases 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 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 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- RTPCQAKIYNLFPG-UHFFFAOYSA-N dibutyl 2,2-diethylpropanedioate Chemical compound CCCCOC(=O)C(CC)(CC)C(=O)OCCCC RTPCQAKIYNLFPG-UHFFFAOYSA-N 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 210000002249 digestive system Anatomy 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
- CETRZFQIITUQQL-UHFFFAOYSA-N dmso dimethylsulfoxide Chemical compound CS(C)=O.CS(C)=O CETRZFQIITUQQL-UHFFFAOYSA-N 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 210000002615 epidermis Anatomy 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- OLAMWIPURJGSKE-UHFFFAOYSA-N et2o diethylether Chemical compound CCOCC.CCOCC OLAMWIPURJGSKE-UHFFFAOYSA-N 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 1
- 230000003631 expected effect Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 230000004129 fatty acid metabolism Effects 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 230000002550 fecal effect Effects 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000006260 foam Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 208000001130 gallstones Diseases 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 125000004440 haloalkylsulfinyl group Chemical group 0.000 description 1
- 125000004995 haloalkylthio group Chemical group 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 125000005343 heterocyclic alkyl group Chemical group 0.000 description 1
- 125000006038 hexenyl group Chemical group 0.000 description 1
- 125000005980 hexynyl group Chemical group 0.000 description 1
- 238000004896 high resolution mass spectrometry Methods 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 150000002443 hydroxylamines Chemical class 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000003978 infusion fluid Substances 0.000 description 1
- 238000011221 initial treatment Methods 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 229940102213 injectable suspension Drugs 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 210000004347 intestinal mucosa Anatomy 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000026045 iodination Effects 0.000 description 1
- 238000006192 iodination reaction Methods 0.000 description 1
- 150000002496 iodine Chemical class 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 229940039717 lanolin Drugs 0.000 description 1
- 235000019388 lanolin Nutrition 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 108010022197 lipoprotein cholesterol Proteins 0.000 description 1
- 239000008297 liquid dosage form Substances 0.000 description 1
- 229910000103 lithium hydride Inorganic materials 0.000 description 1
- SIAPCJWMELPYOE-UHFFFAOYSA-N lithium hydride Chemical compound [LiH] SIAPCJWMELPYOE-UHFFFAOYSA-N 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 210000004379 membrane Anatomy 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 125000005905 mesyloxy group Chemical group 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- AGJSNMGHAVDLRQ-IWFBPKFRSA-N methyl (2s)-2-[[(2s)-2-[[(2s)-2-[[(2r)-2-amino-3-sulfanylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxy-2,3-dimethylphenyl)propanoyl]amino]-4-methylsulfanylbutanoate Chemical compound SC[C@H](N)C(=O)N[C@@H](C(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCSC)C(=O)OC)CC1=CC=C(O)C(C)=C1C AGJSNMGHAVDLRQ-IWFBPKFRSA-N 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 description 1
- XKBGEWXEAPTVCK-UHFFFAOYSA-M methyltrioctylammonium chloride Chemical compound [Cl-].CCCCCCCC[N+](C)(CCCCCCCC)CCCCCCCC XKBGEWXEAPTVCK-UHFFFAOYSA-M 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000007932 molded tablet Substances 0.000 description 1
- PHWISQNXPLXQRU-UHFFFAOYSA-N n,n-dimethylcarbamothioyl chloride Chemical compound CN(C)C(Cl)=S PHWISQNXPLXQRU-UHFFFAOYSA-N 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000005445 natural material Substances 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 239000007764 o/w emulsion Substances 0.000 description 1
- 239000004533 oil dispersion Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 150000002924 oxiranes Chemical class 0.000 description 1
- 125000006353 oxyethylene group Chemical group 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 235000010603 pastilles Nutrition 0.000 description 1
- 230000004796 pathophysiological change Effects 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 125000005981 pentynyl group Chemical group 0.000 description 1
- 229940066842 petrolatum Drugs 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- SPEXCGKGVJUPGG-UHFFFAOYSA-N phenyl-(2-sulfanylphenyl)methanone Chemical compound SC1=CC=CC=C1C(=O)C1=CC=CC=C1 SPEXCGKGVJUPGG-UHFFFAOYSA-N 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 229940068917 polyethylene glycols Drugs 0.000 description 1
- 229940100467 polyvinyl acetate phthalate Drugs 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- LBKJNHPKYFYCLL-UHFFFAOYSA-N potassium;trimethyl(oxido)silane Chemical compound [K+].C[Si](C)(C)[O-] LBKJNHPKYFYCLL-UHFFFAOYSA-N 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 208000000876 primary bile acid malabsorption Diseases 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- NQLVQOSNDJXLKG-UHFFFAOYSA-N prosulfocarb Chemical compound CCCN(CCC)C(=O)SCC1=CC=CC=C1 NQLVQOSNDJXLKG-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- YBCAZPLXEGKKFM-UHFFFAOYSA-K ruthenium(iii) chloride Chemical compound [Cl-].[Cl-].[Cl-].[Ru+3] YBCAZPLXEGKKFM-UHFFFAOYSA-K 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 210000000813 small intestine Anatomy 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 125000005504 styryl group Chemical group 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 125000005420 sulfonamido group Chemical group S(=O)(=O)(N*)* 0.000 description 1
- 125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 description 1
- 125000000542 sulfonic acid group Chemical group 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 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
- 231100000583 toxicological profile Toxicity 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 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
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 239000007762 w/o emulsion Substances 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- 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
- C07D495/10—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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biochemistry (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- 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)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Gastroenterology & Hepatology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Peptides Or Proteins (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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 |
Family
ID=22328263
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| 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)
| Country | Link |
|---|---|
| US (1) | US5994391A (pt) |
| EP (2) | EP1091953B1 (pt) |
| JP (3) | JP2002519418A (pt) |
| KR (1) | KR20010083084A (pt) |
| CN (1) | CN1312805A (pt) |
| AP (1) | AP2001002062A0 (pt) |
| AR (1) | AR019880A1 (pt) |
| AT (1) | ATE256122T1 (pt) |
| AU (2) | AU766957B2 (pt) |
| BG (1) | BG105206A (pt) |
| BR (1) | BR9911737A (pt) |
| CA (1) | CA2336315A1 (pt) |
| CO (2) | CO5080807A1 (pt) |
| DE (1) | DE69913530T2 (pt) |
| DK (1) | DK1091953T3 (pt) |
| EA (2) | EA004650B1 (pt) |
| EE (1) | EE200100002A (pt) |
| ES (1) | ES2213373T3 (pt) |
| GE (1) | GEP20032925B (pt) |
| HK (1) | HK1039614A1 (pt) |
| HR (1) | HRP20010004A2 (pt) |
| HU (1) | HUP0102840A2 (pt) |
| ID (1) | ID28221A (pt) |
| IL (1) | IL140576A0 (pt) |
| IS (1) | IS5798A (pt) |
| NO (1) | NO20010016L (pt) |
| NZ (1) | NZ509621A (pt) |
| OA (1) | OA11629A (pt) |
| PL (1) | PL346324A1 (pt) |
| PT (1) | PT1091953E (pt) |
| SG (1) | SG108309A1 (pt) |
| SK (1) | SK20302000A3 (pt) |
| TR (1) | TR200100824T2 (pt) |
| TW (1) | TWI229670B (pt) |
| WO (1) | WO2000001687A1 (pt) |
| YU (1) | YU84400A (pt) |
| ZA (1) | ZA200100028B (pt) |
Families Citing this family (96)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6268392B1 (en) | 1994-09-13 | 2001-07-31 | G. D. Searle & Co. | Combination therapy employing ileal bile acid transport inhibiting benzothiepines and HMG Co-A reductase inhibitors |
| US6642268B2 (en) | 1994-09-13 | 2003-11-04 | G.D. Searle & Co. | Combination therapy employing ileal bile acid transport inhibiting benzothipines and HMG Co-A reductase inhibitors |
| US6262277B1 (en) * | 1994-09-13 | 2001-07-17 | G.D. Searle And Company | Intermediates and processes for the preparation of benzothiepines having activity as inhibitors of ileal bile acid transport and taurocholate uptake |
| BR9814300A (pt) * | 1997-12-19 | 2002-02-05 | Searle & Co | Método de preparação de óxidos de tetraidrobenzotiepina enanciomericamente enriquecidos |
| US6221897B1 (en) * | 1998-06-10 | 2001-04-24 | Aventis Pharma Deutschland Gmbh | Benzothiepine 1,1-dioxide derivatives, a process for their preparation, pharmaceuticals comprising these compounds, and their use |
| DE19825804C2 (de) * | 1998-06-10 | 2000-08-24 | Aventis Pharma Gmbh | 1,4-Benzothiepin-1,1-dioxidderivate, Verfahren zu deren Herstellung und diese Verbindungen enthaltende Arzneimittel |
| EP1140896A1 (en) * | 1998-12-21 | 2001-10-10 | Takeda Chemical Industries, Ltd. | Benzothiepin-anilide derivatives, their production and their use for antagonizing ccr-5 |
| US6458851B1 (en) * | 1998-12-23 | 2002-10-01 | G. D. Searle, Llc | Combinations of ileal bile acid transport inhibitors and cholesteryl ester transfer protein inhibitors for cardiovascular indications |
| AU2157400A (en) | 1998-12-23 | 2000-07-31 | G.D. Searle & Co. | Combinations of cholesteryl ester transfer protein inhibitors and hmg coa reductase inhibitors for cardiovascular indications |
| DK1140184T3 (da) * | 1998-12-23 | 2003-09-29 | Searle Llc | Kombinationer af cholesterylestertransferproteinhæmmere og nikotinsyrederivater til hjertekar indikationer |
| EA200100704A1 (ru) * | 1998-12-23 | 2002-02-28 | Джи.Ди.Сирл Ллс | Комбинация для применения по сердечно-сосудистым показаниям |
| ATE240120T1 (de) | 1998-12-23 | 2003-05-15 | Searle Llc | Kombinationen von ileumgallensäuretransports inhibitoren und fibronsäure derivaten für kardiovaskuläre indikationen |
| JP2002533409A (ja) | 1998-12-23 | 2002-10-08 | ジー．ディー．サール エルエルシー | 心臓血管に適用するためのコレステリルエステル転送タンパク質阻害剤および胆汁酸隔離剤の組み合わせ |
| WO2000038724A1 (en) * | 1998-12-23 | 2000-07-06 | G.D. Searle Llc | Combinations of cholesteryl ester transfer protein inhibitors and fibric acid derivatives for cardiovascular indications |
| KR20010102965A (ko) * | 1998-12-23 | 2001-11-17 | 윌리암스 로저 에이 | 심장혈관의 징후에 대한 회장 담즙산 수송 저해제 및담즙산 격리제의 병용 |
| CA2373464A1 (en) * | 1999-05-18 | 2000-11-23 | Tomomi Ikemoto | Process for the preparation of 2,3-dihydrothiepine derivatives |
| SE0000772D0 (sv) * | 2000-03-08 | 2000-03-08 | Astrazeneca Ab | Chemical compounds |
| US6586434B2 (en) * | 2000-03-10 | 2003-07-01 | G.D. Searle, Llc | Method for the preparation of tetrahydrobenzothiepines |
| WO2001068096A2 (en) * | 2000-03-10 | 2001-09-20 | Pharmacia Corporation | Combination therapy for the prophylaxis and treatment of hyperlipidemic conditions and disorders |
| JP4205340B2 (ja) | 2000-03-24 | 2009-01-07 | ファルマシア コーポレーション | 酸化窒素シンターゼ阻害剤として有用なアミジノ化合物およびその塩 |
| US6545170B2 (en) | 2000-04-13 | 2003-04-08 | Pharmacia Corporation | 2-amino-5, 6 heptenoic acid derivatives useful as nitric oxide synthase inhibitors |
| US6787668B2 (en) | 2000-04-13 | 2004-09-07 | Pharmacia Corporation | 2-amino-4,5 heptenoic acid derivatives useful as nitric oxide synthase inhibitors |
| AR030416A1 (es) | 2000-04-13 | 2003-08-20 | Pharmacia Corp | COMPUESTO DERIVADO HALOGENADO DEL ACIDO 2-AMINO-3,4 HEPTENOICO, COMPOSICION FARMACEUTICA QUE LO COMPRENDE Y SU USO EN LA FABRICACION DE UN MEDICAMENTO uTIL COMO INHIBIDOR DE LA OXIDO NITRICO SINTETASA |
| AR034120A1 (es) | 2000-04-13 | 2004-02-04 | Pharmacia Corp | Compuesto derivado halogenado del acido 2-amino-4,5 heptenoico, composicion farmaceutica que lo comprende y el uso de dicho compuesto y dicha composicion en la fabricacion de un medicamento para inhibir o modular la sintesis de acido nitrico |
| AR032318A1 (es) | 2000-04-13 | 2003-11-05 | Pharmacia Corp | Compuesto derivado halogenado del acido 2-amino-5,6 heptenoico; composicion farmaceutica que lo comprende y su uso en la fabricacion de un medicamento util como inhibidor de la oxido nitrico sintetasa |
| US6956131B2 (en) | 2000-04-13 | 2005-10-18 | Pharmacia Corporation | 2-amino-3, 4 heptenoic compounds useful as nitric oxide synthase inhibitors |
| EA005817B1 (ru) | 2000-08-01 | 2005-06-30 | Фармасиа Корпорейшн | Производные гексагидро-7-1h-азепин-2-илгексановой (или гексеновой) кислоты в качестве ингибиторов индуцибельной синтазы оксида азота |
| AR031129A1 (es) * | 2000-09-15 | 2003-09-10 | Pharmacia Corp | Derivados de los acidos 2-amino-2-alquil-4-hexenoico y -hexinoico utiles como inhibidores de oxido nitrico sintetasa |
| AR030741A1 (es) | 2000-09-15 | 2003-09-03 | Pharmacia Corp | Derivados de los acidos 2-amino-2-alquil-5-heptenoico y - heptinoico utiles como inhibidores de oxido nitrico sintetasa |
| EG26979A (en) | 2000-12-21 | 2015-03-01 | Astrazeneca Ab | Chemical compounds |
| IL156552A0 (en) | 2000-12-21 | 2004-01-04 | Aventis Pharma Gmbh | Diphenyl azetidinone derivatives, method for the production thereof, medicaments containing these compounds, and their use |
| AU2002306868A1 (en) * | 2001-03-28 | 2002-10-15 | Pharmacia Corporation | Therapeutic combinations for cardiovascular and inflammatory indications |
| US20040077625A1 (en) * | 2001-07-25 | 2004-04-22 | Tremont Samuel J. | Novel 1,4-benzothiazepine and 1,5-benzothiazepine compounds as inhibitors of apical sodium codependent bile acid transport abd taurocholate uptake |
| GB0121337D0 (en) | 2001-09-04 | 2001-10-24 | Astrazeneca Ab | Chemical compounds |
| GB0121621D0 (en) | 2001-09-07 | 2001-10-31 | Astrazeneca Ab | Chemical compounds |
| GB0121622D0 (en) | 2001-09-07 | 2001-10-31 | Astrazeneca Ab | Chemical compounds |
| NZ531796A (en) | 2001-09-08 | 2005-10-28 | Astrazeneca Ab | Benzothiazepine and benzothiadiazepine derivatives with ileal bile acid transport (ibat) inhibitory activity for the treatment of hyperlipidaemia |
| CA2460330A1 (en) * | 2001-09-12 | 2003-03-20 | G.D. Searle Llc | Method for the preparation of crystalline tetrahydrobenzothiepines |
| MXPA04003524A (es) * | 2001-11-02 | 2004-07-23 | Searle Llc | Compuestos de benzotiepina monofluorados y difluorados novedosos como inhibidores de transporte de acido biliar co-dependiente de sodio apical (asbt) y captacion de taurocolato. |
| US20030112119A1 (en) * | 2001-12-19 | 2003-06-19 | Hom Wayne C. | Independent teleservicing module with a pager as its means of communication |
| BR0306643A (pt) | 2002-01-17 | 2004-10-19 | Pharmacia Corp | Novos compostos de hidroxi alquil/aril ou ceto tiepina como inibidores do transporte co-dependente de ácido biliar-sódio apical |
| US20040014806A1 (en) * | 2002-03-08 | 2004-01-22 | Pharmacia Corporation | Methods and compositions for lowering levels of blood lipids |
| GB0209467D0 (en) | 2002-04-25 | 2002-06-05 | Astrazeneca Ab | Chemical compounds |
| GB0213669D0 (en) | 2002-06-14 | 2002-07-24 | Astrazeneca Ab | Chemical compounds |
| US7312208B2 (en) | 2002-08-28 | 2007-12-25 | Asahi Kasei Pharma Corporation | Quaternary ammonium compounds |
| ATE531701T1 (de) * | 2002-08-28 | 2011-11-15 | Asahi Kasei Pharma Corp | Neue quaternüre ammoniumverbindungen |
| GB0304194D0 (en) * | 2003-02-25 | 2003-03-26 | Astrazeneca Ab | Chemical compounds |
| GB0307918D0 (en) | 2003-04-05 | 2003-05-14 | Astrazeneca Ab | Therapeutic use |
| WO2005042692A2 (en) * | 2003-10-31 | 2005-05-12 | Forbes Medi-Tech Inc. | A method of inhibiting the expression of genes which mediate cellular cholesterol influx in animal cells and inhibiting the production of proteins resulting from the expression of such genes using cholesterol absorption inhibitors |
| KR20070026392A (ko) * | 2004-02-27 | 2007-03-08 | 아사히 가세이 파마 가부시키가이샤 | 신규 벤조티아제핀 및 벤조티에핀 화합물 |
| DE102006053637B4 (de) * | 2006-11-14 | 2011-06-30 | Sanofi-Aventis Deutschland GmbH, 65929 | Neue mit Fluor substituierte 1,4-Benzothiepin-1,1-Dioxidderivate, diese Verbindungen enthaltende Arzneimittel und deren Verwendung |
| ATE493992T1 (de) * | 2006-11-14 | 2011-01-15 | Sanofi Aventis Deutschland | Neue 1,4-benzothiepin-1,1-dioxidderivate mit verbesserten eigenschaften, verfahren zu deren herstellung, diese verbindungen enthaltende arzneimittel und deren verwendung |
| DE102006053636B4 (de) * | 2006-11-14 | 2008-09-18 | Sanofi-Aventis Deutschland Gmbh | Neue mit Cyclohexylresten substituierte 1,4-Benzothiepin-1,1-Dioxidderivate und deren Verwendung |
| DE102006053635B4 (de) * | 2006-11-14 | 2011-06-30 | Sanofi-Aventis Deutschland GmbH, 65929 | Neue mit Benzylresten substituierte 1,4-Benzothiepin-1,1-Dioxidderivate, diese Verbindungen enthaltende Arzneimittel und deren Verwendung |
| WO2009132832A2 (de) * | 2008-05-02 | 2009-11-05 | Sanofi-Aventis Deutschland Gmbh | Verfahren zur herstellung von 1,4-benzothiepin-1,1-dioxidderivaten |
| DE102008022017A1 (de) | 2008-05-02 | 2009-11-05 | Sanofi-Aventis Deutschland Gmbh | Verfahren zur Herstellung von 1,4-Benzothiepin-1,1-Dioxidderivaten |
| CA2744817C (en) * | 2008-11-26 | 2020-07-07 | Satiogen Pharmaceuticals, Inc. | Bile acid recycling inhibitors for treatment of obesity and diabetes |
| ES2552657T3 (es) | 2010-05-26 | 2015-12-01 | Satiogen Pharmaceuticals, Inc. | Inhibidores del reciclado de ácidos biliares y saciógenos para el tratamiento de diabetes, obesidad, y afecciones gastrointestinales inflamatorias |
| SG190433A1 (en) | 2010-11-08 | 2013-06-28 | Albireo Ab | A pharmaceutical combination comprising an ibat inhibitor and a bile acid binder |
| DK2637668T3 (en) | 2010-11-08 | 2016-08-29 | Albireo Ab | Ibat inhibitors for the treatment of liver diseases |
| US20120114588A1 (en) * | 2010-11-08 | 2012-05-10 | Albireo Ab | Ibat inhibitors for treatment of metabolic disorders and related conditions |
| 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. |
| US20140243281A1 (en) | 2011-10-28 | 2014-08-28 | Lumena Pharmaceuticals, Inc. | Bile acid recycling inhibitors for treatment of pediatric cholestatic liver diseases |
| CA2907214A1 (en) | 2013-03-15 | 2014-09-18 | Lumena Pharmaceuticals, Inc. | Bile acid recycling inhibitors for treatment of barrett's esophagus and gastroesophageal reflux disease |
| KR20230152818A (ko) | 2013-03-15 | 2023-11-03 | 샤이어 휴먼 지네틱 테라피즈 인크. | 원발성 담관염 및 염증성 장 질환 치료용 담즙산 재순환 억제제 |
| 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 |
| EP3012252A1 (en) | 2014-10-24 | 2016-04-27 | Ferring BV | Crystal modifications of elobixibat |
| RU2615769C2 (ru) * | 2015-07-29 | 2017-04-11 | Федеральное Государственное Бюджетное Образовательное Учреждение Высшего Образования "Уфимский Государственный Университет Экономики И Сервиса" | Средство для ингибирования фермента альфа-амилазы |
| ES2874669T3 (es) | 2016-02-09 | 2021-11-05 | Albireo Ab | Formulación oral de colestiramina y uso de la misma |
| US10441605B2 (en) | 2016-02-09 | 2019-10-15 | Albireo Ab | Oral cholestyramine formulation and use thereof |
| US10786529B2 (en) | 2016-02-09 | 2020-09-29 | Albireo Ab | Oral cholestyramine formulation and use thereof |
| RU2750937C2 (ru) | 2016-02-09 | 2021-07-06 | Альбирео Аб | Пероральный состав холестирамина и его применение |
| US10441604B2 (en) | 2016-02-09 | 2019-10-15 | Albireo Ab | Cholestyramine pellets and methods for preparation thereof |
| WO2019032026A1 (en) | 2017-08-09 | 2019-02-14 | Albireo Ab | CHOLESTYRAMINE GRANULES, ORAL FORMULATIONS OF CHOLESTYRAMINE AND THEIR USE |
| JP7328207B2 (ja) | 2017-08-09 | 2023-08-16 | アルビレオ・アクチボラグ | コレスチラミンペレット、経口コレスチラミン製剤、及びそれらの使用 |
| US10793534B2 (en) | 2018-06-05 | 2020-10-06 | Albireo Ab | Benzothia(di)azepine compounds and their use as bile acid modulators |
| CA3100113A1 (en) | 2018-06-05 | 2019-12-12 | Albireo Ab | Benzothia(di)azepine compounds and their use as bile acid modulators |
| WO2019245448A1 (en) | 2018-06-20 | 2019-12-26 | Albireo Ab | Crystal modifications of odevixibat |
| US11801226B2 (en) | 2018-06-20 | 2023-10-31 | Albireo Ab | Pharmaceutical formulation of odevixibat |
| US11007142B2 (en) | 2018-08-09 | 2021-05-18 | Albireo Ab | Oral cholestyramine formulation and use thereof |
| US11549878B2 (en) | 2018-08-09 | 2023-01-10 | Albireo Ab | In vitro method for determining the adsorbing capacity of an insoluble adsorbant |
| US10722457B2 (en) | 2018-08-09 | 2020-07-28 | Albireo Ab | Oral cholestyramine formulation and use thereof |
| US10941127B2 (en) | 2019-02-06 | 2021-03-09 | Albireo Ab | Benzothiadiazepine compounds and their use as bile acid modulators |
| US10975045B2 (en) | 2019-02-06 | 2021-04-13 | Aibireo AB | Benzothiazepine compounds and their use as bile acid modulators |
| BR112021015799A2 (pt) | 2019-02-12 | 2022-01-18 | Mirum Pharmaceuticals Inc | Métodos para aumentar o crescimento em pacientes pediátricos com doença colestática do fígado |
| CA3158276A1 (en) | 2019-12-04 | 2021-06-10 | Per-Goran Gillberg | Benzothia(di)azepine compounds and their use as bile acid modulators |
| CN114761079B (zh) | 2019-12-04 | 2024-05-28 | 阿尔比里奥公司 | 苯并硫杂(二)氮杂环庚三烯化合物及其作为胆汁酸调节剂的用途 |
| US11014898B1 (en) | 2020-12-04 | 2021-05-25 | Albireo Ab | Benzothiazepine compounds and their use as bile acid modulators |
| JP2023504643A (ja) | 2019-12-04 | 2023-02-06 | アルビレオ・アクチボラグ | ベンゾチア（ジ）アゼピン化合物及び胆汁酸モジュレータとしてのそれらの使用 |
| JP2023504644A (ja) | 2019-12-04 | 2023-02-06 | アルビレオ・アクチボラグ | ベンゾチアジアゼピン化合物及び胆汁酸モジュレータとしてのそれらの使用 |
| JP2023537285A (ja) | 2020-08-03 | 2023-08-31 | アルビレオ・アクチボラグ | ベンゾチア（ジ）アゼピン化合物及び胆汁酸モジュレータとしてのそれらの使用 |
| WO2022101379A1 (en) | 2020-11-12 | 2022-05-19 | Albireo Ab | Odevixibat for treating progressive familial intrahepatic cholestasis (pfic) |
| AU2021379076A1 (en) | 2020-11-12 | 2023-06-08 | Albireo Ab | Odevixibat for treating progressive familial intrahepatic cholestasis (pfic) |
| EP4255565A1 (en) | 2020-12-04 | 2023-10-11 | Albireo AB | Benzothia(di)azepine compounds and their use as bile acid modulators |
| US20240173333A1 (en) | 2022-11-03 | 2024-05-30 | Albireo Ab | Treating Alagille Syndrome (ALGS) |
Family Cites Families (37)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3389144A (en) * | 1965-06-08 | 1968-06-18 | Mcneilab Inc | 5-pyridyl-2, 3, 4, 5-tetrahydrobenzothiepin-5-ols |
| US3287370A (en) * | 1965-06-08 | 1966-11-22 | Mcneilab Inc | Tetrahydrobenzothiepins |
| DE1593760A1 (de) * | 1967-02-01 | 1972-06-08 | Boehringer Sohn Ingelheim | Verfahren zur Herstellung neuer Benz-epinderivate |
| US3444176A (en) * | 1967-04-28 | 1969-05-13 | Mcneilab Inc | Certain 4-diloweralkylamino-lower alkyl - 5 - pyridyl (or phenyl)-2,3-dihydro - 1 - benzothiepins and derivatives thereof |
| US3694446A (en) * | 1970-02-24 | 1972-09-26 | William J Houlihan | 5-(substituted-benzyl)-benzocycloheptenes and-1-benzthiepines |
| GB1428110A (en) * | 1972-05-30 | 1976-03-17 | Reckitt & Colmann Prod Ltd | Pharmaceutical antihypertensive and vasodilator compositions |
| US4207239A (en) * | 1977-10-31 | 1980-06-10 | The Upjohn Company | Benzothiepins |
| WO1989001477A1 (en) * | 1987-08-19 | 1989-02-23 | E.I. Du Pont De Nemours And Company | Process for preparing sulfonylurea salts |
| AU626881B2 (en) * | 1988-07-14 | 1992-08-13 | F. Hoffmann-La Roche Ag | Benzofused heterocyclics used as pharmaceuticals |
| DE3901527A1 (de) * | 1989-01-20 | 1990-07-26 | Hoechst Ag | Alkylierte polyethyleniminderivate, verfahren zu ihrer herstellung, ihre verwendung als arzneimittel sowie pharmazeutische praeparate |
| JPH0314576A (ja) * | 1989-06-12 | 1991-01-23 | Yoshitomi Pharmaceut Ind Ltd | １―ベンゾチエピン化合物 |
| DE3930696A1 (de) * | 1989-09-14 | 1991-03-28 | Hoechst Ag | Gallensaeurederivate, verfahren zu ihrer herstellung, verwendung als arzneimittel |
| FR2661676A1 (fr) * | 1990-05-02 | 1991-11-08 | Lipha | Derives d'amino benzocycloalcanes, procedes de preparation et medicaments les contenant. |
| EP0508425A1 (en) * | 1991-04-12 | 1992-10-14 | Schering Corporation | Bicyclic amides as inhibitors of acyl-coenzyme a: cholesterol acyl transferase |
| EP0534316A1 (de) * | 1991-09-21 | 1993-03-31 | Hoechst Aktiengesellschaft | Verwendung von alkylierten Polyethyleniminderivaten zur Anreicherung von Gallensäuren |
| ATE180968T1 (de) * | 1991-12-20 | 1999-06-15 | Hoechst Ag | Polyaspartamidderivate als adsorptionsmittel für gallensäuren, mit gallensäuren beladene polyaspartamidderivate und verfahren zu deren herstellung sowie deren anwendung als arzneimittel |
| US5430116A (en) * | 1991-12-20 | 1995-07-04 | Hoechst Aktiengesellschaft | Polymers and oligomers of bile acid derivatives, process for their preparation and their use as pharmaceuticals |
| NZ245504A (en) * | 1991-12-20 | 1995-08-28 | Hoechst Ag | Bile acid derivatives containing an ethylenically unsaturated grouping |
| GB9203347D0 (en) * | 1992-02-17 | 1992-04-01 | Wellcome Found | Hypolipidaemic compounds |
| EP0559064B1 (de) * | 1992-02-29 | 2001-05-23 | Aventis Research & Technologies GmbH & Co. KG | Komplexe enthaltend Glykosyl-Phosphatidylinositol-Proteine und Cholansäurederivate, Verfahren zu ihrer Herstellung und ihre Verwendung |
| DE59300925D1 (de) * | 1992-03-28 | 1995-12-21 | Hoechst Ag | Arzneimittel aus Polyhydroxymethylenderivaten, Verfahren zu deren Herstellung und Verwendung. |
| CA2093577C (en) * | 1992-05-07 | 2006-01-03 | Michael Klaus | Alkyl or alkoxy substituted s-heterocyclic retinoids |
| FR2698873B1 (fr) * | 1992-12-07 | 1995-02-24 | Lipha | Benzocycloheptènes, benzoxépines et benzothiépines activateurs des canaux potassiques, procédé de préparation, composition pharmaceutique les contenant. |
| IL108634A0 (en) * | 1993-02-15 | 1994-05-30 | Wellcome Found | Hypolipidaemic heterocyclic compounds, their prepatation and pharmaceutical compositions containing them |
| ZA941003B (en) * | 1993-02-15 | 1995-08-14 | Wellcome Found | Hypolipidaemic compounds |
| EP0624593A3 (de) * | 1993-05-08 | 1995-06-07 | Hoechst Ag | Gallensäurederivate, Verfahren zu ihrer Herstellung und Verwendung dieser Verbindungen als Arzneimittel. |
| TW289020B (pt) * | 1993-05-08 | 1996-10-21 | Hoechst Sktiengesellschaft | |
| TW289021B (pt) * | 1993-05-08 | 1996-10-21 | Hoechst Ag | |
| US5491152A (en) * | 1994-03-23 | 1996-02-13 | The Du Pont Merck Pharmaceutical Company | Derivatives of cyclic ethers and sulfides for the treatment of atherosclerosis |
| ZA956647B (en) * | 1994-08-10 | 1997-02-10 | Wellcome Found | Hypolipidaemic compounds. |
| WO1996008484A1 (en) * | 1994-09-13 | 1996-03-21 | Monsanto Company | Novel benzothiepines having activity as inhibitors of ileal bile acid transport and taurocholate uptake |
| US5705524A (en) * | 1994-11-04 | 1998-01-06 | Gilead Sciences, Inc. | Thiepane compounds |
| GB9423172D0 (en) * | 1994-11-17 | 1995-01-04 | Wellcom Foundation The Limited | Hypolipidemic benzothiazepines |
| DE69734100D1 (de) * | 1996-03-11 | 2005-10-06 | G D Searle Llc St Louis | Benzothiepinen mit wirkung als inhibitoren des ileumgallensäuretransports und der taurocholate-aufnahme |
| IL131872A0 (en) * | 1997-03-11 | 2001-03-19 | Searle & Co | Composition comprising an ileal bile acid transport inhibiting benzothiepines and hmg co-a reductase inhibitors |
| US5869528A (en) * | 1997-07-22 | 1999-02-09 | Sigma-Tau Industrie Farmaceutiche Riunite S.P.A. | Therapeutical method for the treatment of attention-deficit/hyperactive disorders |
| BR9814300A (pt) * | 1997-12-19 | 2002-02-05 | Searle & Co | Método de preparação de óxidos de tetraidrobenzotiepina enanciomericamente enriquecidos |
-
1998
- 1998-07-02 US US09/109,551 patent/US5994391A/en not_active Expired - Fee Related
-
1999
- 1999-06-29 NZ NZ509621A patent/NZ509621A/en unknown
- 1999-06-29 SG SG200207701A patent/SG108309A1/en unknown
- 1999-06-29 KR KR1020017000027A patent/KR20010083084A/ko not_active Application Discontinuation
- 1999-06-29 EA EA200100002A patent/EA004650B1/ru not_active IP Right Cessation
- 1999-06-29 TR TR2001/00824T patent/TR200100824T2/xx unknown
- 1999-06-29 HU HU0102840A patent/HUP0102840A2/hu unknown
- 1999-06-29 GE GEAP19995707A patent/GEP20032925B/en unknown
- 1999-06-29 CA CA002336315A patent/CA2336315A1/en not_active Abandoned
- 1999-06-29 JP JP2000558091A patent/JP2002519418A/ja active Pending
- 1999-06-29 AP APAP/P/2001/002062A patent/AP2001002062A0/en unknown
- 1999-06-29 BR BR9911737-1A patent/BR9911737A/pt not_active IP Right Cessation
- 1999-06-29 OA OA1200000365A patent/OA11629A/en unknown
- 1999-06-29 PL PL99346324A patent/PL346324A1/xx unknown
- 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 ID IDW20010002A patent/ID28221A/id unknown
- 1999-06-29 YU YU84400A patent/YU84400A/sh unknown
- 1999-06-29 WO PCT/US1999/012828 patent/WO2000001687A1/en not_active Application Discontinuation
- 1999-06-29 EA EA200400149A patent/EA200400149A1/ru unknown
- 1999-06-29 IL IL14057699A patent/IL140576A0/xx unknown
- 1999-06-29 EP EP03026649A patent/EP1466911A3/en not_active Withdrawn
- 1999-06-29 DK DK99931769T patent/DK1091953T3/da active
- 1999-06-29 DE DE69913530T patent/DE69913530T2/de not_active Expired - Fee Related
- 1999-06-29 CN CN99809602A patent/CN1312805A/zh active Pending
- 1999-06-29 AT AT99931769T patent/ATE256122T1/de not_active IP Right Cessation
- 1999-06-29 PT PT99931769T patent/PT1091953E/pt unknown
- 1999-06-29 AU AU48202/99A patent/AU766957B2/en not_active Ceased
- 1999-06-29 EE EEP200100002A patent/EE200100002A/xx unknown
- 1999-06-29 SK SK2030-2000A patent/SK20302000A3/sk unknown
- 1999-07-02 CO CO99041717D patent/CO5080807A1/es unknown
- 1999-07-02 AR ARP990103234A patent/AR019880A1/es unknown
- 1999-07-02 CO CO99041717A patent/CO4950537A1/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 HR HR20010004A patent/HRP20010004A2/hr not_active Application Discontinuation
- 2001-01-02 NO NO20010016A patent/NO20010016L/no not_active Application Discontinuation
- 2001-01-31 BG BG105206A patent/BG105206A/bg unknown
-
2002
- 2002-02-07 HK HK02100948.1A patent/HK1039614A1/zh 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
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| BG105206A (bg) | Бензотиепини, притежаващи активност като инхибитори на пренасянето на илеална жлъчна киселина и на поглъщането на таурохолат | |
| US6784201B2 (en) | Benzothiepines having activity as inhibitors of ileal bile acid transport and taurocholate uptake | |
| RU2247579C2 (ru) | Комбинированное лечение с применением бензотиепинов, ингибирующих транспорт желчной кислоты в подвздошной кишке, и ингибиторов hmg co-а редуктазы | |
| EP0781278B1 (en) | Novel benzothiepines having activity as inhibitors of ileal bile acid transport and taurocholate uptake | |
| US6642268B2 (en) | Combination therapy employing ileal bile acid transport inhibiting benzothipines and HMG Co-A reductase inhibitors | |
| EP0888333B1 (en) | Novel benzothiepines having activity as inhibitors of ileal bile acid transport and taurocholate uptake | |
| US20020183307A1 (en) | Novel 1,4-benzothiazephine and 1,5-benzothiazepine compounds as inhibitors of apical sodium co-dependent bile acid transport and taurocholate uptake | |
| EP1448546A1 (en) | Novel mono- and di-fluorinated benzothiepine compounds as inhibitors of apical sodium co-dependent bile acid transport (asbt) and taurocholate uptake | |
| US20040077625A1 (en) | Novel 1,4-benzothiazepine and 1,5-benzothiazepine compounds as inhibitors of apical sodium codependent bile acid transport abd taurocholate uptake | |
| US6420417B1 (en) | Combination therapy employing ileal bile acid transport inhibiting benzothiepines and HMG Co-A reductase inhibitors | |
| CZ20004937A3 (cs) | Benzothiepiny, které mají účinek jako inhibitory transportu žlučových kyselin v ileu a vychytávání taurocholátu | |
| MXPA01000208A (en) | Novel benzothiepines having activity as inhibitors of ileal bile acid transport and taurocholate uptake | |
| EP1440972A1 (en) | Novel benzothiepines having pharmaceutical activity. | |
| KR19990087721A (ko) | 회장 담즙산 운반 및 타우로콜레이트 흡수 저해제로서의 활성을 갖는 신규한 벤조티에핀 |