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
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Classifications
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- 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
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- 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
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- 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
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- 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
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- 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
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- 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
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- 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
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- 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
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
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- C07D495/04—Ortho-condensed systems
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/10—Spiro-condensed systems
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- 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
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G65/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
- C08G65/32—Polymers modified by chemical after-treatment
- C08G65/329—Polymers modified by chemical after-treatment with organic compounds
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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 |
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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 |
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US (1) | US5994391A (hu) |
EP (2) | EP1466911A3 (hu) |
JP (3) | JP2002519418A (hu) |
KR (1) | KR20010083084A (hu) |
CN (1) | CN1312805A (hu) |
AP (1) | AP2001002062A0 (hu) |
AR (1) | AR019880A1 (hu) |
AT (1) | ATE256122T1 (hu) |
AU (2) | AU766957B2 (hu) |
BG (1) | BG105206A (hu) |
BR (1) | BR9911737A (hu) |
CA (1) | CA2336315A1 (hu) |
CO (2) | CO4950537A1 (hu) |
DE (1) | DE69913530T2 (hu) |
DK (1) | DK1091953T3 (hu) |
EA (2) | EA004650B1 (hu) |
EE (1) | EE200100002A (hu) |
ES (1) | ES2213373T3 (hu) |
GE (1) | GEP20032925B (hu) |
HK (1) | HK1039614A1 (hu) |
HR (1) | HRP20010004A2 (hu) |
HU (1) | HUP0102840A2 (hu) |
ID (1) | ID28221A (hu) |
IL (1) | IL140576A0 (hu) |
IS (1) | IS5798A (hu) |
NO (1) | NO20010016L (hu) |
NZ (1) | NZ509621A (hu) |
OA (1) | OA11629A (hu) |
PL (1) | PL346324A1 (hu) |
PT (1) | PT1091953E (hu) |
SG (1) | SG108309A1 (hu) |
SK (1) | SK20302000A3 (hu) |
TR (1) | TR200100824T2 (hu) |
TW (1) | TWI229670B (hu) |
WO (1) | WO2000001687A1 (hu) |
YU (1) | YU84400A (hu) |
ZA (1) | ZA200100028B (hu) |
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EP0548794B1 (de) * | 1991-12-20 | 1999-06-09 | Hoechst Aktiengesellschaft | Polyaspartamidderivate als Adsorptionsmittel für Gallensäuren, mit Gallensäuren beladene Polyaspartamidderivate und Verfahren zu deren Herstellung sowie deren Anwendung als Arzneimittel |
EP0549967B1 (de) * | 1991-12-20 | 1996-03-13 | Hoechst Aktiengesellschaft | Polymere und Oligomere von Gallensäurederivaten, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel |
AU664059B2 (en) * | 1991-12-20 | 1995-11-02 | Hoechst Aktiengesellschaft | Ethylenically unsaturated bile acid derivatives, processes for their preparation and precursors |
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 |
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CA2093577C (en) * | 1992-05-07 | 2006-01-03 | Michael Klaus | Alkyl or alkoxy substituted s-heterocyclic retinoids |
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IL108634A0 (en) * | 1993-02-15 | 1994-05-30 | Wellcome Found | Hypolipidaemic heterocyclic compounds, their prepatation and pharmaceutical compositions containing them |
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ZA956647B (en) * | 1994-08-10 | 1997-02-10 | Wellcome Found | Hypolipidaemic compounds. |
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CN1515567A (zh) * | 1996-03-11 | 2004-07-28 | G.D.ɪ����˾ | 具有作为回肠胆汁酸转运和牛磺胆酸盐吸收抑制剂活性的新的苯并噻庚因 |
JP2002500628A (ja) * | 1997-03-11 | 2002-01-08 | ジー.ディー.サール アンド カンパニー | 回腸胆汁酸輸送阻害ベンゾチエピンおよびHMG Co−Aレダクターゼ阻害剤を用いた併用療法 |
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1998
- 1998-07-02 US US09/109,551 patent/US5994391A/en not_active Expired - Fee Related
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1999
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- 1999-06-29 ES ES99931769T patent/ES2213373T3/es not_active Expired - Lifetime
- 1999-06-29 WO PCT/US1999/012828 patent/WO2000001687A1/en not_active Application Discontinuation
- 1999-06-29 EA EA200100002A patent/EA004650B1/ru not_active IP Right Cessation
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- 1999-06-29 DK DK99931769T patent/DK1091953T3/da active
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- 1999-06-29 AU AU48202/99A patent/AU766957B2/en not_active Ceased
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- 1999-06-29 CA CA002336315A patent/CA2336315A1/en not_active Abandoned
- 1999-06-29 EE EEP200100002A patent/EE200100002A/xx unknown
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- 1999-06-29 EP EP03026649A patent/EP1466911A3/en not_active Withdrawn
- 1999-06-29 PT PT99931769T patent/PT1091953E/pt unknown
- 1999-06-29 TR TR2001/00824T patent/TR200100824T2/xx unknown
- 1999-06-29 JP JP2000558091A patent/JP2002519418A/ja active Pending
- 1999-06-29 SG SG200207701A patent/SG108309A1/en unknown
- 1999-06-29 EP EP99931769A patent/EP1091953B1/en not_active Expired - Lifetime
- 1999-06-29 KR KR1020017000027A patent/KR20010083084A/ko not_active Application Discontinuation
- 1999-06-29 BR BR9911737-1A patent/BR9911737A/pt not_active IP Right Cessation
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- 1999-06-29 CN CN99809602A patent/CN1312805A/zh active Pending
- 1999-06-29 DE DE69913530T patent/DE69913530T2/de not_active Expired - Fee Related
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2000
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- 2000-12-29 IS IS5798A patent/IS5798A/is unknown
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2001
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