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 |
|---|---|
| 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 (ja) |
| EP (2) | EP1466911A3 (ja) |
| JP (3) | JP2002519418A (ja) |
| KR (1) | KR20010083084A (ja) |
| CN (1) | CN1312805A (ja) |
| AP (1) | AP2001002062A0 (ja) |
| AR (1) | AR019880A1 (ja) |
| AT (1) | ATE256122T1 (ja) |
| AU (2) | AU766957B2 (ja) |
| BG (1) | BG105206A (ja) |
| BR (1) | BR9911737A (ja) |
| CA (1) | CA2336315A1 (ja) |
| CO (2) | CO4950537A1 (ja) |
| DE (1) | DE69913530T2 (ja) |
| DK (1) | DK1091953T3 (ja) |
| EA (2) | EA004650B1 (ja) |
| EE (1) | EE200100002A (ja) |
| ES (1) | ES2213373T3 (ja) |
| GE (1) | GEP20032925B (ja) |
| HK (1) | HK1039614A1 (ja) |
| HR (1) | HRP20010004A2 (ja) |
| HU (1) | HUP0102840A2 (ja) |
| ID (1) | ID28221A (ja) |
| IL (1) | IL140576A0 (ja) |
| IS (1) | IS5798A (ja) |
| NO (1) | NO20010016L (ja) |
| NZ (1) | NZ509621A (ja) |
| OA (1) | OA11629A (ja) |
| PL (1) | PL346324A1 (ja) |
| PT (1) | PT1091953E (ja) |
| SG (1) | SG108309A1 (ja) |
| SK (1) | SK20302000A3 (ja) |
| TR (1) | TR200100824T2 (ja) |
| TW (1) | TWI229670B (ja) |
| WO (1) | WO2000001687A1 (ja) |
| YU (1) | YU84400A (ja) |
| ZA (1) | ZA200100028B (ja) |
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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 PT PT99931769T patent/PT1091953E/pt unknown
- 1999-06-29 TR TR2001/00824T patent/TR200100824T2/xx unknown
- 1999-06-29 EA EA200100002A patent/EA004650B1/ru not_active IP Right Cessation
- 1999-06-29 DE DE69913530T patent/DE69913530T2/de not_active Expired - Fee Related
- 1999-06-29 NZ NZ509621A patent/NZ509621A/en unknown
- 1999-06-29 HU HU0102840A patent/HUP0102840A2/hu unknown
- 1999-06-29 YU YU84400A patent/YU84400A/sh unknown
- 1999-06-29 CA CA002336315A patent/CA2336315A1/en not_active Abandoned
- 1999-06-29 WO PCT/US1999/012828 patent/WO2000001687A1/en not_active Application Discontinuation
- 1999-06-29 IL IL14057699A patent/IL140576A0/xx unknown
- 1999-06-29 ES ES99931769T patent/ES2213373T3/es not_active Expired - Lifetime
- 1999-06-29 PL PL99346324A patent/PL346324A1/xx unknown
- 1999-06-29 EE EEP200100002A patent/EE200100002A/xx unknown
- 1999-06-29 KR KR1020017000027A patent/KR20010083084A/ko not_active Application Discontinuation
- 1999-06-29 EA EA200400149A patent/EA200400149A1/ru unknown
- 1999-06-29 JP JP2000558091A patent/JP2002519418A/ja active Pending
- 1999-06-29 AT AT99931769T patent/ATE256122T1/de not_active IP Right Cessation
- 1999-06-29 GE GEAP19995707A patent/GEP20032925B/en unknown
- 1999-06-29 AP APAP/P/2001/002062A patent/AP2001002062A0/en unknown
- 1999-06-29 SG SG200207701A patent/SG108309A1/en unknown
- 1999-06-29 SK SK2030-2000A patent/SK20302000A3/sk unknown
- 1999-06-29 EP EP03026649A patent/EP1466911A3/en not_active Withdrawn
- 1999-06-29 EP EP99931769A patent/EP1091953B1/en not_active Expired - Lifetime
- 1999-06-29 AU AU48202/99A patent/AU766957B2/en not_active Ceased
- 1999-06-29 DK DK99931769T patent/DK1091953T3/da active
- 1999-06-29 CN CN99809602A patent/CN1312805A/zh active Pending
- 1999-06-29 BR BR9911737-1A patent/BR9911737A/pt not_active IP Right Cessation
- 1999-07-02 AR ARP990103234A patent/AR019880A1/es unknown
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2000
- 2000-01-07 TW TW088111293A patent/TWI229670B/zh not_active IP Right Cessation
- 2000-12-29 IS IS5798A patent/IS5798A/is unknown
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2001
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- 2001-01-31 BG BG105206A patent/BG105206A/bg unknown
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2002
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2004
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- 2004-02-25 JP JP2004050473A patent/JP2004203891A/ja active Pending
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