CA2362147A1 - Nouvelles benzothiazepines-1,2 presentant une activite d'inhibition de transport d'acide biliaire ileal et d'absorption de taurocholate - Google Patents
Nouvelles benzothiazepines-1,2 presentant une activite d'inhibition de transport d'acide biliaire ileal et d'absorption de taurocholate Download PDFInfo
- Publication number
- CA2362147A1 CA2362147A1 CA002362147A CA2362147A CA2362147A1 CA 2362147 A1 CA2362147 A1 CA 2362147A1 CA 002362147 A CA002362147 A CA 002362147A CA 2362147 A CA2362147 A CA 2362147A CA 2362147 A1 CA2362147 A1 CA 2362147A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- heterocyclyl
- group
- aryl
- independently selected
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
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- 238000011282 treatment Methods 0.000 title claims abstract description 30
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title abstract description 23
- 201000010099 disease Diseases 0.000 title abstract description 13
- FHGWEHGZBUBQKL-UHFFFAOYSA-N 1,2-benzothiazepine Chemical class S1N=CC=CC2=CC=CC=C12 FHGWEHGZBUBQKL-UHFFFAOYSA-N 0.000 title description 17
- 238000011321 prophylaxis Methods 0.000 claims abstract description 17
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 12
- 208000035150 Hypercholesterolemia Diseases 0.000 claims abstract description 7
- 125000000623 heterocyclic group Chemical group 0.000 claims description 592
- -1 heterocyclyl radicals Chemical class 0.000 claims description 425
- 125000000217 alkyl group Chemical group 0.000 claims description 414
- 125000003118 aryl group Chemical group 0.000 claims description 357
- 150000003254 radicals Chemical class 0.000 claims description 282
- 125000000304 alkynyl group Chemical group 0.000 claims description 258
- 150000001875 compounds Chemical class 0.000 claims description 254
- 229910052739 hydrogen Inorganic materials 0.000 claims description 251
- 239000001257 hydrogen Substances 0.000 claims description 248
- 125000003342 alkenyl group Chemical group 0.000 claims description 241
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 215
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 204
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 191
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 188
- 239000004721 Polyphenylene oxide Chemical group 0.000 claims description 183
- 229920000570 polyether Chemical group 0.000 claims description 183
- 229910052799 carbon Inorganic materials 0.000 claims description 145
- 229910052736 halogen Inorganic materials 0.000 claims description 134
- 150000002367 halogens Chemical class 0.000 claims description 132
- 108090000765 processed proteins & peptides Chemical group 0.000 claims description 129
- 125000001188 haloalkyl group Chemical group 0.000 claims description 124
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 115
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 92
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 75
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 72
- 229910052757 nitrogen Inorganic materials 0.000 claims description 65
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 64
- 229920001184 polypeptide Polymers 0.000 claims description 64
- 102000004196 processed proteins & peptides Human genes 0.000 claims description 64
- 125000005843 halogen group Chemical group 0.000 claims description 54
- 125000000539 amino acid group Chemical group 0.000 claims description 53
- 125000001424 substituent group Chemical group 0.000 claims description 52
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 51
- 125000001183 hydrocarbyl group Chemical group 0.000 claims description 48
- 150000003839 salts Chemical group 0.000 claims description 48
- 125000004432 carbon atom Chemical group C* 0.000 claims description 47
- 125000005842 heteroatom Chemical group 0.000 claims description 44
- 150000002431 hydrogen Chemical class 0.000 claims description 44
- 150000001720 carbohydrates Chemical class 0.000 claims description 43
- 125000003545 alkoxy group Chemical group 0.000 claims description 42
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 42
- 125000004948 alkyl aryl alkyl group Chemical group 0.000 claims description 39
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 39
- 125000002252 acyl group Chemical group 0.000 claims description 38
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 38
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 37
- 125000004689 alkyl amino carbonyl alkyl group Chemical group 0.000 claims description 37
- 125000005097 aminocarbonylalkyl group Chemical group 0.000 claims description 37
- 125000004122 cyclic group Chemical group 0.000 claims description 36
- 125000002877 alkyl aryl group Chemical group 0.000 claims description 35
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 35
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 34
- 125000005210 alkyl ammonium group Chemical group 0.000 claims description 32
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 31
- 229910052760 oxygen Inorganic materials 0.000 claims description 31
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 30
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 29
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 28
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 27
- 239000001301 oxygen Substances 0.000 claims description 27
- 150000001450 anions Chemical class 0.000 claims description 25
- 229910052717 sulfur Inorganic materials 0.000 claims description 25
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 23
- 239000011593 sulfur Substances 0.000 claims description 23
- 239000002253 acid Substances 0.000 claims description 22
- 150000005840 aryl radicals Chemical class 0.000 claims description 22
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 21
- 125000005082 alkoxyalkenyl group Chemical group 0.000 claims description 21
- 229910052698 phosphorus Inorganic materials 0.000 claims description 21
- 239000011574 phosphorus Substances 0.000 claims description 21
- 125000003282 alkyl amino group Chemical group 0.000 claims description 20
- 150000001768 cations Chemical class 0.000 claims description 20
- 239000000651 prodrug Substances 0.000 claims description 20
- 229940002612 prodrug Drugs 0.000 claims description 20
- 239000012453 solvate Substances 0.000 claims description 20
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 19
- 150000001721 carbon Chemical group 0.000 claims description 19
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 claims description 19
- 150000001335 aliphatic alkanes Chemical group 0.000 claims description 18
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 17
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 17
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 16
- 125000002950 monocyclic group Chemical group 0.000 claims description 16
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 16
- 150000001413 amino acids Chemical class 0.000 claims description 15
- 125000005160 aryl oxy alkyl group Chemical group 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 15
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 15
- 125000004423 acyloxy group Chemical group 0.000 claims description 14
- 125000005098 aryl alkoxy carbonyl group Chemical group 0.000 claims description 14
- 125000005605 benzo group Chemical group 0.000 claims description 14
- 125000004964 sulfoalkyl group Chemical group 0.000 claims description 14
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 13
- 239000000203 mixture Substances 0.000 claims description 13
- 150000001336 alkenes Chemical class 0.000 claims description 12
- 150000001345 alkine derivatives Chemical class 0.000 claims description 12
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 12
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 10
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-O triethylammonium ion Chemical compound CC[NH+](CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-O 0.000 claims description 10
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 9
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 9
- 125000001544 thienyl group Chemical group 0.000 claims description 9
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 8
- 125000004076 pyridyl group Chemical group 0.000 claims description 8
- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 7
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 7
- 239000002552 dosage form Substances 0.000 claims description 7
- 125000001624 naphthyl group Chemical group 0.000 claims description 7
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 7
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 6
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
- 235000010290 biphenyl Nutrition 0.000 claims description 5
- 239000004305 biphenyl Substances 0.000 claims description 5
- 125000005026 carboxyaryl group Chemical group 0.000 claims description 5
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
- 125000002541 furyl group Chemical group 0.000 claims description 5
- 125000004193 piperazinyl group Chemical group 0.000 claims description 5
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 5
- 125000000335 thiazolyl group Chemical group 0.000 claims description 5
- 102220465932 Beta-1,3-glucuronyltransferase LARGE2_R13A_mutation Human genes 0.000 claims description 4
- FFDGPVCHZBVARC-UHFFFAOYSA-N N,N-dimethylglycine Chemical compound CN(C)CC(O)=O FFDGPVCHZBVARC-UHFFFAOYSA-N 0.000 claims description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
- 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 claims description 4
- 125000004464 hydroxyphenyl group Chemical group 0.000 claims description 4
- 125000002883 imidazolyl group Chemical group 0.000 claims description 4
- 125000001041 indolyl group Chemical group 0.000 claims description 4
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 4
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 claims description 4
- 125000006501 nitrophenyl group Chemical group 0.000 claims description 4
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 4
- 125000006413 ring segment Chemical group 0.000 claims description 4
- 125000001425 triazolyl group Chemical group 0.000 claims description 4
- WWYVZTLIFYLZFM-UHFFFAOYSA-N 1-methylazetidine Chemical compound CN1CCC1 WWYVZTLIFYLZFM-UHFFFAOYSA-N 0.000 claims description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 3
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 claims description 3
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 3
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 3
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 3
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 3
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 3
- AEABQBMUYZBBCW-UHFFFAOYSA-N pentanamide Chemical compound CC[CH]CC(N)=O AEABQBMUYZBBCW-UHFFFAOYSA-N 0.000 claims description 3
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 3
- 125000003386 piperidinyl group Chemical group 0.000 claims description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 3
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 claims description 3
- LZOGWRAKODSTTH-LQFQNGICSA-N (4r,5r)-3,3-dibutyl-7-(dimethylamino)-2-methyl-1,1-dioxo-5-[4-[2-[2-(2-pyridin-1-ium-1-ylethoxy)ethoxy]ethoxy]phenyl]-4,5-dihydro-1$l^{6},2-benzothiazepin-4-ol Chemical compound C1=CC([C@H]2[C@@H](O)C(N(S(=O)(=O)C3=CC=C(C=C32)N(C)C)C)(CCCC)CCCC)=CC=C1OCCOCCOCC[N+]1=CC=CC=C1 LZOGWRAKODSTTH-LQFQNGICSA-N 0.000 claims description 2
- RXYPXQSKLGGKOL-UHFFFAOYSA-N 1,4-dimethylpiperazine Chemical compound CN1CCN(C)CC1 RXYPXQSKLGGKOL-UHFFFAOYSA-N 0.000 claims description 2
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 claims description 2
- AVFZOVWCLRSYKC-UHFFFAOYSA-N 1-methylpyrrolidine Chemical compound CN1CCCC1 AVFZOVWCLRSYKC-UHFFFAOYSA-N 0.000 claims description 2
- ZTNLGPOYWLKXPR-UHFFFAOYSA-N 2-ethenoxypyrimidine Chemical group C=COC1=NC=CC=N1 ZTNLGPOYWLKXPR-UHFFFAOYSA-N 0.000 claims description 2
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 claims description 2
- PQBAWAQIRZIWIV-UHFFFAOYSA-N N-methylpyridinium Chemical compound C[N+]1=CC=CC=C1 PQBAWAQIRZIWIV-UHFFFAOYSA-N 0.000 claims description 2
- 125000002393 azetidinyl group Chemical group 0.000 claims description 2
- 125000004799 bromophenyl group Chemical group 0.000 claims description 2
- 125000000068 chlorophenyl group Chemical group 0.000 claims description 2
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000006125 ethylsulfonyl group Chemical group 0.000 claims description 2
- 125000001207 fluorophenyl group Chemical group 0.000 claims description 2
- 125000006303 iodophenyl group Chemical group 0.000 claims description 2
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000002971 oxazolyl group Chemical group 0.000 claims description 2
- 229960005235 piperonyl butoxide Drugs 0.000 claims description 2
- 125000004591 piperonyl group Chemical group C(C1=CC=2OCOC2C=C1)* 0.000 claims description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 claims description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 2
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 340
- 125000000837 carbohydrate group Chemical group 0.000 claims 55
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims 27
- 125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims 25
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims 21
- 239000003937 drug carrier Substances 0.000 claims 6
- STSYRNZXXQMGHP-UHFFFAOYSA-N (amino-ethoxy-nitromethyl)-(diethylamino)-[dimethylamino-(ethylamino)-(methylamino)methyl]-[hydroxy(methoxy)methyl]azanium Chemical compound OC([N+](C(NCC)(N(C)C)NC)(C(N)([N+](=O)[O-])OCC)N(CC)CC)OC STSYRNZXXQMGHP-UHFFFAOYSA-N 0.000 claims 2
- FOUHQFWUUMJAKD-UHFFFAOYSA-N (amino-ethoxy-nitromethyl)-[(2-bromo-2-chloro-2-fluoroethyl)-ethylamino]-[dimethylamino-(ethylamino)-(methylamino)methyl]-(hydroxy-iodo-methoxymethyl)azanium Chemical compound ClC(CN(CC)[N+](C(NCC)(N(C)C)NC)(C(N)([N+](=O)[O-])OCC)C(OC)(O)I)(Br)F FOUHQFWUUMJAKD-UHFFFAOYSA-N 0.000 claims 2
- 230000000879 anti-atherosclerotic effect Effects 0.000 claims 2
- 230000001315 anti-hyperlipaemic effect Effects 0.000 claims 2
- 230000003143 atherosclerotic effect Effects 0.000 claims 2
- NVTFLQBWZMNINT-FIRIVFDPSA-N (4r,5r)-2-benzyl-3,3-dibutyl-7-(dimethylamino)-5-(3-nitrophenyl)-1,1-dioxo-4,5-dihydro-1$l^{6},2-benzothiazepin-4-ol Chemical compound C1([C@H]2[C@@H](O)C(N(S(=O)(=O)C3=CC=C(C=C32)N(C)C)CC=2C=CC=CC=2)(CCCC)CCCC)=CC=CC([N+]([O-])=O)=C1 NVTFLQBWZMNINT-FIRIVFDPSA-N 0.000 claims 1
- ORHUIBVTSQFDHK-ROJLCIKYSA-N (4r,5r)-2-benzyl-3,3-dibutyl-7-(dimethylamino)-5-(4-methoxyphenyl)-1,1-dioxo-4,5-dihydro-1$l^{6},2-benzothiazepin-4-ol Chemical compound C1([C@H]2[C@@H](O)C(N(S(=O)(=O)C3=CC=C(C=C32)N(C)C)CC=2C=CC=CC=2)(CCCC)CCCC)=CC=C(OC)C=C1 ORHUIBVTSQFDHK-ROJLCIKYSA-N 0.000 claims 1
- FFOAMOASQZPOMD-CZNDPXEESA-N (4r,5r)-2-benzyl-3,3-dibutyl-7-(dimethylamino)-5-[3-(ethylamino)phenyl]-1,1-dioxo-4,5-dihydro-1$l^{6},2-benzothiazepin-4-ol Chemical compound C1([C@H]2[C@@H](O)C(N(S(=O)(=O)C3=CC=C(C=C32)N(C)C)CC=2C=CC=CC=2)(CCCC)CCCC)=CC=CC(NCC)=C1 FFOAMOASQZPOMD-CZNDPXEESA-N 0.000 claims 1
- METJFDMYWVYDOK-DNQXCXABSA-N (4r,5r)-3,3-dibutyl-7-(dimethylamino)-1,1-dioxo-5-phenyl-4,5-dihydro-2h-1$l^{6},2-benzothiazepin-4-ol Chemical compound C1([C@@H]2C3=CC(=CC=C3S(=O)(=O)NC([C@@H]2O)(CCCC)CCCC)N(C)C)=CC=CC=C1 METJFDMYWVYDOK-DNQXCXABSA-N 0.000 claims 1
- TUJPZSYJLFMWCA-JWQCQUIFSA-N (4r,5r)-3,3-dibutyl-7-(dimethylamino)-2-methyl-5-(3-nitrophenyl)-1,1-dioxo-4,5-dihydro-1$l^{6},2-benzothiazepin-4-ol Chemical compound C1([C@H]2[C@@H](O)C(N(S(=O)(=O)C3=CC=C(C=C32)N(C)C)C)(CCCC)CCCC)=CC=CC([N+]([O-])=O)=C1 TUJPZSYJLFMWCA-JWQCQUIFSA-N 0.000 claims 1
- XYVUGRAVQKLPPU-CLJLJLNGSA-N (4r,5r)-3,3-dibutyl-7-(dimethylamino)-5-(3-methoxyphenyl)-2-methyl-1,1-dioxo-4,5-dihydro-1$l^{6},2-benzothiazepin-4-ol Chemical compound C1([C@H]2[C@@H](O)C(N(S(=O)(=O)C3=CC=C(C=C32)N(C)C)C)(CCCC)CCCC)=CC=CC(OC)=C1 XYVUGRAVQKLPPU-CLJLJLNGSA-N 0.000 claims 1
- LDZIKONCRYGLFY-DNQXCXABSA-N (4r,5r)-3,3-dibutyl-7-(dimethylamino)-5-(3-nitrophenyl)-1,1-dioxo-4,5-dihydro-2h-1$l^{6},2-benzothiazepin-4-ol Chemical compound C1([C@@H]2C3=CC(=CC=C3S(=O)(=O)NC([C@@H]2O)(CCCC)CCCC)N(C)C)=CC=CC([N+]([O-])=O)=C1 LDZIKONCRYGLFY-DNQXCXABSA-N 0.000 claims 1
- RJEHRPZAQZYFIL-DNQXCXABSA-N (4r,5r)-3,3-dibutyl-7-(dimethylamino)-5-(4-hydroxyphenyl)-1,1-dioxo-4,5-dihydro-2h-1$l^{6},2-benzothiazepin-4-ol Chemical compound C1([C@@H]2C3=CC(=CC=C3S(=O)(=O)NC([C@@H]2O)(CCCC)CCCC)N(C)C)=CC=C(O)C=C1 RJEHRPZAQZYFIL-DNQXCXABSA-N 0.000 claims 1
- HYBFRSKEZDNMOO-JWQCQUIFSA-N (4r,5r)-3,3-dibutyl-7-(dimethylamino)-5-(4-hydroxyphenyl)-2-methyl-1,1-dioxo-4,5-dihydro-1$l^{6},2-benzothiazepin-4-ol Chemical compound C1([C@H]2[C@@H](O)C(N(S(=O)(=O)C3=CC=C(C=C32)N(C)C)C)(CCCC)CCCC)=CC=C(O)C=C1 HYBFRSKEZDNMOO-JWQCQUIFSA-N 0.000 claims 1
- WVQLVOSWPXPLRD-JWQCQUIFSA-N (4r,5r)-3,3-dibutyl-7-(dimethylamino)-5-(4-methoxyphenyl)-1,1-dioxo-4,5-dihydro-2h-1$l^{6},2-benzothiazepin-4-ol Chemical compound C1([C@@H]2C3=CC(=CC=C3S(=O)(=O)NC([C@@H]2O)(CCCC)CCCC)N(C)C)=CC=C(OC)C=C1 WVQLVOSWPXPLRD-JWQCQUIFSA-N 0.000 claims 1
- ZCJMAJYQZWBZMJ-CLJLJLNGSA-N (4r,5r)-3,3-dibutyl-7-(dimethylamino)-5-(4-methoxyphenyl)-2-methyl-1,1-dioxo-4,5-dihydro-1$l^{6},2-benzothiazepin-4-ol Chemical compound C1([C@H]2[C@@H](O)C(N(S(=O)(=O)C3=CC=C(C=C32)N(C)C)C)(CCCC)CCCC)=CC=C(OC)C=C1 ZCJMAJYQZWBZMJ-CLJLJLNGSA-N 0.000 claims 1
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- 238000006460 hydrolysis reaction Methods 0.000 description 1
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- 230000000871 hypocholesterolemic effect Effects 0.000 description 1
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- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
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- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
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- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
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- 125000002346 iodo group Chemical group I* 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 102000048260 kappa Opioid Receptors Human genes 0.000 description 1
- 150000002584 ketoses Chemical class 0.000 description 1
- CFHGBZLNZZVTAY-UHFFFAOYSA-N lawesson's reagent Chemical compound C1=CC(OC)=CC=C1P1(=S)SP(=S)(C=2C=CC(OC)=CC=2)S1 CFHGBZLNZZVTAY-UHFFFAOYSA-N 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 108010022197 lipoprotein cholesterol Proteins 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 239000000463 material Substances 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
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
- 230000027939 micturition Effects 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 125000006682 monohaloalkyl group Chemical group 0.000 description 1
- 238000011294 monotherapeutic Methods 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 229940035363 muscle relaxants Drugs 0.000 description 1
- 239000003158 myorelaxant agent 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
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 125000005702 oxyalkylene group Chemical group 0.000 description 1
- 125000006353 oxyethylene group Chemical group 0.000 description 1
- UQPUONNXJVWHRM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 UQPUONNXJVWHRM-UHFFFAOYSA-N 0.000 description 1
- 230000008068 pathophysiological alteration Effects 0.000 description 1
- 125000005010 perfluoroalkyl group Chemical group 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 150000004885 piperazines Chemical class 0.000 description 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- 235000010333 potassium nitrate Nutrition 0.000 description 1
- 239000004323 potassium nitrate Substances 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
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- 230000002265 prevention Effects 0.000 description 1
- 208000000876 primary bile acid malabsorption Diseases 0.000 description 1
- 125000001325 propanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000005932 reductive alkylation reaction Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- HSNZZMHEPUFJNZ-SHUUEZRQSA-N sedoheptulose Chemical compound OC[C@@H](O)[C@@H](O)[C@@H](O)[C@H](O)C(=O)CO HSNZZMHEPUFJNZ-SHUUEZRQSA-N 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 125000003003 spiro group Chemical group 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 150000005846 sugar alcohols Chemical class 0.000 description 1
- 125000000446 sulfanediyl group Chemical group *S* 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
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid group Chemical class S(O)(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 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 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
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 1
- CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 150000004044 tetrasaccharides Chemical class 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000001984 thiazolidinyl group Chemical group 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- WTVXIBRMWGUIMI-UHFFFAOYSA-N trifluoro($l^{1}-oxidanylsulfonyl)methane Chemical group [O]S(=O)(=O)C(F)(F)F WTVXIBRMWGUIMI-UHFFFAOYSA-N 0.000 description 1
- 125000004385 trihaloalkyl group Chemical group 0.000 description 1
- WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 1
- CURCMGVZNYCRNY-UHFFFAOYSA-N trimethylazanium;iodide Chemical compound I.CN(C)C CURCMGVZNYCRNY-UHFFFAOYSA-N 0.000 description 1
- 150000004043 trisaccharides Chemical class 0.000 description 1
- 230000003827 upregulation Effects 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
- 229910052727 yttrium Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 108020001588 κ-opioid receptors Proteins 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
-
- 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
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D281/00—Heterocyclic compounds containing rings of more than six members having one nitrogen atom and one sulfur atom as the only ring hetero atoms
- C07D281/02—Seven-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—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
- C07D487/04—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
- 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
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
- C07F9/36—Amides thereof
-
- 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
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
- C07F9/3808—Acyclic saturated acids which can have further substituents on alkyl
-
- 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
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/54—Quaternary phosphonium compounds
- C07F9/5407—Acyclic saturated phosphonium compounds
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Obesity (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
La présente invention concerne de nouvelles benzothiazépines-1,2, des dérivés et des analogues de celles-ci, des compositions pharmaceutiques les contenant et leur utilisation en médecine, particulièrement dans la prophylaxie et/ou le traitement des maladies, des états et/ou des troubles hyperlipidémiques, tels que ceux associés à l'athérosclérose et/ou l'hypercholestérolémie.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11993399P | 1999-02-12 | 1999-02-12 | |
| US60/119,933 | 1999-02-12 | ||
| PCT/US2000/002503 WO2000047568A2 (fr) | 1999-02-12 | 2000-02-10 | Nouvelles benzothiazepines-1,2 presentant une activite d'inhibition de transport d'acide biliaire ileal et d'absorption de taurocholate |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2362147A1 true CA2362147A1 (fr) | 2000-08-17 |
Family
ID=22387268
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002362147A Abandoned CA2362147A1 (fr) | 1999-02-12 | 2000-02-10 | Nouvelles benzothiazepines-1,2 presentant une activite d'inhibition de transport d'acide biliaire ileal et d'absorption de taurocholate |
Country Status (10)
| Country | Link |
|---|---|
| EP (1) | EP1155007A2 (fr) |
| JP (1) | JP2002536440A (fr) |
| KR (1) | KR20020000139A (fr) |
| CN (1) | CN1195748C (fr) |
| AU (1) | AU3694600A (fr) |
| CA (1) | CA2362147A1 (fr) |
| HU (1) | HUP0105409A3 (fr) |
| IL (1) | IL144716A0 (fr) |
| WO (1) | WO2000047568A2 (fr) |
| ZA (1) | ZA200106252B (fr) |
Families Citing this family (57)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| SE0000772D0 (sv) | 2000-03-08 | 2000-03-08 | Astrazeneca Ab | Chemical compounds |
| EG26979A (en) | 2000-12-21 | 2015-03-01 | Astrazeneca Ab | Chemical compounds |
| GB0121337D0 (en) | 2001-09-04 | 2001-10-24 | Astrazeneca Ab | Chemical compounds |
| GB0121622D0 (en) | 2001-09-07 | 2001-10-31 | Astrazeneca Ab | Chemical compounds |
| GB0121621D0 (en) | 2001-09-07 | 2001-10-31 | Astrazeneca Ab | Chemical compounds |
| ATE349214T1 (de) * | 2001-09-08 | 2007-01-15 | Astrazeneca Ab | Benzothiazepin und benzothiadiazepin derivative mit hemmender wirkung auf den säuretransport in den gallengängen zur behandlung von hyperlipidaemia |
| GB0209467D0 (en) | 2002-04-25 | 2002-06-05 | Astrazeneca Ab | Chemical compounds |
| CA2486581A1 (fr) * | 2002-06-11 | 2003-12-18 | Wyeth | Inhibiteurs a substitution phenylsulfonamide de la production de beta-amyloides |
| GB0213669D0 (en) | 2002-06-14 | 2002-07-24 | Astrazeneca Ab | Chemical compounds |
| ATE531701T1 (de) * | 2002-08-28 | 2011-11-15 | Asahi Kasei Pharma Corp | Neue quaternüre ammoniumverbindungen |
| US7312208B2 (en) | 2002-08-28 | 2007-12-25 | Asahi Kasei Pharma Corporation | Quaternary ammonium compounds |
| GB0304194D0 (en) | 2003-02-25 | 2003-03-26 | Astrazeneca Ab | Chemical compounds |
| GB0307918D0 (en) | 2003-04-05 | 2003-05-14 | Astrazeneca Ab | Therapeutic use |
| US7973030B2 (en) | 2004-02-27 | 2011-07-05 | Asahi Kasei Pharma Corporation | Benzothiazepine and benzothiepine compounds |
| WO2011150286A2 (fr) | 2010-05-26 | 2011-12-01 | Satiogen Pharmaceuticals,Inc. | Inhibiteurs et satiogènes de recyclage d'acide biliaire pour traitement du diabète, de l'obésité et d'états inflammatoires gastro-intestinaux |
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Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA956647B (en) * | 1994-08-10 | 1997-02-10 | Wellcome Found | Hypolipidaemic compounds. |
| GB9423172D0 (en) * | 1994-11-17 | 1995-01-04 | Wellcom Foundation The Limited | Hypolipidemic benzothiazepines |
| WO1998002432A1 (fr) * | 1996-07-16 | 1998-01-22 | Takeda Chemical Industries, Ltd. | Composes bicycliques pour commander la miction |
| GB9704208D0 (en) * | 1997-02-28 | 1997-04-16 | Glaxo Group Ltd | Chemical compounds |
-
2000
- 2000-02-10 HU HU0105409A patent/HUP0105409A3/hu unknown
- 2000-02-10 JP JP2000598488A patent/JP2002536440A/ja active Pending
- 2000-02-10 KR KR1020017010201A patent/KR20020000139A/ko not_active Application Discontinuation
- 2000-02-10 CA CA002362147A patent/CA2362147A1/fr not_active Abandoned
- 2000-02-10 AU AU36946/00A patent/AU3694600A/en not_active Abandoned
- 2000-02-10 WO PCT/US2000/002503 patent/WO2000047568A2/fr not_active Application Discontinuation
- 2000-02-10 CN CNB008060282A patent/CN1195748C/zh not_active Expired - Fee Related
- 2000-02-10 EP EP00915720A patent/EP1155007A2/fr not_active Ceased
- 2000-02-10 IL IL14471600A patent/IL144716A0/xx unknown
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2001
- 2001-07-30 ZA ZA200106252A patent/ZA200106252B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| HUP0105409A2 (hu) | 2002-05-29 |
| HUP0105409A3 (en) | 2004-11-29 |
| IL144716A0 (en) | 2002-06-30 |
| WO2000047568A2 (fr) | 2000-08-17 |
| CN1195748C (zh) | 2005-04-06 |
| ZA200106252B (en) | 2002-07-30 |
| EP1155007A2 (fr) | 2001-11-21 |
| KR20020000139A (ko) | 2002-01-04 |
| JP2002536440A (ja) | 2002-10-29 |
| CN1346351A (zh) | 2002-04-24 |
| AU3694600A (en) | 2000-08-29 |
| WO2000047568A3 (fr) | 2000-12-14 |
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