CA2055680A1 - Tricyclic compounds - Google Patents
Tricyclic compoundsInfo
- Publication number
- CA2055680A1 CA2055680A1 CA002055680A CA2055680A CA2055680A1 CA 2055680 A1 CA2055680 A1 CA 2055680A1 CA 002055680 A CA002055680 A CA 002055680A CA 2055680 A CA2055680 A CA 2055680A CA 2055680 A1 CA2055680 A1 CA 2055680A1
- Authority
- CA
- Canada
- Prior art keywords
- compound
- azabicyclo
- oct
- methyl
- formula
- 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
Links
- 150000001875 compounds Chemical class 0.000 title claims abstract description 269
- 238000000034 method Methods 0.000 claims abstract description 94
- 150000003839 salts Chemical class 0.000 claims abstract description 58
- -1 nitro, amino, aminocarbonyl Chemical group 0.000 claims abstract description 49
- 239000001257 hydrogen Substances 0.000 claims abstract description 44
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 44
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 43
- 239000000203 mixture Substances 0.000 claims abstract description 36
- 238000002360 preparation method Methods 0.000 claims abstract description 36
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 22
- 230000008569 process Effects 0.000 claims abstract description 19
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 18
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 13
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 12
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 10
- 150000002367 halogens Chemical class 0.000 claims abstract description 10
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 claims abstract description 8
- 125000001589 carboacyl group Chemical group 0.000 claims abstract description 7
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims abstract description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 50
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 38
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 37
- 201000010099 disease Diseases 0.000 claims description 32
- 206010047700 Vomiting Diseases 0.000 claims description 28
- 238000011282 treatment Methods 0.000 claims description 25
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 24
- 241001465754 Metazoa Species 0.000 claims description 23
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical compound C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 claims description 20
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 19
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 19
- 239000002585 base Substances 0.000 claims description 14
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 13
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 13
- 239000003795 chemical substances by application Substances 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- 208000002193 Pain Diseases 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 10
- RJTZUHVCZIGJMB-UHFFFAOYSA-N hydron;1h-indole;chloride Chemical compound Cl.C1=CC=C2NC=CC2=C1 RJTZUHVCZIGJMB-UHFFFAOYSA-N 0.000 claims description 10
- 230000036407 pain Effects 0.000 claims description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 10
- VSOSXKMEQPYESP-UHFFFAOYSA-N 1,6-naphthyridine Chemical compound C1=CN=CC2=CC=CN=C21 VSOSXKMEQPYESP-UHFFFAOYSA-N 0.000 claims description 7
- 208000024172 Cardiovascular disease Diseases 0.000 claims description 7
- 208000018522 Gastrointestinal disease Diseases 0.000 claims description 7
- 208000019695 Migraine disease Diseases 0.000 claims description 7
- 150000001204 N-oxides Chemical class 0.000 claims description 7
- 208000015114 central nervous system disease Diseases 0.000 claims description 7
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 7
- 241000282414 Homo sapiens Species 0.000 claims description 6
- 229940100198 alkylating agent Drugs 0.000 claims description 6
- 239000002168 alkylating agent Substances 0.000 claims description 6
- 208000035475 disorder Diseases 0.000 claims description 6
- 239000012458 free base Substances 0.000 claims description 6
- 206010027599 migraine Diseases 0.000 claims description 6
- 208000010643 digestive system disease Diseases 0.000 claims description 4
- 208000018685 gastrointestinal system disease Diseases 0.000 claims description 4
- 206010028980 Neoplasm Diseases 0.000 claims description 3
- 201000011510 cancer Diseases 0.000 claims description 3
- 230000005855 radiation Effects 0.000 claims description 3
- OLJPPWKUJOXYBN-UHFFFAOYSA-N 2-(1-azabicyclo[2.2.2]octan-3-yl)-5-methylpyrido[4,3-b]indol-1-one Chemical compound C1N(CC2)CCC2C1N(C1=O)C=CC2=C1C1=CC=CC=C1N2C OLJPPWKUJOXYBN-UHFFFAOYSA-N 0.000 claims description 2
- OLJPPWKUJOXYBN-QGZVFWFLSA-N 2-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-5-methylpyrido[4,3-b]indol-1-one Chemical compound C1N(CC2)CCC2[C@@H]1N(C1=O)C=CC2=C1C1=CC=CC=C1N2C OLJPPWKUJOXYBN-QGZVFWFLSA-N 0.000 claims description 2
- 230000001590 oxidative effect Effects 0.000 claims description 2
- 239000012070 reactive reagent Substances 0.000 claims description 2
- QAPAAMJNJUBIMZ-UHFFFAOYSA-N 1-benzofuran;hydrochloride Chemical compound Cl.C1=CC=C2OC=CC2=C1 QAPAAMJNJUBIMZ-UHFFFAOYSA-N 0.000 claims 2
- SMEWJMFAZINHKH-GOSISDBHSA-N chembl89071 Chemical compound C1N(CC2)CCC2[C@@H]1N1C(=O)C(C2=CC=CC=C2N2CCC3)=C2C3=C1 SMEWJMFAZINHKH-GOSISDBHSA-N 0.000 claims 2
- VLZLPTXRUKQDAU-UHFFFAOYSA-N 2-(1-azabicyclo[2.2.2]octan-3-yl)-5-methyl-3,4-dihydropyrido[4,3-b]indol-1-one Chemical compound C12=CC=CC=C2N(C)C2=C1C(=O)N(C1C3CCN(CC3)C1)CC2 VLZLPTXRUKQDAU-UHFFFAOYSA-N 0.000 claims 1
- JUIJKYDLKVUFOU-UHFFFAOYSA-N 2-(1-azabicyclo[2.2.2]octan-3-yl)-8-hydroxy-5-methylpyrido[4,3-b]indol-1-one Chemical compound C1N(CC2)CCC2C1N(C1=O)C=CC2=C1C1=CC(O)=CC=C1N2C JUIJKYDLKVUFOU-UHFFFAOYSA-N 0.000 claims 1
- VLZLPTXRUKQDAU-KRWDZBQOSA-N 2-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-5-methyl-3,4-dihydropyrido[4,3-b]indol-1-one Chemical compound N12C[C@@H](C(CC1)CC2)N2C(C1=C(N(C=3C=CC=CC13)C)CC2)=O VLZLPTXRUKQDAU-KRWDZBQOSA-N 0.000 claims 1
- OLVQOCMASCQAPC-LMOVPXPDSA-N 2-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-5-methyl-3,4-dihydropyrido[4,3-b]indol-1-one hydrochloride Chemical compound Cl.N12C[C@@H](C(CC1)CC2)N2C(C1=C(N(C=3C=CC=CC13)C)CC2)=O OLVQOCMASCQAPC-LMOVPXPDSA-N 0.000 claims 1
- VLZLPTXRUKQDAU-QGZVFWFLSA-N 2-[(3S)-1-azabicyclo[2.2.2]octan-3-yl]-5-methyl-3,4-dihydropyrido[4,3-b]indol-1-one Chemical compound N12C[C@H](C(CC1)CC2)N2C(C1=C(N(C=3C=CC=CC13)C)CC2)=O VLZLPTXRUKQDAU-QGZVFWFLSA-N 0.000 claims 1
- OLJPPWKUJOXYBN-KRWDZBQOSA-N 2-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-5-methylpyrido[4,3-b]indol-1-one Chemical compound C1N(CC2)CCC2[C@H]1N(C1=O)C=CC2=C1C1=CC=CC=C1N2C OLJPPWKUJOXYBN-KRWDZBQOSA-N 0.000 claims 1
- YDPDRSKBZBNPME-LMOVPXPDSA-N 2-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-5-methylpyrido[4,3-b]indol-1-one;hydrochloride Chemical compound Cl.C1N(CC2)CCC2[C@H]1N(C1=O)C=CC2=C1C1=CC=CC=C1N2C YDPDRSKBZBNPME-LMOVPXPDSA-N 0.000 claims 1
- YDPDRSKBZBNPME-UNTBIKODSA-N 2-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-5-methylpyrido[4,3-b]indol-1-one;hydrochloride Chemical compound Cl.C1N(CC2)CCC2[C@@H]1N(C1=O)C=CC2=C1C1=CC=CC=C1N2C YDPDRSKBZBNPME-UNTBIKODSA-N 0.000 claims 1
- JUIJKYDLKVUFOU-QGZVFWFLSA-N 2-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-8-hydroxy-5-methylpyrido[4,3-b]indol-1-one Chemical compound C1N(CC2)CCC2[C@@H]1N(C1=O)C=CC2=C1C1=CC(O)=CC=C1N2C JUIJKYDLKVUFOU-QGZVFWFLSA-N 0.000 claims 1
- SMEWJMFAZINHKH-SFHVURJKSA-N chembl89678 Chemical compound C1N(CC2)CCC2[C@H]1N1C(=O)C(C2=CC=CC=C2N2CCC3)=C2C3=C1 SMEWJMFAZINHKH-SFHVURJKSA-N 0.000 claims 1
- 231100000433 cytotoxic Toxicity 0.000 claims 1
- 230000001472 cytotoxic effect Effects 0.000 claims 1
- 239000008177 pharmaceutical agent Substances 0.000 claims 1
- 229940127239 5 Hydroxytryptamine receptor antagonist Drugs 0.000 abstract 1
- 239000003420 antiserotonin agent Substances 0.000 abstract 1
- 238000012360 testing method Methods 0.000 description 45
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 41
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
- 230000000694 effects Effects 0.000 description 29
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- 239000000243 solution Substances 0.000 description 18
- 241000699670 Mus sp. Species 0.000 description 17
- 238000003556 assay Methods 0.000 description 16
- 239000003981 vehicle Substances 0.000 description 16
- 229910001868 water Inorganic materials 0.000 description 16
- 102000035037 5-HT3 receptors Human genes 0.000 description 15
- 108091005477 5-HT3 receptors Proteins 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 15
- 235000012054 meals Nutrition 0.000 description 15
- 239000002904 solvent Substances 0.000 description 15
- 241000700159 Rattus Species 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 12
- 229940093499 ethyl acetate Drugs 0.000 description 11
- 235000019439 ethyl acetate Nutrition 0.000 description 11
- 230000009467 reduction Effects 0.000 description 11
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 230000003474 anti-emetic effect Effects 0.000 description 10
- 239000003054 catalyst Substances 0.000 description 10
- 239000003814 drug Substances 0.000 description 10
- WYWNEDARFVJQSG-UHFFFAOYSA-N 2-methylserotonin Chemical compound C1=C(O)C=C2C(CCN)=C(C)NC2=C1 WYWNEDARFVJQSG-UHFFFAOYSA-N 0.000 description 9
- 241000699666 Mus <mouse, genus> Species 0.000 description 9
- 239000004480 active ingredient Substances 0.000 description 9
- 150000001408 amides Chemical group 0.000 description 9
- 229940079593 drug Drugs 0.000 description 9
- 230000004044 response Effects 0.000 description 9
- 208000019901 Anxiety disease Diseases 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 230000036506 anxiety Effects 0.000 description 8
- 230000000949 anxiolytic effect Effects 0.000 description 8
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 8
- 229960004316 cisplatin Drugs 0.000 description 8
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 8
- 239000002895 emetic Substances 0.000 description 8
- 239000011541 reaction mixture Substances 0.000 description 8
- 239000003369 serotonin 5-HT3 receptor antagonist Substances 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 7
- 230000027455 binding Effects 0.000 description 7
- 238000001727 in vivo Methods 0.000 description 7
- 238000001990 intravenous administration Methods 0.000 description 7
- 239000007788 liquid Substances 0.000 description 7
- 210000002784 stomach Anatomy 0.000 description 7
- 230000008673 vomiting Effects 0.000 description 7
- BLZKSRBAQDZAIX-UHFFFAOYSA-N 2-methyl-1-benzothiophene Chemical compound C1=CC=C2SC(C)=CC2=C1 BLZKSRBAQDZAIX-UHFFFAOYSA-N 0.000 description 6
- 241000282472 Canis lupus familiaris Species 0.000 description 6
- 235000013305 food Nutrition 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 239000000543 intermediate Substances 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- IYORQGGVUKCMLZ-OAHLLOKOSA-N n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-1,2-dimethylindole-3-carboxamide Chemical compound C12=CC=CC=C2N(C)C(C)=C1C(=O)N[C@H]1C(CC2)CCN2C1 IYORQGGVUKCMLZ-OAHLLOKOSA-N 0.000 description 6
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- REUAXQZIRFXQML-SSDOTTSWSA-N (3s)-1-azabicyclo[2.2.2]octan-3-amine Chemical compound C1CC2[C@H](N)CN1CC2 REUAXQZIRFXQML-SSDOTTSWSA-N 0.000 description 5
- XYRXQPDMBJNYIU-UHFFFAOYSA-N 1,2-dimethylindole-3-carboxylic acid Chemical compound C1=CC=C2N(C)C(C)=C(C(O)=O)C2=C1 XYRXQPDMBJNYIU-UHFFFAOYSA-N 0.000 description 5
- REUAXQZIRFXQML-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-3-amine Chemical compound C1CC2C(N)CN1CC2 REUAXQZIRFXQML-UHFFFAOYSA-N 0.000 description 5
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 5
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 5
- 206010038776 Retching Diseases 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 230000030136 gastric emptying Effects 0.000 description 5
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 5
- 238000007912 intraperitoneal administration Methods 0.000 description 5
- NXJCBFBQEVOTOW-UHFFFAOYSA-L palladium(2+);dihydroxide Chemical compound O[Pd]O NXJCBFBQEVOTOW-UHFFFAOYSA-L 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 4
- 241000282339 Mustela Species 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 4
- 239000000908 ammonium hydroxide Substances 0.000 description 4
- 239000005557 antagonist Substances 0.000 description 4
- 125000004429 atom Chemical group 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 4
- 210000003169 central nervous system Anatomy 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 230000001684 chronic effect Effects 0.000 description 4
- 229960003920 cocaine Drugs 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 230000002496 gastric effect Effects 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 150000007522 mineralic acids Chemical class 0.000 description 4
- 229960002715 nicotine Drugs 0.000 description 4
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 150000007524 organic acids Chemical class 0.000 description 4
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- XRXDAJYKGWNHTQ-UHFFFAOYSA-N quipazine Chemical compound C1CNCCN1C1=CC=C(C=CC=C2)C2=N1 XRXDAJYKGWNHTQ-UHFFFAOYSA-N 0.000 description 4
- 229950002315 quipazine Drugs 0.000 description 4
- 238000001959 radiotherapy Methods 0.000 description 4
- 230000011514 reflex Effects 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 3
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Classifications
-
- 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
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Hospice & Palliative Care (AREA)
- Otolaryngology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US07/614,326 US5189041A (en) | 1990-11-16 | 1990-11-16 | Tricyclic 5-ht3 receptor antagonists |
| US614,326 | 1990-11-16 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2055680A1 true CA2055680A1 (en) | 1992-05-17 |
Family
ID=24460766
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002055680A Abandoned CA2055680A1 (en) | 1990-11-16 | 1991-11-15 | Tricyclic compounds |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US5189041A (OSRAM) |
| EP (1) | EP0485962A3 (OSRAM) |
| JP (1) | JPH04283587A (OSRAM) |
| KR (1) | KR920009828A (OSRAM) |
| AU (1) | AU8785291A (OSRAM) |
| CA (1) | CA2055680A1 (OSRAM) |
| FI (1) | FI915400A7 (OSRAM) |
| HU (1) | HUT59406A (OSRAM) |
| IE (1) | IE913987A1 (OSRAM) |
| IL (1) | IL100061A0 (OSRAM) |
| IT (1) | IT1250049B (OSRAM) |
| MX (1) | MX9102076A (OSRAM) |
| NO (1) | NO914490L (OSRAM) |
| PL (1) | PL292419A1 (OSRAM) |
| PT (1) | PT99518A (OSRAM) |
| TW (1) | TW208007B (OSRAM) |
| ZA (1) | ZA919078B (OSRAM) |
Families Citing this family (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IE68434B1 (en) * | 1989-11-28 | 1996-06-12 | Syntex Inc | New tricyclic compounds |
| US5852014A (en) * | 1992-03-12 | 1998-12-22 | Smithkline Beecham P.L.C. | Condensed indole derivatives as 5HT4 -receptor antagonists |
| DE69325167T2 (de) * | 1992-03-12 | 2000-01-20 | Smithkline Beecham P.L.C., Brentford | Kondensierte indol-derivate als 5-ht4-rezeptor-antagonisten |
| MX9305947A (es) * | 1992-09-29 | 1994-06-30 | Smithkline Beecham Plc | Compuestos antagonistas del receptor 5-ht4, procedimiento para su preparacion y composiciones farmaceuticas que las contienen. |
| ES2113568T3 (es) * | 1993-04-27 | 1998-05-01 | Solvay Fluor & Derivate | Procedimiento para la preparacion de esteres de acidos carboxilicos a partir de halogenuros de acidos carboxilicos y alcoholes. |
| US6489355B2 (en) * | 1993-12-01 | 2002-12-03 | Eli Lilly And Company | Methods of inhibiting the effects of amyloidogenic proteins |
| US5723103A (en) * | 1994-12-09 | 1998-03-03 | Vanderbilt University | Substituted benzamides and radioligand analogs and methods of use |
| IT1303123B1 (it) * | 1998-10-13 | 2000-10-30 | Rotta Research Lab | Derivati basici di benz(e)isoindol-1-oni e pirrolo(3,4-c)chinolin-1-oni ad attivita' 5ht3 antagonista, loro preparazione ed |
| EP1254115A2 (en) * | 2000-02-11 | 2002-11-06 | Bristol-Myers Squibb Company | Cannabinoid receptor modulators, their processes of preparation, and use of cannabinoid receptor modulators for treating respiratory and non-respiratory diseases |
| EP1284732A2 (en) * | 2000-05-18 | 2003-02-26 | Glaxo Group Limited | Method for treating functional dyspepsia using alosetron |
| AR036040A1 (es) | 2001-06-12 | 2004-08-04 | Upjohn Co | Compuestos de heteroarilo multiciclicos sustituidos con quinuclidinas y composiciones farmaceuticas que los contienen |
| AR036041A1 (es) | 2001-06-12 | 2004-08-04 | Upjohn Co | Compuestos aromaticos heterociclicos sustituidos con quinuclidina y composiciones farmaceuticas que los contienen |
| BR0214016A (pt) | 2001-11-09 | 2004-10-13 | Upjohn Co | Compostos azabicìclico-fenil-fundido heterocìclicos e seu uso como ligandos alfa 7 nachr |
| DE10164139A1 (de) | 2001-12-27 | 2003-07-10 | Bayer Ag | 2-Heteroarylcarbonsäureamide |
| DE10234424A1 (de) | 2002-07-29 | 2004-02-12 | Bayer Ag | Benzothiophen-, Benzofuran- und Indolharnstoffe |
| TWI355936B (en) | 2003-02-18 | 2012-01-11 | Helsinn Healthcare Sa | Uses of palonosetron hydrochloride |
| ITMI20031467A1 (it) * | 2003-07-18 | 2005-01-19 | Acraf | Farmaco attivo nel dolore neuropatico |
| CA2744278C (en) | 2008-11-19 | 2015-09-08 | Envivo Pharmaceuticals, Inc. | Treatment of cognitive disorders with (r)-7-chloro-n-(quinuclidin-3-yl)benzo[b]thiophene-2-carboxamide and pharmaceutically acceptable salts thereof |
| US9145396B2 (en) | 2008-12-01 | 2015-09-29 | Targacept, Inc. | Synthesis and novel salt forms of (R)-5-((E)-2-pyrrolidin-3ylvinyl)pyrimidine |
| CN103221411B (zh) | 2010-05-17 | 2016-05-11 | 富瑞姆制药公司 | (R)-7-氯-N-(奎宁环-3-基)苯并[b]噻吩-2-甲酰胺盐酸盐单水合物的晶型 |
| CA2872005A1 (en) | 2012-05-08 | 2013-11-14 | Forum Pharmaceuticals, Inc. | Methods of maintaining, treating or improving cognitive function |
Family Cites Families (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2121394A1 (fr) * | 1971-01-08 | 1972-08-25 | Anvar | Procédé d'obtention de dérivés d'acides indole carboxyliques et produits préparables par ce procédé. |
| JPS5337696A (en) * | 1976-08-26 | 1978-04-06 | Omnium Chimique Sa | Hexahydrocantinonee6 derivative |
| FR2475394A1 (fr) * | 1980-02-12 | 1981-08-14 | Synthelabo | Compositions pharmaceutiques contenant l'hexahydro-1, 2, 3, 3a, 4, 5, 6h indolo (3, 2, 1 - d. e) (1, 5) naphtyridinone - 6 |
| FI74707C (fi) * | 1982-06-29 | 1988-03-10 | Sandoz Ag | Foerfarande foer framstaellning av terapeutiskt anvaendbara alkylenoeverbryggade piperidylestrar eller -amider av bicykliska karboxylsyror. |
| GB8623142D0 (en) * | 1986-09-26 | 1986-10-29 | Beecham Group Plc | Compounds |
| DE3777805D1 (de) * | 1986-11-21 | 1992-04-30 | Glaxo Group Ltd | Arzneimittel zur behandlung oder vorbeugung des entzugssyndromes. |
| ATE111910T1 (de) * | 1987-09-03 | 1994-10-15 | Glaxo Group Ltd | Lactamderivate. |
| DE3810552A1 (de) * | 1988-03-29 | 1989-10-19 | Sandoz Ag | Ester und amide von indol-, benzo(b)thiopen-, benzo(b)furancarbonsaeuren oder 4-amino-2-methoxy-benzolsaeuren mit n-heterocyclischen oder n-heterobicyclischen alkoholen oder aminen, verfahren zu deren herstellung sie enthaltende pharmazeutische zusammensetzungen sowie applikator zur verabreichung derselben |
| JPH02167280A (ja) * | 1988-08-15 | 1990-06-27 | Glaxo Group Ltd | ラクタム誘導体 |
| EP0377238A1 (en) * | 1988-12-22 | 1990-07-11 | Duphar International Research B.V | New annelated indolo (3,2-c)-lactams |
| GB8904551D0 (en) * | 1989-02-28 | 1989-04-12 | Glaxo Group Ltd | Chemical compounds |
| EP0392663A1 (en) * | 1989-03-13 | 1990-10-17 | Ono Pharmaceutical Co., Ltd. | Carboline derivative as a 5-HT3 receptor antagonist |
| JPH02290878A (ja) * | 1989-04-28 | 1990-11-30 | Ono Pharmaceut Co Ltd | ベンゾチエノ（フロ）ピリジン誘導体 |
-
1990
- 1990-11-16 US US07/614,326 patent/US5189041A/en not_active Expired - Fee Related
-
1991
- 1991-11-05 KR KR1019910020330A patent/KR920009828A/ko not_active Withdrawn
- 1991-11-12 IT ITTO910865A patent/IT1250049B/it active IP Right Grant
- 1991-11-12 EP EP19910119290 patent/EP0485962A3/en not_active Withdrawn
- 1991-11-15 JP JP3300234A patent/JPH04283587A/ja active Pending
- 1991-11-15 MX MX9102076A patent/MX9102076A/es unknown
- 1991-11-15 IL IL100061A patent/IL100061A0/xx unknown
- 1991-11-15 FI FI915400A patent/FI915400A7/fi not_active Application Discontinuation
- 1991-11-15 ZA ZA919078A patent/ZA919078B/xx unknown
- 1991-11-15 IE IE398791A patent/IE913987A1/en not_active Application Discontinuation
- 1991-11-15 PT PT99518A patent/PT99518A/pt not_active Application Discontinuation
- 1991-11-15 PL PL29241991A patent/PL292419A1/xx unknown
- 1991-11-15 HU HU913579A patent/HUT59406A/hu unknown
- 1991-11-15 TW TW080108994A patent/TW208007B/zh active
- 1991-11-15 NO NO91914490A patent/NO914490L/no unknown
- 1991-11-15 AU AU87852/91A patent/AU8785291A/en not_active Abandoned
- 1991-11-15 CA CA002055680A patent/CA2055680A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| IL100061A0 (en) | 1992-08-18 |
| FI915400A0 (fi) | 1991-11-15 |
| FI915400A7 (fi) | 1992-05-17 |
| JPH04283587A (ja) | 1992-10-08 |
| ITTO910865A1 (it) | 1993-05-12 |
| EP0485962A3 (en) | 1992-07-29 |
| ITTO910865A0 (it) | 1991-11-12 |
| HUT59406A (en) | 1992-05-28 |
| TW208007B (OSRAM) | 1993-06-21 |
| US5189041A (en) | 1993-02-23 |
| KR920009828A (ko) | 1992-06-25 |
| IT1250049B (it) | 1995-03-30 |
| PT99518A (pt) | 1992-09-30 |
| ZA919078B (en) | 1993-05-17 |
| AU8785291A (en) | 1992-05-21 |
| IE913987A1 (en) | 1992-05-20 |
| NO914490D0 (no) | 1991-11-15 |
| MX9102076A (es) | 1992-07-08 |
| EP0485962A2 (en) | 1992-05-20 |
| HU913579D0 (en) | 1992-01-28 |
| PL292419A1 (en) | 1993-04-05 |
| NO914490L (no) | 1992-05-18 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |