CZ20021692A3 - Nové N-azabicykloamidové deriváty a jejich pouľití - Google Patents
Nové N-azabicykloamidové deriváty a jejich pouľití Download PDFInfo
- Publication number
- CZ20021692A3 CZ20021692A3 CZ20021692A CZ20021692A CZ20021692A3 CZ 20021692 A3 CZ20021692 A3 CZ 20021692A3 CZ 20021692 A CZ20021692 A CZ 20021692A CZ 20021692 A CZ20021692 A CZ 20021692A CZ 20021692 A3 CZ20021692 A3 CZ 20021692A3
- Authority
- CZ
- Czechia
- Prior art keywords
- oct
- azabicyclo
- propenamide
- hydrogen
- alkyl
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 claims abstract description 97
- 239000001257 hydrogen Substances 0.000 claims abstract description 39
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 39
- 150000003839 salts Chemical class 0.000 claims abstract description 38
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 26
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 22
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 17
- 238000011282 treatment Methods 0.000 claims abstract description 17
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 16
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 14
- 239000001301 oxygen Substances 0.000 claims abstract description 14
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 11
- 208000028017 Psychotic disease Diseases 0.000 claims abstract description 7
- 230000006735 deficit Effects 0.000 claims abstract description 7
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 5
- 239000011593 sulfur Substances 0.000 claims abstract description 5
- -1 -CO 2 R 7 Chemical group 0.000 claims description 101
- 150000001408 amides Chemical class 0.000 claims description 20
- 125000003118 aryl group Chemical group 0.000 claims description 19
- 229910052736 halogen Inorganic materials 0.000 claims description 18
- 150000002367 halogens Chemical class 0.000 claims description 18
- 125000001072 heteroaryl group Chemical group 0.000 claims description 13
- 230000002265 prevention Effects 0.000 claims description 11
- 125000001424 substituent group Chemical group 0.000 claims description 11
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 10
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 10
- 125000004434 sulfur atom Chemical group 0.000 claims description 10
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 9
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 9
- 239000003814 drug Substances 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 238000000034 method Methods 0.000 abstract description 65
- 239000008194 pharmaceutical composition Substances 0.000 abstract description 6
- 230000008569 process Effects 0.000 abstract description 5
- 238000011321 prophylaxis Methods 0.000 abstract 1
- 238000002560 therapeutic procedure Methods 0.000 abstract 1
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 84
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 53
- 239000012458 free base Substances 0.000 description 52
- 239000000243 solution Substances 0.000 description 32
- STZHBULOYDCZET-KLXURFKVSA-N (3r)-1-azabicyclo[2.2.2]octan-3-amine;dihydrochloride Chemical compound Cl.Cl.C1CC2[C@@H](N)CN1CC2 STZHBULOYDCZET-KLXURFKVSA-N 0.000 description 30
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 29
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 23
- 238000006243 chemical reaction Methods 0.000 description 23
- 238000004587 chromatography analysis Methods 0.000 description 23
- 239000000741 silica gel Substances 0.000 description 23
- 229910002027 silica gel Inorganic materials 0.000 description 23
- 229910021529 ammonia Inorganic materials 0.000 description 22
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 22
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 21
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- 239000010410 layer Substances 0.000 description 16
- 239000007787 solid Substances 0.000 description 16
- 239000002253 acid Substances 0.000 description 15
- 239000002904 solvent Substances 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 14
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
- 229910052757 nitrogen Inorganic materials 0.000 description 14
- 239000011541 reaction mixture Substances 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
- 208000035475 disorder Diseases 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 239000003480 eluent Substances 0.000 description 11
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
- 102000019315 Nicotinic acetylcholine receptors Human genes 0.000 description 8
- 108050006807 Nicotinic acetylcholine receptors Proteins 0.000 description 8
- 239000000203 mixture Substances 0.000 description 8
- STZHBULOYDCZET-XCUBXKJBSA-N (3s)-1-azabicyclo[2.2.2]octan-3-amine;dihydrochloride Chemical compound Cl.Cl.C1CC2[C@H](N)CN1CC2 STZHBULOYDCZET-XCUBXKJBSA-N 0.000 description 7
- 125000004093 cyano group Chemical group *C#N 0.000 description 7
- 201000010099 disease Diseases 0.000 description 7
- 229960002715 nicotine Drugs 0.000 description 7
- 239000012044 organic layer Substances 0.000 description 7
- 238000004007 reversed phase HPLC Methods 0.000 description 7
- 239000003643 water by type Substances 0.000 description 7
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 6
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 6
- 239000011539 homogenization buffer Substances 0.000 description 6
- APEJMQOBVMLION-VOTSOKGWSA-N trans-cinnamamide Chemical compound NC(=O)\C=C\C1=CC=CC=C1 APEJMQOBVMLION-VOTSOKGWSA-N 0.000 description 6
- STZHBULOYDCZET-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-3-amine;hydron;dichloride Chemical compound Cl.Cl.C1CC2C(N)CN1CC2 STZHBULOYDCZET-UHFFFAOYSA-N 0.000 description 5
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 5
- 239000012298 atmosphere Substances 0.000 description 5
- 239000002585 base Substances 0.000 description 5
- 230000027455 binding Effects 0.000 description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 4
- 229930182840 (S)-nicotine Natural products 0.000 description 4
- RCLFFPCOTKNDRK-VFQAQYNWSA-N (e)-3-(4-aminophenyl)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]prop-2-enamide Chemical compound C1=CC(N)=CC=C1\C=C\C(=O)N[C@@H]1C(CC2)CCN2C1 RCLFFPCOTKNDRK-VFQAQYNWSA-N 0.000 description 4
- 208000024827 Alzheimer disease Diseases 0.000 description 4
- 208000019901 Anxiety disease Diseases 0.000 description 4
- 208000002193 Pain Diseases 0.000 description 4
- 208000018737 Parkinson disease Diseases 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 230000010933 acylation Effects 0.000 description 4
- 238000005917 acylation reaction Methods 0.000 description 4
- 230000036506 anxiety Effects 0.000 description 4
- 230000008901 benefit Effects 0.000 description 4
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 4
- 229910021538 borax Inorganic materials 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- UQGFMSUEHSUPRD-UHFFFAOYSA-N disodium;3,7-dioxido-2,4,6,8,9-pentaoxa-1,3,5,7-tetraborabicyclo[3.3.1]nonane Chemical compound [Na+].[Na+].O1B([O-])OB2OB([O-])OB1O2 UQGFMSUEHSUPRD-UHFFFAOYSA-N 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 4
- 230000000144 pharmacologic effect Effects 0.000 description 4
- 201000000980 schizophrenia Diseases 0.000 description 4
- 230000005586 smoking cessation Effects 0.000 description 4
- 239000004328 sodium tetraborate Substances 0.000 description 4
- 235000010339 sodium tetraborate Nutrition 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- AHDDRJBFJBDEPW-DTWKUNHWSA-N trans-2-Phenylcyclopropanecarboxylic acid Chemical compound OC(=O)[C@@H]1C[C@H]1C1=CC=CC=C1 AHDDRJBFJBDEPW-DTWKUNHWSA-N 0.000 description 4
- WBYWAXJHAXSJNI-VOTSOKGWSA-N trans-cinnamic acid Chemical compound OC(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-N 0.000 description 4
- PHZYWNWABJJERF-NFAHFFEMSA-N (e)-3-(2-aminophenyl)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]prop-2-enamide Chemical compound NC1=CC=CC=C1\C=C\C(=O)N[C@@H]1C(CC2)CCN2C1 PHZYWNWABJJERF-NFAHFFEMSA-N 0.000 description 3
- MENCFQRKJSFDJH-AATRIKPKSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(2-nitrophenyl)prop-2-enamide Chemical compound [O-][N+](=O)C1=CC=CC=C1\C=C\C(=O)NC1C(CC2)CCN2C1 MENCFQRKJSFDJH-AATRIKPKSA-N 0.000 description 3
- HSTDTPMOYSFAIB-ISUDXETCSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(1h-imidazol-5-yl)prop-2-enamide Chemical compound N([C@@H]1C2CCN(CC2)C1)C(=O)\C=C\C1=CNC=N1 HSTDTPMOYSFAIB-ISUDXETCSA-N 0.000 description 3
- MENCFQRKJSFDJH-GJBLVYBDSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(2-nitrophenyl)prop-2-enamide Chemical compound [O-][N+](=O)C1=CC=CC=C1\C=C\C(=O)N[C@@H]1C(CC2)CCN2C1 MENCFQRKJSFDJH-GJBLVYBDSA-N 0.000 description 3
- LMYLJTJHCPTSPI-VFQAQYNWSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(4-nitrophenyl)prop-2-enamide Chemical compound C1=CC([N+](=O)[O-])=CC=C1\C=C\C(=O)N[C@@H]1C(CC2)CCN2C1 LMYLJTJHCPTSPI-VFQAQYNWSA-N 0.000 description 3
- DXSJNKAJPNKROG-YUKKFKLSSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(5-hydroxypyridin-3-yl)prop-2-enamide Chemical compound OC1=CN=CC(\C=C\C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 DXSJNKAJPNKROG-YUKKFKLSSA-N 0.000 description 3
- NBTHWOKIJJBULB-FAAWYNLUSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(5-methoxypyridin-3-yl)prop-2-enamide Chemical compound COC1=CN=CC(\C=C\C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 NBTHWOKIJJBULB-FAAWYNLUSA-N 0.000 description 3
- MIWLXSRIICDTEX-JWPFQLSCSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(5-nitrofuran-2-yl)prop-2-enamide Chemical compound O1C([N+](=O)[O-])=CC=C1\C=C\C(=O)N[C@@H]1C(CC2)CCN2C1 MIWLXSRIICDTEX-JWPFQLSCSA-N 0.000 description 3
- ATNVHCFFVIVLSM-OOPCZODUSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(furan-2-yl)prop-2-enamide Chemical compound N([C@@H]1C2CCN(CC2)C1)C(=O)\C=C\C1=CC=CO1 ATNVHCFFVIVLSM-OOPCZODUSA-N 0.000 description 3
- WMUJNOJUYWXQSG-AORQRIRUSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(furan-3-yl)prop-2-enamide Chemical compound N([C@@H]1C2CCN(CC2)C1)C(=O)\C=C\C=1C=COC=1 WMUJNOJUYWXQSG-AORQRIRUSA-N 0.000 description 3
- QDJIWDUPQLKWAA-RGDDUWESSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-[3-(trifluoromethyl)phenyl]prop-2-enamide Chemical compound FC(F)(F)C1=CC=CC(\C=C\C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 QDJIWDUPQLKWAA-RGDDUWESSA-N 0.000 description 3
- NZONTOQHVFUZMV-OOPCZODUSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-thiophen-2-ylprop-2-enamide Chemical compound N([C@@H]1C2CCN(CC2)C1)C(=O)\C=C\C1=CC=CS1 NZONTOQHVFUZMV-OOPCZODUSA-N 0.000 description 3
- NIJKEAAXBOXSNC-AORQRIRUSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-thiophen-3-ylprop-2-enamide Chemical compound N([C@@H]1C2CCN(CC2)C1)C(=O)\C=C\C=1C=CSC=1 NIJKEAAXBOXSNC-AORQRIRUSA-N 0.000 description 3
- ODFSOOCVJPIZNA-XHPSBEMXSA-N (z)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-phenylprop-2-enamide Chemical compound N([C@@H]1C2CCN(CC2)C1)C(=O)\C=C/C1=CC=CC=C1 ODFSOOCVJPIZNA-XHPSBEMXSA-N 0.000 description 3
- BRJQKJLCLZBQCK-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octane;prop-2-enamide Chemical class NC(=O)C=C.C1CC2CCN1CC2 BRJQKJLCLZBQCK-UHFFFAOYSA-N 0.000 description 3
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- 208000000044 Amnesia Diseases 0.000 description 3
- 208000020925 Bipolar disease Diseases 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 206010009900 Colitis ulcerative Diseases 0.000 description 3
- 208000023105 Huntington disease Diseases 0.000 description 3
- 208000020358 Learning disease Diseases 0.000 description 3
- 208000009829 Lewy Body Disease Diseases 0.000 description 3
- 201000002832 Lewy body dementia Diseases 0.000 description 3
- 206010026749 Mania Diseases 0.000 description 3
- 208000026139 Memory disease Diseases 0.000 description 3
- 206010057852 Nicotine dependence Diseases 0.000 description 3
- 229920002873 Polyethylenimine Polymers 0.000 description 3
- 208000025569 Tobacco Use disease Diseases 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 208000000323 Tourette Syndrome Diseases 0.000 description 3
- 208000016620 Tourette disease Diseases 0.000 description 3
- 201000006704 Ulcerative Colitis Diseases 0.000 description 3
- 238000005804 alkylation reaction Methods 0.000 description 3
- 239000000908 ammonium hydroxide Substances 0.000 description 3
- 208000028683 bipolar I disease Diseases 0.000 description 3
- 229940098773 bovine serum albumin Drugs 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000003638 chemical reducing agent Substances 0.000 description 3
- 230000001713 cholinergic effect Effects 0.000 description 3
- 208000010877 cognitive disease Diseases 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 125000000524 functional group Chemical group 0.000 description 3
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 3
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 description 3
- 201000003723 learning disability Diseases 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 230000006984 memory degeneration Effects 0.000 description 3
- 208000023060 memory loss Diseases 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 208000015122 neurodegenerative disease Diseases 0.000 description 3
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 230000036407 pain Effects 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 210000000225 synapse Anatomy 0.000 description 3
- AMVYAIXPAGBXOM-AATRIKPKSA-N (E)-2-(trifluoromethyl)cinnamic acid Chemical compound OC(=O)\C=C\C1=CC=CC=C1C(F)(F)F AMVYAIXPAGBXOM-AATRIKPKSA-N 0.000 description 2
- XNCRUNXWPDJHGV-BQYQJAHWSA-N (e)-2-methyl-3-phenylprop-2-enoic acid Chemical compound OC(=O)C(/C)=C/C1=CC=CC=C1 XNCRUNXWPDJHGV-BQYQJAHWSA-N 0.000 description 2
- PHZYWNWABJJERF-AATRIKPKSA-N (e)-3-(2-aminophenyl)-n-(1-azabicyclo[2.2.2]octan-3-yl)prop-2-enamide Chemical compound NC1=CC=CC=C1\C=C\C(=O)NC1C(CC2)CCN2C1 PHZYWNWABJJERF-AATRIKPKSA-N 0.000 description 2
- KJRRTHHNKJBVBO-AATRIKPKSA-N (e)-3-(2-chlorophenyl)prop-2-enoic acid Chemical compound OC(=O)\C=C\C1=CC=CC=C1Cl KJRRTHHNKJBVBO-AATRIKPKSA-N 0.000 description 2
- ZCJLOOJRNPHKAV-ONEGZZNKSA-N (e)-3-(furan-2-yl)prop-2-enoic acid Chemical compound OC(=O)\C=C\C1=CC=CO1 ZCJLOOJRNPHKAV-ONEGZZNKSA-N 0.000 description 2
- PEXWJYDPDXUVSV-BQYQJAHWSA-N (e)-3-phenylbut-2-enoic acid Chemical compound OC(=O)\C=C(/C)C1=CC=CC=C1 PEXWJYDPDXUVSV-BQYQJAHWSA-N 0.000 description 2
- VUVORVXMOLQFMO-ONEGZZNKSA-N (e)-3-pyridin-3-ylprop-2-enoic acid Chemical compound OC(=O)\C=C\C1=CC=CN=C1 VUVORVXMOLQFMO-ONEGZZNKSA-N 0.000 description 2
- HSTDTPMOYSFAIB-OWOJBTEDSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(1h-imidazol-5-yl)prop-2-enamide Chemical compound C1N(CC2)CCC2C1NC(=O)\C=C\C1=CNC=N1 HSTDTPMOYSFAIB-OWOJBTEDSA-N 0.000 description 2
- UCRCSZYDUAPEEU-SNAWJCMRSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(3-iodophenyl)prop-2-enamide Chemical compound IC1=CC=CC(\C=C\C(=O)NC2C3CCN(CC3)C2)=C1 UCRCSZYDUAPEEU-SNAWJCMRSA-N 0.000 description 2
- SYJFKEQPXPZQSF-ZZXKWVIFSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(4-iodophenyl)prop-2-enamide Chemical compound C1=CC(I)=CC=C1\C=C\C(=O)NC1C(CC2)CCN2C1 SYJFKEQPXPZQSF-ZZXKWVIFSA-N 0.000 description 2
- DXSJNKAJPNKROG-OWOJBTEDSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(5-hydroxypyridin-3-yl)prop-2-enamide Chemical compound OC1=CN=CC(\C=C\C(=O)NC2C3CCN(CC3)C2)=C1 DXSJNKAJPNKROG-OWOJBTEDSA-N 0.000 description 2
- NBTHWOKIJJBULB-NSCUHMNNSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(5-methoxypyridin-3-yl)prop-2-enamide Chemical compound COC1=CN=CC(\C=C\C(=O)NC2C3CCN(CC3)C2)=C1 NBTHWOKIJJBULB-NSCUHMNNSA-N 0.000 description 2
- MIWLXSRIICDTEX-HNQUOIGGSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(5-nitrofuran-2-yl)prop-2-enamide Chemical compound O1C([N+](=O)[O-])=CC=C1\C=C\C(=O)NC1C(CC2)CCN2C1 MIWLXSRIICDTEX-HNQUOIGGSA-N 0.000 description 2
- ATNVHCFFVIVLSM-ONEGZZNKSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(furan-2-yl)prop-2-enamide Chemical compound C1N(CC2)CCC2C1NC(=O)\C=C\C1=CC=CO1 ATNVHCFFVIVLSM-ONEGZZNKSA-N 0.000 description 2
- WMUJNOJUYWXQSG-OWOJBTEDSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(furan-3-yl)prop-2-enamide Chemical compound C1N(CC2)CCC2C1NC(=O)\C=C\C=1C=COC=1 WMUJNOJUYWXQSG-OWOJBTEDSA-N 0.000 description 2
- VYJUETVRHRXQFA-AATRIKPKSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-[2-(trifluoromethyl)phenyl]prop-2-enamide Chemical compound FC(F)(F)C1=CC=CC=C1\C=C\C(=O)NC1C(CC2)CCN2C1 VYJUETVRHRXQFA-AATRIKPKSA-N 0.000 description 2
- QDJIWDUPQLKWAA-SNAWJCMRSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-[3-(trifluoromethyl)phenyl]prop-2-enamide Chemical compound FC(F)(F)C1=CC=CC(\C=C\C(=O)NC2C3CCN(CC3)C2)=C1 QDJIWDUPQLKWAA-SNAWJCMRSA-N 0.000 description 2
- ODFSOOCVJPIZNA-VOTSOKGWSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-phenylprop-2-enamide Chemical compound C1N(CC2)CCC2C1NC(=O)\C=C\C1=CC=CC=C1 ODFSOOCVJPIZNA-VOTSOKGWSA-N 0.000 description 2
- NZONTOQHVFUZMV-ONEGZZNKSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-thiophen-2-ylprop-2-enamide Chemical compound C1N(CC2)CCC2C1NC(=O)\C=C\C1=CC=CS1 NZONTOQHVFUZMV-ONEGZZNKSA-N 0.000 description 2
- NIJKEAAXBOXSNC-OWOJBTEDSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-thiophen-3-ylprop-2-enamide Chemical compound C1N(CC2)CCC2C1NC(=O)\C=C\C=1C=CSC=1 NIJKEAAXBOXSNC-OWOJBTEDSA-N 0.000 description 2
- FKRVCWSLGVBIGB-VOTSOKGWSA-N (e)-n-(3-cyano-1-azabicyclo[2.2.2]octan-3-yl)-3-phenylprop-2-enamide Chemical compound C1N(CC2)CCC2C1(C#N)NC(=O)\C=C\C1=CC=CC=C1 FKRVCWSLGVBIGB-VOTSOKGWSA-N 0.000 description 2
- XZVQIURADIYJDK-BQYQJAHWSA-N (e)-n-(3-methyl-1-azabicyclo[2.2.2]octan-3-yl)-3-phenylprop-2-enamide Chemical compound C1N(CC2)CCC2C1(C)NC(=O)\C=C\C1=CC=CC=C1 XZVQIURADIYJDK-BQYQJAHWSA-N 0.000 description 2
- MFIWCTVYPBIGQT-JFDDCEBESA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(2-formamidophenyl)prop-2-enamide Chemical compound O=CNC1=CC=CC=C1\C=C\C(=O)N[C@@H]1C(CC2)CCN2C1 MFIWCTVYPBIGQT-JFDDCEBESA-N 0.000 description 2
- TYYMXUGFPLAOSL-RGDDUWESSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(3-bromophenyl)prop-2-enamide Chemical compound BrC1=CC=CC(\C=C\C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 TYYMXUGFPLAOSL-RGDDUWESSA-N 0.000 description 2
- WARWHFWAFGSZMP-VFQAQYNWSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(4-bromophenyl)prop-2-enamide Chemical compound C1=CC(Br)=CC=C1\C=C\C(=O)N[C@@H]1C(CC2)CCN2C1 WARWHFWAFGSZMP-VFQAQYNWSA-N 0.000 description 2
- VUDAUVWKTXMSDD-GIZXNFQBSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(4-formamidophenyl)prop-2-enamide Chemical compound C1=CC(NC=O)=CC=C1\C=C\C(=O)N[C@@H]1C(CC2)CCN2C1 VUDAUVWKTXMSDD-GIZXNFQBSA-N 0.000 description 2
- QPOFOAHKDBURCL-NNTXTVRGSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-pyridin-2-ylprop-2-enamide Chemical compound N([C@@H]1C2CCN(CC2)C1)C(=O)\C=C\C1=CC=CC=N1 QPOFOAHKDBURCL-NNTXTVRGSA-N 0.000 description 2
- IFRBWXFNEPBBKA-XGACYXMMSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-pyridin-3-ylprop-2-enamide Chemical compound N([C@@H]1C2CCN(CC2)C1)C(=O)\C=C\C1=CC=CN=C1 IFRBWXFNEPBBKA-XGACYXMMSA-N 0.000 description 2
- XELSBDUTKCSMDH-YUKKFKLSSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-pyridin-4-ylprop-2-enamide Chemical compound N([C@@H]1C2CCN(CC2)C1)C(=O)\C=C\C1=CC=NC=C1 XELSBDUTKCSMDH-YUKKFKLSSA-N 0.000 description 2
- MENCFQRKJSFDJH-VBROQKIQSA-N (e)-n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-3-(2-nitrophenyl)prop-2-enamide Chemical compound [O-][N+](=O)C1=CC=CC=C1\C=C\C(=O)N[C@H]1C(CC2)CCN2C1 MENCFQRKJSFDJH-VBROQKIQSA-N 0.000 description 2
- ODFSOOCVJPIZNA-LQYUOIDQSA-N (e)-n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-3-phenylprop-2-enamide Chemical compound N([C@H]1C2CCN(CC2)C1)C(=O)\C=C\C1=CC=CC=C1 ODFSOOCVJPIZNA-LQYUOIDQSA-N 0.000 description 2
- MGQYIEIAFOISHD-LTBFUDJGSA-N (z)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-2-fluoro-3-phenylprop-2-enamide Chemical compound N([C@@H]1C2CCN(CC2)C1)C(=O)C(/F)=C/C1=CC=CC=C1 MGQYIEIAFOISHD-LTBFUDJGSA-N 0.000 description 2
- QODFPISBGYJKDV-XHPSBEMXSA-N (z)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(2-methoxyphenyl)prop-2-enamide Chemical compound COC1=CC=CC=C1\C=C/C(=O)N[C@@H]1C(CC2)CCN2C1 QODFPISBGYJKDV-XHPSBEMXSA-N 0.000 description 2
- HVWIZNLEMLWNOA-KVNDZABWSA-N (z)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-phenylbut-2-enamide Chemical compound N([C@@H]1C2CCN(CC2)C1)C(=O)/C=C(/C)C1=CC=CC=C1 HVWIZNLEMLWNOA-KVNDZABWSA-N 0.000 description 2
- PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 2
- RSWBWHPZXKLUEX-VOTSOKGWSA-N 2-Methylcinnamic Acid Chemical compound CC1=CC=CC=C1\C=C\C(O)=O RSWBWHPZXKLUEX-VOTSOKGWSA-N 0.000 description 2
- KKMZQOIASVGJQE-ONEGZZNKSA-N 2-Thiopheneacrylic acid Chemical compound OC(=O)\C=C\C1=CC=CS1 KKMZQOIASVGJQE-ONEGZZNKSA-N 0.000 description 2
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 description 2
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 2
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 description 2
- BBQDLDVSEDAYAA-AATRIKPKSA-N 2-nitrocinnamic acid Chemical compound OC(=O)\C=C\C1=CC=CC=C1[N+]([O-])=O BBQDLDVSEDAYAA-AATRIKPKSA-N 0.000 description 2
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 2
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 2
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 2
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 2
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 2
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 2
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 2
- 101000783401 Bungarus multicinctus Alpha-bungarotoxin Proteins 0.000 description 2
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 2
- 206010012335 Dependence Diseases 0.000 description 2
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 239000005909 Kieselgur Substances 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
- 241000124008 Mammalia Species 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 229930040373 Paraformaldehyde Natural products 0.000 description 2
- QQONPFPTGQHPMA-UHFFFAOYSA-N Propene Chemical compound CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 2
- 229960004373 acetylcholine Drugs 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- 230000000954 anitussive effect Effects 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 229910000085 borane Inorganic materials 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 2
- 239000012954 diazonium Substances 0.000 description 2
- AFLBAXPZSPPPIW-UHFFFAOYSA-N disodium;dioxidoboranylformonitrile Chemical compound [Na+].[Na+].[O-]B([O-])C#N AFLBAXPZSPPPIW-UHFFFAOYSA-N 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 230000004064 dysfunction Effects 0.000 description 2
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000003365 glass fiber Substances 0.000 description 2
- 210000001320 hippocampus Anatomy 0.000 description 2
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 231100001231 less toxic Toxicity 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 238000006386 neutralization reaction Methods 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- 230000009871 nonspecific binding Effects 0.000 description 2
- 238000002414 normal-phase solid-phase extraction Methods 0.000 description 2
- 230000000269 nucleophilic effect Effects 0.000 description 2
- OUSJHHILXRLTDF-UHFFFAOYSA-N octan-3-amine;dihydrochloride Chemical compound Cl.Cl.CCCCCC(N)CC OUSJHHILXRLTDF-UHFFFAOYSA-N 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 229920002866 paraformaldehyde Polymers 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- XNERWVPQCYSMLC-UHFFFAOYSA-N phenylpropiolic acid Chemical compound OC(=O)C#CC1=CC=CC=C1 XNERWVPQCYSMLC-UHFFFAOYSA-N 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 238000005932 reductive alkylation reaction Methods 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 150000004763 sulfides Chemical class 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 230000005062 synaptic transmission Effects 0.000 description 2
- 238000004809 thin layer chromatography Methods 0.000 description 2
- 230000009466 transformation Effects 0.000 description 2
- 238000000844 transformation Methods 0.000 description 2
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 2
- KVYQKWPZQKGICY-UHFFFAOYSA-N (8-methyl-8-azoniabicyclo[3.2.1]octan-3-yl)azanium;dichloride Chemical compound [Cl-].[Cl-].C1C([NH3+])CC2CCC1[NH+]2C KVYQKWPZQKGICY-UHFFFAOYSA-N 0.000 description 1
- FEGVSPGUHMGGBO-VOTSOKGWSA-N (E)-2-methoxycinnamic acid Chemical compound COC1=CC=CC=C1\C=C\C(O)=O FEGVSPGUHMGGBO-VOTSOKGWSA-N 0.000 description 1
- AFDXODALSZRGIH-QPJJXVBHSA-N (E)-3-(4-methoxyphenyl)prop-2-enoic acid Chemical compound COC1=CC=C(\C=C\C(O)=O)C=C1 AFDXODALSZRGIH-QPJJXVBHSA-N 0.000 description 1
- MPKSATATGYKQTP-UHFFFAOYSA-N (Z)-3-phenylbut-2-enamide Chemical compound CC(=CC(N)=O)C1=CC=CC=C1 MPKSATATGYKQTP-UHFFFAOYSA-N 0.000 description 1
- VTOAFAPBGXLGME-SDNWHVSQSA-N (e)-2,3-diphenylprop-2-enamide Chemical compound C=1C=CC=CC=1/C(C(=O)N)=C\C1=CC=CC=C1 VTOAFAPBGXLGME-SDNWHVSQSA-N 0.000 description 1
- MPUZDPBYKVEHNH-BQYQJAHWSA-N (e)-2-methyl-3-phenylprop-2-enamide Chemical compound NC(=O)C(/C)=C/C1=CC=CC=C1 MPUZDPBYKVEHNH-BQYQJAHWSA-N 0.000 description 1
- IOUDZAFBPDDAMK-AATRIKPKSA-N (e)-3-(2-fluorophenyl)prop-2-enoic acid Chemical compound OC(=O)\C=C\C1=CC=CC=C1F IOUDZAFBPDDAMK-AATRIKPKSA-N 0.000 description 1
- RRLUFPHCTSFKNR-DUXPYHPUSA-N (e)-3-(3,4-dichlorophenyl)prop-2-enoic acid Chemical compound OC(=O)\C=C\C1=CC=C(Cl)C(Cl)=C1 RRLUFPHCTSFKNR-DUXPYHPUSA-N 0.000 description 1
- YEMUSDCFQUBPAL-SNAWJCMRSA-N (e)-3-(3-bromophenyl)prop-2-enoic acid Chemical compound OC(=O)\C=C\C1=CC=CC(Br)=C1 YEMUSDCFQUBPAL-SNAWJCMRSA-N 0.000 description 1
- FFKGOJWPSXRALK-SNAWJCMRSA-N (e)-3-(3-chlorophenyl)prop-2-enoic acid Chemical compound OC(=O)\C=C\C1=CC=CC(Cl)=C1 FFKGOJWPSXRALK-SNAWJCMRSA-N 0.000 description 1
- RTSIUKMGSDOSTI-SNAWJCMRSA-N (e)-3-(3-fluorophenyl)prop-2-enoic acid Chemical compound OC(=O)\C=C\C1=CC=CC(F)=C1 RTSIUKMGSDOSTI-SNAWJCMRSA-N 0.000 description 1
- XQOFQTFBKOHMCW-SNAWJCMRSA-N (e)-3-(3-iodophenyl)prop-2-enoic acid Chemical compound OC(=O)\C=C\C1=CC=CC(I)=C1 XQOFQTFBKOHMCW-SNAWJCMRSA-N 0.000 description 1
- RCLFFPCOTKNDRK-ZZXKWVIFSA-N (e)-3-(4-aminophenyl)-n-(1-azabicyclo[2.2.2]octan-3-yl)prop-2-enamide Chemical compound C1=CC(N)=CC=C1\C=C\C(=O)NC1C(CC2)CCN2C1 RCLFFPCOTKNDRK-ZZXKWVIFSA-N 0.000 description 1
- CPDDDTNAMBSPRN-ZZXKWVIFSA-N (e)-3-(4-bromophenyl)prop-2-enoic acid Chemical compound OC(=O)\C=C\C1=CC=C(Br)C=C1 CPDDDTNAMBSPRN-ZZXKWVIFSA-N 0.000 description 1
- NIDLJAPEZBFHGP-ZZXKWVIFSA-N (e)-3-(4-iodophenyl)prop-2-enoic acid Chemical compound OC(=O)\C=C\C1=CC=C(I)C=C1 NIDLJAPEZBFHGP-ZZXKWVIFSA-N 0.000 description 1
- IENCUXURMYOKEK-OWOJBTEDSA-N (e)-3-(5-hydroxypyridin-3-yl)prop-2-enoic acid Chemical compound OC(=O)\C=C\C1=CN=CC(O)=C1 IENCUXURMYOKEK-OWOJBTEDSA-N 0.000 description 1
- MSXLMJSPKJQXBE-NSCUHMNNSA-N (e)-3-(5-methoxypyridin-3-yl)prop-2-enoic acid Chemical compound COC1=CN=CC(\C=C\C(O)=O)=C1 MSXLMJSPKJQXBE-NSCUHMNNSA-N 0.000 description 1
- JHAPZUDWRRBZHZ-OWOJBTEDSA-N (e)-3-(furan-3-yl)prop-2-enoic acid Chemical compound OC(=O)\C=C\C=1C=COC=1 JHAPZUDWRRBZHZ-OWOJBTEDSA-N 0.000 description 1
- MPKSATATGYKQTP-BQYQJAHWSA-N (e)-3-phenylbut-2-enamide Chemical compound NC(=O)\C=C(/C)C1=CC=CC=C1 MPKSATATGYKQTP-BQYQJAHWSA-N 0.000 description 1
- LKDFTXDJKHGCAC-SNAWJCMRSA-N (e)-3-pyridin-2-ylprop-2-enoic acid Chemical compound OC(=O)\C=C\C1=CC=CC=N1 LKDFTXDJKHGCAC-SNAWJCMRSA-N 0.000 description 1
- VYRYYUKILKRGDN-OWOJBTEDSA-N (e)-3-thiophen-3-ylprop-2-enoic acid Chemical compound OC(=O)\C=C\C=1C=CSC=1 VYRYYUKILKRGDN-OWOJBTEDSA-N 0.000 description 1
- GERXVMRTEYKZPQ-QPJJXVBHSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(4-methoxyphenyl)prop-2-enamide Chemical compound C1=CC(OC)=CC=C1\C=C\C(=O)NC1C(CC2)CCN2C1 GERXVMRTEYKZPQ-QPJJXVBHSA-N 0.000 description 1
- QPOFOAHKDBURCL-SNAWJCMRSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-pyridin-2-ylprop-2-enamide Chemical compound C1N(CC2)CCC2C1NC(=O)\C=C\C1=CC=CC=N1 QPOFOAHKDBURCL-SNAWJCMRSA-N 0.000 description 1
- IFRBWXFNEPBBKA-ONEGZZNKSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-pyridin-3-ylprop-2-enamide Chemical compound C1N(CC2)CCC2C1NC(=O)\C=C\C1=CC=CN=C1 IFRBWXFNEPBBKA-ONEGZZNKSA-N 0.000 description 1
- XELSBDUTKCSMDH-OWOJBTEDSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-pyridin-4-ylprop-2-enamide Chemical compound C1N(CC2)CCC2C1NC(=O)\C=C\C1=CC=NC=C1 XELSBDUTKCSMDH-OWOJBTEDSA-N 0.000 description 1
- QLXOOYGFEACOIW-BQYQJAHWSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-n-methyl-3-phenylprop-2-enamide Chemical compound C1N(CC2)CCC2C1N(C)C(=O)\C=C\C1=CC=CC=C1 QLXOOYGFEACOIW-BQYQJAHWSA-N 0.000 description 1
- FJJBZFQDEHWYCR-MEPUESOJSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-2,3-diphenylprop-2-enamide Chemical compound N([C@@H]1C2CCN(CC2)C1)C(=O)C(\C=1C=CC=CC=1)=C\C1=CC=CC=C1 FJJBZFQDEHWYCR-MEPUESOJSA-N 0.000 description 1
- LBVMWSPLUKLPOJ-BYIUCRAPSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-2-methyl-3-phenylprop-2-enamide Chemical compound N([C@@H]1C2CCN(CC2)C1)C(=O)C(/C)=C/C1=CC=CC=C1 LBVMWSPLUKLPOJ-BYIUCRAPSA-N 0.000 description 1
- JEZKVTBNTCBZAF-NFAHFFEMSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(2-chlorophenyl)prop-2-enamide Chemical compound ClC1=CC=CC=C1\C=C\C(=O)N[C@@H]1C(CC2)CCN2C1 JEZKVTBNTCBZAF-NFAHFFEMSA-N 0.000 description 1
- NVVYTUXHKCMTCD-MOEXGYKKSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(2-methylphenyl)prop-2-enamide Chemical compound CC1=CC=CC=C1\C=C\C(=O)N[C@@H]1C(CC2)CCN2C1 NVVYTUXHKCMTCD-MOEXGYKKSA-N 0.000 description 1
- QOFOUEFCNYRQQX-OMDKTOEGSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(3,4-dichlorophenyl)prop-2-enamide Chemical compound C1=C(Cl)C(Cl)=CC=C1\C=C\C(=O)N[C@@H]1C(CC2)CCN2C1 QOFOUEFCNYRQQX-OMDKTOEGSA-N 0.000 description 1
- OOZULDOHFTVWCS-RGDDUWESSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(3-chlorophenyl)prop-2-enamide Chemical compound ClC1=CC=CC(\C=C\C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 OOZULDOHFTVWCS-RGDDUWESSA-N 0.000 description 1
- YAUMYTQGLWXDIH-RGDDUWESSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(3-fluorophenyl)prop-2-enamide Chemical compound FC1=CC=CC(\C=C\C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 YAUMYTQGLWXDIH-RGDDUWESSA-N 0.000 description 1
- WHMOYHBOLPOUMR-JFDDCEBESA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(3-methoxyphenyl)prop-2-enamide Chemical compound COC1=CC=CC(\C=C\C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 WHMOYHBOLPOUMR-JFDDCEBESA-N 0.000 description 1
- WUSJALGTATXXGB-VFQAQYNWSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(4-chlorophenyl)prop-2-enamide Chemical compound C1=CC(Cl)=CC=C1\C=C\C(=O)N[C@@H]1C(CC2)CCN2C1 WUSJALGTATXXGB-VFQAQYNWSA-N 0.000 description 1
- GBLPTBJUUSMWLC-VFQAQYNWSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(4-fluorophenyl)prop-2-enamide Chemical compound C1=CC(F)=CC=C1\C=C\C(=O)N[C@@H]1C(CC2)CCN2C1 GBLPTBJUUSMWLC-VFQAQYNWSA-N 0.000 description 1
- GERXVMRTEYKZPQ-RRGWEWPQSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(4-methoxyphenyl)prop-2-enamide Chemical compound C1=CC(OC)=CC=C1\C=C\C(=O)N[C@@H]1C(CC2)CCN2C1 GERXVMRTEYKZPQ-RRGWEWPQSA-N 0.000 description 1
- HVWIZNLEMLWNOA-BYIUCRAPSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-phenylbut-2-enamide Chemical compound N([C@@H]1C2CCN(CC2)C1)C(=O)\C=C(/C)C1=CC=CC=C1 HVWIZNLEMLWNOA-BYIUCRAPSA-N 0.000 description 1
- ODFSOOCVJPIZNA-LFAOLKIESA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-phenylprop-2-enamide Chemical compound N([C@@H]1C2CCN(CC2)C1)C(=O)\C=C\C1=CC=CC=C1 ODFSOOCVJPIZNA-LFAOLKIESA-N 0.000 description 1
- LBVMWSPLUKLPOJ-SICOMBFOSA-N (e)-n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-2-methyl-3-phenylprop-2-enamide Chemical compound N([C@H]1C2CCN(CC2)C1)C(=O)C(/C)=C/C1=CC=CC=C1 LBVMWSPLUKLPOJ-SICOMBFOSA-N 0.000 description 1
- JEZKVTBNTCBZAF-LLYBFZRZSA-N (e)-n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-3-(2-chlorophenyl)prop-2-enamide Chemical compound ClC1=CC=CC=C1\C=C\C(=O)N[C@H]1C(CC2)CCN2C1 JEZKVTBNTCBZAF-LLYBFZRZSA-N 0.000 description 1
- NVVYTUXHKCMTCD-FYCOFBDGSA-N (e)-n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-3-(2-methylphenyl)prop-2-enamide Chemical compound CC1=CC=CC=C1\C=C\C(=O)N[C@H]1C(CC2)CCN2C1 NVVYTUXHKCMTCD-FYCOFBDGSA-N 0.000 description 1
- ATNVHCFFVIVLSM-ITDFMYJTSA-N (e)-n-[(3s)-1-azabicyclo[2.2.2]octan-3-yl]-3-(furan-2-yl)prop-2-enamide Chemical compound N([C@H]1C2CCN(CC2)C1)C(=O)\C=C\C1=CC=CO1 ATNVHCFFVIVLSM-ITDFMYJTSA-N 0.000 description 1
- TYRROLYLQRTXJW-VURMDHGXSA-N (z)-2-fluoro-3-phenylprop-2-enamide Chemical compound NC(=O)C(\F)=C\C1=CC=CC=C1 TYRROLYLQRTXJW-VURMDHGXSA-N 0.000 description 1
- QONCEXMULRJPPY-VURMDHGXSA-N (z)-2-fluoro-3-phenylprop-2-enoic acid Chemical compound OC(=O)C(\F)=C\C1=CC=CC=C1 QONCEXMULRJPPY-VURMDHGXSA-N 0.000 description 1
- FEGVSPGUHMGGBO-SREVYHEPSA-N (z)-3-(2-methoxyphenyl)prop-2-enoic acid Chemical compound COC1=CC=CC=C1\C=C/C(O)=O FEGVSPGUHMGGBO-SREVYHEPSA-N 0.000 description 1
- PEXWJYDPDXUVSV-FPLPWBNLSA-N (z)-3-phenylbut-2-enoic acid Chemical compound OC(=O)/C=C(/C)C1=CC=CC=C1 PEXWJYDPDXUVSV-FPLPWBNLSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- WGOBEWKJHHGUQX-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octane prop-2-enoic acid Chemical class C(C=C)(=O)O.N12CCC(CC1)CC2 WGOBEWKJHHGUQX-UHFFFAOYSA-N 0.000 description 1
- GXVUZYLYWKWJIM-UHFFFAOYSA-N 2-(2-aminoethoxy)ethanamine Chemical compound NCCOCCN GXVUZYLYWKWJIM-UHFFFAOYSA-N 0.000 description 1
- ZYHQGITXIJDDKC-UHFFFAOYSA-N 2-[2-(2-aminophenyl)ethyl]aniline Chemical group NC1=CC=CC=C1CCC1=CC=CC=C1N ZYHQGITXIJDDKC-UHFFFAOYSA-N 0.000 description 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- LWOWNIPZHGWKNR-DUXPYHPUSA-N 3-(5-nitro-2-furyl)acrylic acid Chemical compound OC(=O)\C=C\C1=CC=C([N+]([O-])=O)O1 LWOWNIPZHGWKNR-DUXPYHPUSA-N 0.000 description 1
- LZPNXAULYJPXEH-AATRIKPKSA-N 3-Methoxycinnamic acid Chemical compound COC1=CC=CC(\C=C\C(O)=O)=C1 LZPNXAULYJPXEH-AATRIKPKSA-N 0.000 description 1
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 description 1
- 125000006305 3-iodophenyl group Chemical group [H]C1=C([H])C(I)=C([H])C(*)=C1[H] 0.000 description 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 1
- UGNSMKDDFAUGFT-UHFFFAOYSA-N 4,4-dimethyl-2-phenyl-5h-1,3-oxazole Chemical compound CC1(C)COC(C=2C=CC=CC=2)=N1 UGNSMKDDFAUGFT-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- ISMMYAZSUSYVQG-ZZXKWVIFSA-N 4-Fluorocinnamic acid Chemical compound OC(=O)\C=C\C1=CC=C(F)C=C1 ISMMYAZSUSYVQG-ZZXKWVIFSA-N 0.000 description 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
- GXLIFJYFGMHYDY-ZZXKWVIFSA-N 4-chlorocinnamic acid Chemical compound OC(=O)\C=C\C1=CC=C(Cl)C=C1 GXLIFJYFGMHYDY-ZZXKWVIFSA-N 0.000 description 1
- 125000006306 4-iodophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1I 0.000 description 1
- NSXWVWBHCINPIG-UHFFFAOYSA-N 4-methoxyphenylthionophosphine sulfide Chemical class COC1=CC=C(P(=S)=S)C=C1 NSXWVWBHCINPIG-UHFFFAOYSA-N 0.000 description 1
- XMMRNCHTDONGRJ-ZZXKWVIFSA-N 4-nitrocinnamic acid Chemical compound OC(=O)\C=C\C1=CC=C([N+]([O-])=O)C=C1 XMMRNCHTDONGRJ-ZZXKWVIFSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 229930003347 Atropine Natural products 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 208000000094 Chronic Pain Diseases 0.000 description 1
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical class OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- HVWIZNLEMLWNOA-INIZCTEOSA-N N-[(3R)-1-azabicyclo[2.2.2]octan-3-yl]-3-phenylbut-2-enamide Chemical compound N([C@@H]1C2CCN(CC2)C1)C(=O)C=C(C)C1=CC=CC=C1 HVWIZNLEMLWNOA-INIZCTEOSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
- 238000006434 Ritter amidation reaction Methods 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 102000015296 acetylcholine-gated cation-selective channel activity proteins Human genes 0.000 description 1
- 108040006409 acetylcholine-gated cation-selective channel activity proteins Proteins 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 description 1
- 229960000396 atropine Drugs 0.000 description 1
- IVRMZWNICZWHMI-UHFFFAOYSA-N azide group Chemical group [N-]=[N+]=[N-] IVRMZWNICZWHMI-UHFFFAOYSA-N 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- RROBIDXNTUAHFW-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 RROBIDXNTUAHFW-UHFFFAOYSA-N 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000012267 brine Substances 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- AIXAANGOTKPUOY-UHFFFAOYSA-N carbachol Chemical compound [Cl-].C[N+](C)(C)CCOC(N)=O AIXAANGOTKPUOY-UHFFFAOYSA-N 0.000 description 1
- 229960004484 carbachol Drugs 0.000 description 1
- 150000001718 carbodiimides Chemical class 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 150000001793 charged compounds Chemical class 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 230000006949 cholinergic function Effects 0.000 description 1
- APEJMQOBVMLION-SREVYHEPSA-N cis-cinnamamide Chemical compound NC(=O)\C=C/C1=CC=CC=C1 APEJMQOBVMLION-SREVYHEPSA-N 0.000 description 1
- 230000001149 cognitive effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 238000010908 decantation Methods 0.000 description 1
- 150000001989 diazonium salts Chemical group 0.000 description 1
- MUCZHBLJLSDCSD-UHFFFAOYSA-N diisopropyl fluorophosphate Chemical compound CC(C)OP(F)(=O)OC(C)C MUCZHBLJLSDCSD-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229960005051 fluostigmine Drugs 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 230000000971 hippocampal effect Effects 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002576 ketones 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
- 239000007788 liquid Substances 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 150000002688 maleic acid derivatives Chemical class 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 238000006396 nitration reaction Methods 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 230000006340 racemization Effects 0.000 description 1
- 238000007347 radical substitution reaction Methods 0.000 description 1
- 150000003254 radicals Chemical group 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 150000003459 sulfonic acid esters Chemical class 0.000 description 1
- 230000006103 sulfonylation Effects 0.000 description 1
- 238000005694 sulfonylation reaction Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 239000004149 tartrazine Substances 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 125000005500 uronium group Chemical group 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
- BIDDLDNGQCUOJQ-SDNWHVSQSA-N α-phenylcinnamic acid Chemical compound C=1C=CC=CC=1/C(C(=O)O)=C\C1=CC=CC=C1 BIDDLDNGQCUOJQ-SDNWHVSQSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D451/00—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof
- C07D451/02—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof
- C07D451/04—Heterocyclic compounds containing 8-azabicyclo [3.2.1] octane, 9-azabicyclo [3.3.1] nonane, or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane or granatane alkaloids, scopolamine; Cyclic acetals thereof containing not further condensed 8-azabicyclo [3.2.1] octane or 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring systems, e.g. tropane; Cyclic acetals thereof with hetero atoms directly attached in position 3 of the 8-azabicyclo [3.2.1] octane or in position 7 of the 3-oxa-9-azatricyclo [3.3.1.0<2,4>] nonane ring system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/439—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/46—8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
-
- 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
- A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
- A61P25/22—Anxiolytics
-
- 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
- A61P25/24—Antidepressants
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- 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
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/34—Tobacco-abuse
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Epidemiology (AREA)
- Psychiatry (AREA)
- Emergency Medicine (AREA)
- Pain & Pain Management (AREA)
- Psychology (AREA)
- Addiction (AREA)
- Hospice & Palliative Care (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE9904176A SE9904176D0 (sv) | 1999-11-18 | 1999-11-18 | New use |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CZ20021692A3 true CZ20021692A3 (cs) | 2003-01-15 |
Family
ID=20417766
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CZ20021692A CZ20021692A3 (cs) | 1999-11-18 | 2000-11-16 | Nové N-azabicykloamidové deriváty a jejich pouľití |
Country Status (30)
| Country | Link |
|---|---|
| US (1) | US6683090B1 (enExample) |
| EP (1) | EP1233964B1 (enExample) |
| JP (1) | JP2003514818A (enExample) |
| KR (1) | KR20020058014A (enExample) |
| CN (1) | CN1217943C (enExample) |
| AR (1) | AR031680A1 (enExample) |
| AT (1) | ATE298337T1 (enExample) |
| AU (1) | AU784400B2 (enExample) |
| BG (1) | BG106680A (enExample) |
| BR (1) | BR0015624A (enExample) |
| CA (1) | CA2389604A1 (enExample) |
| CO (1) | CO5261607A1 (enExample) |
| CZ (1) | CZ20021692A3 (enExample) |
| DE (1) | DE60020994T2 (enExample) |
| DK (1) | DK1233964T3 (enExample) |
| EE (1) | EE200200251A (enExample) |
| ES (1) | ES2242653T3 (enExample) |
| HU (1) | HUP0204245A3 (enExample) |
| IL (1) | IL149374A0 (enExample) |
| IS (1) | IS6385A (enExample) |
| MX (1) | MXPA02004911A (enExample) |
| NO (1) | NO20022289L (enExample) |
| NZ (1) | NZ518571A (enExample) |
| PL (1) | PL355867A1 (enExample) |
| PT (1) | PT1233964E (enExample) |
| SE (1) | SE9904176D0 (enExample) |
| SK (1) | SK6772002A3 (enExample) |
| UA (1) | UA74172C2 (enExample) |
| WO (1) | WO2001036417A1 (enExample) |
| ZA (1) | ZA200203316B (enExample) |
Families Citing this family (65)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7214686B2 (en) | 1997-06-30 | 2007-05-08 | Targacept, Inc. | Pharmaceutical compositions and methods for effecting dopamine release |
| SE0000540D0 (sv) | 2000-02-18 | 2000-02-18 | Astrazeneca Ab | New compounds |
| WO2002016358A2 (en) * | 2000-08-18 | 2002-02-28 | Pharmacia & Upjohn Company | Quinuclidine-substituted aryl moieties for treatment of disease (nicotinic acetylcholine receptor ligands) |
| WO2002016356A2 (en) * | 2000-08-18 | 2002-02-28 | Pharmacia & Upjohn Company | Quinuclidine-substituted aryl moieties for treatment of disease (nicotinic acetylcholine receptor ligands) |
| AU2001282873A1 (en) | 2000-08-18 | 2002-03-04 | Pharmacia And Upjohn Company | Quinuclidine-substituted aryl compounds for treatment of disease |
| US6492385B2 (en) | 2000-08-18 | 2002-12-10 | Pharmacia & Upjohn Company | Quinuclidine-substituted heteroaryl moieties for treatment of disease |
| JP2004506734A (ja) * | 2000-08-21 | 2004-03-04 | ファルマシア・アンド・アップジョン・カンパニー | 疾患治療用のキヌクリド置換ヘテロアリール部分 |
| WO2002017358A2 (en) * | 2000-08-21 | 2002-02-28 | Pharmacia & Upjohn Company | Quinuclidine-substituted heteroaryl moieties for treatment of disease (nicotinic acetylcholine receptor antagonists) |
| US6599916B2 (en) | 2000-08-21 | 2003-07-29 | Pharmacia & Upjohn Company | Quinuclidine-substituted heteroaryl moieties for treatment of disease |
| PE20021019A1 (es) | 2001-04-19 | 2002-11-13 | Upjohn Co | Grupos azabiciclicos sustituidos |
| 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 |
| EP1406900B1 (en) * | 2001-07-06 | 2006-10-04 | Neurosearch A/S | Novel compounds, their preparation and use |
| US6562816B2 (en) | 2001-08-24 | 2003-05-13 | Pharmacia & Upjohn Company | Substituted-heteroaryl-7-aza[2.2.1]bicycloheptanes for the treatment of disease |
| EA007429B1 (ru) * | 2001-10-02 | 2006-10-27 | Фармация Энд Апджон Компани | Азабициклические замещённые конденсированные гетероарильные соединения |
| EP1453828A2 (en) * | 2001-10-16 | 2004-09-08 | AstraZeneca AB | Azabicyclic compounds for the treatment of fibromyalgia syndrome |
| US6849620B2 (en) | 2001-10-26 | 2005-02-01 | Pfizer Inc | N-(azabicyclo moieties)-substituted hetero-bicyclic aromatic compounds for the treatment of disease |
| JP2005511574A (ja) * | 2001-10-26 | 2005-04-28 | ファルマシア アンド アップジョン カンパニー リミティド ライアビリティー カンパニー | Ｎａｃｈｒアゴニストとしてのｎ−アザビシクロ−置換ヘテロ二環式カルボキサミド |
| CA2466375A1 (en) * | 2001-11-08 | 2003-05-15 | Pharmacia & Upjohn Company | Azabicyclic-substituted-heteroaryl compounds for the treatment of disease |
| MXPA04004373A (es) | 2001-11-09 | 2004-08-11 | Upjohn Co | Compuestos heterociclicos condensados con fenilo azabiciclo para el tratamiento de enfermedades. |
| CA2470567A1 (en) | 2001-12-14 | 2003-06-26 | Targacept, Inc. | Methods and compositions for treatment of central nervous system disorders |
| DE10164139A1 (de) | 2001-12-27 | 2003-07-10 | Bayer Ag | 2-Heteroarylcarbonsäureamide |
| US6852716B2 (en) | 2002-02-15 | 2005-02-08 | Pfizer Inc | Substituted-aryl compounds for treatment of disease |
| CA2476681A1 (en) * | 2002-02-19 | 2003-08-28 | Bruce N. Rogers | Fused bicyclic-n-bridged-heteroaromatic carboxamides for the treatment of disease |
| MXPA04008152A (es) | 2002-02-19 | 2005-09-08 | Upjohn Co | Compuestos azabiciclicos para el tratamiento de enfermedades. |
| EP1513839B1 (en) | 2002-05-30 | 2006-07-26 | Neurosearch A/S | 3-substituted quinuclidines and their use |
| US7176198B2 (en) | 2002-08-01 | 2007-02-13 | Pfizer Inc. | 1H-pyrazole and 1H-pyrrole-azabicyclic compounds for the treatment of disease |
| JP2006501246A (ja) | 2002-08-30 | 2006-01-12 | メモリー・ファーマシューティカルズ・コーポレイション | 神経変性疾患の治療において有用なアナバセイン誘導体 |
| GB0220581D0 (en) | 2002-09-04 | 2002-10-09 | Novartis Ag | Organic Compound |
| AU2003276919B2 (en) | 2002-09-25 | 2013-05-16 | Memory Pharmaceuticals Corporation | Indazoles, benzothiazoles, and benzoisothiazoles, and preparation and uses thereof |
| MXPA05005666A (es) * | 2002-12-11 | 2005-07-26 | Pharmacia & Upjohn Co Llc | Tratamiento de enfermedades con combinaciones de agonistas del receptor nicotinico de acetilcolina alfa-7 y otros compuestos. |
| SI1678172T1 (sl) | 2003-10-15 | 2010-04-30 | Targacept Inc | AzabicikliŽŤne spojine za lajšanje boleŽŤine in zdravljenje motenj centralnega ĹľivŽŤnega sistema |
| US20050234095A1 (en) | 2004-03-25 | 2005-10-20 | Wenge Xie | Indazoles, benzothiazoles, benzoisothiazoles, benzisoxazoles, and preparation and uses thereof |
| AR049401A1 (es) | 2004-06-18 | 2006-07-26 | Novartis Ag | Aza-biciclononanos |
| GB0415746D0 (en) | 2004-07-14 | 2004-08-18 | Novartis Ag | Organic compounds |
| DE602006017235D1 (de) | 2005-08-22 | 2010-11-11 | Targacept Inc | Heteroarylsubstituierte diazatricycloalkane, verfahren zu deren herstellung und deren anwendung |
| WO2007037258A1 (ja) * | 2005-09-28 | 2007-04-05 | Kumamoto University | 注意欠陥・多動性障害の治療薬 |
| GB0521508D0 (en) | 2005-10-21 | 2005-11-30 | Novartis Ag | Organic compounds |
| GB0525672D0 (en) | 2005-12-16 | 2006-01-25 | Novartis Ag | Organic compounds |
| GB0525673D0 (en) | 2005-12-16 | 2006-01-25 | Novartis Ag | Organic compounds |
| WO2008008884A2 (en) * | 2006-07-12 | 2008-01-17 | Cornell Research Foundation, Inc. | Inhibition of beta-amyloid peptide aggregation |
| TW200901974A (en) | 2007-01-16 | 2009-01-16 | Wyeth Corp | Compounds, compositions, and methods of making and using them |
| SA08290475B1 (ar) | 2007-08-02 | 2013-06-22 | Targacept Inc | (2s، 3r)-n-(2-((3-بيردينيل)ميثيل)-1-آزا بيسيكلو[2، 2، 2]أوكت-3-يل)بنزو فيوران-2-كربوكساميد، وصور أملاحه الجديدة وطرق استخدامه |
| CN104193741B (zh) | 2007-10-01 | 2016-08-24 | 阿尔法梅根有限责任公司 | 作为α7-烟碱乙酰胆碱受体配体的奎宁环-4-基甲基1H-吲哚-3-甲酸酯衍生物 |
| RU2481123C2 (ru) | 2008-02-13 | 2013-05-10 | Таргасепт, Инк. | Комбинация агонистов альфа 7 никотиновых рецепторов и антипсихотических средств |
| TW201031664A (en) | 2009-01-26 | 2010-09-01 | Targacept Inc | Preparation and therapeutic applications of (2S,3R)-N-2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)-3,5-difluorobenzamide |
| JP5749797B2 (ja) | 2010-05-17 | 2015-07-15 | フォルム ファーマシューティカルズ、インコーポレイテッド | （ｒ）−７−クロロ−ｎ−（キヌクリジン−３−イル）ベンゾ［ｂ］チオフェン−２−カルボキサミド塩酸塩一水和物の結晶形 |
| FR2974365B1 (fr) * | 2011-04-20 | 2017-08-25 | Centre Nat De La Rech Scient (C N R S) | 1,2,3-triazoles 1,4-disubstituees, leurs procedes de preparation et leurs utilisations diagnostiques et therapeutiques |
| WO2012177856A2 (en) * | 2011-06-21 | 2012-12-27 | Adispell, Inc. | Cognition modification |
| GB201111705D0 (en) | 2011-07-07 | 2011-08-24 | Takeda Pharmaceutical | Compounds and their use |
| GB201111704D0 (en) | 2011-07-07 | 2011-08-24 | Takeda Pharmaceutical | Novel compounds |
| JO3115B1 (ar) | 2011-08-22 | 2017-09-20 | Takeda Pharmaceuticals Co | مركبات بيريدازينون واستخدامها كمثبطات daao |
| CA2872005A1 (en) | 2012-05-08 | 2013-11-14 | Forum Pharmaceuticals, Inc. | Methods of maintaining, treating or improving cognitive function |
| GB201209587D0 (en) | 2012-05-30 | 2012-07-11 | Takeda Pharmaceutical | Therapeutic compounds |
| JP6478923B2 (ja) | 2013-02-07 | 2019-03-06 | ヘプタレス セラピューティクス リミテッドＨｅｐｔａｒｅｓ Ｔｈｅｒａｐｅｕｔｉｃｓ Ｌｉｍｉｔｅｄ | ムスカリンｍ４受容体アゴニストとしてのピペリジン−１−イル及びアゼピン−１−イルカルボキシレート |
| EA029430B1 (ru) | 2013-06-21 | 2018-03-30 | Такеда Фармасьютикл Компани Лимитед | Производные 1-сульфонилпиперидина в качестве модуляторов рецепторов прокинетицина |
| GB201314286D0 (en) | 2013-08-08 | 2013-09-25 | Takeda Pharmaceutical | Therapeutic Compounds |
| GB201318222D0 (en) | 2013-10-15 | 2013-11-27 | Takeda Pharmaceutical | Novel compounds |
| GB201320905D0 (en) | 2013-11-27 | 2014-01-08 | Takeda Pharmaceutical | Therapeutic compounds |
| TW201613864A (en) | 2014-02-20 | 2016-04-16 | Takeda Pharmaceutical | Novel compounds |
| US9434724B2 (en) | 2014-07-11 | 2016-09-06 | Alpharmagen, Llc | Quinuclidines for modulating alpha 7 activity |
| US9724340B2 (en) | 2015-07-31 | 2017-08-08 | Attenua, Inc. | Antitussive compositions and methods |
| GB201616839D0 (en) | 2016-10-04 | 2016-11-16 | Takeda Pharmaceutical Company Limited | Therapeutic compounds |
| GB201619514D0 (en) | 2016-11-18 | 2017-01-04 | Takeda Pharmaceuticals Co | Novel compounds |
| JP2021138648A (ja) | 2020-03-04 | 2021-09-16 | 武田薬品工業株式会社 | 経口固形製剤 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IT1255467B (it) | 1992-07-29 | 1995-11-02 | Dompe Farmaceutici Spa | Ammidi acriliche farmacologicamente attive |
| GB9304500D0 (en) | 1993-03-05 | 1993-04-21 | Glaxo Spa | Heterocyclic compounds |
| SK93297A3 (en) * | 1995-01-10 | 1998-02-04 | Smithkline Beecham Spa | Indole derivatives, method for their producing, pharmaceutical comosition containing the same, and their use |
-
1999
- 1999-11-18 SE SE9904176A patent/SE9904176D0/xx unknown
-
2000
- 2000-11-06 AR ARP000105840A patent/AR031680A1/es not_active Application Discontinuation
- 2000-11-16 EE EEP200200251A patent/EE200200251A/xx unknown
- 2000-11-16 PT PT00981994T patent/PT1233964E/pt unknown
- 2000-11-16 US US10/130,635 patent/US6683090B1/en not_active Expired - Fee Related
- 2000-11-16 PL PL00355867A patent/PL355867A1/xx not_active Application Discontinuation
- 2000-11-16 MX MXPA02004911A patent/MXPA02004911A/es active IP Right Grant
- 2000-11-16 EP EP00981994A patent/EP1233964B1/en not_active Expired - Lifetime
- 2000-11-16 CZ CZ20021692A patent/CZ20021692A3/cs unknown
- 2000-11-16 ES ES00981994T patent/ES2242653T3/es not_active Expired - Lifetime
- 2000-11-16 KR KR1020027006257A patent/KR20020058014A/ko not_active Ceased
- 2000-11-16 UA UA2002065003A patent/UA74172C2/uk unknown
- 2000-11-16 BR BR0015624-8A patent/BR0015624A/pt not_active IP Right Cessation
- 2000-11-16 WO PCT/SE2000/002262 patent/WO2001036417A1/en not_active Ceased
- 2000-11-16 IL IL14937400A patent/IL149374A0/xx unknown
- 2000-11-16 CA CA002389604A patent/CA2389604A1/en not_active Abandoned
- 2000-11-16 AT AT00981994T patent/ATE298337T1/de not_active IP Right Cessation
- 2000-11-16 SK SK677-2002A patent/SK6772002A3/sk unknown
- 2000-11-16 DE DE60020994T patent/DE60020994T2/de not_active Expired - Fee Related
- 2000-11-16 DK DK00981994T patent/DK1233964T3/da active
- 2000-11-16 AU AU19073/01A patent/AU784400B2/en not_active Ceased
- 2000-11-16 JP JP2001538906A patent/JP2003514818A/ja active Pending
- 2000-11-16 HU HU0204245A patent/HUP0204245A3/hu unknown
- 2000-11-16 NZ NZ518571A patent/NZ518571A/en unknown
- 2000-11-16 CN CN008184216A patent/CN1217943C/zh not_active Expired - Fee Related
- 2000-11-17 CO CO00087729A patent/CO5261607A1/es not_active Application Discontinuation
-
2002
- 2002-04-25 ZA ZA200203316A patent/ZA200203316B/xx unknown
- 2002-05-09 BG BG106680A patent/BG106680A/bg unknown
- 2002-05-14 NO NO20022289A patent/NO20022289L/no unknown
- 2002-05-15 IS IS6385A patent/IS6385A/is unknown
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CZ20021692A3 (cs) | Nové N-azabicykloamidové deriváty a jejich pouľití | |
| EP1539764B1 (en) | Aryl-substituted diazabicycloalkanes as nicotinic acetylcholine agonists. | |
| EP1539765B1 (en) | Biaryl diazabicycloalkane amides as nicotinic acetylcholine agonists | |
| RU2263114C2 (ru) | Соединения, лекарственные средства, способы лечения, способ получения соединений | |
| WO2001029034A1 (en) | Quinuclidine acrylamides | |
| IL125620A (en) | Azabicyclic esters of cereal phenylic and pyridylic acids, their preparations and medicinal preparations containing them | |
| US20070249588A1 (en) | Nicotinic Acetylcholine Receptor Ligands | |
| EP1673372B1 (en) | Non-amide nonanes | |
| JP2007515481A (ja) | ニコチン性アセチルコリンレセプターリガンド | |
| CA2592321A1 (en) | Nicotinic acetylcholine receptor ligands | |
| HK1077571B (en) | Biaryl diazabicycloalkane amides as nicotinic acetylcholine agonists | |
| HK1050007B (en) | Novel biarylcarboxamides | |
| HK1047743B (en) | New use and novel n-azabicyclo-amide derivatives |