ES2242653T3 - Nuevo uso y nuevos derivados de n-azabiciclo-amida. - Google Patents
Nuevo uso y nuevos derivados de n-azabiciclo-amida.Info
- Publication number
- ES2242653T3 ES2242653T3 ES00981994T ES00981994T ES2242653T3 ES 2242653 T3 ES2242653 T3 ES 2242653T3 ES 00981994 T ES00981994 T ES 00981994T ES 00981994 T ES00981994 T ES 00981994T ES 2242653 T3 ES2242653 T3 ES 2242653T3
- Authority
- ES
- Spain
- Prior art keywords
- oct
- azabicyclo
- propenamide
- phenylpropenamide
- compound
- 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.)
- Expired - Lifetime
Links
- -1 -CO2R7 Chemical group 0.000 claims abstract description 270
- 150000001875 compounds Chemical class 0.000 claims abstract description 93
- 239000001257 hydrogen Substances 0.000 claims abstract description 48
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 48
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 44
- 150000003839 salts Chemical class 0.000 claims abstract description 38
- 238000011282 treatment Methods 0.000 claims abstract description 30
- 150000002431 hydrogen Chemical group 0.000 claims abstract description 29
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 26
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 24
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 21
- 150000002367 halogens Chemical class 0.000 claims abstract description 21
- 125000003118 aryl group Chemical group 0.000 claims abstract description 20
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 20
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 15
- 239000001301 oxygen Substances 0.000 claims abstract description 15
- 239000011593 sulfur Substances 0.000 claims abstract description 15
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 14
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 14
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 14
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 14
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 13
- 125000001424 substituent group Chemical group 0.000 claims abstract description 11
- 208000028017 Psychotic disease Diseases 0.000 claims abstract description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000003814 drug Substances 0.000 claims abstract description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 8
- 238000002360 preparation method Methods 0.000 claims abstract description 6
- 101100240518 Caenorhabditis elegans nhr-12 gene Proteins 0.000 claims abstract description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 3
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 claims description 46
- 239000000203 mixture Substances 0.000 claims description 36
- 208000035475 disorder Diseases 0.000 claims description 31
- APEJMQOBVMLION-VOTSOKGWSA-N trans-cinnamamide Chemical compound NC(=O)\C=C\C1=CC=CC=C1 APEJMQOBVMLION-VOTSOKGWSA-N 0.000 claims description 28
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 claims description 18
- 229960002715 nicotine Drugs 0.000 claims description 18
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 claims description 18
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 14
- 239000008194 pharmaceutical composition Substances 0.000 claims description 14
- 125000003342 alkenyl group Chemical group 0.000 claims description 12
- 125000000304 alkynyl group Chemical group 0.000 claims description 12
- 125000004429 atom Chemical group 0.000 claims description 12
- 201000010099 disease Diseases 0.000 claims description 12
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 11
- 208000016620 Tourette disease Diseases 0.000 claims description 11
- 208000019901 Anxiety disease Diseases 0.000 claims description 10
- 230000036506 anxiety Effects 0.000 claims description 10
- 230000036407 pain Effects 0.000 claims description 10
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- 201000000980 schizophrenia Diseases 0.000 claims description 10
- 208000000044 Amnesia Diseases 0.000 claims description 9
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 9
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- 208000026139 Memory disease Diseases 0.000 claims description 9
- 208000036626 Mental retardation Diseases 0.000 claims description 9
- 208000018737 Parkinson disease Diseases 0.000 claims description 9
- 208000000323 Tourette Syndrome Diseases 0.000 claims description 9
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 9
- 230000001713 cholinergic effect Effects 0.000 claims description 9
- 208000013403 hyperactivity Diseases 0.000 claims description 9
- 230000006984 memory degeneration Effects 0.000 claims description 9
- 208000023060 memory loss Diseases 0.000 claims description 9
- 210000000225 synapse Anatomy 0.000 claims description 9
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 8
- 208000020925 Bipolar disease Diseases 0.000 claims description 8
- 206010012289 Dementia Diseases 0.000 claims description 8
- 208000028683 bipolar I disease Diseases 0.000 claims description 8
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 8
- 208000024827 Alzheimer disease Diseases 0.000 claims description 7
- 210000004558 lewy body Anatomy 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- ZYHQGITXIJDDKC-UHFFFAOYSA-N 2-[2-(2-aminophenyl)ethyl]aniline Chemical group NC1=CC=CC=C1CCC1=CC=CC=C1N ZYHQGITXIJDDKC-UHFFFAOYSA-N 0.000 claims description 6
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 6
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 claims description 6
- 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 claims description 6
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 6
- 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 claims description 5
- 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 claims description 5
- 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 claims description 5
- 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 claims description 5
- 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 claims description 5
- 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 claims description 5
- 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 claims description 5
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 5
- 125000006305 3-iodophenyl group Chemical group [H]C1=C([H])C(I)=C([H])C(*)=C1[H] 0.000 claims description 5
- MPKSATATGYKQTP-UHFFFAOYSA-N (Z)-3-phenylbut-2-enamide Chemical compound CC(=CC(N)=O)C1=CC=CC=C1 MPKSATATGYKQTP-UHFFFAOYSA-N 0.000 claims 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 claims description 4
- 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 claims description 4
- 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 claims description 4
- 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 claims description 4
- 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 claims description 4
- 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 claims description 4
- 229940079593 drug Drugs 0.000 claims description 4
- 230000000391 smoking effect Effects 0.000 claims description 4
- 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 claims description 3
- 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 claims description 3
- 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 claims description 3
- 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 claims description 3
- 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 claims description 3
- 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 claims description 3
- 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 claims description 3
- 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 claims description 3
- 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 claims description 3
- 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 claims description 3
- 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 claims description 3
- 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 claims description 3
- 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 claims description 3
- 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 claims description 3
- 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 claims description 3
- 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 claims description 3
- 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 claims description 3
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims description 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 3
- 230000000626 neurodegenerative effect Effects 0.000 claims description 3
- 230000005586 smoking cessation Effects 0.000 claims description 3
- 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 claims description 2
- 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 claims description 2
- MPKSATATGYKQTP-BQYQJAHWSA-N (e)-3-phenylbut-2-enamide Chemical compound NC(=O)\C=C(/C)C1=CC=CC=C1 MPKSATATGYKQTP-BQYQJAHWSA-N 0.000 claims description 2
- 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 claims description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000006275 3-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C([H])C(*)=C1[H] 0.000 claims description 2
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 2
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 2
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
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- 125000006306 4-iodophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1I 0.000 claims description 2
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- APEJMQOBVMLION-SREVYHEPSA-N cis-cinnamamide Chemical compound NC(=O)\C=C/C1=CC=CC=C1 APEJMQOBVMLION-SREVYHEPSA-N 0.000 claims description 2
- 239000003701 inert diluent Substances 0.000 claims description 2
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 2
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- KUANXHFSYXKVOB-ZZXKWVIFSA-N (e)-3-(4-aminophenyl)prop-2-enamide Chemical compound NC(=O)\C=C\C1=CC=C(N)C=C1 KUANXHFSYXKVOB-ZZXKWVIFSA-N 0.000 claims 1
- 238000002560 therapeutic procedure Methods 0.000 claims 1
- 125000004434 sulfur atom Chemical group 0.000 abstract description 6
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 abstract 2
- 125000004399 C1-C4 alkenyl group Chemical group 0.000 abstract 2
- 238000000034 method Methods 0.000 description 56
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
- 239000012458 free base Substances 0.000 description 47
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 42
- 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 34
- 239000003480 eluent Substances 0.000 description 28
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 27
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 27
- 239000000243 solution Substances 0.000 description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 21
- 239000000741 silica gel Substances 0.000 description 21
- 229910002027 silica gel Inorganic materials 0.000 description 21
- 238000004587 chromatography analysis Methods 0.000 description 20
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 18
- 239000007787 solid Substances 0.000 description 18
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- 206010067889 Dementia with Lewy bodies Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 1
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- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
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- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 1
- 150000003926 acrylamides Chemical class 0.000 description 1
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- 235000019270 ammonium chloride Nutrition 0.000 description 1
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- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 1
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
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- 125000004122 cyclic group Chemical group 0.000 description 1
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- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
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- VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 1
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- 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
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- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
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- NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 1
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- 238000001819 mass spectrum Methods 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing 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
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- 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
- JASMWYNKLTULAN-UHFFFAOYSA-N octan-3-amine Chemical compound CCCCCC(N)CC JASMWYNKLTULAN-UHFFFAOYSA-N 0.000 description 1
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- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- SBYHFKPVCBCYGV-UHFFFAOYSA-N quinuclidine Chemical compound C1CC2CCN1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-N 0.000 description 1
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- 229910052708 sodium Inorganic materials 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
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- 235000012222 talc Nutrition 0.000 description 1
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- LOIYMIARKYCTBW-OWOJBTEDSA-N trans-urocanic acid Chemical compound OC(=O)\C=C\C1=CNC=N1 LOIYMIARKYCTBW-OWOJBTEDSA-N 0.000 description 1
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- 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
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- 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
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- 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
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- 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
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- 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
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- 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
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- 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)
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- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
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- Chemical Kinetics & Catalysis (AREA)
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- Nitrogen Condensed Heterocyclic Rings (AREA)
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| SE9904176 | 1999-11-18 | ||
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| ES2242653T3 true ES2242653T3 (es) | 2005-11-16 |
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| ES00981994T Expired - Lifetime ES2242653T3 (es) | 1999-11-18 | 2000-11-16 | Nuevo uso y nuevos derivados de n-azabiciclo-amida. |
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| 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 |
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| 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 |
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1999
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- 2000-11-16 US US10/130,635 patent/US6683090B1/en not_active Expired - Fee Related
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