DE60005054T2 - Chinuclidin-acrylamide - Google Patents
Chinuclidin-acrylamide Download PDFInfo
- Publication number
- DE60005054T2 DE60005054T2 DE60005054T DE60005054T DE60005054T2 DE 60005054 T2 DE60005054 T2 DE 60005054T2 DE 60005054 T DE60005054 T DE 60005054T DE 60005054 T DE60005054 T DE 60005054T DE 60005054 T2 DE60005054 T2 DE 60005054T2
- Authority
- DE
- Germany
- Prior art keywords
- azabicyclo
- oct
- propenamide
- methyl
- pyridylthio
- 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
- BRJQKJLCLZBQCK-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octane;prop-2-enamide Chemical compound NC(=O)C=C.C1CC2CCN1CC2 BRJQKJLCLZBQCK-UHFFFAOYSA-N 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 89
- 238000011282 treatment Methods 0.000 claims abstract description 26
- 150000003839 salts Chemical class 0.000 claims abstract description 25
- 238000011321 prophylaxis Methods 0.000 claims abstract description 20
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 15
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 10
- 208000028017 Psychotic disease Diseases 0.000 claims abstract description 6
- 238000002560 therapeutic procedure Methods 0.000 claims abstract description 3
- -1 CO 2 R 5 Chemical group 0.000 claims description 28
- 125000003118 aryl group Chemical group 0.000 claims description 16
- 125000001072 heteroaryl group Chemical group 0.000 claims description 15
- 239000001257 hydrogen Substances 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- 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 claims description 10
- 102000019315 Nicotinic acetylcholine receptors Human genes 0.000 claims description 10
- 108050006807 Nicotinic acetylcholine receptors Proteins 0.000 claims description 10
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- 229960002715 nicotine Drugs 0.000 claims description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 150000002431 hydrogen Chemical class 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 125000004434 sulfur atom Chemical group 0.000 claims description 8
- 208000024827 Alzheimer disease Diseases 0.000 claims description 7
- 201000010099 disease Diseases 0.000 claims description 7
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 7
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 claims description 6
- 125000006650 (C2-C4) alkynyl group Chemical group 0.000 claims description 6
- 208000002193 Pain Diseases 0.000 claims description 6
- 201000000980 schizophrenia Diseases 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 claims description 5
- KZSCMMXQCHXNIV-PPOCWRSBSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-pyridin-2-ylsulfanylprop-2-enamide Chemical compound N([C@@H]1C2CCN(CC2)C1)C(=O)\C=C\SC1=CC=CC=N1 KZSCMMXQCHXNIV-PPOCWRSBSA-N 0.000 claims description 5
- KZSCMMXQCHXNIV-HKBVPSITSA-N (z)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-pyridin-2-ylsulfanylprop-2-enamide Chemical compound N([C@@H]1C2CCN(CC2)C1)C(=O)\C=C/SC1=CC=CC=N1 KZSCMMXQCHXNIV-HKBVPSITSA-N 0.000 claims description 5
- GJKBMIXSYCLYRG-REPPVQDKSA-N (z)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-pyrimidin-2-ylsulfanylprop-2-enamide Chemical compound N([C@@H]1C2CCN(CC2)C1)C(=O)\C=C/SC1=NC=CC=N1 GJKBMIXSYCLYRG-REPPVQDKSA-N 0.000 claims description 5
- 208000019901 Anxiety disease Diseases 0.000 claims description 5
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 claims description 5
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 claims description 5
- 208000020925 Bipolar disease Diseases 0.000 claims description 5
- 208000019888 Circadian rhythm sleep disease Diseases 0.000 claims description 5
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 208000001456 Jet Lag Syndrome Diseases 0.000 claims description 5
- 208000009829 Lewy Body Disease Diseases 0.000 claims description 5
- 201000002832 Lewy body dementia Diseases 0.000 claims description 5
- 206010026749 Mania Diseases 0.000 claims description 5
- 206010057852 Nicotine dependence Diseases 0.000 claims description 5
- 208000018737 Parkinson disease Diseases 0.000 claims description 5
- 208000025569 Tobacco Use disease Diseases 0.000 claims description 5
- 208000000323 Tourette Syndrome Diseases 0.000 claims description 5
- 208000016620 Tourette disease Diseases 0.000 claims description 5
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 5
- 230000036506 anxiety Effects 0.000 claims description 5
- 208000028683 bipolar I disease Diseases 0.000 claims description 5
- 208000033915 jet lag type circadian rhythm sleep disease Diseases 0.000 claims description 5
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 claims description 5
- 230000036407 pain Effects 0.000 claims description 5
- ICLMIHKBDLBDCI-LHXVZLOVSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-([1,3]thiazolo[4,5-b]pyridin-2-ylsulfanyl)prop-2-enamide Chemical compound C1=CC=C2SC(S/C=C/C(N[C@@H]3C4CCN(CC4)C3)=O)=NC2=N1 ICLMIHKBDLBDCI-LHXVZLOVSA-N 0.000 claims description 4
- 208000000044 Amnesia Diseases 0.000 claims description 4
- 208000023105 Huntington disease Diseases 0.000 claims description 4
- 230000001713 cholinergic effect Effects 0.000 claims description 4
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 4
- 230000005586 smoking cessation Effects 0.000 claims description 4
- 210000000225 synapse Anatomy 0.000 claims description 4
- JQEIDFKXAIOCOT-RMKNXTFCSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(3-fluorophenyl)sulfanylprop-2-enamide Chemical compound FC1=CC=CC(S\C=C\C(=O)NC2C3CCN(CC3)C2)=C1 JQEIDFKXAIOCOT-RMKNXTFCSA-N 0.000 claims description 3
- OVBCUYMXSLVZNW-RNVIBTMRSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(1,3-benzothiazol-2-ylsulfanyl)prop-2-enamide Chemical compound C1=CC=C2SC(S/C=C/C(N[C@@H]3C4CCN(CC4)C3)=O)=NC2=C1 OVBCUYMXSLVZNW-RNVIBTMRSA-N 0.000 claims description 3
- DFRCDJNMANEUOX-RNVIBTMRSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(1,3-benzoxazol-2-ylsulfanyl)prop-2-enamide Chemical compound C1=CC=C2OC(S/C=C/C(N[C@@H]3C4CCN(CC4)C3)=O)=NC2=C1 DFRCDJNMANEUOX-RNVIBTMRSA-N 0.000 claims description 3
- ISFXODZDHSDPLN-KFRNIWOLSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(1-methylimidazol-2-yl)sulfanylprop-2-enamide Chemical compound CN1C=CN=C1S\C=C\C(=O)N[C@@H]1C(CC2)CCN2C1 ISFXODZDHSDPLN-KFRNIWOLSA-N 0.000 claims description 3
- OCAWQQJWTRIKGZ-AEBAWRHJSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(1h-imidazol-2-ylsulfanyl)prop-2-enamide Chemical compound N([C@@H]1C2CCN(CC2)C1)C(=O)\C=C\SC1=NC=CN1 OCAWQQJWTRIKGZ-AEBAWRHJSA-N 0.000 claims description 3
- LTYPMDPWOZGHRI-ZHZWZMEUSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(2-methoxyphenyl)sulfanylprop-2-enamide Chemical compound COC1=CC=CC=C1S\C=C\C(=O)N[C@@H]1C(CC2)CCN2C1 LTYPMDPWOZGHRI-ZHZWZMEUSA-N 0.000 claims description 3
- VRAGHHQHEMRZLW-NEXMIYJRSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(2-methylfuran-3-yl)sulfanylprop-2-enamide Chemical compound O1C=CC(S\C=C\C(=O)N[C@@H]2C3CCN(CC3)C2)=C1C VRAGHHQHEMRZLW-NEXMIYJRSA-N 0.000 claims description 3
- KDQHLQDGSUEZLO-SHQCLWGWSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(2-methylphenyl)sulfanylprop-2-enamide Chemical compound CC1=CC=CC=C1S\C=C\C(=O)N[C@@H]1C(CC2)CCN2C1 KDQHLQDGSUEZLO-SHQCLWGWSA-N 0.000 claims description 3
- KDTOXPBRVFGSBE-JCVNQNCUSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(3-methoxyphenyl)sulfanylprop-2-enamide Chemical compound COC1=CC=CC(S\C=C\C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 KDTOXPBRVFGSBE-JCVNQNCUSA-N 0.000 claims description 3
- WLZQYKJPCDLBLY-JCVNQNCUSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(3-methylphenyl)sulfanylprop-2-enamide Chemical compound CC1=CC=CC(S\C=C\C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 WLZQYKJPCDLBLY-JCVNQNCUSA-N 0.000 claims description 3
- KTQRXHIDICAXBQ-VSGCLNPGSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(4-fluorophenyl)sulfanylprop-2-enamide Chemical compound C1=CC(F)=CC=C1S\C=C\C(=O)N[C@@H]1C(CC2)CCN2C1 KTQRXHIDICAXBQ-VSGCLNPGSA-N 0.000 claims description 3
- SCMNIXVFVRESKS-KXKDPZRNSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(4-methoxyphenyl)sulfanylprop-2-enamide Chemical compound C1=CC(OC)=CC=C1S\C=C\C(=O)N[C@@H]1C(CC2)CCN2C1 SCMNIXVFVRESKS-KXKDPZRNSA-N 0.000 claims description 3
- HFGGWDUKVDQHAF-KXKDPZRNSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(4-methylphenyl)sulfanylprop-2-enamide Chemical compound C1=CC(C)=CC=C1S\C=C\C(=O)N[C@@H]1C(CC2)CCN2C1 HFGGWDUKVDQHAF-KXKDPZRNSA-N 0.000 claims description 3
- JWTLOTLUZAUDNW-ZPMKCOPCSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]prop-2-enamide Chemical compound S1C(C)=NN=C1S\C=C\C(=O)N[C@@H]1C(CC2)CCN2C1 JWTLOTLUZAUDNW-ZPMKCOPCSA-N 0.000 claims description 3
- PESOSIYLBKVXMY-SEIPJRMCSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-pyridin-4-ylsulfanylprop-2-enamide Chemical compound N([C@@H]1C2CCN(CC2)C1)C(=O)\C=C\SC1=CC=NC=C1 PESOSIYLBKVXMY-SEIPJRMCSA-N 0.000 claims description 3
- GJKBMIXSYCLYRG-KFRNIWOLSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-pyrimidin-2-ylsulfanylprop-2-enamide Chemical compound N([C@@H]1C2CCN(CC2)C1)C(=O)\C=C\SC1=NC=CC=N1 GJKBMIXSYCLYRG-KFRNIWOLSA-N 0.000 claims description 3
- WNQKTIKCUDTAKX-LHXVZLOVSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-thiophen-2-ylsulfanylprop-2-enamide Chemical compound N([C@@H]1C2CCN(CC2)C1)C(=O)\C=C\SC1=CC=CS1 WNQKTIKCUDTAKX-LHXVZLOVSA-N 0.000 claims description 3
- OVBCUYMXSLVZNW-YHAOYDPOSA-N (z)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(1,3-benzothiazol-2-ylsulfanyl)prop-2-enamide Chemical compound C1=CC=C2SC(S\C=C/C(N[C@@H]3C4CCN(CC4)C3)=O)=NC2=C1 OVBCUYMXSLVZNW-YHAOYDPOSA-N 0.000 claims description 3
- DFRCDJNMANEUOX-YHAOYDPOSA-N (z)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(1,3-benzoxazol-2-ylsulfanyl)prop-2-enamide Chemical compound C1=CC=C2OC(S\C=C/C(N[C@@H]3C4CCN(CC4)C3)=O)=NC2=C1 DFRCDJNMANEUOX-YHAOYDPOSA-N 0.000 claims description 3
- UAHBYMCLKLVWDR-UFVHFEBBSA-N (z)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(1,3-thiazol-2-ylsulfanyl)prop-2-enamide Chemical compound N([C@@H]1C2CCN(CC2)C1)C(=O)\C=C/SC1=NC=CS1 UAHBYMCLKLVWDR-UFVHFEBBSA-N 0.000 claims description 3
- ISFXODZDHSDPLN-REPPVQDKSA-N (z)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(1-methylimidazol-2-yl)sulfanylprop-2-enamide Chemical compound CN1C=CN=C1S\C=C/C(=O)N[C@@H]1C(CC2)CCN2C1 ISFXODZDHSDPLN-REPPVQDKSA-N 0.000 claims description 3
- LTYPMDPWOZGHRI-MSKHEQNASA-N (z)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(2-methoxyphenyl)sulfanylprop-2-enamide Chemical compound COC1=CC=CC=C1S\C=C/C(=O)N[C@@H]1C(CC2)CCN2C1 LTYPMDPWOZGHRI-MSKHEQNASA-N 0.000 claims description 3
- KDQHLQDGSUEZLO-QIENPNARSA-N (z)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(2-methylphenyl)sulfanylprop-2-enamide Chemical compound CC1=CC=CC=C1S\C=C/C(=O)N[C@@H]1C(CC2)CCN2C1 KDQHLQDGSUEZLO-QIENPNARSA-N 0.000 claims description 3
- JQEIDFKXAIOCOT-AJHXJQRKSA-N (z)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(3-fluorophenyl)sulfanylprop-2-enamide Chemical compound FC1=CC=CC(S\C=C/C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 JQEIDFKXAIOCOT-AJHXJQRKSA-N 0.000 claims description 3
- KDTOXPBRVFGSBE-BJIFSAINSA-N (z)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(3-methoxyphenyl)sulfanylprop-2-enamide Chemical compound COC1=CC=CC(S\C=C/C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 KDTOXPBRVFGSBE-BJIFSAINSA-N 0.000 claims description 3
- WLZQYKJPCDLBLY-BJIFSAINSA-N (z)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(3-methylphenyl)sulfanylprop-2-enamide Chemical compound CC1=CC=CC(S\C=C/C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 WLZQYKJPCDLBLY-BJIFSAINSA-N 0.000 claims description 3
- UEOWRBUHJNVLTL-XMELGKRDSA-N (z)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(4-chlorophenyl)sulfanylprop-2-enamide Chemical compound C1=CC(Cl)=CC=C1S\C=C/C(=O)N[C@@H]1C(CC2)CCN2C1 UEOWRBUHJNVLTL-XMELGKRDSA-N 0.000 claims description 3
- KTQRXHIDICAXBQ-XMELGKRDSA-N (z)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(4-fluorophenyl)sulfanylprop-2-enamide Chemical compound C1=CC(F)=CC=C1S\C=C/C(=O)N[C@@H]1C(CC2)CCN2C1 KTQRXHIDICAXBQ-XMELGKRDSA-N 0.000 claims description 3
- SCMNIXVFVRESKS-CLOOOTJHSA-N (z)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(4-methoxyphenyl)sulfanylprop-2-enamide Chemical compound C1=CC(OC)=CC=C1S\C=C/C(=O)N[C@@H]1C(CC2)CCN2C1 SCMNIXVFVRESKS-CLOOOTJHSA-N 0.000 claims description 3
- HFGGWDUKVDQHAF-CLOOOTJHSA-N (z)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(4-methylphenyl)sulfanylprop-2-enamide Chemical compound C1=CC(C)=CC=C1S\C=C/C(=O)N[C@@H]1C(CC2)CCN2C1 HFGGWDUKVDQHAF-CLOOOTJHSA-N 0.000 claims description 3
- ICLMIHKBDLBDCI-LRAPTIAOSA-N (z)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-([1,3]thiazolo[4,5-b]pyridin-2-ylsulfanyl)prop-2-enamide Chemical compound C1=CC=C2SC(S\C=C/C(N[C@@H]3C4CCN(CC4)C3)=O)=NC2=N1 ICLMIHKBDLBDCI-LRAPTIAOSA-N 0.000 claims description 3
- JWTLOTLUZAUDNW-IBHLPDHGSA-N (z)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]prop-2-enamide Chemical compound S1C(C)=NN=C1S\C=C/C(=O)N[C@@H]1C(CC2)CCN2C1 JWTLOTLUZAUDNW-IBHLPDHGSA-N 0.000 claims description 3
- UFEDAHQDKOLAQK-OHYQPGSNSA-N (z)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-[4-(trifluoromethyl)pyrimidin-2-yl]sulfanylprop-2-enamide Chemical compound FC(F)(F)C1=CC=NC(S\C=C/C(=O)N[C@@H]2C3CCN(CC3)C2)=N1 UFEDAHQDKOLAQK-OHYQPGSNSA-N 0.000 claims description 3
- VRUSTLVHEAFHJV-KVNDZABWSA-N (z)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-phenylsulfanylbut-2-enamide Chemical compound N([C@@H]1C2CCN(CC2)C1)C(=O)/C=C(/C)SC1=CC=CC=C1 VRUSTLVHEAFHJV-KVNDZABWSA-N 0.000 claims description 3
- SLIFWZQWWAUARB-SKEYYMKMSA-N (z)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-phenylsulfanylprop-2-enamide;hydrochloride Chemical compound Cl.N([C@@H]1C2CCN(CC2)C1)C(=O)\C=C/SC1=CC=CC=C1 SLIFWZQWWAUARB-SKEYYMKMSA-N 0.000 claims description 3
- PESOSIYLBKVXMY-MFNCVGGLSA-N (z)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-pyridin-4-ylsulfanylprop-2-enamide Chemical compound N([C@@H]1C2CCN(CC2)C1)C(=O)\C=C/SC1=CC=NC=C1 PESOSIYLBKVXMY-MFNCVGGLSA-N 0.000 claims description 3
- WNQKTIKCUDTAKX-LRAPTIAOSA-N (z)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-thiophen-2-ylsulfanylprop-2-enamide Chemical compound N([C@@H]1C2CCN(CC2)C1)C(=O)\C=C/SC1=CC=CS1 WNQKTIKCUDTAKX-LRAPTIAOSA-N 0.000 claims description 3
- 208000014644 Brain disease Diseases 0.000 claims description 3
- 201000004311 Gilles de la Tourette syndrome Diseases 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- OVBCUYMXSLVZNW-JXMROGBWSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(1,3-benzothiazol-2-ylsulfanyl)prop-2-enamide Chemical compound C1=CC=C2SC(S/C=C/C(NC3C4CCN(CC4)C3)=O)=NC2=C1 OVBCUYMXSLVZNW-JXMROGBWSA-N 0.000 claims description 2
- DFRCDJNMANEUOX-JXMROGBWSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(1,3-benzoxazol-2-ylsulfanyl)prop-2-enamide Chemical compound C1=CC=C2OC(S/C=C/C(NC3C4CCN(CC4)C3)=O)=NC2=C1 DFRCDJNMANEUOX-JXMROGBWSA-N 0.000 claims description 2
- ISFXODZDHSDPLN-RUDMXATFSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(1-methylimidazol-2-yl)sulfanylprop-2-enamide Chemical compound CN1C=CN=C1S\C=C\C(=O)NC1C(CC2)CCN2C1 ISFXODZDHSDPLN-RUDMXATFSA-N 0.000 claims description 2
- OCAWQQJWTRIKGZ-FPYGCLRLSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(1h-imidazol-2-ylsulfanyl)prop-2-enamide Chemical compound C1N(CC2)CCC2C1NC(=O)\C=C\SC1=NC=CN1 OCAWQQJWTRIKGZ-FPYGCLRLSA-N 0.000 claims description 2
- LTYPMDPWOZGHRI-DHZHZOJOSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(2-methoxyphenyl)sulfanylprop-2-enamide Chemical compound COC1=CC=CC=C1S\C=C\C(=O)NC1C(CC2)CCN2C1 LTYPMDPWOZGHRI-DHZHZOJOSA-N 0.000 claims description 2
- VRAGHHQHEMRZLW-WEVVVXLNSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(2-methylfuran-3-yl)sulfanylprop-2-enamide Chemical compound O1C=CC(S\C=C\C(=O)NC2C3CCN(CC3)C2)=C1C VRAGHHQHEMRZLW-WEVVVXLNSA-N 0.000 claims description 2
- WLZQYKJPCDLBLY-JXMROGBWSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(3-methylphenyl)sulfanylprop-2-enamide Chemical compound CC1=CC=CC(S\C=C\C(=O)NC2C3CCN(CC3)C2)=C1 WLZQYKJPCDLBLY-JXMROGBWSA-N 0.000 claims description 2
- KTQRXHIDICAXBQ-JXMROGBWSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(4-fluorophenyl)sulfanylprop-2-enamide Chemical compound C1=CC(F)=CC=C1S\C=C\C(=O)NC1C(CC2)CCN2C1 KTQRXHIDICAXBQ-JXMROGBWSA-N 0.000 claims description 2
- SCMNIXVFVRESKS-DHZHZOJOSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(4-methoxyphenyl)sulfanylprop-2-enamide Chemical compound C1=CC(OC)=CC=C1S\C=C\C(=O)NC1C(CC2)CCN2C1 SCMNIXVFVRESKS-DHZHZOJOSA-N 0.000 claims description 2
- KZSCMMXQCHXNIV-UXBLZVDNSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-pyridin-2-ylsulfanylprop-2-enamide Chemical compound C1N(CC2)CCC2C1NC(=O)\C=C\SC1=CC=CC=N1 KZSCMMXQCHXNIV-UXBLZVDNSA-N 0.000 claims description 2
- PESOSIYLBKVXMY-BJMVGYQFSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-pyridin-4-ylsulfanylprop-2-enamide Chemical compound C1N(CC2)CCC2C1NC(=O)\C=C\SC1=CC=NC=C1 PESOSIYLBKVXMY-BJMVGYQFSA-N 0.000 claims description 2
- GJKBMIXSYCLYRG-RUDMXATFSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-pyrimidin-2-ylsulfanylprop-2-enamide Chemical compound C1N(CC2)CCC2C1NC(=O)\C=C\SC1=NC=CC=N1 GJKBMIXSYCLYRG-RUDMXATFSA-N 0.000 claims description 2
- WNQKTIKCUDTAKX-WEVVVXLNSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-thiophen-2-ylsulfanylprop-2-enamide Chemical compound C1N(CC2)CCC2C1NC(=O)\C=C\SC1=CC=CS1 WNQKTIKCUDTAKX-WEVVVXLNSA-N 0.000 claims description 2
- OVBCUYMXSLVZNW-YFHOEESVSA-N (z)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(1,3-benzothiazol-2-ylsulfanyl)prop-2-enamide Chemical compound C1=CC=C2SC(S\C=C/C(NC3C4CCN(CC4)C3)=O)=NC2=C1 OVBCUYMXSLVZNW-YFHOEESVSA-N 0.000 claims description 2
- DFRCDJNMANEUOX-YFHOEESVSA-N (z)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(1,3-benzoxazol-2-ylsulfanyl)prop-2-enamide Chemical compound C1=CC=C2OC(S\C=C/C(NC3C4CCN(CC4)C3)=O)=NC2=C1 DFRCDJNMANEUOX-YFHOEESVSA-N 0.000 claims description 2
- UAHBYMCLKLVWDR-CLTKARDFSA-N (z)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(1,3-thiazol-2-ylsulfanyl)prop-2-enamide Chemical compound C1N(CC2)CCC2C1NC(=O)\C=C/SC1=NC=CS1 UAHBYMCLKLVWDR-CLTKARDFSA-N 0.000 claims description 2
- ISFXODZDHSDPLN-WTKPLQERSA-N (z)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(1-methylimidazol-2-yl)sulfanylprop-2-enamide Chemical compound CN1C=CN=C1S\C=C/C(=O)NC1C(CC2)CCN2C1 ISFXODZDHSDPLN-WTKPLQERSA-N 0.000 claims description 2
- LTYPMDPWOZGHRI-FLIBITNWSA-N (z)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(2-methoxyphenyl)sulfanylprop-2-enamide Chemical compound COC1=CC=CC=C1S\C=C/C(=O)NC1C(CC2)CCN2C1 LTYPMDPWOZGHRI-FLIBITNWSA-N 0.000 claims description 2
- KDQHLQDGSUEZLO-FLIBITNWSA-N (z)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(2-methylphenyl)sulfanylprop-2-enamide Chemical compound CC1=CC=CC=C1S\C=C/C(=O)NC1C(CC2)CCN2C1 KDQHLQDGSUEZLO-FLIBITNWSA-N 0.000 claims description 2
- JQEIDFKXAIOCOT-TWGQIWQCSA-N (z)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(3-fluorophenyl)sulfanylprop-2-enamide Chemical compound FC1=CC=CC(S\C=C/C(=O)NC2C3CCN(CC3)C2)=C1 JQEIDFKXAIOCOT-TWGQIWQCSA-N 0.000 claims description 2
- KDTOXPBRVFGSBE-YFHOEESVSA-N (z)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(3-methoxyphenyl)sulfanylprop-2-enamide Chemical compound COC1=CC=CC(S\C=C/C(=O)NC2C3CCN(CC3)C2)=C1 KDTOXPBRVFGSBE-YFHOEESVSA-N 0.000 claims description 2
- UEOWRBUHJNVLTL-YFHOEESVSA-N (z)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(4-chlorophenyl)sulfanylprop-2-enamide Chemical compound C1=CC(Cl)=CC=C1S\C=C/C(=O)NC1C(CC2)CCN2C1 UEOWRBUHJNVLTL-YFHOEESVSA-N 0.000 claims description 2
- KTQRXHIDICAXBQ-YFHOEESVSA-N (z)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(4-fluorophenyl)sulfanylprop-2-enamide Chemical compound C1=CC(F)=CC=C1S\C=C/C(=O)NC1C(CC2)CCN2C1 KTQRXHIDICAXBQ-YFHOEESVSA-N 0.000 claims description 2
- SCMNIXVFVRESKS-FLIBITNWSA-N (z)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(4-methoxyphenyl)sulfanylprop-2-enamide Chemical compound C1=CC(OC)=CC=C1S\C=C/C(=O)NC1C(CC2)CCN2C1 SCMNIXVFVRESKS-FLIBITNWSA-N 0.000 claims description 2
- HFGGWDUKVDQHAF-FLIBITNWSA-N (z)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(4-methylphenyl)sulfanylprop-2-enamide Chemical compound C1=CC(C)=CC=C1S\C=C/C(=O)NC1C(CC2)CCN2C1 HFGGWDUKVDQHAF-FLIBITNWSA-N 0.000 claims description 2
- ICLMIHKBDLBDCI-UITAMQMPSA-N (z)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-([1,3]thiazolo[4,5-b]pyridin-2-ylsulfanyl)prop-2-enamide Chemical compound C1=CC=C2SC(S\C=C/C(NC3C4CCN(CC4)C3)=O)=NC2=N1 ICLMIHKBDLBDCI-UITAMQMPSA-N 0.000 claims description 2
- JWTLOTLUZAUDNW-DAXSKMNVSA-N (z)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]prop-2-enamide Chemical compound S1C(C)=NN=C1S\C=C/C(=O)NC1C(CC2)CCN2C1 JWTLOTLUZAUDNW-DAXSKMNVSA-N 0.000 claims description 2
- UFEDAHQDKOLAQK-YWEYNIOJSA-N (z)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-[4-(trifluoromethyl)pyrimidin-2-yl]sulfanylprop-2-enamide Chemical compound FC(F)(F)C1=CC=NC(S\C=C/C(=O)NC2C3CCN(CC3)C2)=N1 UFEDAHQDKOLAQK-YWEYNIOJSA-N 0.000 claims description 2
- VRUSTLVHEAFHJV-QBFSEMIESA-N (z)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-phenylsulfanylbut-2-enamide Chemical compound C1N(CC2)CCC2C1NC(=O)/C=C(/C)SC1=CC=CC=C1 VRUSTLVHEAFHJV-QBFSEMIESA-N 0.000 claims description 2
- SLIFWZQWWAUARB-MKFZHGHUSA-N (z)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-phenylsulfanylprop-2-enamide;hydrochloride Chemical compound Cl.C1N(CC2)CCC2C1NC(=O)\C=C/SC1=CC=CC=C1 SLIFWZQWWAUARB-MKFZHGHUSA-N 0.000 claims description 2
- KZSCMMXQCHXNIV-POHAHGRESA-N (z)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-pyridin-2-ylsulfanylprop-2-enamide Chemical compound C1N(CC2)CCC2C1NC(=O)\C=C/SC1=CC=CC=N1 KZSCMMXQCHXNIV-POHAHGRESA-N 0.000 claims description 2
- PESOSIYLBKVXMY-YHYXMXQVSA-N (z)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-pyridin-4-ylsulfanylprop-2-enamide Chemical compound C1N(CC2)CCC2C1NC(=O)\C=C/SC1=CC=NC=C1 PESOSIYLBKVXMY-YHYXMXQVSA-N 0.000 claims description 2
- GJKBMIXSYCLYRG-WTKPLQERSA-N (z)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-pyrimidin-2-ylsulfanylprop-2-enamide Chemical compound C1N(CC2)CCC2C1NC(=O)\C=C/SC1=NC=CC=N1 GJKBMIXSYCLYRG-WTKPLQERSA-N 0.000 claims description 2
- WNQKTIKCUDTAKX-UITAMQMPSA-N (z)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-thiophen-2-ylsulfanylprop-2-enamide Chemical compound C1N(CC2)CCC2C1NC(=O)\C=C/SC1=CC=CS1 WNQKTIKCUDTAKX-UITAMQMPSA-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
- 230000007278 cognition impairment Effects 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 2
- 208000031091 Amnestic disease Diseases 0.000 claims 3
- 230000006986 amnesia Effects 0.000 claims 3
- 230000004770 neurodegeneration Effects 0.000 claims 3
- 230000004913 activation Effects 0.000 claims 2
- HFGGWDUKVDQHAF-DHZHZOJOSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(4-methylphenyl)sulfanylprop-2-enamide Chemical compound C1=CC(C)=CC=C1S\C=C\C(=O)NC1C(CC2)CCN2C1 HFGGWDUKVDQHAF-DHZHZOJOSA-N 0.000 claims 1
- JWTLOTLUZAUDNW-QPJJXVBHSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]prop-2-enamide Chemical compound S1C(C)=NN=C1S\C=C\C(=O)NC1C(CC2)CCN2C1 JWTLOTLUZAUDNW-QPJJXVBHSA-N 0.000 claims 1
- 206010012335 Dependence Diseases 0.000 claims 1
- 206010013496 Disturbance in attention Diseases 0.000 claims 1
- 238000005562 fading Methods 0.000 claims 1
- 201000003723 learning disability Diseases 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 33
- 230000006735 deficit Effects 0.000 abstract description 2
- 230000008569 process Effects 0.000 abstract description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 78
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 52
- 239000000203 mixture Substances 0.000 description 25
- 239000003480 eluent Substances 0.000 description 24
- OXHBMBUYHWMWKM-UHFFFAOYSA-N n-(4-bromo-2-methoxyphenyl)acetamide Chemical compound COC1=CC(Br)=CC=C1NC(C)=O OXHBMBUYHWMWKM-UHFFFAOYSA-N 0.000 description 24
- 238000010898 silica gel chromatography Methods 0.000 description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 10
- 239000002253 acid Substances 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 0 *C(*)=CC(N(*)N)=O Chemical compound *C(*)=CC(N(*)N)=O 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 5
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-diisopropylethylamine Substances CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 5
- 230000027455 binding Effects 0.000 description 5
- 239000003446 ligand Substances 0.000 description 5
- 229930182840 (S)-nicotine Natural products 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- 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 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 230000029936 alkylation Effects 0.000 description 4
- 238000005804 alkylation reaction Methods 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
- 229920002873 Polyethylenimine Polymers 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 102000015296 acetylcholine-gated cation-selective channel activity proteins Human genes 0.000 description 3
- 108040006409 acetylcholine-gated cation-selective channel activity proteins Proteins 0.000 description 3
- 239000000556 agonist Substances 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
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000007822 coupling agent Substances 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
- JQEIDFKXAIOCOT-PPYMECGQSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(3-fluorophenyl)sulfanylprop-2-enamide Chemical compound FC1=CC=CC(S\C=C\C(=O)N[C@@H]2C3CCN(CC3)C2)=C1 JQEIDFKXAIOCOT-PPYMECGQSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 101000783401 Bungarus multicinctus Alpha-bungarotoxin Proteins 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
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 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 2
- 150000007513 acids Chemical class 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- 208000035475 disorder Diseases 0.000 description 2
- 239000003937 drug carrier Substances 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
- 239000003365 glass fiber Substances 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
- 230000009871 nonspecific binding Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 238000005932 reductive alkylation reaction Methods 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 230000009870 specific binding Effects 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 235000002906 tartaric acid Nutrition 0.000 description 2
- 239000011975 tartaric acid Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 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 1
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
- KDQHLQDGSUEZLO-DHZHZOJOSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(2-methylphenyl)sulfanylprop-2-enamide Chemical compound CC1=CC=CC=C1S\C=C\C(=O)NC1C(CC2)CCN2C1 KDQHLQDGSUEZLO-DHZHZOJOSA-N 0.000 description 1
- KDTOXPBRVFGSBE-JXMROGBWSA-N (e)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(3-methoxyphenyl)sulfanylprop-2-enamide Chemical compound COC1=CC=CC(S\C=C\C(=O)NC2C3CCN(CC3)C2)=C1 KDTOXPBRVFGSBE-JXMROGBWSA-N 0.000 description 1
- PIHCYZAEHYGLFA-SHQCLWGWSA-N (e)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-phenylsulfanylprop-2-enamide Chemical compound N([C@@H]1C2CCN(CC2)C1)C(=O)\C=C\SC1=CC=CC=C1 PIHCYZAEHYGLFA-SHQCLWGWSA-N 0.000 description 1
- VRAGHHQHEMRZLW-UITAMQMPSA-N (z)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(2-methylfuran-3-yl)sulfanylprop-2-enamide Chemical compound O1C=CC(S\C=C/C(=O)NC2C3CCN(CC3)C2)=C1C VRAGHHQHEMRZLW-UITAMQMPSA-N 0.000 description 1
- WLZQYKJPCDLBLY-YFHOEESVSA-N (z)-n-(1-azabicyclo[2.2.2]octan-3-yl)-3-(3-methylphenyl)sulfanylprop-2-enamide Chemical compound CC1=CC=CC(S\C=C/C(=O)NC2C3CCN(CC3)C2)=C1 WLZQYKJPCDLBLY-YFHOEESVSA-N 0.000 description 1
- VRAGHHQHEMRZLW-QGOGUYACSA-N (z)-n-[(3r)-1-azabicyclo[2.2.2]octan-3-yl]-3-(2-methylfuran-3-yl)sulfanylprop-2-enamide Chemical compound O1C=CC(S\C=C/C(=O)N[C@@H]2C3CCN(CC3)C2)=C1C VRAGHHQHEMRZLW-QGOGUYACSA-N 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- PJUPKRYGDFTMTM-UHFFFAOYSA-N 1-hydroxybenzotriazole;hydrate Chemical compound O.C1=CC=C2N(O)N=NC2=C1 PJUPKRYGDFTMTM-UHFFFAOYSA-N 0.000 description 1
- GXVUZYLYWKWJIM-UHFFFAOYSA-N 2-(2-aminoethoxy)ethanamine Chemical compound NCCOCCN GXVUZYLYWKWJIM-UHFFFAOYSA-N 0.000 description 1
- UGTOKFCNYKRYPH-UHFFFAOYSA-N 3-(1,3-benzothiazol-2-ylsulfanyl)prop-2-enoic acid Chemical compound C1=CC=C2SC(SC=CC(=O)O)=NC2=C1 UGTOKFCNYKRYPH-UHFFFAOYSA-N 0.000 description 1
- KAKAJIWQXIDWEE-UHFFFAOYSA-N 3-(1,3-benzoxazol-2-ylsulfanyl)prop-2-enoic acid Chemical compound C1=CC=C2OC(SC=CC(=O)O)=NC2=C1 KAKAJIWQXIDWEE-UHFFFAOYSA-N 0.000 description 1
- MQLONYFTFGXQHS-UHFFFAOYSA-N 3-(1,3-thiazol-2-ylsulfanyl)prop-2-enoic acid Chemical compound OC(=O)C=CSC1=NC=CS1 MQLONYFTFGXQHS-UHFFFAOYSA-N 0.000 description 1
- XRYXTSHJCLIBCC-UHFFFAOYSA-N 3-(1-methylimidazol-2-yl)sulfanylprop-2-enoic acid Chemical compound CN1C=CN=C1SC=CC(O)=O XRYXTSHJCLIBCC-UHFFFAOYSA-N 0.000 description 1
- JFJAOHVZAPGZAW-UHFFFAOYSA-N 3-(1h-imidazol-2-ylsulfanyl)prop-2-enoic acid Chemical group OC(=O)C=CSC1=NC=CN1 JFJAOHVZAPGZAW-UHFFFAOYSA-N 0.000 description 1
- QOBZIMQBBLTRRP-UHFFFAOYSA-N 3-(2-methoxyphenyl)sulfanylprop-2-enoic acid Chemical compound COC1=CC=CC=C1SC=CC(O)=O QOBZIMQBBLTRRP-UHFFFAOYSA-N 0.000 description 1
- JIVXIOZRNOKKEE-UHFFFAOYSA-N 3-(2-methylfuran-3-yl)sulfanylprop-2-enoic acid Chemical compound CC=1OC=CC=1SC=CC(O)=O JIVXIOZRNOKKEE-UHFFFAOYSA-N 0.000 description 1
- OIDNAQOGQSKNQP-UHFFFAOYSA-N 3-(2-methylphenyl)sulfanylprop-2-enoic acid Chemical compound CC1=CC=CC=C1SC=CC(O)=O OIDNAQOGQSKNQP-UHFFFAOYSA-N 0.000 description 1
- KIWMRXFLYNDJRH-UHFFFAOYSA-N 3-(3-fluorophenyl)sulfanylprop-2-enoic acid Chemical compound OC(=O)C=CSC1=CC=CC(F)=C1 KIWMRXFLYNDJRH-UHFFFAOYSA-N 0.000 description 1
- SVLZFQKGXLCCNU-UHFFFAOYSA-N 3-(3-methoxyphenyl)sulfanylprop-2-enoic acid Chemical compound COC1=CC=CC(SC=CC(O)=O)=C1 SVLZFQKGXLCCNU-UHFFFAOYSA-N 0.000 description 1
- KEMKNAOEEOTYOT-UHFFFAOYSA-N 3-(3-methylphenyl)sulfanylprop-2-enoic acid Chemical compound CC1=CC=CC(SC=CC(O)=O)=C1 KEMKNAOEEOTYOT-UHFFFAOYSA-N 0.000 description 1
- ANLFEWNSVQFKHJ-UHFFFAOYSA-N 3-(4-chlorophenyl)sulfanylprop-2-enoic acid Chemical compound OC(=O)C=CSC1=CC=C(Cl)C=C1 ANLFEWNSVQFKHJ-UHFFFAOYSA-N 0.000 description 1
- HRLKEJODFYSVDL-UHFFFAOYSA-N 3-(4-fluorophenyl)sulfanylprop-2-enoic acid Chemical compound OC(=O)C=CSC1=CC=C(F)C=C1 HRLKEJODFYSVDL-UHFFFAOYSA-N 0.000 description 1
- UWMBTHXPFXCCHA-UHFFFAOYSA-N 3-(4-methoxyphenyl)sulfanylprop-2-enoic acid Chemical compound COC1=CC=C(SC=CC(O)=O)C=C1 UWMBTHXPFXCCHA-UHFFFAOYSA-N 0.000 description 1
- VKDXMULQZDVYFG-UHFFFAOYSA-N 3-(4-methylphenyl)sulfanylprop-2-enoic acid Chemical compound CC1=CC=C(SC=CC(O)=O)C=C1 VKDXMULQZDVYFG-UHFFFAOYSA-N 0.000 description 1
- ZORSNIDRWJDPHN-UHFFFAOYSA-N 3-([1,3]thiazolo[4,5-b]pyridin-2-ylsulfanyl)prop-2-enoic acid Chemical compound C1=CC=C2SC(SC=CC(=O)O)=NC2=N1 ZORSNIDRWJDPHN-UHFFFAOYSA-N 0.000 description 1
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 1
- VLALGJWCJHZCNL-UHFFFAOYSA-N 3-[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanyl]prop-2-enoic acid Chemical compound CC1=NN=C(SC=CC(O)=O)S1 VLALGJWCJHZCNL-UHFFFAOYSA-N 0.000 description 1
- VCCCOFCUIBHVBO-UHFFFAOYSA-N 3-[4-(trifluoromethyl)pyrimidin-2-yl]sulfanylprop-2-enoic acid Chemical compound OC(=O)C=CSC1=NC=CC(C(F)(F)F)=N1 VCCCOFCUIBHVBO-UHFFFAOYSA-N 0.000 description 1
- BZOCNUJYSFQJEB-UHFFFAOYSA-N 3-phenylsulfanylbut-2-enoic acid Chemical compound OC(=O)C=C(C)SC1=CC=CC=C1 BZOCNUJYSFQJEB-UHFFFAOYSA-N 0.000 description 1
- DLFJGWQWPLDNBM-UHFFFAOYSA-N 3-pyridin-2-ylsulfanylprop-2-enoic acid Chemical compound OC(=O)C=CSC1=CC=CC=N1 DLFJGWQWPLDNBM-UHFFFAOYSA-N 0.000 description 1
- DTZLPFLJZFZOQO-UHFFFAOYSA-N 3-pyridin-4-ylsulfanylprop-2-enoic acid Chemical compound OC(=O)C=CSC1=CC=NC=C1 DTZLPFLJZFZOQO-UHFFFAOYSA-N 0.000 description 1
- DNZKZIHGVKGOHI-UHFFFAOYSA-N 3-pyrimidin-2-ylsulfanylprop-2-enoic acid Chemical compound OC(=O)C=CSC1=NC=CC=N1 DNZKZIHGVKGOHI-UHFFFAOYSA-N 0.000 description 1
- ZUPMSIDGFWTDHY-UHFFFAOYSA-N 3-thiophen-2-ylsulfanylprop-2-enoic acid Chemical compound OC(=O)C=CSC1=CC=CS1 ZUPMSIDGFWTDHY-UHFFFAOYSA-N 0.000 description 1
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-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
- 125000004399 C1-C4 alkenyl group Chemical group 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 108010009685 Cholinergic Receptors Proteins 0.000 description 1
- 208000000094 Chronic Pain Diseases 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-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
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-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
- 241000124008 Mammalia Species 0.000 description 1
- 208000026139 Memory disease Diseases 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical group CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 102000034337 acetylcholine receptors Human genes 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 230000036592 analgesia Effects 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 230000000954 anitussive effect Effects 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 229940054051 antipsychotic indole derivative Drugs 0.000 description 1
- 239000003434 antitussive agent Substances 0.000 description 1
- 229940124584 antitussives Drugs 0.000 description 1
- 239000008346 aqueous phase Substances 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
- 150000001540 azides Chemical class 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 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
- 150000001793 charged compounds Chemical class 0.000 description 1
- 238000004296 chiral HPLC Methods 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000002026 chloroform extract Substances 0.000 description 1
- 230000006949 cholinergic function Effects 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 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 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
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 238000007405 data analysis Methods 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
- 239000008298 dragée 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
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229960005051 fluostigmine Drugs 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 230000000971 hippocampal effect Effects 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- 239000011539 homogenization buffer Substances 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
- 150000002475 indoles Chemical class 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
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 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
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 230000007257 malfunction Effects 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 229940126601 medicinal product Drugs 0.000 description 1
- 230000006984 memory degeneration Effects 0.000 description 1
- 208000023060 memory loss Diseases 0.000 description 1
- 238000005649 metathesis reaction Methods 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 239000012452 mother liquor Substances 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
- 230000001537 neural effect Effects 0.000 description 1
- 230000004112 neuroprotection Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 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
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 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
- 239000001301 oxygen Substances 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 229960004889 salicylic acid Drugs 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
- 239000011780 sodium chloride Substances 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
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 239000012453 solvate 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
- 239000000829 suppository Substances 0.000 description 1
- 230000005062 synaptic transmission Effects 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
- 239000004149 tartrazine Substances 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 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
- 230000001225 therapeutic 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
- 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
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
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—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
-
- 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)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Pain & Pain Management (AREA)
- Addiction (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Hydrogenated Pyridines (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| SE9903760 | 1999-10-18 | ||
| SE9903760A SE9903760D0 (sv) | 1999-10-18 | 1999-10-18 | New compounds |
| PCT/SE2000/001993 WO2001029034A1 (en) | 1999-10-18 | 2000-10-13 | Quinuclidine acrylamides |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60005054D1 DE60005054D1 (de) | 2003-10-09 |
| DE60005054T2 true DE60005054T2 (de) | 2004-07-08 |
Family
ID=20417402
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60005054T Expired - Lifetime DE60005054T2 (de) | 1999-10-18 | 2000-10-13 | Chinuclidin-acrylamide |
Country Status (14)
| Country | Link |
|---|---|
| US (1) | US6642246B1 (enExample) |
| EP (1) | EP1235826B1 (enExample) |
| JP (1) | JP2003512374A (enExample) |
| AT (1) | ATE248837T1 (enExample) |
| AU (1) | AU1069001A (enExample) |
| CO (1) | CO5271691A1 (enExample) |
| DE (1) | DE60005054T2 (enExample) |
| DK (1) | DK1235826T3 (enExample) |
| ES (1) | ES2204711T3 (enExample) |
| HK (1) | HK1048313B (enExample) |
| MY (1) | MY136240A (enExample) |
| PT (1) | PT1235826E (enExample) |
| SE (1) | SE9903760D0 (enExample) |
| WO (1) | WO2001029034A1 (enExample) |
Families Citing this family (44)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2002016358A2 (en) * | 2000-08-18 | 2002-02-28 | Pharmacia & Upjohn Company | Quinuclidine-substituted aryl moieties for treatment of disease (nicotinic acetylcholine receptor ligands) |
| WO2002016357A2 (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) |
| PE20021019A1 (es) | 2001-04-19 | 2002-11-13 | Upjohn Co | Grupos azabiciclicos sustituidos |
| WO2003018585A1 (en) | 2001-08-24 | 2003-03-06 | Pharmacia & Upjohn Company | Substituted-heteroaryl-7-aza[2.2.1]bicycloheptanes for the treatment of disease |
| US20040259909A1 (en) * | 2001-10-16 | 2004-12-23 | Mccarthy Dennis | Treatment of fibromyalgia syndrome |
| EP1442037A1 (en) | 2001-11-09 | 2004-08-04 | PHARMACIA & UPJOHN COMPANY | Azabicyclic-phenyl-fused-heterocyclic compounds and their use as alpha7 nachr ligands |
| DE10164139A1 (de) | 2001-12-27 | 2003-07-10 | Bayer Ag | 2-Heteroarylcarbonsäureamide |
| AU2003210730A1 (en) | 2002-02-15 | 2003-09-09 | Pharmacia And Upjohn Company | Azabicyclo-substituted benzoylamides and thioamides for treatment of cns-related disorders |
| US6858613B2 (en) | 2002-02-19 | 2005-02-22 | Pfizer Inc. | Fused bicyclic-N-bridged-heteroaromatic carboxamides for the treatment of disease |
| GB0220581D0 (en) | 2002-09-04 | 2002-10-09 | Novartis Ag | Organic Compound |
| KR101129933B1 (ko) * | 2002-09-25 | 2012-03-23 | 메모리 파마슈티칼스 코포레이션 | 인다졸, 벤조티아졸 및 벤조이소티아졸 및 그의 제조 및용도 |
| JP4824578B2 (ja) | 2003-12-22 | 2011-11-30 | メモリー・ファーマシューティカルズ・コーポレイション | インドール類、１，２−ベンズイソオキサゾール類、および１，２−ベンゾイソチアゾール類、ならびにそれらの製造と使用 |
| JP4995075B2 (ja) | 2004-03-25 | 2012-08-08 | メモリー・ファーマシューティカルズ・コーポレイション | インダゾール、ベンゾチアゾール、ベンゾイソチアゾール、ベンズイソキサゾール、ならびにそれらの調製および使用 |
| JP2007534692A (ja) | 2004-04-22 | 2007-11-29 | メモリー・ファーマシューティカルズ・コーポレイション | インドール、１ｈ−インダゾール、１，２−ベンズイソキサゾール、１，２−ベンゾイソチアゾール、ならびにその調製および使用 |
| WO2005111038A2 (en) | 2004-05-07 | 2005-11-24 | Memory Pharmaceuticals Corporation | 1h-indazoles, benzothiazoles, 1,2-benzoisoxazoles, 1,2-benzoisothiazoles, and chromones and preparation and uses thereof |
| PE20060437A1 (es) | 2004-06-18 | 2006-06-08 | Novartis Ag | COMPUESTOS AZA-BICICLONONANOS COMO LIGANDOS COLINERGICOS DE nAChR |
| GB0415746D0 (en) | 2004-07-14 | 2004-08-18 | Novartis Ag | Organic compounds |
| GB0424564D0 (en) | 2004-11-05 | 2004-12-08 | Novartis Ag | Organic compounds |
| US7625924B2 (en) | 2004-12-22 | 2009-12-01 | Memory Pharmaceuticals Corporation | Nicotinic alpha-7 receptor ligands and preparation and uses thereof |
| US8106066B2 (en) | 2005-09-23 | 2012-01-31 | Memory Pharmaceuticals Corporation | Indazoles, benzothiazoles, benzoisothiazoles, benzisoxazoles, pyrazolopyridines, isothiazolopyridines, and preparation and uses thereof |
| GB0521508D0 (en) | 2005-10-21 | 2005-11-30 | Novartis Ag | Organic compounds |
| GB0525673D0 (en) | 2005-12-16 | 2006-01-25 | Novartis Ag | Organic compounds |
| GB0525672D0 (en) | 2005-12-16 | 2006-01-25 | Novartis Ag | Organic compounds |
| ES2396126T3 (es) * | 2008-04-15 | 2013-02-19 | Eisai R&D Management Co., Ltd. | Compuesto de 3-fenilpirazol[5,1-b]tiazol |
| WO2009154563A1 (en) | 2008-06-20 | 2009-12-23 | Astrazeneca Ab | Dibenzothiazepine derivatives and use thereof |
| EP2243476A1 (en) * | 2009-04-17 | 2010-10-27 | Centre National de la Recherche Scientifique | Compounds for the treatment of mitochondrial diseases |
| AR078521A1 (es) * | 2009-10-08 | 2011-11-16 | Eisai R&D Man Co Ltd | Compuesto pirazolotiazol |
| ES2570657T3 (es) | 2010-05-17 | 2016-05-19 | Forum Pharmaceuticals Inc | Una forma cristalina de hidrocloruro de (R)-7-cloro-n-(quinuclidin-3-il)benzo[b]tiofeno-2-carboxamida monohidrato |
| GB201111704D0 (en) | 2011-07-07 | 2011-08-24 | Takeda Pharmaceutical | Novel compounds |
| GB201111705D0 (en) | 2011-07-07 | 2011-08-24 | Takeda Pharmaceutical | Compounds and their use |
| JO3115B1 (ar) | 2011-08-22 | 2017-09-20 | Takeda Pharmaceuticals Co | مركبات بيريدازينون واستخدامها كمثبطات daao |
| WO2013169646A1 (en) | 2012-05-08 | 2013-11-14 | Envivo Pharmaceuticals, Inc. | Methods of maintaining, treating or improving cognitive function |
| GB201209587D0 (en) | 2012-05-30 | 2012-07-11 | Takeda Pharmaceutical | Therapeutic compounds |
| ES2694299T3 (es) | 2013-02-07 | 2018-12-19 | Heptares Therapeutics Limited | Carboxilatos de piperidin-1-ilo y azepin-1-ilo como agonistas del receptor muscarínico M4 |
| 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 |
| CN103923105B (zh) * | 2014-04-17 | 2016-08-24 | 北京大学 | 2-中氮茚甲酰胺类化合物及其制备和用途 |
| 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 (5)
| 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 |
| TR199700625T1 (xx) | 1995-01-10 | 1998-02-21 | Smithkline Beecham S.P.A. | Osteoporoz (kemik erimesi) tedavisinde yararl� olan indol t�revleri. |
| AU7083596A (en) * | 1995-09-22 | 1997-04-09 | Novo Nordisk A/S | Novel substituted azacyclic or azabicyclic compounds |
| IL127668A0 (en) | 1996-07-09 | 1999-10-28 | Smithkline Beecham Spa | Indole derivatives for the treatment of osteoporosis |
-
1999
- 1999-10-18 SE SE9903760A patent/SE9903760D0/xx unknown
-
2000
- 2000-10-13 AT AT00971959T patent/ATE248837T1/de active
- 2000-10-13 EP EP00971959A patent/EP1235826B1/en not_active Expired - Lifetime
- 2000-10-13 US US10/110,663 patent/US6642246B1/en not_active Expired - Fee Related
- 2000-10-13 JP JP2001531833A patent/JP2003512374A/ja active Pending
- 2000-10-13 HK HK03100456.4A patent/HK1048313B/en not_active IP Right Cessation
- 2000-10-13 PT PT00971959T patent/PT1235826E/pt unknown
- 2000-10-13 AU AU10690/01A patent/AU1069001A/en not_active Abandoned
- 2000-10-13 WO PCT/SE2000/001993 patent/WO2001029034A1/en not_active Ceased
- 2000-10-13 DE DE60005054T patent/DE60005054T2/de not_active Expired - Lifetime
- 2000-10-13 DK DK00971959T patent/DK1235826T3/da active
- 2000-10-13 ES ES00971959T patent/ES2204711T3/es not_active Expired - Lifetime
- 2000-10-16 MY MYPI20004849A patent/MY136240A/en unknown
- 2000-10-17 CO CO00078738A patent/CO5271691A1/es not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| ATE248837T1 (de) | 2003-09-15 |
| SE9903760D0 (sv) | 1999-10-18 |
| AU1069001A (en) | 2001-04-30 |
| EP1235826A1 (en) | 2002-09-04 |
| PT1235826E (pt) | 2004-01-30 |
| DE60005054D1 (de) | 2003-10-09 |
| DK1235826T3 (da) | 2003-11-24 |
| CO5271691A1 (es) | 2003-04-30 |
| WO2001029034A1 (en) | 2001-04-26 |
| ES2204711T3 (es) | 2004-05-01 |
| EP1235826B1 (en) | 2003-09-03 |
| MY136240A (en) | 2008-08-29 |
| US6642246B1 (en) | 2003-11-04 |
| JP2003512374A (ja) | 2003-04-02 |
| HK1048313A1 (en) | 2003-03-28 |
| HK1048313B (en) | 2003-12-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE60005054T2 (de) | Chinuclidin-acrylamide | |
| DE60020994T2 (de) | Neue verwendung sowie neue n-azabicycloamid-verbindungen | |
| DE69713295T2 (de) | Azabicyclishe carbaniumsaureester zur therapeutsichen verwendung | |
| DE60100996T2 (de) | Biarylcarboxamide | |
| DE60311853T2 (de) | Neue 1,4-diazabicycloalkanderivate, deren herstellung und verwendung | |
| DE69516524T2 (de) | Therapeutisch verwendbare spiro-azabicyclische verbindungen | |
| EP1448530B1 (de) | Heteroarylcarbonsäureamide | |
| DE69908185T2 (de) | Therapeutisch nützliche arylalkylamine von spirofuropyridinen | |
| DE69827977T2 (de) | Spiro [1-azabicyclo[2.2.2]octan-3,2'(3'H)-furo[2,3-b]pyridin zur Verwendung in der Behandlung von psychotischen und intellektuellen Störungen | |
| EP1461335B1 (de) | 2-heteroarylcarbonsäureamide | |
| DE69208877T2 (de) | Chinuclidinderivate | |
| EP1487834B1 (de) | Aza-bicyclische n-biarylamide mit affinität zum alpha7 nikotinischen acetylcholin-rezeptor | |
| DE69815161T2 (de) | Azindolethylaminderivate als Nikotin-acetylcholin-Rezeptor Bindung Verbindungen | |
| EP1458716B1 (de) | Bicyclische n-arylamide | |
| DE60218032T2 (de) | Neuer, für die therapie geeigneter ligand für nikotinische acetylcholinrezeptoren | |
| DE69329018T2 (de) | Heterocyclische verbindungen, deren herstellung und verwendung | |
| EP1487835B1 (de) | Essig- und propionsäureamide | |
| CH626344A5 (enExample) | ||
| DE69127072T2 (de) | Substituierte harnstoffe, herstellung und verwendung | |
| DE69205312T2 (de) | Substituierte Imidazol-2-one Derivate und Verfahren zu deren Herstellung. | |
| DE69514315T2 (de) | AZABICYCLOALKYLDERIVATE VON IMIDAZO[1,5-a]INDOL-3-ONE ALS 5HT3 ANTAGONISTEN | |
| DE10334724A1 (de) | N-Biarylamide | |
| DE10162442A1 (de) | Monocyclische N-Aryl-amide | |
| DE2821813A1 (de) | Neue, in 11-stellung substituierte 5, 11-dihydro-6h-pyrido eckige klammer auf 2,3-b eckige klammer zu eckige klammer auf 1,4 eckige klammer zu benzodiazepin-6-one, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel | |
| DE602004006767T2 (de) | Nichtamidnonane |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition |