DE60011269T2 - Azaidole mit serotonin rezeptor affinität - Google Patents
Azaidole mit serotonin rezeptor affinität Download PDFInfo
- Publication number
- DE60011269T2 DE60011269T2 DE60011269T DE60011269T DE60011269T2 DE 60011269 T2 DE60011269 T2 DE 60011269T2 DE 60011269 T DE60011269 T DE 60011269T DE 60011269 T DE60011269 T DE 60011269T DE 60011269 T2 DE60011269 T2 DE 60011269T2
- Authority
- DE
- Germany
- Prior art keywords
- azaindole
- indolizinyl
- hexahydro
- octahydro
- mmol
- 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
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 title description 7
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 108
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 18
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 6
- 125000003107 substituted aryl group Chemical group 0.000 claims abstract description 6
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 claims description 112
- -1 1,2,3,5,8,8a-hexahydro-7-indolizinyl Chemical group 0.000 claims description 34
- SHUJGWWKEOGIKB-UHFFFAOYSA-N 3-(1,2,3,5,6,7,8,8a-octahydroindolizin-7-yl)-1h-pyrrolo[3,2-c]pyridine Chemical compound C1=NC=C2C(C3CC4CCCN4CC3)=CNC2=C1 SHUJGWWKEOGIKB-UHFFFAOYSA-N 0.000 claims description 30
- 150000003839 salts Chemical class 0.000 claims description 26
- VMSVWNATGMTCJN-UHFFFAOYSA-N 3-(1,2,3,5,8,8a-hexahydroindolizin-7-yl)-1h-pyrrolo[3,2-c]pyridine Chemical compound C1=NC=C2C(C=3CC4CCCN4CC=3)=CNC2=C1 VMSVWNATGMTCJN-UHFFFAOYSA-N 0.000 claims description 23
- PGAVHYCWYWOJFQ-UHFFFAOYSA-N 3-(1,2,3,5,8,8a-hexahydroindolizin-7-yl)-1h-pyrrolo[2,3-b]pyridine Chemical compound C1=CC=C2C(C=3CC4CCCN4CC=3)=CNC2=N1 PGAVHYCWYWOJFQ-UHFFFAOYSA-N 0.000 claims description 21
- ALOYIHSIDZIWBV-UHFFFAOYSA-N 3-(1,2,3,5,6,7,8,8a-octahydroindolizin-7-yl)-1h-pyrrolo[3,2-b]pyridine Chemical compound C1=CN=C2C(C3CC4CCCN4CC3)=CNC2=C1 ALOYIHSIDZIWBV-UHFFFAOYSA-N 0.000 claims description 15
- 238000000034 method Methods 0.000 claims description 15
- MVJAGLGXNLMRTO-UHFFFAOYSA-N 3-(1,2,3,5,6,7,8,8a-octahydroindolizin-7-yl)-1-naphthalen-1-ylsulfonylpyrrolo[3,2-b]pyridine Chemical compound C1=C(C2CC3CCCN3CC2)C2=NC=CC=C2N1S(=O)(=O)C1=CC=CC2=CC=CC=C12 MVJAGLGXNLMRTO-UHFFFAOYSA-N 0.000 claims description 12
- WGWMVQWFVUCIBS-UHFFFAOYSA-N 3-(1,2,3,5,6,7,8,8a-octahydroindolizin-7-yl)-1-naphthalen-2-ylsulfonylpyrrolo[2,3-b]pyridine Chemical compound C1=C(C2CC3CCCN3CC2)C2=CC=CN=C2N1S(=O)(=O)C1=CC=C(C=CC=C2)C2=C1 WGWMVQWFVUCIBS-UHFFFAOYSA-N 0.000 claims description 11
- RVMWHFCJSMACCF-UHFFFAOYSA-N 3-(1-methyl-3,6-dihydro-2h-pyridin-4-yl)-1h-pyrrolo[3,2-c]pyridine Chemical compound C1N(C)CCC(C=2C3=CN=CC=C3NC=2)=C1 RVMWHFCJSMACCF-UHFFFAOYSA-N 0.000 claims description 11
- 239000012453 solvate Substances 0.000 claims description 11
- ZBEMBSSWUTWKCX-UHFFFAOYSA-N 3-(1,2,3,5,6,7,8,8a-octahydroindolizin-7-yl)-1-naphthalen-1-ylsulfonylpyrrolo[2,3-c]pyridine Chemical compound C1=C(C2CC3CCCN3CC2)C2=CC=NC=C2N1S(=O)(=O)C1=CC=CC2=CC=CC=C12 ZBEMBSSWUTWKCX-UHFFFAOYSA-N 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- 238000011282 treatment Methods 0.000 claims description 10
- VEPOXPKPYHBHDK-UHFFFAOYSA-N 2-[3-(1,2,3,5,6,7,8,8a-octahydroindolizin-7-yl)-2,5-dichlorophenyl]sulfonyl-1h-pyrrolo[3,2-c]pyridine Chemical compound N1=CC=C2NC(S(=O)(=O)C=3C(Cl)=C(C4CC5CCCN5CC4)C=C(C=3)Cl)=CC2=C1 VEPOXPKPYHBHDK-UHFFFAOYSA-N 0.000 claims description 9
- FXIXQCNASYENJN-UHFFFAOYSA-N 3-(1,2,3,5,6,7,8,8a-octahydroindolizin-7-yl)-1-(benzenesulfonyl)pyrrolo[3,2-c]pyridine Chemical compound C1=C(C2CC3CCCN3CC2)C2=CN=CC=C2N1S(=O)(=O)C1=CC=CC=C1 FXIXQCNASYENJN-UHFFFAOYSA-N 0.000 claims description 9
- YVNFPVDQZZAGMA-UHFFFAOYSA-N 3-(1,2,3,5,6,7,8,8a-octahydroindolizin-7-yl)-1-naphthalen-1-ylsulfonylpyrrolo[3,2-c]pyridine Chemical compound C1=C(C2CC3CCCN3CC2)C2=CN=CC=C2N1S(=O)(=O)C1=CC=CC2=CC=CC=C12 YVNFPVDQZZAGMA-UHFFFAOYSA-N 0.000 claims description 9
- PRKUGFVPSCNSIB-UHFFFAOYSA-N 3-(1,2,3,5,6,7,8,8a-octahydroindolizin-7-yl)-1-naphthalen-2-ylsulfonylpyrrolo[3,2-b]pyridine Chemical compound C1=C(C2CC3CCCN3CC2)C2=NC=CC=C2N1S(=O)(=O)C1=CC=C(C=CC=C2)C2=C1 PRKUGFVPSCNSIB-UHFFFAOYSA-N 0.000 claims description 9
- XPTMXVRFXINZSY-UHFFFAOYSA-N 3-(1,2,3,5,6,7,8,8a-octahydroindolizin-7-yl)-1-naphthalen-2-ylsulfonylpyrrolo[3,2-c]pyridine Chemical compound C1=C(C2CC3CCCN3CC2)C2=CN=CC=C2N1S(=O)(=O)C1=CC=C(C=CC=C2)C2=C1 XPTMXVRFXINZSY-UHFFFAOYSA-N 0.000 claims description 9
- BSYSGGLVESLGTK-UHFFFAOYSA-N 3-(1,2,3,5,8,8a-hexahydroindolizin-7-yl)-1-(benzenesulfonyl)pyrrolo[3,2-c]pyridine Chemical compound C1=C(C=2CC3CCCN3CC=2)C2=CN=CC=C2N1S(=O)(=O)C1=CC=CC=C1 BSYSGGLVESLGTK-UHFFFAOYSA-N 0.000 claims description 9
- GAKAACVLHNWCAS-UHFFFAOYSA-N 3-(1-methylpiperidin-4-yl)-1h-pyrrolo[3,2-c]pyridine Chemical compound C1CN(C)CCC1C1=CNC2=CC=NC=C12 GAKAACVLHNWCAS-UHFFFAOYSA-N 0.000 claims description 9
- LFDOZYLVNQASGA-UHFFFAOYSA-N 3-(1,2,3,5,8,8a-hexahydroindolizin-7-yl)-1-naphthalen-1-ylsulfonylpyrrolo[2,3-b]pyridine Chemical compound C1=C(C=2CC3CCCN3CC=2)C2=CC=CN=C2N1S(=O)(=O)C1=CC=CC2=CC=CC=C12 LFDOZYLVNQASGA-UHFFFAOYSA-N 0.000 claims description 8
- NSQLQBSRFTUZMT-UHFFFAOYSA-N 3-(1,2,3,5,8,8a-hexahydroindolizin-7-yl)-1-naphthalen-1-ylsulfonylpyrrolo[3,2-c]pyridine Chemical compound C1=C(C=2CC3CCCN3CC=2)C2=CN=CC=C2N1S(=O)(=O)C1=CC=CC2=CC=CC=C12 NSQLQBSRFTUZMT-UHFFFAOYSA-N 0.000 claims description 8
- IJAWXADAXNQWQU-UHFFFAOYSA-N [3-(1,2,3,5,8,8a-hexahydroindolizin-7-yl)pyrrolo[2,3-b]pyridin-1-yl]-(2,6-dichlorophenyl)methanone Chemical compound ClC1=CC=CC(Cl)=C1C(=O)N1C2=NC=CC=C2C(C=2CC3CCCN3CC=2)=C1 IJAWXADAXNQWQU-UHFFFAOYSA-N 0.000 claims description 8
- 125000001624 naphthyl group Chemical group 0.000 claims description 8
- HIJXDWIOHRJBSG-UHFFFAOYSA-N 1-(benzenesulfonyl)-3-(1-methyl-3,6-dihydro-2h-pyridin-4-yl)pyrrolo[3,2-c]pyridine Chemical compound C1N(C)CCC(C=2C3=CN=CC=C3N(C=2)S(=O)(=O)C=2C=CC=CC=2)=C1 HIJXDWIOHRJBSG-UHFFFAOYSA-N 0.000 claims description 7
- ZXIIOYMPSDKYNZ-UHFFFAOYSA-N 3-(1,2,3,5,6,7,8,8a-octahydroindolizin-7-yl)-1-(benzenesulfonyl)pyrrolo[2,3-b]pyridine Chemical compound C1=C(C2CC3CCCN3CC2)C2=CC=CN=C2N1S(=O)(=O)C1=CC=CC=C1 ZXIIOYMPSDKYNZ-UHFFFAOYSA-N 0.000 claims description 7
- CICGWVYPAWNNIE-UHFFFAOYSA-N 3-(1,2,3,5,6,7,8,8a-octahydroindolizin-7-yl)-1-naphthalen-1-ylsulfonylpyrrolo[2,3-b]pyridine Chemical compound C1=C(C2CC3CCCN3CC2)C2=CC=CN=C2N1S(=O)(=O)C1=CC=CC2=CC=CC=C12 CICGWVYPAWNNIE-UHFFFAOYSA-N 0.000 claims description 7
- PMSPULBCDNOMJD-UHFFFAOYSA-N 3-(1,2,3,5,6,7,8,8a-octahydroindolizin-7-yl)-1h-pyrrolo[2,3-b]pyridine Chemical compound C1=CC=C2C(C3CC4CCCN4CC3)=CNC2=N1 PMSPULBCDNOMJD-UHFFFAOYSA-N 0.000 claims description 7
- GHWNZIPAARWORE-UHFFFAOYSA-N 3-(1,2,3,5,8,8a-hexahydroindolizin-7-yl)-1-(4-fluorophenyl)sulfonylpyrrolo[3,2-c]pyridine Chemical compound C1=CC(F)=CC=C1S(=O)(=O)N1C2=CC=NC=C2C(C=2CC3CCCN3CC=2)=C1 GHWNZIPAARWORE-UHFFFAOYSA-N 0.000 claims description 7
- NDWHDDHSRAPPGC-UHFFFAOYSA-N 3-(1,2,3,5,8,8a-hexahydroindolizin-7-yl)-1-(4-methylphenyl)sulfonylpyrrolo[2,3-b]pyridine Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1C2=NC=CC=C2C(C=2CC3CCCN3CC=2)=C1 NDWHDDHSRAPPGC-UHFFFAOYSA-N 0.000 claims description 7
- XGDVMSACWHVPTH-UHFFFAOYSA-N 3-(1,2,3,5,8,8a-hexahydroindolizin-7-yl)-1-naphthalen-2-ylsulfonylpyrrolo[3,2-c]pyridine Chemical compound C1=C(C=2CC3CCCN3CC=2)C2=CN=CC=C2N1S(=O)(=O)C1=CC=C(C=CC=C2)C2=C1 XGDVMSACWHVPTH-UHFFFAOYSA-N 0.000 claims description 7
- NRJBSWIXUSQBTR-UHFFFAOYSA-N [3-(1,2,3,5,8,8a-hexahydroindolizin-7-yl)pyrrolo[2,3-b]pyridin-1-yl]-phenylmethanone Chemical compound C1=C(C=2CC3CCCN3CC=2)C2=CC=CN=C2N1C(=O)C1=CC=CC=C1 NRJBSWIXUSQBTR-UHFFFAOYSA-N 0.000 claims description 7
- QTYPXLJOSPIRQV-UHFFFAOYSA-N [3-(1,2,3,5,8,8a-hexahydroindolizin-7-yl)pyrrolo[3,2-c]pyridin-1-yl]-(2,6-dimethoxyphenyl)methanone Chemical compound COC1=CC=CC(OC)=C1C(=O)N1C2=CC=NC=C2C(C=2CC3CCCN3CC=2)=C1 QTYPXLJOSPIRQV-UHFFFAOYSA-N 0.000 claims description 7
- GQFNRPSMGBVAET-UHFFFAOYSA-N [3-(1,2,3,5,8,8a-hexahydroindolizin-7-yl)pyrrolo[3,2-c]pyridin-1-yl]-phenylmethanone Chemical compound C1=C(C=2CC3CCCN3CC=2)C2=CN=CC=C2N1C(=O)C1=CC=CC=C1 GQFNRPSMGBVAET-UHFFFAOYSA-N 0.000 claims description 7
- RQCPJSGQGXUPTB-UHFFFAOYSA-N [3-(1-methyl-3,6-dihydro-2h-pyridin-4-yl)pyrrolo[2,3-b]pyridin-1-yl]-phenylmethanone Chemical compound C1N(C)CCC(C=2C3=CC=CN=C3N(C(=O)C=3C=CC=CC=3)C=2)=C1 RQCPJSGQGXUPTB-UHFFFAOYSA-N 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- TYNVLZIAWGVTJU-UHFFFAOYSA-N (4-fluorophenyl)-[3-(1-methyl-3,6-dihydro-2h-pyridin-4-yl)pyrrolo[2,3-b]pyridin-1-yl]methanone Chemical compound C1N(C)CCC(C=2C3=CC=CN=C3N(C(=O)C=3C=CC(F)=CC=3)C=2)=C1 TYNVLZIAWGVTJU-UHFFFAOYSA-N 0.000 claims description 6
- MIDYODKZIIWWHK-UHFFFAOYSA-N 1-(benzenesulfonyl)-3-(1-methyl-3,6-dihydro-2h-pyridin-4-yl)pyrrolo[2,3-b]pyridine Chemical compound C1N(C)CCC(C=2C3=CC=CN=C3N(C=2)S(=O)(=O)C=2C=CC=CC=2)=C1 MIDYODKZIIWWHK-UHFFFAOYSA-N 0.000 claims description 6
- KUYBTFPEERPPTD-UHFFFAOYSA-N 2-(1-naphthalen-1-ylsulfonylpyrrolo[3,2-c]pyridin-3-yl)-2,3,4,6,7,8,9,9a-octahydro-1h-quinolizine Chemical compound C1=C(C2CC3CCCCN3CC2)C2=CN=CC=C2N1S(=O)(=O)C1=CC=CC2=CC=CC=C12 KUYBTFPEERPPTD-UHFFFAOYSA-N 0.000 claims description 6
- BQZSPRXNXIAPCX-UHFFFAOYSA-N 3-(1,2,3,5,8,8a-hexahydroindolizin-7-yl)-1h-pyrrolo[3,2-b]pyridine Chemical compound C1=CN=C2C(C=3CC4CCCN4CC=3)=CNC2=C1 BQZSPRXNXIAPCX-UHFFFAOYSA-N 0.000 claims description 6
- NJGJYYJRKPMKJU-UHFFFAOYSA-N [3-(1,2,3,5,8,8a-hexahydroindolizin-7-yl)pyrrolo[3,2-c]pyridin-1-yl]-(2,6-dichlorophenyl)methanone Chemical compound ClC1=CC=CC(Cl)=C1C(=O)N1C2=CC=NC=C2C(C=2CC3CCCN3CC=2)=C1 NJGJYYJRKPMKJU-UHFFFAOYSA-N 0.000 claims description 6
- IOWGFNLEWKXDGN-UHFFFAOYSA-N [3-(1,2,3,5,8,8a-hexahydroindolizin-7-yl)pyrrolo[3,2-c]pyridin-1-yl]-(2-chlorophenyl)methanone Chemical compound ClC1=CC=CC=C1C(=O)N1C2=CC=NC=C2C(C=2CC3CCCN3CC=2)=C1 IOWGFNLEWKXDGN-UHFFFAOYSA-N 0.000 claims description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
- BJWXITQMNYHOQB-UHFFFAOYSA-N (2,6-dichlorophenyl)-[3-(1-methyl-3,6-dihydro-2h-pyridin-4-yl)pyrrolo[3,2-c]pyridin-1-yl]methanone Chemical compound C1N(C)CCC(C=2C3=CN=CC=C3N(C(=O)C=3C(=CC=CC=3Cl)Cl)C=2)=C1 BJWXITQMNYHOQB-UHFFFAOYSA-N 0.000 claims description 5
- UIXDVQSRWYQJHJ-UHFFFAOYSA-N (2,6-dichlorophenyl)-[3-(1-methylpiperidin-4-yl)pyrrolo[3,2-c]pyridin-1-yl]methanone Chemical compound C1CN(C)CCC1C(C1=CN=CC=C11)=CN1C(=O)C1=C(Cl)C=CC=C1Cl UIXDVQSRWYQJHJ-UHFFFAOYSA-N 0.000 claims description 5
- LIXZPQVPTSYTPT-UHFFFAOYSA-N 1-(benzenesulfonyl)-3-(1-methylpiperidin-4-yl)pyrrolo[3,2-c]pyridine Chemical compound C1CN(C)CCC1C1=CN(S(=O)(=O)C=2C=CC=CC=2)C2=CC=NC=C12 LIXZPQVPTSYTPT-UHFFFAOYSA-N 0.000 claims description 5
- GXIKJOYLWCYVQN-UHFFFAOYSA-N 3-(1,2,3,5,6,7,8,8a-octahydroindolizin-7-yl)-1h-pyrrolo[2,3-c]pyridine Chemical compound N1=CC=C2C(C3CC4CCCN4CC3)=CNC2=C1 GXIKJOYLWCYVQN-UHFFFAOYSA-N 0.000 claims description 5
- NCAXBIMSXYSCKX-UHFFFAOYSA-N 3-(1,2,3,5,8,8a-hexahydroindolizin-7-yl)-1-(4-fluorophenyl)sulfonylpyrrolo[2,3-b]pyridine Chemical compound C1=CC(F)=CC=C1S(=O)(=O)N1C2=NC=CC=C2C(C=2CC3CCCN3CC=2)=C1 NCAXBIMSXYSCKX-UHFFFAOYSA-N 0.000 claims description 5
- RJPGZBOOXLUXIS-UHFFFAOYSA-N [3-(1,2,3,5,8,8a-hexahydroindolizin-7-yl)pyrrolo[2,3-b]pyridin-1-yl]-(2,6-dimethoxyphenyl)methanone Chemical compound COC1=CC=CC(OC)=C1C(=O)N1C2=NC=CC=C2C(C=2CC3CCCN3CC=2)=C1 RJPGZBOOXLUXIS-UHFFFAOYSA-N 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 239000003751 serotonin 6 antagonist Substances 0.000 claims description 4
- LOLMEVLMDDIURX-UHFFFAOYSA-N 3-(1,2,3,5,8,8a-hexahydroindolizin-7-yl)-1-(4-chlorophenyl)sulfonylpyrrolo[2,3-b]pyridine Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N1C2=NC=CC=C2C(C=2CC3CCCN3CC=2)=C1 LOLMEVLMDDIURX-UHFFFAOYSA-N 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 2
- 125000002950 monocyclic group Chemical group 0.000 claims description 2
- 125000004001 thioalkyl group Chemical group 0.000 claims description 2
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
- FBCOYBBVGZOJHZ-UHFFFAOYSA-N 3-(1,2,3,5,8,8a-hexahydroindolizin-7-yl)-1-(4-chlorophenyl)sulfonylpyrrolo[3,2-c]pyridine Chemical compound C1=CC(Cl)=CC=C1S(=O)(=O)N1C2=CC=NC=C2C(C=2CC3CCCN3CC=2)=C1 FBCOYBBVGZOJHZ-UHFFFAOYSA-N 0.000 claims 1
- 125000001999 4-Methoxybenzoyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C(*)=O 0.000 claims 1
- 230000003042 antagnostic effect Effects 0.000 claims 1
- 230000005764 inhibitory process Effects 0.000 abstract description 9
- 201000000980 schizophrenia Diseases 0.000 abstract description 6
- 239000003814 drug Substances 0.000 abstract description 5
- 108091005435 5-HT6 receptors Proteins 0.000 abstract 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 182
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 84
- WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 46
- 102000005962 receptors Human genes 0.000 description 37
- 108020003175 receptors Proteins 0.000 description 37
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 29
- DASJFYAPNPUBGG-UHFFFAOYSA-N naphthalene-1-sulfonyl chloride Chemical compound C1=CC=C2C(S(=O)(=O)Cl)=CC=CC2=C1 DASJFYAPNPUBGG-UHFFFAOYSA-N 0.000 description 24
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- 239000000203 mixture Substances 0.000 description 20
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 18
- CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 15
- 239000002253 acid Substances 0.000 description 14
- OPECTNGATDYLSS-UHFFFAOYSA-N naphthalene-2-sulfonyl chloride Chemical compound C1=CC=CC2=CC(S(=O)(=O)Cl)=CC=C21 OPECTNGATDYLSS-UHFFFAOYSA-N 0.000 description 14
- 239000002904 solvent Substances 0.000 description 13
- 238000012360 testing method Methods 0.000 description 13
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- 229940076279 serotonin Drugs 0.000 description 12
- QPFARDFRKAIVOF-UHFFFAOYSA-N 3-(1-methyl-3,6-dihydro-2h-pyridin-4-yl)-1h-pyrrolo[2,3-b]pyridine Chemical compound C1N(C)CCC(C=2C3=CC=CN=C3NC=2)=C1 QPFARDFRKAIVOF-UHFFFAOYSA-N 0.000 description 11
- SAIMZEWINXIYCT-UHFFFAOYSA-N 3-(1,2,3,5,8,8a-hexahydroindolizin-7-yl)-1h-pyrrolo[2,3-c]pyridine Chemical compound N1=CC=C2C(C=3CC4CCCN4CC=3)=CNC2=C1 SAIMZEWINXIYCT-UHFFFAOYSA-N 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 10
- 230000002285 radioactive effect Effects 0.000 description 10
- 238000002360 preparation method Methods 0.000 description 9
- 102000030621 adenylate cyclase Human genes 0.000 description 8
- 108060000200 adenylate cyclase Proteins 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 125000006239 protecting group Chemical group 0.000 description 8
- SRSKXJVMVSSSHB-UHFFFAOYSA-N 1h-pyrrolo[3,2-c]pyridine Chemical class N1=CC=C2NC=CC2=C1 SRSKXJVMVSSSHB-UHFFFAOYSA-N 0.000 description 7
- FANGSOMZRLKCRU-UHFFFAOYSA-N 3-(1,2,3,5,8,8a-hexahydroindolizin-7-yl)-1-(4-methylphenyl)sulfonylpyrrolo[3,2-c]pyridine Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N1C2=CC=NC=C2C(C=2CC3CCCN3CC=2)=C1 FANGSOMZRLKCRU-UHFFFAOYSA-N 0.000 description 7
- VSLFARANIWFODR-UHFFFAOYSA-N 3-(1,2,3,5,8,8a-hexahydroindolizin-7-yl)-1-naphthalen-2-ylsulfonylpyrrolo[2,3-b]pyridine Chemical compound C1=C(C=2CC3CCCN3CC=2)C2=CC=CN=C2N1S(=O)(=O)C1=CC=C(C=CC=C2)C2=C1 VSLFARANIWFODR-UHFFFAOYSA-N 0.000 description 7
- BFXHJFKKRGVUMU-UHFFFAOYSA-N 4-fluorobenzenesulfonyl chloride Chemical compound FC1=CC=C(S(Cl)(=O)=O)C=C1 BFXHJFKKRGVUMU-UHFFFAOYSA-N 0.000 description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- 239000003446 ligand Substances 0.000 description 7
- 229910052763 palladium Inorganic materials 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 230000000638 stimulation Effects 0.000 description 7
- WGFKJBUKBWWQRR-UHFFFAOYSA-N (4-methoxyphenyl)-[3-(1-methyl-3,6-dihydro-2h-pyridin-4-yl)pyrrolo[2,3-b]pyridin-1-yl]methanone Chemical compound C1=CC(OC)=CC=C1C(=O)N1C2=NC=CC=C2C(C=2CCN(C)CC=2)=C1 WGFKJBUKBWWQRR-UHFFFAOYSA-N 0.000 description 6
- CSGQRPHJYSLUOB-UHFFFAOYSA-N 1-(4-fluorophenyl)sulfonyl-3-(1-methyl-3,6-dihydro-2h-pyridin-4-yl)pyrrolo[2,3-b]pyridine Chemical compound C1N(C)CCC(C=2C3=CC=CN=C3N(C=2)S(=O)(=O)C=2C=CC(F)=CC=2)=C1 CSGQRPHJYSLUOB-UHFFFAOYSA-N 0.000 description 6
- PMWBNLNNRYVXEV-UHFFFAOYSA-N 1-(4-methoxyphenyl)sulfonyl-3-(1-methyl-3,6-dihydro-2h-pyridin-4-yl)pyrrolo[2,3-b]pyridine Chemical compound C1=CC(OC)=CC=C1S(=O)(=O)N1C2=NC=CC=C2C(C=2CCN(C)CC=2)=C1 PMWBNLNNRYVXEV-UHFFFAOYSA-N 0.000 description 6
- MVXVYAKCVDQRLW-UHFFFAOYSA-N 1h-pyrrolo[2,3-b]pyridine Chemical compound C1=CN=C2NC=CC2=C1 MVXVYAKCVDQRLW-UHFFFAOYSA-N 0.000 description 6
- BXCOSWRSIISQSL-UHFFFAOYSA-N 2,5-dichlorobenzenesulfonyl chloride Chemical compound ClC1=CC=C(Cl)C(S(Cl)(=O)=O)=C1 BXCOSWRSIISQSL-UHFFFAOYSA-N 0.000 description 6
- AWYUZTSYTKLODW-UHFFFAOYSA-N 3-(1,2,3,5,8,8a-hexahydroindolizin-7-yl)-1-(benzenesulfonyl)pyrrolo[2,3-b]pyridine Chemical compound C1=C(C=2CC3CCCN3CC=2)C2=CC=CN=C2N1S(=O)(=O)C1=CC=CC=C1 AWYUZTSYTKLODW-UHFFFAOYSA-N 0.000 description 6
- DKMNUGORMDRDSC-UHFFFAOYSA-N 3-(1,2,3,5,8,8a-hexahydroindolizin-7-yl)-1-naphthalen-1-ylsulfonylpyrrolo[2,3-c]pyridine Chemical compound C1=C(C=2CC3CCCN3CC=2)C2=CC=NC=C2N1S(=O)(=O)C1=CC=CC2=CC=CC=C12 DKMNUGORMDRDSC-UHFFFAOYSA-N 0.000 description 6
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 6
- 239000012442 inert solvent Substances 0.000 description 6
- 239000000651 prodrug Substances 0.000 description 6
- 229940002612 prodrug Drugs 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- ONIKNECPXCLUHT-UHFFFAOYSA-N 2-chlorobenzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1Cl ONIKNECPXCLUHT-UHFFFAOYSA-N 0.000 description 5
- 230000002378 acidificating effect Effects 0.000 description 5
- 239000000556 agonist Substances 0.000 description 5
- 239000005557 antagonist Substances 0.000 description 5
- 230000027455 binding Effects 0.000 description 5
- 238000011534 incubation Methods 0.000 description 5
- 239000003921 oil Substances 0.000 description 5
- 235000019198 oils Nutrition 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- JBLIDPPHFGWTKU-UHFFFAOYSA-N 2,6-dichlorobenzoyl chloride Chemical compound ClC(=O)C1=C(Cl)C=CC=C1Cl JBLIDPPHFGWTKU-UHFFFAOYSA-N 0.000 description 4
- NDXRPDJVAUCBOH-UHFFFAOYSA-N 2,6-dimethoxybenzoyl chloride Chemical compound COC1=CC=CC(OC)=C1C(Cl)=O NDXRPDJVAUCBOH-UHFFFAOYSA-N 0.000 description 4
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 4
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 4
- 208000028017 Psychotic disease Diseases 0.000 description 4
- 239000002552 dosage form Substances 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000010561 standard procedure Methods 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- XWIYUCRMWCHYJR-UHFFFAOYSA-N 1h-pyrrolo[3,2-b]pyridine Chemical compound C1=CC=C2NC=CC2=N1 XWIYUCRMWCHYJR-UHFFFAOYSA-N 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 3
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 102000014630 G protein-coupled serotonin receptor activity proteins Human genes 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 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
- 239000004480 active ingredient Substances 0.000 description 3
- 239000000443 aerosol Substances 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 210000003169 central nervous system Anatomy 0.000 description 3
- 239000003153 chemical reaction reagent 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
- 238000004440 column chromatography Methods 0.000 description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 150000002148 esters Chemical class 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000007937 lozenge Substances 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 239000002287 radioligand Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- VOWZLIDMGVQIJJ-UHFFFAOYSA-N 1-[3-(1,2,3,5,6,7,8,8a-octahydroindolizin-7-yl)-2,5-dichlorophenyl]sulfonylpyrrolo[3,2-c]pyridine Chemical compound C1=CC2=CN=CC=C2N1S(=O)(=O)C1=CC(Cl)=CC(C2CC3CCCN3CC2)=C1Cl VOWZLIDMGVQIJJ-UHFFFAOYSA-N 0.000 description 2
- HUUPVABNAQUEJW-UHFFFAOYSA-N 1-methylpiperidin-4-one Chemical compound CN1CCC(=O)CC1 HUUPVABNAQUEJW-UHFFFAOYSA-N 0.000 description 2
- XLKDJOPOOHHZAN-UHFFFAOYSA-N 1h-pyrrolo[2,3-c]pyridine Chemical compound C1=NC=C2NC=CC2=C1 XLKDJOPOOHHZAN-UHFFFAOYSA-N 0.000 description 2
- 125000004098 2,6-dichlorobenzoyl group Chemical group O=C([*])C1=C(Cl)C([H])=C([H])C([H])=C1Cl 0.000 description 2
- GKOQFJOONFQSDQ-UHFFFAOYSA-N 4-(1-naphthalen-1-ylsulfonylpyrrolo[3,2-c]pyridin-3-yl)-2,3,4,6,7,8,9,9a-octahydro-1h-quinolizine Chemical compound C1=C(C2N3CCCCC3CCC2)C2=CN=CC=C2N1S(=O)(=O)C1=CC=CC2=CC=CC=C12 GKOQFJOONFQSDQ-UHFFFAOYSA-N 0.000 description 2
- CZKLEJHVLCMVQR-UHFFFAOYSA-N 4-fluorobenzoyl chloride Chemical compound FC1=CC=C(C(Cl)=O)C=C1 CZKLEJHVLCMVQR-UHFFFAOYSA-N 0.000 description 2
- DTJVECUKADWGMO-UHFFFAOYSA-N 4-methoxybenzenesulfonyl chloride Chemical compound COC1=CC=C(S(Cl)(=O)=O)C=C1 DTJVECUKADWGMO-UHFFFAOYSA-N 0.000 description 2
- 208000024827 Alzheimer disease Diseases 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 208000020925 Bipolar disease Diseases 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 2
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- 208000023105 Huntington disease Diseases 0.000 description 2
- 208000026139 Memory disease Diseases 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- 208000012902 Nervous system disease Diseases 0.000 description 2
- 208000025966 Neurological disease Diseases 0.000 description 2
- 208000018737 Parkinson disease Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical compound [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 2
- 239000004479 aerosol dispenser Substances 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- MXMOTZIXVICDSD-UHFFFAOYSA-N anisoyl chloride Chemical compound COC1=CC=C(C(Cl)=O)C=C1 MXMOTZIXVICDSD-UHFFFAOYSA-N 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 125000005334 azaindolyl group Chemical class N1N=C(C2=CC=CC=C12)* 0.000 description 2
- 208000028683 bipolar I disease Diseases 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- 239000010949 copper Substances 0.000 description 2
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 239000006185 dispersion Substances 0.000 description 2
- 239000006196 drop Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000012894 fetal calf serum Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 125000000623 heterocyclic group Chemical group 0.000 description 2
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 150000007522 mineralic acids Chemical class 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000008188 pellet Substances 0.000 description 2
- 239000002953 phosphate buffered saline Substances 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000003380 propellant Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000002464 receptor antagonist Substances 0.000 description 2
- 229940044551 receptor antagonist Drugs 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- 229910052722 tritium Inorganic materials 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- 125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 1
- CQTKSBAHMPWPQD-UHFFFAOYSA-N 2,3,5,6,8,8a-hexahydro-1h-indolizin-7-one Chemical compound C1C(=O)CCN2CCCC21 CQTKSBAHMPWPQD-UHFFFAOYSA-N 0.000 description 1
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
- APIXJSLKIYYUKG-UHFFFAOYSA-N 3 Isobutyl 1 methylxanthine Chemical compound O=C1N(C)C(=O)N(CC(C)C)C2=C1N=CN2 APIXJSLKIYYUKG-UHFFFAOYSA-N 0.000 description 1
- OFCNTYBPPAQCRE-UHFFFAOYSA-N 3-(2-aminoethyl)-3h-indol-5-ol Chemical compound C1=C(O)C=C2C(CCN)C=NC2=C1 OFCNTYBPPAQCRE-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-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
- 235000003911 Arachis Nutrition 0.000 description 1
- 244000105624 Arachis hypogaea Species 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 229940126062 Compound A Drugs 0.000 description 1
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 description 1
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 1
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 1
- 206010012239 Delusion Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 238000011891 EIA kit Methods 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 102000018899 Glutamate Receptors Human genes 0.000 description 1
- 108010027915 Glutamate Receptors Proteins 0.000 description 1
- 208000004547 Hallucinations Diseases 0.000 description 1
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- 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 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 102000003840 Opioid Receptors Human genes 0.000 description 1
- 108090000137 Opioid Receptors Proteins 0.000 description 1
- 102000016979 Other receptors Human genes 0.000 description 1
- DPWPWRLQFGFJFI-UHFFFAOYSA-N Pargyline Chemical compound C#CCN(C)CC1=CC=CC=C1 DPWPWRLQFGFJFI-UHFFFAOYSA-N 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 125000005042 acyloxymethyl group Chemical group 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000012296 anti-solvent Substances 0.000 description 1
- 239000008365 aqueous carrier Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 150000001502 aryl halides Chemical class 0.000 description 1
- 125000005279 aryl sulfonyloxy group Chemical group 0.000 description 1
- 238000006254 arylation reaction Methods 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 1
- 150000007514 bases Chemical class 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000002619 bicyclic group Chemical group 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
- 239000000872 buffer Substances 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 150000004657 carbamic acid derivatives Chemical class 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 206010007776 catatonia Diseases 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- VDQQXEISLMTGAB-UHFFFAOYSA-N chloramine T Chemical compound [Na+].CC1=CC=C(S(=O)(=O)[N-]Cl)C=C1 VDQQXEISLMTGAB-UHFFFAOYSA-N 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000010367 cloning Methods 0.000 description 1
- QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 description 1
- 229960004170 clozapine Drugs 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 229940095074 cyclic amp Drugs 0.000 description 1
- 231100000868 delusion Toxicity 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- VFNGKCDDZUSWLR-UHFFFAOYSA-L disulfate(2-) Chemical compound [O-]S(=O)(=O)OS([O-])(=O)=O VFNGKCDDZUSWLR-UHFFFAOYSA-L 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000003821 enantio-separation Methods 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- NBVXSUQYWXRMNV-UHFFFAOYSA-N fluoromethane Chemical compound FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 238000002825 functional assay Methods 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- ZTQSADJAYQOCDD-UHFFFAOYSA-N ginsenoside-Rd2 Natural products C1CC(C2(CCC3C(C)(C)C(OC4C(C(O)C(O)C(CO)O4)O)CCC3(C)C2CC2O)C)(C)C2C1C(C)(CCC=C(C)C)OC(C(C(O)C1O)O)OC1COC1OCC(O)C(O)C1O ZTQSADJAYQOCDD-UHFFFAOYSA-N 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 238000003018 immunoassay Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000026045 iodination Effects 0.000 description 1
- 238000006192 iodination reaction Methods 0.000 description 1
- 150000002497 iodine compounds Chemical class 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 201000010901 lateral sclerosis Diseases 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 239000012669 liquid formulation Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910052987 metal hydride Inorganic materials 0.000 description 1
- 150000004681 metal hydrides Chemical class 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 208000005264 motor neuron disease Diseases 0.000 description 1
- 239000006199 nebulizer Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 238000002414 normal-phase solid-phase extraction Methods 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 150000003891 oxalate salts Chemical class 0.000 description 1
- 229960001779 pargyline Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- 230000000171 quenching effect Effects 0.000 description 1
- LJPZHJUSICYOIX-UHFFFAOYSA-N quinolizidine Chemical compound C1CCCC2CCCCN21 LJPZHJUSICYOIX-UHFFFAOYSA-N 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000001688 serotonin response Effects 0.000 description 1
- 239000012679 serum free medium Substances 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- FVAUCKIRQBBSSJ-FXMLPJBTSA-M sodium;iodine-125(1-) Chemical compound [Na+].[125I-] FVAUCKIRQBBSSJ-FXMLPJBTSA-M 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 208000027765 speech disease Diseases 0.000 description 1
- 238000004544 sputter deposition Methods 0.000 description 1
- 238000005797 stannylation reaction Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- YOEWQQVKRJEPAE-UHFFFAOYSA-L succinylcholine chloride (anhydrous) Chemical compound [Cl-].[Cl-].C[N+](C)(C)CCOC(=O)CCC(=O)OCC[N+](C)(C)C YOEWQQVKRJEPAE-UHFFFAOYSA-L 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical compound OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 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
- UUBIWGRMBVAUIK-UHFFFAOYSA-N tetracyclo[5.5.2.04,13.010,14]tetradeca-1(13),4,6,10(14),11-pentaene Chemical compound C1CC2=CC=C3CCC4=CC=C1C2=C43 UUBIWGRMBVAUIK-UHFFFAOYSA-N 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 150000003573 thiols Chemical class 0.000 description 1
- 229960001479 tosylchloramide sodium Drugs 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 150000003628 tricarboxylic acids Chemical class 0.000 description 1
- LYRCQNDYYRPFMF-UHFFFAOYSA-N trimethyltin Chemical class C[Sn](C)C LYRCQNDYYRPFMF-UHFFFAOYSA-N 0.000 description 1
- CCRMAATUKBYMPA-UHFFFAOYSA-N trimethyltin Chemical compound C[Sn](C)C.C[Sn](C)C CCRMAATUKBYMPA-UHFFFAOYSA-N 0.000 description 1
- 238000003828 vacuum filtration Methods 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
- 235000021419 vinegar Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- 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
- A61P25/24—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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Pain & Pain Management (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicinal Preparation (AREA)
- Materials For Medical Uses (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US14834399P | 1999-08-12 | 1999-08-12 | |
| US148343P | 1999-08-12 | ||
| PCT/IB2000/001122 WO2001012629A1 (en) | 1999-08-12 | 2000-08-14 | Azaindoles having serotonin receptor affinity |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE60011269D1 DE60011269D1 (de) | 2004-07-08 |
| DE60011269T2 true DE60011269T2 (de) | 2005-06-23 |
Family
ID=22525363
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE60011269T Expired - Lifetime DE60011269T2 (de) | 1999-08-12 | 2000-08-14 | Azaidole mit serotonin rezeptor affinität |
Country Status (10)
| Country | Link |
|---|---|
| EP (1) | EP1204662B1 (enExample) |
| JP (1) | JP4969004B2 (enExample) |
| AT (1) | ATE268330T1 (enExample) |
| AU (1) | AU779832B2 (enExample) |
| CA (1) | CA2382247C (enExample) |
| DE (1) | DE60011269T2 (enExample) |
| DK (1) | DK1204662T3 (enExample) |
| ES (1) | ES2222219T3 (enExample) |
| MX (1) | MXPA02001473A (enExample) |
| WO (1) | WO2001012629A1 (enExample) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10030037A1 (de) | 2000-06-17 | 2001-12-20 | Mann & Hummel Filter | Zylindrische Filterpatrone mit Stützrohr |
| ITRM20010356A1 (it) * | 2001-06-21 | 2002-12-23 | Sigma Tau Ind Farmaceuti | "5-alogeno derivati della triptamina utili come ligandi del recettore5-ht6 e/o 5-ht7 della serotonina. |
| HUP0402640A3 (en) * | 2001-12-20 | 2012-09-28 | Wyeth Corp | Indolylalkylamine derivatives as 5-hydroxytryptamine-6 ligands, process for their preparation and pharmaceutical compositions thereof |
| TW200301251A (en) * | 2001-12-20 | 2003-07-01 | Wyeth Corp | Azaindolylalkylamine derivatives as 5-hydroxytryptamine-6 ligands |
| GB0202679D0 (en) * | 2002-02-05 | 2002-03-20 | Glaxo Group Ltd | Novel compounds |
| ATE346068T1 (de) * | 2002-03-27 | 2006-12-15 | Glaxo Group Ltd | Chinolin- und aza-indolderivate und deren verwendung als 5-ht6 liganden |
| UA78999C2 (en) * | 2002-06-04 | 2007-05-10 | Wyeth Corp | 1-(aminoalkyl)-3-sulfonylazaindoles as ligands of 5-hydroxytryptamine-6 |
| EP1897876A3 (en) | 2002-06-20 | 2009-03-18 | Biovitrum AB (publ) | Compounds useful for the treatment of obesity, type II diabetes and CNS disorders |
| TW200403243A (en) | 2002-07-18 | 2004-03-01 | Wyeth Corp | 1-Heterocyclylalkyl-3-sulfonylazaindole or-azaindazole derivatives as 5-hydroxytryptamine-6 ligands |
| EP1592772A2 (en) * | 2003-01-31 | 2005-11-09 | Pfizer Products Incorporated | 5ht7 antagonists and inverse agonists |
| CN100482662C (zh) * | 2003-02-14 | 2009-04-29 | 惠氏公司 | 作为5-羟基色胺-6配体的杂环基-3-磺酰基氮杂吲哚或-氮杂吲唑衍生物 |
| JP2006528186A (ja) * | 2003-07-23 | 2006-12-14 | ワイス | ５−ヒドロキシトリプタミン−６リガンドとしてのスルホニルジヒドロベンゾイミダゾロン化合物 |
| ES2222828B1 (es) * | 2003-07-30 | 2006-04-16 | Laboratorios Del Dr. Esteve, S.A. | Derivados de 1-sulfonilindoles, su preparacion y su aplicacion como medicamentos. |
| AU2007217040A1 (en) * | 2006-02-17 | 2007-08-30 | Memory Pharmaceuticals Corporation | Compounds having 5-HT6 receptor affinity |
| EP2046741B1 (en) * | 2006-07-03 | 2012-10-31 | Proximagen Ltd. | Indoles as 5-ht6 modulators |
| WO2012160464A1 (en) * | 2011-05-26 | 2012-11-29 | Daiichi Sankyo Company, Limited | Heterocyclic compounds as protein kinase inhibitors |
| EP3083588B1 (en) | 2013-12-20 | 2020-12-09 | Sunshine Lake Pharma Co., Ltd. | Aromatic heterocyclic compounds and their application in pharmaceuticals |
| EP3166924B1 (en) | 2014-07-08 | 2019-02-20 | Sunshine Lake Pharma Co., Ltd. | Aromatic heterocyclic derivatives and pharmaceutical applications thereof |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR9406128A (pt) * | 1993-03-01 | 1996-02-27 | Merck Sharp & Dohme | Uso de um composto processo para o tratamento e/ou prevençao de distúrbios psicóticos composto composiçao farmacêutica processos para a preparaçao de um composto e de uma composiçao farmacêutica |
| US5846982A (en) * | 1996-06-14 | 1998-12-08 | Eli Lilly And Company | Inhibition of serotonin reuptake |
| EP0875513A1 (en) * | 1997-04-14 | 1998-11-04 | Eli Lilly And Company | Substituted heteroaromatic 5-HT 1F agonists |
| US5905084A (en) * | 1997-11-14 | 1999-05-18 | Eli Lilly And Company | 5-HTIF -agonists effective in treating migraine |
| US6562809B1 (en) * | 1998-09-18 | 2003-05-13 | Nps Allelix Corp. | 3-bicycloindole compounds |
-
2000
- 2000-08-14 MX MXPA02001473A patent/MXPA02001473A/es active IP Right Grant
- 2000-08-14 AT AT00949846T patent/ATE268330T1/de active
- 2000-08-14 ES ES00949846T patent/ES2222219T3/es not_active Expired - Lifetime
- 2000-08-14 WO PCT/IB2000/001122 patent/WO2001012629A1/en not_active Ceased
- 2000-08-14 EP EP00949846A patent/EP1204662B1/en not_active Expired - Lifetime
- 2000-08-14 AU AU63103/00A patent/AU779832B2/en not_active Ceased
- 2000-08-14 DK DK00949846T patent/DK1204662T3/da active
- 2000-08-14 DE DE60011269T patent/DE60011269T2/de not_active Expired - Lifetime
- 2000-08-14 JP JP2001517527A patent/JP4969004B2/ja not_active Expired - Fee Related
- 2000-08-14 CA CA2382247A patent/CA2382247C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| JP4969004B2 (ja) | 2012-07-04 |
| JP2003507380A (ja) | 2003-02-25 |
| ES2222219T3 (es) | 2005-02-01 |
| WO2001012629A1 (en) | 2001-02-22 |
| DE60011269D1 (de) | 2004-07-08 |
| DK1204662T3 (da) | 2004-10-04 |
| CA2382247A1 (en) | 2001-02-22 |
| EP1204662B1 (en) | 2004-06-02 |
| AU6310300A (en) | 2001-03-13 |
| CA2382247C (en) | 2010-09-28 |
| MXPA02001473A (es) | 2003-07-21 |
| EP1204662A1 (en) | 2002-05-15 |
| AU779832B2 (en) | 2005-02-10 |
| ATE268330T1 (de) | 2004-06-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| DE60011269T2 (de) | Azaidole mit serotonin rezeptor affinität | |
| DE69911798T2 (de) | Bicyclische piperidin- und piperazin-verbindungen mit 5-ht6-rezeptor-affinität | |
| DE69937372T2 (de) | Piperidin-indol derivate mit 5-ht6 affinität | |
| US8148394B2 (en) | Azaindoles having serotonin receptor affinity | |
| US9271971B2 (en) | Pyrido[3,4-B]indoles and methods of use | |
| DE602004011806T2 (de) | Verwendung tricyclischer verbindungen als inhibitoren des glycintransports | |
| DE60125335T2 (de) | Azacyclische verbindungen zur verwendung in der behandlung von mit serotonin verwandten krankheiten | |
| DE69531476T2 (de) | Serotonergische Modulatoren | |
| WO2011038162A1 (en) | Pyrido(3,4-b)indoles and methods of use | |
| CA2742322A1 (en) | Azepino[4,5-b]indoles and methods of use | |
| WO2011014695A1 (en) | New 2,3,4,5-tetrahydro-1h-pyrido[4,3-b] indoles and methods of use | |
| WO2011038164A1 (en) | Bridged heterocyclic compounds and methods of use | |
| DE69815700T2 (de) | Tetrahydro gamma-carboline | |
| US6191141B1 (en) | Azaindoles having serotonin receptor affinity | |
| DE60102106T2 (de) | Diazacyclooctanverbindungen und ihre therapeutische Verwendung | |
| DE68905363T2 (de) | Heterotetracyclische laktamderivate, verfahren zu ihrer herstellung und pharmazeutische zubereitungen, die sie enthalten. | |
| JPH08501548A (ja) | 抗精神病薬としての環状ベンジルアミノ、ベンジルアミド及びベンジルイミド誘導体 | |
| KR20200118008A (ko) | 테트라하이드로피롤계 화합물, 그의 제조방법, 약학조성물 및 용도 | |
| AU2013203580A1 (en) | Bridged heterocyclic compounds and methods of use | |
| AU2013203691A1 (en) | Pyrido[3,4-b]indoles and methods of use | |
| AU2013203574A1 (en) | Pyrido [4,3-b] indoles and methods of use |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8364 | No opposition during term of opposition | ||
| 8327 | Change in the person/name/address of the patent owner |
Owner name: NPS PHARMACEUTICALS,INC., BEDMINSTER, N.J., US |