CA2236834A1 - Derives de piperidine et de tetrahydropyridine - Google Patents
Derives de piperidine et de tetrahydropyridine Download PDFInfo
- Publication number
- CA2236834A1 CA2236834A1 CA 2236834 CA2236834A CA2236834A1 CA 2236834 A1 CA2236834 A1 CA 2236834A1 CA 2236834 CA2236834 CA 2236834 CA 2236834 A CA2236834 A CA 2236834A CA 2236834 A1 CA2236834 A1 CA 2236834A1
- Authority
- CA
- Canada
- Prior art keywords
- propyl
- indol
- triazol
- piperidine
- compound
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 title claims abstract description 122
- VSWICNJIUPRZIK-UHFFFAOYSA-N 2-piperideine Chemical class C1CNC=CC1 VSWICNJIUPRZIK-UHFFFAOYSA-N 0.000 title abstract description 6
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 13
- 239000000556 agonist Substances 0.000 claims abstract description 10
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 6
- 101710138068 5-hydroxytryptamine receptor 1D Proteins 0.000 claims abstract description 5
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 4
- 102100027493 5-hydroxytryptamine receptor 1D Human genes 0.000 claims abstract 3
- 101100321769 Takifugu rubripes htr1d gene Proteins 0.000 claims abstract 3
- 230000002265 prevention Effects 0.000 claims abstract 3
- 150000001875 compounds Chemical class 0.000 claims description 179
- -1 aminosulphonyl Chemical group 0.000 claims description 128
- 238000000034 method Methods 0.000 claims description 111
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 57
- 229910052739 hydrogen Inorganic materials 0.000 claims description 48
- 239000001257 hydrogen Substances 0.000 claims description 44
- 125000000217 alkyl group Chemical group 0.000 claims description 42
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 28
- 125000001072 heteroaryl group Chemical group 0.000 claims description 25
- 150000003839 salts Chemical class 0.000 claims description 25
- 150000002431 hydrogen Chemical class 0.000 claims description 22
- 229910052757 nitrogen Inorganic materials 0.000 claims description 22
- 125000001424 substituent group Chemical group 0.000 claims description 22
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 18
- 239000000651 prodrug Substances 0.000 claims description 17
- 229940002612 prodrug Drugs 0.000 claims description 17
- 125000003118 aryl group Chemical group 0.000 claims description 16
- 229910052736 halogen Inorganic materials 0.000 claims description 16
- 150000002367 halogens Chemical class 0.000 claims description 16
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 16
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 15
- 239000001301 oxygen Substances 0.000 claims description 15
- 229910052760 oxygen Inorganic materials 0.000 claims description 15
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 14
- 239000005864 Sulphur Chemical group 0.000 claims description 14
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 14
- 125000001153 fluoro group Chemical group F* 0.000 claims description 13
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 13
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 11
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 11
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- 230000008569 process Effects 0.000 claims description 10
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical class C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 9
- 238000010561 standard procedure Methods 0.000 claims description 9
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 8
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 8
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 8
- 150000003852 triazoles Chemical class 0.000 claims description 8
- 125000001425 triazolyl group Chemical group 0.000 claims description 8
- 238000007126 N-alkylation reaction Methods 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 6
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 6
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical class C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 6
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 6
- 229910052731 fluorine Inorganic materials 0.000 claims description 6
- 125000004193 piperazinyl group Chemical class 0.000 claims description 6
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 5
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 5
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 4
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 4
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 3
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 3
- 125000006598 aminocarbonylamino group Chemical group 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 3
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 3
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 3
- 125000004076 pyridyl group Chemical group 0.000 claims description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- 150000003536 tetrazoles Chemical class 0.000 claims description 3
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 claims description 3
- 125000000335 thiazolyl group Chemical group 0.000 claims description 3
- 125000001544 thienyl group Chemical group 0.000 claims description 3
- 125000003944 tolyl group Chemical group 0.000 claims description 3
- 229910052720 vanadium Inorganic materials 0.000 claims description 3
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 2
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 2
- DOLFSYNUZKAKRT-UHFFFAOYSA-N 3-[2-fluoro-3-[1-(2-phenylpropyl)piperidin-4-yl]propyl]-5-(1,2,4-triazol-4-yl)-1h-indole Chemical compound C=1C=CC=CC=1C(C)CN(CC1)CCC1CC(F)CC(C1=C2)=CNC1=CC=C2N1C=NN=C1 DOLFSYNUZKAKRT-UHFFFAOYSA-N 0.000 claims description 2
- GTFSCSYEJVIJEU-UHFFFAOYSA-N 3-[3-[1-(3,3-dimethylbutyl)piperidin-4-yl]propyl]-5-(1,2,4-triazol-4-yl)-1h-indole Chemical compound C1CN(CCC(C)(C)C)CCC1CCCC1=CNC2=CC=C(N3C=NN=C3)C=C12 GTFSCSYEJVIJEU-UHFFFAOYSA-N 0.000 claims description 2
- CXMHQBLUKUGQDS-HXUWFJFHSA-N 3-[3-[1-[(2s)-2-pyridin-3-ylpropyl]piperidin-4-yl]propyl]-5-(1,2,4-triazol-4-yl)-1h-indole Chemical compound C([C@@H](C)C=1C=NC=CC=1)N(CC1)CCC1CCCC(C1=C2)=CNC1=CC=C2N1C=NN=C1 CXMHQBLUKUGQDS-HXUWFJFHSA-N 0.000 claims description 2
- ARITVDZVAAVCHM-UHFFFAOYSA-N 3-[3-[1-[2-(2,6-dichlorophenyl)propyl]piperidin-4-yl]propyl]-5-(1,2,4-triazol-4-yl)-1h-indole Chemical compound ClC=1C=CC=C(Cl)C=1C(C)CN(CC1)CCC1CCCC(C1=C2)=CNC1=CC=C2N1C=NN=C1 ARITVDZVAAVCHM-UHFFFAOYSA-N 0.000 claims description 2
- CEBXMVWPFONHBJ-UHFFFAOYSA-N 3-[3-[1-[2-(4-methoxypyridin-3-yl)propyl]piperidin-4-yl]propyl]-5-(1,2,4-triazol-4-yl)-1h-indole Chemical compound COC1=CC=NC=C1C(C)CN1CCC(CCCC=2C3=CC(=CC=C3NC=2)N2C=NN=C2)CC1 CEBXMVWPFONHBJ-UHFFFAOYSA-N 0.000 claims description 2
- HHUHSVIQHVIKHY-UHFFFAOYSA-N 3-[3-[4-fluoro-1-(2-phenylpropyl)piperidin-4-yl]propyl]-5-(1,2,4-triazol-4-yl)-1h-indole Chemical compound C=1C=CC=CC=1C(C)CN(CC1)CCC1(F)CCCC(C1=C2)=CNC1=CC=C2N1C=NN=C1 HHUHSVIQHVIKHY-UHFFFAOYSA-N 0.000 claims description 2
- ACHTUNLIYNQHGL-UHFFFAOYSA-N 5-(1,2,4-triazol-4-yl)-3-[3-[1-[2-[4-(trifluoromethyl)phenyl]ethyl]piperidin-4-yl]propyl]-1h-indole Chemical compound C1=CC(C(F)(F)F)=CC=C1CCN1CCC(CCCC=2C3=CC(=CC=C3NC=2)N2C=NN=C2)CC1 ACHTUNLIYNQHGL-UHFFFAOYSA-N 0.000 claims description 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
- 150000001539 azetidines Chemical class 0.000 claims description 2
- 125000002883 imidazolyl group Chemical group 0.000 claims description 2
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 claims description 2
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical compound C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 125000003107 substituted aryl group Chemical group 0.000 claims description 2
- 229930192474 thiophene Natural products 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 10
- RPXLZVOGZQWPOV-UQTORGHUSA-N (4s)-4-[[3-[3-[1-(2-phenylpropyl)piperidin-4-yl]propyl]-1h-indol-5-yl]methyl]-1,3-oxazolidin-2-one Chemical compound C=1C=CC=CC=1C(C)CN(CC1)CCC1CCCC(C1=C2)=CNC1=CC=C2C[C@H]1COC(=O)N1 RPXLZVOGZQWPOV-UQTORGHUSA-N 0.000 claims 1
- VITPBIRRYBRMLY-UHFFFAOYSA-N 1-[1-(2-phenylpropyl)piperidin-4-yl]-3-[5-(1,2,4-triazol-4-yl)-1h-indol-3-yl]propan-2-ol Chemical compound C=1C=CC=CC=1C(C)CN(CC1)CCC1CC(O)CC(C1=C2)=CNC1=CC=C2N1C=NN=C1 VITPBIRRYBRMLY-UHFFFAOYSA-N 0.000 claims 1
- IMUWCCZDFMSWAD-UHFFFAOYSA-N 1-[1-(2-phenylpropyl)piperidin-4-yl]-3-[5-(1,2,4-triazol-4-yl)-1h-indol-3-yl]propan-2-one Chemical compound C=1C=CC=CC=1C(C)CN(CC1)CCC1CC(=O)CC(C1=C2)=CNC1=CC=C2N1C=NN=C1 IMUWCCZDFMSWAD-UHFFFAOYSA-N 0.000 claims 1
- BJIHSBSJXZMHBL-UHFFFAOYSA-N 1-phenyl-2-[4-[3-[5-(1,2,4-triazol-4-yl)-1h-indol-3-yl]propyl]piperidin-1-yl]ethanone Chemical compound C=1C=CC=CC=1C(=O)CN(CC1)CCC1CCCC(C1=C2)=CNC1=CC=C2N1C=NN=C1 BJIHSBSJXZMHBL-UHFFFAOYSA-N 0.000 claims 1
- DFHSJCQYXAHBLJ-UHFFFAOYSA-N 2-[1-[4-[3-[5-(1,2,4-triazol-4-yl)-1h-indol-3-yl]propyl]piperidin-1-yl]propan-2-yl]-1,3-thiazole Chemical compound N=1C=CSC=1C(C)CN(CC1)CCC1CCCC(C1=C2)=CNC1=CC=C2N1C=NN=C1 DFHSJCQYXAHBLJ-UHFFFAOYSA-N 0.000 claims 1
- AGGXUIBKRIZUDT-UHFFFAOYSA-N 2-phenyl-1-[4-[3-[5-(1,2,4-triazol-4-yl)-1h-indol-3-yl]propyl]piperidin-1-yl]propan-2-ol Chemical compound C=1C=CC=CC=1C(O)(C)CN(CC1)CCC1CCCC(C1=C2)=CNC1=CC=C2N1C=NN=C1 AGGXUIBKRIZUDT-UHFFFAOYSA-N 0.000 claims 1
- MNOJTYZXEUSFSS-UHFFFAOYSA-N 3-[1-[4-[3-[5-(1,2,4-triazol-4-yl)-1h-indol-3-yl]propyl]piperidin-1-yl]propan-2-yl]benzenesulfonamide Chemical compound C=1C=CC(S(N)(=O)=O)=CC=1C(C)CN(CC1)CCC1CCCC(C1=C2)=CNC1=CC=C2N1C=NN=C1 MNOJTYZXEUSFSS-UHFFFAOYSA-N 0.000 claims 1
- ZXYFVOOEOPXNHY-UHFFFAOYSA-N 3-[3-[1-(2-phenylethyl)piperidin-4-yl]propyl]-5-(1,2,4-triazol-4-yl)-1h-indole Chemical compound C=1NC2=CC=C(N3C=NN=C3)C=C2C=1CCCC(CC1)CCN1CCC1=CC=CC=C1 ZXYFVOOEOPXNHY-UHFFFAOYSA-N 0.000 claims 1
- QABDZPJZBUJMAQ-UHFFFAOYSA-N 3-[3-[1-(2-phenylpropyl)piperidin-4-yl]propyl]-5-(1,2,4-triazol-4-yl)-1h-indole Chemical compound C=1C=CC=CC=1C(C)CN(CC1)CCC1CCCC(C1=C2)=CNC1=CC=C2N1C=NN=C1 QABDZPJZBUJMAQ-UHFFFAOYSA-N 0.000 claims 1
- FFAIOJMMYBMFTL-UHFFFAOYSA-N 3-[3-[1-(2-pyrazol-1-ylpropyl)piperidin-4-yl]propyl]-5-(1,2,4-triazol-4-yl)-1h-indole Chemical compound C1=CC=NN1C(C)CN(CC1)CCC1CCCC(C1=C2)=CNC1=CC=C2N1C=NN=C1 FFAIOJMMYBMFTL-UHFFFAOYSA-N 0.000 claims 1
- YGKWYQGQUQPZMZ-UHFFFAOYSA-N 3-[3-[1-(2-pyridazin-3-ylpropyl)piperidin-4-yl]propyl]-5-(1,2,4-triazol-4-yl)-1h-indole Chemical compound C=1C=CN=NC=1C(C)CN(CC1)CCC1CCCC(C1=C2)=CNC1=CC=C2N1C=NN=C1 YGKWYQGQUQPZMZ-UHFFFAOYSA-N 0.000 claims 1
- FRJYRFQRFZQIDW-UHFFFAOYSA-N 3-[3-[1-(2-pyridin-2-ylpropyl)piperidin-4-yl]propyl]-5-(1,2,4-triazol-4-yl)-1h-indole Chemical compound C=1C=CC=NC=1C(C)CN(CC1)CCC1CCCC(C1=C2)=CNC1=CC=C2N1C=NN=C1 FRJYRFQRFZQIDW-UHFFFAOYSA-N 0.000 claims 1
- CXMHQBLUKUGQDS-UHFFFAOYSA-N 3-[3-[1-(2-pyridin-3-ylpropyl)piperidin-4-yl]propyl]-5-(1,2,4-triazol-4-yl)-1h-indole Chemical compound C=1C=CN=CC=1C(C)CN(CC1)CCC1CCCC(C1=C2)=CNC1=CC=C2N1C=NN=C1 CXMHQBLUKUGQDS-UHFFFAOYSA-N 0.000 claims 1
- LBNSGBKZNXAQLZ-UHFFFAOYSA-N 3-[3-[1-(2-pyridin-4-ylpropyl)piperidin-4-yl]propyl]-5-(1,2,4-triazol-4-yl)-1h-indole Chemical compound C=1C=NC=CC=1C(C)CN(CC1)CCC1CCCC(C1=C2)=CNC1=CC=C2N1C=NN=C1 LBNSGBKZNXAQLZ-UHFFFAOYSA-N 0.000 claims 1
- ICRBWYRJOSITKJ-UHFFFAOYSA-N 3-[3-[1-(2-pyrimidin-2-ylpropyl)piperidin-4-yl]propyl]-5-(1,2,4-triazol-4-yl)-1h-indole Chemical compound N=1C=CC=NC=1C(C)CN(CC1)CCC1CCCC(C1=C2)=CNC1=CC=C2N1C=NN=C1 ICRBWYRJOSITKJ-UHFFFAOYSA-N 0.000 claims 1
- KOBHFVPROGDUGE-UHFFFAOYSA-N 3-[3-[1-(2-thiophen-3-ylpropyl)piperidin-4-yl]propyl]-5-(1,2,4-triazol-4-yl)-1h-indole Chemical compound C1=CSC=C1C(C)CN(CC1)CCC1CCCC(C1=C2)=CNC1=CC=C2N1C=NN=C1 KOBHFVPROGDUGE-UHFFFAOYSA-N 0.000 claims 1
- FFQMMFAZPMIYMW-UHFFFAOYSA-N 3-[3-[1-(3-phenylpropyl)piperidin-4-yl]propyl]-5-(1,2,4-triazol-4-yl)-1h-indole Chemical compound C=1NC2=CC=C(N3C=NN=C3)C=C2C=1CCCC(CC1)CCN1CCCC1=CC=CC=C1 FFQMMFAZPMIYMW-UHFFFAOYSA-N 0.000 claims 1
- QABDZPJZBUJMAQ-NRFANRHFSA-N 3-[3-[1-[(2r)-2-phenylpropyl]piperidin-4-yl]propyl]-5-(1,2,4-triazol-4-yl)-1h-indole Chemical compound C([C@H](C)C=1C=CC=CC=1)N(CC1)CCC1CCCC(C1=C2)=CNC1=CC=C2N1C=NN=C1 QABDZPJZBUJMAQ-NRFANRHFSA-N 0.000 claims 1
- CXMHQBLUKUGQDS-FQEVSTJZSA-N 3-[3-[1-[(2r)-2-pyridin-3-ylpropyl]piperidin-4-yl]propyl]-5-(1,2,4-triazol-4-yl)-1h-indole Chemical compound C([C@H](C)C=1C=NC=CC=1)N(CC1)CCC1CCCC(C1=C2)=CNC1=CC=C2N1C=NN=C1 CXMHQBLUKUGQDS-FQEVSTJZSA-N 0.000 claims 1
- PSHZCAYZMIGWCG-HXUWFJFHSA-N 3-[3-[1-[(2s)-2-(4-fluorophenyl)propyl]piperidin-4-yl]propyl]-5-(1,2,4-triazol-4-yl)-1h-indole Chemical compound C([C@@H](C)C=1C=CC(F)=CC=1)N(CC1)CCC1CCCC(C1=C2)=CNC1=CC=C2N1C=NN=C1 PSHZCAYZMIGWCG-HXUWFJFHSA-N 0.000 claims 1
- JDYZUMABFVDOFV-UHFFFAOYSA-N 3-[3-[1-[2-(2-chlorophenyl)propyl]piperidin-4-yl]propyl]-5-(1,2,4-triazol-4-yl)-1h-indole Chemical compound C=1C=CC=C(Cl)C=1C(C)CN(CC1)CCC1CCCC(C1=C2)=CNC1=CC=C2N1C=NN=C1 JDYZUMABFVDOFV-UHFFFAOYSA-N 0.000 claims 1
- FGAWFURNOBRVBU-UHFFFAOYSA-N 3-[3-[1-[2-(2-fluorophenyl)ethyl]piperidin-4-yl]propyl]-5-(1,2,4-triazol-4-yl)-1h-indole Chemical compound FC1=CC=CC=C1CCN1CCC(CCCC=2C3=CC(=CC=C3NC=2)N2C=NN=C2)CC1 FGAWFURNOBRVBU-UHFFFAOYSA-N 0.000 claims 1
- UEKLJBXXRFKFIC-UHFFFAOYSA-N 3-[3-[1-[2-(2-fluorophenyl)propyl]piperidin-4-yl]propyl]-5-(1,2,4-triazol-4-yl)-1h-indole Chemical compound C=1C=CC=C(F)C=1C(C)CN(CC1)CCC1CCCC(C1=C2)=CNC1=CC=C2N1C=NN=C1 UEKLJBXXRFKFIC-UHFFFAOYSA-N 0.000 claims 1
- RTIHCYHUHPGUHO-UHFFFAOYSA-N 3-[3-[1-[2-(2-methoxyphenyl)propyl]piperidin-4-yl]propyl]-5-(1,2,4-triazol-4-yl)-1h-indole Chemical compound COC1=CC=CC=C1C(C)CN1CCC(CCCC=2C3=CC(=CC=C3NC=2)N2C=NN=C2)CC1 RTIHCYHUHPGUHO-UHFFFAOYSA-N 0.000 claims 1
- UVAMBZYMSIFFEE-UHFFFAOYSA-N 3-[3-[1-[2-(2-methoxypyridin-3-yl)propyl]piperidin-4-yl]propyl]-5-(1,2,4-triazol-4-yl)-1h-indole Chemical compound COC1=NC=CC=C1C(C)CN1CCC(CCCC=2C3=CC(=CC=C3NC=2)N2C=NN=C2)CC1 UVAMBZYMSIFFEE-UHFFFAOYSA-N 0.000 claims 1
- HYFMZYSCMRPVFE-UHFFFAOYSA-N 3-[3-[1-[2-(3,4-difluorophenyl)ethyl]piperidin-4-yl]propyl]-5-(1,2,4-triazol-4-yl)-1h-indole Chemical compound C1=C(F)C(F)=CC=C1CCN1CCC(CCCC=2C3=CC(=CC=C3NC=2)N2C=NN=C2)CC1 HYFMZYSCMRPVFE-UHFFFAOYSA-N 0.000 claims 1
- GABHPXFPBVKAPM-UHFFFAOYSA-N 3-[3-[1-[2-(3-chlorophenyl)propyl]piperidin-4-yl]propyl]-5-(1,2,4-triazol-4-yl)-1h-indole Chemical compound C=1C=CC(Cl)=CC=1C(C)CN(CC1)CCC1CCCC(C1=C2)=CNC1=CC=C2N1C=NN=C1 GABHPXFPBVKAPM-UHFFFAOYSA-N 0.000 claims 1
- CQQYJTNAZXLSEU-UHFFFAOYSA-N 3-[3-[1-[2-(3-fluorophenyl)ethyl]piperidin-4-yl]propyl]-5-(1,2,4-triazol-4-yl)-1h-indole Chemical compound FC1=CC=CC(CCN2CCC(CCCC=3C4=CC(=CC=C4NC=3)N3C=NN=C3)CC2)=C1 CQQYJTNAZXLSEU-UHFFFAOYSA-N 0.000 claims 1
- NWJAWKJKYJOALI-UHFFFAOYSA-N 3-[3-[1-[2-(3-fluorophenyl)propyl]piperidin-4-yl]propyl]-5-(1,2,4-triazol-4-yl)-1h-indole Chemical compound C=1C=CC(F)=CC=1C(C)CN(CC1)CCC1CCCC(C1=C2)=CNC1=CC=C2N1C=NN=C1 NWJAWKJKYJOALI-UHFFFAOYSA-N 0.000 claims 1
- DBNYAXFBBRKWBK-UHFFFAOYSA-N 3-[3-[1-[2-(3-methoxyphenyl)propyl]piperidin-4-yl]propyl]-5-(1,2,4-triazol-4-yl)-1h-indole Chemical compound COC1=CC=CC(C(C)CN2CCC(CCCC=3C4=CC(=CC=C4NC=3)N3C=NN=C3)CC2)=C1 DBNYAXFBBRKWBK-UHFFFAOYSA-N 0.000 claims 1
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- 125000006287 difluorobenzyl group Chemical group 0.000 description 1
- 229940043279 diisopropylamine Drugs 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
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- 239000003480 eluent Substances 0.000 description 1
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- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 1
- ZIFVPGWZQORZPR-UHFFFAOYSA-N ethyl 2-(1,3-thiazol-2-yl)propanoate Chemical compound CCOC(=O)C(C)C1=NC=CS1 ZIFVPGWZQORZPR-UHFFFAOYSA-N 0.000 description 1
- OUMDBJXPIFUCKH-UHFFFAOYSA-N ethyl 2-(2,6-dichlorophenyl)propanoate Chemical compound CCOC(=O)C(C)C1=C(Cl)C=CC=C1Cl OUMDBJXPIFUCKH-UHFFFAOYSA-N 0.000 description 1
- ARFLASKVLJTEJD-UHFFFAOYSA-N ethyl 2-bromopropanoate Chemical compound CCOC(=O)C(C)Br ARFLASKVLJTEJD-UHFFFAOYSA-N 0.000 description 1
- VCDOPMNGJGSWFX-UHFFFAOYSA-N ethyl 2-pyrazol-1-ylpropanoate Chemical compound CCOC(=O)C(C)N1C=CC=N1 VCDOPMNGJGSWFX-UHFFFAOYSA-N 0.000 description 1
- RPWXYCRIAGBAGY-UHFFFAOYSA-N ethyl 2-pyridin-3-ylacetate Chemical compound CCOC(=O)CC1=CC=CN=C1 RPWXYCRIAGBAGY-UHFFFAOYSA-N 0.000 description 1
- RPEUEJTZHRHZQD-UHFFFAOYSA-N ethyl 2-pyridin-3-ylpropanoate Chemical compound CCOC(=O)C(C)C1=CC=CN=C1 RPEUEJTZHRHZQD-UHFFFAOYSA-N 0.000 description 1
- DXIQUQYLOVOVHV-UHFFFAOYSA-N ethyl 2-pyrimidin-2-ylpropanoate Chemical compound CCOC(=O)C(C)C1=NC=CC=N1 DXIQUQYLOVOVHV-UHFFFAOYSA-N 0.000 description 1
- FZBNQIWPYCUPAP-UHFFFAOYSA-N ethyl 2-thiophen-3-ylacetate Chemical compound CCOC(=O)CC=1C=CSC=1 FZBNQIWPYCUPAP-UHFFFAOYSA-N 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000020375 flavoured syrup Nutrition 0.000 description 1
- 125000001207 fluorophenyl group Chemical group 0.000 description 1
- CNUDBTRUORMMPA-UHFFFAOYSA-N formylthiophene Chemical compound O=CC1=CC=CS1 CNUDBTRUORMMPA-UHFFFAOYSA-N 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- HYBBIBNJHNGZAN-UHFFFAOYSA-N furfural Chemical compound O=CC1=CC=CO1 HYBBIBNJHNGZAN-UHFFFAOYSA-N 0.000 description 1
- 125000002541 furyl group Chemical group 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
- 239000011521 glass Substances 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 1
- 150000002390 heteroarenes Chemical class 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000008240 homogeneous mixture Substances 0.000 description 1
- 150000002429 hydrazines Chemical class 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 150000002440 hydroxy compounds Chemical class 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- XJTQJERLRPWUGL-UHFFFAOYSA-N iodomethylbenzene Chemical compound ICC1=CC=CC=C1 XJTQJERLRPWUGL-UHFFFAOYSA-N 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 159000000003 magnesium salts Chemical class 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- BRMYZIKAHFEUFJ-UHFFFAOYSA-L mercury diacetate Chemical compound CC(=O)O[Hg]OC(C)=O BRMYZIKAHFEUFJ-UHFFFAOYSA-L 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 238000010369 molecular cloning Methods 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- AMQJEAYHLZJPGS-UHFFFAOYSA-N n-butyl carbinol Natural products CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 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
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 1
- 229920001206 natural gum Polymers 0.000 description 1
- 230000009871 nonspecific binding Effects 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
- 229920002113 octoxynol Polymers 0.000 description 1
- 239000012053 oil suspension Substances 0.000 description 1
- 239000013110 organic ligand Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 210000001672 ovary Anatomy 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 125000000160 oxazolidinyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- 238000005949 ozonolysis reaction Methods 0.000 description 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 1
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 239000003182 parenteral nutrition solution Substances 0.000 description 1
- 208000007777 paroxysmal Hemicrania Diseases 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- CRWVOXFUXPYTRK-UHFFFAOYSA-N pent-4-yn-1-ol Chemical compound OCCCC#C CRWVOXFUXPYTRK-UHFFFAOYSA-N 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- IMACFCSSMIZSPP-UHFFFAOYSA-N phenacyl chloride Chemical compound ClCC(=O)C1=CC=CC=C1 IMACFCSSMIZSPP-UHFFFAOYSA-N 0.000 description 1
- 229940100595 phenylacetaldehyde Drugs 0.000 description 1
- 229940067157 phenylhydrazine Drugs 0.000 description 1
- HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical compound NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 description 1
- 229940038531 phenylhydrazine hydrochloride Drugs 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 229920000137 polyphosphoric acid Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- GKKCIDNWFBPDBW-UHFFFAOYSA-N potassium;cyanic acid Chemical compound [K+].OC#N GKKCIDNWFBPDBW-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000011533 pre-incubation Methods 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- 238000004237 preparative chromatography Methods 0.000 description 1
- 238000012746 preparative thin layer chromatography Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- DOKHEARVIDLSFF-UHFFFAOYSA-N prop-1-en-1-ol Chemical group CC=CO DOKHEARVIDLSFF-UHFFFAOYSA-N 0.000 description 1
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 1
- YORCIIVHUBAYBQ-UHFFFAOYSA-N propargyl bromide Chemical compound BrCC#C YORCIIVHUBAYBQ-UHFFFAOYSA-N 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 239000002287 radioligand Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000005932 reductive alkylation reaction Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 238000000611 regression analysis Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000375 suspending agent Substances 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
- 239000011975 tartaric acid Substances 0.000 description 1
- 229960001367 tartaric acid Drugs 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- QSSWCFFAFFJEAY-UHFFFAOYSA-N tert-butyl 4-(2-hydroxy-5-triethylsilylpent-4-ynyl)piperidine-1-carboxylate Chemical compound CC[Si](CC)(CC)C#CCC(O)CC1CCN(C(=O)OC(C)(C)C)CC1 QSSWCFFAFFJEAY-UHFFFAOYSA-N 0.000 description 1
- ROUYFJUVMYHXFJ-UHFFFAOYSA-N tert-butyl 4-oxopiperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCC(=O)CC1 ROUYFJUVMYHXFJ-UHFFFAOYSA-N 0.000 description 1
- MFPWEWYKQYMWRO-UHFFFAOYSA-N tert-butyl carboxy carbonate Chemical compound CC(C)(C)OC(=O)OC(O)=O MFPWEWYKQYMWRO-UHFFFAOYSA-N 0.000 description 1
- RQCNHUCCQJMSRG-UHFFFAOYSA-N tert-butyl piperidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CCCCC1 RQCNHUCCQJMSRG-UHFFFAOYSA-N 0.000 description 1
- 125000004853 tetrahydropyridinyl group Chemical class N1(CCCC=C1)* 0.000 description 1
- 125000000383 tetramethylene group Chemical group [H]C([H])([*:1])C([H])([H])C([H])([H])C([H])([H])[*:2] 0.000 description 1
- 238000011287 therapeutic dose Methods 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 description 1
- 125000005302 thiazolylmethyl group Chemical group [H]C1=C([H])N=C(S1)C([H])([H])* 0.000 description 1
- 125000003396 thiol group Chemical class [H]S* 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- FWSPXZXVNVQHIF-UHFFFAOYSA-N triethyl(ethynyl)silane Chemical group CC[Si](CC)(CC)C#C FWSPXZXVNVQHIF-UHFFFAOYSA-N 0.000 description 1
- JLTRXTDYQLMHGR-UHFFFAOYSA-N trimethylaluminium Chemical compound C[Al](C)C JLTRXTDYQLMHGR-UHFFFAOYSA-N 0.000 description 1
- BPLKQGGAXWRFOE-UHFFFAOYSA-M trimethylsulfoxonium iodide Chemical compound [I-].C[S+](C)(C)=O BPLKQGGAXWRFOE-UHFFFAOYSA-M 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 150000003672 ureas Chemical class 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 239000005526 vasoconstrictor agent Substances 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000011995 wilkinson's catalyst Substances 0.000 description 1
- UTODFRQBVUVYOB-UHFFFAOYSA-P wilkinson's catalyst Chemical compound [Cl-].C1=CC=CC=C1P(C=1C=CC=CC=1)(C=1C=CC=CC=1)[Rh+](P(C=1C=CC=CC=1)(C=1C=CC=CC=1)C=1C=CC=CC=1)P(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 UTODFRQBVUVYOB-UHFFFAOYSA-P 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Landscapes
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Cette invention concerne une classe de dérivés de pipéridine et de tétrahydropyridine, liés au niveau de leur position 4 par l'intermédiaire d'une chaîne alkylène à une fraction condensée, bicyclique, hétéroaromatique du type indolyle, et substitués en outre en position 1 par une fraction alkyle, alkényle, alkynyle, cycloalkyl-alkyle, aryl-alkyle ou hétéroalkyl-alkyle éventuellement substituée. Ces dérivés sont des antagonistes sélectifs des récepteurs du type 5-HT¿1?, du fait qu'ils s'avèrent être des puissants agonistes du sous-type récepteur 5-HT¿1D.alpha.? d'origine humaine et possèdent une affinité sélective au moins 10 fois supérieure pour le sous-type récepteur HT¿1D.alpha.? que pour le sous-type 5-HT¿1D.beta.?. Ces dérivés s'avèrent, par conséquent, utiles s'agissant du traitement et/ou de la prévention de troubles cliniques, en particulier de la migraine et de troubles associés, pour lesquels un agoniste sélectif vis-à-vis des sous-types des récepteurs 5-HT¿1D? est indiqué, et ils présentent l'avantage de provoquer des effets secondaires moins nombreux, notamment du type troubles cardiovasculaires adverses, que ceux associés aux agonistes du récepteur 5-HT¿1D? non sélectifs vis-à-vis des sous-types.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9523583.4A GB9523583D0 (en) | 1995-11-17 | 1995-11-17 | Therapeutic agents |
| GB9523583.4 | 1995-11-17 | ||
| PCT/GB1996/002795 WO1997019073A1 (fr) | 1995-11-17 | 1996-11-14 | Derives de piperidine et de tetrahydropyridine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2236834A1 true CA2236834A1 (fr) | 1997-05-29 |
Family
ID=29404381
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA 2236834 Abandoned CA2236834A1 (fr) | 1995-11-17 | 1996-11-14 | Derives de piperidine et de tetrahydropyridine |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA2236834A1 (fr) |
-
1996
- 1996-11-14 CA CA 2236834 patent/CA2236834A1/fr not_active Abandoned
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| Date | Code | Title | Description |
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| FZDE | Dead |