CA2133077A1 - Azacyclic compounds - Google Patents
Azacyclic compoundsInfo
- Publication number
- CA2133077A1 CA2133077A1 CA002133077A CA2133077A CA2133077A1 CA 2133077 A1 CA2133077 A1 CA 2133077A1 CA 002133077 A CA002133077 A CA 002133077A CA 2133077 A CA2133077 A CA 2133077A CA 2133077 A1 CA2133077 A1 CA 2133077A1
- Authority
- CA
- Canada
- Prior art keywords
- methyloxy
- phenyl
- methyl
- trifluoromethyl
- phenylpiperidino
- 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
- 150000004030 azacyclic compounds Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 252
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 42
- 150000003839 salts Chemical class 0.000 claims abstract description 31
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 28
- 125000004043 oxo group Chemical group O=* 0.000 claims abstract description 23
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 19
- 108060008037 tachykinin Proteins 0.000 claims abstract description 15
- 102000003141 Tachykinin Human genes 0.000 claims abstract description 14
- 125000003831 tetrazolyl group Chemical group 0.000 claims abstract description 14
- 239000000651 prodrug Substances 0.000 claims abstract description 13
- 229940002612 prodrug Drugs 0.000 claims abstract description 13
- 125000002541 furyl group Chemical group 0.000 claims abstract description 11
- 125000004076 pyridyl group Chemical group 0.000 claims abstract description 11
- 125000001544 thienyl group Chemical group 0.000 claims abstract description 11
- 125000000335 thiazolyl group Chemical group 0.000 claims abstract description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 9
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 claims abstract description 9
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 8
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 7
- 125000005493 quinolyl group Chemical group 0.000 claims abstract description 7
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 7
- 229910052701 rubidium Inorganic materials 0.000 claims abstract description 6
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 claims abstract description 6
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims abstract description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 5
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims abstract description 5
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 5
- 229910003827 NRaRb Inorganic materials 0.000 claims abstract description 4
- 241000036848 Porzana carolina Species 0.000 claims abstract description 4
- 125000001475 halogen functional group Chemical group 0.000 claims abstract 14
- 125000001183 hydrocarbyl group Chemical group 0.000 claims abstract 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 95
- 238000000034 method Methods 0.000 claims description 94
- -1 2-phenylpiperidino Chemical group 0.000 claims description 83
- 238000006243 chemical reaction Methods 0.000 claims description 55
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 37
- 239000000203 mixture Substances 0.000 claims description 35
- 239000002904 solvent Substances 0.000 claims description 30
- 239000002585 base Substances 0.000 claims description 27
- 208000035475 disorder Diseases 0.000 claims description 25
- 229910052799 carbon Inorganic materials 0.000 claims description 24
- 230000008569 process Effects 0.000 claims description 24
- 125000001424 substituent group Chemical group 0.000 claims description 17
- 125000001425 triazolyl group Chemical group 0.000 claims description 15
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 14
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 14
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 12
- 229910052727 yttrium Inorganic materials 0.000 claims description 12
- 125000002883 imidazolyl group Chemical group 0.000 claims description 11
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 10
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 10
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 10
- 208000002193 Pain Diseases 0.000 claims description 9
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 9
- 125000002971 oxazolyl group Chemical group 0.000 claims description 9
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 9
- 125000004306 triazinyl group Chemical group 0.000 claims description 9
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 125000001072 heteroaryl group Chemical group 0.000 claims description 8
- 208000019695 Migraine disease Diseases 0.000 claims description 7
- 229910052783 alkali metal Inorganic materials 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 206010027599 migraine Diseases 0.000 claims description 7
- 150000003852 triazoles Chemical group 0.000 claims description 7
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 6
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical group [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 claims description 6
- 229940124630 bronchodilator Drugs 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 230000002265 prevention Effects 0.000 claims description 6
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 5
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 125000000464 thioxo group Chemical group S=* 0.000 claims description 4
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical group C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 claims description 3
- 206010061218 Inflammation Diseases 0.000 claims description 3
- 239000003153 chemical reaction reagent Substances 0.000 claims description 3
- 230000004054 inflammatory process Effects 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- 208000023504 respiratory system disease Diseases 0.000 claims description 3
- 229910000288 alkali metal carbonate Inorganic materials 0.000 claims description 2
- 150000008041 alkali metal carbonates Chemical class 0.000 claims description 2
- 229910000102 alkali metal hydride Inorganic materials 0.000 claims description 2
- 150000008046 alkali metal hydrides Chemical class 0.000 claims description 2
- 150000001340 alkali metals Chemical class 0.000 claims description 2
- JYZIHLWOWKMNNX-UHFFFAOYSA-N benzimidazole Chemical compound C1=C[CH]C2=NC=NC2=C1 JYZIHLWOWKMNNX-UHFFFAOYSA-N 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 claims description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 3
- 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 2
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims 2
- MJASXLMPDFPCCD-GMAHTHKFSA-N (2s,3s)-3-[(2,3-dimethylphenyl)methoxy]-2-phenyl-1-(1h-1,2,4-triazol-5-ylmethyl)piperidine Chemical compound CC1=CC=CC(CO[C@@H]2[C@@H](N(CC3=NNC=N3)CCC2)C=2C=CC=CC=2)=C1C MJASXLMPDFPCCD-GMAHTHKFSA-N 0.000 claims 1
- HSNYRKWYZZLMIB-FPOVZHCZSA-N (2s,3s)-3-[(3,5-dichlorophenyl)methoxy]-2-phenyl-1-(1h-1,2,4-triazol-5-ylmethyl)piperidine Chemical compound ClC1=CC(Cl)=CC(CO[C@@H]2[C@@H](N(CC3=NNC=N3)CCC2)C=2C=CC=CC=2)=C1 HSNYRKWYZZLMIB-FPOVZHCZSA-N 0.000 claims 1
- MNYUNWUAYIFYQL-NQERJWCQSA-N (2s,3s)-3-[(3,5-dichlorophenyl)methoxy]-2-phenyl-1-[(1r)-1-(1h-1,2,4-triazol-5-yl)ethyl]piperidine Chemical compound O([C@H]1CCCN([C@H]1C=1C=CC=CC=1)[C@H](C)C=1NN=CN=1)CC1=CC(Cl)=CC(Cl)=C1 MNYUNWUAYIFYQL-NQERJWCQSA-N 0.000 claims 1
- MNYUNWUAYIFYQL-JHVJFLLYSA-N (2s,3s)-3-[(3,5-dichlorophenyl)methoxy]-2-phenyl-1-[(1s)-1-(1h-1,2,4-triazol-5-yl)ethyl]piperidine Chemical compound O([C@H]1CCCN([C@H]1C=1C=CC=CC=1)[C@@H](C)C=1NN=CN=1)CC1=CC(Cl)=CC(Cl)=C1 MNYUNWUAYIFYQL-JHVJFLLYSA-N 0.000 claims 1
- HBAPMWYWEYPKLS-UNMCSNQZSA-N (2s,3s)-3-[[3,5-bis(trifluoromethyl)phenyl]methoxy]-1-(1h-imidazol-2-ylmethyl)-2-phenylpiperidine Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(CO[C@@H]2[C@@H](N(CC=3NC=CN=3)CCC2)C=2C=CC=CC=2)=C1 HBAPMWYWEYPKLS-UNMCSNQZSA-N 0.000 claims 1
- ZTMDGDHDXPIEIO-VXKWHMMOSA-N (2s,3s)-3-[[3,5-bis(trifluoromethyl)phenyl]methoxy]-1-(1h-imidazol-5-ylmethyl)-2-phenylpiperidine Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(CO[C@@H]2[C@@H](N(CC=3N=CNC=3)CCC2)C=2C=CC=CC=2)=C1 ZTMDGDHDXPIEIO-VXKWHMMOSA-N 0.000 claims 1
- LBGYIRCBWRLHAB-FPOVZHCZSA-N (2s,3s)-3-[[3,5-bis(trifluoromethyl)phenyl]methoxy]-1-[(1-methyltetrazol-5-yl)methyl]-2-phenylpiperidine Chemical compound CN1N=NN=C1CN1[C@@H](C=2C=CC=CC=2)[C@@H](OCC=2C=C(C=C(C=2)C(F)(F)F)C(F)(F)F)CCC1 LBGYIRCBWRLHAB-FPOVZHCZSA-N 0.000 claims 1
- HHYXMPLEGVKQIW-FPOVZHCZSA-N (2s,3s)-3-[[3,5-bis(trifluoromethyl)phenyl]methoxy]-2-phenyl-1-(1h-1,2,4-triazol-5-ylmethyl)piperidine Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(CO[C@@H]2[C@@H](N(CC3=NNC=N3)CCC2)C=2C=CC=CC=2)=C1 HHYXMPLEGVKQIW-FPOVZHCZSA-N 0.000 claims 1
- LFFPDSZQTVWQEP-ICSRJNTNSA-N (2s,3s)-3-[[3,5-bis(trifluoromethyl)phenyl]methoxy]-2-phenyl-1-(2h-tetrazol-5-ylmethyl)piperidine Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(CO[C@@H]2[C@@H](N(CC=3NN=NN=3)CCC2)C=2C=CC=CC=2)=C1 LFFPDSZQTVWQEP-ICSRJNTNSA-N 0.000 claims 1
- BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 claims 1
- PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 claims 1
- WJXWYVCHKFCAHN-UNMCSNQZSA-N 2-[[(2s,3s)-3-[[3,5-bis(trifluoromethyl)phenyl]methoxy]-2-phenylpiperidin-1-yl]methyl]-1,3,5-triazine Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(CO[C@@H]2[C@@H](N(CC=3N=CN=CN=3)CCC2)C=2C=CC=CC=2)=C1 WJXWYVCHKFCAHN-UNMCSNQZSA-N 0.000 claims 1
- XXFWFTYVCMKLNC-GOTSBHOMSA-N 2-[[(2s,3s)-3-[[3,5-bis(trifluoromethyl)phenyl]methoxy]-2-phenylpiperidin-1-yl]methyl]pyrazine Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(CO[C@@H]2[C@@H](N(CC=3N=CC=NC=3)CCC2)C=2C=CC=CC=2)=C1 XXFWFTYVCMKLNC-GOTSBHOMSA-N 0.000 claims 1
- OCDSEQGFFLVIQL-FPOVZHCZSA-N 3-[[(2s,3s)-3-[[3,5-bis(trifluoromethyl)phenyl]methoxy]-2-phenylpiperidin-1-yl]methyl]-1,2,4-oxadiazole Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(CO[C@@H]2[C@@H](N(CC3=NOC=N3)CCC2)C=2C=CC=CC=2)=C1 OCDSEQGFFLVIQL-FPOVZHCZSA-N 0.000 claims 1
- FJIAUTWSMWNNLK-FPOVZHCZSA-N 3-[[(2s,3s)-3-[[3,5-bis(trifluoromethyl)phenyl]methoxy]-2-phenylpiperidin-1-yl]methyl]-1,2,4-thiadiazole Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(CO[C@@H]2[C@@H](N(CC3=NSC=N3)CCC2)C=2C=CC=CC=2)=C1 FJIAUTWSMWNNLK-FPOVZHCZSA-N 0.000 claims 1
- YAXIJXRGDRITNG-UNMCSNQZSA-N 3-[[(2s,3s)-3-[[3,5-bis(trifluoromethyl)phenyl]methoxy]-2-phenylpiperidin-1-yl]methyl]-1,2,4-triazine Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(CO[C@@H]2[C@@H](N(CC=3N=NC=CN=3)CCC2)C=2C=CC=CC=2)=C1 YAXIJXRGDRITNG-UNMCSNQZSA-N 0.000 claims 1
- OQCSCTORNKFQSP-ICSRJNTNSA-N 3-[[(2s,3s)-3-[[3,5-bis(trifluoromethyl)phenyl]methoxy]-2-phenylpiperidin-1-yl]methyl]-5-iodo-1,2,4-thiadiazole Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(CO[C@@H]2[C@@H](N(CC=3N=C(I)SN=3)CCC2)C=2C=CC=CC=2)=C1 OQCSCTORNKFQSP-ICSRJNTNSA-N 0.000 claims 1
- CVIOZXUVUOYBPC-FPOVZHCZSA-N 3-[[(2s,3s)-3-[[3,5-bis(trifluoromethyl)phenyl]methoxy]-2-phenylpiperidin-1-yl]methyl]-5-methoxy-1,2,4-thiadiazole Chemical compound S1C(OC)=NC(CN2[C@H]([C@@H](OCC=3C=C(C=C(C=3)C(F)(F)F)C(F)(F)F)CCC2)C=2C=CC=CC=2)=N1 CVIOZXUVUOYBPC-FPOVZHCZSA-N 0.000 claims 1
- VSOOWLLBBZTTBC-GOTSBHOMSA-N 3-[[(2s,3s)-3-[[3,5-bis(trifluoromethyl)phenyl]methoxy]-2-phenylpiperidin-1-yl]methyl]pyridazine Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(CO[C@@H]2[C@@H](N(CC=3N=NC=CC=3)CCC2)C=2C=CC=CC=2)=C1 VSOOWLLBBZTTBC-GOTSBHOMSA-N 0.000 claims 1
- FNWYNXVBSUEUGT-VXKWHMMOSA-N 4-[[(2s,3s)-3-[[3,5-bis(trifluoromethyl)phenyl]methoxy]-2-phenylpiperidin-1-yl]methyl]-1,3-oxazole Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(CO[C@@H]2[C@@H](N(CC=3N=COC=3)CCC2)C=2C=CC=CC=2)=C1 FNWYNXVBSUEUGT-VXKWHMMOSA-N 0.000 claims 1
- DHZWYBHNEZPMFT-GOTSBHOMSA-N 4-[[(2s,3s)-3-[[3,5-bis(trifluoromethyl)phenyl]methoxy]-2-phenylpiperidin-1-yl]methyl]-2-methyl-1,3-thiazole Chemical compound S1C(C)=NC(CN2[C@H]([C@@H](OCC=3C=C(C=C(C=3)C(F)(F)F)C(F)(F)F)CCC2)C=2C=CC=CC=2)=C1 DHZWYBHNEZPMFT-GOTSBHOMSA-N 0.000 claims 1
- RYNYCSWFXFCKOE-ICSRJNTNSA-N 5-[[(2s,3s)-3-[[3,5-bis(trifluoromethyl)phenyl]methoxy]-2-phenylpiperidin-1-yl]methyl]-1,2,4-oxadiazol-3-amine Chemical compound NC1=NOC(CN2[C@H]([C@@H](OCC=3C=C(C=C(C=3)C(F)(F)F)C(F)(F)F)CCC2)C=2C=CC=CC=2)=N1 RYNYCSWFXFCKOE-ICSRJNTNSA-N 0.000 claims 1
- CUTCCLOSPUUMEJ-UNMCSNQZSA-N 6-[[(2s,3s)-3-[[3,5-bis(trifluoromethyl)phenyl]methoxy]-2-phenylpiperidin-1-yl]methyl]-1h-pyrimidine-2,4-dione Chemical compound FC(F)(F)C1=CC(C(F)(F)F)=CC(CO[C@@H]2[C@@H](N(CC=3NC(=O)NC(=O)C=3)CCC2)C=2C=CC=CC=2)=C1 CUTCCLOSPUUMEJ-UNMCSNQZSA-N 0.000 claims 1
- 206010036376 Postherpetic Neuralgia Diseases 0.000 claims 1
- 230000002917 arthritic effect Effects 0.000 claims 1
- MAPRDOKILZKGDP-UHFFFAOYSA-N bromo-chloro-iodomethanesulfonic acid Chemical compound OS(=O)(=O)C(Cl)(Br)I MAPRDOKILZKGDP-UHFFFAOYSA-N 0.000 claims 1
- 150000002460 imidazoles Chemical class 0.000 claims 1
- 150000003536 tetrazoles Chemical class 0.000 claims 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 claims 1
- 150000003918 triazines Chemical class 0.000 claims 1
- 239000005557 antagonist Substances 0.000 abstract description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 236
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 127
- 238000005481 NMR spectroscopy Methods 0.000 description 101
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 95
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 86
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 82
- 235000019439 ethyl acetate Nutrition 0.000 description 79
- 239000000243 solution Substances 0.000 description 69
- 239000007787 solid Substances 0.000 description 60
- 239000000047 product Substances 0.000 description 58
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 57
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 54
- 229910052739 hydrogen Inorganic materials 0.000 description 52
- 239000003921 oil Substances 0.000 description 52
- 235000019198 oils Nutrition 0.000 description 52
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 49
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 48
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 46
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 43
- 235000019341 magnesium sulphate Nutrition 0.000 description 43
- 239000000377 silicon dioxide Substances 0.000 description 41
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 39
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 36
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 35
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 34
- 238000004587 chromatography analysis Methods 0.000 description 30
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 29
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 29
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 28
- 239000012267 brine Substances 0.000 description 27
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 26
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 24
- 239000000543 intermediate Substances 0.000 description 22
- 125000005843 halogen group Chemical group 0.000 description 21
- 229910000027 potassium carbonate Inorganic materials 0.000 description 19
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 18
- 239000012044 organic layer Substances 0.000 description 18
- 229910052708 sodium Inorganic materials 0.000 description 18
- 239000011734 sodium Substances 0.000 description 18
- 229910052757 nitrogen Inorganic materials 0.000 description 17
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- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 1
- FWFGVMYFCODZRD-UHFFFAOYSA-N oxidanium;hydrogen sulfate Chemical compound O.OS(O)(=O)=O FWFGVMYFCODZRD-UHFFFAOYSA-N 0.000 description 1
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- 235000013874 shellac Nutrition 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
- 235000017550 sodium carbonate Nutrition 0.000 description 1
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- 238000000638 solvent extraction Methods 0.000 description 1
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- 235000002906 tartaric acid Nutrition 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 101150084216 thiB gene Proteins 0.000 description 1
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- QIQITDHWZYEEPA-UHFFFAOYSA-N thiophene-2-carbonyl chloride Chemical compound ClC(=O)C1=CC=CS1 QIQITDHWZYEEPA-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 239000003053 toxin Substances 0.000 description 1
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- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 229940055764 triaz Drugs 0.000 description 1
- MASNJXDMMSOROP-UHFFFAOYSA-N triethylsilane 2,2,2-trifluoroacetic acid Chemical compound CC[SiH](CC)CC.OC(=O)C(F)(F)F MASNJXDMMSOROP-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/12—Oxygen or sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D211/54—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
Applications Claiming Priority (8)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB929208323A GB9208323D0 (en) | 1992-04-15 | 1992-04-15 | Therapeutic agents |
GB9208323.7 | 1992-04-15 | ||
GB929216065A GB9216065D0 (en) | 1992-07-28 | 1992-07-28 | Therapeutic agents |
GB9216065.4 | 1992-07-28 | ||
GB929219686A GB9219686D0 (en) | 1992-09-17 | 1992-09-17 | Therapeutic agents |
GB9219686.4 | 1992-09-17 | ||
GB9226069.4 | 1992-12-14 | ||
GB929226069A GB9226069D0 (en) | 1992-12-14 | 1992-12-14 | Therapeutic agents |
Publications (1)
Publication Number | Publication Date |
---|---|
CA2133077A1 true CA2133077A1 (en) | 1993-10-28 |
Family
ID=27450859
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002133077A Abandoned CA2133077A1 (en) | 1992-04-15 | 1993-04-14 | Azacyclic compounds |
Country Status (5)
Country | Link |
---|---|
EP (1) | EP0636130A1 (de) |
JP (1) | JPH07505648A (de) |
AU (1) | AU675786B2 (de) |
CA (1) | CA2133077A1 (de) |
WO (1) | WO1993021181A1 (de) |
Families Citing this family (54)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2700472B1 (fr) | 1993-01-19 | 1995-02-17 | Rhone Poulenc Rorer Sa | Association synergisante ayant un effet antagoniste des récepteurs NK1 et NK2. |
US5633266A (en) * | 1993-02-18 | 1997-05-27 | Merck Sharp & Dohme Ltd. | Azacyclic compounds compositions containing them and their use as tachykinin antagonists |
ATE170174T1 (de) * | 1994-01-13 | 1998-09-15 | Merck Sharp & Dohme | Gem-bissubstituierte azazyclische tachykinin- antagonisten |
EP0741704A1 (de) * | 1994-01-28 | 1996-11-13 | MERCK SHARP & DOHME LTD. | Aralkylamino-substituierte azacyclische therapeutische mittel |
ATE387429T1 (de) | 1999-11-03 | 2008-03-15 | Amr Technology Inc | Arly- und heteroaryl-substituierte tetrahydroisoquinoline und ihre verwendung als hemmer der wiederaufnahme von norepinephrin, dopamin und serotonin |
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US4968678A (en) * | 1988-02-19 | 1990-11-06 | Eli Lilly And Company | Tetrazole excitatory amino acid receptor antagonists |
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IL111730A (en) * | 1993-11-29 | 1998-12-06 | Fujisawa Pharmaceutical Co | Piperazine derivatives, processes for their preparation and pharmaceutical preparations containing them |
-
1993
- 1993-04-14 WO PCT/GB1993/000788 patent/WO1993021181A1/en not_active Application Discontinuation
- 1993-04-14 EP EP93910151A patent/EP0636130A1/de not_active Withdrawn
- 1993-04-14 JP JP5518131A patent/JPH07505648A/ja active Pending
- 1993-04-14 CA CA002133077A patent/CA2133077A1/en not_active Abandoned
- 1993-04-14 AU AU40765/93A patent/AU675786B2/en not_active Ceased
Also Published As
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JPH07505648A (ja) | 1995-06-22 |
EP0636130A1 (de) | 1995-02-01 |
WO1993021181A1 (en) | 1993-10-28 |
AU675786B2 (en) | 1997-02-20 |
AU4076593A (en) | 1993-11-18 |
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