CA2448602C - Pyrimidine, triazine and pyrazine derivatives as glutamate receptors - Google Patents
Pyrimidine, triazine and pyrazine derivatives as glutamate receptors Download PDFInfo
- Publication number
- CA2448602C CA2448602C CA002448602A CA2448602A CA2448602C CA 2448602 C CA2448602 C CA 2448602C CA 002448602 A CA002448602 A CA 002448602A CA 2448602 A CA2448602 A CA 2448602A CA 2448602 C CA2448602 C CA 2448602C
- Authority
- CA
- Canada
- Prior art keywords
- phenyl
- carbonitrile
- fluoro
- pyrimidine
- formula
- 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 - Fee Related
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- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 title abstract description 5
- JYEUMXHLPRZUAT-UHFFFAOYSA-N 1,2,3-triazine Chemical compound C1=CN=NN=C1 JYEUMXHLPRZUAT-UHFFFAOYSA-N 0.000 title abstract description 4
- 150000003216 pyrazines Chemical class 0.000 title abstract description 3
- 108010027915 Glutamate Receptors Proteins 0.000 title description 2
- 102000018899 Glutamate Receptors Human genes 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 141
- 150000003839 salts Chemical class 0.000 claims abstract description 51
- 239000003814 drug Substances 0.000 claims abstract description 15
- 230000001684 chronic effect Effects 0.000 claims abstract description 14
- 230000002265 prevention Effects 0.000 claims abstract description 13
- 230000001154 acute effect Effects 0.000 claims abstract description 12
- 208000012902 Nervous system disease Diseases 0.000 claims abstract description 11
- 208000025966 Neurological disease Diseases 0.000 claims abstract description 11
- 238000000034 method Methods 0.000 claims description 101
- 229910052739 hydrogen Inorganic materials 0.000 claims description 80
- 239000001257 hydrogen Substances 0.000 claims description 79
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 59
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N EtOH Substances CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 48
- 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims description 37
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 25
- 125000001153 fluoro group Chemical group F* 0.000 claims description 23
- 229910052736 halogen Inorganic materials 0.000 claims description 22
- 150000002367 halogens Chemical class 0.000 claims description 22
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 19
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 14
- 150000002431 hydrogen Chemical class 0.000 claims description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 10
- 239000012038 nucleophile Substances 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- OYPINQOONHKTGV-UHFFFAOYSA-N 2,4-bis(cyclopropylamino)-6-(4-phenylpiperazin-1-yl)pyrimidine-5-carbonitrile Chemical compound N1=C(NC2CC2)N=C(N2CCN(CC2)C=2C=CC=CC=2)C(C#N)=C1NC1CC1 OYPINQOONHKTGV-UHFFFAOYSA-N 0.000 claims description 5
- ATHYGWDFZLNGSU-UHFFFAOYSA-N 2-(cyclopropylamino)-4-(2-hydroxyethylamino)-6-(4-phenylpiperidin-1-yl)pyrimidine-5-carbonitrile Chemical compound N=1C(N2CCC(CC2)C=2C=CC=CC=2)=C(C#N)C(NCCO)=NC=1NC1CC1 ATHYGWDFZLNGSU-UHFFFAOYSA-N 0.000 claims description 4
- GUIBPEGBMRNZEX-UHFFFAOYSA-N 2-(cyclopropylmethylamino)-4-(2-hydroxyethylamino)-6-(4-phenylpiperazin-1-yl)pyrimidine-5-carbonitrile Chemical compound N=1C(N2CCN(CC2)C=2C=CC=CC=2)=C(C#N)C(NCCO)=NC=1NCC1CC1 GUIBPEGBMRNZEX-UHFFFAOYSA-N 0.000 claims description 4
- RYGSYSQTYIDSSG-UHFFFAOYSA-N 5-ethyl-6-methyl-3-(4-phenylpiperidin-1-yl)pyrazine-2-carbonitrile Chemical compound N1=C(C)C(CC)=NC(N2CCC(CC2)C=2C=CC=CC=2)=C1C#N RYGSYSQTYIDSSG-UHFFFAOYSA-N 0.000 claims description 4
- ARTMWBNETUDYDF-UHFFFAOYSA-N 6-ethyl-5-methyl-3-(4-phenylpiperidin-1-yl)pyrazine-2-carbonitrile Chemical compound N1=C(C)C(CC)=NC(C#N)=C1N1CCC(C=2C=CC=CC=2)CC1 ARTMWBNETUDYDF-UHFFFAOYSA-N 0.000 claims description 4
- 230000008569 process Effects 0.000 claims description 4
- SZDRMFIBAQVXRC-UHFFFAOYSA-N 2-(cyclopropylamino)-4-(2-hydroxyethylamino)-6-(4-phenylpiperazin-1-yl)pyrimidine-5-carbonitrile Chemical compound N=1C(N2CCN(CC2)C=2C=CC=CC=2)=C(C#N)C(NCCO)=NC=1NC1CC1 SZDRMFIBAQVXRC-UHFFFAOYSA-N 0.000 claims description 3
- XPCJOWNVLUTJEY-UHFFFAOYSA-N 2-(cyclopropylamino)-4-[4-(4-fluorophenyl)piperazin-1-yl]-6-(2-hydroxyethylamino)pyrimidine-5-carbonitrile Chemical compound N=1C(N2CCN(CC2)C=2C=CC(F)=CC=2)=C(C#N)C(NCCO)=NC=1NC1CC1 XPCJOWNVLUTJEY-UHFFFAOYSA-N 0.000 claims description 3
- ZZTVMDZWZADEJR-UHFFFAOYSA-N 2-(cyclopropylmethylamino)-4-(2-hydroxyethylamino)-6-(4-phenylpiperidin-1-yl)pyrimidine-5-carbonitrile Chemical compound N=1C(N2CCC(CC2)C=2C=CC=CC=2)=C(C#N)C(NCCO)=NC=1NCC1CC1 ZZTVMDZWZADEJR-UHFFFAOYSA-N 0.000 claims description 3
- MLLHCQYZLJRAMG-UHFFFAOYSA-N 2-(cyclopropylmethylamino)-4-[4-(4-fluorophenyl)piperazin-1-yl]-6-(2-hydroxyethylamino)pyrimidine-5-carbonitrile Chemical compound N=1C(N2CCN(CC2)C=2C=CC(F)=CC=2)=C(C#N)C(NCCO)=NC=1NCC1CC1 MLLHCQYZLJRAMG-UHFFFAOYSA-N 0.000 claims description 3
- UFNWEBRZVIBAKV-UHFFFAOYSA-N 2-(cyclopropylmethylamino)-4-[4-(4-fluorophenyl)piperidin-1-yl]-6-(2-hydroxyethylamino)pyrimidine-5-carbonitrile Chemical compound N=1C(N2CCC(CC2)C=2C=CC(F)=CC=2)=C(C#N)C(NCCO)=NC=1NCC1CC1 UFNWEBRZVIBAKV-UHFFFAOYSA-N 0.000 claims description 3
- WETWIACDXYEMAE-UHFFFAOYSA-N 3-(2-hydroxyethylamino)-5-(4-phenyl-3,6-dihydro-2h-pyridin-1-yl)-1,2,4-triazine-6-carbonitrile Chemical compound OCCNC1=NN=C(C#N)C(N2CC=C(CC2)C=2C=CC=CC=2)=N1 WETWIACDXYEMAE-UHFFFAOYSA-N 0.000 claims description 3
- CAVHNPFNSQJIBO-UHFFFAOYSA-N 3-[4-(4-fluorophenyl)piperazin-1-yl]-5-methyl-6-phenylpyrazine-2-carbonitrile Chemical compound N#CC=1N=C(C=2C=CC=CC=2)C(C)=NC=1N(CC1)CCN1C1=CC=C(F)C=C1 CAVHNPFNSQJIBO-UHFFFAOYSA-N 0.000 claims description 3
- MMAPBDNEHOMSQD-UHFFFAOYSA-N 3-ethyl-6-[4-(4-fluorophenyl)piperazin-1-yl]-2-methyl-5-nitropyrimidin-4-one Chemical compound O=C1N(CC)C(C)=NC(N2CCN(CC2)C=2C=CC(F)=CC=2)=C1[N+]([O-])=O MMAPBDNEHOMSQD-UHFFFAOYSA-N 0.000 claims description 3
- MUJXTUPZYNZRIG-UHFFFAOYSA-N 4-(2-hydroxyethylamino)-6-(4-phenylpiperidin-1-yl)-2-(pyridin-3-ylmethylamino)pyrimidine-5-carbonitrile Chemical compound N=1C(N2CCC(CC2)C=2C=CC=CC=2)=C(C#N)C(NCCO)=NC=1NCC1=CC=CN=C1 MUJXTUPZYNZRIG-UHFFFAOYSA-N 0.000 claims description 3
- DBVWLINRVSEHBF-UHFFFAOYSA-N 4-[4-(4-fluorophenyl)piperidin-1-yl]-2-(2-hydroxyethylamino)-6-(2,2,2-trifluoroethoxy)pyrimidine-5-carbonitrile Chemical compound OCCNC1=NC(OCC(F)(F)F)=C(C#N)C(N2CCC(CC2)C=2C=CC(F)=CC=2)=N1 DBVWLINRVSEHBF-UHFFFAOYSA-N 0.000 claims description 3
- JZYSFRCVPMRUKL-UHFFFAOYSA-N 4-[4-(4-fluorophenyl)piperidin-1-yl]-2-(pyridin-3-ylmethylamino)-6-(2,2,2-trifluoroethoxy)pyrimidine-5-carbonitrile Chemical compound C1=CC(F)=CC=C1C1CCN(C=2C(=C(OCC(F)(F)F)N=C(NCC=3C=NC=CC=3)N=2)C#N)CC1 JZYSFRCVPMRUKL-UHFFFAOYSA-N 0.000 claims description 3
- SWWDHOHMVFMUDK-UHFFFAOYSA-N 4-chloro-2-(2-hydroxyethylamino)-6-(4-phenylpiperidin-1-yl)pyrimidine-5-carbonitrile Chemical compound OCCNC1=NC(Cl)=C(C#N)C(N2CCC(CC2)C=2C=CC=CC=2)=N1 SWWDHOHMVFMUDK-UHFFFAOYSA-N 0.000 claims description 3
- DUTMZYIWHLQZTH-UHFFFAOYSA-N 5-ethyl-6-methyl-3-(4-phenyl-3,6-dihydro-2h-pyridin-1-yl)pyrazine-2-carbonitrile Chemical compound N1=C(C)C(CC)=NC(N2CC=C(CC2)C=2C=CC=CC=2)=C1C#N DUTMZYIWHLQZTH-UHFFFAOYSA-N 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- XQJJVSKZRKYETA-UHFFFAOYSA-N 2-(2-hydroxyethylamino)-4-(4-phenylpiperidin-1-yl)-6-(2,2,2-trifluoroethoxy)pyrimidine-5-carbonitrile Chemical compound OCCNC1=NC(OCC(F)(F)F)=C(C#N)C(N2CCC(CC2)C=2C=CC=CC=2)=N1 XQJJVSKZRKYETA-UHFFFAOYSA-N 0.000 claims description 2
- KAYMQNZOONGXTI-UHFFFAOYSA-N 4-(4-phenylpiperidin-1-yl)-2-(pyridin-3-ylmethylamino)-6-(2,2,2-trifluoroethoxy)pyrimidine-5-carbonitrile Chemical compound N=1C(N2CCC(CC2)C=2C=CC=CC=2)=C(C#N)C(OCC(F)(F)F)=NC=1NCC1=CC=CN=C1 KAYMQNZOONGXTI-UHFFFAOYSA-N 0.000 claims description 2
- NUUCWXKVRPMGDL-UHFFFAOYSA-N 6-ethyl-5-methyl-3-(4-phenyl-3,6-dihydro-2h-pyridin-1-yl)pyrazine-2-carbonitrile Chemical compound N1=C(C)C(CC)=NC(C#N)=C1N1CC=C(C=2C=CC=CC=2)CC1 NUUCWXKVRPMGDL-UHFFFAOYSA-N 0.000 claims description 2
- XGWHHFSNYXBNAY-UHFFFAOYSA-N 6-ethyl-5-methyl-3-(4-phenylpiperazin-1-yl)pyrazine-2-carbonitrile Chemical compound N1=C(C)C(CC)=NC(C#N)=C1N1CCN(C=2C=CC=CC=2)CC1 XGWHHFSNYXBNAY-UHFFFAOYSA-N 0.000 claims description 2
- 125000004055 thiomethyl group Chemical group [H]SC([H])([H])* 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 147
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 129
- 239000007787 solid Substances 0.000 description 94
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 91
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 71
- 239000000203 mixture Substances 0.000 description 61
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 46
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 45
- 239000000243 solution Substances 0.000 description 44
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 36
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 34
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 30
- -1 pyridin-3-ylmethyl Chemical group 0.000 description 30
- 230000002829 reductive effect Effects 0.000 description 30
- 239000011541 reaction mixture Substances 0.000 description 29
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
- 239000003480 eluent Substances 0.000 description 25
- 229910000027 potassium carbonate Inorganic materials 0.000 description 24
- 239000000741 silica gel Substances 0.000 description 24
- 229910002027 silica gel Inorganic materials 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 22
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
- YZTJYBJCZXZGCT-UHFFFAOYSA-N phenylpiperazine Chemical class C1CNCCN1C1=CC=CC=C1 YZTJYBJCZXZGCT-UHFFFAOYSA-N 0.000 description 19
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 239000003921 oil Substances 0.000 description 18
- 235000019198 oils Nutrition 0.000 description 18
- RMFVUDAGEWRNHG-UHFFFAOYSA-N 4-chloro-2,6-bis(2-hydroxyethylamino)pyrimidine-5-carbonitrile Chemical compound OCCNC1=NC(Cl)=C(C#N)C(NCCO)=N1 RMFVUDAGEWRNHG-UHFFFAOYSA-N 0.000 description 17
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 16
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 15
- 239000002585 base Substances 0.000 description 15
- 239000002904 solvent Substances 0.000 description 15
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- 229940093499 ethyl acetate Drugs 0.000 description 14
- 235000019439 ethyl acetate Nutrition 0.000 description 14
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 14
- WEPCXNAHHDXYIU-UHFFFAOYSA-N 4,6-dichloro-2-(2-hydroxyethylamino)pyrimidine-5-carbonitrile Chemical compound OCCNC1=NC(Cl)=C(C#N)C(Cl)=N1 WEPCXNAHHDXYIU-UHFFFAOYSA-N 0.000 description 13
- AHSWRBPLPKWWOE-UHFFFAOYSA-N 6-[4-(4-fluorophenyl)piperidin-1-yl]-2-methyl-5-nitro-1h-pyrimidin-4-one Chemical compound O=C1NC(C)=NC(N2CCC(CC2)C=2C=CC(F)=CC=2)=C1[N+]([O-])=O AHSWRBPLPKWWOE-UHFFFAOYSA-N 0.000 description 13
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 13
- AVJKDKWRVSSJPK-UHFFFAOYSA-N 1-(4-fluorophenyl)piperazine Chemical compound C1=CC(F)=CC=C1N1CCNCC1 AVJKDKWRVSSJPK-UHFFFAOYSA-N 0.000 description 12
- IAJCAZVXGKGAQK-UHFFFAOYSA-N 2,4,6-trichloropyrimidine-5-carbonitrile Chemical compound ClC1=NC(Cl)=C(C#N)C(Cl)=N1 IAJCAZVXGKGAQK-UHFFFAOYSA-N 0.000 description 12
- 125000000217 alkyl group Chemical group 0.000 description 12
- UTBULQCHEUWJNV-UHFFFAOYSA-N 4-phenylpiperidine Chemical compound C1CNCCC1C1=CC=CC=C1 UTBULQCHEUWJNV-UHFFFAOYSA-N 0.000 description 11
- RAMWFXUFWNNURD-UHFFFAOYSA-N 6-[4-(4-fluorophenyl)piperazin-1-yl]-2-methyl-5-nitro-1h-pyrimidin-4-one Chemical compound O=C1NC(C)=NC(N2CCN(CC2)C=2C=CC(F)=CC=2)=C1[N+]([O-])=O RAMWFXUFWNNURD-UHFFFAOYSA-N 0.000 description 11
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 11
- 235000019341 magnesium sulphate Nutrition 0.000 description 11
- 239000012071 phase Substances 0.000 description 11
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000012074 organic phase Substances 0.000 description 9
- ILPIXXSCUKTFGB-UHFFFAOYSA-N 4-(4-fluorophenyl)piperidine;hydrochloride Chemical compound Cl.C1=CC(F)=CC=C1C1CCNCC1 ILPIXXSCUKTFGB-UHFFFAOYSA-N 0.000 description 8
- LQSHZAMNMMADNI-UHFFFAOYSA-N 4-chloro-2-(cyclopropylamino)-6-(2-hydroxyethylamino)pyrimidine-5-carbonitrile Chemical compound ClC1=C(C#N)C(NCCO)=NC(NC2CC2)=N1 LQSHZAMNMMADNI-UHFFFAOYSA-N 0.000 description 8
- UFBXJALDOGTXGL-UHFFFAOYSA-N 4-chloro-6-(2-hydroxyethylamino)-2-(pyridin-3-ylmethylamino)pyrimidine-5-carbonitrile Chemical compound ClC1=C(C#N)C(NCCO)=NC(NCC=2C=NC=CC=2)=N1 UFBXJALDOGTXGL-UHFFFAOYSA-N 0.000 description 8
- MGVLZTSOZFVVKR-UHFFFAOYSA-N 6-bromo-2-methyl-5-nitro-1h-pyrimidin-4-one Chemical compound CC1=NC(Br)=C([N+]([O-])=O)C(=O)N1 MGVLZTSOZFVVKR-UHFFFAOYSA-N 0.000 description 8
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 8
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
- 239000002775 capsule Substances 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
- 239000000843 powder Substances 0.000 description 8
- 229910052938 sodium sulfate Inorganic materials 0.000 description 8
- 235000011152 sodium sulphate Nutrition 0.000 description 8
- XNLQAQYLXYAYNH-UHFFFAOYSA-N 3-chloro-6-ethyl-5-methylpyrazine-2-carbonitrile Chemical compound CCC1=NC(C#N)=C(Cl)N=C1C XNLQAQYLXYAYNH-UHFFFAOYSA-N 0.000 description 7
- 108010010914 Metabotropic glutamate receptors Proteins 0.000 description 7
- 102000016193 Metabotropic glutamate receptors Human genes 0.000 description 7
- 150000001412 amines Chemical class 0.000 description 7
- 239000007864 aqueous solution Substances 0.000 description 7
- 239000000969 carrier Substances 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
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- NIGABBJLWQTUHQ-UHFFFAOYSA-N 2-amino-4-bromo-6-methylsulfanylpyrimidine-5-carbonitrile Chemical compound CSC1=NC(N)=NC(Br)=C1C#N NIGABBJLWQTUHQ-UHFFFAOYSA-N 0.000 description 6
- PVMFSFJXLROPKO-UHFFFAOYSA-N 3-chloro-5-ethyl-6-methylpyrazine-2-carbonitrile Chemical compound CCC1=NC(Cl)=C(C#N)N=C1C PVMFSFJXLROPKO-UHFFFAOYSA-N 0.000 description 6
- LYPOLXZGVYHYTO-UHFFFAOYSA-N 4-chloro-6-(cyclopropylmethylamino)-2-(2-hydroxyethylamino)pyrimidine-5-carbonitrile Chemical compound OCCNC1=NC(Cl)=C(C#N)C(NCC2CC2)=N1 LYPOLXZGVYHYTO-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- IGSKHXTUVXSOMB-UHFFFAOYSA-N cyclopropylmethanamine Chemical compound NCC1CC1 IGSKHXTUVXSOMB-UHFFFAOYSA-N 0.000 description 6
- 238000000354 decomposition reaction Methods 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 6
- 235000017557 sodium bicarbonate Nutrition 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- FAZSTBCWNTWANH-UHFFFAOYSA-N 1-phenyl-3,4-dihydro-2h-pyridine Chemical class C1CCC=CN1C1=CC=CC=C1 FAZSTBCWNTWANH-UHFFFAOYSA-N 0.000 description 5
- LLSKXGRDUPMXLC-UHFFFAOYSA-N 1-phenylpiperidine Chemical class C1CCCCN1C1=CC=CC=C1 LLSKXGRDUPMXLC-UHFFFAOYSA-N 0.000 description 5
- OPUSKONZRUOWDP-UHFFFAOYSA-N 2-methyl-5-nitro-6-(4-phenylpiperidin-1-yl)-1h-pyrimidin-4-one Chemical compound O=C1NC(C)=NC(N2CCC(CC2)C=2C=CC=CC=2)=C1[N+]([O-])=O OPUSKONZRUOWDP-UHFFFAOYSA-N 0.000 description 5
- LCRXVZUADRMZHU-UHFFFAOYSA-N 3-bromo-5-chloropyrazine-2-carbonitrile Chemical compound ClC1=CN=C(C#N)C(Br)=N1 LCRXVZUADRMZHU-UHFFFAOYSA-N 0.000 description 5
- CTTBTYWBXXWBMU-UHFFFAOYSA-N 4-(4-fluorophenyl)-1,2,3,6-tetrahydropyridine;hydrochloride Chemical compound Cl.C1=CC(F)=CC=C1C1=CCNCC1 CTTBTYWBXXWBMU-UHFFFAOYSA-N 0.000 description 5
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- 108010038450 metabotropic glutamate receptor 6 Proteins 0.000 description 1
- 108010038449 metabotropic glutamate receptor 7 Proteins 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
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- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
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- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 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
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- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
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- 102000004169 proteins and genes Human genes 0.000 description 1
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- AOCSUUGBCMTKJH-UHFFFAOYSA-N tert-butyl n-(2-aminoethyl)carbamate Chemical compound CC(C)(C)OC(=O)NCCN AOCSUUGBCMTKJH-UHFFFAOYSA-N 0.000 description 1
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- MTQPZXNVDIKRAK-UHFFFAOYSA-N tert-butyl-(4-chlorobutoxy)-dimethylsilane Chemical compound CC(C)(C)[Si](C)(C)OCCCCCl MTQPZXNVDIKRAK-UHFFFAOYSA-N 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
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- 125000003652 trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 1
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- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
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- C07D239/48—Two nitrogen atoms
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- C07D241/24—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D241/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms
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- C07D253/02—Heterocyclic compounds containing six-membered rings having three nitrogen atoms as the only ring hetero atoms, not provided for by group C07D251/00 not condensed with other rings
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- C07D253/075—Two hetero atoms, in positions 3 and 5
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- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP01113379.0 | 2001-06-01 | ||
| EP01113379 | 2001-06-01 | ||
| PCT/EP2002/005788 WO2002098864A1 (en) | 2001-06-01 | 2002-05-27 | Pyrimidine, triazine and pyrazine derivatives as glutamate receptors |
Publications (2)
| Publication Number | Publication Date |
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| CA2448602A1 CA2448602A1 (en) | 2002-12-12 |
| CA2448602C true CA2448602C (en) | 2009-03-31 |
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| Application Number | Title | Priority Date | Filing Date |
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| CA002448602A Expired - Fee Related CA2448602C (en) | 2001-06-01 | 2002-05-27 | Pyrimidine, triazine and pyrazine derivatives as glutamate receptors |
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|---|---|
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| WO (1) | WO2002098864A1 (enExample) |
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|---|---|---|---|---|
| DE10238722A1 (de) | 2002-08-23 | 2004-03-11 | Bayer Ag | Selektive Phosphodiesterase 9A-Inhibitoren als Arzneimittel zur Verbesserung kognitiver Prozesse |
| DE10238724A1 (de) | 2002-08-23 | 2004-03-04 | Bayer Ag | Alkyl-substituierte Pyrazolpyrimidine |
| EP1927594A1 (en) * | 2003-01-14 | 2008-06-04 | Arena Pharmaceuticals, Inc. | 1,2,3-Trisubstituted aryl and heteroaryl derivatives as modulators of metabolism and the prophylaxis and treatment of disorders related thereto such as diabetes and hyperglycemia |
| UA92450C2 (ru) * | 2003-01-14 | 2010-11-10 | Арена Фармасьютикалз, Инк. | 1,2,3-тризамещенные арильные и гетероарильные производные как модуляторы метаболизма, профилактика и лечение расстройств, связанных с ним, таких как диабет и гипергликемия |
| BRPI0406761A (pt) * | 2003-01-14 | 2005-12-20 | Arena Pharm Inc | Derivados de arila e heteroarila 1,2,3-trissubstituìdos como moduladores do metabolismo e a profilaxia e tratamento de distúrbios relacionados a estes tais como diabetes e hiper-glicemia |
| JP2006521358A (ja) * | 2003-03-26 | 2006-09-21 | メルク エンド カムパニー インコーポレーテッド | 代謝調節型グルタミン酸受容体のベンズアミドモジュレータ |
| DE10320785A1 (de) | 2003-05-09 | 2004-11-25 | Bayer Healthcare Ag | 6-Arylmethyl-substituierte Pyrazolopyrimidine |
| DE10328479A1 (de) | 2003-06-25 | 2005-01-13 | Bayer Ag | 6-Arylamino-5-cyano-4-pyrimidinone |
| AR045047A1 (es) * | 2003-07-11 | 2005-10-12 | Arena Pharm Inc | Derivados arilo y heteroarilo trisustituidos como moduladores del metabolismo y de la profilaxis y tratamiento de desordenes relacionados con los mismos |
| AR045697A1 (es) | 2003-07-14 | 2005-11-09 | Arena Pharm Inc | Aril y heteroaril derivados fusionados como moduladores del metabolismo y la prevencion y tratamiento de trastornos relacionados con el mismo |
| EP1644358A2 (en) * | 2003-07-16 | 2006-04-12 | Neurogen Corporation | Biaryl piperazinyl-pyridine analogues |
| PE20050483A1 (es) | 2003-10-31 | 2005-08-25 | Arena Pharm Inc | Derivados de tetrazol de formula (i), sus composiciones farmaceuticas y procesos para producir composiciones farmaceuticas |
| GB0325956D0 (en) * | 2003-11-06 | 2003-12-10 | Addex Pharmaceuticals Sa | Novel compounds |
| SE0303492D0 (sv) * | 2003-12-19 | 2003-12-19 | Astrazeneca Ab | New use VII |
| DE102004001873A1 (de) * | 2004-01-14 | 2005-09-29 | Bayer Healthcare Ag | Cyanopyrimidinone |
| MY145822A (en) * | 2004-08-13 | 2012-04-30 | Neurogen Corp | Substituted biaryl piperazinyl-pyridine analogues |
| BRPI0515499A (pt) | 2004-09-20 | 2008-07-29 | Xenon Pharmaceuticals Inc | derivados de piridina para a inibição de estearoil-coa-desaturase humana |
| WO2007081630A2 (en) * | 2005-12-21 | 2007-07-19 | Janssen Pharmaceutica, N.V. | Substituted pyrimidinyl kinase inhibitors |
| US8153791B2 (en) * | 2005-12-21 | 2012-04-10 | Janssen Pharmaceutica N.V. | Substituted pyrimidinyl oxime kinase inhibitors |
| US8278446B2 (en) * | 2005-12-21 | 2012-10-02 | Janssen Pharmaceutica N.V. | Process for preparing substituted diaminopyrimidine oximes |
| US7834178B2 (en) * | 2006-03-01 | 2010-11-16 | Bristol-Myers Squibb Company | Triazine 11-beta hydroxysteroid dehydrogenase type 1 inhibitors |
| WO2007109783A2 (en) * | 2006-03-23 | 2007-09-27 | Janssen Pharmaceutica, N.V. | Substituted pyrimidine kinase inhibitors |
| US8648085B2 (en) | 2007-11-30 | 2014-02-11 | Boehringer Ingelheim International Gmbh | 1, 5-dihydro-pyrazolo (3, 4-D) pyrimidin-4-one derivatives and their use as PDE9A mudulators for the treatment of CNS disorders |
| CA2720049A1 (en) | 2008-03-31 | 2009-10-08 | Zenyaku Kogyo Kabushikikaisha | Pyrimidine derivative having cell protecting effect and uses thereof |
| UA105362C2 (en) | 2008-04-02 | 2014-05-12 | Бьорингер Ингельхайм Интернациональ Гмбх | 1-heterocyclyl-1, 5-dihydro-pyrazolo [3, 4-d] pyrimidin-4-one derivatives and their use as pde9a modulators |
| JP5453431B2 (ja) | 2008-09-08 | 2014-03-26 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | ピラゾロピリミジン及びcns障害の治療のためのそれらの使用 |
| PT2414363E (pt) | 2009-03-31 | 2014-02-26 | Boehringer Ingelheim Int | Derivados de 1-heterociclil-1,5-di-hidro-pirazolo[3,4- d]pirimidin-4-ona e sua utilização como moduladores de pde9a |
| NZ603725A (en) | 2010-08-12 | 2015-04-24 | Boehringer Ingelheim Int | 6-cycloalkyl-1,5-dihydro-pyrazolo [3,4-d] pyrimidin-4-one derivatives and their use as pde9a inhibitors |
| SG188548A1 (en) | 2010-09-22 | 2013-04-30 | Arena Pharm Inc | Modulators of the gpr119 receptor and the treatment of disorders related thereto |
| US8809345B2 (en) | 2011-02-15 | 2014-08-19 | Boehringer Ingelheim International Gmbh | 6-cycloalkyl-pyrazolopyrimidinones for the treatment of CNS disorders |
| JP6484640B2 (ja) * | 2014-02-14 | 2019-03-13 | 武田薬品工業株式会社 | Gpr6のピラジンモジュレーター |
| AU2016205361C1 (en) | 2015-01-06 | 2021-04-08 | Arena Pharmaceuticals, Inc. | Methods of treating conditions related to the S1P1 receptor |
| CA3002551A1 (en) | 2015-06-22 | 2016-12-29 | Arena Pharmaceuticals, Inc. | Crystalline l-arginine salt of (r)-2-(7-(4-cyclopentyl-3-(trifluoromethyl)benzyloxy)-1,2,3,4-tetrahydrocyclo-penta[b]indol-3-yl)acetic acid(com pound 1)for use in s1p1 receptor-associated disorders |
| CN105125571B (zh) * | 2015-07-17 | 2018-11-06 | 四川大学 | Prmt1抑制剂在制备治疗可卡因成瘾的药物中的用途 |
| CA3053418A1 (en) | 2017-02-16 | 2018-08-23 | Arena Pharmaceuticals, Inc. | Compounds and methods for treatment of primary biliary cholangitis |
| EP3600312B1 (en) * | 2017-03-26 | 2023-05-17 | Takeda Pharmaceutical Company Limited | Piperidinyl- and piperazinyl-substituted heteroaromatic carboxamides as modulators of gpr6 |
| CA3102136A1 (en) | 2018-06-06 | 2019-12-12 | Arena Pharmaceuticals, Inc. | Methods of treating conditions related to the s1p1 receptor |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| EP1074549B1 (en) * | 1999-08-06 | 2003-11-19 | F. Hoffmann-La Roche Ag | Tetrahydro-benzo(d)azepines and their use as antagonists at metabotropic glutamate receptors |
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2002
- 2002-05-27 DK DK02748720.6T patent/DK1397351T3/da active
- 2002-05-27 CA CA002448602A patent/CA2448602C/en not_active Expired - Fee Related
- 2002-05-27 AT AT02748720T patent/ATE448210T1/de not_active IP Right Cessation
- 2002-05-27 WO PCT/EP2002/005788 patent/WO2002098864A1/en not_active Ceased
- 2002-05-27 AU AU2002319183A patent/AU2002319183B2/en not_active Ceased
- 2002-05-27 EP EP02748720A patent/EP1397351B1/en not_active Expired - Lifetime
- 2002-05-27 ES ES02748720T patent/ES2332505T3/es not_active Expired - Lifetime
- 2002-05-27 JP JP2003501988A patent/JP4049742B2/ja not_active Expired - Fee Related
- 2002-05-27 KR KR1020037015685A patent/KR100602927B1/ko not_active Expired - Fee Related
- 2002-05-27 DE DE60234338T patent/DE60234338D1/de not_active Expired - Lifetime
- 2002-05-27 BR BR0210102-5A patent/BR0210102A/pt not_active Application Discontinuation
- 2002-05-27 PT PT02748720T patent/PT1397351E/pt unknown
- 2002-05-27 MX MXPA03010822A patent/MXPA03010822A/es active IP Right Grant
- 2002-05-27 CN CNB028109872A patent/CN1245391C/zh not_active Expired - Fee Related
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- 2002-05-31 AR ARP020102040A patent/AR036075A1/es unknown
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Also Published As
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|---|---|
| US20030060466A1 (en) | 2003-03-27 |
| DE60234338D1 (de) | 2009-12-24 |
| PT1397351E (pt) | 2010-01-04 |
| ATE448210T1 (de) | 2009-11-15 |
| US6673795B2 (en) | 2004-01-06 |
| BR0210102A (pt) | 2004-06-08 |
| ZA200308859B (en) | 2005-02-14 |
| EP1397351A1 (en) | 2004-03-17 |
| EP1397351B1 (en) | 2009-11-11 |
| CA2448602A1 (en) | 2002-12-12 |
| KR100602927B1 (ko) | 2006-07-20 |
| AU2002319183B2 (en) | 2007-05-10 |
| KR20040003039A (ko) | 2004-01-07 |
| JP2004536814A (ja) | 2004-12-09 |
| AR036075A1 (es) | 2004-08-11 |
| CN1512988A (zh) | 2004-07-14 |
| JP4049742B2 (ja) | 2008-02-20 |
| MXPA03010822A (es) | 2004-02-17 |
| ES2332505T3 (es) | 2010-02-08 |
| CN1245391C (zh) | 2006-03-15 |
| DK1397351T3 (da) | 2010-01-18 |
| WO2002098864A1 (en) | 2002-12-12 |
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