JP2002535407A - Ｇａｂａ受容体のリガンドとしてのトリアゾロピリダジン誘導体 - Google Patents
Ｇａｂａ受容体のリガンドとしてのトリアゾロピリダジン誘導体Info
- Publication number
- JP2002535407A JP2002535407A JP2000596008A JP2000596008A JP2002535407A JP 2002535407 A JP2002535407 A JP 2002535407A JP 2000596008 A JP2000596008 A JP 2000596008A JP 2000596008 A JP2000596008 A JP 2000596008A JP 2002535407 A JP2002535407 A JP 2002535407A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- formula
- pharmaceutically acceptable
- triazolo
- pyridazine
- 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.)
- Withdrawn
Links
- 239000003446 ligand Substances 0.000 title abstract description 9
- CBHTTYDJRXOHHL-UHFFFAOYSA-N 2h-triazolo[4,5-c]pyridazine Chemical class N1=NC=CC2=C1N=NN2 CBHTTYDJRXOHHL-UHFFFAOYSA-N 0.000 title description 3
- 102000005915 GABA Receptors Human genes 0.000 title 1
- 108010005551 GABA Receptors Proteins 0.000 title 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims abstract description 11
- 208000019901 Anxiety disease Diseases 0.000 claims abstract description 9
- 230000036506 anxiety Effects 0.000 claims abstract description 7
- 230000002265 prevention Effects 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 132
- 239000000203 mixture Substances 0.000 claims description 31
- 150000003839 salts Chemical class 0.000 claims description 26
- 238000000034 method Methods 0.000 claims description 25
- -1 2,5-difluorophenyl Chemical group 0.000 claims description 16
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 8
- 229910052731 fluorine Inorganic materials 0.000 claims description 8
- 239000011737 fluorine Substances 0.000 claims description 8
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 5
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
- 229910001961 silver nitrate Inorganic materials 0.000 claims description 4
- 239000003054 catalyst Substances 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 229910052723 transition metal Inorganic materials 0.000 claims description 3
- 150000003624 transition metals Chemical class 0.000 claims description 3
- LDGXFPTUGULLJC-UHFFFAOYSA-N 5h-[1,2,4]triazolo[4,3-b]pyridazin-6-one Chemical compound N1C(=O)C=CC2=NN=CN21 LDGXFPTUGULLJC-UHFFFAOYSA-N 0.000 claims description 2
- XQHMYEGDXRPXAH-UHFFFAOYSA-N 7-tert-butyl-6-[(2-ethyl-1,2,4-triazol-3-yl)methoxy]-3-(2,3,6-trifluorophenyl)-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CCN1N=CN=C1COC(C(=C1)C(C)(C)C)=NN2C1=NN=C2C1=C(F)C=CC(F)=C1F XQHMYEGDXRPXAH-UHFFFAOYSA-N 0.000 claims description 2
- NLPXMPSTTIFCJL-UHFFFAOYSA-N 7-tert-butyl-6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-3-(2,3,6-trifluorophenyl)-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CN1N=CN=C1COC(C(=C1)C(C)(C)C)=NN2C1=NN=C2C1=C(F)C=CC(F)=C1F NLPXMPSTTIFCJL-UHFFFAOYSA-N 0.000 claims description 2
- YRACHDVMKITFAZ-UHFFFAOYSA-N [1,2,4]triazolo[4,3-b]pyridazine Chemical compound C1=CC=NN2C=NN=C21 YRACHDVMKITFAZ-UHFFFAOYSA-N 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 238000003795 desorption Methods 0.000 claims 2
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 claims 1
- JRKICGRDRMAZLK-UHFFFAOYSA-L peroxydisulfate Chemical compound [O-]S(=O)(=O)OOS([O-])(=O)=O JRKICGRDRMAZLK-UHFFFAOYSA-L 0.000 claims 1
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 abstract description 39
- 229960003692 gamma aminobutyric acid Drugs 0.000 abstract description 38
- 206010010904 Convulsion Diseases 0.000 abstract description 5
- 230000036461 convulsion Effects 0.000 abstract description 4
- 150000004892 pyridazines Chemical class 0.000 abstract description 2
- 208000015114 central nervous system disease Diseases 0.000 abstract 1
- PQIOSYKVBBWRRI-UHFFFAOYSA-N methylphosphonyl difluoride Chemical group CP(F)(F)=O PQIOSYKVBBWRRI-UHFFFAOYSA-N 0.000 abstract 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract 1
- 108020003175 receptors Proteins 0.000 description 35
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
- 102000005962 receptors Human genes 0.000 description 33
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 21
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 20
- 210000004027 cell Anatomy 0.000 description 20
- 239000011541 reaction mixture Substances 0.000 description 19
- 239000002904 solvent Substances 0.000 description 19
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 18
- 239000000243 solution Substances 0.000 description 16
- 230000027455 binding Effects 0.000 description 15
- 238000006243 chemical reaction Methods 0.000 description 14
- 239000007787 solid Substances 0.000 description 14
- 239000000543 intermediate Substances 0.000 description 13
- 230000002829 reductive effect Effects 0.000 description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethyl sulfoxide Natural products CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- 238000005481 NMR spectroscopy Methods 0.000 description 11
- 238000000524 positive electrospray ionisation mass spectrometry Methods 0.000 description 11
- 239000000047 product Substances 0.000 description 11
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 229940049706 benzodiazepine Drugs 0.000 description 8
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical group [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 7
- 239000002253 acid Substances 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical group [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- ROOXNKNUYICQNP-UHFFFAOYSA-N ammonium persulfate Chemical compound [NH4+].[NH4+].[O-]S(=O)(=O)OOS([O-])(=O)=O ROOXNKNUYICQNP-UHFFFAOYSA-N 0.000 description 6
- 239000012131 assay buffer Substances 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- ZXEKIIBDNHEJCQ-UHFFFAOYSA-N isobutanol Chemical compound CC(C)CO ZXEKIIBDNHEJCQ-UHFFFAOYSA-N 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 5
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical group CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- 239000000556 agonist Substances 0.000 description 5
- 238000003556 assay Methods 0.000 description 5
- 239000000460 chlorine Substances 0.000 description 5
- 239000012442 inert solvent Substances 0.000 description 5
- 239000012299 nitrogen atmosphere Substances 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 239000012312 sodium hydride Substances 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 4
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 230000000949 anxiolytic effect Effects 0.000 description 4
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical group [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 4
- 229910000024 caesium carbonate Inorganic materials 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 239000003480 eluent Substances 0.000 description 4
- 229960004381 flumazenil Drugs 0.000 description 4
- 125000005843 halogen group Chemical group 0.000 description 4
- 239000012074 organic phase Substances 0.000 description 4
- 239000002953 phosphate buffered saline Substances 0.000 description 4
- 239000006187 pill Substances 0.000 description 4
- 238000007363 ring formation reaction Methods 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000003483 4 aminobutyric acid A receptor stimulating agent Substances 0.000 description 3
- NQFZRBJDRTUSRM-UHFFFAOYSA-N 7-tert-butyl-3-(2,5-difluorophenyl)-6-[(2-ethyl-1,2,4-triazol-3-yl)methoxy]-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CCN1N=CN=C1COC(C(=C1)C(C)(C)C)=NN2C1=NN=C2C1=CC(F)=CC=C1F NQFZRBJDRTUSRM-UHFFFAOYSA-N 0.000 description 3
- WUWBLFOIBOCSJK-UHFFFAOYSA-N 7-tert-butyl-3-(2,6-difluorophenyl)-6-[(2-ethyl-1,2,4-triazol-3-yl)methoxy]-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound CCN1N=CN=C1COC(C(=C1)C(C)(C)C)=NN2C1=NN=C2C1=C(F)C=CC=C1F WUWBLFOIBOCSJK-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 206010039897 Sedation Diseases 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- 206010047700 Vomiting Diseases 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 229910001870 ammonium persulfate Inorganic materials 0.000 description 3
- 210000004556 brain Anatomy 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 208000035475 disorder Diseases 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000000921 elemental analysis Methods 0.000 description 3
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- 150000002429 hydrazines Chemical class 0.000 description 3
- 229940035429 isobutyl alcohol Drugs 0.000 description 3
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- 238000001356 surgical procedure Methods 0.000 description 3
- NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- DTUZXHRABOWYAE-UHFFFAOYSA-N 4-tert-butyl-3,6-dichloropyridazine Chemical compound CC(C)(C)C1=CC(Cl)=NN=C1Cl DTUZXHRABOWYAE-UHFFFAOYSA-N 0.000 description 2
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 2
- FCSKOFQQCWLGMV-UHFFFAOYSA-N 5-{5-[2-chloro-4-(4,5-dihydro-1,3-oxazol-2-yl)phenoxy]pentyl}-3-methylisoxazole Chemical compound O1N=C(C)C=C1CCCCCOC1=CC=C(C=2OCCN=2)C=C1Cl FCSKOFQQCWLGMV-UHFFFAOYSA-N 0.000 description 2
- 208000008811 Agoraphobia Diseases 0.000 description 2
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
- 208000020925 Bipolar disease Diseases 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- 208000020401 Depressive disease Diseases 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- 108090000862 Ion Channels Proteins 0.000 description 2
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- 108090000543 Ligand-Gated Ion Channels Proteins 0.000 description 2
- 102000004086 Ligand-Gated Ion Channels Human genes 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
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- 239000002262 Schiff base Substances 0.000 description 2
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- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 2
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- 230000000147 hypnotic effect Effects 0.000 description 2
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- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 2
- BQDUNOMMYOKHEP-UHFFFAOYSA-N l-838,417 Chemical compound CN1N=CN=C1COC(C(=C1)C(C)(C)C)=NN2C1=NN=C2C1=CC(F)=CC=C1F BQDUNOMMYOKHEP-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000005567 liquid scintillation counting Methods 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 2
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Vascular Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9901743.6 | 1999-01-27 | ||
| GBGB9901744.4A GB9901744D0 (en) | 1999-01-27 | 1999-01-27 | Therapeutic agents |
| GB9901744.4 | 1999-01-27 | ||
| GBGB9901743.6A GB9901743D0 (en) | 1999-01-27 | 1999-01-27 | Therapeutic agents |
| GB9912429.9 | 1999-05-27 | ||
| GBGB9912429.9A GB9912429D0 (en) | 1999-05-27 | 1999-05-27 | Therapeutic agents |
| PCT/GB2000/000183 WO2000044752A1 (en) | 1999-01-27 | 2000-01-19 | Triazolo-pyridazine derivatives as ligands for gaba receptors |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2002535407A true JP2002535407A (ja) | 2002-10-22 |
| JP2002535407A5 JP2002535407A5 (enExample) | 2007-03-08 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000596008A Withdrawn JP2002535407A (ja) | 1999-01-27 | 2000-01-19 | Ｇａｂａ受容体のリガンドとしてのトリアゾロピリダジン誘導体 |
Country Status (9)
| Country | Link |
|---|---|
| US (2) | US6500828B1 (enExample) |
| EP (1) | EP1149102B1 (enExample) |
| JP (1) | JP2002535407A (enExample) |
| AT (1) | ATE284403T1 (enExample) |
| AU (1) | AU772947B2 (enExample) |
| CA (1) | CA2359008C (enExample) |
| DE (1) | DE60016566T2 (enExample) |
| ES (1) | ES2232416T3 (enExample) |
| WO (1) | WO2000044752A1 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2012501346A (ja) * | 2008-08-29 | 2012-01-19 | コンサート ファーマシューティカルズ インコーポレイテッド | 置換トリアゾロ−ピリダジン誘導体 |
Families Citing this family (25)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0000564D0 (en) * | 2000-01-11 | 2000-03-01 | Merck Sharp & Dohme | Therapeutic agents |
| AU2002251266A1 (en) | 2001-04-10 | 2002-10-28 | Merck Sharp And Dohme Limited | Inhibitors of akt activity |
| US6958334B2 (en) | 2001-04-10 | 2005-10-25 | Merck & Co., Inc. | Inhibitors of Akt activity |
| WO2002083139A1 (en) | 2001-04-10 | 2002-10-24 | Merck & Co., Inc. | Inhibitors of akt activity |
| WO2004048980A1 (en) * | 2002-11-28 | 2004-06-10 | Neurosearch A/S | Method for screening for compounds as potential sedatives or anxiolytics |
| WO2006061428A2 (en) * | 2004-12-10 | 2006-06-15 | Universität Zürich | Gaba-a alpha 2 and alpha 3 receptor agonists for treating neuropathic, inflammatory and migraine associated pain |
| EP2258359A3 (en) | 2005-08-26 | 2011-04-06 | Braincells, Inc. | Neurogenesis by muscarinic receptor modulation with sabcomelin |
| US7678363B2 (en) | 2005-08-26 | 2010-03-16 | Braincells Inc | Methods of treating psychiatric conditions comprising administration of muscarinic agents in combination with SSRIs |
| WO2007047978A2 (en) | 2005-10-21 | 2007-04-26 | Braincells, Inc. | Modulation of neurogenesis by pde inhibition |
| AU2006308889A1 (en) | 2005-10-31 | 2007-05-10 | Braincells, Inc. | GABA receptor mediated modulation of neurogenesis |
| US20100216734A1 (en) | 2006-03-08 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis by nootropic agents |
| WO2007134077A2 (en) | 2006-05-09 | 2007-11-22 | Braincells, Inc. | 5 ht receptor mediated neurogenesis |
| CA2651813A1 (en) | 2006-05-09 | 2007-11-22 | Braincells, Inc. | Neurogenesis by modulating angiotensin |
| CA2662491A1 (en) | 2006-09-08 | 2008-03-13 | Braincells, Inc. | Combinations containing a 4-acylaminopyridine derivative |
| WO2010099217A1 (en) | 2009-02-25 | 2010-09-02 | Braincells, Inc. | Modulation of neurogenesis using d-cycloserine combinations |
| WO2011005520A1 (en) | 2009-06-23 | 2011-01-13 | Concert Pharmaceuticals, Inc. | Deuterium-modified triazolo-pyridazine derivatives as gaba-a receptor modulators |
| US8278460B2 (en) | 2009-10-15 | 2012-10-02 | Concert Pharmaceuticals, Inc. | Substituted benzimidazoles |
| US20150099753A1 (en) * | 2012-05-11 | 2015-04-09 | Concert Pharmaceuticals Inc. | Form 5 polymorph of 7-(tert-butyl-d9)-3-(2,5-difluorophenyl)-6-((1-methyl-1h-1,2,4-triazol-5-yl)methoxy)-[1,2,4]triazolo[4,3-b]pyridazine |
| JP2015516440A (ja) * | 2012-05-11 | 2015-06-11 | コンサート ファーマシューティカルズ インコーポレイテッド | ７−（ｔｅｒｔ−ブチル−ｄ９）−３−（２，５−ジフルオロフェニル）−６−（（１−メチル−１Ｈ−１，２，４−トリアゾール−５−イル）メトキシ）−［１，２，４］トリアゾロ［４，３−ｂ］ピリダジンの２型多形 |
| US20150158870A1 (en) * | 2012-05-11 | 2015-06-11 | Concert Pharmaceuticals Inc. | Polymorphs of 7-(tert-butyl-d9)-3-(2,5-difluorophenyl)-6-((1-methyl-1h-1,2,4-triazol-5-yl)methoxy)-[1,2,4]triazolo[4,3-b]pyridazine |
| WO2015095549A1 (en) * | 2013-12-18 | 2015-06-25 | Concert Pharmaceuticals, Inc. | Dosage regimen for gabaa receptor subtype selective drug |
| LT3849976T (lt) | 2018-09-13 | 2023-02-10 | Saniona A/S | Gaba a receptoriaus ligandas |
| EP4511025A1 (en) * | 2022-04-20 | 2025-02-26 | Engrail Therapeutics, Inc. | GABAa RECEPTOR MODULATOR SALTS, PARTICLES, AND USES THEREOF |
| CN115837022B (zh) * | 2023-02-20 | 2023-04-25 | 中山大学附属第八医院（深圳福田） | 1,2,4三唑并4,3-b哒嗪衍生物在制备抗衰老药物中的应用 |
| WO2025141131A1 (en) | 2023-12-27 | 2025-07-03 | Saniona A/S | A gabaa receptor ligand and the use thereof in medicine, in particular in the treatment of epilepsy |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL127911A0 (en) * | 1996-07-25 | 1999-11-30 | Merck Sharp & Dohme | Substituted triazolo-pyridazine derivatives as ligands for gaba receptors |
-
2000
- 2000-01-19 AT AT00900748T patent/ATE284403T1/de not_active IP Right Cessation
- 2000-01-19 AU AU30669/00A patent/AU772947B2/en not_active Ceased
- 2000-01-19 US US09/890,000 patent/US6500828B1/en not_active Expired - Fee Related
- 2000-01-19 JP JP2000596008A patent/JP2002535407A/ja not_active Withdrawn
- 2000-01-19 WO PCT/GB2000/000183 patent/WO2000044752A1/en not_active Ceased
- 2000-01-19 ES ES00900748T patent/ES2232416T3/es not_active Expired - Lifetime
- 2000-01-19 EP EP00900748A patent/EP1149102B1/en not_active Expired - Lifetime
- 2000-01-19 CA CA002359008A patent/CA2359008C/en not_active Expired - Fee Related
- 2000-01-19 DE DE60016566T patent/DE60016566T2/de not_active Expired - Fee Related
-
2002
- 2002-12-20 US US10/324,968 patent/US20030158203A1/en not_active Abandoned
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2012501346A (ja) * | 2008-08-29 | 2012-01-19 | コンサート ファーマシューティカルズ インコーポレイテッド | 置換トリアゾロ−ピリダジン誘導体 |
| JP2013100322A (ja) * | 2008-08-29 | 2013-05-23 | Concert Pharmaceuticals Inc | 置換トリアゾロ−ピリダジン誘導体 |
| JP2014058518A (ja) * | 2008-08-29 | 2014-04-03 | Concert Pharmaceuticals Inc | 置換トリアゾロ−ピリダジン誘導体 |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2359008A1 (en) | 2000-08-03 |
| US6500828B1 (en) | 2002-12-31 |
| ATE284403T1 (de) | 2004-12-15 |
| DE60016566T2 (de) | 2005-12-15 |
| AU772947B2 (en) | 2004-05-13 |
| CA2359008C (en) | 2008-05-20 |
| US20030158203A1 (en) | 2003-08-21 |
| EP1149102B1 (en) | 2004-12-08 |
| DE60016566D1 (de) | 2005-01-13 |
| EP1149102A1 (en) | 2001-10-31 |
| AU3066900A (en) | 2000-08-18 |
| ES2232416T3 (es) | 2005-06-01 |
| WO2000044752A1 (en) | 2000-08-03 |
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