ES2451542T3 - Derivados de triazolo-piridazina sustituidos - Google Patents
Derivados de triazolo-piridazina sustituidos Download PDFInfo
- Publication number
- ES2451542T3 ES2451542T3 ES09810685T ES09810685T ES2451542T3 ES 2451542 T3 ES2451542 T3 ES 2451542T3 ES 09810685 T ES09810685 T ES 09810685T ES 09810685 T ES09810685 T ES 09810685T ES 2451542 T3 ES2451542 T3 ES 2451542T3
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- Spain
- Prior art keywords
- compound
- deuterium
- pharmaceutically acceptable
- compounds
- formula
- Prior art date
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- CBHTTYDJRXOHHL-UHFFFAOYSA-N 2h-triazolo[4,5-c]pyridazine Chemical class N1=NC=CC2=C1N=NN2 CBHTTYDJRXOHHL-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 148
- 229910052805 deuterium Inorganic materials 0.000 claims abstract description 41
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims abstract description 39
- 150000003839 salts Chemical class 0.000 claims abstract description 25
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 13
- 239000001257 hydrogen Substances 0.000 claims abstract description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 10
- 125000004431 deuterium atom Chemical group 0.000 claims abstract description 5
- 101710085469 CD2 homolog Chemical group 0.000 claims abstract description 3
- 102100036364 Cadherin-2 Human genes 0.000 claims abstract description 3
- 101000714537 Homo sapiens Cadherin-2 Chemical group 0.000 claims abstract description 3
- 150000002431 hydrogen Chemical group 0.000 claims abstract description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims abstract description 3
- 239000000203 mixture Substances 0.000 claims description 62
- 239000003814 drug Substances 0.000 claims description 37
- 229940124597 therapeutic agent Drugs 0.000 claims description 32
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 31
- 201000010099 disease Diseases 0.000 claims description 19
- 238000011282 treatment Methods 0.000 claims description 18
- 230000000155 isotopic effect Effects 0.000 claims description 15
- 208000035475 disorder Diseases 0.000 claims description 12
- 125000004429 atom Chemical group 0.000 claims description 11
- 208000019695 Migraine disease Diseases 0.000 claims description 7
- 208000002193 Pain Diseases 0.000 claims description 7
- 206010027599 migraine Diseases 0.000 claims description 7
- 208000019901 Anxiety disease Diseases 0.000 claims description 6
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- 208000021722 neuropathic pain Diseases 0.000 claims 3
- 108050005493 CD3 protein, epsilon/gamma/delta subunit Chemical group 0.000 abstract 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
- 238000000034 method Methods 0.000 description 26
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- -1 pyrosulfate Chemical compound 0.000 description 21
- 235000002639 sodium chloride Nutrition 0.000 description 21
- 238000006243 chemical reaction Methods 0.000 description 18
- 238000003786 synthesis reaction Methods 0.000 description 18
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 16
- 230000015572 biosynthetic process Effects 0.000 description 16
- 239000000543 intermediate Substances 0.000 description 16
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 14
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 239000008194 pharmaceutical composition Substances 0.000 description 13
- 241000700159 Rattus Species 0.000 description 12
- 238000010348 incorporation Methods 0.000 description 12
- KSAVQLQVUXSOCR-UHFFFAOYSA-M sodium lauroyl sarcosinate Chemical compound [Na+].CCCCCCCCCCCC(=O)N(C)CC([O-])=O KSAVQLQVUXSOCR-UHFFFAOYSA-M 0.000 description 12
- 239000002253 acid Substances 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 10
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- 210000001853 liver microsome Anatomy 0.000 description 9
- 230000002829 reductive effect Effects 0.000 description 9
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- WFOVEDJTASPCIR-UHFFFAOYSA-N 3-[(4-methyl-5-pyridin-4-yl-1,2,4-triazol-3-yl)methylamino]-n-[[2-(trifluoromethyl)phenyl]methyl]benzamide Chemical compound N=1N=C(C=2C=CN=CC=2)N(C)C=1CNC(C=1)=CC=CC=1C(=O)NCC1=CC=CC=C1C(F)(F)F WFOVEDJTASPCIR-UHFFFAOYSA-N 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
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- 238000001990 intravenous administration Methods 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 230000001225 therapeutic effect Effects 0.000 description 6
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 6
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 5
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 5
- 239000002202 Polyethylene glycol Substances 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
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- 235000019253 formic acid Nutrition 0.000 description 5
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- 229920001223 polyethylene glycol Polymers 0.000 description 5
- 239000002243 precursor Substances 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 229910000104 sodium hydride Inorganic materials 0.000 description 5
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 4
- NSPMIYGKQJPBQR-UHFFFAOYSA-N 4H-1,2,4-triazole Chemical compound C=1N=CNN=1 NSPMIYGKQJPBQR-UHFFFAOYSA-N 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 4
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
- 229910019142 PO4 Inorganic materials 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 239000008280 blood Substances 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 239000003937 drug carrier Substances 0.000 description 4
- 238000000921 elemental analysis Methods 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 230000002757 inflammatory effect Effects 0.000 description 4
- 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 4
- 230000014759 maintenance of location Effects 0.000 description 4
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 4
- 230000002981 neuropathic effect Effects 0.000 description 4
- 239000010452 phosphate Substances 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- 239000003643 water by type Substances 0.000 description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 3
- 102000004300 GABA-A Receptors Human genes 0.000 description 3
- 108090000839 GABA-A Receptors Proteins 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- 208000012902 Nervous system disease Diseases 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 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
- 229940093915 gynecological organic acid Drugs 0.000 description 3
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- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 3
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- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- 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 2
- GUSWJGOYDXFJSI-UHFFFAOYSA-N 3,6-dichloropyridazine Chemical compound ClC1=CC=C(Cl)N=N1 GUSWJGOYDXFJSI-UHFFFAOYSA-N 0.000 description 2
- BQDUNOMMYOKHEP-MGKWXGLJSA-N 3-(2,5-difluorophenyl)-7-[1,1,1,3,3,3-hexadeuterio-2-(trideuteriomethyl)propan-2-yl]-6-[[2-(trideuteriomethyl)-1,2,4-triazol-3-yl]methoxy]-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound [2H]C([2H])([2H])N1N=CN=C1COC(C(=C1)C(C([2H])([2H])[2H])(C([2H])([2H])[2H])C([2H])([2H])[2H])=NN2C1=NN=C2C1=CC(F)=CC=C1F BQDUNOMMYOKHEP-MGKWXGLJSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
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- 229910001629 magnesium chloride Inorganic materials 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
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- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 2
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- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 1
- HCSBTDBGTNZOAB-UHFFFAOYSA-N 2,3-dinitrobenzoic acid Chemical compound OC(=O)C1=CC=CC([N+]([O-])=O)=C1[N+]([O-])=O HCSBTDBGTNZOAB-UHFFFAOYSA-N 0.000 description 1
- CHHHXKFHOYLYRE-UHFFFAOYSA-M 2,4-Hexadienoic acid, potassium salt (1:1), (2E,4E)- Chemical compound [K+].CC=CC=CC([O-])=O CHHHXKFHOYLYRE-UHFFFAOYSA-M 0.000 description 1
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- DTUZXHRABOWYAE-GQALSZNTSA-N 3,6-dichloro-4-[1,1,1,3,3,3-hexadeuterio-2-(trideuteriomethyl)propan-2-yl]pyridazine Chemical compound [2H]C([2H])([2H])C(C([2H])([2H])[2H])(C([2H])([2H])[2H])C1=CC(Cl)=NN=C1Cl DTUZXHRABOWYAE-GQALSZNTSA-N 0.000 description 1
- BQDUNOMMYOKHEP-GQALSZNTSA-N 3-(2,5-difluorophenyl)-7-[1,1,1,3,3,3-hexadeuterio-2-(trideuteriomethyl)propan-2-yl]-6-[(2-methyl-1,2,4-triazol-3-yl)methoxy]-[1,2,4]triazolo[4,3-b]pyridazine Chemical compound N12N=C(OCC=3N(N=CN=3)C)C(C(C([2H])([2H])[2H])(C([2H])([2H])[2H])C([2H])([2H])[2H])=CC2=NN=C1C1=CC(F)=CC=C1F BQDUNOMMYOKHEP-GQALSZNTSA-N 0.000 description 1
- WHBMMWSBFZVSSR-UHFFFAOYSA-N 3-hydroxybutyric acid Chemical compound CC(O)CC(O)=O WHBMMWSBFZVSSR-UHFFFAOYSA-N 0.000 description 1
- 239000003140 4 aminobutyric acid A receptor blocking agent Substances 0.000 description 1
- PXACTUVBBMDKRW-UHFFFAOYSA-N 4-bromobenzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=C(Br)C=C1 PXACTUVBBMDKRW-UHFFFAOYSA-N 0.000 description 1
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- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/5025—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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
- A61P25/06—Antimigraine agents
-
- 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
- A61P25/08—Antiepileptics; Anticonvulsants
-
- 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
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B59/00—Introduction of isotopes of elements into organic compounds ; Labelled organic compounds per se
- C07B59/002—Heterocyclic compounds
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Neurology (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US9329308P | 2008-08-29 | 2008-08-29 | |
| US93293P | 2008-08-29 | ||
| PCT/US2009/055427 WO2010025407A1 (en) | 2008-08-29 | 2009-08-28 | Substituted triazolo-pyridazine derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2451542T3 true ES2451542T3 (es) | 2014-03-27 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ES09810685T Active ES2451542T3 (es) | 2008-08-29 | 2009-08-28 | Derivados de triazolo-piridazina sustituidos |
Country Status (17)
| Country | Link |
|---|---|
| US (4) | US8003646B2 (enExample) |
| EP (2) | EP2716158A1 (enExample) |
| JP (3) | JP5183808B2 (enExample) |
| KR (1) | KR20110063479A (enExample) |
| CN (2) | CN102176826B (enExample) |
| AU (1) | AU2009285533B2 (enExample) |
| BR (1) | BRPI0912928A2 (enExample) |
| CA (1) | CA2735549A1 (enExample) |
| DK (1) | DK2328414T3 (enExample) |
| EA (1) | EA020071B1 (enExample) |
| ES (1) | ES2451542T3 (enExample) |
| HR (1) | HRP20140195T1 (enExample) |
| MX (1) | MX2011002278A (enExample) |
| PL (1) | PL2328414T3 (enExample) |
| PT (1) | PT2328414E (enExample) |
| WO (1) | WO2010025407A1 (enExample) |
| ZA (1) | ZA201102123B (enExample) |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| MX2011002278A (es) | 2008-08-29 | 2011-04-14 | Concert Pharmaceuticals Inc | Derivados de triazolo-piridazina sustituidos. |
| EP2340782A4 (en) | 2008-10-03 | 2014-04-02 | Inst Alberto Luiz Coimbra De Pos Graduacao E Pesquisa De Engenharia Coppe Ufrj | METHOD AND DEVICE FOR REMOVING METAL FRAGMENTS AND METAL ELEMENTS FROM TOOTH ROOT CHANNELS |
| JP2012531419A (ja) | 2009-06-23 | 2012-12-10 | 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 | Ｇａｂａ−ａ受容体修飾物質としての重水素修飾されたトリアゾロピリダジン誘導体 |
| KR20140077963A (ko) | 2011-10-20 | 2014-06-24 | 글락소스미스클라인 엘엘씨 | 시르투인 조절제로서의 치환된 비시클릭 아자-헤테로사이클 및 유사체 |
| KR20140077964A (ko) * | 2011-10-20 | 2014-06-24 | 글락소스미스클라인 엘엘씨 | 시르투인 조절제로서의 치환된 비시클릭 아자-헤테로사이클 및 유사체 |
| BR112014016930A8 (pt) | 2012-01-11 | 2017-12-26 | Bayer Ip Gmbh | compostos tetrazol-5-il- e triazol-5-il-arila e uso destes como herbicidas |
| 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 |
| WO2015052178A1 (en) | 2013-10-10 | 2015-04-16 | Basf Se | 1,2,5-oxadiazole compounds and their use as herbicides |
| WO2015052173A1 (en) | 2013-10-10 | 2015-04-16 | Basf Se | Tetrazole and triazole compounds and their use as herbicides |
| WO2015095549A1 (en) * | 2013-12-18 | 2015-06-25 | Concert Pharmaceuticals, Inc. | Dosage regimen for gabaa receptor subtype selective drug |
| EA201691582A1 (ru) | 2014-02-07 | 2017-01-30 | Оспекс Фармасьютикалз, Инк. | Новые фармацевтические препараты |
| CN104474549A (zh) * | 2014-11-24 | 2015-04-01 | 王寿世 | 异丙酚和gabaa受体拮抗剂在制备麻醉药物中的用途 |
| CN104353078B (zh) * | 2014-11-24 | 2017-10-24 | 王寿世 | 一种麻醉用药物组合物 |
| US10026332B1 (en) | 2017-04-10 | 2018-07-17 | Jasmine Gupta | Method to deliver contextual educational information utilizing smart wearables |
| WO2020191047A1 (en) * | 2019-03-18 | 2020-09-24 | Neurocycle Therapeutics, Inc. | Use of gabaa receptor modulators for treatment of pain |
| WO2023205722A1 (en) * | 2022-04-20 | 2023-10-26 | Engrail Therapeutics, Inc. | Gabaa receptor modulator salts, particles, and uses thereof |
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|---|---|---|---|---|
| GB9321162D0 (en) | 1993-10-13 | 1993-12-01 | Boots Co Plc | Therapeutic agents |
| US6221335B1 (en) | 1994-03-25 | 2001-04-24 | Isotechnika, Inc. | Method of using deuterated calcium channel blockers |
| AU707748B2 (en) | 1994-03-25 | 1999-07-22 | Isotechnika Inc. | Enhancement of the efficacy of drugs by deuteration |
| IL127911A0 (en) * | 1996-07-25 | 1999-11-30 | Merck Sharp & Dohme | Substituted triazolo-pyridazine derivatives as ligands for gaba receptors |
| MXPA00007135A (es) * | 1998-01-21 | 2002-11-07 | Merck Sharp & Dohme | Derivados de triazolo-piridazina como ligandos para receptores gaba. |
| US6440710B1 (en) | 1998-12-10 | 2002-08-27 | The Scripps Research Institute | Antibody-catalyzed deuteration, tritiation, dedeuteration or detritiation of carbonyl compounds |
| ES2232416T3 (es) * | 1999-01-27 | 2005-06-01 | MERCK SHARP & DOHME LTD. | Derivados de triazolo-piridazina como ligandos para receptores gaba. |
| ES2193921T3 (es) | 1999-12-03 | 2003-11-16 | Pfizer Prod Inc | Compuestos de sulfamoilheteroaril-pirazol como agentes antinflamatorios/analgesicos. |
| US20020165217A1 (en) * | 2001-05-01 | 2002-11-07 | Pfizer Inc. | Combination treatment for anxiety and depression |
| TW200413273A (en) | 2002-11-15 | 2004-08-01 | Wako Pure Chem Ind Ltd | Heavy hydrogenation method of heterocyclic rings |
| DE60315876T2 (de) * | 2002-11-28 | 2008-05-21 | Neurosearch A/S | Verfahren zum screening für verbindungen mit sedativer oder anxiolytischer potenz |
| 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 |
| US7598273B2 (en) | 2005-10-06 | 2009-10-06 | Auspex Pharmaceuticals, Inc | Inhibitors of the gastric H+, K+-ATPase with enhanced therapeutic properties |
| US7750168B2 (en) | 2006-02-10 | 2010-07-06 | Sigma-Aldrich Co. | Stabilized deuteroborane-tetrahydrofuran complex |
| JO2630B1 (en) | 2006-04-13 | 2012-06-17 | نوفارتيس ايه جي | Organic compounds |
| CN101594870A (zh) * | 2006-08-22 | 2009-12-02 | 康塞特医药品有限公司 | 4-氨基喹唑啉衍生物及其使用方法 |
| EP2059241A1 (en) | 2006-09-05 | 2009-05-20 | Schering Corporation | Pharmaceutical combinations for lipid management and in the treatment of atherosclerosis and hepatic steatosis |
| BRPI0809171A2 (pt) * | 2007-04-02 | 2014-09-16 | Auspex Pharmaceuticals Inc | "composto, composição farmacêutica, método para tratamento,prevençõ ou melhora de um ou mais , sintomas de uma desordem mediada pela endotelina em um sujeito, método de inibição de ligação d euma endotelina a um receptor eta ou etb e método para modular a atividade mediada pelo receptor de endotelina" |
| MX2011002278A (es) * | 2008-08-29 | 2011-04-14 | Concert Pharmaceuticals Inc | Derivados de triazolo-piridazina sustituidos. |
-
2009
- 2009-08-28 MX MX2011002278A patent/MX2011002278A/es active IP Right Grant
- 2009-08-28 KR KR20117006632A patent/KR20110063479A/ko not_active Ceased
- 2009-08-28 WO PCT/US2009/055427 patent/WO2010025407A1/en not_active Ceased
- 2009-08-28 CA CA 2735549 patent/CA2735549A1/en not_active Abandoned
- 2009-08-28 PT PT98106859T patent/PT2328414E/pt unknown
- 2009-08-28 BR BRPI0912928-6A patent/BRPI0912928A2/pt not_active IP Right Cessation
- 2009-08-28 EA EA201100409A patent/EA020071B1/ru not_active IP Right Cessation
- 2009-08-28 PL PL09810685T patent/PL2328414T3/pl unknown
- 2009-08-28 EP EP20130196185 patent/EP2716158A1/en not_active Withdrawn
- 2009-08-28 HR HRP20140195AT patent/HRP20140195T1/hr unknown
- 2009-08-28 DK DK09810685.9T patent/DK2328414T3/en active
- 2009-08-28 CN CN200980140350.5A patent/CN102176826B/zh not_active Expired - Fee Related
- 2009-08-28 EP EP20090810685 patent/EP2328414B1/en active Active
- 2009-08-28 AU AU2009285533A patent/AU2009285533B2/en not_active Ceased
- 2009-08-28 ES ES09810685T patent/ES2451542T3/es active Active
- 2009-08-28 JP JP2011525250A patent/JP5183808B2/ja not_active Expired - Fee Related
- 2009-08-28 CN CN201410346402.7A patent/CN104098578A/zh active Pending
- 2009-08-28 US US12/550,346 patent/US8003646B2/en active Active
-
2011
- 2011-03-22 ZA ZA2011/02123A patent/ZA201102123B/en unknown
- 2011-06-30 US US13/174,662 patent/US8399467B2/en active Active
-
2013
- 2013-01-15 JP JP2013004449A patent/JP5373982B2/ja not_active Expired - Fee Related
- 2013-03-18 US US13/846,119 patent/US8921366B2/en active Active
- 2013-09-19 JP JP2013194060A patent/JP2014058518A/ja active Pending
-
2014
- 2014-12-23 US US14/581,843 patent/US20150111895A1/en not_active Abandoned
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