JP4757382B2 - 神経保護作用を有するトリアゾロン - Google Patents
神経保護作用を有するトリアゾロン Download PDFInfo
- Publication number
- JP4757382B2 JP4757382B2 JP2000544654A JP2000544654A JP4757382B2 JP 4757382 B2 JP4757382 B2 JP 4757382B2 JP 2000544654 A JP2000544654 A JP 2000544654A JP 2000544654 A JP2000544654 A JP 2000544654A JP 4757382 B2 JP4757382 B2 JP 4757382B2
- Authority
- JP
- Japan
- Prior art keywords
- phenyl
- triazol
- methyl
- fluorophenyl
- methylphenyl
- 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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- 230000000324 neuroprotective effect Effects 0.000 title description 12
- FFSJPOPLSWBGQY-UHFFFAOYSA-N triazol-4-one Chemical compound O=C1C=NN=N1 FFSJPOPLSWBGQY-UHFFFAOYSA-N 0.000 title description 10
- 150000001875 compounds Chemical class 0.000 claims abstract description 29
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 25
- 206010021143 Hypoxia Diseases 0.000 claims abstract description 15
- 150000003839 salts Chemical class 0.000 claims abstract description 12
- 206010008120 Cerebral ischaemia Diseases 0.000 claims abstract description 11
- 201000006474 Brain Ischemia Diseases 0.000 claims abstract description 10
- 206010008118 cerebral infarction Diseases 0.000 claims abstract description 10
- 210000004556 brain Anatomy 0.000 claims abstract description 9
- 208000015122 neurodegenerative disease Diseases 0.000 claims abstract description 9
- 230000007954 hypoxia Effects 0.000 claims abstract description 8
- 230000000302 ischemic effect Effects 0.000 claims abstract description 8
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 7
- 206010002660 Anoxia Diseases 0.000 claims abstract description 7
- 241000976983 Anoxia Species 0.000 claims abstract description 7
- 206010048962 Brain oedema Diseases 0.000 claims abstract description 7
- 208000023105 Huntington disease Diseases 0.000 claims abstract description 7
- 208000013016 Hypoglycemia Diseases 0.000 claims abstract description 7
- 208000030886 Traumatic Brain injury Diseases 0.000 claims abstract description 7
- 230000007953 anoxia Effects 0.000 claims abstract description 7
- 230000004770 neurodegeneration Effects 0.000 claims abstract description 7
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims abstract description 6
- 208000016988 Hemorrhagic Stroke Diseases 0.000 claims abstract description 6
- 208000032382 Ischaemic stroke Diseases 0.000 claims abstract description 6
- 208000018737 Parkinson disease Diseases 0.000 claims abstract description 6
- 208000028017 Psychotic disease Diseases 0.000 claims abstract description 6
- 208000009205 Tinnitus Diseases 0.000 claims abstract description 6
- 201000002342 diabetic polyneuropathy Diseases 0.000 claims abstract description 6
- 201000000980 schizophrenia Diseases 0.000 claims abstract description 6
- 208000005809 status epilepticus Diseases 0.000 claims abstract description 6
- 231100000886 tinnitus Toxicity 0.000 claims abstract description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 17
- 208000006752 brain edema Diseases 0.000 claims description 6
- 230000002218 hypoglycaemic effect Effects 0.000 claims description 6
- WQQQBUSFBWNHBP-UHFFFAOYSA-N 2-(2-bromophenyl)-4-methyl-5-phenyl-1,2,4-triazol-3-one Chemical compound O=C1N(C)C(C=2C=CC=CC=2)=NN1C1=CC=CC=C1Br WQQQBUSFBWNHBP-UHFFFAOYSA-N 0.000 claims description 5
- RDRFRPPFKKMMRP-UHFFFAOYSA-N 2-(2-bromophenyl)-5-phenyl-1h-1,2,4-triazol-3-one Chemical compound BrC1=CC=CC=C1N1C(=O)N=C(C=2C=CC=CC=2)N1 RDRFRPPFKKMMRP-UHFFFAOYSA-N 0.000 claims description 5
- INMMNVZYBDVSRD-UHFFFAOYSA-N 2-(2-chlorophenyl)-4-methyl-5-phenyl-1,2,4-triazol-3-one Chemical compound O=C1N(C)C(C=2C=CC=CC=2)=NN1C1=CC=CC=C1Cl INMMNVZYBDVSRD-UHFFFAOYSA-N 0.000 claims description 5
- WXAFVRHIIVGONB-UHFFFAOYSA-N 2-(2-chlorophenyl)-5-phenyl-1h-1,2,4-triazol-3-one Chemical compound ClC1=CC=CC=C1N1C(=O)N=C(C=2C=CC=CC=2)N1 WXAFVRHIIVGONB-UHFFFAOYSA-N 0.000 claims description 5
- WSFBWWSTYAIQRM-UHFFFAOYSA-N 2-(2-fluorophenyl)-4-methyl-5-phenyl-1,2,4-triazol-3-one Chemical compound O=C1N(C)C(C=2C=CC=CC=2)=NN1C1=CC=CC=C1F WSFBWWSTYAIQRM-UHFFFAOYSA-N 0.000 claims description 5
- RMUFQLARBJMEGP-UHFFFAOYSA-N 2-(2-fluorophenyl)-5-phenyl-1h-1,2,4-triazol-3-one Chemical compound FC1=CC=CC=C1N1C(=O)N=C(C=2C=CC=CC=2)N1 RMUFQLARBJMEGP-UHFFFAOYSA-N 0.000 claims description 5
- WFZHETRZFDYADE-UHFFFAOYSA-N 2-(2-methoxyphenyl)-5-phenyl-1h-1,2,4-triazol-3-one Chemical compound COC1=CC=CC=C1N1C(=O)N=C(C=2C=CC=CC=2)N1 WFZHETRZFDYADE-UHFFFAOYSA-N 0.000 claims description 5
- CZSRPGZWVHZYHU-UHFFFAOYSA-N 2-(3-fluorophenyl)-4-methyl-5-phenyl-1,2,4-triazol-3-one Chemical compound O=C1N(C)C(C=2C=CC=CC=2)=NN1C1=CC=CC(F)=C1 CZSRPGZWVHZYHU-UHFFFAOYSA-N 0.000 claims description 5
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 5
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 5
- OZJSBBHULNYLNO-UHFFFAOYSA-N 5-(2-methoxyphenyl)-4-methyl-2-phenyl-1,2,4-triazol-3-one Chemical compound COC1=CC=CC=C1C(N(C1=O)C)=NN1C1=CC=CC=C1 OZJSBBHULNYLNO-UHFFFAOYSA-N 0.000 claims description 5
- 208000000884 Airway Obstruction Diseases 0.000 claims description 5
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- 238000007917 intracranial administration Methods 0.000 claims description 5
- 208000010125 myocardial infarction Diseases 0.000 claims description 5
- AFVIXVDGHPMYPR-UHFFFAOYSA-N 4-methyl-2-(3-methylphenyl)-5-phenyl-1,2,4-triazol-3-one Chemical compound CC1=CC=CC(N2C(N(C)C(C=3C=CC=CC=3)=N2)=O)=C1 AFVIXVDGHPMYPR-UHFFFAOYSA-N 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- VQRFKKRMXQLDBF-UHFFFAOYSA-N 2-(2-ethylphenyl)-5-phenyl-1h-1,2,4-triazol-3-one Chemical compound CCC1=CC=CC=C1N1C(=O)N=C(C=2C=CC=CC=2)N1 VQRFKKRMXQLDBF-UHFFFAOYSA-N 0.000 claims description 3
- UEVPEVDGRGLBGH-UHFFFAOYSA-N 2-(2-methylphenyl)-5-phenyl-1h-1,2,4-triazol-3-one Chemical compound CC1=CC=CC=C1N1C(=O)N=C(C=2C=CC=CC=2)N1 UEVPEVDGRGLBGH-UHFFFAOYSA-N 0.000 claims description 3
- JWEIKIHJEWDSGD-UHFFFAOYSA-N 2-(3-methoxyphenyl)-4-methyl-5-phenyl-1,2,4-triazol-3-one Chemical compound COC1=CC=CC(N2C(N(C)C(C=3C=CC=CC=3)=N2)=O)=C1 JWEIKIHJEWDSGD-UHFFFAOYSA-N 0.000 claims description 3
- PDPPFKHBXYBDFM-UHFFFAOYSA-N 2-(3-methylphenyl)-5-phenyl-1h-1,2,4-triazol-3-one Chemical compound CC1=CC=CC(N2C(N=C(N2)C=2C=CC=CC=2)=O)=C1 PDPPFKHBXYBDFM-UHFFFAOYSA-N 0.000 claims description 3
- TWTRMRDPHGZDOD-UHFFFAOYSA-N 5-(4-methoxyphenyl)-4-methyl-2-phenyl-1,2,4-triazol-3-one Chemical compound C1=CC(OC)=CC=C1C(N(C1=O)C)=NN1C1=CC=CC=C1 TWTRMRDPHGZDOD-UHFFFAOYSA-N 0.000 claims description 3
- 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 8
- 206010021118 Hypotonia Diseases 0.000 abstract 1
- 206010061216 Infarction Diseases 0.000 abstract 1
- 208000007379 Muscle Hypotonia Diseases 0.000 abstract 1
- 206010028923 Neonatal asphyxia Diseases 0.000 abstract 1
- 208000037212 Neonatal hypoxic and ischemic brain injury Diseases 0.000 abstract 1
- 230000000747 cardiac effect Effects 0.000 abstract 1
- 230000007574 infarction Effects 0.000 abstract 1
- 201000009941 intracranial hypertension Diseases 0.000 abstract 1
- 201000010901 lateral sclerosis Diseases 0.000 abstract 1
- 208000005264 motor neuron disease Diseases 0.000 abstract 1
- 208000033300 perinatal asphyxia Diseases 0.000 abstract 1
- 230000001225 therapeutic effect Effects 0.000 abstract 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 49
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 41
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 30
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 29
- 239000001257 hydrogen Substances 0.000 description 28
- 229910052739 hydrogen Inorganic materials 0.000 description 28
- 150000002431 hydrogen Chemical class 0.000 description 24
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 22
- 239000000460 chlorine Substances 0.000 description 19
- 229910052801 chlorine Inorganic materials 0.000 description 19
- -1 2,4-dibromophenyl Chemical group 0.000 description 18
- 239000000203 mixture Substances 0.000 description 18
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 17
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 17
- 229910052794 bromium Inorganic materials 0.000 description 17
- 229910052736 halogen Inorganic materials 0.000 description 17
- 150000002367 halogens Chemical class 0.000 description 17
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 17
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 16
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 16
- 239000013543 active substance Substances 0.000 description 15
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Chemical group C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 15
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 14
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- 125000000217 alkyl group Chemical group 0.000 description 14
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 13
- 229910052731 fluorine Inorganic materials 0.000 description 13
- 239000011737 fluorine Substances 0.000 description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 12
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
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- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 125000005981 pentynyl group Chemical group 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920002689 polyvinyl acetate Polymers 0.000 description 1
- 239000011118 polyvinyl acetate Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 239000002510 pyrogen Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 229940076279 serotonin Drugs 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000005694 substituted alkenylalkyl group Chemical group 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 125000004426 substituted alkynyl group Chemical group 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-L sulfite Chemical compound [O-]S([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-L 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000000946 synaptic effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000002700 tablet coating Substances 0.000 description 1
- 238000009492 tablet coating Methods 0.000 description 1
- RAOIDOHSFRTOEL-UHFFFAOYSA-N tetrahydrothiophene Chemical compound C1CCSC1 RAOIDOHSFRTOEL-UHFFFAOYSA-N 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- 235000010215 titanium dioxide Nutrition 0.000 description 1
- 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
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- 235000012141 vanillin Nutrition 0.000 description 1
- MWOOGOJBHIARFG-UHFFFAOYSA-N vanillin Chemical compound COC1=CC(C=O)=CC=C1O MWOOGOJBHIARFG-UHFFFAOYSA-N 0.000 description 1
- FGQOOHJZONJGDT-UHFFFAOYSA-N vanillin Natural products COC1=CC(O)=CC(C=O)=C1 FGQOOHJZONJGDT-UHFFFAOYSA-N 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
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
- C07D401/04—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
-
- 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
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles 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
- C07D249/12—Oxygen or sulfur atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Heart & Thoracic Surgery (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Urology & Nephrology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE19816882A DE19816882A1 (de) | 1998-04-17 | 1998-04-17 | Triazolone mit neuroprotektiver Wirkung |
| DE19816882.9 | 1998-04-17 | ||
| PCT/EP1999/002498 WO1999054315A2 (de) | 1998-04-17 | 1999-04-14 | Triazolone mit neuroprotektiver wirkung |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2002512236A JP2002512236A (ja) | 2002-04-23 |
| JP2002512236A5 JP2002512236A5 (https=) | 2006-06-15 |
| JP4757382B2 true JP4757382B2 (ja) | 2011-08-24 |
Family
ID=7864724
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000544654A Expired - Fee Related JP4757382B2 (ja) | 1998-04-17 | 1999-04-14 | 神経保護作用を有するトリアゾロン |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US6492407B2 (https=) |
| EP (1) | EP1071671B1 (https=) |
| JP (1) | JP4757382B2 (https=) |
| AT (1) | ATE301112T1 (https=) |
| CA (1) | CA2327784C (https=) |
| DE (2) | DE19816882A1 (https=) |
| WO (1) | WO1999054315A2 (https=) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6613786B2 (en) | 2001-11-02 | 2003-09-02 | Bristol-Myers Squibb Company | Thiophenyl triazol-3-one derivatives as smooth muscle relaxants |
| US7520862B2 (en) | 2004-02-03 | 2009-04-21 | Neuro Diagnostic Devices, Inc. | Cerebral spinal fluid shunt evaluation system |
| DE102006024024A1 (de) | 2006-05-23 | 2007-11-29 | Bayer Healthcare Aktiengesellschaft | Substituierte Arylimidazolone und -triazolone sowie ihre Verwendung |
| DE102008060967A1 (de) | 2008-12-06 | 2010-06-10 | Bayer Schering Pharma Aktiengesellschaft | Substituierte Phenylsulfonyltriazolone und ihre Verwendung |
| DE102009013642A1 (de) | 2009-03-18 | 2010-09-23 | Bayer Schering Pharma Aktiengesellschaft | Substituierte Phenylalaninderivate und deren Verwendung |
| DE102010001064A1 (de) | 2009-03-18 | 2010-09-23 | Bayer Schering Pharma Aktiengesellschaft | Substituierte 2-Acetamido-5-Aryl-1,2,4-triazolone und deren Verwendung |
| DE102009028929A1 (de) | 2009-08-27 | 2011-07-07 | Bayer Schering Pharma Aktiengesellschaft, 13353 | Heterocyclisch-substituierte 2-Acetamido-5-Aryl-1,2,4-triazolone und deren Verwendung |
| UA109650C2 (xx) | 2010-02-27 | 2015-09-25 | Біс-арилзв'язані арилтриазолони та їх застосування | |
| DE102010040187A1 (de) | 2010-09-02 | 2012-03-08 | Bayer Schering Pharma Aktiengesellschaft | Substituierte N-Phenethyl-triazolonacetamide und ihre Verwendung |
| DE102010040924A1 (de) * | 2010-09-16 | 2012-03-22 | Bayer Schering Pharma Aktiengesellschaft | Substituierte Phenylacet- und Phenylpropanamide und ihre Verwendung |
| EP2753179A4 (en) * | 2011-09-09 | 2015-03-04 | Univ Leland Stanford Junior | TOPICAL ITRACONAZOLE FORMULATIONS AND THEIR USE |
| TWI568722B (zh) | 2012-06-15 | 2017-02-01 | 葛蘭馬克製藥公司 | 作爲ｍＰＧＥＳ－１抑制劑之三唑酮化合物 |
| SI3215498T1 (sl) | 2014-11-03 | 2018-11-30 | Bayer Pharma Aktiengesellschaft | Hidroksialkil-substituirani derivati feniltriazola in njihove uporabe |
| US9988367B2 (en) | 2016-05-03 | 2018-06-05 | Bayer Pharma Aktiengesellschaft | Amide-substituted pyridinyltriazole derivatives and uses thereof |
| TW201945346A (zh) | 2018-04-10 | 2019-12-01 | 德商拜耳廠股份有限公司 | 2,4,5-三取代的1,2,4-三唑酮之製備方法 |
| EP3870159B1 (en) * | 2018-10-26 | 2024-11-13 | University of South Florida | Drug for treating tinnitus |
Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5653662A (en) * | 1979-10-08 | 1981-05-13 | Nippon Nohyaku Co Ltd | Preparation of delta2-1,2,4-triazolin-5-ones |
| JPS58225070A (ja) * | 1982-06-23 | 1983-12-27 | Nippon Nohyaku Co Ltd | Δ↑２−１，２，４−トリアゾリン−５−オン誘導体及び製法並びにその用途 |
| JPS6219574A (ja) * | 1985-07-12 | 1987-01-28 | チバ ― ガイギー アクチエンゲゼルシャフト | 新規トリアゾ−ル化合物 |
| JPS63170313A (ja) * | 1986-12-19 | 1988-07-14 | メレルダウファーマスーティカルズ インコーポレーテッド | ５−アリール−３ｈ−１，２，４，−トリアゾール−３−オン類の抗痙攣剤としての用途 |
| JPS63170312A (ja) * | 1986-12-19 | 1988-07-14 | メレルダウファーマスーティカルズ インコーポレーテッド | ５−アリール−３ｈ−１，２，４−トリアゾール−３−オン類の神経変性障害の処置への用途 |
| JPS63201175A (ja) * | 1987-01-27 | 1988-08-19 | メレルダウファーマスーティカルズ インコーポレーテッド | ５‐アリール‐２，４‐ジアルキル‐３ｈ‐１，２，４‐トリアゾール‐３‐チオン類の製法 |
| US5120347A (en) * | 1990-06-21 | 1992-06-09 | Rohm And Haas Company | Aryl triazole herbicides |
| WO1998004135A1 (en) * | 1996-07-31 | 1998-02-05 | Bristol-Myers Squibb Company | Diphenyl heterocycles as potassium channel modulators |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1311651A (en) * | 1969-05-08 | 1973-03-28 | Gold Aubert P | Salts of delta2-1,2,4-triazolin-5-one derivatives |
| GB8429307D0 (en) * | 1984-11-20 | 1984-12-27 | Shell Int Research | Heterocyclic herbicides |
| DK570987A (da) * | 1986-12-01 | 1988-06-02 | Hoffmann La Roche | Oxadiazol-, thiadiazol- og triazolforbindelser |
| US5436252A (en) * | 1986-12-19 | 1995-07-25 | Merrell Dow Pharmaceuticals Inc. | 5-aryl-3H-1,2,4-triazol-3-ones and their use in the treatment of neurodegenerative disorders |
| US5256793A (en) * | 1992-05-13 | 1993-10-26 | Fmc Corporation | Triazolinone ring formation in tert-butanol |
| IT1256387B (it) * | 1992-11-13 | 1995-12-04 | Acraf | Procedimento per preparare triazoloni |
| US5597809A (en) * | 1994-06-23 | 1997-01-28 | Massachusetts Eye & Ear Infirmary | Treatment of optic neuritis |
| US6114334A (en) * | 1995-07-13 | 2000-09-05 | Knoll Aktiengesellschaft | Piperazine derivatives as therapeutic agents |
| US5756755A (en) * | 1996-08-26 | 1998-05-26 | Fmc Corporation | Difluoromethylation of 4,5-dihydro-1-phenyl-3-methyl-1,2,4-triazol-5(1H)-ones with glymes as solvents |
-
1998
- 1998-04-17 DE DE19816882A patent/DE19816882A1/de not_active Withdrawn
-
1999
- 1999-04-14 EP EP99915760A patent/EP1071671B1/de not_active Expired - Lifetime
- 1999-04-14 CA CA002327784A patent/CA2327784C/en not_active Expired - Fee Related
- 1999-04-14 DE DE59912358T patent/DE59912358D1/de not_active Expired - Lifetime
- 1999-04-14 WO PCT/EP1999/002498 patent/WO1999054315A2/de not_active Ceased
- 1999-04-14 JP JP2000544654A patent/JP4757382B2/ja not_active Expired - Fee Related
- 1999-04-14 AT AT99915760T patent/ATE301112T1/de not_active IP Right Cessation
-
2001
- 2001-04-23 US US09/840,281 patent/US6492407B2/en not_active Expired - Lifetime
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5653662A (en) * | 1979-10-08 | 1981-05-13 | Nippon Nohyaku Co Ltd | Preparation of delta2-1,2,4-triazolin-5-ones |
| JPS58225070A (ja) * | 1982-06-23 | 1983-12-27 | Nippon Nohyaku Co Ltd | Δ↑２−１，２，４−トリアゾリン−５−オン誘導体及び製法並びにその用途 |
| JPS6219574A (ja) * | 1985-07-12 | 1987-01-28 | チバ ― ガイギー アクチエンゲゼルシャフト | 新規トリアゾ−ル化合物 |
| JPS63170313A (ja) * | 1986-12-19 | 1988-07-14 | メレルダウファーマスーティカルズ インコーポレーテッド | ５−アリール−３ｈ−１，２，４，−トリアゾール−３−オン類の抗痙攣剤としての用途 |
| JPS63170312A (ja) * | 1986-12-19 | 1988-07-14 | メレルダウファーマスーティカルズ インコーポレーテッド | ５−アリール−３ｈ−１，２，４−トリアゾール−３−オン類の神経変性障害の処置への用途 |
| JPS63201175A (ja) * | 1987-01-27 | 1988-08-19 | メレルダウファーマスーティカルズ インコーポレーテッド | ５‐アリール‐２，４‐ジアルキル‐３ｈ‐１，２，４‐トリアゾール‐３‐チオン類の製法 |
| US5120347A (en) * | 1990-06-21 | 1992-06-09 | Rohm And Haas Company | Aryl triazole herbicides |
| WO1998004135A1 (en) * | 1996-07-31 | 1998-02-05 | Bristol-Myers Squibb Company | Diphenyl heterocycles as potassium channel modulators |
Also Published As
| Publication number | Publication date |
|---|---|
| CA2327784A1 (en) | 1999-10-28 |
| DE19816882A1 (de) | 1999-10-21 |
| WO1999054315A2 (de) | 1999-10-28 |
| EP1071671A2 (de) | 2001-01-31 |
| EP1071671B1 (de) | 2005-08-03 |
| US6492407B2 (en) | 2002-12-10 |
| DE59912358D1 (de) | 2005-09-08 |
| US20020045651A1 (en) | 2002-04-18 |
| CA2327784C (en) | 2008-03-18 |
| WO1999054315A3 (de) | 1999-12-29 |
| JP2002512236A (ja) | 2002-04-23 |
| ATE301112T1 (de) | 2005-08-15 |
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