ZA200505258B - 3-Substituted-4-pyrimidone derivatives - Google Patents
3-Substituted-4-pyrimidone derivatives Download PDFInfo
- Publication number
- ZA200505258B ZA200505258B ZA200505258A ZA200505258A ZA200505258B ZA 200505258 B ZA200505258 B ZA 200505258B ZA 200505258 A ZA200505258 A ZA 200505258A ZA 200505258 A ZA200505258 A ZA 200505258A ZA 200505258 B ZA200505258 B ZA 200505258B
- Authority
- ZA
- South Africa
- Prior art keywords
- pyrimidin
- pyridin
- dihydro
- methyl
- group
- Prior art date
Links
- -1 3-Substituted-4-pyrimidone Chemical class 0.000 title description 50
- 239000003814 drug Substances 0.000 claims description 29
- 150000003839 salts Chemical class 0.000 claims description 24
- 201000010099 disease Diseases 0.000 claims description 18
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 18
- 125000000217 alkyl group Chemical group 0.000 claims description 16
- 208000024827 Alzheimer disease Diseases 0.000 claims description 14
- 239000004480 active ingredient Substances 0.000 claims description 14
- 239000012453 solvate Substances 0.000 claims description 14
- 230000001225 therapeutic effect Effects 0.000 claims description 12
- 239000000126 substance Substances 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 230000003449 preventive effect Effects 0.000 claims description 10
- 206010028980 Neoplasm Diseases 0.000 claims description 9
- 201000011240 Frontotemporal dementia Diseases 0.000 claims description 8
- 208000014674 injury Diseases 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 210000004556 brain Anatomy 0.000 claims description 7
- 230000004770 neurodegeneration Effects 0.000 claims description 7
- 208000015122 neurodegenerative disease Diseases 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- 150000008318 pyrimidones Chemical class 0.000 claims description 7
- 108010061506 tau-protein kinase Proteins 0.000 claims description 7
- 208000009829 Lewy Body Disease Diseases 0.000 claims description 6
- 201000002832 Lewy body dementia Diseases 0.000 claims description 6
- 208000006011 Stroke Diseases 0.000 claims description 6
- 230000000302 ischemic effect Effects 0.000 claims description 6
- 125000001624 naphthyl group Chemical group 0.000 claims description 6
- 206010008111 Cerebral haemorrhage Diseases 0.000 claims description 5
- 201000010374 Down Syndrome Diseases 0.000 claims description 5
- 208000037658 Parkinson-dementia complex of Guam Diseases 0.000 claims description 5
- 208000027089 Parkinsonian disease Diseases 0.000 claims description 5
- 206010034010 Parkinsonism Diseases 0.000 claims description 5
- 208000036757 Postencephalitic parkinsonism Diseases 0.000 claims description 5
- 208000034799 Tauopathies Diseases 0.000 claims description 5
- 206010014599 encephalitis Diseases 0.000 claims description 5
- 125000000623 heterocyclic group Chemical group 0.000 claims description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 5
- 208000000170 postencephalitic Parkinson disease Diseases 0.000 claims description 5
- 201000002212 progressive supranuclear palsy Diseases 0.000 claims description 5
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 5
- 201000004384 Alopecia Diseases 0.000 claims description 4
- 208000004736 B-Cell Leukemia Diseases 0.000 claims description 4
- 206010006187 Breast cancer Diseases 0.000 claims description 4
- 208000026310 Breast neoplasm Diseases 0.000 claims description 4
- 208000011990 Corticobasal Degeneration Diseases 0.000 claims description 4
- 206010012289 Dementia Diseases 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- 208000010412 Glaucoma Diseases 0.000 claims description 4
- 208000008589 Obesity Diseases 0.000 claims description 4
- 208000000609 Pick Disease of the Brain Diseases 0.000 claims description 4
- 206010038923 Retinopathy Diseases 0.000 claims description 4
- 208000000389 T-cell leukemia Diseases 0.000 claims description 4
- 208000028530 T-cell lymphoblastic leukemia/lymphoma Diseases 0.000 claims description 4
- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 4
- 201000004810 Vascular dementia Diseases 0.000 claims description 4
- 241000700605 Viruses Species 0.000 claims description 4
- 230000001154 acute effect Effects 0.000 claims description 4
- 206010064930 age-related macular degeneration Diseases 0.000 claims description 4
- 231100000360 alopecia Toxicity 0.000 claims description 4
- 125000004429 atom Chemical group 0.000 claims description 4
- 208000028683 bipolar I disease Diseases 0.000 claims description 4
- 206010012601 diabetes mellitus Diseases 0.000 claims description 4
- 208000002780 macular degeneration Diseases 0.000 claims description 4
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 4
- 235000020824 obesity Nutrition 0.000 claims description 4
- 208000027232 peripheral nervous system disease Diseases 0.000 claims description 4
- 208000033808 peripheral neuropathy Diseases 0.000 claims description 4
- 201000000980 schizophrenia Diseases 0.000 claims description 4
- 210000000278 spinal cord Anatomy 0.000 claims description 4
- 201000002510 thyroid cancer Diseases 0.000 claims description 4
- 230000008733 trauma Effects 0.000 claims description 4
- 230000008736 traumatic injury Effects 0.000 claims description 4
- KTZQTRPPVKQPFO-UHFFFAOYSA-N 1,2-benzoxazole Chemical group C1=CC=C2C=NOC2=C1 KTZQTRPPVKQPFO-UHFFFAOYSA-N 0.000 claims description 3
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 3
- 208000013403 hyperactivity Diseases 0.000 claims description 3
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical group C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 claims description 3
- 239000003112 inhibitor Substances 0.000 claims description 3
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims description 3
- 125000004434 sulfur atom Chemical group 0.000 claims description 3
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical group C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 claims description 3
- IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical group C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 claims description 2
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical group C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 2
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical group C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 claims description 2
- DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 claims description 2
- QFCDMTTYNIOFJJ-UHFFFAOYSA-N 2-[5-(4-chlorophenyl)-3,6-dihydro-2h-pyridin-1-yl]-3-methyl-6-pyrimidin-4-ylpyrimidin-4-one Chemical compound C=1C(=O)N(C)C(N2CC(=CCC2)C=2C=CC(Cl)=CC=2)=NC=1C1=CC=NC=N1 QFCDMTTYNIOFJJ-UHFFFAOYSA-N 0.000 claims description 2
- GABZOZSSTNKPPN-UHFFFAOYSA-N 3-methyl-2-(5-phenyl-3,6-dihydro-2h-pyridin-1-yl)-6-pyrimidin-4-ylpyrimidin-4-one Chemical compound C=1C(=O)N(C)C(N2CC(=CCC2)C=2C=CC=CC=2)=NC=1C1=CC=NC=N1 GABZOZSSTNKPPN-UHFFFAOYSA-N 0.000 claims description 2
- UWYNUSUFHKTMMI-UHFFFAOYSA-N 3-methyl-6-pyrimidin-4-yl-2-(5-thiophen-3-yl-3,6-dihydro-2h-pyridin-1-yl)pyrimidin-4-one Chemical compound C=1C(=O)N(C)C(N2CC(=CCC2)C2=CSC=C2)=NC=1C1=CC=NC=N1 UWYNUSUFHKTMMI-UHFFFAOYSA-N 0.000 claims description 2
- 206010059245 Angiopathy Diseases 0.000 claims description 2
- ZCFLFBCLHODMGL-UHFFFAOYSA-N 2-(5-benzyl-3,6-dihydro-2h-pyridin-1-yl)-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical compound C=1C(=O)N(C)C(N2CC(CC=3C=CC=CC=3)=CCC2)=NC=1C1=CC=NC=C1 ZCFLFBCLHODMGL-UHFFFAOYSA-N 0.000 claims 1
- NXJXUFJIYXVEHW-UHFFFAOYSA-N 2-[5-(2,4-difluorophenyl)-3,6-dihydro-2h-pyridin-1-yl]-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical compound C=1C(=O)N(C)C(N2CC(=CCC2)C=2C(=CC(F)=CC=2)F)=NC=1C1=CC=NC=C1 NXJXUFJIYXVEHW-UHFFFAOYSA-N 0.000 claims 1
- SAQIHQVZCKHOSP-UHFFFAOYSA-N 2-[5-(2-chlorophenyl)-3,6-dihydro-2h-pyridin-1-yl]-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical compound C=1C(=O)N(C)C(N2CC(=CCC2)C=2C(=CC=CC=2)Cl)=NC=1C1=CC=NC=C1 SAQIHQVZCKHOSP-UHFFFAOYSA-N 0.000 claims 1
- GNORATGDGNMNEE-UHFFFAOYSA-N 2-[5-(2-fluorophenyl)-3,6-dihydro-2h-pyridin-1-yl]-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical compound C=1C(=O)N(C)C(N2CC(=CCC2)C=2C(=CC=CC=2)F)=NC=1C1=CC=NC=C1 GNORATGDGNMNEE-UHFFFAOYSA-N 0.000 claims 1
- MKTBIIAYDCBXJL-UHFFFAOYSA-N 2-[5-(4-fluorophenyl)-3,6-dihydro-2h-pyridin-1-yl]-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical compound C=1C(=O)N(C)C(N2CC(=CCC2)C=2C=CC(F)=CC=2)=NC=1C1=CC=NC=C1 MKTBIIAYDCBXJL-UHFFFAOYSA-N 0.000 claims 1
- KGYGZGYPGNIUNA-UHFFFAOYSA-N 2-[5-(4-fluorophenyl)-3,6-dihydro-2h-pyridin-1-yl]-3-methyl-6-pyrimidin-4-ylpyrimidin-4-one Chemical compound C=1C(=O)N(C)C(N2CC(=CCC2)C=2C=CC(F)=CC=2)=NC=1C1=CC=NC=N1 KGYGZGYPGNIUNA-UHFFFAOYSA-N 0.000 claims 1
- QJRLGEPQHVTEAQ-UHFFFAOYSA-N 2-[5-(4-methoxyphenyl)-3,6-dihydro-2h-pyridin-1-yl]-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical compound C1=CC(OC)=CC=C1C1=CCCN(C=2N(C(=O)C=C(N=2)C=2C=CN=CC=2)C)C1 QJRLGEPQHVTEAQ-UHFFFAOYSA-N 0.000 claims 1
- AAPWPODZBJDLRI-UHFFFAOYSA-N 2-ethyl-6-pyrimidin-4-yl-1h-pyrimidin-4-one Chemical compound O=C1NC(CC)=NC(C=2N=CN=CC=2)=C1 AAPWPODZBJDLRI-UHFFFAOYSA-N 0.000 claims 1
- SJDKYNKIPNEWFL-UHFFFAOYSA-N 3-methyl-2-(5-phenyl-3,6-dihydro-2h-pyridin-1-yl)-6-pyridin-4-ylpyrimidin-4-one Chemical compound C=1C(=O)N(C)C(N2CC(=CCC2)C=2C=CC=CC=2)=NC=1C1=CC=NC=C1 SJDKYNKIPNEWFL-UHFFFAOYSA-N 0.000 claims 1
- WJQDOPWCPACMFC-UHFFFAOYSA-N 3-methyl-6-pyridin-4-yl-2-(5-thiophen-3-yl-3,6-dihydro-2h-pyridin-1-yl)pyrimidin-4-one Chemical compound C=1C(=O)N(C)C(N2CC(=CCC2)C2=CSC=C2)=NC=1C1=CC=NC=C1 WJQDOPWCPACMFC-UHFFFAOYSA-N 0.000 claims 1
- XXAXVMUWHZHZMJ-UHFFFAOYSA-N Chymopapain Chemical compound OC1=CC(S(O)(=O)=O)=CC(S(O)(=O)=O)=C1O XXAXVMUWHZHZMJ-UHFFFAOYSA-N 0.000 claims 1
- 108090001069 Chymopapain Proteins 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 description 40
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- 239000002904 solvent Substances 0.000 description 14
- 125000001424 substituent group Chemical group 0.000 description 12
- 102100037495 Thiamin pyrophosphokinase 1 Human genes 0.000 description 11
- 101710203399 Thiamin pyrophosphokinase 1 Proteins 0.000 description 11
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 9
- 210000002569 neuron Anatomy 0.000 description 9
- 230000030833 cell death Effects 0.000 description 7
- 239000008194 pharmaceutical composition Substances 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 5
- 125000003545 alkoxy group Chemical group 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 5
- 235000018102 proteins Nutrition 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- SFBUZLPJTDBGAC-UHFFFAOYSA-N thiopyran-2-imine Chemical class N=C1C=CC=CS1 SFBUZLPJTDBGAC-UHFFFAOYSA-N 0.000 description 5
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 4
- 150000001413 amino acids Chemical group 0.000 description 4
- 239000002585 base Substances 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 150000001805 chlorine compounds Chemical class 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 125000005843 halogen group Chemical group 0.000 description 4
- 150000004677 hydrates Chemical class 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 4
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- 238000000034 method Methods 0.000 description 4
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- 102000013498 tau Proteins Human genes 0.000 description 4
- 108010026424 tau Proteins Proteins 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 208000037259 Amyloid Plaque Diseases 0.000 description 3
- 208000005145 Cerebral amyloid angiopathy Diseases 0.000 description 3
- 241000581652 Hagenia abyssinica Species 0.000 description 3
- 206010029350 Neurotoxicity Diseases 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- 208000018737 Parkinson disease Diseases 0.000 description 3
- 206010044221 Toxic encephalopathy Diseases 0.000 description 3
- 230000002159 abnormal effect Effects 0.000 description 3
- 238000009825 accumulation Methods 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 3
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 3
- 239000012320 chlorinating reagent Substances 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
- 125000004093 cyano group Chemical group *C#N 0.000 description 3
- 125000000753 cycloalkyl group Chemical group 0.000 description 3
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 3
- 125000002510 isobutoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])O* 0.000 description 3
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 3
- 210000002682 neurofibrillary tangle Anatomy 0.000 description 3
- 231100000228 neurotoxicity Toxicity 0.000 description 3
- 230000007135 neurotoxicity Effects 0.000 description 3
- 108020004707 nucleic acids Proteins 0.000 description 3
- 102000039446 nucleic acids Human genes 0.000 description 3
- 150000007523 nucleic acids Chemical class 0.000 description 3
- 230000036285 pathological change Effects 0.000 description 3
- 231100000915 pathological change Toxicity 0.000 description 3
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 3
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 3
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
- SEPPVOUBHWNCAW-FNORWQNLSA-N (E)-4-oxonon-2-enal Chemical compound CCCCCC(=O)\C=C\C=O SEPPVOUBHWNCAW-FNORWQNLSA-N 0.000 description 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 2
- HBEDSQVIWPRPAY-UHFFFAOYSA-N 2,3-dihydrobenzofuran Chemical compound C1=CC=C2OCCC2=C1 HBEDSQVIWPRPAY-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- LLBZPESJRQGYMB-UHFFFAOYSA-N 4-one Natural products O1C(C(=O)CC)CC(C)C11C2(C)CCC(C3(C)C(C(C)(CO)C(OC4C(C(O)C(O)C(COC5C(C(O)C(O)CO5)OC5C(C(OC6C(C(O)C(O)C(CO)O6)O)C(O)C(CO)O5)OC5C(C(O)C(O)C(C)O5)O)O4)O)CC3)CC3)=C3C2(C)CC1 LLBZPESJRQGYMB-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 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
- 102000018899 Glutamate Receptors Human genes 0.000 description 2
- 108010027915 Glutamate Receptors Proteins 0.000 description 2
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- 102000015499 Presenilins Human genes 0.000 description 2
- 108010050254 Presenilins Proteins 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 230000001476 alcoholic effect Effects 0.000 description 2
- 125000004414 alkyl thio group Chemical group 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 239000012300 argon atmosphere Substances 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 230000002490 cerebral effect Effects 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 239000002299 complementary DNA Substances 0.000 description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 2
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 2
- 230000034994 death Effects 0.000 description 2
- 125000004663 dialkyl amino group Chemical group 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 125000004705 ethylthio group Chemical group C(C)S* 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- 239000004220 glutamic acid Substances 0.000 description 2
- 235000013922 glutamic acid Nutrition 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 238000011835 investigation Methods 0.000 description 2
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 2
- 125000005921 isopentoxy group Chemical group 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 2
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 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 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 125000004115 pentoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 230000026731 phosphorylation Effects 0.000 description 2
- 238000006366 phosphorylation reaction Methods 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000000714 pyrimidinyl group Chemical group 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- YSMODUONRAFBET-CRCLSJGQSA-N (2r,5s)-2,6-diamino-5-hydroxyhexanoic acid Chemical compound NC[C@@H](O)CC[C@@H](N)C(O)=O YSMODUONRAFBET-CRCLSJGQSA-N 0.000 description 1
- SDOFMBGMRVAJNF-VANKVMQKSA-N (2s,3s,4s,5r)-6-aminohexane-1,2,3,4,5-pentol Chemical compound NC[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O)CO SDOFMBGMRVAJNF-VANKVMQKSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- CXWGKAYMVASWDQ-UHFFFAOYSA-N 1,2-dithiane Chemical group C1CCSSC1 CXWGKAYMVASWDQ-UHFFFAOYSA-N 0.000 description 1
- CZSRXHJVZUBEGW-UHFFFAOYSA-N 1,2-thiazolidine Chemical group C1CNSC1 CZSRXHJVZUBEGW-UHFFFAOYSA-N 0.000 description 1
- FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical group C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 description 1
- BXQNSPXDWSNUKE-UHFFFAOYSA-N 1,3-benzothiazole 1-oxide Chemical group C1=CC=C2S(=O)C=NC2=C1 BXQNSPXDWSNUKE-UHFFFAOYSA-N 0.000 description 1
- FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical group N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 1
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 1
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 description 1
- INXGKFCUVKMXLP-UHFFFAOYSA-N 2-(5-benzyl-3,6-dihydro-2h-pyridin-1-yl)-3-methyl-6-pyrimidin-4-ylpyrimidin-4-one Chemical compound C=1C(=O)N(C)C(N2CC(CC=3C=CC=CC=3)=CCC2)=NC=1C1=CC=NC=N1 INXGKFCUVKMXLP-UHFFFAOYSA-N 0.000 description 1
- PDPYEDSRJHZOMG-UHFFFAOYSA-N 2-[5-(2,4-dichlorophenyl)-3,6-dihydro-2h-pyridin-1-yl]-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical compound C=1C(=O)N(C)C(N2CC(=CCC2)C=2C(=CC(Cl)=CC=2)Cl)=NC=1C1=CC=NC=C1 PDPYEDSRJHZOMG-UHFFFAOYSA-N 0.000 description 1
- KYPSEMVWIWWAJB-UHFFFAOYSA-N 2-[5-(2,6-dimethoxyphenyl)-3,6-dihydro-2h-pyridin-1-yl]-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical compound COC1=CC=CC(OC)=C1C1=CCCN(C=2N(C(=O)C=C(N=2)C=2C=CN=CC=2)C)C1 KYPSEMVWIWWAJB-UHFFFAOYSA-N 0.000 description 1
- VYWAAZQJQSEHEI-UHFFFAOYSA-N 2-[5-[(4-fluorophenoxy)methyl]-3,6-dihydro-2h-pyridin-1-yl]-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical compound C=1C(=O)N(C)C(N2CC(COC=3C=CC(F)=CC=3)=CCC2)=NC=1C1=CC=NC=C1 VYWAAZQJQSEHEI-UHFFFAOYSA-N 0.000 description 1
- QEYCGLYTYRKDSB-UHFFFAOYSA-N 2-[5-[(4-fluorophenoxy)methyl]-3,6-dihydro-2h-pyridin-1-yl]-3-methyl-6-pyrimidin-4-ylpyrimidin-4-one Chemical compound C=1C(=O)N(C)C(N2CC(COC=3C=CC(F)=CC=3)=CCC2)=NC=1C1=CC=NC=N1 QEYCGLYTYRKDSB-UHFFFAOYSA-N 0.000 description 1
- 229940058020 2-amino-2-methyl-1-propanol Drugs 0.000 description 1
- UXGVMFHEKMGWMA-UHFFFAOYSA-N 2-benzofuran Chemical group C1=CC=CC2=COC=C21 UXGVMFHEKMGWMA-UHFFFAOYSA-N 0.000 description 1
- ASSKVPFEZFQQNQ-UHFFFAOYSA-N 2-benzoxazolinone Chemical group C1=CC=C2OC(O)=NC2=C1 ASSKVPFEZFQQNQ-UHFFFAOYSA-N 0.000 description 1
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- TZPQPZWAYZYDGJ-UHFFFAOYSA-N 3-methyl-2-[5-(2-phenylphenyl)-3,6-dihydro-2h-pyridin-1-yl]-6-pyrimidin-4-ylpyrimidin-4-one Chemical compound C=1C(=O)N(C)C(N2CC(=CCC2)C=2C(=CC=CC=2)C=2C=CC=CC=2)=NC=1C1=CC=NC=N1 TZPQPZWAYZYDGJ-UHFFFAOYSA-N 0.000 description 1
- QTRICUXXEYIREZ-UHFFFAOYSA-N 3-methyl-6-pyridin-4-yl-2-(5-thiophen-2-yl-3,6-dihydro-2h-pyridin-1-yl)pyrimidin-4-one Chemical compound C=1C(=O)N(C)C(N2CC(=CCC2)C=2SC=CC=2)=NC=1C1=CC=NC=C1 QTRICUXXEYIREZ-UHFFFAOYSA-N 0.000 description 1
- WVHRSJCPOQRHBN-UHFFFAOYSA-N 3-methyl-6-pyrimidin-4-yl-2-[5-[2-(trifluoromethyl)phenyl]-3,6-dihydro-2h-pyridin-1-yl]pyrimidin-4-one Chemical compound C=1C(=O)N(C)C(N2CC(=CCC2)C=2C(=CC=CC=2)C(F)(F)F)=NC=1C1=CC=NC=N1 WVHRSJCPOQRHBN-UHFFFAOYSA-N 0.000 description 1
- ZELWEUNNOYOJAC-UHFFFAOYSA-N 3-methyl-6-pyrimidin-4-yl-2-[5-[4-(pyrrolidine-1-carbonyl)phenyl]-3,6-dihydro-2h-pyridin-1-yl]pyrimidin-4-one Chemical compound C=1C(=O)N(C)C(N2CC(=CCC2)C=2C=CC(=CC=2)C(=O)N2CCCC2)=NC=1C1=CC=NC=N1 ZELWEUNNOYOJAC-UHFFFAOYSA-N 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- 125000002471 4H-quinolizinyl group Chemical group C=1(C=CCN2C=CC=CC12)* 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical group N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 1
- 102000003678 AMPA Receptors Human genes 0.000 description 1
- 108090000078 AMPA Receptors Proteins 0.000 description 1
- 101710137189 Amyloid-beta A4 protein Proteins 0.000 description 1
- 101710151993 Amyloid-beta precursor protein Proteins 0.000 description 1
- 102100022704 Amyloid-beta precursor protein Human genes 0.000 description 1
- 102000009091 Amyloidogenic Proteins Human genes 0.000 description 1
- 108010048112 Amyloidogenic Proteins Proteins 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 235000011960 Brassica ruvo Nutrition 0.000 description 1
- 229910014585 C2-Ce Inorganic materials 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
- BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical group C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 1
- 108091007911 GSKs Proteins 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- 108010014905 Glycogen Synthase Kinase 3 Proteins 0.000 description 1
- 102000002254 Glycogen Synthase Kinase 3 Human genes 0.000 description 1
- 102000004103 Glycogen Synthase Kinases Human genes 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 102000029749 Microtubule Human genes 0.000 description 1
- 108091022875 Microtubule Proteins 0.000 description 1
- 102000009664 Microtubule-Associated Proteins Human genes 0.000 description 1
- 108010020004 Microtubule-Associated Proteins Proteins 0.000 description 1
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 1
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- DHXVGJBLRPWPCS-UHFFFAOYSA-N Tetrahydropyran Chemical group C1CCOCC1 DHXVGJBLRPWPCS-UHFFFAOYSA-N 0.000 description 1
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 1
- 235000018936 Vitellaria paradoxa Nutrition 0.000 description 1
- 235000011054 acetic acid Nutrition 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 238000005054 agglomeration Methods 0.000 description 1
- 230000002776 aggregation Effects 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 125000003282 alkyl amino group Chemical group 0.000 description 1
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
- VLSMHEGGTFMBBZ-UHFFFAOYSA-N alpha-Kainic acid Natural products CC(=C)C1CNC(C(O)=O)C1CC(O)=O VLSMHEGGTFMBBZ-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- CBTVGIZVANVGBH-UHFFFAOYSA-N aminomethyl propanol Chemical compound CC(C)(N)CO CBTVGIZVANVGBH-UHFFFAOYSA-N 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- BNBQRQQYDMDJAH-UHFFFAOYSA-N benzodioxan Chemical group C1=CC=C2OCCOC2=C1 BNBQRQQYDMDJAH-UHFFFAOYSA-N 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical group C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 1
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000006309 butyl amino group Chemical group 0.000 description 1
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 208000026106 cerebrovascular disease Diseases 0.000 description 1
- VZWXIQHBIQLMPN-UHFFFAOYSA-N chromane Chemical group C1=CC=C2CCCOC2=C1 VZWXIQHBIQLMPN-UHFFFAOYSA-N 0.000 description 1
- QZHPTGXQGDFGEN-UHFFFAOYSA-N chromene Chemical group C1=CC=C2C=C[CH]OC2=C1 QZHPTGXQGDFGEN-UHFFFAOYSA-N 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 125000000259 cinnolinyl group Chemical group N1=NC(=CC2=CC=CC=C12)* 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- 125000000000 cycloalkoxy group Chemical group 0.000 description 1
- 125000001352 cyclobutyloxy group Chemical group C1(CCC1)O* 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000002933 cyclohexyloxy group Chemical group C1(CCCCC1)O* 0.000 description 1
- 125000001887 cyclopentyloxy group Chemical group C1(CCCC1)O* 0.000 description 1
- 125000000131 cyclopropyloxy group Chemical group C1(CC1)O* 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000006264 diethylaminomethyl group Chemical group [H]C([H])([H])C([H])([H])N(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000000532 dioxanyl group Chemical group 0.000 description 1
- 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 208000025688 early-onset autosomal dominant Alzheimer disease Diseases 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 125000006534 ethyl amino methyl group Chemical group [H]N(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 1
- 208000015756 familial Alzheimer disease Diseases 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 229960004275 glycolic acid Drugs 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- 125000002632 imidazolidinyl group Chemical group 0.000 description 1
- 125000002636 imidazolinyl group Chemical group 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000006316 iso-butyl amino group Chemical group [H]N(*)C([H])([H])C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- HEBMCVBCEDMUOF-UHFFFAOYSA-N isochromane Chemical group C1=CC=C2COCCC2=C1 HEBMCVBCEDMUOF-UHFFFAOYSA-N 0.000 description 1
- GWVMLCQWXVFZCN-UHFFFAOYSA-N isoindoline Chemical group C1=CC=C2CNCC2=C1 GWVMLCQWXVFZCN-UHFFFAOYSA-N 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical group C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 description 1
- 125000003965 isoxazolidinyl group Chemical group 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- VLSMHEGGTFMBBZ-OOZYFLPDSA-N kainic acid Chemical compound CC(=C)[C@H]1CN[C@H](C(O)=O)[C@H]1CC(O)=O VLSMHEGGTFMBBZ-OOZYFLPDSA-N 0.000 description 1
- 229950006874 kainic acid Drugs 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229960000448 lactic acid Drugs 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 125000006533 methyl amino methyl group Chemical group [H]N(C([H])([H])[H])C([H])([H])* 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 210000004688 microtubule Anatomy 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 231100000189 neurotoxic Toxicity 0.000 description 1
- 230000002887 neurotoxic effect Effects 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 125000001400 nonyl 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])C([H])([H])[H] 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical group C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 125000000160 oxazolidinyl group Chemical group 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 125000004894 pentylamino group Chemical group C(CCCC)N* 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- LFSXCDWNBUNEEM-UHFFFAOYSA-N phthalazine Chemical group C1=NN=CC2=CC=CC=C21 LFSXCDWNBUNEEM-UHFFFAOYSA-N 0.000 description 1
- 125000005543 phthalimide group Chemical group 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000006308 propyl amino group Chemical group 0.000 description 1
- CPNGPNLZQNNVQM-UHFFFAOYSA-N pteridine Chemical group N1=CN=CC2=NC=CN=C21 CPNGPNLZQNNVQM-UHFFFAOYSA-N 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
- 125000002755 pyrazolinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical group C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- ILVXOBCQQYKLDS-UHFFFAOYSA-N pyridine N-oxide Chemical group [O-][N+]1=CC=CC=C1 ILVXOBCQQYKLDS-UHFFFAOYSA-N 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 238000012216 screening Methods 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 1
- 239000007901 soft capsule Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000006318 tert-butyl amino group Chemical group [H]N(*)C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical group C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 125000002948 undecyl 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])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 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
- C07D401/14—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 three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- 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
- A61P25/18—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
- A61P25/28—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
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- 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
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Ophthalmology & Optometry (AREA)
- Psychiatry (AREA)
- Obesity (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Oncology (AREA)
- Psychology (AREA)
- Hospice & Palliative Care (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2002383301 | 2002-12-16 | ||
JP2002383300 | 2002-12-16 |
Publications (1)
Publication Number | Publication Date |
---|---|
ZA200505258B true ZA200505258B (en) | 2006-09-27 |
Family
ID=32599307
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ZA200505258A ZA200505258B (en) | 2002-12-16 | 2003-12-12 | 3-Substituted-4-pyrimidone derivatives |
Country Status (13)
Country | Link |
---|---|
US (1) | US7683069B2 (zh) |
EP (1) | EP1572681B1 (zh) |
JP (1) | JP4616003B2 (zh) |
KR (1) | KR100956052B1 (zh) |
CN (1) | CN1726209B (zh) |
BR (1) | BR0316785A (zh) |
CA (1) | CA2510170C (zh) |
EA (1) | EA009027B1 (zh) |
MX (1) | MXPA05006394A (zh) |
NO (1) | NO20053449L (zh) |
NZ (1) | NZ541074A (zh) |
WO (1) | WO2004055007A1 (zh) |
ZA (1) | ZA200505258B (zh) |
Families Citing this family (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AR023052A1 (es) | 1998-09-25 | 2002-09-04 | Mitsuharu Yoshimura Milton | Derivados de pirimidona |
PL368816A1 (en) | 2001-09-21 | 2005-04-04 | Mitsubishi Pharma Corporation | 3-substituted-4-pyrimidone derivatives |
EA007576B1 (ru) | 2001-09-21 | 2006-12-29 | Мицубиси Фарма Корпорейшн | Производные 3-замещенных 4-пиримидонов |
TWI357408B (en) | 2003-03-26 | 2012-02-01 | Mitsubishi Tanabe Pharma Corp | 3-substituted-4-pyrimidone derivatives |
AR050865A1 (es) | 2004-09-09 | 2006-11-29 | Sanofi Aventis | Derivados de 2- morfolino-4-pirimidona |
WO2006041405A1 (en) * | 2004-10-15 | 2006-04-20 | Astrazeneca Ab | Substituted amino-pyrimidones and uses thereof |
JP2008516945A (ja) * | 2004-10-15 | 2008-05-22 | アストラゼネカ・アクチエボラーグ | 置換されたアミノ化合物およびそれらの使用 |
TW200813015A (en) * | 2006-03-15 | 2008-03-16 | Mitsubishi Pharma Corp | 2-(cyclic amino)-pyrimidone derivatives |
US20100292205A1 (en) * | 2006-08-23 | 2010-11-18 | Pfizer Inc. | Pyrimidone Compounds As GSK-3 Inhibitors |
EP1992625A1 (en) | 2007-05-16 | 2008-11-19 | Sanofi-Aventis | Arylamide pyrimidone compounds |
EP1992621A1 (en) | 2007-05-16 | 2008-11-19 | Sanofi-Aventis | Heteroarylamide-substituted pyrimidone derivatives for the treatment of neurodegenerative diseases |
EP1992620A1 (en) | 2007-05-16 | 2008-11-19 | Sanofi-Aventis | Arylamide pyrimidone derivatives for the treatment of neurodegenerative diseases |
EP1992624A1 (en) | 2007-05-16 | 2008-11-19 | Sanofi-Aventis | Heteroarylamide pyrimidone compounds |
JP5535310B2 (ja) * | 2009-08-13 | 2014-07-02 | 田辺三菱製薬株式会社 | タウプロテインキナーゼ1阻害剤としてのピリミドン誘導体 |
Family Cites Families (31)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS559099B2 (zh) | 1972-08-07 | 1980-03-07 | ||
JPS4935633A (zh) | 1972-08-09 | 1974-04-02 | ||
JPS4935632A (zh) | 1972-08-10 | 1974-04-02 | ||
JPS5124008B2 (zh) | 1972-08-10 | 1976-07-21 | ||
JPS5271481A (en) | 1975-12-10 | 1977-06-14 | Yoshitomi Pharmaceut Ind Ltd | Synthesis of pyridylpyrimidines |
JPS52139085A (en) * | 1976-05-13 | 1977-11-19 | Hokuriku Pharmaceutical | 22allylpiperazine derivative and method for its preparation |
IN151188B (zh) * | 1978-02-13 | 1983-03-05 | Smith Kline French Lab | |
US4507302A (en) * | 1979-03-19 | 1985-03-26 | The Upjohn Company | Method for treating arthritis with 6-aryl pyrimidine compounds |
US4619933A (en) * | 1979-09-28 | 1986-10-28 | The Upjohn Company | 6-aryl pyrimidines for treating aplastic anemia |
US4725600A (en) * | 1984-07-13 | 1988-02-16 | Fujisawa Pharmaceutical Co., Ltd. | Pyrimidine compounds having activity as a cardiotonic anti-hypertensive cerebrovascular vasodilator and anti-platelet aggregation agent |
EP0354179B1 (de) | 1988-07-29 | 1994-08-17 | Ciba-Geigy Ag | Thiouracile als Stabilisatoren für chlorhaltige Polymerisate |
ES2136654T3 (es) | 1991-12-06 | 1999-12-01 | Max Planck Gesellschaft | Herramientas para el diagnostico y tratamiento de la enfermedad de alzheimer. |
DE4206145A1 (de) * | 1992-02-28 | 1993-09-02 | Basf Ag | Herbizide n-((pyrimidin-2-yl)aminocarbonyl)benzolfulfonamide |
JP3324611B2 (ja) | 1992-07-03 | 2002-09-17 | 三菱化学株式会社 | タウ蛋白質のリン酸化方法 |
JPH06329551A (ja) | 1993-03-22 | 1994-11-29 | Mitsubishi Kasei Corp | アルツハイマー病の予防または治療薬およびそのスクリーニング方法 |
CA2174080A1 (en) * | 1993-10-12 | 1995-04-20 | Paul Edward Aldrich | 1n-alkyl-n-arylpyrimidinamines and derivatives thereof |
FR2736053B1 (fr) * | 1995-06-28 | 1997-09-19 | Sanofi Sa | Nouvelles 1-phenylalkyl-1,2,3,6-tetrahydropyridines |
US6410729B1 (en) * | 1996-12-05 | 2002-06-25 | Amgen Inc. | Substituted pyrimidine compounds and methods of use |
AR038955A1 (es) | 1996-12-05 | 2005-02-02 | Amgen Inc | Compuestos de pirimidinona y piridona sustituidos y metodos para su uso |
NZ335997A (en) | 1996-12-05 | 2001-08-31 | Amgen Inc | Substituted pyrimidine compounds for treating TNF and interleukin diseases |
US6096753A (en) * | 1996-12-05 | 2000-08-01 | Amgen Inc. | Substituted pyrimidinone and pyridone compounds and methods of use |
WO1998024780A2 (en) | 1996-12-05 | 1998-06-11 | Amgen Inc. | Substituted pyrimidinone and pyridinone compounds and their use |
EP0976745B1 (en) * | 1997-03-26 | 2003-08-13 | Taisho Pharmaceutical Co., Ltd | 4-tetrahydropyridylpyrimidine derivatives |
AR023052A1 (es) * | 1998-09-25 | 2002-09-04 | Mitsuharu Yoshimura Milton | Derivados de pirimidona |
BR0108611A (pt) * | 2000-02-25 | 2003-05-06 | Hoffmann La Roche | Moduladores de receptor de adenosina |
EP1136482A1 (en) | 2000-03-23 | 2001-09-26 | Sanofi-Synthelabo | 2-Amino-3-(alkyl)-pyrimidone derivatives as GSK3beta inhibitors |
WO2001070728A1 (en) * | 2000-03-23 | 2001-09-27 | Sanofi-Synthelabo | 2-[nitrogen-heterocyclic]pyrimidone derivatives |
BRPI0111596B8 (pt) * | 2000-06-12 | 2022-07-26 | Eisai Co Ltd | Composto piridona, processo de produção do composto, composição farmacêutica, e uso do dito composto |
EA007576B1 (ru) * | 2001-09-21 | 2006-12-29 | Мицубиси Фарма Корпорейшн | Производные 3-замещенных 4-пиримидонов |
PL368816A1 (en) * | 2001-09-21 | 2005-04-04 | Mitsubishi Pharma Corporation | 3-substituted-4-pyrimidone derivatives |
TWI357408B (en) * | 2003-03-26 | 2012-02-01 | Mitsubishi Tanabe Pharma Corp | 3-substituted-4-pyrimidone derivatives |
-
2003
- 2003-12-12 ZA ZA200505258A patent/ZA200505258B/en unknown
- 2003-12-12 EA EA200500984A patent/EA009027B1/ru not_active IP Right Cessation
- 2003-12-12 MX MXPA05006394A patent/MXPA05006394A/es active IP Right Grant
- 2003-12-12 US US10/538,766 patent/US7683069B2/en not_active Expired - Fee Related
- 2003-12-12 JP JP2004560630A patent/JP4616003B2/ja not_active Expired - Fee Related
- 2003-12-12 CN CN200380106258XA patent/CN1726209B/zh not_active Expired - Fee Related
- 2003-12-12 WO PCT/JP2003/015968 patent/WO2004055007A1/en active Application Filing
- 2003-12-12 NZ NZ541074A patent/NZ541074A/en unknown
- 2003-12-12 BR BR0316785-2A patent/BR0316785A/pt not_active IP Right Cessation
- 2003-12-12 CA CA2510170A patent/CA2510170C/en not_active Expired - Fee Related
- 2003-12-12 EP EP03778893.2A patent/EP1572681B1/en not_active Expired - Lifetime
- 2003-12-12 KR KR1020057011109A patent/KR100956052B1/ko not_active IP Right Cessation
-
2005
- 2005-07-15 NO NO20053449A patent/NO20053449L/no not_active Application Discontinuation
Also Published As
Publication number | Publication date |
---|---|
US20070142409A1 (en) | 2007-06-21 |
CN1726209A (zh) | 2006-01-25 |
KR20050099496A (ko) | 2005-10-13 |
EA200500984A1 (ru) | 2005-12-29 |
KR100956052B1 (ko) | 2010-05-06 |
AU2003285777A8 (en) | 2004-07-09 |
EP1572681A1 (en) | 2005-09-14 |
BR0316785A (pt) | 2005-10-25 |
US7683069B2 (en) | 2010-03-23 |
WO2004055007A1 (en) | 2004-07-01 |
AU2003285777A1 (en) | 2004-07-09 |
EP1572681B1 (en) | 2014-01-22 |
CA2510170C (en) | 2011-05-24 |
CA2510170A1 (en) | 2004-07-01 |
JP4616003B2 (ja) | 2011-01-19 |
NO20053449L (no) | 2005-07-15 |
MXPA05006394A (es) | 2007-04-16 |
NZ541074A (en) | 2008-04-30 |
EA009027B1 (ru) | 2007-10-26 |
JP2006510684A (ja) | 2006-03-30 |
CN1726209B (zh) | 2011-04-13 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
KR100754596B1 (ko) | 3-치환-4-피리미돈 유도체 | |
KR100881821B1 (ko) | 3-치환-4-피리미돈 유도체 | |
CA2520027C (en) | 2,3,6-trisubstituted-4-pyrimidone derivatives | |
AU2002337498A1 (en) | 3-substituted-4-pyrimidone derivatives | |
AU2002337499A1 (en) | 3-substituted-4-pyrimidone derivatives | |
EP2160388B1 (en) | Arylamide pyrimidone compounds | |
ZA200505258B (en) | 3-Substituted-4-pyrimidone derivatives | |
EP2148866B1 (en) | Arylamide pyrimidone derivatives for the treatment of neurodegenerative diseases | |
WO2001070683A2 (en) | 3-substituted-4-pyrimidone derivatives | |
WO2011019089A1 (en) | Pyrimidone derivatives used as tau protein kinase 1 inhibitors | |
AU2003285777B2 (en) | 3-substituted-4-pyrimidone derivatives | |
ZA200401845B (en) | 3-substituted-4-pyrimidone derivatives. |