NO325781B1 - 3-substituert 4-pyrimidonderivater - Google Patents

3-substituert 4-pyrimidonderivater Download PDF

Info

Publication number: NO325781B1
Authority: NO; Norway
Prior art keywords: group; ring; methyl; pyrimidin; pyridin
Prior art date: 2001-09-21

Application number

NO20041600A

Other languages

English (en)

Norwegian (no)

Other versions

NO20041600L (no

Inventor

Fumiaki Uehara

Keiichi Aritomo

Aya Shoda

Shinsuke Hiki

Masahiro Okuyama

Yoshihiro Usui

Mitsuru Ooizumi

Kazutishi Watanabe

Koichi Yamakoshi

Original Assignee

Mitsubishi Pharma Corp

Priority date (The priority date 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 date listed.)

2001-09-21

Filing date

2004-04-20

Publication date

2008-07-14

2004-04-20 Application filed by Mitsubishi Pharma Corp filed Critical Mitsubishi Pharma Corp

2004-06-16 Publication of NO20041600L publication Critical patent/NO20041600L/no

2008-07-14 Publication of NO325781B1 publication Critical patent/NO325781B1/no

Links

-1 3-substituted 4-pyrimidone Chemical class 0.000 title claims description 240
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 47
150000008318 pyrimidones Chemical class 0.000 claims abstract description 46
150000003839 salts Chemical class 0.000 claims abstract description 43
125000001624 naphthyl group Chemical group 0.000 claims abstract description 34
125000000217 alkyl group Chemical group 0.000 claims abstract description 30
239000012453 solvate Substances 0.000 claims abstract description 29
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 21
CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical group C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 claims abstract description 12
125000001424 substituent group Chemical group 0.000 claims description 36
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 30
201000010099 disease Diseases 0.000 claims description 29
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 29
239000003814 drug Substances 0.000 claims description 26
229940079593 drug Drugs 0.000 claims description 25
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 23
UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 19
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 18
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 18
208000024827 Alzheimer disease Diseases 0.000 claims description 17
239000004480 active ingredient Substances 0.000 claims description 17
125000003277 amino group Chemical group 0.000 claims description 17
229910052736 halogen Inorganic materials 0.000 claims description 17
150000002367 halogens Chemical class 0.000 claims description 17
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 15
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 15
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 15
230000001225 therapeutic effect Effects 0.000 claims description 15
FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical group C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 claims description 14
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 14
238000002360 preparation method Methods 0.000 claims description 14
125000003545 alkoxy group Chemical group 0.000 claims description 13
BNBQRQQYDMDJAH-UHFFFAOYSA-N benzodioxan Chemical group C1=CC=C2OCCOC2=C1 BNBQRQQYDMDJAH-UHFFFAOYSA-N 0.000 claims description 12
230000003449 preventive effect Effects 0.000 claims description 12
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 11
125000004093 cyano group Chemical group *C#N 0.000 claims description 11
GWVMLCQWXVFZCN-UHFFFAOYSA-N isoindoline Chemical group C1=CC=C2CNCC2=C1 GWVMLCQWXVFZCN-UHFFFAOYSA-N 0.000 claims description 10
125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 claims description 10
125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims description 10
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 9
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 9
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 9
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 9
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 9
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 9
FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical group C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 claims description 8
201000011240 Frontotemporal dementia Diseases 0.000 claims description 8
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 8
125000001041 indolyl group Chemical group 0.000 claims description 8
208000014674 injury Diseases 0.000 claims description 8
230000004770 neurodegeneration Effects 0.000 claims description 8
208000015122 neurodegenerative disease Diseases 0.000 claims description 8
210000004556 brain Anatomy 0.000 claims description 7
125000003387 indolinyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 claims description 7
125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 6
IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical group C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 claims description 6
HBEDSQVIWPRPAY-UHFFFAOYSA-N 2,3-dihydrobenzofuran Chemical group C1=CC=C2OCCC2=C1 HBEDSQVIWPRPAY-UHFFFAOYSA-N 0.000 claims description 6
AXIIEOPSQHRYCU-UHFFFAOYSA-N 2-methyl-1,3-dihydroisoindole Chemical group C1=CC=C2CN(C)CC2=C1 AXIIEOPSQHRYCU-UHFFFAOYSA-N 0.000 claims description 6
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 6
FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 6
125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 6
IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical group C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 claims description 6
239000000460 chlorine Substances 0.000 claims description 6
229910052801 chlorine Inorganic materials 0.000 claims description 6
125000000753 cycloalkyl group Chemical group 0.000 claims description 6
229910052731 fluorine Inorganic materials 0.000 claims description 6
239000011737 fluorine Substances 0.000 claims description 6
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical group C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 claims description 6
125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 claims description 6
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 5
208000005145 Cerebral amyloid angiopathy Diseases 0.000 claims description 5
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
108091000080 Phosphotransferase Proteins 0.000 claims description 5
208000036757 Postencephalitic parkinsonism Diseases 0.000 claims description 5
125000004432 carbon atom Chemical group C* 0.000 claims description 5
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 5
230000000302 ischemic effect Effects 0.000 claims description 5
102000020233 phosphotransferase Human genes 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
230000002784 sclerotic effect Effects 0.000 claims description 5
125000000355 1,3-benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 4
MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical group CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 claims description 4
AWBOSXFRPFZLOP-UHFFFAOYSA-N 2,1,3-benzoxadiazole Chemical group C1=CC=CC2=NON=C21 AWBOSXFRPFZLOP-UHFFFAOYSA-N 0.000 claims description 4
LXBGSDVWAMZHDD-UHFFFAOYSA-N 2-methyl-1h-imidazole Chemical group CC1=NC=CN1 LXBGSDVWAMZHDD-UHFFFAOYSA-N 0.000 claims description 4
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
208000010412 Glaucoma Diseases 0.000 claims description 4
206010028980 Neoplasm Diseases 0.000 claims description 4
208000008589 Obesity Diseases 0.000 claims description 4
208000027089 Parkinsonian disease Diseases 0.000 claims description 4
206010034010 Parkinsonism Diseases 0.000 claims description 4
208000000609 Pick Disease of the Brain Diseases 0.000 claims description 4
208000017442 Retinal disease Diseases 0.000 claims description 4
206010038923 Retinopathy 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
231100000360 alopecia Toxicity 0.000 claims description 4
208000028683 bipolar I disease Diseases 0.000 claims description 4
206010014599 encephalitis Diseases 0.000 claims description 4
LPAGFVYQRIESJQ-UHFFFAOYSA-N indoline Chemical group C1=CC=C2NCCC2=C1 LPAGFVYQRIESJQ-UHFFFAOYSA-N 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
208000033808 peripheral neuropathy Diseases 0.000 claims description 4
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 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
125000004400 (C1-C12) alkyl group Chemical group 0.000 claims description 3
RPMITZJMOPAUMG-UHFFFAOYSA-N 2,3,4,4a-tetrahydro-1H-benzo[7]annulene Chemical group C1=CC=CC2CCCCC2=C1 RPMITZJMOPAUMG-UHFFFAOYSA-N 0.000 claims description 3
206010044688 Trisomy 21 Diseases 0.000 claims description 3
229910052799 carbon Inorganic materials 0.000 claims description 3
239000003112 inhibitor Substances 0.000 claims description 3
125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 3
HOXGZVUCAYFWGR-KQQUZDAGSA-N (3e,5e)-octa-1,3,5-triene Chemical group CC\C=C\C=C\C=C HOXGZVUCAYFWGR-KQQUZDAGSA-N 0.000 claims description 2
KTZQTRPPVKQPFO-UHFFFAOYSA-N 1,2-benzoxazole Chemical group C1=CC=C2C=NOC2=C1 KTZQTRPPVKQPFO-UHFFFAOYSA-N 0.000 claims description 2
125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
XXOQJWXDRPURJK-UHFFFAOYSA-N 2,3,4,5-tetrahydro-1-benzoxepine Chemical group O1CCCCC2=CC=CC=C21 XXOQJWXDRPURJK-UHFFFAOYSA-N 0.000 claims description 2
NXCQEVQGDRISRL-UHFFFAOYSA-N 2-(2-benzoylmorpholin-4-yl)-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical compound C=1C(=O)N(C)C(N2CC(OCC2)C(=O)C=2C=CC=CC=2)=NC=1C1=CC=NC=C1 NXCQEVQGDRISRL-UHFFFAOYSA-N 0.000 claims description 2
DXFCUZGJPYQFIU-UHFFFAOYSA-N 2-(3-benzoylpiperidin-1-yl)-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical compound C=1C(=O)N(C)C(N2CC(CCC2)C(=O)C=2C=CC=CC=2)=NC=1C1=CC=NC=C1 DXFCUZGJPYQFIU-UHFFFAOYSA-N 0.000 claims description 2
SKSYOLBNGGRQAC-GOSISDBHSA-N 2-[(2s)-2-(2,4-difluoro-6-methoxyphenyl)morpholin-4-yl]-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical compound COC1=CC(F)=CC(F)=C1[C@@H]1OCCN(C=2N(C(=O)C=C(N=2)C=2C=CN=CC=2)C)C1 SKSYOLBNGGRQAC-GOSISDBHSA-N 0.000 claims description 2
NCPUWAGCDXDIPX-HXUWFJFHSA-N 2-[(2s)-2-(2,4-dimethoxyphenyl)morpholin-4-yl]-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical compound COC1=CC(OC)=CC=C1[C@@H]1OCCN(C=2N(C(=O)C=C(N=2)C=2C=CN=CC=2)C)C1 NCPUWAGCDXDIPX-HXUWFJFHSA-N 0.000 claims description 2
MBVYGBUUQIDTAQ-HXUWFJFHSA-N 2-[(2s)-2-(2,5-dimethoxyphenyl)morpholin-4-yl]-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical compound COC1=CC=C(OC)C([C@@H]2OCCN(C2)C=2N(C(=O)C=C(N=2)C=2C=CN=CC=2)C)=C1 MBVYGBUUQIDTAQ-HXUWFJFHSA-N 0.000 claims description 2
MBEKVLSSEYOCSP-QGZVFWFLSA-N 2-[(2s)-2-(2,6-dichlorophenyl)morpholin-4-yl]-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical compound C=1C(=O)N(C)C(N2C[C@@H](OCC2)C=2C(=CC=CC=2Cl)Cl)=NC=1C1=CC=NC=C1 MBEKVLSSEYOCSP-QGZVFWFLSA-N 0.000 claims description 2
ITAUXPSETNVANZ-LJQANCHMSA-N 2-[(2s)-2-(2,6-dimethoxyphenyl)morpholin-4-yl]-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical compound COC1=CC=CC(OC)=C1[C@@H]1OCCN(C=2N(C(=O)C=C(N=2)C=2C=CN=CC=2)C)C1 ITAUXPSETNVANZ-LJQANCHMSA-N 0.000 claims description 2
JFCBDPQANHNOJC-GOSISDBHSA-N 2-[(2s)-2-(2-chlorophenyl)morpholin-4-yl]-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical compound C=1C(=O)N(C)C(N2C[C@@H](OCC2)C=2C(=CC=CC=2)Cl)=NC=1C1=CC=NC=C1 JFCBDPQANHNOJC-GOSISDBHSA-N 0.000 claims description 2
NUWBPSCILGWYJD-GOSISDBHSA-N 2-[(2s)-2-(3-bromophenyl)morpholin-4-yl]-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical compound C=1C(=O)N(C)C(N2C[C@@H](OCC2)C=2C=C(Br)C=CC=2)=NC=1C1=CC=NC=C1 NUWBPSCILGWYJD-GOSISDBHSA-N 0.000 claims description 2
WYVWRIBBJCVZBU-LJQANCHMSA-N 2-[(2s)-2-(3-methoxyphenyl)morpholin-4-yl]-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical compound COC1=CC=CC([C@@H]2OCCN(C2)C=2N(C(=O)C=C(N=2)C=2C=CN=CC=2)C)=C1 WYVWRIBBJCVZBU-LJQANCHMSA-N 0.000 claims description 2
PDXVBCFBVCQTFC-GOSISDBHSA-N 2-[(2s)-2-(4-bromophenyl)morpholin-4-yl]-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical compound C=1C(=O)N(C)C(N2C[C@@H](OCC2)C=2C=CC(Br)=CC=2)=NC=1C1=CC=NC=C1 PDXVBCFBVCQTFC-GOSISDBHSA-N 0.000 claims description 2
RSGNGUPSUUTVML-LJQANCHMSA-N 2-[(2s)-2-(4-fluoro-2-methoxyphenyl)morpholin-4-yl]-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical compound COC1=CC(F)=CC=C1[C@@H]1OCCN(C=2N(C(=O)C=C(N=2)C=2C=CN=CC=2)C)C1 RSGNGUPSUUTVML-LJQANCHMSA-N 0.000 claims description 2
AMMSSQAWYDICPE-LJQANCHMSA-N 2-[(2s)-2-(4-methoxyphenyl)morpholin-4-yl]-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical compound C1=CC(OC)=CC=C1[C@@H]1OCCN(C=2N(C(=O)C=C(N=2)C=2C=CN=CC=2)C)C1 AMMSSQAWYDICPE-LJQANCHMSA-N 0.000 claims description 2
SKSYOLBNGGRQAC-UHFFFAOYSA-N 2-[2-(2,4-difluoro-6-methoxyphenyl)morpholin-4-yl]-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical compound COC1=CC(F)=CC(F)=C1C1OCCN(C=2N(C(=O)C=C(N=2)C=2C=CN=CC=2)C)C1 SKSYOLBNGGRQAC-UHFFFAOYSA-N 0.000 claims description 2
OYTNQXCKJVXNFQ-UHFFFAOYSA-N 2-[2-(2,4-difluorophenyl)morpholin-4-yl]-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical compound C=1C(=O)N(C)C(N2CC(OCC2)C=2C(=CC(F)=CC=2)F)=NC=1C1=CC=NC=C1 OYTNQXCKJVXNFQ-UHFFFAOYSA-N 0.000 claims description 2
MBVYGBUUQIDTAQ-UHFFFAOYSA-N 2-[2-(2,5-dimethoxyphenyl)morpholin-4-yl]-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical compound COC1=CC=C(OC)C(C2OCCN(C2)C=2N(C(=O)C=C(N=2)C=2C=CN=CC=2)C)=C1 MBVYGBUUQIDTAQ-UHFFFAOYSA-N 0.000 claims description 2
UUJZZJCEWDZFCY-UHFFFAOYSA-N 2-[2-(2,6-difluorophenyl)morpholin-4-yl]-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical compound C=1C(=O)N(C)C(N2CC(OCC2)C=2C(=CC=CC=2F)F)=NC=1C1=CC=NC=C1 UUJZZJCEWDZFCY-UHFFFAOYSA-N 0.000 claims description 2
ITAUXPSETNVANZ-UHFFFAOYSA-N 2-[2-(2,6-dimethoxyphenyl)morpholin-4-yl]-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical compound COC1=CC=CC(OC)=C1C1OCCN(C=2N(C(=O)C=C(N=2)C=2C=CN=CC=2)C)C1 ITAUXPSETNVANZ-UHFFFAOYSA-N 0.000 claims description 2
GXTQJAFEQFYDTA-UHFFFAOYSA-N 2-[2-(2-bromo-4-fluorophenyl)morpholin-4-yl]-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical compound C=1C(=O)N(C)C(N2CC(OCC2)C=2C(=CC(F)=CC=2)Br)=NC=1C1=CC=NC=C1 GXTQJAFEQFYDTA-UHFFFAOYSA-N 0.000 claims description 2
JHNWKTOHLFPYOV-UHFFFAOYSA-N 2-[2-(2-bromophenyl)morpholin-4-yl]-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical compound C=1C(=O)N(C)C(N2CC(OCC2)C=2C(=CC=CC=2)Br)=NC=1C1=CC=NC=C1 JHNWKTOHLFPYOV-UHFFFAOYSA-N 0.000 claims description 2
BDBDSBMMKVJRJC-UHFFFAOYSA-N 2-[2-(2-chloro-6-fluorophenyl)morpholin-4-yl]-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical compound C=1C(=O)N(C)C(N2CC(OCC2)C=2C(=CC=CC=2F)Cl)=NC=1C1=CC=NC=C1 BDBDSBMMKVJRJC-UHFFFAOYSA-N 0.000 claims description 2
JFCBDPQANHNOJC-UHFFFAOYSA-N 2-[2-(2-chlorophenyl)morpholin-4-yl]-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical compound C=1C(=O)N(C)C(N2CC(OCC2)C=2C(=CC=CC=2)Cl)=NC=1C1=CC=NC=C1 JFCBDPQANHNOJC-UHFFFAOYSA-N 0.000 claims description 2
KVAYRHJOQRDMSZ-UHFFFAOYSA-N 2-[2-(2-methoxybenzoyl)morpholin-4-yl]-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical compound COC1=CC=CC=C1C(=O)C1OCCN(C=2N(C(=O)C=C(N=2)C=2C=CN=CC=2)C)C1 KVAYRHJOQRDMSZ-UHFFFAOYSA-N 0.000 claims description 2
RXCKTOIDABXJLT-UHFFFAOYSA-N 2-[2-(2-methoxyphenyl)morpholin-4-yl]-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical compound COC1=CC=CC=C1C1OCCN(C=2N(C(=O)C=C(N=2)C=2C=CN=CC=2)C)C1 RXCKTOIDABXJLT-UHFFFAOYSA-N 0.000 claims description 2
NUWBPSCILGWYJD-UHFFFAOYSA-N 2-[2-(3-bromophenyl)morpholin-4-yl]-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical compound C=1C(=O)N(C)C(N2CC(OCC2)C=2C=C(Br)C=CC=2)=NC=1C1=CC=NC=C1 NUWBPSCILGWYJD-UHFFFAOYSA-N 0.000 claims description 2
BBNWEEMYFMVCSH-UHFFFAOYSA-N 2-[2-(3-chlorophenyl)morpholin-4-yl]-3-methyl-6-pyridin-4-ylpyrimidin-4-one Chemical compound C=1C(=O)N(C)C(N2CC(OCC2)C=2C=C(Cl)C=CC=2)=NC=1C1=CC=NC=C1 BBNWEEMYFMVCSH-UHFFFAOYSA-N 0.000 claims description 2
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Classifications

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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
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- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/34—One oxygen atom
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/56—One oxygen atom and one sulfur atom
- 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
- 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

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Chemical & Material Sciences (AREA)
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Bioinformatics & Cheminformatics (AREA)
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General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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Veterinary Medicine (AREA)
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Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
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NO20041600A 2001-09-21 2004-04-20 3-substituert 4-pyrimidonderivater NO325781B1 (no)

Applications Claiming Priority (5)

Application Number	Priority Date	Filing Date	Title
JP2001331675		2001-09-21
JP2001331674		2001-09-21
JP2001331677		2001-09-21
JP2001331678		2001-09-21
PCT/JP2002/009685 WO2003037888A1 (en)	2001-09-21	2002-09-20	3-substituted-4-pyrimidone derivatives

Publications (2)

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NO20041600L NO20041600L (no)	2004-06-16
NO325781B1 true NO325781B1 (no)	2008-07-14

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US (1)	US7427615B2 (de)
EP (1)	EP1427720B1 (de)
JP (1)	JP4347050B2 (de)
KR (1)	KR100881821B1 (de)
CN (1)	CN100488958C (de)
AT (1)	ATE424393T1 (de)
AU (1)	AU2002337499B2 (de)
BR (1)	BR0212892A (de)
CA (1)	CA2460121C (de)
CY (1)	CY1110317T1 (de)
DE (1)	DE60231414D1 (de)
DK (1)	DK1427720T3 (de)
EA (1)	EA007576B1 (de)
ES (1)	ES2323576T3 (de)
HU (1)	HUP0401900A3 (de)
IL (2)	IL160700A0 (de)
MX (1)	MXPA04002662A (de)
NO (1)	NO325781B1 (de)
NZ (1)	NZ531636A (de)
PL (1)	PL368671A1 (de)
PT (1)	PT1427720E (de)
SI (1)	SI1427720T1 (de)
TW (1)	TWI265164B (de)
WO (1)	WO2003037888A1 (de)

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Publication number	Priority date	Publication date	Assignee	Title
TWI241298B (en)	1998-09-25	2005-10-11	Mitsubishi Chem Corp	Pyrimidone derivatives
KR100754596B1 (ko)	2001-09-21	2007-09-05	미쯔비시 웰 파마 가부시키가이샤	3-치환-4-피리미돈 유도체
MXPA05006394A (es) *	2002-12-16	2007-04-16	Mitsubishi Pharma Corp	Derivados de 4-pirimidona 3-sustituida.
US7550590B2 (en)	2003-03-25	2009-06-23	Takeda Pharmaceutical Company Limited	Dipeptidyl peptidase inhibitors
TWI357408B (en) *	2003-03-26	2012-02-01	Mitsubishi Tanabe Pharma Corp	3-substituted-4-pyrimidone derivatives
KR20060041309A (ko)	2003-08-13	2006-05-11	다케다 야쿠힌 고교 가부시키가이샤	４-피리미돈 유도체 및 펩티딜 펩티다제 저해제로서의 그의용도
US7790734B2 (en)	2003-09-08	2010-09-07	Takeda Pharmaceutical Company Limited	Dipeptidyl peptidase inhibitors
GB0325956D0 (en)	2003-11-06	2003-12-10	Addex Pharmaceuticals Sa	Novel compounds
CN102127057A (zh)	2004-03-15	2011-07-20	武田药品工业株式会社	二肽基肽酶抑制剂
AR050865A1 (es) *	2004-09-09	2006-11-29	Sanofi Aventis	Derivados de 2- morfolino-4-pirimidona
PT1805164E (pt) *	2004-09-29	2011-04-11	Sanofi Aventis	Derivados de 6-(piridinil)-4-pirimidona como inibidores de proteína-cinase tau 1
WO2006041405A1 (en) *	2004-10-15	2006-04-20	Astrazeneca Ab	Substituted amino-pyrimidones and uses thereof
EP1802587A4 (de) *	2004-10-15	2010-02-17	Astrazeneca Ab	Substituierte aminoverbindungen und deren anwendungen
WO2006068978A2 (en)	2004-12-21	2006-06-29	Takeda Pharmaceutial Company Limited	Dipeptidyl peptidase inhibitors
GB0510142D0 (en) *	2005-05-18	2005-06-22	Addex Pharmaceuticals Sa	Novel compounds A1
GB0510141D0 (en)	2005-05-18	2005-06-22	Addex Pharmaceuticals Sa	Novel compounds B3
GEP20135838B (en)	2005-09-14	2013-06-10	Takeda Pharmaceutical	Dipeptidyl peptidase inhibitors usage at diabetes treatment
CN101360723A (zh)	2005-09-16	2009-02-04	武田药品工业株式会社	制备嘧啶二酮衍生物的方法
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
US8324383B2 (en)	2006-09-13	2012-12-04	Takeda Pharmaceutical Company Limited	Methods of making polymorphs of benzoate salt of 2-[[6-[(3R)-3-amino-1-piperidinyl]-3,4-dihydro-3-methyl-2,4-dioxo-1(2H)-pyrimidinyl]methyl]-benzonitrile
TW200838536A (en)	2006-11-29	2008-10-01	Takeda Pharmaceutical	Polymorphs of succinate salt of 2-[6-(3-amino-piperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethy]-4-fluor-benzonitrile and methods of use therefor
AR064660A1 (es) *	2006-12-26	2009-04-15	Mitsubishi Tanabe Pharma Corp	Derivados de pirimidinona 6-heterociclica 2-sustituida, medicamentos que los contienen y usos para prevenir y/o tratar enfermedades neurodegenerativas entre otras
US8093236B2 (en)	2007-03-13	2012-01-10	Takeda Pharmaceuticals Company Limited	Weekly administration of dipeptidyl peptidase inhibitors
CN101842371A (zh) *	2007-09-14	2010-09-22	赛诺菲-安万特公司	3-甲基-2-((2S)-2-(4-(3-甲基-1,2,4-噁二唑-5-基)苯基)吗啉基)-6-(嘧啶-4-基)嘧啶-4(3H)-酮作为tau蛋白激酶抑制剂
AU2008297817A1 (en)	2007-09-14	2009-03-19	Mitsubishi Tanabe Pharma Corporation	6-pyrimidinyl-pyrimid-4-one derivative
AR076014A1 (es) *	2009-04-02	2011-05-11	Sanofi Aventis	Derivados de 3- (1,4) oxazepan -4-pirimidona
WO2011019089A1 (en)	2009-08-13	2011-02-17	Mitsubishi Tanabe Pharma Corporation	Pyrimidone derivatives used as tau protein kinase 1 inhibitors
WO2011019090A1 (en)	2009-08-13	2011-02-17	Mitsubishi Tanabe Pharma Corporation	Pyrimidone derivatives used as tau protein kinase 1 inhibitors
US20130123281A1 (en) *	2011-11-11	2013-05-16	Beta Cat Pharmaceuticals, Llc	Compositions and Methods for Inhibition of TBL-1 Binding to Disease-Associated Molecules
NZ730123A (en)	2014-09-29	2023-05-26	Chemocentryx Inc	Processes and intermediates in the preparation of c5ar antagonists
CN108601790B (zh)	2016-01-14	2026-01-27	凯莫森特里克斯股份有限公司	C3肾小球病的治疗方法

Family Cites Families (29)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPS4935631B1 (de)	1970-12-28	1974-09-25
JPS559099B2 (de)	1972-08-07	1980-03-07
JPS4935633A (de)	1972-08-09	1974-04-02
JPS4935632A (de)	1972-08-10	1974-04-02
JPS5124008B2 (de)	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
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
ATE398176T1 (de)	1991-12-06	2008-07-15	Max Planck Gesellschaft	Phosphorylierungsepitope aus dem tau-protein zur diagnose und behandlung der alzheimer-krankheit
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
US5300477A (en) *	1992-07-17	1994-04-05	Rohm And Haas Company	2-arylpyrimidines and herbicidal use thereof
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
JPH07179442A (ja) *	1993-10-08	1995-07-18	Sagami Chem Res Center	４−イミノオキサゾリジン−２−オン誘導体、それらの製造方法、及びそれらを有効成分とする除草剤
PL313973A1 (en)	1993-10-12	1996-08-05	Du Pont Merck Pharma	1 n-alkyl-n-arylopyrimidin amines and their derivatives
AU733877C (en)	1996-12-05	2003-05-08	Amgen, Inc.	Substituted pyrimidine compounds and their use
US6096753A (en)	1996-12-05	2000-08-01	Amgen Inc.	Substituted pyrimidinone and pyridone 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
US6410729B1 (en)	1996-12-05	2002-06-25	Amgen Inc.	Substituted pyrimidine compounds and methods of use
TWI241298B (en)	1998-09-25	2005-10-11	Mitsubishi Chem Corp	Pyrimidone derivatives
JP4064671B2 (ja)	2000-02-25	2008-03-19	エフ．ホフマン−ラロシュアーゲー	アデノシン受容体モジュレーター
WO2001070728A1 (en)	2000-03-23	2001-09-27	Sanofi-Synthelabo	2-[nitrogen-heterocyclic]pyrimidone derivatives
EP1136482A1 (de)	2000-03-23	2001-09-26	Sanofi-Synthelabo	2-Amino-3-(alkyl)-pyrimidonderivate als GSK3beta-Hemmer
KR100754596B1 (ko)	2001-09-21	2007-09-05	미쯔비시 웰 파마 가부시키가이샤	3-치환-4-피리미돈 유도체
MXPA05006394A (es)	2002-12-16	2007-04-16	Mitsubishi Pharma Corp	Derivados de 4-pirimidona 3-sustituida.
TWI357408B (en)	2003-03-26	2012-02-01	Mitsubishi Tanabe Pharma Corp	3-substituted-4-pyrimidone derivatives

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SI1427720T1 (sl)	2009-08-31
EP1427720A1 (de)	2004-06-16
HUP0401900A2 (hu)	2004-12-28
ATE424393T1 (de)	2009-03-15
MXPA04002662A (es)	2004-11-22
JP4347050B2 (ja)	2009-10-21
US20050090490A1 (en)	2005-04-28
AU2002337499B2 (en)	2007-08-23
CY1110317T1 (el)	2015-01-14
CA2460121C (en)	2010-11-02
ES2323576T3 (es)	2009-07-21
CN100488958C (zh)	2009-05-20
EA200400453A1 (ru)	2004-08-26
TWI265164B (en)	2006-11-01
PL368671A1 (en)	2005-04-04
EA007576B1 (ru)	2006-12-29
WO2003037888A1 (en)	2003-05-08
PT1427720E (pt)	2009-04-27
NZ531636A (en)	2005-11-25
CA2460121A1 (en)	2003-05-08
NO20041600L (no)	2004-06-16
US7427615B2 (en)	2008-09-23
DE60231414D1 (de)	2009-04-16
HUP0401900A3 (en)	2005-08-29
IL160700A (en)	2009-09-22
EP1427720B1 (de)	2009-03-04
KR20040054689A (ko)	2004-06-25
CN1556804A (zh)	2004-12-22
DK1427720T3 (da)	2009-05-04
JP2005510506A (ja)	2005-04-21
BR0212892A (pt)	2004-08-03
IL160700A0 (en)	2004-08-31
KR100881821B1 (ko)	2009-02-03

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Publication	Publication Date	Title
NO325781B1 (no)	2008-07-14	3-substituert 4-pyrimidonderivater
JP4368682B2 (ja)	2009-11-18	３−置換−４−ピリミドン誘導体
AU2002337498A1 (en)	2003-06-26	3-substituted-4-pyrimidone derivatives
AU2002337499A1 (en)	2003-07-10	3-substituted-4-pyrimidone derivatives
KR20050111613A (ko)	2005-11-25	2,3,6-트리치환된-4-피리미돈 유도체
JP5060287B2 (ja)	2012-10-31	２−モルホリノ−４−ピリミドン化合物
CA2510170C (en)	2011-05-24	3-substituted-4-pyrimidone derivatives
AU2003285777B2 (en)	2010-02-11	3-substituted-4-pyrimidone derivatives
CN1810802B (zh)	2011-04-27	3-取代的-4-嘧啶酮衍生物
HK1068608B (en)	2006-07-21	3-substituted-4-pyrimidone derivatives