NO329565B1 - Substituerte 2-pyridinyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-on og 7-pyridinyl-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)on-derivater, anvendelser av slike derivater, og legemidler og inhibitorer omfattende slike derivater - Google Patents
Substituerte 2-pyridinyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-on og 7-pyridinyl-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)on-derivater, anvendelser av slike derivater, og legemidler og inhibitorer omfattende slike derivater Download PDFInfo
- Publication number
- NO329565B1 NO329565B1 NO20041141A NO20041141A NO329565B1 NO 329565 B1 NO329565 B1 NO 329565B1 NO 20041141 A NO20041141 A NO 20041141A NO 20041141 A NO20041141 A NO 20041141A NO 329565 B1 NO329565 B1 NO 329565B1
- Authority
- NO
- Norway
- Prior art keywords
- pyridin
- pyrimidin
- pyrimido
- tetrahydro
- dimethyl
- Prior art date
Links
- 239000003814 drug Substances 0.000 title claims abstract description 30
- 229940079593 drug Drugs 0.000 title claims description 25
- 239000003112 inhibitor Substances 0.000 title claims description 12
- YHPVIBUEXBEHPV-UHFFFAOYSA-N 2,6-dihydro-1h-pyrimidin-5-one Chemical class O=C1CNCN=C1 YHPVIBUEXBEHPV-UHFFFAOYSA-N 0.000 title 1
- KTZSHRGZRORXJO-UHFFFAOYSA-N 2-pyridin-2-yl-1,6,7,8-tetrahydropyrimido[1,2-a]pyrimidin-4-one Chemical class N1=C2NCCCN2C(=O)C=C1C1=CC=CC=N1 KTZSHRGZRORXJO-UHFFFAOYSA-N 0.000 title 1
- 150000003839 salts Chemical class 0.000 claims abstract description 40
- 101150053721 Cdk5 gene Proteins 0.000 claims abstract description 34
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 24
- 239000004480 active ingredient Substances 0.000 claims abstract description 20
- 150000008318 pyrimidones Chemical class 0.000 claims abstract description 19
- 230000003449 preventive effect Effects 0.000 claims abstract description 18
- 230000004770 neurodegeneration Effects 0.000 claims abstract description 17
- 230000001225 therapeutic effect Effects 0.000 claims abstract description 17
- 208000015122 neurodegenerative disease Diseases 0.000 claims abstract description 16
- 230000002159 abnormal effect Effects 0.000 claims abstract description 14
- 125000005843 halogen group Chemical group 0.000 claims abstract description 14
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 13
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims abstract description 13
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 10
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 8
- WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical group C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 claims abstract description 7
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims abstract description 7
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 5
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 5
- 125000001624 naphthyl group Chemical group 0.000 claims abstract description 4
- DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 claims description 129
- 150000001875 compounds Chemical class 0.000 claims description 80
- -1 hydroxyiminomethylene group Chemical group 0.000 claims description 20
- 230000000694 effects Effects 0.000 claims description 19
- 201000010099 disease Diseases 0.000 claims description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 17
- 239000012453 solvate Substances 0.000 claims description 15
- 239000000126 substance Substances 0.000 claims description 14
- 102000019058 Glycogen Synthase Kinase 3 beta Human genes 0.000 claims description 11
- 108010051975 Glycogen Synthase Kinase 3 beta Proteins 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- 206010028980 Neoplasm Diseases 0.000 claims description 10
- 208000014674 injury Diseases 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 208000034799 Tauopathies Diseases 0.000 claims description 7
- SOQCSKKKURIFCX-UHFFFAOYSA-N pyrimido[1,2-a]pyrimidin-6-one Chemical compound N1=CC=CN2C(=O)C=CN=C21 SOQCSKKKURIFCX-UHFFFAOYSA-N 0.000 claims description 7
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 7
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- 125000003277 amino group Chemical group 0.000 claims description 6
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 6
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- VNHNILNXYRRAKL-XCWJXAQQSA-N 9-[(2s)-2-hydroxy-2-phenylethyl]-8-methyl-2-pyridin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C([C@@H](O)C=1C=CC=CC=1)N1C(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 VNHNILNXYRRAKL-XCWJXAQQSA-N 0.000 claims description 5
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- 230000005586 smoking cessation Effects 0.000 claims description 5
- 230000008736 traumatic injury Effects 0.000 claims description 5
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 4
- 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 claims description 4
- 208000004736 B-Cell Leukemia Diseases 0.000 claims description 4
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- 208000024770 Thyroid neoplasm Diseases 0.000 claims description 4
- 241000700605 Viruses Species 0.000 claims description 4
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 4
- 201000002510 thyroid cancer Diseases 0.000 claims description 4
- JYFONUFKTJUZBE-UHFFFAOYSA-N 3-fluoro-8-methyl-9-phenacyl-2-pyridin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C=CC=CC=1C(=O)CN1C(C)CCN(C(C=2F)=O)C1=NC=2C1=CC=NC=C1 JYFONUFKTJUZBE-UHFFFAOYSA-N 0.000 claims description 3
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 3
- GCKUUGPSDVVKQF-UHFFFAOYSA-N 1-(2-hydroxy-2-phenylethyl)-2,2-dimethyl-7-pyridin-4-yl-3h-imidazo[1,2-a]pyrimidin-5-one Chemical compound C=1C=CC=CC=1C(O)CN1C(C)(C)CN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 GCKUUGPSDVVKQF-UHFFFAOYSA-N 0.000 claims description 2
- AZPXHIKRAWMQPU-LJQANCHMSA-N 1-[(2s)-2-(3,4-dichlorophenyl)-2-hydroxyethyl]-2,2-dimethyl-8-pyridin-4-yl-3,4-dihydropyrimido[1,2-a]pyrimidin-6-one Chemical compound C([C@@H](O)C=1C=C(Cl)C(Cl)=CC=1)N1C(C)(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 AZPXHIKRAWMQPU-LJQANCHMSA-N 0.000 claims description 2
- YTNAXSLQYJSLNO-LJQANCHMSA-N 1-[(2s)-2-(4-fluorophenyl)-2-hydroxyethyl]-2,2-dimethyl-8-pyridin-4-yl-3,4-dihydropyrimido[1,2-a]pyrimidin-6-one Chemical compound C([C@@H](O)C=1C=CC(F)=CC=1)N1C(C)(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 YTNAXSLQYJSLNO-LJQANCHMSA-N 0.000 claims description 2
- ZNWZLYFCWYHOON-HXUWFJFHSA-N 1-[(2s)-2-hydroxy-2-(4-methylphenyl)ethyl]-2,2-dimethyl-8-pyridin-4-yl-3,4-dihydropyrimido[1,2-a]pyrimidin-6-one Chemical compound C1=CC(C)=CC=C1[C@H](O)CN1C(C)(C)CCN2C(=O)C=C(C=3C=CN=CC=3)N=C21 ZNWZLYFCWYHOON-HXUWFJFHSA-N 0.000 claims description 2
- KCRDVZBSGQOCQQ-HSZRJFAPSA-N 1-[(2s)-2-hydroxy-2-naphthalen-2-ylethyl]-2,2-dimethyl-8-pyridin-4-yl-3,4-dihydropyrimido[1,2-a]pyrimidin-6-one Chemical compound C([C@@H](O)C=1C=C2C=CC=CC2=CC=1)N1C(C)(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 KCRDVZBSGQOCQQ-HSZRJFAPSA-N 0.000 claims description 2
- JRPRRFDQCPRIDD-UHFFFAOYSA-N 1-[1-(7-methoxy-1,3-benzodioxol-5-yl)-1-oxopropan-2-yl]-2,2-dimethyl-7-pyridin-4-yl-3h-imidazo[1,2-a]pyrimidin-5-one Chemical compound C=1C=2OCOC=2C(OC)=CC=1C(=O)C(C)N(C(CN1C(=O)C=2)(C)C)C1=NC=2C1=CC=NC=C1 JRPRRFDQCPRIDD-UHFFFAOYSA-N 0.000 claims description 2
- GQRHZFVCOMJVOU-UHFFFAOYSA-N 1-[2-(3-bromophenyl)-2-oxoethyl]-2,2-dimethyl-8-pyridin-4-yl-3,4-dihydropyrimido[1,2-a]pyrimidin-6-one Chemical compound C=1C=CC(Br)=CC=1C(=O)CN1C(C)(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 GQRHZFVCOMJVOU-UHFFFAOYSA-N 0.000 claims description 2
- AOCMWFYPWGCXGQ-UHFFFAOYSA-N 1-[2-(3-fluorophenyl)-2-oxoethyl]-2,2-dimethyl-8-pyridin-4-yl-3,4-dihydropyrimido[1,2-a]pyrimidin-6-one Chemical compound C=1C=CC(F)=CC=1C(=O)CN1C(C)(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 AOCMWFYPWGCXGQ-UHFFFAOYSA-N 0.000 claims description 2
- AGNIHDIIYUFISY-UHFFFAOYSA-N 1-[2-(4-chlorophenyl)-2-oxoethyl]-2,2-dimethyl-7-pyridin-4-yl-3h-imidazo[1,2-a]pyrimidin-5-one Chemical compound C=1C=C(Cl)C=CC=1C(=O)CN1C(C)(C)CN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 AGNIHDIIYUFISY-UHFFFAOYSA-N 0.000 claims description 2
- DEHUABWNDZALHV-UHFFFAOYSA-N 1-[2-(4-fluorophenyl)-2-oxoethyl]-2,2-dimethyl-7-pyridin-4-yl-3h-imidazo[1,2-a]pyrimidin-5-one Chemical compound C=1C=C(F)C=CC=1C(=O)CN1C(C)(C)CN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 DEHUABWNDZALHV-UHFFFAOYSA-N 0.000 claims description 2
- DTHWETGQWDYWJS-UHFFFAOYSA-N 1-[3-(2-fluorophenyl)propyl]-2,2-dimethyl-7-pyridin-4-yl-3h-imidazo[1,2-a]pyrimidin-5-one Chemical compound C=1C=CC=C(F)C=1CCCN1C(C)(C)CN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 DTHWETGQWDYWJS-UHFFFAOYSA-N 0.000 claims description 2
- ZOCUUTDWFLKCDA-UHFFFAOYSA-N 2,2-dimethyl-1-(2-naphthalen-2-yl-2-oxoethyl)-7-pyridin-4-yl-3h-imidazo[1,2-a]pyrimidin-5-one Chemical compound C=1C=C2C=CC=CC2=CC=1C(=O)CN1C(C)(C)CN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 ZOCUUTDWFLKCDA-UHFFFAOYSA-N 0.000 claims description 2
- BDIWMRJHLMZART-KRWDZBQOSA-N 2,2-dimethyl-1-[(2r)-2-phenylpropyl]-8-pyridin-4-yl-3,4-dihydropyrimido[1,2-a]pyrimidin-6-one Chemical compound C([C@H](C)C=1C=CC=CC=1)N(C(CCN1C(=O)C=2)(C)C)C1=NC=2C1=CC=NC=C1 BDIWMRJHLMZART-KRWDZBQOSA-N 0.000 claims description 2
- TZJIBXFNUKACEO-UHFFFAOYSA-N 2,2-dimethyl-1-[2-(4-methylphenyl)-2-oxoethyl]-7-pyridin-4-yl-3h-imidazo[1,2-a]pyrimidin-5-one Chemical compound C1=CC(C)=CC=C1C(=O)CN1C(C)(C)CN2C(=O)C=C(C=3C=CN=CC=3)N=C21 TZJIBXFNUKACEO-UHFFFAOYSA-N 0.000 claims description 2
- FVMDCJODWAHQOT-UHFFFAOYSA-N 3-bromo-8-methyl-9-phenacyl-2-pyridin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C=CC=CC=1C(=O)CN1C(C)CCN(C(C=2Br)=O)C1=NC=2C1=CC=NC=C1 FVMDCJODWAHQOT-UHFFFAOYSA-N 0.000 claims description 2
- PWSHMWZAAFMHPL-UHFFFAOYSA-N 4-[2-(2,2-dimethyl-6-oxo-8-pyridin-4-yl-3,4-dihydropyrimido[1,2-a]pyrimidin-1-yl)-1-hydroxyethyl]benzonitrile Chemical compound C=1C=C(C#N)C=CC=1C(O)CN1C(C)(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 PWSHMWZAAFMHPL-UHFFFAOYSA-N 0.000 claims description 2
- XQHCHRASJUWYNZ-UHFFFAOYSA-N 8-ethyl-9-[2-hydroxy-2-(4-methylphenyl)ethyl]-2-pyridin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C=C(C)C=CC=1C(O)CN1C(CC)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 XQHCHRASJUWYNZ-UHFFFAOYSA-N 0.000 claims description 2
- AOOWJOHVPVTKOA-UHFFFAOYSA-N 8-methyl-9-(naphthalen-1-ylmethyl)-2-pyridin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C=CC2=CC=CC=C2C=1CN1C(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 AOOWJOHVPVTKOA-UHFFFAOYSA-N 0.000 claims description 2
- KPAHGNDTEMQJQV-UHFFFAOYSA-N 8-methyl-9-phenacyl-2-pyridin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C=CC=CC=1C(=O)CN1C(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 KPAHGNDTEMQJQV-UHFFFAOYSA-N 0.000 claims description 2
- PNCLYIAQLGQBKS-UHFFFAOYSA-N 9-[2-(1,3-benzodioxol-5-yl)-2-oxoethyl]-8-methyl-2-pyridin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C=C2OCOC2=CC=1C(=O)CN1C(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 PNCLYIAQLGQBKS-UHFFFAOYSA-N 0.000 claims description 2
- JXQWNGFKIGPCTI-UHFFFAOYSA-N 9-[2-(2,5-dimethoxyphenyl)ethyl]-8-methyl-2-pyridin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound COC1=CC=C(OC)C(CCN2C=3N(C(C=C(N=3)C=3C=CN=CC=3)=O)CCC2C)=C1 JXQWNGFKIGPCTI-UHFFFAOYSA-N 0.000 claims description 2
- BVHQAQWAFVJHAS-UHFFFAOYSA-N 9-[2-(2-methoxyphenyl)ethyl]-8-methyl-2-pyridin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound COC1=CC=CC=C1CCN1C2=NC(C=3C=CN=CC=3)=CC(=O)N2CCC1C BVHQAQWAFVJHAS-UHFFFAOYSA-N 0.000 claims description 2
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- FXABWOQPQRAQSK-UHFFFAOYSA-N 9-[2-(3-bromophenyl)-2-oxoethyl]-8-ethyl-2-pyridin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C=CC(Br)=CC=1C(=O)CN1C(CC)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 FXABWOQPQRAQSK-UHFFFAOYSA-N 0.000 claims description 2
- CONZPBCZGZXIPL-UHFFFAOYSA-N 9-[2-(3-chlorophenyl)-2-oxoethyl]-8-methyl-2-pyridin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C=CC(Cl)=CC=1C(=O)CN1C(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 CONZPBCZGZXIPL-UHFFFAOYSA-N 0.000 claims description 2
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- 125000001769 aryl amino group Chemical group 0.000 claims description 2
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- AHMTVEZDCPQIOF-LJQANCHMSA-N 1-[(2s)-2-(4-chlorophenyl)-2-hydroxyethyl]-2,2-dimethyl-8-pyridin-4-yl-3,4-dihydropyrimido[1,2-a]pyrimidin-6-one Chemical compound C([C@@H](O)C=1C=CC(Cl)=CC=1)N1C(C)(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 AHMTVEZDCPQIOF-LJQANCHMSA-N 0.000 claims 1
- QYBOQUKCLGAHOV-RUZDIDTESA-N 1-[(2s)-2-hydroxy-2-(4-phenylphenyl)ethyl]-2,2-dimethyl-8-pyridin-4-yl-3,4-dihydropyrimido[1,2-a]pyrimidin-6-one Chemical compound C([C@@H](O)C=1C=CC(=CC=1)C=1C=CC=CC=1)N1C(C)(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 QYBOQUKCLGAHOV-RUZDIDTESA-N 0.000 claims 1
- AZPXHIKRAWMQPU-UHFFFAOYSA-N 1-[2-(3,4-dichlorophenyl)-2-hydroxyethyl]-2,2-dimethyl-8-pyridin-4-yl-3,4-dihydropyrimido[1,2-a]pyrimidin-6-one Chemical compound C=1C=C(Cl)C(Cl)=CC=1C(O)CN1C(C)(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 AZPXHIKRAWMQPU-UHFFFAOYSA-N 0.000 claims 1
- RWDKFQPGXYHJQT-UHFFFAOYSA-N 1-[2-(3-methoxyphenyl)-2-oxoethyl]-2,2-dimethyl-7-pyridin-4-yl-3h-imidazo[1,2-a]pyrimidin-5-one Chemical compound COC1=CC=CC(C(=O)CN2C(CN3C(=O)C=C(N=C32)C=2C=CN=CC=2)(C)C)=C1 RWDKFQPGXYHJQT-UHFFFAOYSA-N 0.000 claims 1
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- 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
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
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- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
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- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
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- 235000003270 potassium fluoride Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
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- 230000000861 pro-apoptotic effect Effects 0.000 description 1
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- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
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- 125000006308 propyl amino group Chemical group 0.000 description 1
- 230000026938 proteasomal ubiquitin-dependent protein catabolic process Effects 0.000 description 1
- RVQZKNOMKUSGCI-UHFFFAOYSA-N pyridine-4-carbonyl chloride Chemical compound ClC(=O)C1=CC=NC=C1 RVQZKNOMKUSGCI-UHFFFAOYSA-N 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 125000005920 sec-butoxy group Chemical group 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000013207 serial dilution Methods 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
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- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
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- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
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- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 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
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 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 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 238000010798 ubiquitination Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
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Classifications
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- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/44—Radicals substituted by doubly-bound oxygen, sulfur, or nitrogen atoms, or by two such atoms singly-bound to the same carbon atom
- C07D213/46—Oxygen atoms
- C07D213/50—Ketonic radicals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP01402432A EP1295885A1 (en) | 2001-09-21 | 2001-09-21 | Substituted 2-pyridinyl-6,7,8,9-tetrahydropyrimido(1,2-a)pyrimidin-4-one and 7-pyridinyl-2,3-dihydroimidazo(1,2-a)pyrimidin-5(1H)one derivatives |
| EP02290489A EP1340761A1 (en) | 2002-02-28 | 2002-02-28 | Substituted 2-pyridinyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-one and 7-pyridinyl-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)one derivatives |
| PCT/EP2002/011128 WO2003027116A2 (en) | 2001-09-21 | 2002-09-19 | Substituted 2-pyridinyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-one and 7-pyridinyl-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1h)one derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NO20041141L NO20041141L (no) | 2004-06-21 |
| NO329565B1 true NO329565B1 (no) | 2010-11-15 |
Family
ID=26077256
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO20041141A NO329565B1 (no) | 2001-09-21 | 2004-03-18 | Substituerte 2-pyridinyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-on og 7-pyridinyl-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)on-derivater, anvendelser av slike derivater, og legemidler og inhibitorer omfattende slike derivater |
Country Status (25)
| Country | Link |
|---|---|
| US (2) | US7214682B2 (es) |
| EP (2) | EP1674456B1 (es) |
| JP (3) | JP4570362B2 (es) |
| KR (1) | KR100868841B1 (es) |
| CN (2) | CN100398541C (es) |
| AR (1) | AR036600A1 (es) |
| AT (2) | ATE303388T1 (es) |
| AU (1) | AU2002350487C1 (es) |
| BR (1) | BR0212896A (es) |
| CA (1) | CA2457965C (es) |
| CY (1) | CY1108341T1 (es) |
| DE (2) | DE60205921T2 (es) |
| DK (2) | DK1430057T3 (es) |
| EA (1) | EA006859B1 (es) |
| ES (2) | ES2247398T3 (es) |
| HK (1) | HK1091208A1 (es) |
| HU (1) | HUP0500328A3 (es) |
| IL (2) | IL160402A0 (es) |
| MX (1) | MXPA04002629A (es) |
| NO (1) | NO329565B1 (es) |
| NZ (2) | NZ531243A (es) |
| PL (1) | PL370349A1 (es) |
| PT (1) | PT1674456E (es) |
| SI (1) | SI1430057T1 (es) |
| WO (1) | WO2003027116A2 (es) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK1430057T3 (da) * | 2001-09-21 | 2006-01-16 | Sanofi Aventis | Substituerede 2-pyridinyl-6,7,8, 9-tetrahydropyrimido [1,2-a] pyrimidin-4-on- og 7-pyridinyl-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)onderivater |
| TWI335221B (en) | 2001-09-27 | 2011-01-01 | Alcon Inc | Inhibtors of glycogen synthase kinase-3 (gsk-3) for treating glaucoma |
| EP1454900A1 (en) | 2003-03-07 | 2004-09-08 | Sanofi-Synthelabo | Process for the preparation of pyridinyl and pyrimidinyl mono-fluorinated beta keto-esters |
| EP1454909B1 (en) * | 2003-03-07 | 2008-08-20 | Sanofi Aventis | 8'-pyridinyl-dihydrospiro (cycloalkyl) -pyrimido (1,2-a) pyrimidin-6-one and 8'-pyrimidinyl-dihydrospiro (cycloalkyl) pyrimido (1,2-a) pyrimidin-6 derivatives -one and their use against neurodegenerative diseases |
| EP1557417B1 (en) * | 2003-12-19 | 2007-03-07 | Sanofi-Aventis | Substituted 8'-pyri(mi)dinyl-dihydrospiro-[cycloalkylamine]-pyrimido[1,2-a] pyrimidin-6-one derivatives |
| ATE393157T1 (de) | 2004-01-22 | 2008-05-15 | Amgen Inc | Substituierte heterocyclische verbindungen und anwendungsverfahren |
| EP2258358A3 (en) | 2005-08-26 | 2011-09-07 | Braincells, Inc. | Neurogenesis with acetylcholinesterase inhibitor |
| CA2620333A1 (en) | 2005-08-26 | 2007-03-01 | Braincells, Inc. | Neurogenesis by muscarinic receptor modulation |
| EP1940389A2 (en) | 2005-10-21 | 2008-07-09 | Braincells, Inc. | Modulation of neurogenesis by pde inhibition |
| WO2007053596A1 (en) | 2005-10-31 | 2007-05-10 | Braincells, Inc. | Gaba receptor mediated modulation of neurogenesis |
| US20100216734A1 (en) | 2006-03-08 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis by nootropic agents |
| CA2651813A1 (en) | 2006-05-09 | 2007-11-22 | Braincells, Inc. | Neurogenesis by modulating angiotensin |
| US20100184806A1 (en) | 2006-09-19 | 2010-07-22 | Braincells, Inc. | Modulation of neurogenesis by ppar agents |
| CN101735211B (zh) * | 2008-11-04 | 2012-11-14 | 复旦大学 | 2,3-二氢[1,5]苯并噻氮杂*类化合物或其盐在制备GSK-3β抑制剂中的用途 |
| US20100216805A1 (en) | 2009-02-25 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis using d-cycloserine combinations |
| FR2947551B1 (fr) * | 2009-07-02 | 2012-05-18 | Sanofi Aventis | Nouveaux derives de 1,2,3,4-tetrahydro-pyrimido{1,2-a)pyrimidin-6-one, leur preparation et leur utilisation pharmaceutique comme inhibiteurs de phosphorylation d'akt (pkb) |
| AR077363A1 (es) * | 2009-07-02 | 2011-08-24 | Sanofi Aventis | DERIVADOS DE 1,2,3,4- TETRAHIDRO-PIRIMIDO{1,2-A} PIRIMIDIN-6-ONA, SU PREPARACIoN, SU UTILIZACIoN EN QUIMIOTERAPIA Y SUS COMPOSICIONES FARMACEUTICAS. |
| FR2947550B1 (fr) * | 2009-07-02 | 2012-05-18 | Sanofi Aventis | Nouveaux derives de 2,3-dihydro-1h-imidazo{1,2-a}pyrimidin-5-one, leur preparation et leur utilisation pharmaceutique comme inhibiteurs de phosphorylation d'akt (pkb) |
| HUE034503T2 (en) | 2009-07-02 | 2018-02-28 | Sanofi Sa | 2,3-Dihydro-1-imidazo [1,2-a] pyrimidin-5-one derivatives, their preparation process and their use in medicine |
| EP2655375B1 (fr) * | 2010-12-23 | 2014-12-03 | Sanofi | Derives de pyrimidinone, leur preparation et leur utilisation pharmaceutique |
| FR2992314B1 (fr) | 2012-06-22 | 2015-10-16 | Sanofi Sa | Nouveaux derives de 2,3-dihydro-1h-imidazo{1,2-a}pyrimidin-5-one et 1,2,3,4-tetrahydro-pyrimido{1,2-a}pyrimidin-6-one comportant une morpholine substituee, leur preparation et leur utilisation pharmaceutique |
| CA2945263A1 (en) | 2014-04-09 | 2015-10-15 | Christopher Rudd | Use of gsk-3 inhibitors or activators which modulate pd-1 or t-bet expression to modulate t cell immunity |
| CN109836427B (zh) * | 2017-11-29 | 2022-04-15 | 暨南大学 | 嘧啶并嘧啶酮类化合物及其应用 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1998016528A1 (en) * | 1996-10-11 | 1998-04-23 | Chiron Corporation | Purine inhibitors of glycogen synthase kinase 3 (gsk3) |
| WO1998024780A2 (en) * | 1996-12-05 | 1998-06-11 | Amgen Inc. | Substituted pyrimidinone and pyridinone compounds and their use |
| DE69919707T2 (de) | 1998-06-19 | 2005-09-01 | Chiron Corp., Emeryville | Glycogen synthase kinase 3 inhibitoren |
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| JP2000264888A (ja) * | 1999-01-11 | 2000-09-26 | Sagami Chem Res Center | 双環性ピリミジン誘導体、それらの製造中間体及びそれらの製造方法、並びにそれらを有効成分とする除草剤 |
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| DK1430057T3 (da) * | 2001-09-21 | 2006-01-16 | Sanofi Aventis | Substituerede 2-pyridinyl-6,7,8, 9-tetrahydropyrimido [1,2-a] pyrimidin-4-on- og 7-pyridinyl-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)onderivater |
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