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 PDF

Info

Publication number: NO329565B1
Authority: NO; Norway
Prior art keywords: pyridin; pyrimidin; pyrimido; tetrahydro; dimethyl
Prior art date: 2001-09-21

Application number

NO20041141A

Other languages

English (en)

Norwegian (no)

Other versions

NO20041141L (no

Inventor

Patrick Lardenois

Alain Nedelec

Thierry Gallet

Alistair Lochead

Severin Marguerie

Mourad Saady

Franck Slowinski

Philippe Yaiche

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

2004-03-18

Publication date

2010-11-15

2001-09-21 Priority claimed from EP01402432A external-priority patent/EP1295885A1/de

2002-02-28 Priority claimed from EP02290489A external-priority patent/EP1340761A1/de

2004-03-18 Application filed by Mitsubishi Pharma Corp filed Critical Mitsubishi Pharma Corp

2004-06-21 Publication of NO20041141L publication Critical patent/NO20041141L/no

2010-11-15 Publication of NO329565B1 publication Critical patent/NO329565B1/no

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
208000018737 Parkinson disease Diseases 0.000 claims description 6
125000003277 amino group Chemical group 0.000 claims description 6
206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 6
201000011510 cancer Diseases 0.000 claims description 6
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
201000004384 Alopecia Diseases 0.000 claims description 5
208000010412 Glaucoma Diseases 0.000 claims description 5
208000008589 Obesity Diseases 0.000 claims description 5
206010038923 Retinopathy Diseases 0.000 claims description 5
208000006011 Stroke Diseases 0.000 claims description 5
201000004810 Vascular dementia Diseases 0.000 claims description 5
231100000360 alopecia Toxicity 0.000 claims description 5
208000028683 bipolar I disease Diseases 0.000 claims description 5
230000007213 cerebrovascular event Effects 0.000 claims description 5
206010015037 epilepsy Diseases 0.000 claims description 5
235000020824 obesity Nutrition 0.000 claims description 5
208000027232 peripheral nervous system disease Diseases 0.000 claims description 5
208000033808 peripheral neuropathy Diseases 0.000 claims description 5
201000000980 schizophrenia Diseases 0.000 claims description 5
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
206010006187 Breast cancer Diseases 0.000 claims description 4
208000026310 Breast neoplasm Diseases 0.000 claims description 4
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
KIUILNWIRAXKSO-UHFFFAOYSA-N 9-[2-(3,5-dichlorophenyl)-2-hydroxyethyl]-8-methyl-2-pyridin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C(Cl)=CC(Cl)=CC=1C(O)CN1C(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 KIUILNWIRAXKSO-UHFFFAOYSA-N 0.000 claims description 2
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
LXKIDCIONDUINK-UHFFFAOYSA-N 9-[2-(3-methoxyphenyl)-2-oxoethyl]-8-methyl-2-pyridin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound COC1=CC=CC(C(=O)CN2C=3N(C(C=C(N=3)C=3C=CN=CC=3)=O)CCC2C)=C1 LXKIDCIONDUINK-UHFFFAOYSA-N 0.000 claims description 2
ZOPKXRZJCFVKND-UHFFFAOYSA-N 9-[2-(4-fluorophenyl)ethyl]-8-methyl-2-pyridin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C=C(F)C=CC=1CCN1C(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 ZOPKXRZJCFVKND-UHFFFAOYSA-N 0.000 claims description 2
125000001769 aryl amino group Chemical group 0.000 claims description 2
125000004093 cyano group Chemical group *C#N 0.000 claims description 2
PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical group C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 claims description 2
229940126601 medicinal product Drugs 0.000 claims description 2
125000001424 substituent group Chemical group 0.000 claims description 2
CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical group C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 claims description 2
GLMIQONSAMBPKR-LJQANCHMSA-N 1-[(2s)-2-(3-bromophenyl)-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(Br)C=CC=1)N1C(C)(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 GLMIQONSAMBPKR-LJQANCHMSA-N 0.000 claims 1
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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125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
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
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
239000003765 sweetening agent Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
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
239000008158 vegetable oil Substances 0.000 description 1
239000000080 wetting agent Substances 0.000 description 1

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- 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
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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

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NO20041141A 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 NO329565B1 (no)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
EP01402432A EP1295885A1 (de)	2001-09-21	2001-09-21	Substituierte 2-pyridinyl-6,7,8,9-tetrahydropyrimido(1,2-a)pyrimidin-4-on- und 7-pyridinyl-2,3-dihydroimidazo(1,2-a)pyrimidin-5(1H)onderivate
EP02290489A EP1340761A1 (de)	2002-02-28	2002-02-28	Substituierte 2-Pyridinyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-on und 7-Pyridinyl-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)onderivate
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

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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 (24)

Country	Link
US (2)	US7214682B2 (de)
EP (2)	EP1674456B1 (de)
JP (3)	JP4570362B2 (de)
KR (1)	KR100868841B1 (de)
CN (2)	CN1247585C (de)
AR (1)	AR036600A1 (de)
AT (2)	ATE401309T1 (de)
AU (1)	AU2002350487C1 (de)
BR (1)	BR0212896A (de)
CA (1)	CA2457965C (de)
CY (1)	CY1108341T1 (de)
DE (2)	DE60227718D1 (de)
DK (2)	DK1430057T3 (de)
EA (1)	EA006859B1 (de)
ES (2)	ES2310787T3 (de)
HU (1)	HUP0500328A3 (de)
IL (2)	IL160402A0 (de)
MX (1)	MXPA04002629A (de)
NO (1)	NO329565B1 (de)
NZ (2)	NZ547205A (de)
PL (1)	PL370349A1 (de)
PT (1)	PT1674456E (de)
SI (1)	SI1430057T1 (de)
WO (1)	WO2003027116A2 (de)

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TWI335221B (en)	2001-09-27	2011-01-01	Alcon Inc	Inhibtors of glycogen synthase kinase-3 (gsk-3) for treating glaucoma
EP1454909B1 (de) *	2003-03-07	2008-08-20	Sanofi Aventis	8'-pyridinyl-dihydrospiro-(cycloalkyl)-pyrimido(1,2-a) pyrimidin-6-one und 8'-pyrimidinyl-dihydrospiro-(cycloalkyl)-pyrimido(1,2-a)pyrimidin-6-one Derivate und deren Benutzung gegen neurodegenerative Krankheiten
EP1454900A1 (de)	2003-03-07	2004-09-08	Sanofi-Synthelabo	Verfahren zur herstellung von pyridinyl und pyrimidinyl mono-fluorierten beta-keto Estern
EP1557417B1 (de) *	2003-12-19	2007-03-07	Sanofi-Aventis	Substituierte 8'-pyri(mi)dinyl-dihydrospiro-[cycloalkylamine]-pyrimido[1,2-a]pyrimidin-6-one Derivate
US7504403B2 (en)	2004-01-22	2009-03-17	Amgen Inc.	Substituted heterocyclic compounds and methods of use
EP2258359A3 (de)	2005-08-26	2011-04-06	Braincells, Inc.	Neurogenese durch Modulation des Muscarinrezeptors mit Sabcomelin
JP2009506069A (ja)	2005-08-26	2009-02-12	ブレインセルス，インコーポレイティド	ムスカリン性受容体調節による神経発生
US7985756B2 (en)	2005-10-21	2011-07-26	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
WO2007134136A2 (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
WO2010099217A1 (en)	2009-02-25	2010-09-02	Braincells, Inc.	Modulation of neurogenesis using d-cycloserine combinations
MX2012000103A (es) *	2009-07-02	2012-05-22	Sanofi Sa	Nuevos derivados de 1,2,3,4-tetrahidro-pirimido (1,2-a) pirimidin-6-ona, su preparacion y su uso farmaceutica.
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)
ES2627428T3 (es) *	2009-07-02	2017-07-28	Sanofi	Nuevos derivados de 2,3-dihidro-1H-imidazo{1,2-a}pirimidin-5-ona, su preparación y su utilización farmacéutica
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)
US8815853B2 (en)	2010-12-23	2014-08-26	Sanofi	Pyrimidinone derivatives, preparation thereof and pharmaceutical use thereof
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
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CN100335479C (zh) *	1999-12-17	2007-09-05	希龙公司	糖元合成酶激酶3的双环抑制剂
AU1224902A (en) *	2000-09-01	2002-03-13	Sanofi Synthelabo	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
NZ547205A (en) *	2001-09-21	2007-11-30	Sanofi Aventis	Intermediates of 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

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Also Published As

Publication number	Publication date
KR20040029486A (ko)	2004-04-06
DK1674456T3 (da)	2008-10-27
JP4570362B2 (ja)	2010-10-27
ATE401309T1 (de)	2008-08-15
ES2310787T3 (es)	2009-01-16
PL370349A1 (en)	2005-05-16
EA200400237A1 (ru)	2004-10-28
ATE303388T1 (de)	2005-09-15
AU2002350487C1 (en)	2008-10-02
EP1674456B1 (de)	2008-07-16
HUP0500328A3 (en)	2009-12-28
DE60205921T2 (de)	2006-06-22
AU2002350487B2 (en)	2008-01-31
EP1430057A2 (de)	2004-06-23
IL160402A0 (en)	2004-07-25
MXPA04002629A (es)	2005-02-17
HK1091208A1 (zh)	2007-01-12
HUP0500328A2 (hu)	2005-07-28
SI1430057T1 (sl)	2006-02-28
KR100868841B1 (ko)	2008-11-14
AR036600A1 (es)	2004-09-22
WO2003027116A3 (en)	2003-08-28
BR0212896A (pt)	2004-10-13
JP2010159303A (ja)	2010-07-22
EP1674456A2 (de)	2006-06-28
CN100398541C (zh)	2008-07-02
JP2005504810A (ja)	2005-02-17
EA006859B1 (ru)	2006-04-28
EP1430057B1 (de)	2005-08-31
EP1674456A3 (de)	2006-07-05
US20050049261A1 (en)	2005-03-03
CA2457965A1 (en)	2003-04-03
CA2457965C (en)	2010-06-01
US7214682B2 (en)	2007-05-08
NZ531243A (en)	2006-08-31
CN1817884A (zh)	2006-08-16
CN1247585C (zh)	2006-03-29
US20070167461A1 (en)	2007-07-19
DE60205921D1 (de)	2005-10-06
IL160402A (en)	2008-08-07
JP2010209089A (ja)	2010-09-24
US7462621B2 (en)	2008-12-09
NZ547205A (en)	2007-11-30
DE60227718D1 (de)	2008-08-28
NO20041141L (no)	2004-06-21
DK1430057T3 (da)	2006-01-16
ES2247398T3 (es)	2006-03-01
PT1674456E (pt)	2008-09-11
WO2003027116A2 (en)	2003-04-03
CY1108341T1 (el)	2014-02-12
CN1556809A (zh)	2004-12-22

Legal Events

Date	Code	Title	Description
2013-04-22	MM1K	Lapsed by not paying the annual fees

Publication	Publication Date	Title
US7462621B2 (en)	2008-12-09	Use of 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 as therapeutic agents
US7781440B2 (en)	2010-08-24	Use of substituted 2-pyrimidinyl-6,7,8,9-tetrahydropyrimido[1,2-a] pyrimidin-4-one and 7-pyrimidinyl-2,3-dihydroimidazo[1,2-a] pyrimidin-5(1H)one derivatives
US7465737B2 (en)	2008-12-16	Heteroaryl substituted 2-pyridinyl and 2-pyrimidinyl -6,7,8,9-tetrahydropyrimido[1,2-a] pyrimidin-4-one derivatives
AU2002350487A1 (en)	2003-06-26	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
EP1295885A1 (de)	2003-03-26	Substituierte 2-pyridinyl-6,7,8,9-tetrahydropyrimido(1,2-a)pyrimidin-4-on- und 7-pyridinyl-2,3-dihydroimidazo(1,2-a)pyrimidin-5(1H)onderivate
EP1295884A1 (de)	2003-03-26	2-Pyrimidinyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-on and 7-Pyrimidinyl-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)on Derivate
NO329756B1 (no)	2010-12-13	Imidazo[1,2-a]pyrimidonderivat, anvendelser derav,legemiddel og GSK3beta-inhibitor
EP1340761A1 (de)	2003-09-03	Substituierte 2-Pyridinyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-on und 7-Pyridinyl-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)onderivate
EP1340760A1 (de)	2003-09-03	Substituierte 2-Pyrimidinyl-6,7,8,9-tetrahydro[1,2-a]pyrimidin-4-on und 7-Pyrimidinyl-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)onderivate
HK1091208B (en)	2009-02-13	Pyrimidinone derivatives and 3-ketoester