NO329566B1 - Subsitituerte 2-pyrimidinyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-on og 7-pyrimidinyl-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)on-derivater for nevrodegenerative lidelser, anvendelser av slike derivater, og legemidler og inhibitorer omfattende slike derivater - Google Patents
Subsitituerte 2-pyrimidinyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-on og 7-pyrimidinyl-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)on-derivater for nevrodegenerative lidelser, anvendelser av slike derivater, og legemidler og inhibitorer omfattende slike derivater Download PDFInfo
- Publication number
- NO329566B1 NO329566B1 NO20041142A NO20041142A NO329566B1 NO 329566 B1 NO329566 B1 NO 329566B1 NO 20041142 A NO20041142 A NO 20041142A NO 20041142 A NO20041142 A NO 20041142A NO 329566 B1 NO329566 B1 NO 329566B1
- Authority
- NO
- Norway
- Prior art keywords
- pyrimidin
- dimethyl
- tetrahydropyrimido
- ethyl
- tetrahydro
- Prior art date
Links
- 239000003814 drug Substances 0.000 title claims description 28
- 229940079593 drug Drugs 0.000 title claims description 25
- 208000015122 neurodegenerative disease Diseases 0.000 title claims description 16
- 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 description 2
- JOQYRATWFVJNPN-UHFFFAOYSA-N 2-pyrimidin-2-yl-1,6,7,8-tetrahydropyrimido[1,2-a]pyrimidin-4-one Chemical class N1=C2NCCCN2C(=O)C=C1C1=NC=CC=N1 JOQYRATWFVJNPN-UHFFFAOYSA-N 0.000 title 1
- DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 claims description 77
- 150000003839 salts Chemical class 0.000 claims description 36
- 101150053721 Cdk5 gene Proteins 0.000 claims description 35
- 150000008318 pyrimidones Chemical class 0.000 claims description 24
- 230000000694 effects Effects 0.000 claims description 19
- 239000004480 active ingredient Substances 0.000 claims description 18
- 201000010099 disease Diseases 0.000 claims description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 17
- 230000003449 preventive effect Effects 0.000 claims description 17
- 230000004770 neurodegeneration Effects 0.000 claims description 16
- 230000001225 therapeutic effect Effects 0.000 claims description 16
- 239000012453 solvate Substances 0.000 claims description 15
- 239000000126 substance Substances 0.000 claims description 14
- 230000002159 abnormal effect Effects 0.000 claims description 13
- 208000024827 Alzheimer disease Diseases 0.000 claims description 12
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
- -1 methylenedioxy group Chemical group 0.000 claims description 12
- 125000005843 halogen group Chemical group 0.000 claims description 11
- 206010028980 Neoplasm Diseases 0.000 claims description 10
- 208000014674 injury Diseases 0.000 claims description 10
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 208000034799 Tauopathies Diseases 0.000 claims description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 7
- 208000018737 Parkinson disease Diseases 0.000 claims description 6
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 6
- 201000011510 cancer Diseases 0.000 claims description 6
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 6
- 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
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 5
- 230000007213 cerebrovascular event Effects 0.000 claims description 5
- 206010015037 epilepsy Diseases 0.000 claims description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 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
- ISCAYZWVXZIATE-UHFFFAOYSA-N 9-[2-(1,3-benzodioxol-5-yl)-2-hydroxypropyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C=C2OCOC2=CC=1C(O)(C)CN1CC(C)(C)CN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 ISCAYZWVXZIATE-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
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 125000004434 sulfur atom Chemical group 0.000 claims description 4
- 201000002510 thyroid cancer Diseases 0.000 claims description 4
- JXTLMBKDSODFPI-GOSISDBHSA-N 1-[(2s)-2-(4-fluorophenyl)-2-hydroxyethyl]-2,2-dimethyl-8-pyrimidin-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=N1 JXTLMBKDSODFPI-GOSISDBHSA-N 0.000 claims description 3
- UPABIKMQIWDQRX-OAHLLOKOSA-N 3-chloro-9-[(2s)-2-hydroxy-2-phenylethyl]-2-pyrimidin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C([C@@H](O)C=1C=CC=CC=1)N1CCCN(C(C=2Cl)=O)C1=NC=2C1=CC=NC=N1 UPABIKMQIWDQRX-OAHLLOKOSA-N 0.000 claims description 3
- HHRCYLBOIIEQND-UHFFFAOYSA-N 7,7-difluoro-9-phenacyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(C=3N=CN=CC=3)=CC(=O)N2CC(F)(F)CN1CC(=O)C1=CC=CC=C1 HHRCYLBOIIEQND-UHFFFAOYSA-N 0.000 claims description 3
- RSSUFAPBPBUNGT-UHFFFAOYSA-N 8-ethyl-9-phenacyl-2-pyrimidin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C=CC=CC=1C(=O)CN1C(CC)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 RSSUFAPBPBUNGT-UHFFFAOYSA-N 0.000 claims description 3
- VSTSQEQSVVIOFG-GOSISDBHSA-N 9-[(2s)-2-hydroxy-2-phenylethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C1([C@H](O)CN2CC(CN3C(=O)C=C(N=C32)C=2N=CN=CC=2)(C)C)=CC=CC=C1 VSTSQEQSVVIOFG-GOSISDBHSA-N 0.000 claims description 3
- GDMHYIGDBVTRGJ-UHFFFAOYSA-N 9-[2-(4-fluoro-2-methoxyphenyl)ethyl]-8-methyl-2-pyrimidin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound COC1=CC(F)=CC=C1CCN1C2=NC(C=3N=CN=CC=3)=CC(=O)N2CCC1C GDMHYIGDBVTRGJ-UHFFFAOYSA-N 0.000 claims description 3
- 229940126601 medicinal product Drugs 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical group C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 claims description 3
- AXHBGCGWHQUDHP-UHFFFAOYSA-N 1-(2-hydroxy-2-phenylethyl)-7-pyrimidin-4-yl-2,3-dihydroimidazo[1,2-a]pyrimidin-5-one Chemical compound C=1C=CC=CC=1C(O)CN1CCN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 AXHBGCGWHQUDHP-UHFFFAOYSA-N 0.000 claims description 2
- CUNCRFJPZHRDAI-UHFFFAOYSA-N 1-(3-phenylpropyl)-7-pyrimidin-4-yl-2,3-dihydroimidazo[1,2-a]pyrimidin-5-one Chemical compound C1CN2C(=O)C=C(C=3N=CN=CC=3)N=C2N1CCCC1=CC=CC=C1 CUNCRFJPZHRDAI-UHFFFAOYSA-N 0.000 claims description 2
- MTEGVLTYGHZTFA-SFHVURJKSA-N 1-[(2r)-2-hydroxy-2-phenylethyl]-2,2-dimethyl-8-pyrimidin-4-yl-3,4-dihydropyrimido[1,2-a]pyrimidin-6-one Chemical compound C([C@H](O)C=1C=CC=CC=1)N1C(C)(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 MTEGVLTYGHZTFA-SFHVURJKSA-N 0.000 claims description 2
- OASZKWJIZANUOC-GOSISDBHSA-N 1-[(2s)-2-(4-chlorophenyl)-2-hydroxyethyl]-2,2-dimethyl-8-pyrimidin-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=N1 OASZKWJIZANUOC-GOSISDBHSA-N 0.000 claims description 2
- QSVCNQIOSOBPKJ-LJQANCHMSA-N 1-[(2s)-2-hydroxy-2-(3-methoxyphenyl)ethyl]-2,2-dimethyl-8-pyrimidin-4-yl-3,4-dihydropyrimido[1,2-a]pyrimidin-6-one Chemical compound COC1=CC=CC([C@H](O)CN2C(CCN3C(=O)C=C(N=C32)C=2N=CN=CC=2)(C)C)=C1 QSVCNQIOSOBPKJ-LJQANCHMSA-N 0.000 claims description 2
- OYOBATCURUPFTQ-XMMPIXPASA-N 1-[(2s)-2-hydroxy-2-(4-phenylphenyl)ethyl]-2,2-dimethyl-8-pyrimidin-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=N1 OYOBATCURUPFTQ-XMMPIXPASA-N 0.000 claims description 2
- MTEGVLTYGHZTFA-GOSISDBHSA-N 1-[(2s)-2-hydroxy-2-phenylethyl]-2,2-dimethyl-8-pyrimidin-4-yl-3,4-dihydropyrimido[1,2-a]pyrimidin-6-one Chemical compound C([C@@H](O)C=1C=CC=CC=1)N1C(C)(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 MTEGVLTYGHZTFA-GOSISDBHSA-N 0.000 claims description 2
- RYRSMJYUGPHPHJ-UHFFFAOYSA-N 1-[1-(7-methoxy-1,3-benzodioxol-5-yl)-1-oxopropan-2-yl]-2,2-dimethyl-7-pyrimidin-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=N1 RYRSMJYUGPHPHJ-UHFFFAOYSA-N 0.000 claims description 2
- SHYKKMHZWRIVGQ-UHFFFAOYSA-N 1-[2-(2,5-dimethoxyphenyl)-2-oxoethyl]-2,2-dimethyl-8-pyrimidin-4-yl-3,4-dihydropyrimido[1,2-a]pyrimidin-6-one Chemical compound COC1=CC=C(OC)C(C(=O)CN2C(CCN3C(=O)C=C(N=C32)C=2N=CN=CC=2)(C)C)=C1 SHYKKMHZWRIVGQ-UHFFFAOYSA-N 0.000 claims description 2
- SBEFMIIFRAMMBX-UHFFFAOYSA-N 1-[2-(2,5-dimethoxyphenyl)ethyl]-2,2-dimethyl-8-pyrimidin-4-yl-3,4-dihydropyrimido[1,2-a]pyrimidin-6-one Chemical compound COC1=CC=C(OC)C(CCN2C(CCN3C(=O)C=C(N=C32)C=2N=CN=CC=2)(C)C)=C1 SBEFMIIFRAMMBX-UHFFFAOYSA-N 0.000 claims description 2
- LNIBLCFLZBCHCD-UHFFFAOYSA-N 1-[2-(3-bromophenyl)-2-oxoethyl]-2,2-dimethyl-8-pyrimidin-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=N1 LNIBLCFLZBCHCD-UHFFFAOYSA-N 0.000 claims description 2
- MQLUOXJDZPMJKY-UHFFFAOYSA-N 1-[2-(3-fluorophenyl)-2-oxoethyl]-2,2-dimethyl-8-pyrimidin-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=N1 MQLUOXJDZPMJKY-UHFFFAOYSA-N 0.000 claims description 2
- XRIALZKEPHNILZ-UHFFFAOYSA-N 1-[2-(3-methoxyphenyl)-2-oxoethyl]-2,2-dimethyl-7-pyrimidin-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=2N=CN=CC=2)(C)C)=C1 XRIALZKEPHNILZ-UHFFFAOYSA-N 0.000 claims description 2
- DEHJEJDOMUCLTL-UHFFFAOYSA-N 1-[2-(4-fluorophenyl)-2-oxoethyl]-2,2-dimethyl-8-pyrimidin-4-yl-3,4-dihydropyrimido[1,2-a]pyrimidin-6-one Chemical compound C=1C=C(F)C=CC=1C(=O)CN1C(C)(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 DEHJEJDOMUCLTL-UHFFFAOYSA-N 0.000 claims description 2
- UAWXTXTYLDSPNE-UHFFFAOYSA-N 1-[2-(4-fluorophenyl)ethyl]-2,2-dimethyl-8-pyrimidin-4-yl-3,4-dihydropyrimido[1,2-a]pyrimidin-6-one Chemical compound C=1C=C(F)C=CC=1CCN1C(C)(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 UAWXTXTYLDSPNE-UHFFFAOYSA-N 0.000 claims description 2
- HWIFLBROPOSOCD-UHFFFAOYSA-N 1-phenacyl-7-pyrimidin-4-yl-2,3-dihydroimidazo[1,2-a]pyrimidin-5-one Chemical compound C=1C=CC=CC=1C(=O)CN1CCN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 HWIFLBROPOSOCD-UHFFFAOYSA-N 0.000 claims description 2
- NTHLTKWFKAWZAQ-UHFFFAOYSA-N 2,2-dimethyl-1-(2-naphthalen-2-yl-2-oxoethyl)-7-pyrimidin-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=N1 NTHLTKWFKAWZAQ-UHFFFAOYSA-N 0.000 claims description 2
- MSYZGARDEOLCLA-UHFFFAOYSA-N 2,2-dimethyl-1-(2-naphthalen-2-yl-2-oxoethyl)-8-pyrimidin-4-yl-3,4-dihydropyrimido[1,2-a]pyrimidin-6-one Chemical compound C=1C=C2C=CC=CC2=CC=1C(=O)CN1C(C)(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 MSYZGARDEOLCLA-UHFFFAOYSA-N 0.000 claims description 2
- MOYSCQHVNAMLKL-UHFFFAOYSA-N 2,2-dimethyl-1-[2-oxo-2-(4-phenylphenyl)ethyl]-7-pyrimidin-4-yl-3h-imidazo[1,2-a]pyrimidin-5-one Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1C(=O)CN1C(C)(C)CN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 MOYSCQHVNAMLKL-UHFFFAOYSA-N 0.000 claims description 2
- WPHRFOFOLSSKQC-UHFFFAOYSA-N 3-bromo-8-methyl-9-phenacyl-2-pyrimidin-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=N1 WPHRFOFOLSSKQC-UHFFFAOYSA-N 0.000 claims description 2
- FGBZFHGGVJSDQC-UHFFFAOYSA-N 4-[2-(7,7-dimethyl-4-oxo-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-9-yl)ethyl]benzonitrile Chemical compound C12=NC(C=3N=CN=CC=3)=CC(=O)N2CC(C)(C)CN1CCC1=CC=C(C#N)C=C1 FGBZFHGGVJSDQC-UHFFFAOYSA-N 0.000 claims description 2
- UEXSCECVRXZVSG-UHFFFAOYSA-N 7,7-dimethyl-2-pyrimidin-4-yl-9-[2-[2-(trifluoromethyl)phenyl]ethyl]-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(C=3N=CN=CC=3)=CC(=O)N2CC(C)(C)CN1CCC1=CC=CC=C1C(F)(F)F UEXSCECVRXZVSG-UHFFFAOYSA-N 0.000 claims description 2
- RGZZUWVSTHRKAO-UHFFFAOYSA-N 7,7-dimethyl-9-(2-naphthalen-1-ylethyl)-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C(=O)N2CC(C)(C)CN(CCC=3C4=CC=CC=C4C=CC=3)C2=NC=1C1=CC=NC=N1 RGZZUWVSTHRKAO-UHFFFAOYSA-N 0.000 claims description 2
- VZSBPAJBKZFFKL-UHFFFAOYSA-N 7,7-dimethyl-9-(2-phenylethyl)-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(C=3N=CN=CC=3)=CC(=O)N2CC(C)(C)CN1CCC1=CC=CC=C1 VZSBPAJBKZFFKL-UHFFFAOYSA-N 0.000 claims description 2
- VDWDWRZYKHOPHX-UHFFFAOYSA-N 7,7-dimethyl-9-[2-(4-methylphenyl)-2-oxoethyl]-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C1=CC(C)=CC=C1C(=O)CN1C2=NC(C=3N=CN=CC=3)=CC(=O)N2CC(C)(C)C1 VDWDWRZYKHOPHX-UHFFFAOYSA-N 0.000 claims description 2
- ONFKNLUAHBLFES-UHFFFAOYSA-N 7,7-dimethyl-9-[2-(4-nitrophenyl)ethyl]-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(C=3N=CN=CC=3)=CC(=O)N2CC(C)(C)CN1CCC1=CC=C([N+]([O-])=O)C=C1 ONFKNLUAHBLFES-UHFFFAOYSA-N 0.000 claims description 2
- JNVODGABEMBXEM-UHFFFAOYSA-N 7,7-dimethyl-9-phenacyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(C=3N=CN=CC=3)=CC(=O)N2CC(C)(C)CN1CC(=O)C1=CC=CC=C1 JNVODGABEMBXEM-UHFFFAOYSA-N 0.000 claims description 2
- UAGOWXXTSLUWJG-LRTDYKAYSA-N 8-ethyl-9-[(2s)-2-hydroxy-2-phenylethyl]-2-pyrimidin-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(CC)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 UAGOWXXTSLUWJG-LRTDYKAYSA-N 0.000 claims description 2
- VFRYPTRFAMUTIN-UHFFFAOYSA-N 8-ethyl-9-[2-hydroxy-2-(4-methylphenyl)ethyl]-2-pyrimidin-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=N1 VFRYPTRFAMUTIN-UHFFFAOYSA-N 0.000 claims description 2
- CKHQGPGOHMEQEH-UHFFFAOYSA-N 8-methyl-9-phenacyl-2-pyrimidin-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=N1 CKHQGPGOHMEQEH-UHFFFAOYSA-N 0.000 claims description 2
- LRABFKHJBUBRRB-UHFFFAOYSA-N 9-(1-hydroxy-1-phenylpropan-2-yl)-2-pyrimidin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C1CCN(C(C=C(N=2)C=3N=CN=CC=3)=O)C=2N1C(C)C(O)C1=CC=CC=C1 LRABFKHJBUBRRB-UHFFFAOYSA-N 0.000 claims description 2
- ZBLKRFQQDZIFKI-UHFFFAOYSA-N 9-(1-oxo-1-phenylpropan-2-yl)-2-pyrimidin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C=CC=CC=1C(=O)C(C)N1CCCN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 ZBLKRFQQDZIFKI-UHFFFAOYSA-N 0.000 claims description 2
- TVQWNCBJUIHCMZ-UHFFFAOYSA-N 9-(2,3-dihydro-1h-inden-2-ylmethyl)-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C(=O)N2CC(C)(C)CN(CC3CC4=CC=CC=C4C3)C2=NC=1C1=CC=NC=N1 TVQWNCBJUIHCMZ-UHFFFAOYSA-N 0.000 claims description 2
- QSTLBZBANHGTKL-UHFFFAOYSA-N 9-(2-hydroxy-2-phenylpropyl)-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C=CC=CC=1C(O)(C)CN1CC(C)(C)CN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 QSTLBZBANHGTKL-UHFFFAOYSA-N 0.000 claims description 2
- ALFQUEYHNFZDHU-UHFFFAOYSA-N 9-(2-naphthalen-2-yl-2-oxoethyl)-2-pyrimidin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C=C2C=CC=CC2=CC=1C(=O)CN1CCCN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 ALFQUEYHNFZDHU-UHFFFAOYSA-N 0.000 claims description 2
- RPOOVWZKUDZTBV-UHFFFAOYSA-N 9-(2-phenylsulfanylethyl)-2-pyrimidin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C1CCN2C(=O)C=C(C=3N=CN=CC=3)N=C2N1CCSC1=CC=CC=C1 RPOOVWZKUDZTBV-UHFFFAOYSA-N 0.000 claims description 2
- JYHMMTLLSOAYSW-UHFFFAOYSA-N 9-(3-oxo-3-phenylpropyl)-2-pyrimidin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C=CC=CC=1C(=O)CCN1CCCN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 JYHMMTLLSOAYSW-UHFFFAOYSA-N 0.000 claims description 2
- OZITZBLPTIRHMN-KRWDZBQOSA-N 9-[(2r)-2-(3-chlorophenyl)-2-hydroxyethyl]-2-pyrimidin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C([C@H](O)C=1C=C(Cl)C=CC=1)N1CCCN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 OZITZBLPTIRHMN-KRWDZBQOSA-N 0.000 claims description 2
- LYWFCKAUWKCCIH-JOCHJYFZSA-N 9-[(2s)-2-(cyclopropylmethoxy)-2-phenylethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound O([C@H](CN1CC(CN2C(=O)C=C(N=C21)C=1N=CN=CC=1)(C)C)C=1C=CC=CC=1)CC1CC1 LYWFCKAUWKCCIH-JOCHJYFZSA-N 0.000 claims description 2
- PCFMMISULNYZQC-HXUWFJFHSA-N 9-[(2s)-2-ethoxy-2-phenylethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C([C@@H](OCC)C=1C=CC=CC=1)N1CC(C)(C)CN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 PCFMMISULNYZQC-HXUWFJFHSA-N 0.000 claims description 2
- OWFJQLPPFBQKFX-XPKAQORNSA-N 9-[(2s)-2-hydroxy-2-phenylethyl]-8-methyl-2-pyrimidin-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=N1 OWFJQLPPFBQKFX-XPKAQORNSA-N 0.000 claims description 2
- MIMMMZQIYLNJMK-UHFFFAOYSA-N 9-[1-(7-methoxy-1,3-benzodioxol-5-yl)-1-oxopropan-2-yl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C=2OCOC=2C(OC)=CC=1C(=O)C(C)N1CC(C)(C)CN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 MIMMMZQIYLNJMK-UHFFFAOYSA-N 0.000 claims description 2
- VARSTKFWEVFRTB-UHFFFAOYSA-N 9-[2-(1,3-benzodioxol-5-yl)-2-oxoethyl]-8-methyl-2-pyrimidin-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=N1 VARSTKFWEVFRTB-UHFFFAOYSA-N 0.000 claims description 2
- FVAOHKMJFIIHOP-UHFFFAOYSA-N 9-[2-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-oxoethyl]-8-methyl-2-pyrimidin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C=C2OCCOC2=CC=1C(=O)CN1C(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 FVAOHKMJFIIHOP-UHFFFAOYSA-N 0.000 claims description 2
- HNKMGBNHXPCHPG-UHFFFAOYSA-N 9-[2-(2,4-dichloro-5-fluorophenyl)ethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(C=3N=CN=CC=3)=CC(=O)N2CC(C)(C)CN1CCC1=CC(F)=C(Cl)C=C1Cl HNKMGBNHXPCHPG-UHFFFAOYSA-N 0.000 claims description 2
- OFBNNDKJMQTZRJ-UHFFFAOYSA-N 9-[2-(2,5-dimethoxyphenyl)-2-hydroxyethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound COC1=CC=C(OC)C(C(O)CN2C=3N(C(C=C(N=3)C=3N=CN=CC=3)=O)CC(C)(C)C2)=C1 OFBNNDKJMQTZRJ-UHFFFAOYSA-N 0.000 claims description 2
- IXEXOXMYDHHOAT-UHFFFAOYSA-N 9-[2-(2,5-dimethoxyphenyl)-2-methoxyethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C(OC)=CC=C(OC)C=1C(OC)CN1CC(C)(C)CN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 IXEXOXMYDHHOAT-UHFFFAOYSA-N 0.000 claims description 2
- JPEZRYPUMJXDDL-UHFFFAOYSA-N 9-[2-(2,5-dimethoxyphenyl)-2-oxoethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound COC1=CC=C(OC)C(C(=O)CN2C=3N(C(C=C(N=3)C=3N=CN=CC=3)=O)CC(C)(C)C2)=C1 JPEZRYPUMJXDDL-UHFFFAOYSA-N 0.000 claims description 2
- JBTJFCLSEQVMPB-UHFFFAOYSA-N 9-[2-(2,6-dichlorophenyl)ethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(C=3N=CN=CC=3)=CC(=O)N2CC(C)(C)CN1CCC1=C(Cl)C=CC=C1Cl JBTJFCLSEQVMPB-UHFFFAOYSA-N 0.000 claims description 2
- ACQRNHAWOMSYDY-UHFFFAOYSA-N 9-[2-(2-chlorophenyl)ethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(C=3N=CN=CC=3)=CC(=O)N2CC(C)(C)CN1CCC1=CC=CC=C1Cl ACQRNHAWOMSYDY-UHFFFAOYSA-N 0.000 claims description 2
- NESJZLRWAKVWJS-UHFFFAOYSA-N 9-[2-(2-methoxyphenyl)ethyl]-8-methyl-2-pyrimidin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound COC1=CC=CC=C1CCN1C2=NC(C=3N=CN=CC=3)=CC(=O)N2CCC1C NESJZLRWAKVWJS-UHFFFAOYSA-N 0.000 claims description 2
- ATOOZGCGINQTEE-UHFFFAOYSA-N 9-[2-(3,4-dimethoxyphenyl)ethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C1=C(OC)C(OC)=CC=C1CCN1C2=NC(C=3N=CN=CC=3)=CC(=O)N2CC(C)(C)C1 ATOOZGCGINQTEE-UHFFFAOYSA-N 0.000 claims description 2
- OZITZBLPTIRHMN-UHFFFAOYSA-N 9-[2-(3-chlorophenyl)-2-hydroxyethyl]-2-pyrimidin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C=CC(Cl)=CC=1C(O)CN1CCCN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 OZITZBLPTIRHMN-UHFFFAOYSA-N 0.000 claims description 2
- XLVUJHLIYNEXEG-UHFFFAOYSA-N 9-[2-(3-chlorophenyl)-2-oxoethyl]-8-methyl-2-pyrimidin-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=N1 XLVUJHLIYNEXEG-UHFFFAOYSA-N 0.000 claims description 2
- JUXLCSDVEIIFGG-UHFFFAOYSA-N 9-[2-(3-fluorophenyl)-2-hydroxyethyl]-8-methyl-2-pyrimidin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C=CC(F)=CC=1C(O)CN1C(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 JUXLCSDVEIIFGG-UHFFFAOYSA-N 0.000 claims description 2
- ZIGRIJHILZLVCB-UHFFFAOYSA-N 9-[2-(3-fluorophenyl)-2-methoxyethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C=CC(F)=CC=1C(OC)CN1CC(C)(C)CN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 ZIGRIJHILZLVCB-UHFFFAOYSA-N 0.000 claims description 2
- MWWUQSZKCDHRKQ-UHFFFAOYSA-N 9-[2-(3-fluorophenyl)-2-oxoethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(C=3N=CN=CC=3)=CC(=O)N2CC(C)(C)CN1CC(=O)C1=CC=CC(F)=C1 MWWUQSZKCDHRKQ-UHFFFAOYSA-N 0.000 claims description 2
- DYSMDBUESPUQHM-UHFFFAOYSA-N 9-[2-(3-fluorophenyl)ethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(C=3N=CN=CC=3)=CC(=O)N2CC(C)(C)CN1CCC1=CC=CC(F)=C1 DYSMDBUESPUQHM-UHFFFAOYSA-N 0.000 claims description 2
- POPKOCATLUOLLI-UHFFFAOYSA-N 9-[2-(3-methoxyphenyl)-2-oxoethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound COC1=CC=CC(C(=O)CN2C=3N(C(C=C(N=3)C=3N=CN=CC=3)=O)CC(C)(C)C2)=C1 POPKOCATLUOLLI-UHFFFAOYSA-N 0.000 claims description 2
- GDPPPVIAKJNBAA-UHFFFAOYSA-N 9-[2-(4-bromophenyl)ethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(C=3N=CN=CC=3)=CC(=O)N2CC(C)(C)CN1CCC1=CC=C(Br)C=C1 GDPPPVIAKJNBAA-UHFFFAOYSA-N 0.000 claims description 2
- JHYNOWLBQOXZEU-UHFFFAOYSA-N 9-[2-(4-chlorophenyl)-2-hydroxyethyl]-8-ethyl-2-pyrimidin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C=C(Cl)C=CC=1C(O)CN1C(CC)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 JHYNOWLBQOXZEU-UHFFFAOYSA-N 0.000 claims description 2
- NPVFSLKLHCCPMU-UHFFFAOYSA-N 9-[2-(4-chlorophenyl)-2-oxoethyl]-2-pyrimidin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C1=CC(Cl)=CC=C1C(=O)CN1C2=NC(C=3N=CN=CC=3)=CC(=O)N2CCC1 NPVFSLKLHCCPMU-UHFFFAOYSA-N 0.000 claims description 2
- RQPJDVAAGWDVCV-UHFFFAOYSA-N 9-[2-(4-ethoxyphenyl)ethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C1=CC(OCC)=CC=C1CCN1C2=NC(C=3N=CN=CC=3)=CC(=O)N2CC(C)(C)C1 RQPJDVAAGWDVCV-UHFFFAOYSA-N 0.000 claims description 2
- ADVSIMKBVPUUOQ-UHFFFAOYSA-N 9-[2-(4-fluoro-2-methoxyphenyl)-2-hydroxyethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound COC1=CC(F)=CC=C1C(O)CN1C2=NC(C=3N=CN=CC=3)=CC(=O)N2CC(C)(C)C1 ADVSIMKBVPUUOQ-UHFFFAOYSA-N 0.000 claims description 2
- LJJQKSSBIQWGCB-UHFFFAOYSA-N 9-[2-(4-fluoro-2-methoxyphenyl)-2-methoxyethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C=C(F)C=C(OC)C=1C(OC)CN1CC(C)(C)CN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 LJJQKSSBIQWGCB-UHFFFAOYSA-N 0.000 claims description 2
- RCGAKGAQZBPSPH-UHFFFAOYSA-N 9-[2-(4-fluoro-2-methoxyphenyl)-2-oxoethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound COC1=CC(F)=CC=C1C(=O)CN1C2=NC(C=3N=CN=CC=3)=CC(=O)N2CC(C)(C)C1 RCGAKGAQZBPSPH-UHFFFAOYSA-N 0.000 claims description 2
- AJTHLDUNEXERHE-UHFFFAOYSA-N 9-[2-(4-fluoro-2-methoxyphenyl)ethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound COC1=CC(F)=CC=C1CCN1C2=NC(C=3N=CN=CC=3)=CC(=O)N2CC(C)(C)C1 AJTHLDUNEXERHE-UHFFFAOYSA-N 0.000 claims description 2
- PVRLZGZPZIKSDZ-UHFFFAOYSA-N 9-[2-(4-fluorophenyl)-2-oxoethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(C=3N=CN=CC=3)=CC(=O)N2CC(C)(C)CN1CC(=O)C1=CC=C(F)C=C1 PVRLZGZPZIKSDZ-UHFFFAOYSA-N 0.000 claims description 2
- FYETXARJIGXOAB-UHFFFAOYSA-N 9-[2-(4-fluorophenyl)ethyl]-8-methyl-2-pyrimidin-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=N1 FYETXARJIGXOAB-UHFFFAOYSA-N 0.000 claims description 2
- GHEOMQQDGCLZEC-UHFFFAOYSA-N 9-[2-(5-chloro-2,3-dihydro-1-benzofuran-7-yl)ethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C(=O)N2CC(C)(C)CN(CCC=3C=4OCCC=4C=C(Cl)C=3)C2=NC=1C1=CC=NC=N1 GHEOMQQDGCLZEC-UHFFFAOYSA-N 0.000 claims description 2
- XGYZKYZYYINFNN-UHFFFAOYSA-N 9-[2-ethoxy-2-(2-methoxyphenyl)ethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C=CC=C(OC)C=1C(OCC)CN1CC(C)(C)CN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 XGYZKYZYYINFNN-UHFFFAOYSA-N 0.000 claims description 2
- VVIMLOSLZIERMY-UHFFFAOYSA-N 9-[2-hydroxy-2-(2-methoxyphenyl)ethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound COC1=CC=CC=C1C(O)CN1C2=NC(C=3N=CN=CC=3)=CC(=O)N2CC(C)(C)C1 VVIMLOSLZIERMY-UHFFFAOYSA-N 0.000 claims description 2
- KBAQZBSBQPYLEX-UHFFFAOYSA-N 9-[2-hydroxy-2-(2-methoxyphenyl)propyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound COC1=CC=CC=C1C(C)(O)CN1C2=NC(C=3N=CN=CC=3)=CC(=O)N2CC(C)(C)C1 KBAQZBSBQPYLEX-UHFFFAOYSA-N 0.000 claims description 2
- UCHKNZAEDTWMMV-UHFFFAOYSA-N 9-[2-methoxy-2-(2-methoxyphenyl)ethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C=CC=C(OC)C=1C(OC)CN1CC(C)(C)CN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 UCHKNZAEDTWMMV-UHFFFAOYSA-N 0.000 claims description 2
- XBTDKLVPGQHDBF-UHFFFAOYSA-N 9-[2-oxo-2-(4-phenylphenyl)ethyl]-2-pyrimidin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1C(=O)CN1CCCN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 XBTDKLVPGQHDBF-UHFFFAOYSA-N 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzenecarbonitrile Natural products N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims 2
- 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 2
- DTXSYSMKQLINMN-LJQANCHMSA-N 1-[(2s)-2-(2,4-dimethoxyphenyl)-2-hydroxyethyl]-2,2-dimethyl-8-pyrimidin-4-yl-3,4-dihydropyrimido[1,2-a]pyrimidin-6-one Chemical compound COC1=CC(OC)=CC=C1[C@H](O)CN1C(C)(C)CCN2C(=O)C=C(C=3N=CN=CC=3)N=C21 DTXSYSMKQLINMN-LJQANCHMSA-N 0.000 claims 1
- WRPLTKNVIWLLSB-GOSISDBHSA-N 1-[(2s)-2-(3,4-dichlorophenyl)-2-hydroxyethyl]-2,2-dimethyl-8-pyrimidin-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=N1 WRPLTKNVIWLLSB-GOSISDBHSA-N 0.000 claims 1
- OUSNNMDJVDSAGR-GOSISDBHSA-N 1-[(2s)-2-(3-bromophenyl)-2-hydroxyethyl]-2,2-dimethyl-8-pyrimidin-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=N1 OUSNNMDJVDSAGR-GOSISDBHSA-N 0.000 claims 1
- KBCLTIQEDJXGOE-LJQANCHMSA-N 1-[(2s)-2-hydroxy-2-(4-methoxyphenyl)ethyl]-2,2-dimethyl-8-pyrimidin-4-yl-3,4-dihydropyrimido[1,2-a]pyrimidin-6-one Chemical compound C1=CC(OC)=CC=C1[C@H](O)CN1C(C)(C)CCN2C(=O)C=C(C=3N=CN=CC=3)N=C21 KBCLTIQEDJXGOE-LJQANCHMSA-N 0.000 claims 1
- JGMYXDYVLCDSBV-UHFFFAOYSA-N 1-[2-(4-fluorophenyl)-2-oxoethyl]-2,2-dimethyl-7-pyrimidin-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=N1 JGMYXDYVLCDSBV-UHFFFAOYSA-N 0.000 claims 1
- YKUBCMIBPUJDJV-UHFFFAOYSA-N 1-[3-(2-fluorophenyl)propyl]-2,2-dimethyl-7-pyrimidin-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=N1 YKUBCMIBPUJDJV-UHFFFAOYSA-N 0.000 claims 1
- DTXZPAWYSXZQEI-UHFFFAOYSA-N 2,2-dimethyl-1-(naphthalen-1-ylmethyl)-8-pyrimidin-4-yl-3,4-dihydropyrimido[1,2-a]pyrimidin-6-one Chemical compound C=1C=CC2=CC=CC=C2C=1CN1C(C)(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 DTXZPAWYSXZQEI-UHFFFAOYSA-N 0.000 claims 1
- VIVOCWGAKYMITJ-UHFFFAOYSA-N 2,2-dimethyl-1-[2-oxo-2-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)ethyl]-7-pyrimidin-4-yl-3h-imidazo[1,2-a]pyrimidin-5-one Chemical compound C=1C=C(C(CCC2(C)C)(C)C)C2=CC=1C(=O)CN1C(C)(C)CN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 VIVOCWGAKYMITJ-UHFFFAOYSA-N 0.000 claims 1
- KMPWWLUXBDFAOR-UHFFFAOYSA-N 7,7-dimethyl-2-pyrimidin-4-yl-9-[2-(2,4,5-trifluorophenyl)ethyl]-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(C=3N=CN=CC=3)=CC(=O)N2CC(C)(C)CN1CCC1=CC(F)=C(F)C=C1F KMPWWLUXBDFAOR-UHFFFAOYSA-N 0.000 claims 1
- NODAAAHZMPLSNI-UHFFFAOYSA-N 7,7-dimethyl-9-[2-(2-methylphenyl)ethyl]-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound CC1=CC=CC=C1CCN1C2=NC(C=3N=CN=CC=3)=CC(=O)N2CC(C)(C)C1 NODAAAHZMPLSNI-UHFFFAOYSA-N 0.000 claims 1
- RMSGCAUPLYMPMU-UHFFFAOYSA-N 8-methyl-9-(naphthalen-2-ylmethyl)-2-pyrimidin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C=C2C=CC=CC2=CC=1CN1C(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 RMSGCAUPLYMPMU-UHFFFAOYSA-N 0.000 claims 1
- YEUNKPUKALOQKS-UHFFFAOYSA-N 9-(2-hydroxy-2-phenylethyl)-2-pyrimidin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C=CC=CC=1C(O)CN1CCCN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 YEUNKPUKALOQKS-UHFFFAOYSA-N 0.000 claims 1
- OGMRABWROMAUHP-UHFFFAOYSA-N 9-(3-phenylpropyl)-2-pyrimidin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C1CCN2C(=O)C=C(C=3N=CN=CC=3)N=C2N1CCCC1=CC=CC=C1 OGMRABWROMAUHP-UHFFFAOYSA-N 0.000 claims 1
- VEOGAYWTJFTWAT-UHFFFAOYSA-N 9-[2-(2,4-difluorophenyl)ethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(C=3N=CN=CC=3)=CC(=O)N2CC(C)(C)CN1CCC1=CC=C(F)C=C1F VEOGAYWTJFTWAT-UHFFFAOYSA-N 0.000 claims 1
- CCLZSXWGIICCKG-UHFFFAOYSA-N 9-[2-(2,5-dimethoxyphenyl)-2-ethoxyethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C(OC)=CC=C(OC)C=1C(OCC)CN1CC(C)(C)CN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 CCLZSXWGIICCKG-UHFFFAOYSA-N 0.000 claims 1
- FGUBITOCQKWRNH-UHFFFAOYSA-N 9-[2-(2,5-dimethoxyphenyl)ethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound COC1=CC=C(OC)C(CCN2C=3N(C(C=C(N=3)C=3N=CN=CC=3)=O)CC(C)(C)C2)=C1 FGUBITOCQKWRNH-UHFFFAOYSA-N 0.000 claims 1
- UYEKLCBPXOBYFP-UHFFFAOYSA-N 9-[2-(2,5-dimethoxyphenyl)ethyl]-8-methyl-2-pyrimidin-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=3N=CN=CC=3)=O)CCC2C)=C1 UYEKLCBPXOBYFP-UHFFFAOYSA-N 0.000 claims 1
- VYAWMHAXXFDTTO-UHFFFAOYSA-N 9-[2-(2,6-dimethoxyphenyl)ethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound COC1=CC=CC(OC)=C1CCN1C2=NC(C=3N=CN=CC=3)=CC(=O)N2CC(C)(C)C1 VYAWMHAXXFDTTO-UHFFFAOYSA-N 0.000 claims 1
- AOMVKGLRQDWSAH-UHFFFAOYSA-N 9-[2-(2-ethoxy-4-fluorophenyl)ethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound CCOC1=CC(F)=CC=C1CCN1C2=NC(C=3N=CN=CC=3)=CC(=O)N2CC(C)(C)C1 AOMVKGLRQDWSAH-UHFFFAOYSA-N 0.000 claims 1
- MUIICCYYXNNECR-UHFFFAOYSA-N 9-[2-(2-methoxyphenyl)ethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound COC1=CC=CC=C1CCN1C2=NC(C=3N=CN=CC=3)=CC(=O)N2CC(C)(C)C1 MUIICCYYXNNECR-UHFFFAOYSA-N 0.000 claims 1
- KMKNDSJVGVRVPA-UHFFFAOYSA-N 9-[2-(3,5-dichlorophenyl)-2-hydroxyethyl]-8-methyl-2-pyrimidin-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=N1 KMKNDSJVGVRVPA-UHFFFAOYSA-N 0.000 claims 1
- AUBZYRUDLSFDDO-UHFFFAOYSA-N 9-[2-(3-chlorophenyl)-2-oxoethyl]-2-pyrimidin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound ClC1=CC=CC(C(=O)CN2C=3N(C(C=C(N=3)C=3N=CN=CC=3)=O)CCC2)=C1 AUBZYRUDLSFDDO-UHFFFAOYSA-N 0.000 claims 1
- DHTMJVWLVKGKCL-UHFFFAOYSA-N 9-[2-(3-chlorophenyl)-2-oxoethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(C=3N=CN=CC=3)=CC(=O)N2CC(C)(C)CN1CC(=O)C1=CC=CC(Cl)=C1 DHTMJVWLVKGKCL-UHFFFAOYSA-N 0.000 claims 1
- AYNRCEXLWIVWGV-UHFFFAOYSA-N 9-[2-(3-chlorophenyl)ethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(C=3N=CN=CC=3)=CC(=O)N2CC(C)(C)CN1CCC1=CC=CC(Cl)=C1 AYNRCEXLWIVWGV-UHFFFAOYSA-N 0.000 claims 1
- BVWLJFCVRSXPQR-UHFFFAOYSA-N 9-[2-(3-fluorophenyl)-2-hydroxyethyl]-2-pyrimidin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C=CC(F)=CC=1C(O)CN1CCCN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 BVWLJFCVRSXPQR-UHFFFAOYSA-N 0.000 claims 1
- JDDDXSSSVWKADR-UHFFFAOYSA-N 9-[2-(3-fluorophenyl)-2-hydroxyethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(C=3N=CN=CC=3)=CC(=O)N2CC(C)(C)CN1CC(O)C1=CC=CC(F)=C1 JDDDXSSSVWKADR-UHFFFAOYSA-N 0.000 claims 1
- VPABSYADDLKIRZ-UHFFFAOYSA-N 9-[2-(3-fluorophenyl)-2-oxoethyl]-2-pyrimidin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound FC1=CC=CC(C(=O)CN2C=3N(C(C=C(N=3)C=3N=CN=CC=3)=O)CCC2)=C1 VPABSYADDLKIRZ-UHFFFAOYSA-N 0.000 claims 1
- MHTXWYWYZFVZHT-UHFFFAOYSA-N 9-[2-(3-methoxyphenyl)-2-oxoethyl]-2-pyrimidin-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=3N=CN=CC=3)=O)CCC2)=C1 MHTXWYWYZFVZHT-UHFFFAOYSA-N 0.000 claims 1
- MZSQFYRGHUBDFX-UHFFFAOYSA-N 9-[2-(4-fluoro-2-hydroxyphenyl)ethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(C=3N=CN=CC=3)=CC(=O)N2CC(C)(C)CN1CCC1=CC=C(F)C=C1O MZSQFYRGHUBDFX-UHFFFAOYSA-N 0.000 claims 1
- APCCXHIEOYGKTI-UHFFFAOYSA-N 9-[2-(4-fluoro-2-methoxyphenyl)ethyl]-2-pyrimidin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound COC1=CC(F)=CC=C1CCN1C2=NC(C=3N=CN=CC=3)=CC(=O)N2CCC1 APCCXHIEOYGKTI-UHFFFAOYSA-N 0.000 claims 1
- IVQDWJHSRYDMEW-UHFFFAOYSA-N 9-[2-(4-fluoro-2-propan-2-yloxyphenyl)ethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound CC(C)OC1=CC(F)=CC=C1CCN1C2=NC(C=3N=CN=CC=3)=CC(=O)N2CC(C)(C)C1 IVQDWJHSRYDMEW-UHFFFAOYSA-N 0.000 claims 1
- XYYRQFQVUZESAL-UHFFFAOYSA-N 9-[2-(4-fluorophenyl)-2-hydroxypropyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C=C(F)C=CC=1C(O)(C)CN1CC(C)(C)CN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 XYYRQFQVUZESAL-UHFFFAOYSA-N 0.000 claims 1
- MFUPHHYWUXNUDJ-UHFFFAOYSA-N 9-[2-(4-fluorophenyl)-2-oxoethyl]-2-pyrimidin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C1=CC(F)=CC=C1C(=O)CN1C2=NC(C=3N=CN=CC=3)=CC(=O)N2CCC1 MFUPHHYWUXNUDJ-UHFFFAOYSA-N 0.000 claims 1
- KDCKXHLAVKXGHJ-UHFFFAOYSA-N 9-[2-(4-fluorophenyl)ethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(C=3N=CN=CC=3)=CC(=O)N2CC(C)(C)CN1CCC1=CC=C(F)C=C1 KDCKXHLAVKXGHJ-UHFFFAOYSA-N 0.000 claims 1
- YEEZKFASIXBZFA-UHFFFAOYSA-N 9-[2-(4-methoxyphenyl)ethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C1=CC(OC)=CC=C1CCN1C2=NC(C=3N=CN=CC=3)=CC(=O)N2CC(C)(C)C1 YEEZKFASIXBZFA-UHFFFAOYSA-N 0.000 claims 1
- UVVHORHRXRFAOO-UHFFFAOYSA-N 9-phenacyl-2-pyrimidin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C=CC=CC=1C(=O)CN1CCCN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 UVVHORHRXRFAOO-UHFFFAOYSA-N 0.000 claims 1
- 208000030886 Traumatic Brain injury Diseases 0.000 claims 1
- WQGWDDDVZFFDIG-UHFFFAOYSA-N pyrogallol Chemical compound OC1=CC=CC(O)=C1O WQGWDDDVZFFDIG-UHFFFAOYSA-N 0.000 claims 1
- 208000020431 spinal cord injury Diseases 0.000 claims 1
- 230000009529 traumatic brain injury Effects 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 81
- 150000001875 compounds Chemical class 0.000 description 67
- 239000000203 mixture Substances 0.000 description 60
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 42
- 239000000243 solution Substances 0.000 description 41
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 36
- 102100022563 Tubulin polymerization-promoting protein Human genes 0.000 description 31
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
- 239000000047 product Substances 0.000 description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 25
- 238000000034 method Methods 0.000 description 22
- 239000011541 reaction mixture Substances 0.000 description 21
- 230000008018 melting Effects 0.000 description 20
- 238000002844 melting Methods 0.000 description 20
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 20
- 239000000725 suspension Substances 0.000 description 20
- 239000000284 extract Substances 0.000 description 18
- 238000002360 preparation method Methods 0.000 description 17
- 238000003756 stirring Methods 0.000 description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
- 239000007864 aqueous solution Substances 0.000 description 15
- 238000004587 chromatography analysis Methods 0.000 description 15
- 229920006395 saturated elastomer Polymers 0.000 description 15
- 239000000741 silica gel Substances 0.000 description 15
- 229910002027 silica gel Inorganic materials 0.000 description 15
- 239000002904 solvent Substances 0.000 description 15
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 13
- 239000012312 sodium hydride Substances 0.000 description 13
- 229910000104 sodium hydride Inorganic materials 0.000 description 13
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 12
- 239000002480 mineral oil Substances 0.000 description 12
- 235000010446 mineral oil Nutrition 0.000 description 12
- 239000011780 sodium chloride Substances 0.000 description 12
- 102000013498 tau Proteins Human genes 0.000 description 11
- 108010026424 tau Proteins Proteins 0.000 description 11
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
- 239000000825 pharmaceutical preparation Substances 0.000 description 10
- 229910000027 potassium carbonate Inorganic materials 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 230000026731 phosphorylation Effects 0.000 description 9
- 238000006366 phosphorylation reaction Methods 0.000 description 9
- 238000000746 purification Methods 0.000 description 9
- 206010012289 Dementia Diseases 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- 239000012043 crude product Substances 0.000 description 8
- 238000001704 evaporation Methods 0.000 description 8
- 230000008020 evaporation Effects 0.000 description 8
- 230000002401 inhibitory effect Effects 0.000 description 8
- 238000010992 reflux Methods 0.000 description 8
- 239000002253 acid Substances 0.000 description 7
- IGRUUQSUGJLZCM-UHFFFAOYSA-N ethyl 3-oxo-3-pyrimidin-4-ylpropanoate Chemical compound CCOC(=O)CC(=O)C1=CC=NC=N1 IGRUUQSUGJLZCM-UHFFFAOYSA-N 0.000 description 7
- 239000000546 pharmaceutical excipient Substances 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 102000004190 Enzymes Human genes 0.000 description 5
- 108090000790 Enzymes Proteins 0.000 description 5
- 229910021529 ammonia Inorganic materials 0.000 description 5
- 210000004556 brain Anatomy 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 150000004677 hydrates Chemical class 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
- FFNHAPICNDDQAK-UHFFFAOYSA-N 2-(4-fluoro-2-methoxyphenyl)ethyl methanesulfonate Chemical compound COC1=CC(F)=CC=C1CCOS(C)(=O)=O FFNHAPICNDDQAK-UHFFFAOYSA-N 0.000 description 4
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
- 208000011990 Corticobasal Degeneration Diseases 0.000 description 4
- 102000013717 Cyclin-Dependent Kinase 5 Human genes 0.000 description 4
- 108010025454 Cyclin-Dependent Kinase 5 Proteins 0.000 description 4
- 201000011240 Frontotemporal dementia Diseases 0.000 description 4
- 102000001267 GSK3 Human genes 0.000 description 4
- 108060006662 GSK3 Proteins 0.000 description 4
- 102000019058 Glycogen Synthase Kinase 3 beta Human genes 0.000 description 4
- 108010051975 Glycogen Synthase Kinase 3 beta Proteins 0.000 description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 4
- 108091000080 Phosphotransferase Proteins 0.000 description 4
- 208000000609 Pick Disease of the Brain Diseases 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 206010064930 age-related macular degeneration Diseases 0.000 description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- 230000006951 hyperphosphorylation Effects 0.000 description 4
- 208000002780 macular degeneration Diseases 0.000 description 4
- NFVJNJQRWPQVOA-UHFFFAOYSA-N n-[2-chloro-5-(trifluoromethyl)phenyl]-2-[3-(4-ethyl-5-ethylsulfanyl-1,2,4-triazol-3-yl)piperidin-1-yl]acetamide Chemical compound CCN1C(SCC)=NN=C1C1CN(CC(=O)NC=2C(=CC=C(C=2)C(F)(F)F)Cl)CCC1 NFVJNJQRWPQVOA-UHFFFAOYSA-N 0.000 description 4
- 102000020233 phosphotransferase Human genes 0.000 description 4
- 201000002212 progressive supranuclear palsy Diseases 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- 210000000278 spinal cord Anatomy 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- 230000008733 trauma Effects 0.000 description 4
- XWCQSILTDPAWDP-MRVPVSSYSA-N (1s)-2-chloro-1-phenylethanol Chemical compound ClC[C@@H](O)C1=CC=CC=C1 XWCQSILTDPAWDP-MRVPVSSYSA-N 0.000 description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 3
- STCVGMFBMVWNDI-UHFFFAOYSA-N 1-[2-(4-fluoro-2-methoxyphenyl)ethyl]-2,2-dimethyl-8-pyrimidin-4-yl-3,4-dihydropyrimido[1,2-a]pyrimidin-6-one Chemical compound COC1=CC(F)=CC=C1CCN1C(C)(C)CCN2C(=O)C=C(C=3N=CN=CC=3)N=C21 STCVGMFBMVWNDI-UHFFFAOYSA-N 0.000 description 3
- WFSWJFIOLPQSBL-UHFFFAOYSA-N 3-methyl-9-phenacyl-2-pyrimidin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C1CCN2C(=O)C(C)=C(C=3N=CN=CC=3)N=C2N1CC(=O)C1=CC=CC=C1 WFSWJFIOLPQSBL-UHFFFAOYSA-N 0.000 description 3
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 3
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 3
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 3
- 206010048010 Withdrawal syndrome Diseases 0.000 description 3
- 235000011054 acetic acid Nutrition 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 3
- 229910052739 hydrogen Inorganic materials 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 210000002569 neuron Anatomy 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 230000001575 pathological effect Effects 0.000 description 3
- LIGACIXOYTUXAW-UHFFFAOYSA-N phenacyl bromide Chemical compound BrCC(=O)C1=CC=CC=C1 LIGACIXOYTUXAW-UHFFFAOYSA-N 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 239000007901 soft capsule Substances 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- DAHHEUQBMDBSLO-MRVPVSSYSA-N (1s)-2-bromo-1-phenylethanol Chemical compound BrC[C@@H](O)C1=CC=CC=C1 DAHHEUQBMDBSLO-MRVPVSSYSA-N 0.000 description 2
- PLXDAQYNLACOTA-UHFFFAOYSA-N 1,4,5,6-tetrahydropyrimidin-2-amine;dihydrochloride Chemical compound Cl.Cl.NC1=NCCCN1 PLXDAQYNLACOTA-UHFFFAOYSA-N 0.000 description 2
- BQVGJTBFGJUZQT-UHFFFAOYSA-N 2,2-dimethyl-1-phenacyl-8-pyrimidin-4-yl-3,4-dihydropyrimido[1,2-a]pyrimidin-6-one Chemical compound C=1C=CC=CC=1C(=O)CN1C(C)(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 BQVGJTBFGJUZQT-UHFFFAOYSA-N 0.000 description 2
- BFZVQKSSUJLRJX-UHFFFAOYSA-N 2-(4-fluoro-2-methoxyphenyl)ethanol Chemical compound COC1=CC(F)=CC=C1CCO BFZVQKSSUJLRJX-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- NDTLPGSBLDKERL-UHFFFAOYSA-N 5,5-difluoro-4,6-dihydro-1h-pyrimidin-2-amine Chemical compound NC1=NCC(F)(F)CN1 NDTLPGSBLDKERL-UHFFFAOYSA-N 0.000 description 2
- APIMCJUQJDDGRL-UHFFFAOYSA-N 7,7-dimethyl-9-(2-oxopropyl)-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound CC(=O)CN1CC(C)(C)CN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 APIMCJUQJDDGRL-UHFFFAOYSA-N 0.000 description 2
- GZHAWDQBDQOIJK-UHFFFAOYSA-N 8-ethyl-2-pyrimidin-4-yl-1,6,7,8-tetrahydropyrimido[1,2-a]pyrimidin-4-one Chemical compound N1C(CC)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 GZHAWDQBDQOIJK-UHFFFAOYSA-N 0.000 description 2
- 101710137189 Amyloid-beta A4 protein Proteins 0.000 description 2
- 101710151993 Amyloid-beta precursor protein Proteins 0.000 description 2
- 102100022704 Amyloid-beta precursor protein Human genes 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 102000008130 Cyclic AMP-Dependent Protein Kinases Human genes 0.000 description 2
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 2
- 102000012749 Dopamine and cAMP-Regulated Phosphoprotein 32 Human genes 0.000 description 2
- 108010090047 Dopamine and cAMP-Regulated Phosphoprotein 32 Proteins 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
- 208000037273 Pathologic Processes Diseases 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- 108091008611 Protein Kinase B Proteins 0.000 description 2
- 102100033810 RAC-alpha serine/threonine-protein kinase Human genes 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 125000003277 amino group Chemical group 0.000 description 2
- DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 230000001640 apoptogenic effect Effects 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 150000007514 bases Chemical class 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 238000005341 cation exchange Methods 0.000 description 2
- 210000004027 cell Anatomy 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 229940110456 cocoa butter Drugs 0.000 description 2
- 235000019868 cocoa butter Nutrition 0.000 description 2
- 210000004292 cytoskeleton Anatomy 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 206010012601 diabetes mellitus Diseases 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 125000000524 functional group Chemical group 0.000 description 2
- 230000014509 gene expression Effects 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000003701 inert diluent Substances 0.000 description 2
- 238000001802 infusion Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 229910052744 lithium Inorganic materials 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- 229910001629 magnesium chloride Inorganic materials 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 125000005905 mesyloxy group Chemical group 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 230000009054 pathological process Effects 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 229920000137 polyphosphoric acid Polymers 0.000 description 2
- 235000019260 propionic acid Nutrition 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 2
- 239000012429 reaction media Substances 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 2
- 238000004611 spectroscopical analysis Methods 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 108010061506 tau-protein kinase Proteins 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 2
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- MTCFGRXMJLQNBG-REOHCLBHSA-N (2S)-2-Amino-3-hydroxypropansäure Chemical compound OC[C@H](N)C(O)=O MTCFGRXMJLQNBG-REOHCLBHSA-N 0.000 description 1
- SDOFMBGMRVAJNF-VANKVMQKSA-N (2s,3s,4s,5r)-6-aminohexane-1,2,3,4,5-pentol Chemical compound NC[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O)CO SDOFMBGMRVAJNF-VANKVMQKSA-N 0.000 description 1
- VMKAFJQFKBASMU-KRWDZBQOSA-N (3as)-1-methyl-3,3-diphenyl-3a,4,5,6-tetrahydropyrrolo[1,2-c][1,3,2]oxazaborole Chemical compound C([C@H]12)CCN1B(C)OC2(C=1C=CC=CC=1)C1=CC=CC=C1 VMKAFJQFKBASMU-KRWDZBQOSA-N 0.000 description 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- WBYWAXJHAXSJNI-VOTSOKGWSA-M .beta-Phenylacrylic acid Natural products [O-]C(=O)\C=C\C1=CC=CC=C1 WBYWAXJHAXSJNI-VOTSOKGWSA-M 0.000 description 1
- OPCJOXGBLDJWRM-UHFFFAOYSA-N 1,2-diamino-2-methylpropane Chemical compound CC(C)(N)CN OPCJOXGBLDJWRM-UHFFFAOYSA-N 0.000 description 1
- PKDKBIAEYAWCPS-GOSISDBHSA-N 1-[(2s)-2-(3-fluorophenyl)-2-hydroxyethyl]-2,2-dimethyl-8-pyrimidin-4-yl-3,4-dihydropyrimido[1,2-a]pyrimidin-6-one Chemical compound C([C@@H](O)C=1C=C(F)C=CC=1)N1C(C)(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 PKDKBIAEYAWCPS-GOSISDBHSA-N 0.000 description 1
- CTMMSJPGFUOEOD-LJQANCHMSA-N 1-[(2s)-2-hydroxy-2-(4-methylphenyl)ethyl]-2,2-dimethyl-8-pyrimidin-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=3N=CN=CC=3)N=C21 CTMMSJPGFUOEOD-LJQANCHMSA-N 0.000 description 1
- ZPWSUYXWSPIFDI-UHFFFAOYSA-N 1-[2-(3-methoxyphenyl)-2-oxoethyl]-2,2-dimethyl-8-pyrimidin-4-yl-3,4-dihydropyrimido[1,2-a]pyrimidin-6-one Chemical compound COC1=CC=CC(C(=O)CN2C(CCN3C(=O)C=C(N=C32)C=2N=CN=CC=2)(C)C)=C1 ZPWSUYXWSPIFDI-UHFFFAOYSA-N 0.000 description 1
- AZQGFLHNGKMBLC-UHFFFAOYSA-N 1-[2-(4-chlorophenyl)-2-oxoethyl]-2,2-dimethyl-8-pyrimidin-4-yl-3,4-dihydropyrimido[1,2-a]pyrimidin-6-one Chemical compound C=1C=C(Cl)C=CC=1C(=O)CN1C(C)(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 AZQGFLHNGKMBLC-UHFFFAOYSA-N 0.000 description 1
- RWIHRDRNIFZJRW-UHFFFAOYSA-N 1-[2-(4-methoxyphenyl)-2-oxoethyl]-2,2-dimethyl-8-pyrimidin-4-yl-3,4-dihydropyrimido[1,2-a]pyrimidin-6-one Chemical compound C1=CC(OC)=CC=C1C(=O)CN1C(C)(C)CCN2C(=O)C=C(C=3N=CN=CC=3)N=C21 RWIHRDRNIFZJRW-UHFFFAOYSA-N 0.000 description 1
- AVFZOVWCLRSYKC-UHFFFAOYSA-N 1-methylpyrrolidine Chemical compound CN1CCCC1 AVFZOVWCLRSYKC-UHFFFAOYSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- FSKGUQBJHKBPLI-UHFFFAOYSA-N 2,2-difluoropropane-1,3-diamine;dihydrochloride Chemical compound Cl.Cl.NCC(F)(F)CN FSKGUQBJHKBPLI-UHFFFAOYSA-N 0.000 description 1
- WYFAGZUTWPIHRA-UHFFFAOYSA-N 2,2-dimethyl-1-[2-(4-methylphenyl)-2-oxoethyl]-7-pyrimidin-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=3N=CN=CC=3)N=C21 WYFAGZUTWPIHRA-UHFFFAOYSA-N 0.000 description 1
- OFQHQZIOQYYEKD-UHFFFAOYSA-N 2,2-dimethyl-1-[2-(4-methylphenyl)-2-oxoethyl]-8-pyrimidin-4-yl-3,4-dihydropyrimido[1,2-a]pyrimidin-6-one Chemical compound C1=CC(C)=CC=C1C(=O)CN1C(C)(C)CCN2C(=O)C=C(C=3N=CN=CC=3)N=C21 OFQHQZIOQYYEKD-UHFFFAOYSA-N 0.000 description 1
- OTVBFYWUKHGANV-UHFFFAOYSA-N 2,2-dimethyl-1-[2-oxo-2-(4-phenylphenyl)ethyl]-8-pyrimidin-4-yl-3,4-dihydropyrimido[1,2-a]pyrimidin-6-one Chemical compound C=1C=C(C=2C=CC=CC=2)C=CC=1C(=O)CN1C(C)(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 OTVBFYWUKHGANV-UHFFFAOYSA-N 0.000 description 1
- JWADUXODFOOFHD-UHFFFAOYSA-N 2,2-dimethyl-7-pyrimidin-4-yl-3,8-dihydroimidazo[1,2-a]pyrimidin-5-one Chemical compound N1C(C)(C)CN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 JWADUXODFOOFHD-UHFFFAOYSA-N 0.000 description 1
- QXPUFNQUVYBBHO-UHFFFAOYSA-N 2,2-dimethyl-8-pyrimidin-4-yl-4,9-dihydro-3h-pyrimido[1,2-a]pyrimidin-6-one Chemical compound N1C(C)(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 QXPUFNQUVYBBHO-UHFFFAOYSA-N 0.000 description 1
- 125000000301 2-(3-chlorophenyl)ethyl group Chemical group [H]C1=C([H])C(=C([H])C(Cl)=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- TUHNRCPWPMJXQN-UHFFFAOYSA-N 2-(4-fluoro-2-methoxyphenyl)acetic acid Chemical compound COC1=CC(F)=CC=C1CC(O)=O TUHNRCPWPMJXQN-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- ZJFWCELATJMDNO-UHFFFAOYSA-N 2-bromo-1-(4-fluorophenyl)ethanone Chemical compound FC1=CC=C(C(=O)CBr)C=C1 ZJFWCELATJMDNO-UHFFFAOYSA-N 0.000 description 1
- DAHHEUQBMDBSLO-UHFFFAOYSA-N 2-bromo-1-phenylethanol Chemical compound BrCC(O)C1=CC=CC=C1 DAHHEUQBMDBSLO-UHFFFAOYSA-N 0.000 description 1
- PBIUDEUWYGBHDW-UHFFFAOYSA-N 2-chloro-1-pyridin-3-ylethanone;hydrochloride Chemical compound Cl.ClCC(=O)C1=CC=CN=C1 PBIUDEUWYGBHDW-UHFFFAOYSA-N 0.000 description 1
- QDJPXFPRYRDYJZ-UHFFFAOYSA-N 3-(2-fluorophenyl)propyl methanesulfonate Chemical compound CS(=O)(=O)OCCCC1=CC=CC=C1F QDJPXFPRYRDYJZ-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- SLUYEZHWAHGANQ-UHFFFAOYSA-N 3h-imidazo[1,2-a]pyrimidin-5-one Chemical compound O=C1C=CN=C2N=CCN12 SLUYEZHWAHGANQ-UHFFFAOYSA-N 0.000 description 1
- DVGCGTOCDCVWLM-UHFFFAOYSA-N 3h-imidazo[1,2-a]pyrimidin-5-one;hydrochloride Chemical compound Cl.O=C1C=CN=C2N=CCN12 DVGCGTOCDCVWLM-UHFFFAOYSA-N 0.000 description 1
- FUIMHYMMDKZDOV-LJQANCHMSA-N 4-[(1s)-2-(2,2-dimethyl-6-oxo-8-pyrimidin-4-yl-3,4-dihydropyrimido[1,2-a]pyrimidin-1-yl)-1-hydroxyethyl]benzonitrile Chemical compound C([C@@H](O)C=1C=CC(=CC=1)C#N)N1C(C)(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 FUIMHYMMDKZDOV-LJQANCHMSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- LLBZPESJRQGYMB-UHFFFAOYSA-N 4-one Natural products O1C(C(=O)CC)CC(C)C11C2(C)CCC(C3(C)C(C(C)(CO)C(OC4C(C(O)C(O)C(COC5C(C(O)C(O)CO5)OC5C(C(OC6C(C(O)C(O)C(CO)O6)O)C(O)C(CO)O5)OC5C(C(O)C(O)C(C)O5)O)O4)O)CC3)CC3)=C3C2(C)CC1 LLBZPESJRQGYMB-UHFFFAOYSA-N 0.000 description 1
- BDTRIDKONHOQQN-UHFFFAOYSA-N 4h-pyrimidin-5-one Chemical compound O=C1CN=CN=C1 BDTRIDKONHOQQN-UHFFFAOYSA-N 0.000 description 1
- JPQIZEWXWKGDNS-UHFFFAOYSA-N 5,5-dimethyl-4,6-dihydro-1h-pyrimidin-2-amine;hydrochloride Chemical compound Cl.CC1(C)CNC(N)=NC1 JPQIZEWXWKGDNS-UHFFFAOYSA-N 0.000 description 1
- 229940117976 5-hydroxylysine Drugs 0.000 description 1
- FIQSYLKJORMQFZ-UHFFFAOYSA-N 6-ethyl-1,4,5,6-tetrahydropyrimidin-2-amine;hydrochloride Chemical compound Cl.CCC1CCN=C(N)N1 FIQSYLKJORMQFZ-UHFFFAOYSA-N 0.000 description 1
- ZNOIAHOPHBDPRB-UHFFFAOYSA-N 6-methyl-1,4,5,6-tetrahydropyrimidin-2-amine;hydrochloride Chemical compound Cl.CC1CCN=C(N)N1 ZNOIAHOPHBDPRB-UHFFFAOYSA-N 0.000 description 1
- MUZQOTCZAGDYCT-UHFFFAOYSA-N 7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydro-1h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C(=O)N2CC(C)(C)CNC2=NC=1C1=CC=NC=N1 MUZQOTCZAGDYCT-UHFFFAOYSA-N 0.000 description 1
- NPTULHRIYSEPBU-UHFFFAOYSA-N 7,7-dimethyl-2-pyrimidin-4-yl-9-[2-(3,4,5-trimethoxyphenyl)ethyl]-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound COC1=C(OC)C(OC)=CC(CCN2C=3N(C(C=C(N=3)C=3N=CN=CC=3)=O)CC(C)(C)C2)=C1 NPTULHRIYSEPBU-UHFFFAOYSA-N 0.000 description 1
- LLUZIIPWWSEHIB-UHFFFAOYSA-N 7,7-dimethyl-9-(2-naphthalen-2-yl-2-oxoethyl)-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C(=O)N2CC(C)(C)CN(CC(=O)C=3C=C4C=CC=CC4=CC=3)C2=NC=1C1=CC=NC=N1 LLUZIIPWWSEHIB-UHFFFAOYSA-N 0.000 description 1
- HIQPHWRGPLGGGC-UHFFFAOYSA-N 7,7-dimethyl-9-[2-(4-methylphenyl)ethyl]-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C1=CC(C)=CC=C1CCN1C2=NC(C=3N=CN=CC=3)=CC(=O)N2CC(C)(C)C1 HIQPHWRGPLGGGC-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- RAZSOSQSMQVSHL-UHFFFAOYSA-N 8-methyl-2-pyrimidin-4-yl-1,6,7,8-tetrahydropyrimido[1,2-a]pyrimidin-4-one Chemical compound N1C(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 RAZSOSQSMQVSHL-UHFFFAOYSA-N 0.000 description 1
- DVGBDDAYLMRVKH-UHFFFAOYSA-N 8-methyl-9-(naphthalen-1-ylmethyl)-2-pyrimidin-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=N1 DVGBDDAYLMRVKH-UHFFFAOYSA-N 0.000 description 1
- AJAURZRWMDDLNB-UHFFFAOYSA-N 9-(2-cyclohexylethyl)-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(C=3N=CN=CC=3)=CC(=O)N2CC(C)(C)CN1CCC1CCCCC1 AJAURZRWMDDLNB-UHFFFAOYSA-N 0.000 description 1
- RECOUFVINZDODV-UHFFFAOYSA-N 9-(3-hydroxy-3-phenylpropyl)-2-pyrimidin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C=CC=CC=1C(O)CCN1CCCN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 RECOUFVINZDODV-UHFFFAOYSA-N 0.000 description 1
- YEUNKPUKALOQKS-KRWDZBQOSA-N 9-[(2r)-2-hydroxy-2-phenylethyl]-2-pyrimidin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C([C@H](O)C=1C=CC=CC=1)N1CCCN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 YEUNKPUKALOQKS-KRWDZBQOSA-N 0.000 description 1
- JBQAGPFHLANJSM-IBGZPJMESA-N 9-[(2r)-2-methoxy-2-phenylethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C([C@H](OC)C=1C=CC=CC=1)N1CC(C)(C)CN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 JBQAGPFHLANJSM-IBGZPJMESA-N 0.000 description 1
- OAIRVONWLRPUKR-FUBQLUNQSA-N 9-[(2r)-2-methoxy-2-phenylethyl]-8-methyl-2-pyrimidin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C([C@H](OC)C=1C=CC=CC=1)N1C(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 OAIRVONWLRPUKR-FUBQLUNQSA-N 0.000 description 1
- YEUNKPUKALOQKS-QGZVFWFLSA-N 9-[(2s)-2-hydroxy-2-phenylethyl]-2-pyrimidin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C([C@@H](O)C=1C=CC=CC=1)N1CCCN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 YEUNKPUKALOQKS-QGZVFWFLSA-N 0.000 description 1
- SFXQREYYISLCSC-UHFFFAOYSA-N 9-[1-(7-methoxy-1,3-benzodioxol-5-yl)-1-oxopropan-2-yl]-2-pyrimidin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C=2OCOC=2C(OC)=CC=1C(=O)C(C)N1CCCN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 SFXQREYYISLCSC-UHFFFAOYSA-N 0.000 description 1
- WKRILJUDRCFUPN-UHFFFAOYSA-N 9-[1-hydroxy-1-(7-methoxy-1,3-benzodioxol-5-yl)propan-2-yl]-2-pyrimidin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C=2OCOC=2C(OC)=CC=1C(O)C(C)N1CCCN(C(C=2)=O)C1=NC=2C1=CC=NC=N1 WKRILJUDRCFUPN-UHFFFAOYSA-N 0.000 description 1
- QEARLQUACQCHKA-UHFFFAOYSA-N 9-[2-(2,4-dichlorophenyl)ethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(C=3N=CN=CC=3)=CC(=O)N2CC(C)(C)CN1CCC1=CC=C(Cl)C=C1Cl QEARLQUACQCHKA-UHFFFAOYSA-N 0.000 description 1
- RIJHGTBCOXSHAB-UHFFFAOYSA-N 9-[2-(2-chloro-4-fluorophenyl)ethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(C=3N=CN=CC=3)=CC(=O)N2CC(C)(C)CN1CCC1=CC=C(F)C=C1Cl RIJHGTBCOXSHAB-UHFFFAOYSA-N 0.000 description 1
- PHUASWGMHSHGIP-UHFFFAOYSA-N 9-[2-(2-fluorophenyl)ethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(C=3N=CN=CC=3)=CC(=O)N2CC(C)(C)CN1CCC1=CC=CC=C1F PHUASWGMHSHGIP-UHFFFAOYSA-N 0.000 description 1
- QFCCBOFDMPEWTI-UHFFFAOYSA-N 9-[2-(2-methoxyphenyl)-2-oxoethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound COC1=CC=CC=C1C(=O)CN1C2=NC(C=3N=CN=CC=3)=CC(=O)N2CC(C)(C)C1 QFCCBOFDMPEWTI-UHFFFAOYSA-N 0.000 description 1
- WOVZHKYLVUEFMR-UHFFFAOYSA-N 9-[2-(3-chlorophenyl)-2-hydroxyethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(C=3N=CN=CC=3)=CC(=O)N2CC(C)(C)CN1CC(O)C1=CC=CC(Cl)=C1 WOVZHKYLVUEFMR-UHFFFAOYSA-N 0.000 description 1
- SUWDHEVDHFLMQK-UHFFFAOYSA-N 9-[2-(3-methoxyphenyl)-2-oxoethyl]-8-methyl-2-pyrimidin-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=3N=CN=CC=3)=O)CCC2C)=C1 SUWDHEVDHFLMQK-UHFFFAOYSA-N 0.000 description 1
- OJXLUDGXGXKXML-UHFFFAOYSA-N 9-[2-(4-chlorophenyl)-2-oxoethyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(C=3N=CN=CC=3)=CC(=O)N2CC(C)(C)CN1CC(=O)C1=CC=C(Cl)C=C1 OJXLUDGXGXKXML-UHFFFAOYSA-N 0.000 description 1
- FCMXTBZFPBVDID-UHFFFAOYSA-N 9-[2-(4-methylphenyl)-2-oxoethyl]-2-pyrimidin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C1=CC(C)=CC=C1C(=O)CN1C2=NC(C=3N=CN=CC=3)=CC(=O)N2CCC1 FCMXTBZFPBVDID-UHFFFAOYSA-N 0.000 description 1
- AQSOKGOZIBOQIG-UHFFFAOYSA-N 9-[2-hydroxy-2-(3-methoxyphenyl)propyl]-7,7-dimethyl-2-pyrimidin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound COC1=CC=CC(C(C)(O)CN2C=3N(C(C=C(N=3)C=3N=CN=CC=3)=O)CC(C)(C)C2)=C1 AQSOKGOZIBOQIG-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 239000005995 Aluminium silicate Substances 0.000 description 1
- 108020005544 Antisense RNA Proteins 0.000 description 1
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 1
- 239000004475 Arginine Substances 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 102000015735 Beta-catenin Human genes 0.000 description 1
- 108060000903 Beta-catenin Proteins 0.000 description 1
- 108091007914 CDKs Proteins 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-SREVYHEPSA-N Cinnamic acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1 WBYWAXJHAXSJNI-SREVYHEPSA-N 0.000 description 1
- 108010049894 Cyclic AMP-Dependent Protein Kinases Proteins 0.000 description 1
- 102000003903 Cyclin-dependent kinases Human genes 0.000 description 1
- 108090000266 Cyclin-dependent kinases Proteins 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 239000004375 Dextrin Substances 0.000 description 1
- 229920001353 Dextrin Polymers 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
- LVGKNOAMLMIIKO-UHFFFAOYSA-N Elaidinsaeure-aethylester Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC LVGKNOAMLMIIKO-UHFFFAOYSA-N 0.000 description 1
- 108091007911 GSKs Proteins 0.000 description 1
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 108010001483 Glycogen Synthase Proteins 0.000 description 1
- 102000004103 Glycogen Synthase Kinases Human genes 0.000 description 1
- 108010033040 Histones Proteins 0.000 description 1
- 102000006947 Histones Human genes 0.000 description 1
- 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- ODKSFYDXXFIFQN-BYPYZUCNSA-P L-argininium(2+) Chemical compound NC(=[NH2+])NCCC[C@H]([NH3+])C(O)=O ODKSFYDXXFIFQN-BYPYZUCNSA-P 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
- 125000002842 L-seryl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])O[H] 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 239000005639 Lauric acid Substances 0.000 description 1
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 1
- 239000004472 Lysine Substances 0.000 description 1
- 102000043136 MAP kinase family Human genes 0.000 description 1
- 108091054455 MAP kinase family Proteins 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 229930045534 Me ester-Cyclohexaneundecanoic acid Natural products 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 1
- 102000029749 Microtubule Human genes 0.000 description 1
- 108091022875 Microtubule Proteins 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 1
- AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 108010025020 Nerve Growth Factor Proteins 0.000 description 1
- 102000007072 Nerve Growth Factors Human genes 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 101700056750 PAK1 Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 1
- 102000009516 Protein Serine-Threonine Kinases Human genes 0.000 description 1
- 108010009341 Protein Serine-Threonine Kinases Proteins 0.000 description 1
- LCTONWCANYUPML-UHFFFAOYSA-M Pyruvate Chemical compound CC(=O)C([O-])=O LCTONWCANYUPML-UHFFFAOYSA-M 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 102100031206 Serine/threonine-protein kinase N1 Human genes 0.000 description 1
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 102000017299 Synapsin-1 Human genes 0.000 description 1
- 108050005241 Synapsin-1 Proteins 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
- 229960004373 acetylcholine Drugs 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 235000012211 aluminium silicate Nutrition 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- CBTVGIZVANVGBH-UHFFFAOYSA-N aminomethyl propanol Chemical compound CC(C)(N)CO CBTVGIZVANVGBH-UHFFFAOYSA-N 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000003708 ampul Substances 0.000 description 1
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 230000002424 anti-apoptotic effect Effects 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- ODKSFYDXXFIFQN-UHFFFAOYSA-N arginine Natural products OC(=O)C(N)CCCNC(N)=N ODKSFYDXXFIFQN-UHFFFAOYSA-N 0.000 description 1
- 125000001769 aryl amino group Chemical group 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000006309 butyl amino group Chemical group 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 230000030833 cell death Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 230000021617 central nervous system development Effects 0.000 description 1
- BULLHNJGPPOUOX-UHFFFAOYSA-N chloroacetone Chemical compound CC(=O)CCl BULLHNJGPPOUOX-UHFFFAOYSA-N 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 235000013985 cinnamic acid Nutrition 0.000 description 1
- 229930016911 cinnamic acid Natural products 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 230000007278 cognition impairment Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 230000002301 combined effect Effects 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000007822 coupling agent Substances 0.000 description 1
- ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- YSMODUONRAFBET-UHFFFAOYSA-N delta-DL-hydroxylysine Natural products NCC(O)CCC(N)C(O)=O YSMODUONRAFBET-UHFFFAOYSA-N 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000003831 deregulation Effects 0.000 description 1
- 230000001687 destabilization Effects 0.000 description 1
- 235000019425 dextrin Nutrition 0.000 description 1
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 230000004069 differentiation Effects 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- YSMODUONRAFBET-UHNVWZDZSA-N erythro-5-hydroxy-L-lysine Chemical compound NC[C@H](O)CC[C@H](N)C(O)=O YSMODUONRAFBET-UHNVWZDZSA-N 0.000 description 1
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 description 1
- 125000005677 ethinylene group Chemical group [*:2]C#C[*:1] 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- IPLCEBMDTNGMNS-UHFFFAOYSA-N ethyl 2-methyl-3-oxo-3-pyrimidin-4-ylpropanoate Chemical compound CCOC(=O)C(C)C(=O)C1=CC=NC=N1 IPLCEBMDTNGMNS-UHFFFAOYSA-N 0.000 description 1
- IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 1
- 229940093471 ethyl oleate Drugs 0.000 description 1
- LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 229940097043 glucuronic acid Drugs 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 229960004275 glycolic acid Drugs 0.000 description 1
- 239000003102 growth factor Substances 0.000 description 1
- 229960000789 guanidine hydrochloride Drugs 0.000 description 1
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 239000007902 hard capsule Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 1
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical group C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000006882 induction of apoptosis Effects 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 125000006316 iso-butyl amino group Chemical group [H]N(*)C([H])([H])C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000002510 isobutoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])O* 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004491 isohexyl group Chemical group C(CCC(C)C)* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- NLYAJNPCOHFWQQ-UHFFFAOYSA-N kaolin Chemical compound O.O.O=[Al]O[Si](=O)O[Si](=O)O[Al]=O NLYAJNPCOHFWQQ-UHFFFAOYSA-N 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 229960000448 lactic acid Drugs 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- ACKFDYCQCBEDNU-UHFFFAOYSA-J lead(2+);tetraacetate Chemical compound [Pb+2].CC([O-])=O.CC([O-])=O.CC([O-])=O.CC([O-])=O ACKFDYCQCBEDNU-UHFFFAOYSA-J 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- UEGPKNKPLBYCNK-UHFFFAOYSA-L magnesium acetate Chemical compound [Mg+2].CC([O-])=O.CC([O-])=O UEGPKNKPLBYCNK-UHFFFAOYSA-L 0.000 description 1
- KLRLIDQAFFVFCV-UHFFFAOYSA-M magnesium;5h-1,3-benzodioxol-5-ide;bromide Chemical compound [Mg+2].[Br-].C1=[C-]C=C2OCOC2=C1 KLRLIDQAFFVFCV-UHFFFAOYSA-M 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 239000002609 medium Substances 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- ZTPUBQUAEKODHV-UHFFFAOYSA-N methyl 2-(4-fluoro-2-methoxyphenyl)acetate Chemical compound COC(=O)CC1=CC=C(F)C=C1OC ZTPUBQUAEKODHV-UHFFFAOYSA-N 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- POULHZVOKOAJMA-UHFFFAOYSA-N methyl undecanoic acid Natural products CCCCCCCCCCCC(O)=O POULHZVOKOAJMA-UHFFFAOYSA-N 0.000 description 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
- 210000004688 microtubule Anatomy 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000005184 naphthylamino group Chemical group C1(=CC=CC2=CC=CC=C12)N* 0.000 description 1
- 125000005186 naphthyloxy group Chemical group C1(=CC=CC2=CC=CC=C12)O* 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 210000001577 neostriatum Anatomy 0.000 description 1
- 210000002682 neurofibrillary tangle Anatomy 0.000 description 1
- 210000005044 neurofilament Anatomy 0.000 description 1
- 230000017511 neuron migration Effects 0.000 description 1
- 230000014511 neuron projection development Effects 0.000 description 1
- 230000006576 neuronal survival Effects 0.000 description 1
- 230000002981 neuropathic effect Effects 0.000 description 1
- 230000002887 neurotoxic effect Effects 0.000 description 1
- 239000002581 neurotoxin Substances 0.000 description 1
- 230000000508 neurotrophic effect Effects 0.000 description 1
- 239000003900 neurotrophic factor Substances 0.000 description 1
- 239000011664 nicotinic acid Substances 0.000 description 1
- 235000001968 nicotinic acid Nutrition 0.000 description 1
- 229960003512 nicotinic acid Drugs 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 230000036963 noncompetitive effect Effects 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 125000004894 pentylamino group Chemical group C(CCCC)N* 0.000 description 1
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 description 1
- 230000000865 phosphorylative effect Effects 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000000861 pro-apoptotic effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 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
- 230000009822 protein phosphorylation Effects 0.000 description 1
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
- YPOXGDJGKBXRFP-UHFFFAOYSA-N pyrimidine-4-carboxylic acid Chemical group OC(=O)C1=CC=NC=N1 YPOXGDJGKBXRFP-UHFFFAOYSA-N 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
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 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
- 125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 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
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/14—Drugs for dermatological disorders for baldness or alopecia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
- A61P25/34—Tobacco-abuse
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Diabetes (AREA)
- Psychiatry (AREA)
- Hematology (AREA)
- Ophthalmology & Optometry (AREA)
- Physical Education & Sports Medicine (AREA)
- Cardiology (AREA)
- Epidemiology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Heart & Thoracic Surgery (AREA)
- Dermatology (AREA)
- Pain & Pain Management (AREA)
- Endocrinology (AREA)
- Obesity (AREA)
- Addiction (AREA)
- Urology & Nephrology (AREA)
- Anesthesiology (AREA)
- Oncology (AREA)
- Hospice & Palliative Care (AREA)
- Psychology (AREA)
- Pulmonology (AREA)
- Vascular Medicine (AREA)
- Emergency Medicine (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP01402431A EP1295884A1 (en) | 2001-09-21 | 2001-09-21 | 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 |
EP02290488A EP1340760A1 (en) | 2002-02-28 | 2002-02-28 | 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 |
PCT/EP2002/011127 WO2003027115A1 (en) | 2001-09-21 | 2002-09-19 | 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 for neurodegenerative disorders |
Publications (2)
Publication Number | Publication Date |
---|---|
NO20041142L NO20041142L (no) | 2004-06-21 |
NO329566B1 true NO329566B1 (no) | 2010-11-15 |
Family
ID=26077255
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO20041142A NO329566B1 (no) | 2001-09-21 | 2004-03-18 | Subsitituerte 2-pyrimidinyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-on og 7-pyrimidinyl-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)on-derivater for nevrodegenerative lidelser, anvendelser av slike derivater, og legemidler og inhibitorer omfattende slike derivater |
Country Status (24)
Country | Link |
---|---|
US (2) | US7388005B2 (es) |
EP (1) | EP1430056B1 (es) |
JP (2) | JP4570361B2 (es) |
KR (1) | KR100868840B1 (es) |
CN (1) | CN1247586C (es) |
AR (1) | AR036599A1 (es) |
AT (1) | ATE307815T1 (es) |
AU (1) | AU2002342798C1 (es) |
BR (1) | BR0212904A (es) |
CA (1) | CA2457952C (es) |
CY (1) | CY1105553T1 (es) |
DE (1) | DE60206946T2 (es) |
DK (1) | DK1430056T3 (es) |
EA (2) | EA009456B1 (es) |
ES (1) | ES2250721T3 (es) |
HK (1) | HK1091495A1 (es) |
HU (1) | HUP0500332A3 (es) |
IL (2) | IL160397A0 (es) |
MX (1) | MXPA04002632A (es) |
NO (1) | NO329566B1 (es) |
NZ (1) | NZ531244A (es) |
PL (1) | PL370535A1 (es) |
SI (1) | SI1430056T1 (es) |
WO (1) | WO2003027115A1 (es) |
Families Citing this family (30)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
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 |
CN101198609A (zh) * | 2005-06-14 | 2008-06-11 | 先灵公司 | 天冬氨酰基蛋白酶抑制剂 |
CA2620333A1 (en) | 2005-08-26 | 2007-03-01 | Braincells, Inc. | Neurogenesis by muscarinic receptor modulation |
EP2258359A3 (en) | 2005-08-26 | 2011-04-06 | Braincells, Inc. | Neurogenesis by muscarinic receptor modulation with sabcomelin |
EP2377530A3 (en) | 2005-10-21 | 2012-06-20 | 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 |
JP2009536669A (ja) | 2006-05-09 | 2009-10-15 | ブレインセルス,インコーポレイティド | アンジオテンシン調節による神経新生 |
US20100184806A1 (en) | 2006-09-19 | 2010-07-22 | Braincells, Inc. | Modulation of neurogenesis by ppar agents |
EP1939187A1 (en) * | 2006-12-20 | 2008-07-02 | Sanofi-Aventis | Substituted heteroaryl pyridopyrimidone derivatives |
EP1992624A1 (en) * | 2007-05-16 | 2008-11-19 | Sanofi-Aventis | Heteroarylamide pyrimidone compounds |
EP1992621A1 (en) | 2007-05-16 | 2008-11-19 | Sanofi-Aventis | Heteroarylamide-substituted pyrimidone derivatives for the treatment of neurodegenerative diseases |
EP1992620A1 (en) * | 2007-05-16 | 2008-11-19 | Sanofi-Aventis | Arylamide pyrimidone derivatives for the treatment of neurodegenerative diseases |
EP1992625A1 (en) | 2007-05-16 | 2008-11-19 | Sanofi-Aventis | Arylamide pyrimidone compounds |
EP2085400A1 (en) * | 2008-01-29 | 2009-08-05 | Sanofi-Aventis | Substituted heteroarylamide oxazepinopyrimidone derivatives |
EP2085399A1 (en) * | 2008-01-29 | 2009-08-05 | Sanofi-Aventis | substituted arylamide oxazepinopyrimidone derivatives |
EP2090578A1 (en) * | 2008-01-29 | 2009-08-19 | Sanofi-Aventis | Substituted arylamide diazepinopyrimidone derivatives for the treatment of neurodegenerative diseases caused by abnormal activity of GSK3-beta |
EP2090579A1 (en) * | 2008-01-29 | 2009-08-19 | Sanofi-Aventis | Substituted heteroarylamide diazepinopyrimidone derivatives |
EP2138494A1 (en) | 2008-06-26 | 2009-12-30 | Sanofi-Aventis | Substituted alkyl pyrimidin-4-one derivatives |
EP2138498A1 (en) | 2008-06-26 | 2009-12-30 | sanofi-aventis | Substituted tricyclic derivatives against neurodegenerative diseases |
EP2138495A1 (en) | 2008-06-26 | 2009-12-30 | sanofi-aventis | Substituted pyrimido[2,1-a]isoquinolin-4-one derivatives |
EP2138492A1 (en) | 2008-06-26 | 2009-12-30 | Sanofi-Aventis | Substituted pyrimidin-4-one derivatives |
EP2138488A1 (en) | 2008-06-26 | 2009-12-30 | sanofi-aventis | 4-(pyridin-4-yl)-1H-[1,3,5]triazin-2-one derivatives as GSK3-beta inhibitors for the treatment of neurodegenerative diseases |
EP2138485A1 (en) | 2008-06-26 | 2009-12-30 | sanofi-aventis | Substituted N-Oxide pyrazine derivatives |
EP2138493A1 (en) | 2008-06-26 | 2009-12-30 | Sanofi-Aventis | Substituted pyrimidone derivatives |
US20100216805A1 (en) | 2009-02-25 | 2010-08-26 | Braincells, Inc. | Modulation of neurogenesis using d-cycloserine combinations |
US8421890B2 (en) | 2010-01-15 | 2013-04-16 | Picofield Technologies, Inc. | Electronic imager using an impedance sensor grid array and method of making |
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 |
Family Cites Families (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3865836A (en) * | 1972-12-08 | 1975-02-11 | Janssen Pharmaceutica Nv | Bicyclic imidazoles |
SU600143A1 (ru) * | 1976-12-06 | 1978-03-30 | Ордена Трудового Красного Знамени Институт Органического Синтеза Ан Латвийской Сср | Способ получени гетероциклических систем, содержащих бормзамещенный имидазол |
JPS63216886A (ja) * | 1987-03-05 | 1988-09-09 | Sumitomo Chem Co Ltd | ピリミドピリミジン誘導体およびその製造法 |
JP2862958B2 (ja) * | 1990-06-09 | 1999-03-03 | 三協化学株式会社 | 感熱転写記録用色素 |
US6153618A (en) * | 1996-10-11 | 2000-11-28 | Chiron Corporation | Inhibitors of glycogen synthase 3 kinase |
IL130181A0 (en) * | 1996-12-05 | 2000-06-01 | Amgen Inc | Substituted pyrimidone and pyridone compounds and methods of use |
NZ506417A (en) * | 1998-02-17 | 2003-05-30 | Tularik Inc | Anti-viral pyrimidine derivatives |
ATE303383T1 (de) * | 1999-12-17 | 2005-09-15 | Chiron Corp | Bizyklische inhibitoren von glycogen synthase kinase 3 |
FR2804959B1 (fr) | 2000-02-15 | 2006-04-28 | Centre Nat Rech Scient | Utilisation de derives de paullones pour la fabrication de medicaments |
-
2002
- 2002-09-19 AU AU2002342798A patent/AU2002342798C1/en not_active Ceased
- 2002-09-19 MX MXPA04002632A patent/MXPA04002632A/es active IP Right Grant
- 2002-09-19 IL IL16039702A patent/IL160397A0/xx unknown
- 2002-09-19 JP JP2003530703A patent/JP4570361B2/ja not_active Expired - Fee Related
- 2002-09-19 EA EA200600196A patent/EA009456B1/ru not_active IP Right Cessation
- 2002-09-19 CN CNB028183398A patent/CN1247586C/zh not_active Expired - Fee Related
- 2002-09-19 ES ES02779461T patent/ES2250721T3/es not_active Expired - Lifetime
- 2002-09-19 EA EA200400236A patent/EA007165B1/ru not_active IP Right Cessation
- 2002-09-19 PL PL02370535A patent/PL370535A1/xx unknown
- 2002-09-19 EP EP02779461A patent/EP1430056B1/en not_active Expired - Lifetime
- 2002-09-19 BR BR0212904-3A patent/BR0212904A/pt not_active Application Discontinuation
- 2002-09-19 NZ NZ531244A patent/NZ531244A/en not_active IP Right Cessation
- 2002-09-19 CA CA002457952A patent/CA2457952C/en not_active Expired - Fee Related
- 2002-09-19 KR KR1020047004138A patent/KR100868840B1/ko not_active IP Right Cessation
- 2002-09-19 US US10/490,136 patent/US7388005B2/en not_active Expired - Fee Related
- 2002-09-19 DE DE60206946T patent/DE60206946T2/de not_active Expired - Lifetime
- 2002-09-19 AT AT02779461T patent/ATE307815T1/de active
- 2002-09-19 WO PCT/EP2002/011127 patent/WO2003027115A1/en active IP Right Grant
- 2002-09-19 SI SI200230235T patent/SI1430056T1/sl unknown
- 2002-09-19 HU HU0500332A patent/HUP0500332A3/hu unknown
- 2002-09-19 DK DK02779461T patent/DK1430056T3/da active
- 2002-09-20 AR ARP020103540A patent/AR036599A1/es unknown
-
2004
- 2004-02-15 IL IL160397A patent/IL160397A/en not_active IP Right Cessation
- 2004-03-18 NO NO20041142A patent/NO329566B1/no not_active IP Right Cessation
-
2006
- 2006-01-09 CY CY20061100020T patent/CY1105553T1/el unknown
- 2006-11-21 HK HK06112764A patent/HK1091495A1/xx not_active IP Right Cessation
-
2008
- 2008-05-14 US US12/120,496 patent/US7781440B2/en not_active Expired - Fee Related
-
2010
- 2010-04-21 JP JP2010097989A patent/JP2010189422A/ja active Pending
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
NO329566B1 (no) | Subsitituerte 2-pyrimidinyl-6,7,8,9-tetrahydropyrimido[1,2-a]pyrimidin-4-on og 7-pyrimidinyl-2,3-dihydroimidazo[1,2-a]pyrimidin-5(1H)on-derivater for nevrodegenerative lidelser, anvendelser av slike derivater, og legemidler og inhibitorer omfattende slike derivater | |
US7462621B2 (en) | 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 | |
KR101069984B1 (ko) | 치환된8'-피리디닐-디히드로스피로-[시클로알킬]-피리미도[1,2-a]피리미딘-6-온 및8'-피리미디닐-디히드로스피로-[시클로알킬]-피리미도[1,2-a]피리미딘-6-온 유도체 및 신경퇴행성 질환에 대한 그의용도 | |
AU2002342798A1 (en) | 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 for neurodegenerative disorders | |
AU2002350487A1 (en) | 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 (en) | 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 | |
EP1295884A1 (en) | 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 | |
JP4484524B2 (ja) | 1−[アルキル]、1−[(ヘテロアリール)アルキル]および1−[(アリール)アルキル]−7−(ピリミジン−4−イル)−イミダゾ[1,2−a]ピリミジン−5(1H)−オン誘導体 | |
EP1340761A1 (en) | 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 | |
EP1340760A1 (en) | 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 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
MM1K | Lapsed by not paying the annual fees |