NZ531243A - 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 - Google Patents

Info

Publication number

NZ531243A

NZ531243A NZ531243A NZ53124302A NZ531243A NZ 531243 A NZ531243 A NZ 531243A NZ 531243 A NZ531243 A NZ 531243A NZ 53124302 A NZ53124302 A NZ 53124302A NZ 531243 A NZ531243 A NZ 531243A

Authority

NZ

New Zealand

Prior art keywords

pyridin

pyrimidin

tetrahydro

pyrimido

ethyl

Prior art date

2001-09-21

Links

• Espacenet
• Global Dossier
• Discuss

• UKTRHSHXBSPNQA-UHFFFAOYSA-N 7-pyridin-2-yl-3,8-dihydro-2h-imidazo[1,2-a]pyrimidin-5-one Chemical class N1=C2NCCN2C(=O)C=C1C1=CC=CC=N1 UKTRHSHXBSPNQA-UHFFFAOYSA-N 0.000 title description 2
• KTZSHRGZRORXJO-UHFFFAOYSA-N 2-pyridin-2-yl-1,6,7,8-tetrahydropyrimido[1,2-a]pyrimidin-4-one Chemical class N1=C2NCCCN2C(=O)C=C1C1=CC=CC=N1 KTZSHRGZRORXJO-UHFFFAOYSA-N 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 84
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 49
• 101150053721 Cdk5 gene Proteins 0.000 claims abstract description 33
• 239000003814 drug Substances 0.000 claims abstract description 32
• -1 hydroxyiminomethylene Chemical group 0.000 claims abstract description 31
• 125000003545 alkoxy group Chemical group 0.000 claims abstract description 20
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 20
• 230000000694 effects Effects 0.000 claims abstract description 20
• 201000010099 disease Diseases 0.000 claims abstract description 19
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 19
• 150000008318 pyrimidones Chemical class 0.000 claims abstract description 18
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 16
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims abstract description 15
• 230000002159 abnormal effect Effects 0.000 claims abstract description 14
• 125000001570 methylene group Chemical class [H]C([H])([*:1])[*:2] 0.000 claims abstract description 9
• WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 claims abstract description 7
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims abstract description 6
• 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 claims abstract description 6
• 125000005677 ethinylene group Chemical group [*:2]C#C[*:1] 0.000 claims abstract description 6
• 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 5
• 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 5
• 125000001424 substituent group Chemical group 0.000 claims abstract description 5
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims abstract description 5
• DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 claims description 65
• 239000000203 mixture Substances 0.000 claims description 55
• 150000003839 salts Chemical class 0.000 claims description 45
• SOQCSKKKURIFCX-UHFFFAOYSA-N pyrimido[1,2-a]pyrimidin-6-one Chemical compound N1=CC=CN2C(=O)C=CN=C21 SOQCSKKKURIFCX-UHFFFAOYSA-N 0.000 claims description 29
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 28
• 238000000034 method Methods 0.000 claims description 24
• LCKCIHLNWFCXLK-UHFFFAOYSA-N 1,4,7,8-tetrahydropyrimido[1,2-a]pyrimidin-6-one Chemical compound N1C=CCN2C(=O)CCN=C21 LCKCIHLNWFCXLK-UHFFFAOYSA-N 0.000 claims description 19
• 239000004480 active ingredient Substances 0.000 claims description 19
• 125000005843 halogen group Chemical group 0.000 claims description 17
• 238000002360 preparation method Methods 0.000 claims description 17
• 230000003449 preventive effect Effects 0.000 claims description 16
• 230000001225 therapeutic effect Effects 0.000 claims description 16
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 15
• 230000004770 neurodegeneration Effects 0.000 claims description 15
• 208000015122 neurodegenerative disease Diseases 0.000 claims description 15
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
• 239000012453 solvate Substances 0.000 claims description 14
• 239000000126 substance Substances 0.000 claims description 14
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 13
• 208000014674 injury Diseases 0.000 claims description 12
• 208000024827 Alzheimer disease Diseases 0.000 claims description 10
• 206010028980 Neoplasm Diseases 0.000 claims description 10
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
• 239000003112 inhibitor Substances 0.000 claims description 10
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical group C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 9
• 208000006011 Stroke Diseases 0.000 claims description 9
• 101000983970 Conus catus Alpha-conotoxin CIB Proteins 0.000 claims description 8
• 208000034799 Tauopathies Diseases 0.000 claims description 7
• 230000002401 inhibitory effect Effects 0.000 claims description 7
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 7
• QMJBSXGXBOBMPC-UHFFFAOYSA-N 1,6,7,8-tetrahydropyrimido[1,2-a]pyrimidin-4-one Chemical compound N1CCCN2C(=O)C=CN=C21 QMJBSXGXBOBMPC-UHFFFAOYSA-N 0.000 claims description 6
• 208000018737 Parkinson disease Diseases 0.000 claims description 6
• 125000003277 amino group Chemical group 0.000 claims description 6
• 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 6
• 125000001769 aryl amino group Chemical group 0.000 claims description 6
• 210000004556 brain Anatomy 0.000 claims description 6
• 239000007924 injection Substances 0.000 claims description 6
• 238000002347 injection Methods 0.000 claims description 6
• 239000011780 sodium chloride Substances 0.000 claims description 6
• 229910052717 sulfur Inorganic materials 0.000 claims description 6
• 125000004434 sulfur atom Chemical group 0.000 claims description 6
• 230000008733 trauma Effects 0.000 claims description 6
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 5
• 201000004384 Alopecia Diseases 0.000 claims description 5
• 208000010412 Glaucoma Diseases 0.000 claims description 5
• 208000008589 Obesity Diseases 0.000 claims description 5
• 206010038923 Retinopathy Diseases 0.000 claims description 5
• 201000004810 Vascular dementia Diseases 0.000 claims description 5
• 231100000360 alopecia Toxicity 0.000 claims description 5
• 125000004104 aryloxy group Chemical group 0.000 claims description 5
• 208000028683 bipolar I disease Diseases 0.000 claims description 5
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 5
• 206010015037 epilepsy Diseases 0.000 claims description 5
• 125000001624 naphthyl group Chemical group 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
• 210000000278 spinal cord Anatomy 0.000 claims description 5
• 230000008736 traumatic injury Effects 0.000 claims description 5
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 5
• SLUYEZHWAHGANQ-UHFFFAOYSA-N 3h-imidazo[1,2-a]pyrimidin-5-one Chemical compound O=C1C=CN=C2N=CCN12 SLUYEZHWAHGANQ-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
• 208000000389 T-cell leukemia Diseases 0.000 claims description 4
• 208000028530 T-cell lymphoblastic leukemia/lymphoma Diseases 0.000 claims description 4
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical group C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 4
• 208000024770 Thyroid neoplasm Diseases 0.000 claims description 4
• 241000700605 Viruses Species 0.000 claims description 4
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 4
• 125000004658 aryl carbonyl amino group Chemical group 0.000 claims description 4
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
• 125000002883 imidazolyl group Chemical group 0.000 claims description 4
• PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical group C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 claims description 4
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 4
• 208000002154 non-small cell lung carcinoma Diseases 0.000 claims description 4
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 4
• 230000005586 smoking cessation Effects 0.000 claims description 4
• 125000003375 sulfoxide group Chemical group 0.000 claims description 4
• CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical group C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 claims description 4
• 201000002510 thyroid cancer Diseases 0.000 claims description 4
• 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 3
• 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 3
• 239000007901 soft capsule Substances 0.000 claims description 3
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
• JRPRRFDQCPRIDD-UHFFFAOYSA-N 1-[1-(7-methoxy-1,3-benzodioxol-5-yl)-1-oxopropan-2-yl]-2,2-dimethyl-7-pyridin-4-yl-3h-imidazo[1,2-a]pyrimidin-5-one Chemical compound C=1C=2OCOC=2C(OC)=CC=1C(=O)C(C)N(C(CN1C(=O)C=2)(C)C)C1=NC=2C1=CC=NC=C1 JRPRRFDQCPRIDD-UHFFFAOYSA-N 0.000 claims description 2
• 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 claims description 2
• DMNDGFMEMXFZJL-UHFFFAOYSA-N 2,2-dimethyl-1-(6-oxo-4-phenylcyclohexa-2,4-dien-1-yl)-7-pyridin-4-yl-3h-imidazo[1,2-a]pyrimidin-5-one Chemical compound C1=CC(C=2C=CC=CC=2)=CC(=O)C1N1C(C)(C)CN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 DMNDGFMEMXFZJL-UHFFFAOYSA-N 0.000 claims description 2
• JYFONUFKTJUZBE-UHFFFAOYSA-N 3-fluoro-8-methyl-9-phenacyl-2-pyridin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C=CC=CC=1C(=O)CN1C(C)CCN(C(C=2F)=O)C1=NC=2C1=CC=NC=C1 JYFONUFKTJUZBE-UHFFFAOYSA-N 0.000 claims description 2
• OSKKMMHBJDNVNW-QGZVFWFLSA-N 3-fluoro-9-[(2s)-2-hydroxy-2-phenylethyl]-7,7-dimethyl-2-pyridin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C1([C@H](O)CN2CC(CN3C(=O)C(F)=C(C=4C=CN=CC=4)N=C32)(C)C)=CC=CC=C1 OSKKMMHBJDNVNW-QGZVFWFLSA-N 0.000 claims description 2
• AOOWJOHVPVTKOA-UHFFFAOYSA-N 8-methyl-9-(naphthalen-1-ylmethyl)-2-pyridin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C=CC2=CC=CC=C2C=1CN1C(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 AOOWJOHVPVTKOA-UHFFFAOYSA-N 0.000 claims description 2
• SEGHJVUZNBUMTI-UHFFFAOYSA-N 9-(2-amino-2-phenylethyl)-7,7-dimethyl-2-pyridin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(C=3C=CN=CC=3)=CC(=O)N2CC(C)(C)CN1CC(N)C1=CC=CC=C1 SEGHJVUZNBUMTI-UHFFFAOYSA-N 0.000 claims description 2
• VUBGURPABXJCEQ-UHFFFAOYSA-N 9-(2-hydroxy-2-phenylethyl)-7,7-dimethyl-2-pyridin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(C=3C=CN=CC=3)=CC(=O)N2CC(C)(C)CN1CC(O)C1=CC=CC=C1 VUBGURPABXJCEQ-UHFFFAOYSA-N 0.000 claims description 2
• OHPPAHMCGKFBEJ-UHFFFAOYSA-N 9-[3-(2-fluorophenyl)propyl]-7-hydroxy-2-pyridin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(C=3C=CN=CC=3)=CC(=O)N2CC(O)CN1CCCC1=CC=CC=C1F OHPPAHMCGKFBEJ-UHFFFAOYSA-N 0.000 claims description 2
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Substances N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 2
• 239000001913 cellulose Substances 0.000 claims description 2
• 229920002678 cellulose Polymers 0.000 claims description 2
• 238000009472 formulation Methods 0.000 claims description 2
• 239000000787 lecithin Substances 0.000 claims description 2
• 229940067606 lecithin Drugs 0.000 claims description 2
• 235000010445 lecithin Nutrition 0.000 claims description 2
• 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
• 239000004615 ingredient Substances 0.000 claims 3
• PNHZWBOOHNVDGO-UHFFFAOYSA-N 9-(2-hydroxy-2-phenylpropyl)-7,7-dimethyl-2-pyridin-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=C1 PNHZWBOOHNVDGO-UHFFFAOYSA-N 0.000 claims 2
• VNHNILNXYRRAKL-XCWJXAQQSA-N 9-[(2s)-2-hydroxy-2-phenylethyl]-8-methyl-2-pyridin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C([C@@H](O)C=1C=CC=CC=1)N1C(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 VNHNILNXYRRAKL-XCWJXAQQSA-N 0.000 claims 2
• 125000005278 alkyl sulfonyloxy group Chemical group 0.000 claims 2
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims 2
• GCKUUGPSDVVKQF-UHFFFAOYSA-N 1-(2-hydroxy-2-phenylethyl)-2,2-dimethyl-7-pyridin-4-yl-3h-imidazo[1,2-a]pyrimidin-5-one Chemical compound C=1C=CC=CC=1C(O)CN1C(C)(C)CN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 GCKUUGPSDVVKQF-UHFFFAOYSA-N 0.000 claims 1
• AZPXHIKRAWMQPU-LJQANCHMSA-N 1-[(2s)-2-(3,4-dichlorophenyl)-2-hydroxyethyl]-2,2-dimethyl-8-pyridin-4-yl-3,4-dihydropyrimido[1,2-a]pyrimidin-6-one Chemical compound C([C@@H](O)C=1C=C(Cl)C(Cl)=CC=1)N1C(C)(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 AZPXHIKRAWMQPU-LJQANCHMSA-N 0.000 claims 1
• GLMIQONSAMBPKR-LJQANCHMSA-N 1-[(2s)-2-(3-bromophenyl)-2-hydroxyethyl]-2,2-dimethyl-8-pyridin-4-yl-3,4-dihydropyrimido[1,2-a]pyrimidin-6-one Chemical compound C([C@@H](O)C=1C=C(Br)C=CC=1)N1C(C)(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 GLMIQONSAMBPKR-LJQANCHMSA-N 0.000 claims 1
• QYBOQUKCLGAHOV-RUZDIDTESA-N 1-[(2s)-2-hydroxy-2-(4-phenylphenyl)ethyl]-2,2-dimethyl-8-pyridin-4-yl-3,4-dihydropyrimido[1,2-a]pyrimidin-6-one Chemical compound C([C@@H](O)C=1C=CC(=CC=1)C=1C=CC=CC=1)N1C(C)(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 QYBOQUKCLGAHOV-RUZDIDTESA-N 0.000 claims 1
• KCRDVZBSGQOCQQ-HSZRJFAPSA-N 1-[(2s)-2-hydroxy-2-naphthalen-2-ylethyl]-2,2-dimethyl-8-pyridin-4-yl-3,4-dihydropyrimido[1,2-a]pyrimidin-6-one Chemical compound C([C@@H](O)C=1C=C2C=CC=CC2=CC=1)N1C(C)(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 KCRDVZBSGQOCQQ-HSZRJFAPSA-N 0.000 claims 1
• KSDJBRKKADSAEJ-LJQANCHMSA-N 1-[(2s)-2-hydroxy-2-phenylethyl]-2,2-dimethyl-8-pyridin-4-yl-3,4-dihydropyrimido[1,2-a]pyrimidin-6-one Chemical compound C([C@@H](O)C=1C=CC=CC=1)N1C(C)(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 KSDJBRKKADSAEJ-LJQANCHMSA-N 0.000 claims 1
• AZPXHIKRAWMQPU-UHFFFAOYSA-N 1-[2-(3,4-dichlorophenyl)-2-hydroxyethyl]-2,2-dimethyl-8-pyridin-4-yl-3,4-dihydropyrimido[1,2-a]pyrimidin-6-one Chemical compound C=1C=C(Cl)C(Cl)=CC=1C(O)CN1C(C)(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 AZPXHIKRAWMQPU-UHFFFAOYSA-N 0.000 claims 1
• AOCMWFYPWGCXGQ-UHFFFAOYSA-N 1-[2-(3-fluorophenyl)-2-oxoethyl]-2,2-dimethyl-8-pyridin-4-yl-3,4-dihydropyrimido[1,2-a]pyrimidin-6-one Chemical compound C=1C=CC(F)=CC=1C(=O)CN1C(C)(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 AOCMWFYPWGCXGQ-UHFFFAOYSA-N 0.000 claims 1
• RWDKFQPGXYHJQT-UHFFFAOYSA-N 1-[2-(3-methoxyphenyl)-2-oxoethyl]-2,2-dimethyl-7-pyridin-4-yl-3h-imidazo[1,2-a]pyrimidin-5-one Chemical compound COC1=CC=CC(C(=O)CN2C(CN3C(=O)C=C(N=C32)C=2C=CN=CC=2)(C)C)=C1 RWDKFQPGXYHJQT-UHFFFAOYSA-N 0.000 claims 1
• DTHWETGQWDYWJS-UHFFFAOYSA-N 1-[3-(2-fluorophenyl)propyl]-2,2-dimethyl-7-pyridin-4-yl-3h-imidazo[1,2-a]pyrimidin-5-one Chemical compound C=1C=CC=C(F)C=1CCCN1C(C)(C)CN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 DTHWETGQWDYWJS-UHFFFAOYSA-N 0.000 claims 1
• ZOCUUTDWFLKCDA-UHFFFAOYSA-N 2,2-dimethyl-1-(2-naphthalen-2-yl-2-oxoethyl)-7-pyridin-4-yl-3h-imidazo[1,2-a]pyrimidin-5-one Chemical compound C=1C=C2C=CC=CC2=CC=1C(=O)CN1C(C)(C)CN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 ZOCUUTDWFLKCDA-UHFFFAOYSA-N 0.000 claims 1
• HZCFJXRUCLMQSC-UHFFFAOYSA-N 2,2-dimethyl-1-(naphthalen-1-ylmethyl)-8-pyridin-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=C1 HZCFJXRUCLMQSC-UHFFFAOYSA-N 0.000 claims 1
• BDIWMRJHLMZART-KRWDZBQOSA-N 2,2-dimethyl-1-[(2r)-2-phenylpropyl]-8-pyridin-4-yl-3,4-dihydropyrimido[1,2-a]pyrimidin-6-one Chemical compound C([C@H](C)C=1C=CC=CC=1)N(C(CCN1C(=O)C=2)(C)C)C1=NC=2C1=CC=NC=C1 BDIWMRJHLMZART-KRWDZBQOSA-N 0.000 claims 1
• LNOAYBRKNOFTMC-UHFFFAOYSA-N 2,2-dimethyl-1-phenacyl-7-pyridin-4-yl-3h-imidazo[1,2-a]pyrimidin-5-one Chemical compound C=1C=CC=CC=1C(=O)CN1C(C)(C)CN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 LNOAYBRKNOFTMC-UHFFFAOYSA-N 0.000 claims 1
• MCUHBUUHPAZBNA-UHFFFAOYSA-N 2,2-dimethyl-1-phenacyl-8-pyridin-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=C1 MCUHBUUHPAZBNA-UHFFFAOYSA-N 0.000 claims 1
• ITQOFNXQVVBJJR-UHFFFAOYSA-N 3-bromo-7,7-dimethyl-9-phenacyl-2-pyridin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(C=3C=CN=CC=3)=C(Br)C(=O)N2CC(C)(C)CN1CC(=O)C1=CC=CC=C1 ITQOFNXQVVBJJR-UHFFFAOYSA-N 0.000 claims 1
• FVMDCJODWAHQOT-UHFFFAOYSA-N 3-bromo-8-methyl-9-phenacyl-2-pyridin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C=CC=CC=1C(=O)CN1C(C)CCN(C(C=2Br)=O)C1=NC=2C1=CC=NC=C1 FVMDCJODWAHQOT-UHFFFAOYSA-N 0.000 claims 1
• AKEQIXQIUQCLRV-UHFFFAOYSA-N 3-fluoro-7,7-dimethyl-9-phenacyl-2-pyridin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(C=3C=CN=CC=3)=C(F)C(=O)N2CC(C)(C)CN1CC(=O)C1=CC=CC=C1 AKEQIXQIUQCLRV-UHFFFAOYSA-N 0.000 claims 1
• VNZBIFYIYRGIGE-KRWDZBQOSA-N 3-fluoro-9-[(2r)-2-methoxy-2-phenylethyl]-2-pyridin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C([C@H](OC)C=1C=CC=CC=1)N1CCCN(C(C=2F)=O)C1=NC=2C1=CC=NC=C1 VNZBIFYIYRGIGE-KRWDZBQOSA-N 0.000 claims 1
• VNZBIFYIYRGIGE-QGZVFWFLSA-N 3-fluoro-9-[(2s)-2-methoxy-2-phenylethyl]-2-pyridin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C([C@@H](OC)C=1C=CC=CC=1)N1CCCN(C(C=2F)=O)C1=NC=2C1=CC=NC=C1 VNZBIFYIYRGIGE-QGZVFWFLSA-N 0.000 claims 1
• JOUKKLJOBAMPEF-QGZVFWFLSA-N 7,7-difluoro-9-[(2s)-2-hydroxy-2-phenylethyl]-2-pyridin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C([C@@H](O)C=1C=CC=CC=1)N1CC(F)(F)CN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 JOUKKLJOBAMPEF-QGZVFWFLSA-N 0.000 claims 1
• HGOQLVPPIJYQRV-UHFFFAOYSA-N 7,7-dimethyl-9-(2-naphthalen-2-yl-2-oxoethyl)-2-pyridin-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=C1 HGOQLVPPIJYQRV-UHFFFAOYSA-N 0.000 claims 1
• BUWYWMUJLPTXIT-UHFFFAOYSA-N 7,7-dimethyl-9-[2-(4-methylphenyl)-2-oxoethyl]-2-pyridin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C1=CC(C)=CC=C1C(=O)CN1C2=NC(C=3C=CN=CC=3)=CC(=O)N2CC(C)(C)C1 BUWYWMUJLPTXIT-UHFFFAOYSA-N 0.000 claims 1
• ZJPJAGLAFWZTIF-UHFFFAOYSA-N 7,7-dimethyl-9-[2-oxo-2-(4-phenylphenyl)ethyl]-2-pyridin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(C=3C=CN=CC=3)=CC(=O)N2CC(C)(C)CN1CC(=O)C(C=C1)=CC=C1C1=CC=CC=C1 ZJPJAGLAFWZTIF-UHFFFAOYSA-N 0.000 claims 1
• TYDDJMNZESHZSM-UHFFFAOYSA-N 7,7-dimethyl-9-[2-oxo-2-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)ethyl]-2-pyridin-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(C(CCC4(C)C)(C)C)=CC=3)C2=NC=1C1=CC=NC=C1 TYDDJMNZESHZSM-UHFFFAOYSA-N 0.000 claims 1
• ZQHDYPPISDMHHF-ROPPNANJSA-N 8-ethyl-9-[(2s)-2-hydroxy-2-phenylethyl]-2-pyridin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C([C@@H](O)C=1C=CC=CC=1)N1C(CC)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 ZQHDYPPISDMHHF-ROPPNANJSA-N 0.000 claims 1
• BTGAHQHARQHZIP-UHFFFAOYSA-N 8-methyl-9-(naphthalen-2-ylmethyl)-2-pyridin-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=C1 BTGAHQHARQHZIP-UHFFFAOYSA-N 0.000 claims 1
• CLGGXXZHSXCCCD-UHFFFAOYSA-N 9-(2-hydroxy-2-phenylethyl)-7-methyl-2-pyridin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(C=3C=CN=CC=3)=CC(=O)N2CC(C)CN1CC(O)C1=CC=CC=C1 CLGGXXZHSXCCCD-UHFFFAOYSA-N 0.000 claims 1
• HUSZKCSHVUINFW-UHFFFAOYSA-N 9-(2-hydroxy-3-phenoxypropyl)-7,7-dimethyl-2-pyridin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(C=3C=CN=CC=3)=CC(=O)N2CC(C)(C)CN1CC(O)COC1=CC=CC=C1 HUSZKCSHVUINFW-UHFFFAOYSA-N 0.000 claims 1
• HOTQKBOMYZRYDT-UHFFFAOYSA-N 9-(3-anilino-2-hydroxypropyl)-7,7-dimethyl-2-pyridin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(C=3C=CN=CC=3)=CC(=O)N2CC(C)(C)CN1CC(O)CNC1=CC=CC=C1 HOTQKBOMYZRYDT-UHFFFAOYSA-N 0.000 claims 1
• OPSQBNLOFHOYAS-GOSISDBHSA-N 9-[(2s)-2-hydroxy-2-phenylethyl]-3-methyl-2-pyridin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C1([C@H](O)CN2C3=NC(=C(C(N3CCC2)=O)C)C=2C=CN=CC=2)=CC=CC=C1 OPSQBNLOFHOYAS-GOSISDBHSA-N 0.000 claims 1
• BVHQAQWAFVJHAS-UHFFFAOYSA-N 9-[2-(2-methoxyphenyl)ethyl]-8-methyl-2-pyridin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound COC1=CC=CC=C1CCN1C2=NC(C=3C=CN=CC=3)=CC(=O)N2CCC1C BVHQAQWAFVJHAS-UHFFFAOYSA-N 0.000 claims 1
• KIUILNWIRAXKSO-UHFFFAOYSA-N 9-[2-(3,5-dichlorophenyl)-2-hydroxyethyl]-8-methyl-2-pyridin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C(Cl)=CC(Cl)=CC=1C(O)CN1C(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 KIUILNWIRAXKSO-UHFFFAOYSA-N 0.000 claims 1
• CONZPBCZGZXIPL-UHFFFAOYSA-N 9-[2-(3-chlorophenyl)-2-oxoethyl]-8-methyl-2-pyridin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C=CC(Cl)=CC=1C(=O)CN1C(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 CONZPBCZGZXIPL-UHFFFAOYSA-N 0.000 claims 1
• SPZPXCGDOOSOSX-UHFFFAOYSA-N 9-[2-(3-fluorophenyl)-2-hydroxyethyl]-8-methyl-2-pyridin-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=C1 SPZPXCGDOOSOSX-UHFFFAOYSA-N 0.000 claims 1
• MUALUVZVPKVPBD-UHFFFAOYSA-N 9-[2-(3-fluorophenyl)-2-oxoethyl]-7,7-dimethyl-2-pyridin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(C=3C=CN=CC=3)=CC(=O)N2CC(C)(C)CN1CC(=O)C1=CC=CC(F)=C1 MUALUVZVPKVPBD-UHFFFAOYSA-N 0.000 claims 1
• BAUNTAIRSQTONO-UHFFFAOYSA-N 9-[2-(4-chlorophenyl)-2-hydroxyethyl]-8-ethyl-2-pyridin-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=C1 BAUNTAIRSQTONO-UHFFFAOYSA-N 0.000 claims 1
• OCAGNILQVQSZQT-UHFFFAOYSA-N 9-[2-(4-chlorophenyl)-2-oxoethyl]-7,7-dimethyl-2-pyridin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(C=3C=CN=CC=3)=CC(=O)N2CC(C)(C)CN1CC(=O)C1=CC=C(Cl)C=C1 OCAGNILQVQSZQT-UHFFFAOYSA-N 0.000 claims 1
• ULYQQRGTXXERFK-UHFFFAOYSA-N 9-[2-(4-chlorophenyl)-2-oxoethyl]-8-ethyl-2-pyridin-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=C1 ULYQQRGTXXERFK-UHFFFAOYSA-N 0.000 claims 1
• SCQPFZMUJALLTN-UHFFFAOYSA-N 9-[2-(4-fluorophenyl)-2-oxoethyl]-7,7-dimethyl-2-pyridin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(C=3C=CN=CC=3)=CC(=O)N2CC(C)(C)CN1CC(=O)C1=CC=C(F)C=C1 SCQPFZMUJALLTN-UHFFFAOYSA-N 0.000 claims 1
• ZDXBMBCNMWWQGX-UHFFFAOYSA-N 9-[3-(2-fluorophenyl)propyl]-7,7-dimethyl-2-pyridin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(C=3C=CN=CC=3)=CC(=O)N2CC(C)(C)CN1CCCC1=CC=CC=C1F ZDXBMBCNMWWQGX-UHFFFAOYSA-N 0.000 claims 1
• LQHKDHRGLLCXFL-UHFFFAOYSA-N 9-[3-(2-fluorophenyl)propyl]-7-methoxy-2-pyridin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(C=3C=CN=CC=3)=CC(=O)N2CC(OC)CN1CCCC1=CC=CC=C1F LQHKDHRGLLCXFL-UHFFFAOYSA-N 0.000 claims 1
• 229920002261 Corn starch Polymers 0.000 claims 1
• NIPNSKYNPDTRPC-UHFFFAOYSA-N N-[2-oxo-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethyl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(CNC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 NIPNSKYNPDTRPC-UHFFFAOYSA-N 0.000 claims 1
• 239000003708 ampul Substances 0.000 claims 1
• 201000011510 cancer Diseases 0.000 claims 1
• 239000008120 corn starch Substances 0.000 claims 1
• 229940099112 cornstarch Drugs 0.000 claims 1
• 239000012153 distilled water Substances 0.000 claims 1
• 229940080428 lactose 200 mg Drugs 0.000 claims 1
• 235000019359 magnesium stearate Nutrition 0.000 claims 1
• 239000004006 olive oil Substances 0.000 claims 1
• 235000008390 olive oil Nutrition 0.000 claims 1
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims 1
• 150000003230 pyrimidines Chemical class 0.000 claims 1
• 238000004519 manufacturing process Methods 0.000 abstract description 4
• 229910052736 halogen Inorganic materials 0.000 abstract description 3
• 150000002367 halogens Chemical class 0.000 abstract description 3
• 239000001257 hydrogen Substances 0.000 abstract description 3
• 229910052739 hydrogen Inorganic materials 0.000 abstract description 3
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 abstract 2
• 239000005864 Sulphur Substances 0.000 abstract 2
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract 2
• 239000001301 oxygen Substances 0.000 abstract 2
• 229910052760 oxygen Inorganic materials 0.000 abstract 2
• 150000002431 hydrogen Chemical class 0.000 abstract 1
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 abstract 1
• 150000002829 nitrogen Chemical class 0.000 abstract 1
• 150000003462 sulfoxides Chemical class 0.000 abstract 1
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 78
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 56
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 55
• 239000012458 free base Substances 0.000 description 54
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 40
• 239000000243 solution Substances 0.000 description 37
• 239000000047 product Substances 0.000 description 36
• 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 34
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 32
• ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 31
• 239000000725 suspension Substances 0.000 description 28
• 102100022563 Tubulin polymerization-promoting protein Human genes 0.000 description 26
• 239000002904 solvent Substances 0.000 description 23
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 18
• 238000003756 stirring Methods 0.000 description 17
• 239000011541 reaction mixture Substances 0.000 description 15
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 12
• 239000012312 sodium hydride Substances 0.000 description 12
• 229910000104 sodium hydride Inorganic materials 0.000 description 12
• 239000002480 mineral oil Substances 0.000 description 11
• 235000010446 mineral oil Nutrition 0.000 description 11
• 102000013498 tau Proteins Human genes 0.000 description 11
• 108010026424 tau Proteins Proteins 0.000 description 11
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
• 238000001704 evaporation Methods 0.000 description 10
• 239000008194 pharmaceutical composition Substances 0.000 description 10
• 239000007787 solid Substances 0.000 description 10
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
• 239000007864 aqueous solution Substances 0.000 description 9
• 239000012043 crude product Substances 0.000 description 9
• 230000008020 evaporation Effects 0.000 description 9
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 9
• 230000026731 phosphorylation Effects 0.000 description 9
• 238000006366 phosphorylation reaction Methods 0.000 description 9
• 229910000027 potassium carbonate Inorganic materials 0.000 description 9
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical class N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
• 206010012289 Dementia Diseases 0.000 description 8
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 8
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
• 238000006243 chemical reaction Methods 0.000 description 8
• 239000012074 organic phase Substances 0.000 description 8
• 238000010992 reflux Methods 0.000 description 8
• 239000000741 silica gel Substances 0.000 description 8
• 229910002027 silica gel Inorganic materials 0.000 description 8
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
• 238000004587 chromatography analysis Methods 0.000 description 7
• 150000004677 hydrates Chemical class 0.000 description 7
• 239000000546 pharmaceutical excipient Substances 0.000 description 7
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 7
• 229920006395 saturated elastomer Polymers 0.000 description 7
• 238000010898 silica gel chromatography Methods 0.000 description 7
• 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 6
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
• 239000002253 acid Substances 0.000 description 6
• 239000000284 extract Substances 0.000 description 6
• 230000005764 inhibitory process Effects 0.000 description 6
• 239000007788 liquid Substances 0.000 description 6
• 238000000746 purification Methods 0.000 description 6
• 102000004190 Enzymes Human genes 0.000 description 5
• 108090000790 Enzymes Proteins 0.000 description 5
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 5
• 238000001914 filtration Methods 0.000 description 5
• LIGACIXOYTUXAW-UHFFFAOYSA-N phenacyl bromide Chemical compound BrCC(=O)C1=CC=CC=C1 LIGACIXOYTUXAW-UHFFFAOYSA-N 0.000 description 5
• 239000002244 precipitate Substances 0.000 description 5
• 230000004083 survival effect Effects 0.000 description 5
• 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
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 4
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
• PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 4
• 108091000080 Phosphotransferase Proteins 0.000 description 4
• 208000000609 Pick Disease of the Brain Diseases 0.000 description 4
• 206010064930 age-related macular degeneration Diseases 0.000 description 4
• 229910021529 ammonia Inorganic materials 0.000 description 4
• 239000002585 base Substances 0.000 description 4
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
• 125000004432 carbon atom Chemical group C* 0.000 description 4
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 4
• PCJNYGPKMQQCPX-UHFFFAOYSA-N ethyl 3-oxo-3-pyridin-4-ylpropanoate Chemical compound CCOC(=O)CC(=O)C1=CC=NC=C1 PCJNYGPKMQQCPX-UHFFFAOYSA-N 0.000 description 4
• 230000006951 hyperphosphorylation Effects 0.000 description 4
• 208000002780 macular degeneration Diseases 0.000 description 4
• 102000020233 phosphotransferase Human genes 0.000 description 4
• 229910052938 sodium sulfate Inorganic materials 0.000 description 4
• 235000011152 sodium sulphate Nutrition 0.000 description 4
• 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 3
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 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
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 3
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 3
• ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-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
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 3
• 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 3
• 206010048010 Withdrawal syndrome Diseases 0.000 description 3
• 230000002378 acidificating effect Effects 0.000 description 3
• 150000007513 acids Chemical class 0.000 description 3
• 229910052794 bromium Inorganic materials 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
• 206010012601 diabetes mellitus Diseases 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
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
• 230000001537 neural effect Effects 0.000 description 3
• 210000002569 neuron Anatomy 0.000 description 3
• 230000001575 pathological effect Effects 0.000 description 3
• 108090000765 processed proteins & peptides Proteins 0.000 description 3
• 201000002212 progressive supranuclear palsy Diseases 0.000 description 3
• 125000006239 protecting group Chemical group 0.000 description 3
• 239000000829 suppository Substances 0.000 description 3
• XWCQSILTDPAWDP-MRVPVSSYSA-N (1s)-2-chloro-1-phenylethanol Chemical compound ClC[C@@H](O)C1=CC=CC=C1 XWCQSILTDPAWDP-MRVPVSSYSA-N 0.000 description 2
• JYFXGHYCZNUAPO-UHFFFAOYSA-N 2,2-dimethyl-7-pyridin-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=C1 JYFXGHYCZNUAPO-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
• UPFPEZPTKOPRFH-UHFFFAOYSA-N 3,6-dimethyl-2-pyridin-4-yl-1,6,7,8-tetrahydropyrimido[1,2-a]pyrimidin-4-one Chemical compound CC=1C(=O)N2C(C)CCN=C2NC=1C1=CC=NC=C1 UPFPEZPTKOPRFH-UHFFFAOYSA-N 0.000 description 2
• ZCFPCDAOMSGDII-UHFFFAOYSA-N 7,7-dimethyl-2-pyridin-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=C1 ZCFPCDAOMSGDII-UHFFFAOYSA-N 0.000 description 2
• QSGNEFYXNGYMNG-UHFFFAOYSA-N 8-ethyl-2-pyridin-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=C1 QSGNEFYXNGYMNG-UHFFFAOYSA-N 0.000 description 2
• ZPUXIZBUTRHTJD-FSRHSHDFSA-N 9-[(2s)-2-hydroxy-2-phenylethyl]-7,7-dimethyl-2-pyridin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one;hydrochloride Chemical compound Cl.C1([C@H](O)CN2CC(CN3C(=O)C=C(N=C32)C=2C=CN=CC=2)(C)C)=CC=CC=C1 ZPUXIZBUTRHTJD-FSRHSHDFSA-N 0.000 description 2
• JEUZRQZJRJQMHS-UHFFFAOYSA-N 9-[2-(4-fluoro-2-methoxyphenyl)ethyl]-8-methyl-2-pyridin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound COC1=CC(F)=CC=C1CCN1C2=NC(C=3C=CN=CC=3)=CC(=O)N2CCC1C JEUZRQZJRJQMHS-UHFFFAOYSA-N 0.000 description 2
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-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
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
• CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
• 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
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
• VIZNSCZGEUYTQP-UHFFFAOYSA-N Cl.C=1C=CC=C(F)C=1CCCN1C(C)(C)CN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 Chemical compound Cl.C=1C=CC=C(F)C=1CCCN1C(C)(C)CN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 VIZNSCZGEUYTQP-UHFFFAOYSA-N 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
• 102000001267 GSK3 Human genes 0.000 description 2
• 108060006662 GSK3 Proteins 0.000 description 2
• AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
• ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 2
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
• JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
• 208000037273 Pathologic Processes Diseases 0.000 description 2
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 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
• 244000299461 Theobroma cacao Species 0.000 description 2
• 235000005764 Theobroma cacao ssp. cacao Nutrition 0.000 description 2
• 235000005767 Theobroma cacao ssp. sphaerocarpum Nutrition 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
• 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
• 235000014121 butter Nutrition 0.000 description 2
• 235000001046 cacaotero Nutrition 0.000 description 2
• 238000005341 cation exchange Methods 0.000 description 2
• 210000004027 cell Anatomy 0.000 description 2
• 239000003795 chemical substances by application Substances 0.000 description 2
• 229910052801 chlorine Inorganic materials 0.000 description 2
• 238000010511 deprotection reaction Methods 0.000 description 2
• 229960004132 diethyl ether Drugs 0.000 description 2
• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
• 229910052731 fluorine Inorganic materials 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
• 230000000670 limiting effect Effects 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
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 2
• 239000000463 material Substances 0.000 description 2
• VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 2
• 229940098779 methanesulfonic acid Drugs 0.000 description 2
• 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 2
• 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 2
• 230000002887 neurotoxic effect Effects 0.000 description 2
• 239000011664 nicotinic acid Substances 0.000 description 2
• 235000001968 nicotinic acid Nutrition 0.000 description 2
• 229960003512 nicotinic acid Drugs 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
• 235000006408 oxalic acid Nutrition 0.000 description 2
• 238000007911 parenteral administration Methods 0.000 description 2
• 230000009054 pathological process Effects 0.000 description 2
• 235000011007 phosphoric acid Nutrition 0.000 description 2
• 229920000137 polyphosphoric acid Polymers 0.000 description 2
• NROKBHXJSPEDAR-UHFFFAOYSA-M potassium fluoride Chemical compound [F-].[K+] NROKBHXJSPEDAR-UHFFFAOYSA-M 0.000 description 2
• 235000019260 propionic acid Nutrition 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
• 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
• NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-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
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 description 1
• 125000000229 (C1-C4)alkoxy 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
• PEHDFSFYZKSKGH-UHFFFAOYSA-N 1,4,5,6-tetrahydropyrimidin-2-amine Chemical compound NC1=NCCCN1 PEHDFSFYZKSKGH-UHFFFAOYSA-N 0.000 description 1
• UJXBRPKDAZVQQR-UHFFFAOYSA-N 1,4,7,8-tetrahydropyrimido[1,2-a]pyrimidin-6-one hydrochloride Chemical compound Cl.N1C=2N(C(CC1)=O)CC=CN2 UJXBRPKDAZVQQR-UHFFFAOYSA-N 0.000 description 1
• VFAHCURDJBNWCN-UHFFFAOYSA-N 1-(3-bromopropyl)-2-fluorobenzene Chemical compound FC1=CC=CC=C1CCCBr VFAHCURDJBNWCN-UHFFFAOYSA-N 0.000 description 1
• YOXBPWVWNQROBJ-UHFFFAOYSA-N 1-(4-fluoro-2-methoxyphenyl)ethanone Chemical compound COC1=CC(F)=CC=C1C(C)=O YOXBPWVWNQROBJ-UHFFFAOYSA-N 0.000 description 1
• NUNOKVFHRMPMKF-FSRHSHDFSA-N 1-[(2s)-2-hydroxy-2-phenylethyl]-2,2-dimethyl-8-pyridin-4-yl-3,4-dihydropyrimido[1,2-a]pyrimidin-6-one;hydrochloride Chemical compound Cl.C([C@@H](O)C=1C=CC=CC=1)N1C(C)(C)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 NUNOKVFHRMPMKF-FSRHSHDFSA-N 0.000 description 1
• WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 1
• AGNIHDIIYUFISY-UHFFFAOYSA-N 1-[2-(4-chlorophenyl)-2-oxoethyl]-2,2-dimethyl-7-pyridin-4-yl-3h-imidazo[1,2-a]pyrimidin-5-one Chemical compound C=1C=C(Cl)C=CC=1C(=O)CN1C(C)(C)CN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 AGNIHDIIYUFISY-UHFFFAOYSA-N 0.000 description 1
• STYSMRNYBVGWCB-UHFFFAOYSA-N 1-[2-(4-fluoro-2-methoxyphenyl)ethyl]-2,2-dimethyl-8-pyridin-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=3C=CN=CC=3)N=C21 STYSMRNYBVGWCB-UHFFFAOYSA-N 0.000 description 1
• DEHUABWNDZALHV-UHFFFAOYSA-N 1-[2-(4-fluorophenyl)-2-oxoethyl]-2,2-dimethyl-7-pyridin-4-yl-3h-imidazo[1,2-a]pyrimidin-5-one Chemical compound C=1C=C(F)C=CC=1C(=O)CN1C(C)(C)CN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 DEHUABWNDZALHV-UHFFFAOYSA-N 0.000 description 1
• HFPPZQKUJWIBJI-UHFFFAOYSA-N 2,2-difluoropropane-1,3-diamine Chemical compound NCC(F)(F)CN HFPPZQKUJWIBJI-UHFFFAOYSA-N 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
• SOQGMZRHXAUXIN-UHFFFAOYSA-N 2-[2-(7,7-dimethyl-4-oxo-2-pyridin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-9-yl)-1-phenylethyl]isoindole-1,3-dione Chemical compound C12=NC(C=3C=CN=CC=3)=CC(=O)N2CC(C)(C)CN1CC(N1C(C2=CC=CC=C2C1=O)=O)C1=CC=CC=C1 SOQGMZRHXAUXIN-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
• SRBOTHNAQBMOJA-UHFFFAOYSA-N 2-amino-1,4,5,6-tetrahydropyrimidin-5-ol Chemical compound NC1=NCC(O)CN1 SRBOTHNAQBMOJA-UHFFFAOYSA-N 0.000 description 1
• 229940058020 2-amino-2-methyl-1-propanol Drugs 0.000 description 1
• ZFMVWTHVXNBHNJ-UHFFFAOYSA-N 2-methylpropane-1,3-diamine;hydrochloride Chemical compound Cl.NCC(C)CN ZFMVWTHVXNBHNJ-UHFFFAOYSA-N 0.000 description 1
• TUQPSMBVVMPFJS-UHFFFAOYSA-N 2-pyridin-4-yl-1,6,7,8-tetrahydropyrimido[1,2-a]pyrimidin-4-one Chemical compound N1=C2NCCCN2C(=O)C=C1C1=CC=NC=C1 TUQPSMBVVMPFJS-UHFFFAOYSA-N 0.000 description 1
• QBWKPGNFQQJGFY-QLFBSQMISA-N 3-[(1r)-1-[(2r,6s)-2,6-dimethylmorpholin-4-yl]ethyl]-n-[6-methyl-3-(1h-pyrazol-4-yl)imidazo[1,2-a]pyrazin-8-yl]-1,2-thiazol-5-amine Chemical compound N1([C@H](C)C2=NSC(NC=3C4=NC=C(N4C=C(C)N=3)C3=CNN=C3)=C2)C[C@H](C)O[C@H](C)C1 QBWKPGNFQQJGFY-QLFBSQMISA-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
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 1
• GTENUNHWSWQEDE-UHFFFAOYSA-N 3-methyl-2-pyridin-4-yl-1,6,7,8-tetrahydropyrimido[1,2-a]pyrimidin-4-one Chemical compound N1=C2NCCCN2C(=O)C(C)=C1C1=CC=NC=C1 GTENUNHWSWQEDE-UHFFFAOYSA-N 0.000 description 1
• NGWJGDDSSXHWHA-UHFFFAOYSA-N 3-methyl-9-phenacyl-2-pyridin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C1CCN2C(=O)C(C)=C(C=3C=CN=CC=3)N=C2N1CC(=O)C1=CC=CC=C1 NGWJGDDSSXHWHA-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
• QTFVHGKLPDHRSZ-UHFFFAOYSA-N 5-methyl-1,4,5,6-tetrahydropyrimidin-2-amine;hydrochloride Chemical compound Cl.CC1CNC(N)=NC1 QTFVHGKLPDHRSZ-UHFFFAOYSA-N 0.000 description 1
• YGIPWHRKWHXPMS-UHFFFAOYSA-N 6,6-dimethyl-4,5-dihydro-1h-pyrimidin-2-amine;hydrobromide Chemical compound Br.CC1(C)CCN=C(N)N1 YGIPWHRKWHXPMS-UHFFFAOYSA-N 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
• RJLQHBANAKMDBQ-UHFFFAOYSA-N 7,7-difluoro-9-phenacyl-2-pyridin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(C=3C=CN=CC=3)=CC(=O)N2CC(F)(F)CN1CC(=O)C1=CC=CC=C1 RJLQHBANAKMDBQ-UHFFFAOYSA-N 0.000 description 1
• KIQGJBZJVOGHEB-UHFFFAOYSA-N 7,7-dimethyl-9-phenacyl-2-pyridin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(C=3C=CN=CC=3)=CC(=O)N2CC(C)(C)CN1CC(=O)C1=CC=CC=C1 KIQGJBZJVOGHEB-UHFFFAOYSA-N 0.000 description 1
• ODVSZCFWDUUXKP-UHFFFAOYSA-N 7-hydroxy-2-pyridin-4-yl-1,6,7,8-tetrahydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C(=O)N2CC(O)CNC2=NC=1C1=CC=NC=C1 ODVSZCFWDUUXKP-UHFFFAOYSA-N 0.000 description 1
• DLZRYSQEHNDRAD-UHFFFAOYSA-N 7-methyl-2-pyridin-4-yl-1,6,7,8-tetrahydropyrimido[1,2-a]pyrimidin-4-one Chemical compound C=1C(=O)N2CC(C)CNC2=NC=1C1=CC=NC=C1 DLZRYSQEHNDRAD-UHFFFAOYSA-N 0.000 description 1
• ZPJRIESFKZNCRZ-UHFFFAOYSA-N 7-methyl-9-phenacyl-2-pyridin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(C=3C=CN=CC=3)=CC(=O)N2CC(C)CN1CC(=O)C1=CC=CC=C1 ZPJRIESFKZNCRZ-UHFFFAOYSA-N 0.000 description 1
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
• UYVOTPGJAYOWDJ-UHFFFAOYSA-N 8-ethyl-9-phenacyl-2-pyridin-4-yl-7,8-dihydro-6h-pyrimido[1,2-a]pyrimidin-4-one;hydrochloride Chemical compound Cl.C=1C=CC=CC=1C(=O)CN1C(CC)CCN(C(C=2)=O)C1=NC=2C1=CC=NC=C1 UYVOTPGJAYOWDJ-UHFFFAOYSA-N 0.000 description 1
• ZPETZUBJYGWOOD-UHFFFAOYSA-N 8-methyl-2-pyridin-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=C1 ZPETZUBJYGWOOD-UHFFFAOYSA-N 0.000 description 1
• QGISERMGLQRMLF-UHFFFAOYSA-N 9-(2-amino-2-phenylethyl)-7,7-dimethyl-2-pyridin-4-yl-6,8-dihydropyrimido[1,2-a]pyrimidin-4-one;hydrochloride Chemical compound Cl.C12=NC(C=3C=CN=CC=3)=CC(=O)N2CC(C)(C)CN1CC(N)C1=CC=CC=C1 QGISERMGLQRMLF-UHFFFAOYSA-N 0.000 description 1
• VUBGURPABXJCEQ-LJQANCHMSA-N 9-[(2s)-2-hydroxy-2-phenylethyl]-7,7-dimethyl-2-pyridin-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=2C=CN=CC=2)(C)C)=CC=CC=C1 VUBGURPABXJCEQ-LJQANCHMSA-N 0.000 description 1
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 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
• VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 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
• 108091007914 CDKs Proteins 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-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
• 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
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
• 108091007911 GSKs Proteins 0.000 description 1
• 102000038624 GSKs Human genes 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
• 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
• 229940124913 IPOL Drugs 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
• 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
• 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
• 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
• 206010033799 Paralysis Diseases 0.000 description 1
• 239000002202 Polyethylene glycol Substances 0.000 description 1
• 229920001213 Polysorbate 20 Polymers 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-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
• 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
• 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
• OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
• 239000007983 Tris buffer Substances 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
• PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-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
• 239000000908 ammonium hydroxide Substances 0.000 description 1
• 230000002424 anti-apoptotic effect Effects 0.000 description 1
• 239000012736 aqueous medium Substances 0.000 description 1
• 239000008346 aqueous phase 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
• 229910052786 argon Inorganic materials 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
• 125000004429 atom Chemical group 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
• 210000005013 brain tissue Anatomy 0.000 description 1
• 239000012267 brine Substances 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
• OKTJSMMVPCPJKN-YPZZEJLDSA-N carbon-10 atom Chemical group [10C] OKTJSMMVPCPJKN-YPZZEJLDSA-N 0.000 description 1
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 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
• 210000003169 central nervous system Anatomy 0.000 description 1
• 230000021617 central nervous system development Effects 0.000 description 1
• 239000000460 chlorine Substances 0.000 description 1
• 125000001309 chloro group Chemical group Cl* 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
• 230000001149 cognitive effect Effects 0.000 description 1
• 239000003086 colorant Substances 0.000 description 1
• 230000002301 combined effect Effects 0.000 description 1
• 229940125846 compound 25 Drugs 0.000 description 1
• 230000001010 compromised effect Effects 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
• 230000003436 cytoskeletal effect Effects 0.000 description 1
• 210000004292 cytoskeleton Anatomy 0.000 description 1
• 230000006378 damage Effects 0.000 description 1
• 230000006735 deficit 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
• FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 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
• 229960001760 dimethyl sulfoxide Drugs 0.000 description 1
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
• 208000035475 disorder Diseases 0.000 description 1
• 239000000839 emulsion Substances 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
• 150000002148 esters Chemical class 0.000 description 1
• 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
• ULNDTPIRBQGESN-UHFFFAOYSA-N ethyl 2-bromo-2-fluoroacetate Chemical compound CCOC(=O)C(F)Br ULNDTPIRBQGESN-UHFFFAOYSA-N 0.000 description 1
• AXTIULGXKGAAAV-UHFFFAOYSA-N ethyl 2-fluoro-3-oxo-2-pyridin-4-ylpropanoate Chemical compound CCOC(=O)C(F)(C=O)C1=CC=NC=C1 AXTIULGXKGAAAV-UHFFFAOYSA-N 0.000 description 1
• OVBYBYWXJJPZQG-UHFFFAOYSA-N ethyl 2-methyl-3-oxo-3-pyridin-4-ylpropanoate Chemical compound CCOC(=O)C(C)C(=O)C1=CC=NC=C1 OVBYBYWXJJPZQG-UHFFFAOYSA-N 0.000 description 1
• FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
• LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
• 229940093471 ethyl oleate Drugs 0.000 description 1
• 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 1
• 238000003818 flash chromatography Methods 0.000 description 1
• 239000011737 fluorine Substances 0.000 description 1
• 125000001153 fluoro group Chemical group F* 0.000 description 1
• 235000003599 food sweetener Nutrition 0.000 description 1
• 239000001530 fumaric acid Substances 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
• 239000007902 hard capsule Substances 0.000 description 1
• 125000000623 heterocyclic group Chemical group 0.000 description 1
• IKDUDTNKRLTJSI-UHFFFAOYSA-N hydrazine monohydrate Substances O.NN IKDUDTNKRLTJSI-UHFFFAOYSA-N 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
• CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-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
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
• 208000028867 ischemia Diseases 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
• 150000002632 lipids Chemical class 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
• VZCYOOQTPOCHFL-UPHRSURJSA-L maleate(2-) Chemical compound [O-]C(=O)\C=C/C([O-])=O VZCYOOQTPOCHFL-UPHRSURJSA-L 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
• 239000002609 medium Substances 0.000 description 1
• 230000004060 metabolic process Effects 0.000 description 1
• QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 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
• 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
• 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
• 230000002981 neuropathic effect Effects 0.000 description 1
• 231100000189 neurotoxic Toxicity 0.000 description 1
• 230000000508 neurotrophic effect Effects 0.000 description 1
• 239000003900 neurotrophic factor Substances 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
• 230000002018 overexpression Effects 0.000 description 1
• 208000021090 palsy Diseases 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
• XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
• 239000002504 physiological saline solution Substances 0.000 description 1
• 229920001223 polyethylene glycol Polymers 0.000 description 1
• 229920000642 polymer Polymers 0.000 description 1
• 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 1
• 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 1
• 229920000136 polysorbate Polymers 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 239000011698 potassium fluoride Substances 0.000 description 1
• 235000003270 potassium fluoride Nutrition 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
• 230000000750 progressive effect Effects 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
• RVQZKNOMKUSGCI-UHFFFAOYSA-N pyridine-4-carbonyl chloride Chemical compound ClC(=O)C1=CC=NC=C1 RVQZKNOMKUSGCI-UHFFFAOYSA-N 0.000 description 1
• 230000002829 reductive effect Effects 0.000 description 1
• 229960004889 salicylic acid Drugs 0.000 description 1
• 125000005920 sec-butoxy group Chemical group 0.000 description 1
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
• 238000013207 serial dilution Methods 0.000 description 1
• 230000019491 signal transduction Effects 0.000 description 1
• 230000000391 smoking effect Effects 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
• 235000017557 sodium bicarbonate Nutrition 0.000 description 1
• 239000012279 sodium borohydride Substances 0.000 description 1
• 229910000033 sodium borohydride Inorganic materials 0.000 description 1
• 229910000029 sodium carbonate Inorganic materials 0.000 description 1
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 238000007920 subcutaneous administration Methods 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 239000003765 sweetening agent Substances 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 125000006318 tert-butyl amino group Chemical group [H]N(*)C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
• 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
• TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
• 238000001665 trituration Methods 0.000 description 1
• 235000015112 vegetable and seed oil Nutrition 0.000 description 1
• 239000008158 vegetable oil Substances 0.000 description 1