BR112014019750B1 - Composto, composição farmacêutica e seus usos - Google Patents

Info

Publication number

BR112014019750B1

BR112014019750B1 BR112014019750-4A BR112014019750A BR112014019750B1 BR 112014019750 B1 BR112014019750 B1 BR 112014019750B1 BR 112014019750 A BR112014019750 A BR 112014019750A BR 112014019750 B1 BR112014019750 B1 BR 112014019750B1

Authority

BR

Brazil

Prior art keywords

pyrimidin

pyrido

pyrazin

methyl

pyridin

Prior art date

2012-02-10

Links

• Espacenet
• Global Dossier
• Discuss

• 150000001875 compounds Chemical class 0.000 title claims abstract description 1242
• 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 48
• 208000002320 spinal muscular atrophy Diseases 0.000 claims abstract description 256
• 108020004999 messenger RNA Proteins 0.000 claims abstract description 247
• 101150081851 SMN1 gene Proteins 0.000 claims abstract description 196
• 238000000034 method Methods 0.000 claims abstract description 87
• 101100203482 Drosophila melanogaster Smn gene Proteins 0.000 claims abstract description 54
• 101150069235 Snrpn gene Proteins 0.000 claims abstract description 54
• 238000011282 treatment Methods 0.000 claims abstract description 33
• -1 piperazin-i-yl Chemical group 0.000 claims description 901
• 102100021947 Survival motor neuron protein Human genes 0.000 claims description 546
• 101000617738 Homo sapiens Survival motor neuron protein Proteins 0.000 claims description 518
• 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 207
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 145
• 125000000623 heterocyclic group Chemical group 0.000 claims description 142
• 101150015954 SMN2 gene Proteins 0.000 claims description 138
• 125000001424 substituent group Chemical group 0.000 claims description 127
• GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 claims description 110
• 125000001072 heteroaryl group Chemical group 0.000 claims description 94
• 150000003839 salts Chemical class 0.000 claims description 76
• 125000003118 aryl group Chemical group 0.000 claims description 67
• 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 55
• 125000004076 pyridyl group Chemical group 0.000 claims description 54
• 239000003814 drug Substances 0.000 claims description 42
• 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 35
• 229910052736 halogen Inorganic materials 0.000 claims description 25
• 150000002367 halogens Chemical class 0.000 claims description 24
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 23
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 23
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 21
• 125000004939 6-pyridyl group Chemical group N1=CC=CC=C1* 0.000 claims description 21
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 21
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 20
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 18
• 239000003085 diluting agent Substances 0.000 claims description 15
• 229910052739 hydrogen Inorganic materials 0.000 claims description 15
• 239000001257 hydrogen Substances 0.000 claims description 15
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 15
• 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 15
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 14
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 13
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
• 239000002253 acid Substances 0.000 claims description 12
• 125000003386 piperidinyl group Chemical group 0.000 claims description 12
• OQHQOOLVQDEIGL-UHFFFAOYSA-N 2-methyl-2,7-diazaspiro[4.4]nonane Chemical compound C1N(C)CCC11CNCC1 OQHQOOLVQDEIGL-UHFFFAOYSA-N 0.000 claims description 11
• 239000003937 drug carrier Substances 0.000 claims description 11
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 10
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 9
• 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 9
• 125000004193 piperazinyl group Chemical group 0.000 claims description 9
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 9
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 9
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 8
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 8
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 7
• 125000004566 azetidin-1-yl group Chemical group N1(CCC1)* 0.000 claims description 6
• 125000002393 azetidinyl group Chemical group 0.000 claims description 6
• 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
• 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
• 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 claims description 6
• 125000004043 oxo group Chemical group O=* 0.000 claims description 5
• 125000004938 5-pyridyl group Chemical group N1=CC=CC(=C1)* 0.000 claims description 4
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
• CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 4
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical group [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 4
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 4
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 4
• 239000012458 free base Substances 0.000 claims description 4
• 125000006299 oxetan-3-yl group Chemical group [H]C1([H])OC([H])([H])C1([H])* 0.000 claims description 4
• 125000005960 1,4-diazepanyl group Chemical group 0.000 claims description 3
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 3
• 239000011780 sodium chloride Substances 0.000 claims description 3
• 150000001805 chlorine compounds Chemical group 0.000 claims description 2
• 125000004531 indol-5-yl group Chemical group [H]N1C([H])=C([H])C2=C([H])C(*)=C([H])C([H])=C12 0.000 claims description 2
• DNCYBUMDUBHIJZ-UHFFFAOYSA-N 1h-pyrimidin-6-one Chemical compound O=C1C=CN=CN1 DNCYBUMDUBHIJZ-UHFFFAOYSA-N 0.000 claims 43
• RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims 21
• NYJWYCAHJRGKMI-UHFFFAOYSA-N pyrido[1,2-a]pyrimidin-4-one Chemical compound C1=CC=CN2C(=O)C=CN=C21 NYJWYCAHJRGKMI-UHFFFAOYSA-N 0.000 claims 18
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims 16
• 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 15
• 125000004484 1-methylpiperidin-4-yl group Chemical group CN1CCC(CC1)* 0.000 claims 9
• 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 claims 6
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 6
• DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 claims 4
• SBADHNHELWJBMW-UHFFFAOYSA-N 2-(2,8-dimethylimidazo[1,2-a]pyridin-6-yl)-7-(1-ethylpiperidin-4-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(CC)CCC1C1=CN2C(=O)C=C(C3=CN4C=C(C)N=C4C(C)=C3)N=C2C=C1 SBADHNHELWJBMW-UHFFFAOYSA-N 0.000 claims 3
• IHNXTKFBGKSKPW-UHFFFAOYSA-N 2-(2,8-dimethylimidazo[1,2-a]pyridin-6-yl)-7-(1-propan-2-ylpiperidin-4-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(C(C)C)CCC1C1=CN2C(=O)C=C(C3=CN4C=C(C)N=C4C(C)=C3)N=C2C=C1 IHNXTKFBGKSKPW-UHFFFAOYSA-N 0.000 claims 3
• XDZMFYNAUKNGDI-UHFFFAOYSA-N 2-(4,6-dimethylpyrazolo[1,5-a]pyrazin-2-yl)-9-methyl-7-piperazin-1-ylpyrido[1,2-a]pyrimidin-4-one Chemical compound C1=C2C(C)=NC(C)=CN2N=C1C(N=C1C(C)=C2)=CC(=O)N1C=C2N1CCNCC1 XDZMFYNAUKNGDI-UHFFFAOYSA-N 0.000 claims 3
• AVWJMBZZOAFETI-UHFFFAOYSA-N 2-(6-methyl-4-propylpyrazolo[1,5-a]pyrazin-2-yl)-7-piperidin-4-ylpyrido[1,2-a]pyrimidin-4-one Chemical compound C1=C2C(CCC)=NC(C)=CN2N=C1C(N=C1C=C2)=CC(=O)N1C=C2C1CCNCC1 AVWJMBZZOAFETI-UHFFFAOYSA-N 0.000 claims 3
• DMKAKYCYGHVVQX-UHFFFAOYSA-N 2-(8-ethyl-2-methylimidazo[1,2-a]pyridin-6-yl)-7-(1-methylpiperidin-4-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C=1N2C=C(C)N=C2C(CC)=CC=1C(N=C1C=C2)=CC(=O)N1C=C2C1CCN(C)CC1 DMKAKYCYGHVVQX-UHFFFAOYSA-N 0.000 claims 3
• 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims 3
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 3
• VKBXHPYPNYCDBH-UHFFFAOYSA-N 2-(2,8-dimethylimidazo[1,2-a]pyridin-6-yl)-7-(4-methylpiperazin-1-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(C)CCN1C1=CN2C(=O)C=C(C3=CN4C=C(C)N=C4C(C)=C3)N=C2C=C1 VKBXHPYPNYCDBH-UHFFFAOYSA-N 0.000 claims 2
• VVSQYKQUEZFGBX-AWEZNQCLSA-N 2-(2-methylimidazo[1,2-a]pyridin-6-yl)-7-[(3s)-3-methylpiperazin-1-yl]pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN[C@@H](C)CN1C1=CN2C(=O)C=C(C3=CN4C=C(C)N=C4C=C3)N=C2C=C1 VVSQYKQUEZFGBX-AWEZNQCLSA-N 0.000 claims 2
• CAHSFXLOBMVRGR-UHFFFAOYSA-N 2-(4,6-dimethylpyrazolo[1,5-a]pyrazin-2-yl)-7-(1-ethylpiperidin-4-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(CC)CCC1C1=CN2C(=O)C=C(C3=NN4C=C(C)N=C(C)C4=C3)N=C2C=C1 CAHSFXLOBMVRGR-UHFFFAOYSA-N 0.000 claims 2
• VMDJMSCZABSTOU-UHFFFAOYSA-N 2-(4,6-dimethylpyrazolo[1,5-a]pyrazin-2-yl)-7-(1-propan-2-ylpiperidin-4-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(C(C)C)CCC1C1=CN2C(=O)C=C(C3=NN4C=C(C)N=C(C)C4=C3)N=C2C=C1 VMDJMSCZABSTOU-UHFFFAOYSA-N 0.000 claims 2
• WLKCQJYEPSGQOS-UHFFFAOYSA-N 2-(4,6-dimethylpyrazolo[1,5-a]pyrazin-2-yl)-7-(1-propylpiperidin-4-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(CCC)CCC1C1=CN2C(=O)C=C(C3=NN4C=C(C)N=C(C)C4=C3)N=C2C=C1 WLKCQJYEPSGQOS-UHFFFAOYSA-N 0.000 claims 2
• XAQIBZIVIVBYPA-MRXNPFEDSA-N 2-(4,6-dimethylpyrazolo[1,5-a]pyrazin-2-yl)-7-[(3r)-4-ethyl-3-methylpiperazin-1-yl]pyrido[1,2-a]pyrimidin-4-one Chemical compound C1[C@@H](C)N(CC)CCN1C1=CN2C(=O)C=C(C3=NN4C=C(C)N=C(C)C4=C3)N=C2C=C1 XAQIBZIVIVBYPA-MRXNPFEDSA-N 0.000 claims 2
• OHXBTGLLYWHKMH-CQSZACIVSA-N 2-(4,6-dimethylpyrazolo[1,5-a]pyrazin-2-yl)-9-methyl-7-[(3r)-3-methylpiperazin-1-yl]pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN[C@H](C)CN1C1=CN2C(=O)C=C(C3=NN4C=C(C)N=C(C)C4=C3)N=C2C(C)=C1 OHXBTGLLYWHKMH-CQSZACIVSA-N 0.000 claims 2
• NXZDIUPGWXVWNC-UHFFFAOYSA-N 2-(4-ethyl-6-methylpyrazolo[1,5-a]pyrazin-2-yl)-7-(1-propan-2-ylpiperidin-4-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1=C2C(CC)=NC(C)=CN2N=C1C(N=C1C=C2)=CC(=O)N1C=C2C1CCN(C(C)C)CC1 NXZDIUPGWXVWNC-UHFFFAOYSA-N 0.000 claims 2
• OPPLDAFJJQDEHB-UHFFFAOYSA-N 2-(4-ethyl-6-methylpyrazolo[1,5-a]pyrazin-2-yl)-7-(1-propylpiperidin-4-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(CCC)CCC1C1=CN2C(=O)C=C(C3=NN4C=C(C)N=C(CC)C4=C3)N=C2C=C1 OPPLDAFJJQDEHB-UHFFFAOYSA-N 0.000 claims 2
• QATKMCTWUDXGKK-UHFFFAOYSA-N 2-(4-ethyl-6-methylpyrazolo[1,5-a]pyrazin-2-yl)-7-(4-ethylpiperazin-1-yl)-9-methylpyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(CC)CCN1C1=CN2C(=O)C=C(C3=NN4C=C(C)N=C(CC)C4=C3)N=C2C(C)=C1 QATKMCTWUDXGKK-UHFFFAOYSA-N 0.000 claims 2
• WJQNQABSGAQWIX-UHFFFAOYSA-N 2-(4-ethyl-6-methylpyrazolo[1,5-a]pyrazin-2-yl)-7-(4-ethylpiperazin-1-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(CC)CCN1C1=CN2C(=O)C=C(C3=NN4C=C(C)N=C(CC)C4=C3)N=C2C=C1 WJQNQABSGAQWIX-UHFFFAOYSA-N 0.000 claims 2
• PJDFGVLSZLGLQH-UHFFFAOYSA-N 2-(4-ethyl-6-methylpyrazolo[1,5-a]pyrazin-2-yl)-7-(4-propan-2-ylpiperazin-1-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1=C2C(CC)=NC(C)=CN2N=C1C(N=C1C=C2)=CC(=O)N1C=C2N1CCN(C(C)C)CC1 PJDFGVLSZLGLQH-UHFFFAOYSA-N 0.000 claims 2
• BHVGJQJQAHVDLT-UHFFFAOYSA-N 2-(4-ethyl-6-methylpyrazolo[1,5-a]pyrazin-2-yl)-7-(4-propylpiperazin-1-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(CCC)CCN1C1=CN2C(=O)C=C(C3=NN4C=C(C)N=C(CC)C4=C3)N=C2C=C1 BHVGJQJQAHVDLT-UHFFFAOYSA-N 0.000 claims 2
• CNDGKNQXKNWKEQ-UHFFFAOYSA-N 2-(4-ethyl-6-methylpyrazolo[1,5-a]pyrazin-2-yl)-9-methyl-7-piperidin-4-ylpyrido[1,2-a]pyrimidin-4-one Chemical compound C1=C2C(CC)=NC(C)=CN2N=C1C(N=C1C(C)=C2)=CC(=O)N1C=C2C1CCNCC1 CNDGKNQXKNWKEQ-UHFFFAOYSA-N 0.000 claims 2
• LRUVWYLKRMAYPJ-UHFFFAOYSA-N 2-(6-methyl-4-propylpyrazolo[1,5-a]pyrazin-2-yl)-7-piperazin-1-ylpyrido[1,2-a]pyrimidin-4-one Chemical compound C1=C2C(CCC)=NC(C)=CN2N=C1C(N=C1C=C2)=CC(=O)N1C=C2N1CCNCC1 LRUVWYLKRMAYPJ-UHFFFAOYSA-N 0.000 claims 2
• JDAHQIKOGBIPBF-UHFFFAOYSA-N 2-(8-ethyl-2-methylimidazo[1,2-a]pyridin-6-yl)-7-(1-ethylpiperidin-4-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(CC)CCC1C1=CN2C(=O)C=C(C3=CN4C=C(C)N=C4C(CC)=C3)N=C2C=C1 JDAHQIKOGBIPBF-UHFFFAOYSA-N 0.000 claims 2
• ADCVHNMCENDNNJ-GOSISDBHSA-N 2-(8-ethyl-2-methylimidazo[1,2-a]pyridin-6-yl)-7-[(3r)-4-ethyl-3-methylpiperazin-1-yl]pyrido[1,2-a]pyrimidin-4-one Chemical compound C1[C@@H](C)N(CC)CCN1C1=CN2C(=O)C=C(C3=CN4C=C(C)N=C4C(CC)=C3)N=C2C=C1 ADCVHNMCENDNNJ-GOSISDBHSA-N 0.000 claims 2
• TYPQZWUOAZWGNP-UHFFFAOYSA-N 2-(8-ethyl-2-methylimidazo[1,2-a]pyridin-6-yl)-7-piperazin-1-ylpyrido[1,2-a]pyrimidin-4-one Chemical compound C=1N2C=C(C)N=C2C(CC)=CC=1C(N=C1C=C2)=CC(=O)N1C=C2N1CCNCC1 TYPQZWUOAZWGNP-UHFFFAOYSA-N 0.000 claims 2
• KGSWNDSEVUMJBC-UHFFFAOYSA-N 2-(8-ethyl-2-methylimidazo[1,2-a]pyridin-6-yl)-7-piperidin-4-ylpyrido[1,2-a]pyrimidin-4-one Chemical compound C=1N2C=C(C)N=C2C(CC)=CC=1C(N=C1C=C2)=CC(=O)N1C=C2C1CCNCC1 KGSWNDSEVUMJBC-UHFFFAOYSA-N 0.000 claims 2
• 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims 2
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims 2
• BVZSUFRWSFYEHO-UHFFFAOYSA-N 7-(1-ethylpiperidin-4-yl)-2-(2-methylimidazo[1,2-a]pyridin-6-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(CC)CCC1C1=CN2C(=O)C=C(C3=CN4C=C(C)N=C4C=C3)N=C2C=C1 BVZSUFRWSFYEHO-UHFFFAOYSA-N 0.000 claims 2
• ICFJWVNLOQWVEG-UHFFFAOYSA-N 7-(1-ethylpiperidin-4-yl)-2-(2-methylimidazo[1,2-a]pyridin-7-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(CC)CCC1C1=CN2C(=O)C=C(C3=CC4=NC(C)=CN4C=C3)N=C2C=C1 ICFJWVNLOQWVEG-UHFFFAOYSA-N 0.000 claims 2
• HYHGGJQVCPJLRG-UHFFFAOYSA-N 7-(4-ethylpiperazin-1-yl)-2-(2-methylimidazo[1,2-a]pyridin-7-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(CC)CCN1C1=CN2C(=O)C=C(C3=CC4=NC(C)=CN4C=C3)N=C2C=C1 HYHGGJQVCPJLRG-UHFFFAOYSA-N 0.000 claims 2
• 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims 2
• 125000006308 propyl amino group Chemical group 0.000 claims 2
• 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims 1
• HNEGJTWNOOWEMH-UHFFFAOYSA-N 1-fluoropropane Chemical group [CH2]CCF HNEGJTWNOOWEMH-UHFFFAOYSA-N 0.000 claims 1
• MYUPVYZHSRSOMG-INIZCTEOSA-N 2-(2,7-dimethylindazol-5-yl)-7-[(3s)-3,4-dimethylpiperazin-1-yl]pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(C)[C@@H](C)CN1C1=CN2C(=O)C=C(C3=CC4=CN(C)N=C4C(C)=C3)N=C2C=C1 MYUPVYZHSRSOMG-INIZCTEOSA-N 0.000 claims 1
• OFVMCPPKZFDWOQ-HNNXBMFYSA-N 2-(2,7-dimethylindazol-5-yl)-7-[(3s)-3-methylpiperazin-1-yl]pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN[C@@H](C)CN1C1=CN2C(=O)C=C(C3=CC4=CN(C)N=C4C(C)=C3)N=C2C=C1 OFVMCPPKZFDWOQ-HNNXBMFYSA-N 0.000 claims 1
• FOLOAVVSQXMKRV-UHFFFAOYSA-N 2-(2,8-dimethylimidazo[1,2-a]pyridin-6-yl)-7-(1-methylpiperidin-4-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(C)CCC1C1=CN2C(=O)C=C(C3=CN4C=C(C)N=C4C(C)=C3)N=C2C=C1 FOLOAVVSQXMKRV-UHFFFAOYSA-N 0.000 claims 1
• DFYQXPGNOPPUGS-UHFFFAOYSA-N 2-(2,8-dimethylimidazo[1,2-a]pyridin-6-yl)-7-(4-ethylpiperazin-1-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(CC)CCN1C1=CN2C(=O)C=C(C3=CN4C=C(C)N=C4C(C)=C3)N=C2C=C1 DFYQXPGNOPPUGS-UHFFFAOYSA-N 0.000 claims 1
• WEPNPSKDGNUNDP-UHFFFAOYSA-N 2-(2,8-dimethylimidazo[1,2-a]pyridin-6-yl)-7-[1-(2-hydroxyethyl)piperidin-4-yl]pyrido[1,2-a]pyrimidin-4-one Chemical compound C1=C(C)C2=NC(C)=CN2C=C1C(N=C1C=C2)=CC(=O)N1C=C2C1CCN(CCO)CC1 WEPNPSKDGNUNDP-UHFFFAOYSA-N 0.000 claims 1
• XSUQLWOIPSMMSX-UHFFFAOYSA-N 2-(2-methyl-1,3-benzothiazol-5-yl)-7-(4-methyl-1,4-diazepan-1-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(C)CCCN1C1=CN2C(=O)C=C(C=3C=C4N=C(C)SC4=CC=3)N=C2C=C1 XSUQLWOIPSMMSX-UHFFFAOYSA-N 0.000 claims 1
• KLPKGCBAANJRGL-UHFFFAOYSA-N 2-(2-methyl-1,3-benzothiazol-5-yl)-7-(4-methylpiperazin-1-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(C)CCN1C1=CN2C(=O)C=C(C=3C=C4N=C(C)SC4=CC=3)N=C2C=C1 KLPKGCBAANJRGL-UHFFFAOYSA-N 0.000 claims 1
• FCJFBUROMMKJRC-ZDUSSCGKSA-N 2-(2-methyl-1,3-benzothiazol-5-yl)-7-[(3s)-3-methylpiperazin-1-yl]pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN[C@@H](C)CN1C1=CN2C(=O)C=C(C=3C=C4N=C(C)SC4=CC=3)N=C2C=C1 FCJFBUROMMKJRC-ZDUSSCGKSA-N 0.000 claims 1
• GDVOABXZNBIUEI-UHFFFAOYSA-N 2-(2-methyl-1,3-benzothiazol-6-yl)-7-(1,2,3,6-tetrahydropyridin-4-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1=C2SC(C)=NC2=CC=C1C(N=C1C=C2)=CC(=O)N1C=C2C1=CCNCC1 GDVOABXZNBIUEI-UHFFFAOYSA-N 0.000 claims 1
• UXHOGSTYMVHLMY-ZDUSSCGKSA-N 2-(2-methyl-1,3-benzothiazol-6-yl)-7-[(3s)-3-methylpiperazin-1-yl]pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN[C@@H](C)CN1C1=CN2C(=O)C=C(C=3C=C4SC(C)=NC4=CC=3)N=C2C=C1 UXHOGSTYMVHLMY-ZDUSSCGKSA-N 0.000 claims 1
• WIRNEEAZZNLZFV-UHFFFAOYSA-N 2-(2-methyl-1,3-benzoxazol-6-yl)-7-(1,2,3,6-tetrahydropyridin-4-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1=C2OC(C)=NC2=CC=C1C(N=C1C=C2)=CC(=O)N1C=C2C1=CCNCC1 WIRNEEAZZNLZFV-UHFFFAOYSA-N 0.000 claims 1
• QHGQLEZVCXCAHB-CYBMUJFWSA-N 2-(2-methyl-1,3-benzoxazol-6-yl)-7-[(3r)-3-methylpiperazin-1-yl]pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN[C@H](C)CN1C1=CN2C(=O)C=C(C=3C=C4OC(C)=NC4=CC=3)N=C2C=C1 QHGQLEZVCXCAHB-CYBMUJFWSA-N 0.000 claims 1
• KPSRRUBULZYDKZ-UHFFFAOYSA-N 2-(2-methylimidazo[1,2-a]pyridin-6-yl)-7-(1-propan-2-ylpiperidin-4-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(C(C)C)CCC1C1=CN2C(=O)C=C(C3=CN4C=C(C)N=C4C=C3)N=C2C=C1 KPSRRUBULZYDKZ-UHFFFAOYSA-N 0.000 claims 1
• STBQDINWEFFVNY-UHFFFAOYSA-N 2-(2-methylimidazo[1,2-a]pyridin-6-yl)-7-(1-propylpiperidin-4-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(CCC)CCC1C1=CN2C(=O)C=C(C3=CN4C=C(C)N=C4C=C3)N=C2C=C1 STBQDINWEFFVNY-UHFFFAOYSA-N 0.000 claims 1
• UVIYXIMQVSSPSU-UHFFFAOYSA-N 2-(2-methylimidazo[1,2-a]pyridin-7-yl)-7-(1-methylpiperidin-4-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(C)CCC1C1=CN2C(=O)C=C(C3=CC4=NC(C)=CN4C=C3)N=C2C=C1 UVIYXIMQVSSPSU-UHFFFAOYSA-N 0.000 claims 1
• IIHMBZPFFIHPBB-UHFFFAOYSA-N 2-(2-methylimidazo[1,2-a]pyridin-7-yl)-7-(4-methylpiperazin-1-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(C)CCN1C1=CN2C(=O)C=C(C3=CC4=NC(C)=CN4C=C3)N=C2C=C1 IIHMBZPFFIHPBB-UHFFFAOYSA-N 0.000 claims 1
• BXLXSLNLMZSTCS-UHFFFAOYSA-N 2-(2-methylindazol-5-yl)-7-(1,2,3,6-tetrahydropyridin-4-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1=CC2=NN(C)C=C2C=C1C(N=C1C=C2)=CC(=O)N1C=C2C1=CCNCC1 BXLXSLNLMZSTCS-UHFFFAOYSA-N 0.000 claims 1
• HUBZPKONQHTHRV-UHFFFAOYSA-N 2-(2-methylindazol-5-yl)-7-(1-propan-2-ylpiperidin-4-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(C(C)C)CCC1C1=CN2C(=O)C=C(C3=CC4=CN(C)N=C4C=C3)N=C2C=C1 HUBZPKONQHTHRV-UHFFFAOYSA-N 0.000 claims 1
• DCLSWIKQWGLODE-UHFFFAOYSA-N 2-(4,6-dimethylpyrazolo[1,5-a]pyrazin-2-yl)-7-(1-methylpiperidin-4-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(C)CCC1C1=CN2C(=O)C=C(C3=NN4C=C(C)N=C(C)C4=C3)N=C2C=C1 DCLSWIKQWGLODE-UHFFFAOYSA-N 0.000 claims 1
• CTRKFPRBODSBDX-UHFFFAOYSA-N 2-(4,6-dimethylpyrazolo[1,5-a]pyrazin-2-yl)-7-(4-ethylpiperazin-1-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(CC)CCN1C1=CN2C(=O)C=C(C3=NN4C=C(C)N=C(C)C4=C3)N=C2C=C1 CTRKFPRBODSBDX-UHFFFAOYSA-N 0.000 claims 1
• ZUYOOCCQYSTVKL-UHFFFAOYSA-N 2-(4,6-dimethylpyrazolo[1,5-a]pyrazin-2-yl)-7-(4-methylpiperazin-1-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(C)CCN1C1=CN2C(=O)C=C(C3=NN4C=C(C)N=C(C)C4=C3)N=C2C=C1 ZUYOOCCQYSTVKL-UHFFFAOYSA-N 0.000 claims 1
• DKDIOPUYCYXLPG-IYBDPMFKSA-N 2-(4,6-dimethylpyrazolo[1,5-a]pyrazin-2-yl)-7-[(3s,5r)-3,4,5-trimethylpiperazin-1-yl]pyrido[1,2-a]pyrimidin-4-one Chemical compound C1[C@@H](C)N(C)[C@@H](C)CN1C1=CN2C(=O)C=C(C3=NN4C=C(C)N=C(C)C4=C3)N=C2C=C1 DKDIOPUYCYXLPG-IYBDPMFKSA-N 0.000 claims 1
• NQLVJSTVKKDOFP-UHFFFAOYSA-N 2-(4,6-dimethylpyrazolo[1,5-a]pyrazin-2-yl)-7-[1-(2-hydroxyethyl)piperidin-4-yl]pyrido[1,2-a]pyrimidin-4-one Chemical compound C1=C2C(C)=NC(C)=CN2N=C1C(N=C1C=C2)=CC(=O)N1C=C2C1CCN(CCO)CC1 NQLVJSTVKKDOFP-UHFFFAOYSA-N 0.000 claims 1
• ZWIUGKSDAUYQBK-UHFFFAOYSA-N 2-(4,6-dimethylpyrazolo[1,5-a]pyrazin-2-yl)-7-[1-(oxetan-3-yl)piperidin-4-yl]pyrido[1,2-a]pyrimidin-4-one Chemical compound C1=C2C(C)=NC(C)=CN2N=C1C(N=C1C=C2)=CC(=O)N1C=C2C(CC1)CCN1C1COC1 ZWIUGKSDAUYQBK-UHFFFAOYSA-N 0.000 claims 1
• MOIXARMKKQDNPM-UHFFFAOYSA-N 2-(4,6-dimethylpyrazolo[1,5-a]pyrazin-2-yl)-7-[4-(2-hydroxyethyl)piperazin-1-yl]pyrido[1,2-a]pyrimidin-4-one Chemical compound C1=C2C(C)=NC(C)=CN2N=C1C(N=C1C=C2)=CC(=O)N1C=C2N1CCN(CCO)CC1 MOIXARMKKQDNPM-UHFFFAOYSA-N 0.000 claims 1
• OAKRTJXBWCRRPK-UHFFFAOYSA-N 2-(4,6-dimethylpyrazolo[1,5-a]pyrazin-2-yl)-7-[4-(piperidin-1-ylmethyl)piperidin-1-yl]pyrido[1,2-a]pyrimidin-4-one Chemical compound C1=C2C(C)=NC(C)=CN2N=C1C(N=C1C=C2)=CC(=O)N1C=C2N(CC1)CCC1CN1CCCCC1 OAKRTJXBWCRRPK-UHFFFAOYSA-N 0.000 claims 1
• JLFYUIUFCVPQEI-UHFFFAOYSA-N 2-(4,6-dimethylpyrazolo[1,5-a]pyrazin-2-yl)-7-piperazin-1-ylpyrido[1,2-a]pyrimidin-4-one Chemical compound C1=C2C(C)=NC(C)=CN2N=C1C(N=C1C=C2)=CC(=O)N1C=C2N1CCNCC1 JLFYUIUFCVPQEI-UHFFFAOYSA-N 0.000 claims 1
• XYFOOAYHCWVOQM-UHFFFAOYSA-N 2-(4,6-dimethylpyrazolo[1,5-a]pyrazin-2-yl)-9-methyl-7-(4-methyl-1,4-diazepan-1-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(C)CCCN1C1=CN2C(=O)C=C(C3=NN4C=C(C)N=C(C)C4=C3)N=C2C(C)=C1 XYFOOAYHCWVOQM-UHFFFAOYSA-N 0.000 claims 1
• OHXBTGLLYWHKMH-AWEZNQCLSA-N 2-(4,6-dimethylpyrazolo[1,5-a]pyrazin-2-yl)-9-methyl-7-[(3s)-3-methylpiperazin-1-yl]pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN[C@@H](C)CN1C1=CN2C(=O)C=C(C3=NN4C=C(C)N=C(C)C4=C3)N=C2C(C)=C1 OHXBTGLLYWHKMH-AWEZNQCLSA-N 0.000 claims 1
• INZVBTQELSVJSH-UHFFFAOYSA-N 2-(4,6-dimethylpyrazolo[1,5-a]pyrazin-2-yl)-9-methyl-7-piperidin-4-ylpyrido[1,2-a]pyrimidin-4-one Chemical compound C1=C2C(C)=NC(C)=CN2N=C1C(N=C1C(C)=C2)=CC(=O)N1C=C2C1CCNCC1 INZVBTQELSVJSH-UHFFFAOYSA-N 0.000 claims 1
• FQPOVGURIHHJQR-UHFFFAOYSA-N 2-(4-cyclopropyl-6-methylpyrazolo[1,5-a]pyrazin-2-yl)-7-(4-methylpiperazin-1-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(C)CCN1C1=CN2C(=O)C=C(C3=NN4C=C(C)N=C(C4=C3)C3CC3)N=C2C=C1 FQPOVGURIHHJQR-UHFFFAOYSA-N 0.000 claims 1
• KKYBJLKEWFRIKV-UHFFFAOYSA-N 2-(4-ethyl-6-methylpyrazolo[1,5-a]pyrazin-2-yl)-7-(1,2,3,6-tetrahydropyridin-4-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1=C2C(CC)=NC(C)=CN2N=C1C(N=C1C=C2)=CC(=O)N1C=C2C1=CCNCC1 KKYBJLKEWFRIKV-UHFFFAOYSA-N 0.000 claims 1
• KFDBDTFAQQMAGO-UHFFFAOYSA-N 2-(4-ethyl-6-methylpyrazolo[1,5-a]pyrazin-2-yl)-7-(1-ethylpiperidin-4-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(CC)CCC1C1=CN2C(=O)C=C(C3=NN4C=C(C)N=C(CC)C4=C3)N=C2C=C1 KFDBDTFAQQMAGO-UHFFFAOYSA-N 0.000 claims 1
• WGUIYFGQOJNUTI-UHFFFAOYSA-N 2-(4-ethyl-6-methylpyrazolo[1,5-a]pyrazin-2-yl)-7-(1-methylpiperidin-4-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1=C2C(CC)=NC(C)=CN2N=C1C(N=C1C=C2)=CC(=O)N1C=C2C1CCN(C)CC1 WGUIYFGQOJNUTI-UHFFFAOYSA-N 0.000 claims 1
• FICLUJLAYRZCAR-UHFFFAOYSA-N 2-(4-ethyl-6-methylpyrazolo[1,5-a]pyrazin-2-yl)-7-(4-methyl-1,4-diazepan-1-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1=C2C(CC)=NC(C)=CN2N=C1C(N=C1C=C2)=CC(=O)N1C=C2N1CCCN(C)CC1 FICLUJLAYRZCAR-UHFFFAOYSA-N 0.000 claims 1
• VGZZMHRFFBUFKC-UHFFFAOYSA-N 2-(4-ethyl-6-methylpyrazolo[1,5-a]pyrazin-2-yl)-7-(4-methylpiperazin-1-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1=C2C(CC)=NC(C)=CN2N=C1C(N=C1C=C2)=CC(=O)N1C=C2N1CCN(C)CC1 VGZZMHRFFBUFKC-UHFFFAOYSA-N 0.000 claims 1
• IVQXSTNGJUUWAL-GOSISDBHSA-N 2-(4-ethyl-6-methylpyrazolo[1,5-a]pyrazin-2-yl)-7-[(3r)-3-methyl-4-propan-2-ylpiperazin-1-yl]pyrido[1,2-a]pyrimidin-4-one Chemical compound C1=C2C(CC)=NC(C)=CN2N=C1C(N=C1C=C2)=CC(=O)N1C=C2N1CCN(C(C)C)[C@H](C)C1 IVQXSTNGJUUWAL-GOSISDBHSA-N 0.000 claims 1
• VRYXYWOBHHFGIM-GOSISDBHSA-N 2-(4-ethyl-6-methylpyrazolo[1,5-a]pyrazin-2-yl)-7-[(3r)-3-methyl-4-propylpiperazin-1-yl]pyrido[1,2-a]pyrimidin-4-one Chemical compound C1[C@@H](C)N(CCC)CCN1C1=CN2C(=O)C=C(C3=NN4C=C(C)N=C(CC)C4=C3)N=C2C=C1 VRYXYWOBHHFGIM-GOSISDBHSA-N 0.000 claims 1
• AZIYEFOSSWYCPA-CQSZACIVSA-N 2-(4-ethyl-6-methylpyrazolo[1,5-a]pyrazin-2-yl)-7-[(3r)-3-methylpiperazin-1-yl]pyrido[1,2-a]pyrimidin-4-one Chemical compound C1=C2C(CC)=NC(C)=CN2N=C1C(N=C1C=C2)=CC(=O)N1C=C2N1CCN[C@H](C)C1 AZIYEFOSSWYCPA-CQSZACIVSA-N 0.000 claims 1
• NZBLSDZPIYBVPX-UHFFFAOYSA-N 2-(4-ethyl-6-methylpyrazolo[1,5-a]pyrazin-2-yl)-7-[1-(3-fluoropropyl)piperidin-4-yl]pyrido[1,2-a]pyrimidin-4-one Chemical compound C1=C2C(CC)=NC(C)=CN2N=C1C(N=C1C=C2)=CC(=O)N1C=C2C1CCN(CCCF)CC1 NZBLSDZPIYBVPX-UHFFFAOYSA-N 0.000 claims 1
• XGEYEHDERJNTGG-UHFFFAOYSA-N 2-(4-ethyl-6-methylpyrazolo[1,5-a]pyrazin-2-yl)-7-[4-(2-fluoroethyl)piperazin-1-yl]pyrido[1,2-a]pyrimidin-4-one Chemical compound C1=C2C(CC)=NC(C)=CN2N=C1C(N=C1C=C2)=CC(=O)N1C=C2N1CCN(CCF)CC1 XGEYEHDERJNTGG-UHFFFAOYSA-N 0.000 claims 1
• PWIOYQQOOWPTDN-UHFFFAOYSA-N 2-(4-ethyl-6-methylpyrazolo[1,5-a]pyrazin-2-yl)-7-[4-(2-hydroxyethyl)piperazin-1-yl]pyrido[1,2-a]pyrimidin-4-one Chemical compound C1=C2C(CC)=NC(C)=CN2N=C1C(N=C1C=C2)=CC(=O)N1C=C2N1CCN(CCO)CC1 PWIOYQQOOWPTDN-UHFFFAOYSA-N 0.000 claims 1
• ZMSVZYJNMNOYAW-UHFFFAOYSA-N 2-(4-ethyl-6-methylpyrazolo[1,5-a]pyrazin-2-yl)-7-[4-(3-fluoropropyl)piperazin-1-yl]pyrido[1,2-a]pyrimidin-4-one Chemical compound C1=C2C(CC)=NC(C)=CN2N=C1C(N=C1C=C2)=CC(=O)N1C=C2N1CCN(CCCF)CC1 ZMSVZYJNMNOYAW-UHFFFAOYSA-N 0.000 claims 1
• QEIBZMAOAFKPSZ-UHFFFAOYSA-N 2-(4-ethyl-6-methylpyrazolo[1,5-a]pyrazin-2-yl)-7-piperidin-4-ylpyrido[1,2-a]pyrimidin-4-one Chemical compound C1=C2C(CC)=NC(C)=CN2N=C1C(N=C1C=C2)=CC(=O)N1C=C2C1CCNCC1 QEIBZMAOAFKPSZ-UHFFFAOYSA-N 0.000 claims 1
• GYFRQCMDLBNZSF-UHFFFAOYSA-N 2-(4-ethyl-6-methylpyrazolo[1,5-a]pyrazin-2-yl)-9-methyl-7-(1-methylpiperidin-4-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1=C2C(CC)=NC(C)=CN2N=C1C(N=C1C(C)=C2)=CC(=O)N1C=C2C1CCN(C)CC1 GYFRQCMDLBNZSF-UHFFFAOYSA-N 0.000 claims 1
• ODTRIHIKMZAFAA-UHFFFAOYSA-N 2-(4-fluoro-2-methyl-1,3-benzoxazol-6-yl)-7-(4-methylpiperazin-1-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(C)CCN1C1=CN2C(=O)C=C(C=3C=C4OC(C)=NC4=C(F)C=3)N=C2C=C1 ODTRIHIKMZAFAA-UHFFFAOYSA-N 0.000 claims 1
• WMGIQXYMZKSCGJ-UHFFFAOYSA-N 2-(4-fluoro-2-methyl-1,3-benzoxazol-6-yl)-7-(4-propylpiperazin-1-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(CCC)CCN1C1=CN2C(=O)C=C(C=3C=C4OC(C)=NC4=C(F)C=3)N=C2C=C1 WMGIQXYMZKSCGJ-UHFFFAOYSA-N 0.000 claims 1
• WJKKVBMVXUZLLP-UHFFFAOYSA-N 2-(4-fluoro-2-methyl-1,3-benzoxazol-6-yl)-7-piperazin-1-ylpyrido[1,2-a]pyrimidin-4-one Chemical compound C1=C2OC(C)=NC2=C(F)C=C1C(N=C1C=C2)=CC(=O)N1C=C2N1CCNCC1 WJKKVBMVXUZLLP-UHFFFAOYSA-N 0.000 claims 1
• ZJNWFWQDPMCSDN-UHFFFAOYSA-N 2-(4-hydroxypiperidin-4-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C=1C(=O)N2C=CC=CC2=NC=1C1(O)CCNCC1 ZJNWFWQDPMCSDN-UHFFFAOYSA-N 0.000 claims 1
• BGMCWVPTRAQUCE-UHFFFAOYSA-N 2-(5,7-dimethylfuro[2,3-c]pyridin-2-yl)-7-(4-ethylpiperazin-1-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(CC)CCN1C1=CN2C(=O)C=C(C=3OC4=C(C)N=C(C)C=C4C=3)N=C2C=C1 BGMCWVPTRAQUCE-UHFFFAOYSA-N 0.000 claims 1
• LRMUCNUZTYXXGR-GASCZTMLSA-N 2-(5,7-dimethylfuro[2,3-c]pyridin-2-yl)-7-[(3r,5s)-3,5-dimethylpiperazin-1-yl]pyrido[1,2-a]pyrimidin-4-one Chemical compound C1[C@@H](C)N[C@@H](C)CN1C1=CN2C(=O)C=C(C=3OC4=C(C)N=C(C)C=C4C=3)N=C2C=C1 LRMUCNUZTYXXGR-GASCZTMLSA-N 0.000 claims 1
• JCGBCDPIZLKDNB-LBPRGKRZSA-N 2-(5-fluoro-6-methoxypyridin-3-yl)-7-[(3s)-3-methylpiperazin-1-yl]pyrido[1,2-a]pyrimidin-4-one Chemical compound C1=C(F)C(OC)=NC=C1C1=CC(=O)N(C=C(C=C2)N3C[C@H](C)NCC3)C2=N1 JCGBCDPIZLKDNB-LBPRGKRZSA-N 0.000 claims 1
• TUYAYLPCPVPDRJ-UHFFFAOYSA-N 2-(6,8-dimethylimidazo[1,2-a]pyrazin-2-yl)-7-piperazin-1-ylpyrido[1,2-a]pyrimidin-4-one Chemical compound N1=C2C(C)=NC(C)=CN2C=C1C(N=C1C=C2)=CC(=O)N1C=C2N1CCNCC1 TUYAYLPCPVPDRJ-UHFFFAOYSA-N 0.000 claims 1
• CUARIEHBYAWZKS-UHFFFAOYSA-N 2-(6-methyl-4-oxo-5h-pyrazolo[1,5-a]pyrazin-2-yl)-7-(4-methylpiperazin-1-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(C)CCN1C1=CN2C(=O)C=C(C3=NN4C(C(NC(C)=C4)=O)=C3)N=C2C=C1 CUARIEHBYAWZKS-UHFFFAOYSA-N 0.000 claims 1
• HDHRQXYWEFGCMZ-UHFFFAOYSA-N 2-(8-chloro-2-methylimidazo[1,2-a]pyridin-6-yl)-7-(1-ethylpiperidin-4-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(CC)CCC1C1=CN2C(=O)C=C(C3=CN4C=C(C)N=C4C(Cl)=C3)N=C2C=C1 HDHRQXYWEFGCMZ-UHFFFAOYSA-N 0.000 claims 1
• BMZLJVHOGPZEAK-UHFFFAOYSA-N 2-(8-chloro-2-methylimidazo[1,2-a]pyridin-6-yl)-7-(1-methylpiperidin-4-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(C)CCC1C1=CN2C(=O)C=C(C3=CN4C=C(C)N=C4C(Cl)=C3)N=C2C=C1 BMZLJVHOGPZEAK-UHFFFAOYSA-N 0.000 claims 1
• ZWVASHQZGDDHGI-UHFFFAOYSA-N 2-(8-chloro-2-methylimidazo[1,2-a]pyridin-6-yl)-7-(1-propan-2-ylpiperidin-4-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(C(C)C)CCC1C1=CN2C(=O)C=C(C3=CN4C=C(C)N=C4C(Cl)=C3)N=C2C=C1 ZWVASHQZGDDHGI-UHFFFAOYSA-N 0.000 claims 1
• PEJOAFFTWMYADX-UHFFFAOYSA-N 2-(8-chloro-2-methylimidazo[1,2-a]pyridin-6-yl)-7-(4-ethylpiperazin-1-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(CC)CCN1C1=CN2C(=O)C=C(C3=CN4C=C(C)N=C4C(Cl)=C3)N=C2C=C1 PEJOAFFTWMYADX-UHFFFAOYSA-N 0.000 claims 1
• VDVZGFFDUGUWID-UHFFFAOYSA-N 2-(8-chloro-2-methylimidazo[1,2-a]pyridin-6-yl)-7-(4-methyl-1,4-diazepan-1-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(C)CCCN1C1=CN2C(=O)C=C(C3=CN4C=C(C)N=C4C(Cl)=C3)N=C2C=C1 VDVZGFFDUGUWID-UHFFFAOYSA-N 0.000 claims 1
• QNBUOAFOCFOIKX-UHFFFAOYSA-N 2-(8-chloro-2-methylimidazo[1,2-a]pyridin-6-yl)-7-(4-propan-2-ylpiperazin-1-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(C(C)C)CCN1C1=CN2C(=O)C=C(C3=CN4C=C(C)N=C4C(Cl)=C3)N=C2C=C1 QNBUOAFOCFOIKX-UHFFFAOYSA-N 0.000 claims 1
• GMFAXLOQWJYWEH-MRXNPFEDSA-N 2-(8-chloro-2-methylimidazo[1,2-a]pyridin-6-yl)-7-[(3r)-4-ethyl-3-methylpiperazin-1-yl]pyrido[1,2-a]pyrimidin-4-one Chemical compound C1[C@@H](C)N(CC)CCN1C1=CN2C(=O)C=C(C3=CN4C=C(C)N=C4C(Cl)=C3)N=C2C=C1 GMFAXLOQWJYWEH-MRXNPFEDSA-N 0.000 claims 1
• NSERVHVSFPIUSO-HNNXBMFYSA-N 2-(8-chloro-2-methylimidazo[1,2-a]pyridin-6-yl)-7-[(3s)-3,4-dimethylpiperazin-1-yl]pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(C)[C@@H](C)CN1C1=CN2C(=O)C=C(C3=CN4C=C(C)N=C4C(Cl)=C3)N=C2C=C1 NSERVHVSFPIUSO-HNNXBMFYSA-N 0.000 claims 1
• GMFAXLOQWJYWEH-INIZCTEOSA-N 2-(8-chloro-2-methylimidazo[1,2-a]pyridin-6-yl)-7-[(3s)-4-ethyl-3-methylpiperazin-1-yl]pyrido[1,2-a]pyrimidin-4-one Chemical compound C1[C@H](C)N(CC)CCN1C1=CN2C(=O)C=C(C3=CN4C=C(C)N=C4C(Cl)=C3)N=C2C=C1 GMFAXLOQWJYWEH-INIZCTEOSA-N 0.000 claims 1
• VDXBDZHSNAQYAR-OKILXGFUSA-N 2-(8-chloro-2-methylimidazo[1,2-a]pyridin-6-yl)-7-[(3s,5r)-3,5-dimethylpiperazin-1-yl]pyrido[1,2-a]pyrimidin-4-one Chemical compound C1[C@@H](C)N[C@@H](C)CN1C1=CN2C(=O)C=C(C3=CN4C=C(C)N=C4C(Cl)=C3)N=C2C=C1 VDXBDZHSNAQYAR-OKILXGFUSA-N 0.000 claims 1
• IRBDSPQBNBCRAZ-UHFFFAOYSA-N 2-(8-chloro-2-methylimidazo[1,2-a]pyridin-6-yl)-7-piperidin-4-ylpyrido[1,2-a]pyrimidin-4-one Chemical compound C1=C(Cl)C2=NC(C)=CN2C=C1C(N=C1C=C2)=CC(=O)N1C=C2C1CCNCC1 IRBDSPQBNBCRAZ-UHFFFAOYSA-N 0.000 claims 1
• QSWRMPQQYQBTOH-OAHLLOKOSA-N 2-(8-cyclopropyl-2-methylimidazo[1,2-a]pyridin-6-yl)-7-[(3r)-3-methylpiperazin-1-yl]pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN[C@H](C)CN1C1=CN2C(=O)C=C(C3=CN4C=C(C)N=C4C(C4CC4)=C3)N=C2C=C1 QSWRMPQQYQBTOH-OAHLLOKOSA-N 0.000 claims 1
• QSWRMPQQYQBTOH-HNNXBMFYSA-N 2-(8-cyclopropyl-2-methylimidazo[1,2-a]pyridin-6-yl)-7-[(3s)-3-methylpiperazin-1-yl]pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN[C@@H](C)CN1C1=CN2C(=O)C=C(C3=CN4C=C(C)N=C4C(C4CC4)=C3)N=C2C=C1 QSWRMPQQYQBTOH-HNNXBMFYSA-N 0.000 claims 1
• MJILSFLDXATUOS-UHFFFAOYSA-N 2-(8-cyclopropyl-2-methylimidazo[1,2-a]pyridin-6-yl)-7-piperazin-1-ylpyrido[1,2-a]pyrimidin-4-one Chemical compound C12=NC(C)=CN2C=C(C=2N=C3C=CC(=CN3C(=O)C=2)N2CCNCC2)C=C1C1CC1 MJILSFLDXATUOS-UHFFFAOYSA-N 0.000 claims 1
• WKLKZLTUZFUWPS-UHFFFAOYSA-N 2-(8-ethyl-2-methylimidazo[1,2-a]pyridin-6-yl)-7-(4-methyl-1,4-diazepan-1-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C=1N2C=C(C)N=C2C(CC)=CC=1C(N=C1C=C2)=CC(=O)N1C=C2N1CCCN(C)CC1 WKLKZLTUZFUWPS-UHFFFAOYSA-N 0.000 claims 1
• UGTJXXHGRUOQHW-OAHLLOKOSA-N 2-(8-ethyl-2-methylimidazo[1,2-a]pyridin-6-yl)-7-[(3r)-3-methylpiperazin-1-yl]pyrido[1,2-a]pyrimidin-4-one Chemical compound C=1N2C=C(C)N=C2C(CC)=CC=1C(N=C1C=C2)=CC(=O)N1C=C2N1CCN[C@H](C)C1 UGTJXXHGRUOQHW-OAHLLOKOSA-N 0.000 claims 1
• NHPIEJFMBMXFHA-UHFFFAOYSA-N 2-(8-ethyl-2-methylimidazo[1,2-a]pyridin-6-yl)-7-[1-(2-hydroxyethyl)piperidin-4-yl]pyrido[1,2-a]pyrimidin-4-one Chemical compound C=1N2C=C(C)N=C2C(CC)=CC=1C(N=C1C=C2)=CC(=O)N1C=C2C1CCN(CCO)CC1 NHPIEJFMBMXFHA-UHFFFAOYSA-N 0.000 claims 1
• GMKDLIOVAWXNLM-UHFFFAOYSA-N 2-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-7-(1-methylpiperidin-4-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(C)CCC1C1=CN2C(=O)C=C(C3=CN4C=C(C)N=C4C(F)=C3)N=C2C=C1 GMKDLIOVAWXNLM-UHFFFAOYSA-N 0.000 claims 1
• XHOYBAGQVFXSAR-UHFFFAOYSA-N 2-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-7-(4-methyl-1,4-diazepan-1-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(C)CCCN1C1=CN2C(=O)C=C(C3=CN4C=C(C)N=C4C(F)=C3)N=C2C=C1 XHOYBAGQVFXSAR-UHFFFAOYSA-N 0.000 claims 1
• SEBPCUZCYYOTMT-UHFFFAOYSA-N 2-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)-7-[4-(2-hydroxyethyl)piperazin-1-yl]pyrido[1,2-a]pyrimidin-4-one Chemical compound C1=C(F)C2=NC(C)=CN2C=C1C(N=C1C=C2)=CC(=O)N1C=C2N1CCN(CCO)CC1 SEBPCUZCYYOTMT-UHFFFAOYSA-N 0.000 claims 1
• NAVSPWBTDOGOHB-UHFFFAOYSA-N 2-[4-(dimethylamino)-6-methylpyrazolo[1,5-a]pyrazin-2-yl]-7-piperazin-1-ylpyrido[1,2-a]pyrimidin-4-one Chemical compound C1=C2C(N(C)C)=NC(C)=CN2N=C1C(N=C1C=C2)=CC(=O)N1C=C2N1CCNCC1 NAVSPWBTDOGOHB-UHFFFAOYSA-N 0.000 claims 1
• YUDBUYQSBPXHPE-UHFFFAOYSA-N 2-[6-(dimethylamino)pyridin-3-yl]-7-(1-methyl-3,6-dihydro-2h-pyridin-4-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1=NC(N(C)C)=CC=C1C1=CC(=O)N(C=C(C=C2)C=3CCN(C)CC=3)C2=N1 YUDBUYQSBPXHPE-UHFFFAOYSA-N 0.000 claims 1
• ISHPVVFZQIFAOW-UHFFFAOYSA-N 2-[8-(hydroxymethyl)-2-methylimidazo[1,2-a]pyridin-6-yl]-7-(4-methylpiperazin-1-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(C)CCN1C1=CN2C(=O)C=C(C3=CN4C=C(C)N=C4C(CO)=C3)N=C2C=C1 ISHPVVFZQIFAOW-UHFFFAOYSA-N 0.000 claims 1
• 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims 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 claims 1
• DFHUWSWQDFQMCY-UHFFFAOYSA-N 7-(1,2,3,3a,4,6,7,7a-octahydropyrrolo[3,2-c]pyridin-5-yl)-2-(4,6-dimethylpyrazolo[1,5-a]pyrazin-2-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CC2NCCC2CN1C(C=CC1=N2)=CN1C(=O)C=C2C1=NN2C=C(C)N=C(C)C2=C1 DFHUWSWQDFQMCY-UHFFFAOYSA-N 0.000 claims 1
• ZIFXFWUDPJRGPU-UHFFFAOYSA-N 7-(1,4-diazepan-1-yl)-2-(2-methylimidazo[1,2-a]pyridin-6-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1=CC2=NC(C)=CN2C=C1C(N=C1C=C2)=CC(=O)N1C=C2N1CCCNCC1 ZIFXFWUDPJRGPU-UHFFFAOYSA-N 0.000 claims 1
• LVAPLRFZTHTLAL-UHFFFAOYSA-N 7-(1-ethyl-3,6-dihydro-2h-pyridin-4-yl)-2-(4-fluoro-2-methyl-1,3-benzoxazol-6-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1N(CC)CCC(C2=CN3C(=O)C=C(N=C3C=C2)C=2C=C3OC(C)=NC3=C(F)C=2)=C1 LVAPLRFZTHTLAL-UHFFFAOYSA-N 0.000 claims 1
• BFBGKCCTJNYZMA-UHFFFAOYSA-N 7-(1-ethylpiperidin-4-yl)-9-methyl-2-(2-methylindazol-5-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(CC)CCC1C1=CN2C(=O)C=C(C3=CC4=CN(C)N=C4C=C3)N=C2C(C)=C1 BFBGKCCTJNYZMA-UHFFFAOYSA-N 0.000 claims 1
• OWVQZRFZDBWDBM-UHFFFAOYSA-N 7-(1-methyl-3,6-dihydro-2h-pyridin-4-yl)-2-(2-methylimidazo[1,2-a]pyridin-6-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1N(C)CCC(C2=CN3C(=O)C=C(N=C3C=C2)C2=CN3C=C(C)N=C3C=C2)=C1 OWVQZRFZDBWDBM-UHFFFAOYSA-N 0.000 claims 1
• JVKXJRATQFXWKQ-UHFFFAOYSA-N 7-(3,3-dimethylpiperazin-1-yl)-2-(2-methyl-1,3-benzothiazol-6-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1=C2SC(C)=NC2=CC=C1C(N=C1C=C2)=CC(=O)N1C=C2N1CCNC(C)(C)C1 JVKXJRATQFXWKQ-UHFFFAOYSA-N 0.000 claims 1
• BMCQICWBUORYQO-UHFFFAOYSA-N 7-(3,3-dimethylpiperazin-1-yl)-2-(2-methyl-1,3-benzoxazol-6-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1=C2OC(C)=NC2=CC=C1C(N=C1C=C2)=CC(=O)N1C=C2N1CCNC(C)(C)C1 BMCQICWBUORYQO-UHFFFAOYSA-N 0.000 claims 1
• QOMRBYVJLHYABG-UHFFFAOYSA-N 7-(3-aminopropyl)-2-(4,6-dimethylpyrazolo[1,5-a]pyrazin-2-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1=C(CCCN)C=CC2=NC(C3=NN4C=C(N=C(C)C4=C3)C)=CC(=O)N21 QOMRBYVJLHYABG-UHFFFAOYSA-N 0.000 claims 1
• IARWGHSMMOWMGK-UHFFFAOYSA-N 7-(4-cyclobutylpiperazin-1-yl)-2-(8-ethyl-2-methylimidazo[1,2-a]pyridin-6-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C=1N2C=C(C)N=C2C(CC)=CC=1C(N=C1C=C2)=CC(=O)N1C=C2N(CC1)CCN1C1CCC1 IARWGHSMMOWMGK-UHFFFAOYSA-N 0.000 claims 1
• CSQFAEXUUNGYIA-UHFFFAOYSA-N 7-(4-ethylpiperazin-1-yl)-2-(4-fluoro-2-methyl-1,3-benzoxazol-6-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(CC)CCN1C1=CN2C(=O)C=C(C=3C=C4OC(C)=NC4=C(F)C=3)N=C2C=C1 CSQFAEXUUNGYIA-UHFFFAOYSA-N 0.000 claims 1
• AGXNBBANBDUUHQ-UHFFFAOYSA-N 7-(4-ethylpiperazin-1-yl)-2-(6-methylpyrazolo[1,5-a]pyrazin-2-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(CC)CCN1C1=CN2C(=O)C=C(C3=NN4C=C(C)N=CC4=C3)N=C2C=C1 AGXNBBANBDUUHQ-UHFFFAOYSA-N 0.000 claims 1
• GUTGDZVWQCCPGY-UHFFFAOYSA-N 7-(4-ethylpiperazin-1-yl)-2-[8-(hydroxymethyl)-2-methylimidazo[1,2-a]pyridin-6-yl]pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(CC)CCN1C1=CN2C(=O)C=C(C3=CN4C=C(C)N=C4C(CO)=C3)N=C2C=C1 GUTGDZVWQCCPGY-UHFFFAOYSA-N 0.000 claims 1
• ZDARBZVPKITNFW-KBPBESRZSA-N 7-[(2s,6s)-2,6-dimethylpiperidin-4-yl]-2-(4,6-dimethylpyrazolo[1,5-a]pyrazin-2-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1[C@H](C)N[C@@H](C)CC1C1=CN2C(=O)C=C(C3=NN4C=C(C)N=C(C)C4=C3)N=C2C=C1 ZDARBZVPKITNFW-KBPBESRZSA-N 0.000 claims 1
• NAGWFGAVPHHVDO-IYBDPMFKSA-N 7-[(3ar,6as)-2,3,3a,4,6,6a-hexahydro-1h-pyrrolo[3,4-c]pyrrol-5-yl]-2-(2-methyl-1,3-benzothiazol-5-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1=CC2=NC(C=3C=C4N=C(SC4=CC=3)C)=CC(=O)N2C=C1N1C[C@H]2CNC[C@H]2C1 NAGWFGAVPHHVDO-IYBDPMFKSA-N 0.000 claims 1
• HDQXAZRTORTBKF-MRXNPFEDSA-N 7-[(3r)-3-(dimethylamino)pyrrolidin-1-yl]-2-(2-methyl-1,3-benzothiazol-6-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1[C@H](N(C)C)CCN1C1=CN2C(=O)C=C(C=3C=C4SC(C)=NC4=CC=3)N=C2C=C1 HDQXAZRTORTBKF-MRXNPFEDSA-N 0.000 claims 1
• UMYNNCLNFBPMLA-MRXNPFEDSA-N 7-[(3r)-3-(dimethylamino)pyrrolidin-1-yl]-2-(2-methyl-1,3-benzoxazol-6-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1[C@H](N(C)C)CCN1C1=CN2C(=O)C=C(C=3C=C4OC(C)=NC4=CC=3)N=C2C=C1 UMYNNCLNFBPMLA-MRXNPFEDSA-N 0.000 claims 1
• GMWAXNUOUZXHEI-BETUJISGSA-N 7-[(3r,5s)-3,5-dimethylpiperazin-1-yl]-2-(5-fluoro-6-methoxypyridin-3-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1=C(F)C(OC)=NC=C1C1=CC(=O)N(C=C(C=C2)N3C[C@@H](C)N[C@@H](C)C3)C2=N1 GMWAXNUOUZXHEI-BETUJISGSA-N 0.000 claims 1
• UMYNNCLNFBPMLA-INIZCTEOSA-N 7-[(3s)-3-(dimethylamino)pyrrolidin-1-yl]-2-(2-methyl-1,3-benzoxazol-6-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1[C@@H](N(C)C)CCN1C1=CN2C(=O)C=C(C=3C=C4OC(C)=NC4=CC=3)N=C2C=C1 UMYNNCLNFBPMLA-INIZCTEOSA-N 0.000 claims 1
• NCSFCWBEYKEMFE-KRWDZBQOSA-N 7-[(3s)-4-cyclobutyl-3-methylpiperazin-1-yl]-2-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C([C@@H]1C)N(C2=CN3C(=O)C=C(N=C3C=C2)C2=CN3C=C(C)N=C3C(F)=C2)CCN1C1CCC1 NCSFCWBEYKEMFE-KRWDZBQOSA-N 0.000 claims 1
• BJFBXBNCUYAWDA-IYBDPMFKSA-N 7-[(3s,5r)-3,5-dimethylpiperazin-1-yl]-2-(6-methyl-4-propylpyrazolo[1,5-a]pyrazin-2-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1=C2C(CCC)=NC(C)=CN2N=C1C(N=C1C=C2)=CC(=O)N1C=C2N1C[C@H](C)N[C@H](C)C1 BJFBXBNCUYAWDA-IYBDPMFKSA-N 0.000 claims 1
• NYUALBMHSLXRIC-IYBDPMFKSA-N 7-[(3s,5r)-3,5-dimethylpiperazin-1-yl]-2-(8-ethyl-2-methylimidazo[1,2-a]pyridin-6-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C=1N2C=C(C)N=C2C(CC)=CC=1C(N=C1C=C2)=CC(=O)N1C=C2N1C[C@H](C)N[C@H](C)C1 NYUALBMHSLXRIC-IYBDPMFKSA-N 0.000 claims 1
• MVGFLJDSEHDEEB-OKILXGFUSA-N 7-[(3s,5r)-3,5-dimethylpiperazin-1-yl]-2-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1[C@@H](C)N[C@@H](C)CN1C1=CN2C(=O)C=C(C3=CN4C=C(C)N=C4C(F)=C3)N=C2C=C1 MVGFLJDSEHDEEB-OKILXGFUSA-N 0.000 claims 1
• ZRMSACWSMCUDPK-QGZVFWFLSA-N 7-[(8ar)-3,4,6,7,8,8a-hexahydro-1h-pyrrolo[1,2-a]pyrazin-2-yl]-2-(2-methyl-1,3-benzothiazol-6-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN2CCC[C@@H]2CN1C(C=CC1=N2)=CN1C(=O)C=C2C1=CC=C2N=C(C)SC2=C1 ZRMSACWSMCUDPK-QGZVFWFLSA-N 0.000 claims 1
• GODBSPPPPGQMSF-QGZVFWFLSA-N 7-[(8ar)-3,4,6,7,8,8a-hexahydro-1h-pyrrolo[1,2-a]pyrazin-2-yl]-2-(2-methyl-1,3-benzoxazol-6-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN2CCC[C@@H]2CN1C(C=CC1=N2)=CN1C(=O)C=C2C1=CC=C2N=C(C)OC2=C1 GODBSPPPPGQMSF-QGZVFWFLSA-N 0.000 claims 1
• ZLZGSDGTNQTUGE-KRWDZBQOSA-N 7-[(8as)-3,4,6,7,8,8a-hexahydro-1h-pyrrolo[1,2-a]pyrazin-2-yl]-2-(2-methyl-1,3-benzothiazol-5-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN2CCC[C@H]2CN1C(C=CC1=N2)=CN1C(=O)C=C2C1=CC=C(SC(C)=N2)C2=C1 ZLZGSDGTNQTUGE-KRWDZBQOSA-N 0.000 claims 1
• ZRMSACWSMCUDPK-KRWDZBQOSA-N 7-[(8as)-3,4,6,7,8,8a-hexahydro-1h-pyrrolo[1,2-a]pyrazin-2-yl]-2-(2-methyl-1,3-benzothiazol-6-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN2CCC[C@H]2CN1C(C=CC1=N2)=CN1C(=O)C=C2C1=CC=C2N=C(C)SC2=C1 ZRMSACWSMCUDPK-KRWDZBQOSA-N 0.000 claims 1
• GODBSPPPPGQMSF-KRWDZBQOSA-N 7-[(8as)-3,4,6,7,8,8a-hexahydro-1h-pyrrolo[1,2-a]pyrazin-2-yl]-2-(2-methyl-1,3-benzoxazol-6-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN2CCC[C@H]2CN1C(C=CC1=N2)=CN1C(=O)C=C2C1=CC=C2N=C(C)OC2=C1 GODBSPPPPGQMSF-KRWDZBQOSA-N 0.000 claims 1
• SXMZSVCKAHLGRC-UHFFFAOYSA-N 7-[1-(2,2-dimethyl-1,3-dioxan-5-yl)piperidin-4-yl]-2-(4-ethyl-6-methylpyrazolo[1,5-a]pyrazin-2-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1=C2C(CC)=NC(C)=CN2N=C1C(N=C1C=C2)=CC(=O)N1C=C2C(CC1)CCN1C1COC(C)(C)OC1 SXMZSVCKAHLGRC-UHFFFAOYSA-N 0.000 claims 1
• JJEXWIIJYJSVTM-UHFFFAOYSA-N 7-[1-(2-hydroxyethyl)-3,6-dihydro-2h-pyridin-4-yl]-2-(2-methyl-1,3-benzothiazol-6-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1=C2SC(C)=NC2=CC=C1C(N=C1C=C2)=CC(=O)N1C=C2C1=CCN(CCO)CC1 JJEXWIIJYJSVTM-UHFFFAOYSA-N 0.000 claims 1
• PYNNNHKYULGHSF-UHFFFAOYSA-N 7-[1-(2-hydroxyethyl)piperidin-4-yl]-9-methyl-2-(1-methylindazol-5-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C=1N(C(C=C(N=2)C=3C=C4C=NN(C)C4=CC=3)=O)C=2C(C)=CC=1C1CCN(CCO)CC1 PYNNNHKYULGHSF-UHFFFAOYSA-N 0.000 claims 1
• GUOXEESYNBUSLF-UHFFFAOYSA-N 7-[4-(dimethylamino)piperidin-1-yl]-2-(2-methyl-1,3-benzothiazol-5-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CC(N(C)C)CCN1C1=CN2C(=O)C=C(C=3C=C4N=C(C)SC4=CC=3)N=C2C=C1 GUOXEESYNBUSLF-UHFFFAOYSA-N 0.000 claims 1
• KKTOAKQEEQBSJS-UHFFFAOYSA-N 7-[4-(dimethylamino)piperidin-1-yl]-2-(2-methyl-1,3-benzothiazol-6-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CC(N(C)C)CCN1C1=CN2C(=O)C=C(C=3C=C4SC(C)=NC4=CC=3)N=C2C=C1 KKTOAKQEEQBSJS-UHFFFAOYSA-N 0.000 claims 1
• SWFOXHNBCPWJRA-UHFFFAOYSA-N 7-[4-(dimethylamino)piperidin-1-yl]-2-(2-methyl-1,3-benzoxazol-6-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CC(N(C)C)CCN1C1=CN2C(=O)C=C(C=3C=C4OC(C)=NC4=CC=3)N=C2C=C1 SWFOXHNBCPWJRA-UHFFFAOYSA-N 0.000 claims 1
• NAXKFFWKFJBBJP-UHFFFAOYSA-N 7-[4-(dimethylamino)piperidin-1-yl]-2-(8-fluoro-2-methylimidazo[1,2-a]pyridin-6-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CC(N(C)C)CCN1C1=CN2C(=O)C=C(C3=CN4C=C(C)N=C4C(F)=C3)N=C2C=C1 NAXKFFWKFJBBJP-UHFFFAOYSA-N 0.000 claims 1
• MKQPRQNFCMSDGC-UHFFFAOYSA-N 9-methyl-2-(2-methylindazol-5-yl)-7-(1-methylpiperidin-4-yl)pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN(C)CCC1C1=CN2C(=O)C=C(C3=CC4=CN(C)N=C4C=C3)N=C2C(C)=C1 MKQPRQNFCMSDGC-UHFFFAOYSA-N 0.000 claims 1
• DWGHFKYCXIMXJG-HNNXBMFYSA-N 9-methyl-2-(2-methylindazol-5-yl)-7-[(3s)-3-methylpiperazin-1-yl]pyrido[1,2-a]pyrimidin-4-one Chemical compound C1CN[C@@H](C)CN1C1=CN2C(=O)C=C(C3=CC4=CN(C)N=C4C=C3)N=C2C(C)=C1 DWGHFKYCXIMXJG-HNNXBMFYSA-N 0.000 claims 1
• XGYRZJSKFOTXRF-OAHLLOKOSA-N C(C)C=1C=2N(C=C(N=1)C)N=C(C=2)C=1N=C2N(C(C=1)=O)C=C(C=C2C)N1C[C@H](NCC1)C Chemical compound C(C)C=1C=2N(C=C(N=1)C)N=C(C=2)C=1N=C2N(C(C=1)=O)C=C(C=C2C)N1C[C@H](NCC1)C XGYRZJSKFOTXRF-OAHLLOKOSA-N 0.000 claims 1
• GGNZLZFRJCNTHW-UHFFFAOYSA-N CC1=CC(=CN2C1=NC(=CC2=O)C=2C=C1C=NN(C1=CC2)C)C2CCN(CC2)C Chemical compound CC1=CC(=CN2C1=NC(=CC2=O)C=2C=C1C=NN(C1=CC2)C)C2CCN(CC2)C GGNZLZFRJCNTHW-UHFFFAOYSA-N 0.000 claims 1
• OKWLAMMSCKXYIQ-KRWDZBQOSA-N CC=1C=2N(C=C(N=1)C)N=C(C=2)C=1N=C2N(C(C=1)=O)C=C(C=C2C)N1C[C@@H](NCC1)CC Chemical compound CC=1C=2N(C=C(N=1)C)N=C(C=2)C=1N=C2N(C(C=1)=O)C=C(C=C2C)N1C[C@@H](NCC1)CC OKWLAMMSCKXYIQ-KRWDZBQOSA-N 0.000 claims 1
• LNZGSQAMRZIZNF-CQSZACIVSA-N C[C@@H]1CN(CCN1C)C=1C=CC=2N(C(C=C(N=2)C2=CC3=C(N=C(O3)C)C=C2)=O)C=1 Chemical compound C[C@@H]1CN(CCN1C)C=1C=CC=2N(C(C=C(N=2)C2=CC3=C(N=C(O3)C)C=C2)=O)C=1 LNZGSQAMRZIZNF-CQSZACIVSA-N 0.000 claims 1
• NPKLHVQOZJGBQS-UHFFFAOYSA-N FC=1C=2N(C=C(C=1)C=1N=C3N(C(C=1)=O)C=C(C=C3)N1CCN(CC1)CCOC)C=C(N=2)C Chemical compound FC=1C=2N(C=C(C=1)C=1N=C3N(C(C=1)=O)C=C(C=C3)N1CCN(CC1)CCOC)C=C(N=2)C NPKLHVQOZJGBQS-UHFFFAOYSA-N 0.000 claims 1
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
• FSNZUULZFNWWFD-UHFFFAOYSA-N OCCN1CCC(=CC1)C=1C=CC=2N(C(C=C(N=2)C=2C=C3C=NN(C3=CC=2)C)=O)C=1 Chemical compound OCCN1CCC(=CC1)C=1C=CC=2N(C(C=C(N=2)C=2C=C3C=NN(C3=CC=2)C)=O)C=1 FSNZUULZFNWWFD-UHFFFAOYSA-N 0.000 claims 1
• MYTKOOVOBCDRPN-UHFFFAOYSA-N imidazo[1,2-a]pyridine-8-carbonitrile Chemical compound N#CC1=CC=CN2C=CN=C12 MYTKOOVOBCDRPN-UHFFFAOYSA-N 0.000 claims 1
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims 1
• 239000000203 mixture Substances 0.000 abstract description 31
• 239000000523 sample Substances 0.000 description 205
• 229910052757 nitrogen Inorganic materials 0.000 description 183
• 150000003254 radicals Chemical class 0.000 description 112
• 229910052701 rubidium Inorganic materials 0.000 description 68
• 210000001519 tissue Anatomy 0.000 description 55
• 108091032973 (ribonucleotides)n+m Proteins 0.000 description 48
• 238000003556 assay Methods 0.000 description 43
• 230000003321 amplification Effects 0.000 description 42
• 238000003199 nucleic acid amplification method Methods 0.000 description 42
• 238000011529 RT qPCR Methods 0.000 description 41
• 238000003762 quantitative reverse transcription PCR Methods 0.000 description 41
• 210000005260 human cell Anatomy 0.000 description 38
• 239000002773 nucleotide Substances 0.000 description 36
• 125000003729 nucleotide group Chemical group 0.000 description 36
• 210000004369 blood Anatomy 0.000 description 35
• 239000008280 blood Substances 0.000 description 35
• 230000008859 change Effects 0.000 description 35
• 230000014509 gene expression Effects 0.000 description 32
• 239000013610 patient sample Substances 0.000 description 31
• 238000005096 rolling process Methods 0.000 description 31
• 101100203485 Homo sapiens SMN2 gene Proteins 0.000 description 25
• 125000005241 heteroarylamino group Chemical group 0.000 description 25
• 230000009286 beneficial effect Effects 0.000 description 21
• 230000004044 response Effects 0.000 description 21
• 230000001225 therapeutic effect Effects 0.000 description 21
• 230000006870 function Effects 0.000 description 19
• 150000007523 nucleic acids Chemical class 0.000 description 19
• 208000024891 symptom Diseases 0.000 description 19
• 229940079593 drug Drugs 0.000 description 18
• 102000053565 human SMN1 Human genes 0.000 description 18
• 108020004414 DNA Proteins 0.000 description 17
• 239000000651 prodrug Substances 0.000 description 17
• 229940002612 prodrug Drugs 0.000 description 17
• 125000005100 aryl amino carbonyl group Chemical group 0.000 description 16
• 125000001769 aryl amino group Chemical group 0.000 description 16
• 239000000460 chlorine Substances 0.000 description 16
• 210000004027 cell Anatomy 0.000 description 15
• 238000001727 in vivo Methods 0.000 description 15
• 230000035772 mutation Effects 0.000 description 15
• 239000003795 chemical substances by application Substances 0.000 description 14
• 238000012217 deletion Methods 0.000 description 14
• 230000037430 deletion Effects 0.000 description 14
• 102000053564 human SMN2 Human genes 0.000 description 14
• 238000000338 in vitro Methods 0.000 description 14
• 238000010171 animal model Methods 0.000 description 13
• 210000000349 chromosome Anatomy 0.000 description 13
• 125000005843 halogen group Chemical group 0.000 description 13
• 125000006517 heterocyclyl carbonyl group Chemical group 0.000 description 13
• 125000005844 heterocyclyloxy group Chemical group 0.000 description 13
• 108090000623 proteins and genes Proteins 0.000 description 13
• 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 12
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 12
• 125000004356 hydroxy functional group Chemical group O* 0.000 description 12
• 210000002161 motor neuron Anatomy 0.000 description 12
• 210000003205 muscle Anatomy 0.000 description 12
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 11
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 11
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 11
• 229910052801 chlorine Inorganic materials 0.000 description 11
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 11
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 11
• 229910052731 fluorine Inorganic materials 0.000 description 11
• 239000011737 fluorine Substances 0.000 description 11
• 230000002779 inactivation Effects 0.000 description 11
• 239000012453 solvate Substances 0.000 description 11
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 10
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 10
• 238000002105 Southern blotting Methods 0.000 description 10
• 230000000692 anti-sense effect Effects 0.000 description 10
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 10
• 229910052794 bromium Inorganic materials 0.000 description 10
• 239000011630 iodine Substances 0.000 description 10
• 229910052740 iodine Inorganic materials 0.000 description 10
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 10
• 125000001544 thienyl group Chemical group 0.000 description 10
• 238000000636 Northern blotting Methods 0.000 description 9
• 125000004429 atom Chemical group 0.000 description 9
• 239000000090 biomarker Substances 0.000 description 9
• 239000002552 dosage form Substances 0.000 description 9
• 230000002441 reversible effect Effects 0.000 description 9
• 241000894007 species Species 0.000 description 9
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
• 208000032225 Proximal spinal muscular atrophy type 1 Diseases 0.000 description 8
• 230000000694 effects Effects 0.000 description 8
• 125000002883 imidazolyl group Chemical group 0.000 description 8
• 108020004707 nucleic acids Proteins 0.000 description 8
• 102000039446 nucleic acids Human genes 0.000 description 8
• 238000002360 preparation method Methods 0.000 description 8
• 208000032471 type 1 spinal muscular atrophy Diseases 0.000 description 8
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
• 125000003971 isoxazolinyl group Chemical group 0.000 description 7
• 238000006467 substitution reaction Methods 0.000 description 7
• 239000003981 vehicle Substances 0.000 description 7
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
• 108700028369 Alleles Proteins 0.000 description 6
• PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
• 108091028043 Nucleic acid sequence Proteins 0.000 description 6
• 230000008901 benefit Effects 0.000 description 6
• 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 6
• 229910052799 carbon Inorganic materials 0.000 description 6
• 238000006243 chemical reaction Methods 0.000 description 6
• 238000012937 correction Methods 0.000 description 6
• OPTASPLRGRRNAP-UHFFFAOYSA-N cytosine Chemical compound NC=1C=CNC(=O)N=1 OPTASPLRGRRNAP-UHFFFAOYSA-N 0.000 description 6
• 125000001041 indolyl group Chemical group 0.000 description 6
• 238000010172 mouse model Methods 0.000 description 6
• 239000000243 solution Substances 0.000 description 6
• 239000002904 solvent Substances 0.000 description 6
• RWQNBRDOKXIBIV-UHFFFAOYSA-N thymine Chemical compound CC1=CNC(=O)NC1=O RWQNBRDOKXIBIV-UHFFFAOYSA-N 0.000 description 6
• 125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 description 5
• 125000005955 1H-indazolyl group Chemical group 0.000 description 5
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 5
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
• 108020004705 Codon Proteins 0.000 description 5
• 108700024394 Exon Proteins 0.000 description 5
• 241001465754 Metazoa Species 0.000 description 5
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 5
• 201000010099 disease Diseases 0.000 description 5
• 210000002950 fibroblast Anatomy 0.000 description 5
• 125000000524 functional group Chemical group 0.000 description 5
• 125000001475 halogen functional group Chemical group 0.000 description 5
• 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 5
• 238000004519 manufacturing process Methods 0.000 description 5
• 238000011160 research Methods 0.000 description 5
• 210000000278 spinal cord Anatomy 0.000 description 5
• 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 description 4
• 125000000355 1,3-benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 4
• 102000053602 DNA Human genes 0.000 description 4
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 4
• 241000282412 Homo Species 0.000 description 4
• 108091092195 Intron Proteins 0.000 description 4
• 208000010428 Muscle Weakness Diseases 0.000 description 4
• 206010028372 Muscular weakness Diseases 0.000 description 4
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 4
• 208000033526 Proximal spinal muscular atrophy type 3 Diseases 0.000 description 4
• 125000002619 bicyclic group Chemical group 0.000 description 4
• 230000027455 binding Effects 0.000 description 4
• 210000004556 brain Anatomy 0.000 description 4
• 150000001721 carbon Chemical group 0.000 description 4
• 125000004432 carbon atom Chemical group C* 0.000 description 4
• 229910052805 deuterium Inorganic materials 0.000 description 4
• 125000006371 dihalo methyl group Chemical group 0.000 description 4
• 231100000673 dose–response relationship Toxicity 0.000 description 4
• 150000002148 esters Chemical class 0.000 description 4
• 239000012634 fragment Substances 0.000 description 4
• 125000004970 halomethyl group Chemical group 0.000 description 4
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 4
• 239000003999 initiator Substances 0.000 description 4
• 125000002757 morpholinyl group Chemical group 0.000 description 4
• 229910052760 oxygen Inorganic materials 0.000 description 4
• 239000000047 product Substances 0.000 description 4
• 125000002098 pyridazinyl group Chemical group 0.000 description 4
• 238000011552 rat model Methods 0.000 description 4
• 230000009467 reduction Effects 0.000 description 4
• 210000000130 stem cell Anatomy 0.000 description 4
• 229910052717 sulfur Inorganic materials 0.000 description 4
• 230000004083 survival effect Effects 0.000 description 4
• 125000006004 trihaloethyl group Chemical group 0.000 description 4
• 125000004953 trihalomethyl group Chemical group 0.000 description 4
• 208000032527 type III spinal muscular atrophy Diseases 0.000 description 4
• 125000005871 1,3-benzodioxolyl group Chemical group 0.000 description 3
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 3
• 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 3
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
• VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 3
• 239000005977 Ethylene Substances 0.000 description 3
• 241000699666 Mus <mouse, genus> Species 0.000 description 3
• 108091034117 Oligonucleotide Proteins 0.000 description 3
• WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 3
• GFFGJBXGBJISGV-UHFFFAOYSA-N adenyl group Chemical class N1=CN=C2N=CNC2=C1N GFFGJBXGBJISGV-UHFFFAOYSA-N 0.000 description 3
• 238000000246 agarose gel electrophoresis Methods 0.000 description 3
• 150000001447 alkali salts Chemical class 0.000 description 3
• 238000004458 analytical method Methods 0.000 description 3
• 238000013459 approach Methods 0.000 description 3
• 239000002585 base Substances 0.000 description 3
• 239000002775 capsule Substances 0.000 description 3
• 210000003169 central nervous system Anatomy 0.000 description 3
• 238000004587 chromatography analysis Methods 0.000 description 3
• 239000002361 compost Substances 0.000 description 3
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 3
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 3
• 229940104302 cytosine Drugs 0.000 description 3
• 230000002950 deficient Effects 0.000 description 3
• 230000007850 degeneration Effects 0.000 description 3
• 238000011161 development Methods 0.000 description 3
• 230000002068 genetic effect Effects 0.000 description 3
• 125000004969 haloethyl group Chemical group 0.000 description 3
• 125000005842 heteroatom Chemical group 0.000 description 3
• 210000003917 human chromosome Anatomy 0.000 description 3
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
• 239000003112 inhibitor Substances 0.000 description 3
• 125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 3
• 239000007788 liquid Substances 0.000 description 3
• 210000004072 lung Anatomy 0.000 description 3
• 230000002503 metabolic effect Effects 0.000 description 3
• 125000002950 monocyclic group Chemical group 0.000 description 3
• 230000007659 motor function Effects 0.000 description 3
• 125000001624 naphthyl group Chemical group 0.000 description 3
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 3
• 210000004940 nucleus Anatomy 0.000 description 3
• 230000008569 process Effects 0.000 description 3
• 230000000241 respiratory effect Effects 0.000 description 3
• 239000003381 stabilizer Substances 0.000 description 3
• 239000000126 substance Substances 0.000 description 3
• 230000009747 swallowing Effects 0.000 description 3
• 239000003826 tablet Substances 0.000 description 3
• 238000012360 testing method Methods 0.000 description 3
• 229940124597 therapeutic agent Drugs 0.000 description 3
• 229940113082 thymine Drugs 0.000 description 3
• 125000006008 trihaloethoxy group Chemical group 0.000 description 3
• 125000004951 trihalomethoxy group Chemical group 0.000 description 3
• VBICKXHEKHSIBG-UHFFFAOYSA-N 1-monostearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 2
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 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
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
• GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 2
• 108091026890 Coding region Proteins 0.000 description 2
• 206010011469 Crying Diseases 0.000 description 2
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
• WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
• VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 description 2
• 241000124008 Mammalia Species 0.000 description 2
• 108091027974 Mature messenger RNA Proteins 0.000 description 2
• 241000699670 Mus sp. Species 0.000 description 2
• 206010028289 Muscle atrophy Diseases 0.000 description 2
• 229910019142 PO4 Inorganic materials 0.000 description 2
• ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
• 208000033550 Proximal spinal muscular atrophy type 4 Diseases 0.000 description 2
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
• 241000700159 Rattus Species 0.000 description 2
• 206010057190 Respiratory tract infections Diseases 0.000 description 2
• 108091081021 Sense strand Proteins 0.000 description 2
• 101150113275 Smn gene Proteins 0.000 description 2
• 208000003954 Spinal Muscular Atrophies of Childhood Diseases 0.000 description 2
• 108091081024 Start codon Proteins 0.000 description 2
• 238000009825 accumulation Methods 0.000 description 2
• 230000002378 acidificating effect Effects 0.000 description 2
• USZYSDMBJDPRIF-SVEJIMAYSA-N aclacinomycin A Chemical compound O([C@H]1[C@@H](O)C[C@@H](O[C@H]1C)O[C@H]1[C@H](C[C@@H](O[C@H]1C)O[C@H]1C[C@]([C@@H](C2=CC=3C(=O)C4=CC=CC(O)=C4C(=O)C=3C(O)=C21)C(=O)OC)(O)CC)N(C)C)[C@H]1CCC(=O)[C@H](C)O1 USZYSDMBJDPRIF-SVEJIMAYSA-N 0.000 description 2
• 229960004176 aclarubicin Drugs 0.000 description 2
• 239000004480 active ingredient Substances 0.000 description 2
• 239000002671 adjuvant Substances 0.000 description 2
• 125000003158 alcohol group Chemical group 0.000 description 2
• 125000003545 alkoxy group Chemical group 0.000 description 2
• 150000001413 amino acids Chemical group 0.000 description 2
• 238000000540 analysis of variance Methods 0.000 description 2
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
• WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
• 230000015572 biosynthetic process Effects 0.000 description 2
• 210000005013 brain tissue Anatomy 0.000 description 2
• 150000001649 bromium compounds Chemical class 0.000 description 2
• 150000004648 butanoic acid derivatives Chemical class 0.000 description 2
• CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 description 2
• 239000011203 carbon fibre reinforced carbon Substances 0.000 description 2
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 2
• 150000001732 carboxylic acid derivatives Chemical group 0.000 description 2
• 238000004113 cell culture Methods 0.000 description 2
• 239000003153 chemical reaction reagent Substances 0.000 description 2
• 239000002299 complementary DNA Substances 0.000 description 2
• 239000013078 crystal Substances 0.000 description 2
• 230000002354 daily effect Effects 0.000 description 2
• 230000034994 death Effects 0.000 description 2
• 230000001934 delay Effects 0.000 description 2
• NIJJYAXOARWZEE-UHFFFAOYSA-N di-n-propyl-acetic acid Natural products CCCC(C(O)=O)CCC NIJJYAXOARWZEE-UHFFFAOYSA-N 0.000 description 2
• 238000001647 drug administration Methods 0.000 description 2
• 238000005516 engineering process Methods 0.000 description 2
• 239000003623 enhancer Substances 0.000 description 2
• 239000000284 extract Substances 0.000 description 2
• 239000000796 flavoring agent Substances 0.000 description 2
• 235000013355 food flavoring agent Nutrition 0.000 description 2
• 125000002541 furyl group Chemical group 0.000 description 2
• 108020001507 fusion proteins Proteins 0.000 description 2
• 102000037865 fusion proteins Human genes 0.000 description 2
• 239000008187 granular material Substances 0.000 description 2
• 239000003276 histone deacetylase inhibitor Substances 0.000 description 2
• 229960001330 hydroxycarbamide Drugs 0.000 description 2
• 238000001802 infusion Methods 0.000 description 2
• 238000003780 insertion Methods 0.000 description 2
• 230000037431 insertion Effects 0.000 description 2
• 238000007918 intramuscular administration Methods 0.000 description 2
• 238000001990 intravenous administration Methods 0.000 description 2
• 238000011835 investigation Methods 0.000 description 2
• 150000004694 iodide salts Chemical class 0.000 description 2
• 238000002955 isolation Methods 0.000 description 2
• 230000004199 lung function Effects 0.000 description 2
• 230000004060 metabolic process Effects 0.000 description 2
• 230000020763 muscle atrophy Effects 0.000 description 2
• 201000000585 muscular atrophy Diseases 0.000 description 2
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
• 230000004770 neurodegeneration Effects 0.000 description 2
• 125000004433 nitrogen atom Chemical group N* 0.000 description 2
• 235000016709 nutrition Nutrition 0.000 description 2
• 239000003921 oil Substances 0.000 description 2
• 235000019198 oils Nutrition 0.000 description 2
• 150000007530 organic bases Chemical class 0.000 description 2
• 239000001301 oxygen Substances 0.000 description 2
• 125000004430 oxygen atom Chemical group O* 0.000 description 2
• 230000007310 pathophysiology Effects 0.000 description 2
• 239000012071 phase Substances 0.000 description 2
• 239000010452 phosphate Substances 0.000 description 2
• NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
• 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
• 125000003367 polycyclic group Chemical group 0.000 description 2
• 239000000843 powder Substances 0.000 description 2
• 125000006239 protecting group Chemical group 0.000 description 2
• 102000004169 proteins and genes Human genes 0.000 description 2
• 238000000746 purification Methods 0.000 description 2
• 238000011002 quantification Methods 0.000 description 2
• 230000029058 respiratory gaseous exchange Effects 0.000 description 2
• 208000020029 respiratory tract infectious disease Diseases 0.000 description 2
• 238000010839 reverse transcription Methods 0.000 description 2
• 229920006395 saturated elastomer Polymers 0.000 description 2
• 229930195734 saturated hydrocarbon Natural products 0.000 description 2
• 230000028327 secretion Effects 0.000 description 2
• 238000001228 spectrum Methods 0.000 description 2
• 238000007920 subcutaneous administration Methods 0.000 description 2
• 125000000547 substituted alkyl group Chemical group 0.000 description 2
• 125000004434 sulfur atom Chemical group 0.000 description 2
• 238000009120 supportive therapy Methods 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
• 238000013518 transcription Methods 0.000 description 2
• 230000035897 transcription Effects 0.000 description 2
• 208000005606 type IV spinal muscular atrophy Diseases 0.000 description 2
• 229930195735 unsaturated hydrocarbon Natural products 0.000 description 2
• MSRILKIQRXUYCT-UHFFFAOYSA-M valproate semisodium Chemical compound [Na+].CCCC(C(O)=O)CCC.CCCC(C([O-])=O)CCC MSRILKIQRXUYCT-UHFFFAOYSA-M 0.000 description 2
• 229960000604 valproic acid Drugs 0.000 description 2
• 239000013598 vector Substances 0.000 description 2
• 230000003612 virological effect Effects 0.000 description 2
• LSPHULWDVZXLIL-UHFFFAOYSA-N (+/-)-Camphoric acid Chemical compound CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-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
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 description 1
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
• 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 description 1
• 125000006625 (C3-C8) cycloalkyloxy group Chemical group 0.000 description 1
• GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 description 1
• 125000001766 1,2,4-oxadiazol-3-yl group Chemical group [H]C1=NC(*)=NO1 0.000 description 1
• KTZQTRPPVKQPFO-UHFFFAOYSA-N 1,2-benzoxazole Chemical class C1=CC=C2C=NOC2=C1 KTZQTRPPVKQPFO-UHFFFAOYSA-N 0.000 description 1
• FKASFBLJDCHBNZ-UHFFFAOYSA-N 1,3,4-oxadiazole Chemical compound C1=NN=CO1 FKASFBLJDCHBNZ-UHFFFAOYSA-N 0.000 description 1
• 125000004227 1,3-benzoxazol-2-yl group Chemical group [H]C1=C([H])C([H])=C2N=C(*)OC2=C1[H] 0.000 description 1
• BCMCBBGGLRIHSE-UHFFFAOYSA-N 1,3-benzoxazole Chemical compound C1=CC=C2OC=NC2=C1 BCMCBBGGLRIHSE-UHFFFAOYSA-N 0.000 description 1
• VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical class CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-N 0.000 description 1
• YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
• BHFXPKPIPBNKFI-UHFFFAOYSA-N 2,3,4,7,8,8a-hexahydro-1h-pyrrolo[1,2-a]pyrazin-6-one Chemical compound C1NCCN2C(=O)CCC21 BHFXPKPIPBNKFI-UHFFFAOYSA-N 0.000 description 1
• WXTMDXOMEHJXQO-UHFFFAOYSA-N 2,5-dihydroxybenzoic acid Chemical compound OC(=O)C1=CC(O)=CC=C1O WXTMDXOMEHJXQO-UHFFFAOYSA-N 0.000 description 1
• AHCIDZDXEZJNJK-OCAPTIKFSA-N 2-[(3aS,6aR)-2,3,3a,4,6,6a-hexahydro-1H-pyrrolo[3,4-c]pyrrol-5-yl]ethanol Chemical compound OCCN1C[C@H]2[C@@H](C1)CNC2 AHCIDZDXEZJNJK-OCAPTIKFSA-N 0.000 description 1
• NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 1
• LBLYYCQCTBFVLH-UHFFFAOYSA-M 2-methylbenzenesulfonate Chemical compound CC1=CC=CC=C1S([O-])(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
• WMPPDTMATNBGJN-UHFFFAOYSA-N 2-phenylethylbromide Chemical class BrCCC1=CC=CC=C1 WMPPDTMATNBGJN-UHFFFAOYSA-N 0.000 description 1
• 108020005345 3' Untranslated Regions Proteins 0.000 description 1
• FEWJPZIEWOKRBE-UHFFFAOYSA-M 3-carboxy-2,3-dihydroxypropanoate Chemical compound OC(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-M 0.000 description 1
• 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
• 108020003589 5' Untranslated Regions Proteins 0.000 description 1
• 229930024421 Adenine Natural products 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
• QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
• 108020000948 Antisense Oligonucleotides Proteins 0.000 description 1
• 206010003084 Areflexia Diseases 0.000 description 1
• 239000004475 Arginine Substances 0.000 description 1
• 208000008037 Arthrogryposis Diseases 0.000 description 1
• BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 description 1
• 241000283690 Bos taurus Species 0.000 description 1
• FERIUCNNQQJTOY-UHFFFAOYSA-M Butyrate Chemical compound CCCC([O-])=O FERIUCNNQQJTOY-UHFFFAOYSA-M 0.000 description 1
• FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Natural products CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 1
• 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 1
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
• 241000282465 Canis Species 0.000 description 1
• OKTJSMMVPCPJKN-NJFSPNSNSA-N Carbon-14 Chemical compound [14C] OKTJSMMVPCPJKN-NJFSPNSNSA-N 0.000 description 1
• KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
• 206010011224 Cough Diseases 0.000 description 1
• RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
• AEMOLEFTQBMNLQ-AQKNRBDQSA-N D-glucopyranuronic acid Chemical compound OC1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O AEMOLEFTQBMNLQ-AQKNRBDQSA-N 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 class C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
• 206010013975 Dyspnoeas Diseases 0.000 description 1
• 241000283073 Equus caballus Species 0.000 description 1
• 241000282324 Felis Species 0.000 description 1
• 108090000331 Firefly luciferases Proteins 0.000 description 1
• VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
• 108010010803 Gelatin Proteins 0.000 description 1
• 208000028782 Hereditary disease Diseases 0.000 description 1
• 208000008454 Hyperhidrosis Diseases 0.000 description 1
• 206010021118 Hypotonia Diseases 0.000 description 1
• 238000004566 IR spectroscopy Methods 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
• 206010050740 Inability to crawl Diseases 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
• JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 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
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
• 108060001084 Luciferase Proteins 0.000 description 1
• 239000005089 Luciferase 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
• FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 1
• 241001024304 Mino Species 0.000 description 1
• 241001529936 Murinae Species 0.000 description 1
• 208000007379 Muscle Hypotonia Diseases 0.000 description 1
• GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
• 229910002651 NO3 Inorganic materials 0.000 description 1
• 208000012902 Nervous system disease Diseases 0.000 description 1
• 208000025966 Neurological disease Diseases 0.000 description 1
• NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
• 108700026244 Open Reading Frames Proteins 0.000 description 1
• 240000007594 Oryza sativa Species 0.000 description 1
• 235000007164 Oryza sativa Nutrition 0.000 description 1
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
• 235000019483 Peanut oil Nutrition 0.000 description 1
• ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical class OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 1
• OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
• 208000033522 Proximal spinal muscular atrophy type 2 Diseases 0.000 description 1
• KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 1
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
• 102000004598 Small Nuclear Ribonucleoproteins Human genes 0.000 description 1
• 108010003165 Small Nuclear Ribonucleoproteins Proteins 0.000 description 1
• 229920002472 Starch Polymers 0.000 description 1
• 241000862969 Stella Species 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
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
• 241000282898 Sus scrofa Species 0.000 description 1
• 208000037063 Thinness Diseases 0.000 description 1
• ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
• 208000026481 Werdnig-Hoffmann disease Diseases 0.000 description 1
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
• 230000001594 aberrant effect Effects 0.000 description 1
• 230000005856 abnormality Effects 0.000 description 1
• 238000010521 absorption reaction Methods 0.000 description 1
• 150000007513 acids Chemical class 0.000 description 1
• 208000037919 acquired disease Diseases 0.000 description 1
• 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
• 239000012190 activator Substances 0.000 description 1
• 239000013543 active substance Substances 0.000 description 1
• 229960000643 adenine Drugs 0.000 description 1
• 125000003342 alkenyl group Chemical group 0.000 description 1
• 125000003282 alkyl amino group Chemical group 0.000 description 1
• 125000002877 alkyl aryl group Chemical group 0.000 description 1
• 125000000217 alkyl group Chemical group 0.000 description 1
• 150000001350 alkyl halides Chemical class 0.000 description 1
• HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
• 229910052782 aluminium Inorganic materials 0.000 description 1
• XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
• 150000001412 amines Chemical class 0.000 description 1
• 125000000539 amino acid group Chemical group 0.000 description 1
• 125000003277 amino group Chemical group 0.000 description 1
• 229940126575 aminoglycoside Drugs 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
• 210000002226 anterior horn cell Anatomy 0.000 description 1
• 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
• 239000002246 antineoplastic agent Substances 0.000 description 1
• 239000000074 antisense oligonucleotide Substances 0.000 description 1
• 238000012230 antisense oligonucleotides Methods 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
• 150000005840 aryl radicals Chemical class 0.000 description 1
• 229940072107 ascorbate Drugs 0.000 description 1
• 235000010323 ascorbic acid Nutrition 0.000 description 1
• 239000011668 ascorbic acid Substances 0.000 description 1
• 238000003149 assay kit Methods 0.000 description 1
• 125000003828 azulenyl group Chemical group 0.000 description 1
• SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
• 229940077388 benzenesulfonate Drugs 0.000 description 1
• 229940050390 benzoate Drugs 0.000 description 1
• 125000004244 benzofuran-2-yl group Chemical group [H]C1=C(*)OC2=C([H])C([H])=C([H])C([H])=C12 0.000 description 1
• 125000004533 benzofuran-5-yl group Chemical group O1C=CC2=C1C=CC(=C2)* 0.000 description 1
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
• IOJUPLGTWVMSFF-UHFFFAOYSA-N benzothiazole Chemical compound C1=CC=C2SC=NC2=C1 IOJUPLGTWVMSFF-UHFFFAOYSA-N 0.000 description 1
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
• 150000005347 biaryls Chemical class 0.000 description 1
• 239000011230 binding agent Substances 0.000 description 1
• 230000004071 biological effect Effects 0.000 description 1
• 230000037396 body weight Effects 0.000 description 1
• 210000000133 brain stem Anatomy 0.000 description 1
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 125000000480 butynyl group Chemical group [*]C#CC([H])([H])C([H])([H])[H] 0.000 description 1
• 239000011575 calcium Substances 0.000 description 1
• 229910052791 calcium Inorganic materials 0.000 description 1
• MIOPJNTWMNEORI-UHFFFAOYSA-N camphorsulfonic acid Chemical compound C1CC2(CS(O)(=O)=O)C(=O)CC1C2(C)C MIOPJNTWMNEORI-UHFFFAOYSA-N 0.000 description 1
• 150000001733 carboxylic acid esters Chemical class 0.000 description 1
• 239000000969 carrier Substances 0.000 description 1
• 230000001413 cellular effect Effects 0.000 description 1
• 238000001311 chemical methods and process Methods 0.000 description 1
• 239000007910 chewable tablet Substances 0.000 description 1
• 238000004296 chiral HPLC Methods 0.000 description 1
• 230000001684 chronic effect Effects 0.000 description 1
• 238000000576 coating method Methods 0.000 description 1
• 238000013329 compounding Methods 0.000 description 1
• 238000001218 confocal laser scanning microscopy Methods 0.000 description 1
• 208000018697 congenital contractures Diseases 0.000 description 1
• 238000010276 construction Methods 0.000 description 1
• 238000001816 cooling Methods 0.000 description 1
• 125000004122 cyclic group Chemical group 0.000 description 1
• 125000001352 cyclobutyloxy group Chemical group C1(CCC1)O* 0.000 description 1
• 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
• 229940127089 cytotoxic agent Drugs 0.000 description 1
• 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 230000006735 deficit Effects 0.000 description 1
• 230000001419 dependent effect Effects 0.000 description 1
• 230000006866 deterioration Effects 0.000 description 1
• 125000004431 deuterium atom Chemical group 0.000 description 1
• 239000008121 dextrose Substances 0.000 description 1
• 150000008050 dialkyl sulfates Chemical class 0.000 description 1
• LMEDOLJKVASKTP-UHFFFAOYSA-N dibutyl sulfate Chemical class CCCCOS(=O)(=O)OCCCC LMEDOLJKVASKTP-UHFFFAOYSA-N 0.000 description 1
• 235000005911 diet Nutrition 0.000 description 1
• 230000037213 diet Effects 0.000 description 1
• ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical class OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
• 125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
• 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
• 239000001177 diphosphate Substances 0.000 description 1
• 235000011180 diphosphates Nutrition 0.000 description 1
• 239000007884 disintegrant Substances 0.000 description 1
• 208000035475 disorder Diseases 0.000 description 1
• 125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
• 210000005069 ears Anatomy 0.000 description 1
• 238000002567 electromyography Methods 0.000 description 1
• 239000000839 emulsion Substances 0.000 description 1
• 238000005538 encapsulation Methods 0.000 description 1
• CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
• 230000001605 fetal effect Effects 0.000 description 1
• 239000000945 filler Substances 0.000 description 1
• 235000013312 flour Nutrition 0.000 description 1
• 125000003983 fluorenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3CC12)* 0.000 description 1
• 238000000799 fluorescence microscopy Methods 0.000 description 1
• 239000007850 fluorescent dye Substances 0.000 description 1
• 238000009472 formulation Methods 0.000 description 1
• 238000001640 fractional crystallisation Methods 0.000 description 1
• 238000004108 freeze drying Methods 0.000 description 1
• 125000004613 furo[2,3-c]pyridinyl group Chemical group O1C(=CC=2C1=CN=CC2)* 0.000 description 1
• 239000000499 gel 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
• 239000010437 gem Substances 0.000 description 1
• 229940050410 gluconate Drugs 0.000 description 1
• 239000008103 glucose Substances 0.000 description 1
• 229940097042 glucuronate Drugs 0.000 description 1
• 229930195712 glutamate Natural products 0.000 description 1
• 229940049906 glutamate Drugs 0.000 description 1
• YQEMORVAKMFKLG-UHFFFAOYSA-N glycerine monostearate Natural products CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 1
• SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
• 150000004820 halides Chemical class 0.000 description 1
• 230000036541 health Effects 0.000 description 1
• 229940121372 histone deacetylase inhibitor Drugs 0.000 description 1
• 238000009396 hybridization Methods 0.000 description 1
• ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
• QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
• 230000007062 hydrolysis Effects 0.000 description 1
• 238000006460 hydrolysis reaction Methods 0.000 description 1
• 230000003301 hydrolyzing effect Effects 0.000 description 1
• WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
• 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 description 1
• 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 description 1
• 125000002632 imidazolidinyl group Chemical group 0.000 description 1
• 125000002636 imidazolinyl group Chemical group 0.000 description 1
• 230000028993 immune response Effects 0.000 description 1
• 238000012744 immunostaining Methods 0.000 description 1
• 230000001771 impaired effect Effects 0.000 description 1
• 238000010348 incorporation Methods 0.000 description 1
• 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
• 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
• 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 description 1
• 238000002347 injection Methods 0.000 description 1
• 239000007924 injection Substances 0.000 description 1
• 150000007529 inorganic bases Chemical class 0.000 description 1
• 230000000968 intestinal effect Effects 0.000 description 1
• 210000004347 intestinal mucosa Anatomy 0.000 description 1
• 238000007912 intraperitoneal administration Methods 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
• PXZQEOJJUGGUIB-UHFFFAOYSA-N isoindolin-1-one Chemical class C1=CC=C2C(=O)NCC2=C1 PXZQEOJJUGGUIB-UHFFFAOYSA-N 0.000 description 1
• 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
• TWBYWOBDOCUKOW-UHFFFAOYSA-M isonicotinate Chemical compound [O-]C(=O)C1=CC=NC=C1 TWBYWOBDOCUKOW-UHFFFAOYSA-M 0.000 description 1
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
• 125000004628 isothiazolidinyl group Chemical group S1N(CCC1)* 0.000 description 1
• 125000005969 isothiazolinyl group Chemical group 0.000 description 1
• 125000001786 isothiazolyl group Chemical group 0.000 description 1
• 125000000842 isoxazolyl group Chemical group 0.000 description 1
• 230000000366 juvenile effect Effects 0.000 description 1
• 201000004815 juvenile spinal muscular atrophy Diseases 0.000 description 1
• 239000008101 lactose Substances 0.000 description 1
• 239000002502 liposome Substances 0.000 description 1
• 229910052744 lithium Inorganic materials 0.000 description 1
• 210000004185 liver Anatomy 0.000 description 1
• 230000007774 longterm Effects 0.000 description 1
• 239000000314 lubricant Substances 0.000 description 1
• 239000011777 magnesium Substances 0.000 description 1
• 229910052749 magnesium Inorganic materials 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
• 238000007726 management method Methods 0.000 description 1
• 239000000463 material Substances 0.000 description 1
• 230000007246 mechanism Effects 0.000 description 1
• 239000002609 medium Substances 0.000 description 1
• 239000003094 microcapsule Substances 0.000 description 1
• 239000011859 microparticle Substances 0.000 description 1
• 239000002480 mineral oil Substances 0.000 description 1
• 235000010446 mineral oil Nutrition 0.000 description 1
• 150000007522 mineralic acids Chemical class 0.000 description 1
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
• 238000001964 muscle biopsy Methods 0.000 description 1
• 238000002703 mutagenesis Methods 0.000 description 1
• 231100000350 mutagenesis Toxicity 0.000 description 1
• 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 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
• PSZYNBSKGUBXEH-UHFFFAOYSA-M naphthalene-1-sulfonate Chemical compound C1=CC=C2C(S(=O)(=O)[O-])=CC=CC2=C1 PSZYNBSKGUBXEH-UHFFFAOYSA-M 0.000 description 1
• 230000032405 negative regulation of neuron apoptotic process Effects 0.000 description 1
• 208000015122 neurodegenerative disease Diseases 0.000 description 1
• 239000004090 neuroprotective agent Substances 0.000 description 1
• 231100000252 nontoxic Toxicity 0.000 description 1
• 230000003000 nontoxic effect Effects 0.000 description 1
• QNTASHOAVRSLMD-FCARAQADSA-N olesoxime Chemical compound C1CC2=C\C(=N/O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 QNTASHOAVRSLMD-FCARAQADSA-N 0.000 description 1
• 229950001051 olesoxime Drugs 0.000 description 1
• 230000003287 optical effect Effects 0.000 description 1
• 239000006186 oral dosage form Substances 0.000 description 1
• 210000000056 organ Anatomy 0.000 description 1
• 150000007524 organic acids Chemical class 0.000 description 1
• 235000005985 organic acids Nutrition 0.000 description 1
• 235000013348 organic food Nutrition 0.000 description 1
• 125000005963 oxadiazolidinyl group Chemical group 0.000 description 1
• 125000005882 oxadiazolinyl group Chemical group 0.000 description 1
• 125000001715 oxadiazolyl group Chemical group 0.000 description 1
• 125000000160 oxazolidinyl group Chemical group 0.000 description 1
• 125000005968 oxazolinyl group Chemical group 0.000 description 1
• 125000002971 oxazolyl group Chemical group 0.000 description 1
• 125000000466 oxiranyl group Chemical group 0.000 description 1
• 229940014662 pantothenate Drugs 0.000 description 1
• 239000011713 pantothenic acid Substances 0.000 description 1
• 235000019161 pantothenic acid Nutrition 0.000 description 1
• 239000000312 peanut oil Substances 0.000 description 1
• 230000035515 penetration Effects 0.000 description 1
• 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
• 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 1
• 239000003208 petroleum Substances 0.000 description 1
• 125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 1
• 229910052698 phosphorus Inorganic materials 0.000 description 1
• 239000011574 phosphorus Substances 0.000 description 1
• 239000006187 pill Substances 0.000 description 1
• 239000011591 potassium Substances 0.000 description 1
• 229910052700 potassium Inorganic materials 0.000 description 1
• 239000002244 precipitate Substances 0.000 description 1
• 239000002243 precursor Substances 0.000 description 1
• 230000035935 pregnancy Effects 0.000 description 1
• 230000002265 prevention Effects 0.000 description 1
• 238000012545 processing Methods 0.000 description 1
• 238000004393 prognosis Methods 0.000 description 1
• 230000000750 progressive effect Effects 0.000 description 1
• 230000001737 promoting effect Effects 0.000 description 1
• 239000001294 propane Substances 0.000 description 1
• 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
• QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
• 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
• 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
• 230000002685 pulmonary effect Effects 0.000 description 1
• 125000000561 purinyl group Chemical group N1=C(N=C2N=CNC2=C1)* 0.000 description 1
• 125000003072 pyrazolidinyl group Chemical group 0.000 description 1
• 125000002755 pyrazolinyl group Chemical group 0.000 description 1
• 125000003226 pyrazolyl group Chemical group 0.000 description 1
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
• 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 1
• 125000001422 pyrrolinyl group Chemical group 0.000 description 1
• 125000000168 pyrrolyl group Chemical group 0.000 description 1
• 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
• 125000004262 quinoxalin-2-yl group Chemical group [H]C1=NC2=C([H])C([H])=C([H])C([H])=C2N=C1* 0.000 description 1
• 239000011541 reaction mixture Substances 0.000 description 1
• 238000001953 recrystallisation Methods 0.000 description 1
• 230000011514 reflex Effects 0.000 description 1
• 230000001105 regulatory effect Effects 0.000 description 1
• 208000023504 respiratory system disease Diseases 0.000 description 1
• 235000009566 rice Nutrition 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
• 238000000926 separation method Methods 0.000 description 1
• 239000008159 sesame oil Substances 0.000 description 1
• 235000011803 sesame oil Nutrition 0.000 description 1
• 238000007086 side reaction Methods 0.000 description 1
• 239000000741 silica gel Substances 0.000 description 1
• 229910002027 silica gel Inorganic materials 0.000 description 1
• 235000020183 skimmed milk Nutrition 0.000 description 1
• 239000011734 sodium Substances 0.000 description 1
• 229910052708 sodium Inorganic materials 0.000 description 1
• RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
• 239000007787 solid Substances 0.000 description 1
• 238000010186 staining Methods 0.000 description 1
• 238000010561 standard procedure Methods 0.000 description 1
• 239000008107 starch Substances 0.000 description 1
• 235000019698 starch Nutrition 0.000 description 1
• 239000007858 starting material Substances 0.000 description 1
• 125000004079 stearyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
• 239000000758 substrate Substances 0.000 description 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 150000003871 sulfonates Chemical class 0.000 description 1
• 239000000725 suspension Substances 0.000 description 1
• 238000013268 sustained release Methods 0.000 description 1
• 239000012730 sustained-release form Substances 0.000 description 1
• 208000013460 sweaty Diseases 0.000 description 1
• 238000003786 synthesis reaction Methods 0.000 description 1
• 239000006188 syrup Substances 0.000 description 1
• 235000020357 syrup Nutrition 0.000 description 1
• 230000009885 systemic effect Effects 0.000 description 1
• 239000000454 talc Substances 0.000 description 1
• 229910052623 talc Inorganic materials 0.000 description 1
• 229940095064 tartrate Drugs 0.000 description 1
• 150000003942 tert-butylamines Chemical class 0.000 description 1
• 125000003831 tetrazolyl group Chemical group 0.000 description 1
• 125000005304 thiadiazolidinyl group Chemical group 0.000 description 1
• 125000005305 thiadiazolinyl group Chemical group 0.000 description 1
• 125000001113 thiadiazolyl group Chemical group 0.000 description 1
• 125000001984 thiazolidinyl group Chemical group 0.000 description 1
• 125000002769 thiazolinyl group Chemical group 0.000 description 1
• 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
• 238000003354 tissue distribution assay Methods 0.000 description 1
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
• 230000000699 topical effect Effects 0.000 description 1
• 231100000331 toxic Toxicity 0.000 description 1
• 230000002588 toxic effect Effects 0.000 description 1
• 231100000440 toxicity profile Toxicity 0.000 description 1
• 108091006106 transcriptional activators Proteins 0.000 description 1
• 230000002103 transcriptional effect Effects 0.000 description 1
• 230000009466 transformation Effects 0.000 description 1
• 238000013519 translation Methods 0.000 description 1
• 238000011269 treatment regimen Methods 0.000 description 1
• 125000004306 triazinyl group Chemical group 0.000 description 1
• 125000005310 triazolidinyl group Chemical group N1(NNCC1)* 0.000 description 1
• 125000005881 triazolinyl group Chemical group 0.000 description 1
• 125000001425 triazolyl group Chemical group 0.000 description 1
• 239000001226 triphosphate Substances 0.000 description 1
• 235000011178 triphosphate Nutrition 0.000 description 1
• 125000002264 triphosphate group Chemical class [H]OP(=O)(O[H])OP(=O)(O[H])OP(=O)(O[H])O* 0.000 description 1
• 208000032521 type II spinal muscular atrophy Diseases 0.000 description 1
• 206010048828 underweight Diseases 0.000 description 1
• 230000002485 urinary effect Effects 0.000 description 1
• 210000004291 uterus Anatomy 0.000 description 1
• 235000013311 vegetables Nutrition 0.000 description 1
• 230000003519 ventilatory effect Effects 0.000 description 1
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
• 229920002554 vinyl polymer Polymers 0.000 description 1
• 230000021542 voluntary musculoskeletal movement Effects 0.000 description 1
• 229910052725 zinc Inorganic materials 0.000 description 1
• 239000011701 zinc Substances 0.000 description 1