CA2890692A1 - Pyrimido [4,5-b]quinoline-4,5 (3h,10h)-diones as nonsense mutation suppressors - Google Patents
Pyrimido [4,5-b]quinoline-4,5 (3h,10h)-diones as nonsense mutation suppressors Download PDFInfo
- Publication number
- CA2890692A1 CA2890692A1 CA2890692A CA2890692A CA2890692A1 CA 2890692 A1 CA2890692 A1 CA 2890692A1 CA 2890692 A CA2890692 A CA 2890692A CA 2890692 A CA2890692 A CA 2890692A CA 2890692 A1 CA2890692 A1 CA 2890692A1
- Authority
- CA
- Canada
- Prior art keywords
- dione
- quinoline
- 4alkyl
- amino
- methyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 108020004485 Nonsense Codon Proteins 0.000 title claims description 55
- 230000037434 nonsense mutation Effects 0.000 title claims description 54
- MJZUERYJESLETK-UHFFFAOYSA-N 1,10-dihydropyrimido[4,5-b]quinoline-4,5-dione Chemical class N1C2=CC=CC=C2C(=O)C2=C1NC=NC2=O MJZUERYJESLETK-UHFFFAOYSA-N 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 164
- 150000003839 salts Chemical class 0.000 claims abstract description 52
- 239000003814 drug Substances 0.000 claims abstract description 21
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 193
- 229910052736 halogen Inorganic materials 0.000 claims description 144
- 125000004122 cyclic group Chemical group 0.000 claims description 142
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 141
- 150000002367 halogens Chemical class 0.000 claims description 133
- 229910052739 hydrogen Inorganic materials 0.000 claims description 128
- 239000001257 hydrogen Substances 0.000 claims description 128
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 127
- 229910052799 carbon Inorganic materials 0.000 claims description 107
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 97
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 97
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 77
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 66
- 229910052757 nitrogen Inorganic materials 0.000 claims description 66
- 125000005842 heteroatom Chemical group 0.000 claims description 65
- 125000006574 non-aromatic ring group Chemical group 0.000 claims description 65
- 229920006395 saturated elastomer Polymers 0.000 claims description 65
- 229910052760 oxygen Inorganic materials 0.000 claims description 64
- 239000001301 oxygen Substances 0.000 claims description 64
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 63
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 63
- 229910052717 sulfur Inorganic materials 0.000 claims description 63
- 239000011593 sulfur Substances 0.000 claims description 63
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 58
- -1 4halogenalkyl Chemical group 0.000 claims description 47
- 125000004432 carbon atom Chemical group C* 0.000 claims description 47
- 125000002950 monocyclic group Chemical group 0.000 claims description 46
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 44
- 201000010099 disease Diseases 0.000 claims description 36
- 125000006645 (C3-C4) cycloalkyl group Chemical group 0.000 claims description 33
- 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims description 33
- 230000000694 effects Effects 0.000 claims description 28
- 238000000034 method Methods 0.000 claims description 24
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 18
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 17
- 125000006413 ring segment Chemical group 0.000 claims description 16
- 239000008194 pharmaceutical composition Substances 0.000 claims description 15
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 12
- KIDUCMGZPJQLPG-UHFFFAOYSA-N 2-ethylsulfanyl-3-phenyl-10h-pyrimido[4,5-b]quinoline-4,5-dione Chemical compound CCSC1=NC=2NC3=CC=CC=C3C(=O)C=2C(=O)N1C1=CC=CC=C1 KIDUCMGZPJQLPG-UHFFFAOYSA-N 0.000 claims description 6
- NZVURNMUTOYLSG-UHFFFAOYSA-N 2-(dimethylamino)-3-phenyl-10h-pyrimido[4,5-b]quinoline-4,5-dione Chemical compound CN(C)C1=NC=2NC3=CC=CC=C3C(=O)C=2C(=O)N1C1=CC=CC=C1 NZVURNMUTOYLSG-UHFFFAOYSA-N 0.000 claims description 5
- UHFVRKUPSAXREP-UHFFFAOYSA-N 10-(2-methoxyethyl)-3-phenyl-2-propan-2-ylpyrimido[4,5-b]quinoline-4,5-dione Chemical compound COCCN1C2=CC=CC=C2C(=O)C(C2=O)=C1N=C(C(C)C)N2C1=CC=CC=C1 UHFVRKUPSAXREP-UHFFFAOYSA-N 0.000 claims description 4
- AJTVCXKJEWUISC-UHFFFAOYSA-N 10-methyl-3-phenyl-2-propan-2-ylpyrimido[4,5-b]quinoline-4,5-dione Chemical compound CC(C)C1=NC=2N(C)C3=CC=CC=C3C(=O)C=2C(=O)N1C1=CC=CC=C1 AJTVCXKJEWUISC-UHFFFAOYSA-N 0.000 claims description 4
- QGXVTZRIRPNXAA-UHFFFAOYSA-N 10-methyl-3-phenyl-2-propylpyrimido[4,5-b]quinoline-4,5-dione Chemical compound CCCC1=NC=2N(C)C3=CC=CC=C3C(=O)C=2C(=O)N1C1=CC=CC=C1 QGXVTZRIRPNXAA-UHFFFAOYSA-N 0.000 claims description 4
- RZDACIUIPZFAOS-UHFFFAOYSA-N 2-ethyl-10-methyl-3-phenylpyrimido[4,5-b]quinoline-4,5-dione Chemical compound CCC1=NC=2N(C)C3=CC=CC=C3C(=O)C=2C(=O)N1C1=CC=CC=C1 RZDACIUIPZFAOS-UHFFFAOYSA-N 0.000 claims description 4
- GYHJCEAIAWFIAJ-UHFFFAOYSA-N 3-phenyl-2-propan-2-yl-10-propylpyrimido[4,5-b]quinoline-4,5-dione Chemical compound CCCN1C2=CC=CC=C2C(=O)C(C2=O)=C1N=C(C(C)C)N2C1=CC=CC=C1 GYHJCEAIAWFIAJ-UHFFFAOYSA-N 0.000 claims description 4
- RUDPWFWGJOMQEX-UHFFFAOYSA-N 3-phenyl-2-propan-2-yl-10h-pyrimido[4,5-b]quinoline-4,5-dione Chemical compound CC(C)C1=NC=2NC3=CC=CC=C3C(=O)C=2C(=O)N1C1=CC=CC=C1 RUDPWFWGJOMQEX-UHFFFAOYSA-N 0.000 claims description 4
- LCTKQYSVDGAHAD-UHFFFAOYSA-N 5-phenyl-4-propan-2-yl-1,3,5-triazatetracyclo[7.6.1.02,7.013,16]hexadeca-2(7),3,9,11,13(16)-pentaene-6,8-dione Chemical compound CC(C)C1=NC=2N(C=34)CCC4=CC=CC=3C(=O)C=2C(=O)N1C1=CC=CC=C1 LCTKQYSVDGAHAD-UHFFFAOYSA-N 0.000 claims description 4
- 239000013543 active substance Substances 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 50
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 25
- 125000005843 halogen group Chemical group 0.000 claims 10
- AFLBQLGPVYRZJR-UHFFFAOYSA-N 10-methyl-2-pentyl-3-phenylpyrimido[4,5-b]quinoline-4,5-dione Chemical compound CCCCCC1=NC=2N(C)C3=CC=CC=C3C(=O)C=2C(=O)N1C1=CC=CC=C1 AFLBQLGPVYRZJR-UHFFFAOYSA-N 0.000 claims 3
- PMPNXFKPNSJZJF-UHFFFAOYSA-N 3-(3,5-dimethylphenyl)-10-methyl-2-pentylpyrimido[4,5-b]quinoline-4,5-dione Chemical compound CCCCCC1=NC=2N(C)C3=CC=CC=C3C(=O)C=2C(=O)N1C1=CC(C)=CC(C)=C1 PMPNXFKPNSJZJF-UHFFFAOYSA-N 0.000 claims 3
- YRIYCZQXKIZHNK-UHFFFAOYSA-N 3-(3,5-dimethylphenyl)-10-methyl-2-propan-2-ylpyrimido[4,5-b]quinoline-4,5-dione Chemical compound CC(C)C1=NC=2N(C)C3=CC=CC=C3C(=O)C=2C(=O)N1C1=CC(C)=CC(C)=C1 YRIYCZQXKIZHNK-UHFFFAOYSA-N 0.000 claims 3
- WQQLNMTUVMLBTP-UHFFFAOYSA-N 3-(3,5-dimethylphenyl)-10-methyl-2-propylpyrimido[4,5-b]quinoline-4,5-dione Chemical compound CCCC1=NC=2N(C)C3=CC=CC=C3C(=O)C=2C(=O)N1C1=CC(C)=CC(C)=C1 WQQLNMTUVMLBTP-UHFFFAOYSA-N 0.000 claims 3
- OKGWETOVKKQGOC-UHFFFAOYSA-N 3-(3,5-dimethylphenyl)-2-ethyl-10-methylpyrimido[4,5-b]quinoline-4,5-dione Chemical compound CCC1=NC=2N(C)C3=CC=CC=C3C(=O)C=2C(=O)N1C1=CC(C)=CC(C)=C1 OKGWETOVKKQGOC-UHFFFAOYSA-N 0.000 claims 3
- YLGSYGGBTZEXLF-UHFFFAOYSA-N 10-(2-aminoethyl)-2-cyclobutyl-3-phenylpyrimido[4,5-b]quinoline-4,5-dione Chemical compound NCCN1C2=CC=CC=C2C(=O)C(C(N2C=3C=CC=CC=3)=O)=C1N=C2C1CCC1 YLGSYGGBTZEXLF-UHFFFAOYSA-N 0.000 claims 2
- GVSJTYPPSYDOAF-UHFFFAOYSA-N 10-(2-aminoethyl)-3-phenyl-2-propan-2-ylpyrimido[4,5-b]quinoline-4,5-dione Chemical compound CC(C)C1=NC=2N(CCN)C3=CC=CC=C3C(=O)C=2C(=O)N1C1=CC=CC=C1 GVSJTYPPSYDOAF-UHFFFAOYSA-N 0.000 claims 2
- ZJUNGAAJIKQNRK-UHFFFAOYSA-N 10-methyl-2-(3-methylcyclobutyl)-3-phenylpyrimido[4,5-b]quinoline-4,5-dione Chemical compound C1C(C)CC1C(N(C1=O)C=2C=CC=CC=2)=NC2=C1C(=O)C1=CC=CC=C1N2C ZJUNGAAJIKQNRK-UHFFFAOYSA-N 0.000 claims 2
- OSKDZKXJXWZSAV-UHFFFAOYSA-N 10-methyl-2-pentan-3-yl-3-phenylpyrimido[4,5-b]quinoline-4,5-dione Chemical compound CCC(CC)C1=NC=2N(C)C3=CC=CC=C3C(=O)C=2C(=O)N1C1=CC=CC=C1 OSKDZKXJXWZSAV-UHFFFAOYSA-N 0.000 claims 2
- FXQBTMJYASRROA-UHFFFAOYSA-N 10-methyl-2-propan-2-yl-3-(2-propan-2-ylphenyl)pyrimido[4,5-b]quinoline-4,5-dione Chemical compound CC(C)C1=CC=CC=C1N1C(=O)C(C(=O)C2=CC=CC=C2N2C)=C2N=C1C(C)C FXQBTMJYASRROA-UHFFFAOYSA-N 0.000 claims 2
- KANGOBNCEMBZOT-UHFFFAOYSA-N 10-methyl-2-propan-2-yl-3-[2-(trifluoromethyl)phenyl]pyrimido[4,5-b]quinoline-4,5-dione Chemical compound CC(C)C1=NC=2N(C)C3=CC=CC=C3C(=O)C=2C(=O)N1C1=CC=CC=C1C(F)(F)F KANGOBNCEMBZOT-UHFFFAOYSA-N 0.000 claims 2
- PMBWCSIBCMQYQI-UHFFFAOYSA-N 10-methyl-3-(2-methylphenyl)-2-propan-2-ylpyrimido[4,5-b]quinoline-4,5-dione Chemical compound CC(C)C1=NC=2N(C)C3=CC=CC=C3C(=O)C=2C(=O)N1C1=CC=CC=C1C PMBWCSIBCMQYQI-UHFFFAOYSA-N 0.000 claims 2
- IPOXGFINNYJLNF-UHFFFAOYSA-N 2-(3,3-dimethylcyclobutyl)-10-methyl-3-phenylpyrimido[4,5-b]quinoline-4,5-dione Chemical compound CN1C2=CC=CC=C2C(=O)C(C(N2C=3C=CC=CC=3)=O)=C1N=C2C1CC(C)(C)C1 IPOXGFINNYJLNF-UHFFFAOYSA-N 0.000 claims 2
- YDNBJEBDWYMWLI-UHFFFAOYSA-N 2-(3-methoxycyclobutyl)-10-methyl-3-phenylpyrimido[4,5-b]quinoline-4,5-dione Chemical compound C1C(OC)CC1C(N(C1=O)C=2C=CC=CC=2)=NC2=C1C(=O)C1=CC=CC=C1N2C YDNBJEBDWYMWLI-UHFFFAOYSA-N 0.000 claims 2
- VBIZBFXISRBSQP-UHFFFAOYSA-N 2-(3-methoxypropyl)-10-methyl-3-phenylpyrimido[4,5-b]quinoline-4,5-dione Chemical compound COCCCC1=NC=2N(C)C3=CC=CC=C3C(=O)C=2C(=O)N1C1=CC=CC=C1 VBIZBFXISRBSQP-UHFFFAOYSA-N 0.000 claims 2
- HPBWLSHITILJGA-UHFFFAOYSA-N 2-(4-methoxybutyl)-10-methyl-3-phenylpyrimido[4,5-b]quinoline-4,5-dione Chemical compound COCCCCC1=NC=2N(C)C3=CC=CC=C3C(=O)C=2C(=O)N1C1=CC=CC=C1 HPBWLSHITILJGA-UHFFFAOYSA-N 0.000 claims 2
- ROFPZFAMQLCEHM-UHFFFAOYSA-N 2-(dimethylamino)-10-methyl-3-phenylpyrimido[4,5-b]quinoline-4,5-dione Chemical compound CN(C)C1=NC=2N(C)C3=CC=CC=C3C(=O)C=2C(=O)N1C1=CC=CC=C1 ROFPZFAMQLCEHM-UHFFFAOYSA-N 0.000 claims 2
- SCUCYCRANOULJA-UHFFFAOYSA-N 2-butan-2-yl-3-cyclopentyl-10-methylpyrimido[4,5-b]quinoline-4,5-dione Chemical compound CCC(C)C1=NC=2N(C)C3=CC=CC=C3C(=O)C=2C(=O)N1C1CCCC1 SCUCYCRANOULJA-UHFFFAOYSA-N 0.000 claims 2
- TWBNGWUKGVLXDW-UHFFFAOYSA-N 2-butyl-10-methyl-3-phenylpyrimido[4,5-b]quinoline-4,5-dione Chemical compound CCCCC1=NC=2N(C)C3=CC=CC=C3C(=O)C=2C(=O)N1C1=CC=CC=C1 TWBNGWUKGVLXDW-UHFFFAOYSA-N 0.000 claims 2
- MQNROLMZODTCLU-UHFFFAOYSA-N 2-cyclobutyl-10-(2-hydroxyethyl)-3-phenylpyrimido[4,5-b]quinoline-4,5-dione Chemical compound OCCN1C2=CC=CC=C2C(=O)C(C(N2C=3C=CC=CC=3)=O)=C1N=C2C1CCC1 MQNROLMZODTCLU-UHFFFAOYSA-N 0.000 claims 2
- XUOTZAUZHWCGHL-UHFFFAOYSA-N 2-cyclobutyl-10-methyl-3-phenylpyrimido[4,5-b]quinoline-4,5-dione Chemical compound CN1C2=CC=CC=C2C(=O)C(C(N2C=3C=CC=CC=3)=O)=C1N=C2C1CCC1 XUOTZAUZHWCGHL-UHFFFAOYSA-N 0.000 claims 2
- RDMZIKXXHILBBJ-UHFFFAOYSA-N 2-cyclobutyl-3-phenyl-10h-pyrimido[4,5-b]quinoline-4,5-dione Chemical compound C1CCC1C1=NC=2NC3=CC=CC=C3C(=O)C=2C(=O)N1C1=CC=CC=C1 RDMZIKXXHILBBJ-UHFFFAOYSA-N 0.000 claims 2
- MVBSDSAQVLFZKR-UHFFFAOYSA-N 2-cyclopentyl-10-methyl-3-phenylpyrimido[4,5-b]quinoline-4,5-dione Chemical compound CN1C2=CC=CC=C2C(=O)C(C(N2C=3C=CC=CC=3)=O)=C1N=C2C1CCCC1 MVBSDSAQVLFZKR-UHFFFAOYSA-N 0.000 claims 2
- SXOVPDSRBVJYOK-UHFFFAOYSA-N 2-cyclopropyl-10-methyl-3-phenylpyrimido[4,5-b]quinoline-4,5-dione Chemical compound CN1C2=CC=CC=C2C(=O)C(C(N2C=3C=CC=CC=3)=O)=C1N=C2C1CC1 SXOVPDSRBVJYOK-UHFFFAOYSA-N 0.000 claims 2
- JVHOJZICPPHKQV-UHFFFAOYSA-N 2-heptyl-10-methyl-3-phenylpyrimido[4,5-b]quinoline-4,5-dione Chemical compound CCCCCCCC1=NC=2N(C)C3=CC=CC=C3C(=O)C=2C(=O)N1C1=CC=CC=C1 JVHOJZICPPHKQV-UHFFFAOYSA-N 0.000 claims 2
- DZSKHIMLIIZWQK-UHFFFAOYSA-N 2-tert-butyl-3-cyclopentyl-10-methylpyrimido[4,5-b]quinoline-4,5-dione Chemical compound CN1C2=CC=CC=C2C(=O)C(C2=O)=C1N=C(C(C)(C)C)N2C1CCCC1 DZSKHIMLIIZWQK-UHFFFAOYSA-N 0.000 claims 2
- HCBOGFQXDPFJHD-UHFFFAOYSA-N 3-(2,6-dichlorophenyl)-10-methyl-2-propan-2-ylpyrimido[4,5-b]quinoline-4,5-dione Chemical compound CC(C)C1=NC=2N(C)C3=CC=CC=C3C(=O)C=2C(=O)N1C1=C(Cl)C=CC=C1Cl HCBOGFQXDPFJHD-UHFFFAOYSA-N 0.000 claims 2
- XUFSQHNFIVPDAO-UHFFFAOYSA-N 3-(2-bromophenyl)-10-methyl-2-propan-2-ylpyrimido[4,5-b]quinoline-4,5-dione Chemical compound CC(C)C1=NC=2N(C)C3=CC=CC=C3C(=O)C=2C(=O)N1C1=CC=CC=C1Br XUFSQHNFIVPDAO-UHFFFAOYSA-N 0.000 claims 2
- JOBBNECOHYFSNQ-UHFFFAOYSA-N 3-(2-chlorophenyl)-10-methyl-2-propan-2-ylpyrimido[4,5-b]quinoline-4,5-dione Chemical compound CC(C)C1=NC=2N(C)C3=CC=CC=C3C(=O)C=2C(=O)N1C1=CC=CC=C1Cl JOBBNECOHYFSNQ-UHFFFAOYSA-N 0.000 claims 2
- XWSUEPKHTKUPCW-UHFFFAOYSA-N 3-(2-fluorophenyl)-10-methyl-2-propan-2-ylpyrimido[4,5-b]quinoline-4,5-dione Chemical compound CC(C)C1=NC=2N(C)C3=CC=CC=C3C(=O)C=2C(=O)N1C1=CC=CC=C1F XWSUEPKHTKUPCW-UHFFFAOYSA-N 0.000 claims 2
- NHGKPNJAMXQUOK-UHFFFAOYSA-N 3-(2-methoxyphenyl)-10-methyl-2-propan-2-ylpyrimido[4,5-b]quinoline-4,5-dione Chemical compound COC1=CC=CC=C1N1C(=O)C(C(=O)C2=CC=CC=C2N2C)=C2N=C1C(C)C NHGKPNJAMXQUOK-UHFFFAOYSA-N 0.000 claims 2
- GWIMOQDSJAIBBL-UHFFFAOYSA-N 3-(3-chlorophenyl)-10-methyl-2-propan-2-ylpyrimido[4,5-b]quinoline-4,5-dione Chemical compound CC(C)C1=NC=2N(C)C3=CC=CC=C3C(=O)C=2C(=O)N1C1=CC=CC(Cl)=C1 GWIMOQDSJAIBBL-UHFFFAOYSA-N 0.000 claims 2
- MSQFXAYKUKJJGP-UHFFFAOYSA-N 3-(3-methoxyphenyl)-10-methyl-2-propan-2-ylpyrimido[4,5-b]quinoline-4,5-dione Chemical compound COC1=CC=CC(N2C(C=3C(=O)C4=CC=CC=C4N(C)C=3N=C2C(C)C)=O)=C1 MSQFXAYKUKJJGP-UHFFFAOYSA-N 0.000 claims 2
- SJIVMSFHBQNOKF-UHFFFAOYSA-N 3-cyclohexyl-10-methyl-2-propan-2-ylpyrimido[4,5-b]quinoline-4,5-dione Chemical compound CC(C)C1=NC=2N(C)C3=CC=CC=C3C(=O)C=2C(=O)N1C1CCCCC1 SJIVMSFHBQNOKF-UHFFFAOYSA-N 0.000 claims 2
- OOCZRFRDHDLJRA-UHFFFAOYSA-N 3-cyclohexyl-10-methyl-2-propylpyrimido[4,5-b]quinoline-4,5-dione Chemical compound CCCC1=NC=2N(C)C3=CC=CC=C3C(=O)C=2C(=O)N1C1CCCCC1 OOCZRFRDHDLJRA-UHFFFAOYSA-N 0.000 claims 2
- XSZRSVDMMTZQJG-UHFFFAOYSA-N 3-cyclopentyl-10-ethyl-2-propan-2-ylpyrimido[4,5-b]quinoline-4,5-dione Chemical compound CCN1C2=CC=CC=C2C(=O)C(C2=O)=C1N=C(C(C)C)N2C1CCCC1 XSZRSVDMMTZQJG-UHFFFAOYSA-N 0.000 claims 2
- QZMBWTOBYSLOSR-UHFFFAOYSA-N 3-cyclopentyl-10-methyl-2-(2-methylpropyl)pyrimido[4,5-b]quinoline-4,5-dione Chemical compound CC(C)CC1=NC=2N(C)C3=CC=CC=C3C(=O)C=2C(=O)N1C1CCCC1 QZMBWTOBYSLOSR-UHFFFAOYSA-N 0.000 claims 2
- GYHLYFIGSOVXRL-UHFFFAOYSA-N 3-cyclopentyl-10-methyl-2-pentylpyrimido[4,5-b]quinoline-4,5-dione Chemical compound CCCCCC1=NC=2N(C)C3=CC=CC=C3C(=O)C=2C(=O)N1C1CCCC1 GYHLYFIGSOVXRL-UHFFFAOYSA-N 0.000 claims 2
- BQFAXUQGGXIZMM-UHFFFAOYSA-N 3-cyclopentyl-10-methyl-2-propan-2-ylpyrimido[4,5-b]quinoline-4,5-dione Chemical compound CC(C)C1=NC=2N(C)C3=CC=CC=C3C(=O)C=2C(=O)N1C1CCCC1 BQFAXUQGGXIZMM-UHFFFAOYSA-N 0.000 claims 2
- MKINHZSCOUWIHE-UHFFFAOYSA-N 3-cyclopentyl-10-methyl-2-propylpyrimido[4,5-b]quinoline-4,5-dione Chemical compound CCCC1=NC=2N(C)C3=CC=CC=C3C(=O)C=2C(=O)N1C1CCCC1 MKINHZSCOUWIHE-UHFFFAOYSA-N 0.000 claims 2
- NMBXOVKFWROLHT-UHFFFAOYSA-N 3-cyclopentyl-10-methyl-4,5-dioxo-2-propan-2-ylpyrimido[4,5-b]quinoline-7-carbonitrile Chemical compound CC(C)C1=NC=2N(C)C3=CC=C(C#N)C=C3C(=O)C=2C(=O)N1C1CCCC1 NMBXOVKFWROLHT-UHFFFAOYSA-N 0.000 claims 2
- YIWNPOLQIUGSPL-UHFFFAOYSA-N 3-cyclopentyl-2-propan-2-yl-10-prop-2-enylpyrimido[4,5-b]quinoline-4,5-dione Chemical compound CC(C)C1=NC=2N(CC=C)C3=CC=CC=C3C(=O)C=2C(=O)N1C1CCCC1 YIWNPOLQIUGSPL-UHFFFAOYSA-N 0.000 claims 2
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- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 238000004704 ultra performance liquid chromatography Methods 0.000 description 1
- 238000011144 upstream manufacturing Methods 0.000 description 1
- 238000010200 validation analysis Methods 0.000 description 1
- 230000000007 visual effect Effects 0.000 description 1
- 238000001262 western blot Methods 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/04—Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/14—Ortho-condensed systems
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Epidemiology (AREA)
- Obesity (AREA)
- Neurology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Endocrinology (AREA)
- Emergency Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Inorganic Chemistry (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201261736748P | 2012-12-13 | 2012-12-13 | |
| US61/736,748 | 2012-12-13 | ||
| PCT/IB2013/060859 WO2014091446A1 (en) | 2012-12-13 | 2013-12-12 | Pyrimido [4,5-b]quinoline-4,5 (3h,10h)-diones as nonsense mutation suppressors |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2890692A1 true CA2890692A1 (en) | 2014-06-19 |
Family
ID=50030361
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2890692A Abandoned CA2890692A1 (en) | 2012-12-13 | 2013-12-12 | Pyrimido [4,5-b]quinoline-4,5 (3h,10h)-diones as nonsense mutation suppressors |
Country Status (24)
| Country | Link |
|---|---|
| US (2) | US9649314B2 (en:Method) |
| EP (1) | EP2931282B1 (en:Method) |
| JP (1) | JP6076498B2 (en:Method) |
| KR (1) | KR101760586B1 (en:Method) |
| CN (2) | CN107569487A (en:Method) |
| AP (1) | AP2015008441A0 (en:Method) |
| AU (1) | AU2013358591B2 (en:Method) |
| BR (1) | BR112015013535A2 (en:Method) |
| CA (1) | CA2890692A1 (en:Method) |
| CL (1) | CL2015001610A1 (en:Method) |
| CR (1) | CR20150314A (en:Method) |
| CU (1) | CU20150061A7 (en:Method) |
| EA (1) | EA028673B1 (en:Method) |
| ES (1) | ES2709034T3 (en:Method) |
| HK (1) | HK1209637A1 (en:Method) |
| IL (1) | IL239244A0 (en:Method) |
| IN (1) | IN2015DN03998A (en:Method) |
| MA (1) | MA38157A1 (en:Method) |
| MX (1) | MX363437B (en:Method) |
| PE (1) | PE20151062A1 (en:Method) |
| PH (1) | PH12015501216A1 (en:Method) |
| SG (1) | SG11201503684WA (en:Method) |
| TN (1) | TN2015000262A1 (en:Method) |
| WO (1) | WO2014091446A1 (en:Method) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2890692A1 (en) | 2012-12-13 | 2014-06-19 | Novartis Ag | Pyrimido [4,5-b]quinoline-4,5 (3h,10h)-diones as nonsense mutation suppressors |
| WO2015186061A1 (en) * | 2014-06-03 | 2015-12-10 | Novartis Ag | Pyridopyrimidinedione derivatives |
| AP2016009545A0 (en) * | 2014-06-03 | 2016-11-30 | Novartis Ag | Naphthyridinedione derivatives |
| CN106459041B (zh) | 2014-06-03 | 2018-10-16 | 诺华股份有限公司 | 嘧啶并[4,5-b]喹啉-4,5(3H,10H)-二酮衍生物 |
| WO2017181193A2 (en) * | 2016-04-15 | 2017-10-19 | The Uab Research Foundation | Methods and compounds for stimulating read-through of premature termination codons |
| EP3762383B1 (en) * | 2018-03-06 | 2023-12-06 | The United States of America, as represented by the Secretary, Department of Health and Human Services | Positive allosteric modulators of dopamine 1 receptor and method of use thereof |
| WO2019225625A1 (ja) * | 2018-05-23 | 2019-11-28 | 京都薬品工業株式会社 | リードスルー誘導剤およびその医薬用途 |
| AU2021341508A1 (en) | 2020-09-10 | 2023-05-25 | Precirix N.V. | Antibody fragment against fap |
| AU2022207648A1 (en) | 2021-01-13 | 2023-07-27 | Monte Rosa Therapeutics Ag | Isoindolinone compounds |
| WO2023203135A1 (en) | 2022-04-22 | 2023-10-26 | Precirix N.V. | Improved radiolabelled antibody |
| WO2023213801A1 (en) | 2022-05-02 | 2023-11-09 | Precirix N.V. | Pre-targeting |
| WO2024194607A1 (en) | 2023-03-17 | 2024-09-26 | Tay Therapeutics Limited | Pyrimido[4,5-b][1,5]naphthyridine-4,5(3h,10h)-dione derivatives for the treatment of diseases associated with ptc mutations, such as e.g. cancer |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
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| JP2884170B2 (ja) * | 1989-08-24 | 1999-04-19 | 株式会社フジモト・ブラザーズ | ５−デアザフラビン系化合物を有効成分とする制癌剤 |
| US5908930A (en) * | 1995-03-15 | 1999-06-01 | Pfizer Inc. | 5,10-dihydropyrimdo 4,5-b!quinolin-4(1H)-one tyrosine kinase inhibitors |
| US6468990B1 (en) | 1999-05-17 | 2002-10-22 | Queen's University At Kingston | Method of inhibiting binding of nerve growth factor to p75 NTR receptor |
| WO2004006906A2 (en) | 2002-07-15 | 2004-01-22 | Combinatorx, Incorporated | Methods for the treatment of neoplasms |
| CA2514733A1 (en) | 2003-02-28 | 2004-09-16 | Transform Pharmaceuticals, Inc. | Pharmaceutical co-crystal compositions of drugs such as carbamazepine, celecoxib, olanzapine, itraconazole, topiramate, modafinil, 5-fluorouracil, hydrochlorothiazide, acetaminophen, aspirin, flurbiprofen, phenytoin and ibuprofen |
| ES2926542T3 (es) | 2003-04-11 | 2022-10-26 | Ptc Therapeutics Inc | Compuestos de ácido 1,2,4-oxadiazol benzoico y su uso para supresión de mutaciones finalizadoras y el tratamiento de enfermedades |
| DK2390255T3 (en) | 2006-04-03 | 2016-11-07 | Technion Res & Dev Foundation | Novel aminoglycosides and uses thereof in the treatment of genetic disorders |
| CN101563349A (zh) | 2006-08-23 | 2009-10-21 | 神经能质公司 | 经卤烷基取代的嘧啶酮衍生物 |
| JP2011507910A (ja) * | 2007-12-21 | 2011-03-10 | ユニバーシティー オブ ロチェスター | 真核生物の寿命を変更するための方法 |
| EP2422817A1 (en) | 2010-07-29 | 2012-02-29 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Flavin-nucleic acid ligand conjugates |
| CN103189060A (zh) * | 2010-08-05 | 2013-07-03 | 里尔法律与医疗卫生第二大学 | 用于对无义突变介导的疾病进行治疗的化合物和含有所述化合物的药物组合物 |
| CA2890692A1 (en) | 2012-12-13 | 2014-06-19 | Novartis Ag | Pyrimido [4,5-b]quinoline-4,5 (3h,10h)-diones as nonsense mutation suppressors |
-
2013
- 2013-12-12 CA CA2890692A patent/CA2890692A1/en not_active Abandoned
- 2013-12-12 KR KR1020157018231A patent/KR101760586B1/ko not_active Expired - Fee Related
- 2013-12-12 JP JP2015547244A patent/JP6076498B2/ja not_active Expired - Fee Related
- 2013-12-12 IN IN3998DEN2015 patent/IN2015DN03998A/en unknown
- 2013-12-12 SG SG11201503684WA patent/SG11201503684WA/en unknown
- 2013-12-12 ES ES13826612T patent/ES2709034T3/es active Active
- 2013-12-12 HK HK15110447.1A patent/HK1209637A1/xx unknown
- 2013-12-12 CN CN201710826258.0A patent/CN107569487A/zh active Pending
- 2013-12-12 PE PE2015000911A patent/PE20151062A1/es not_active Application Discontinuation
- 2013-12-12 AP AP2015008441A patent/AP2015008441A0/xx unknown
- 2013-12-12 WO PCT/IB2013/060859 patent/WO2014091446A1/en active Application Filing
- 2013-12-12 BR BR112015013535A patent/BR112015013535A2/pt not_active Application Discontinuation
- 2013-12-12 AU AU2013358591A patent/AU2013358591B2/en not_active Ceased
- 2013-12-12 EA EA201591105A patent/EA028673B1/ru not_active IP Right Cessation
- 2013-12-12 US US14/652,102 patent/US9649314B2/en not_active Expired - Fee Related
- 2013-12-12 EP EP13826612.7A patent/EP2931282B1/en active Active
- 2013-12-12 MX MX2015007562A patent/MX363437B/es unknown
- 2013-12-12 CN CN201380064035.5A patent/CN104837490B/zh not_active Expired - Fee Related
-
2015
- 2015-05-29 PH PH12015501216A patent/PH12015501216A1/en unknown
- 2015-06-04 IL IL239244A patent/IL239244A0/en unknown
- 2015-06-05 MA MA38157A patent/MA38157A1/fr unknown
- 2015-06-09 TN TNP2015000262A patent/TN2015000262A1/fr unknown
- 2015-06-10 CL CL2015001610A patent/CL2015001610A1/es unknown
- 2015-06-12 CR CR20150314A patent/CR20150314A/es unknown
- 2015-06-12 CU CUP2015000061A patent/CU20150061A7/es unknown
-
2017
- 2017-04-04 US US15/478,778 patent/US20170266189A1/en not_active Abandoned
Also Published As
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| AU2013358591B2 (en) | Pyrimido [4,5-b]quinoline-4,5 (3H,10H)-diones as nonsense mutation suppressors | |
| AU2015270125B2 (en) | Naphthyridinedione derivatives | |
| EP3152207B1 (en) | Pyridopyrimidinedione derivatives as suppressors of non-sens mutations | |
| EP3152208B1 (en) | Pyrimido[4,5-b]quinoline-4,5(3h,10h)-dione derivatives as suppressors of non-sens mutations | |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request |
Effective date: 20181205 |
|
| FZDE | Discontinued |
Effective date: 20210831 |