ES2628369T3 - Compuestos tricíclicos para inhibir el canal CFTR - Google Patents

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Publication number

ES2628369T3

ES2628369T3 ES13826625.9T ES13826625T ES2628369T3 ES 2628369 T3 ES2628369 T3 ES 2628369T3 ES 13826625 T ES13826625 T ES 13826625T ES 2628369 T3 ES2628369 T3 ES 2628369T3

Authority

ES

Spain

Prior art keywords

dimethyl

alkyl

dione

pyrimido

pyrrolo

Prior art date

2012-12-19

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.)

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• 150000001875 compounds Chemical class 0.000 title claims abstract description 328
• -1 halo (C1-C4) alkyl Chemical group 0.000 claims abstract description 442
• 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 191
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 102
• 150000003839 salts Chemical class 0.000 claims abstract description 60
• 239000001257 hydrogen Substances 0.000 claims abstract description 39
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 33
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 30
• 125000001424 substituent group Chemical group 0.000 claims abstract description 27
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 26
• 125000005843 halogen group Chemical group 0.000 claims abstract description 20
• 125000004103 aminoalkyl group Chemical group 0.000 claims abstract description 18
• 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 17
• 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 17
• 125000000217 alkyl group Chemical group 0.000 claims abstract description 16
• 229910052760 oxygen Inorganic materials 0.000 claims abstract description 15
• 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 13
• 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 12
• 229910052717 sulfur Inorganic materials 0.000 claims abstract description 11
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 10
• 125000005842 heteroatom Chemical group 0.000 claims abstract description 10
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 9
• 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract description 8
• 125000000392 cycloalkenyl group Chemical group 0.000 claims abstract description 8
• 125000001188 haloalkyl group Chemical group 0.000 claims abstract description 8
• 125000000335 thiazolyl group Chemical group 0.000 claims abstract description 8
• 125000001544 thienyl group Chemical group 0.000 claims abstract description 8
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 7
• 125000002541 furyl group Chemical group 0.000 claims abstract description 6
• 239000001301 oxygen Substances 0.000 claims abstract description 6
• 125000006526 (C1-C2) alkyl group Chemical group 0.000 claims abstract description 5
• 125000003545 alkoxy group Chemical group 0.000 claims abstract description 5
• 125000003282 alkyl amino group Chemical group 0.000 claims abstract description 5
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 5
• 125000006536 (C1-C2)alkoxy group Chemical group 0.000 claims abstract description 4
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 4
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims abstract description 4
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims abstract description 4
• 125000003341 7 membered heterocyclic group Chemical group 0.000 claims abstract description 4
• MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims abstract description 4
• 125000004438 haloalkoxy group Chemical group 0.000 claims abstract description 4
• 125000004434 sulfur atom Chemical group 0.000 claims abstract description 4
• JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 150
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 61
• 206010012735 Diarrhoea Diseases 0.000 claims description 42
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 42
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 41
• 239000002253 acid Substances 0.000 claims description 31
• 201000010099 disease Diseases 0.000 claims description 30
• 239000003814 drug Substances 0.000 claims description 29
• 239000003795 chemical substances by application Substances 0.000 claims description 25
• 239000008194 pharmaceutical composition Substances 0.000 claims description 20
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 18
• 208000030761 polycystic kidney disease Diseases 0.000 claims description 16
• 229910052799 carbon Inorganic materials 0.000 claims description 13
• 208000035475 disorder Diseases 0.000 claims description 11
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 9
• 125000004429 atom Chemical group 0.000 claims description 9
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 7
• DXASQZJWWGZNSF-UHFFFAOYSA-N n,n-dimethylmethanamine;sulfur trioxide Chemical group CN(C)C.O=S(=O)=O DXASQZJWWGZNSF-UHFFFAOYSA-N 0.000 claims description 6
• ZVWHNWKIKAKMBA-UHFFFAOYSA-N 10-(3-chlorophenyl)-1,3-dimethyl-5-phenyl-8,10-dihydro-7h-pyrimido[1,2]pyrrolo[4,5-a][1,4]thiazine-2,4-dione Chemical compound C=12C(=O)N(C)C(=O)N(C)C2=C2C(C=3C=C(Cl)C=CC=3)SCCN2C=1C1=CC=CC=C1 ZVWHNWKIKAKMBA-UHFFFAOYSA-N 0.000 claims description 5
• NODRNSUBQQBWEJ-UHFFFAOYSA-N 10-(4-chloro-1,3-thiazol-2-yl)-5-[4-(hydroxymethyl)-1,3-thiazol-2-yl]-1,3-dimethyl-8,10-dihydro-7h-pyrimido[1,2]pyrrolo[4,5-a][1,4]thiazine-2,4-dione Chemical compound C=12C(=O)N(C)C(=O)N(C)C2=C2C(C=3SC=C(Cl)N=3)SCCN2C=1C1=NC(CO)=CS1 NODRNSUBQQBWEJ-UHFFFAOYSA-N 0.000 claims description 5
• HCSVUQJBRBZQSY-UHFFFAOYSA-N 10-(5-chlorofuran-2-yl)-5-[4-(hydroxymethyl)-1,3-thiazol-2-yl]-1,3-dimethyl-8,10-dihydro-7h-pyrimido[1,2]pyrrolo[4,5-a][1,4]thiazine-2,4-dione Chemical compound C=12C(=O)N(C)C(=O)N(C)C2=C2C(C=3OC(Cl)=CC=3)SCCN2C=1C1=NC(CO)=CS1 HCSVUQJBRBZQSY-UHFFFAOYSA-N 0.000 claims description 5
• 239000003937 drug carrier Substances 0.000 claims description 5
• DBMBAPUQYZUKHG-UHFFFAOYSA-N 10-(5-chlorofuran-2-yl)-8-(hydroxymethyl)-1,3-dimethyl-5-(4-methyl-1,3-thiazol-2-yl)-8,10-dihydro-7h-pyrimido[1,2]pyrrolo[4,5-a][1,4]thiazine-2,4-dione Chemical compound CC1=CSC(C2=C3C(=O)N(C)C(=O)N(C)C3=C3C(C=4OC(Cl)=CC=4)SC(CO)CN32)=N1 DBMBAPUQYZUKHG-UHFFFAOYSA-N 0.000 claims description 4
• MPDQXBVRCZKRLB-UHFFFAOYSA-N 3-[10-(5-chlorofuran-2-yl)-1,3-dimethyl-2,4-dioxo-8,10-dihydro-7h-pyrimido[1,2]pyrrolo[4,5-a][1,4]thiazin-5-yl]benzonitrile Chemical compound C=12C(=O)N(C)C(=O)N(C)C2=C2C(C=3OC(Cl)=CC=3)SCCN2C=1C1=CC=CC(C#N)=C1 MPDQXBVRCZKRLB-UHFFFAOYSA-N 0.000 claims description 4
• WJHVFGZWIKTOIW-UHFFFAOYSA-N 9-(4-chloro-1,3-thiazol-2-yl)-1,3,8,8-tetramethyl-5-phenyl-7,9-dihydropyrimido[4,5-a]pyrrolizine-2,4-dione Chemical compound CC1(C)CN2C(C=3C=CC=CC=3)=C3C(=O)N(C)C(=O)N(C)C3=C2C1C1=NC(Cl)=CS1 WJHVFGZWIKTOIW-UHFFFAOYSA-N 0.000 claims description 4
• HCSVUQJBRBZQSY-INIZCTEOSA-N (10r)-10-(5-chlorofuran-2-yl)-5-[4-(hydroxymethyl)-1,3-thiazol-2-yl]-1,3-dimethyl-8,10-dihydro-7h-pyrimido[1,2]pyrrolo[4,5-a][1,4]thiazine-2,4-dione Chemical compound S([C@H](C1=C2N(C(N(C)C(=O)C2=2)=O)C)C=3OC(Cl)=CC=3)CCN1C=2C1=NC(CO)=CS1 HCSVUQJBRBZQSY-INIZCTEOSA-N 0.000 claims description 3
• OWDSPKZXDBSXBH-UHFFFAOYSA-N 1,3-dimethyl-10-(4-methyl-1,3-thiazol-2-yl)-5-phenyl-8,10-dihydro-7h-pyrimido[1,2]pyrrolo[4,5-a][1,4]thiazine-2,4-dione Chemical compound CC1=CSC(C2C=3N(C(=C4C(=O)N(C)C(=O)N(C)C4=3)C=3C=CC=CC=3)CCS2)=N1 OWDSPKZXDBSXBH-UHFFFAOYSA-N 0.000 claims description 3
• WNLWOYUQQHELJH-UHFFFAOYSA-N 1,3-dimethyl-5,10-bis(4-methyl-1,3-thiazol-2-yl)-7,8,9,10-tetrahydropyrimido[4,5-a]indolizine-2,4-dione Chemical compound CC1=CSC(C2C=3N(C(=C4C(=O)N(C)C(=O)N(C)C4=3)C=3SC=C(C)N=3)CCC2)=N1 WNLWOYUQQHELJH-UHFFFAOYSA-N 0.000 claims description 3
• MXNCCALGQMGPNA-UHFFFAOYSA-N 10-(4-chloro-1,3-thiazol-2-yl)-1,3-dimethyl-5-(1-methylpyrazol-3-yl)-7,8,9,10-tetrahydropyrimido[4,5-a]indolizine-2,4-dione Chemical compound CN1C=CC(C2=C3C(=O)N(C)C(=O)N(C)C3=C3C(C=4SC=C(Cl)N=4)CCCN32)=N1 MXNCCALGQMGPNA-UHFFFAOYSA-N 0.000 claims description 3
• UJMUZJRWCRZRMO-UHFFFAOYSA-N 10-(4-chloro-1,3-thiazol-2-yl)-5-(3-fluorophenyl)-8-(hydroxymethyl)-1,3-dimethyl-7,8,9,10-tetrahydropyrimido[4,5-a]indolizine-2,4-dione Chemical compound C=12C(=O)N(C)C(=O)N(C)C2=C2C(C=3SC=C(Cl)N=3)CC(CO)CN2C=1C1=CC=CC(F)=C1 UJMUZJRWCRZRMO-UHFFFAOYSA-N 0.000 claims description 3
• JKYQAJRHBLIHNN-UHFFFAOYSA-N 10-(5-chlorofuran-2-yl)-1,3-dimethyl-5-(1-methylimidazol-4-yl)-8,10-dihydro-7h-pyrimido[1,2]pyrrolo[4,5-a][1,4]thiazine-2,4-dione Chemical compound CN1C=NC(C2=C3C(=O)N(C)C(=O)N(C)C3=C3C(C=4OC(Cl)=CC=4)SCCN32)=C1 JKYQAJRHBLIHNN-UHFFFAOYSA-N 0.000 claims description 3
• NRFUJNSPJPMOJX-UHFFFAOYSA-N 10-(5-chlorofuran-2-yl)-1,3-dimethyl-5-(1-methylpyrazol-4-yl)-8,10-dihydro-7h-pyrimido[1,2]pyrrolo[4,5-a][1,4]thiazine-2,4-dione Chemical compound C1=NN(C)C=C1C1=C2C(=O)N(C)C(=O)N(C)C2=C2C(C=3OC(Cl)=CC=3)SCCN21 NRFUJNSPJPMOJX-UHFFFAOYSA-N 0.000 claims description 3
• IVAOJSCNZXBWCF-UHFFFAOYSA-N 10-(5-chlorofuran-2-yl)-1,3-dimethyl-5-(3-methylphenyl)-8,10-dihydro-7h-pyrimido[1,2]pyrrolo[4,5-a][1,4]thiazine-2,4-dione Chemical compound CC1=CC=CC(C2=C3C(=O)N(C)C(=O)N(C)C3=C3C(C=4OC(Cl)=CC=4)SCCN32)=C1 IVAOJSCNZXBWCF-UHFFFAOYSA-N 0.000 claims description 3
• HODVQYQNLRXFNK-UHFFFAOYSA-N 10-(5-chlorofuran-2-yl)-1,3-dimethyl-5-(5-methyl-1,3,4-oxadiazol-2-yl)-8,10-dihydro-7h-pyrimido[1,2]pyrrolo[4,5-a][1,4]thiazine-2,4-dione Chemical compound O1C(C)=NN=C1C1=C2C(=O)N(C)C(=O)N(C)C2=C2C(C=3OC(Cl)=CC=3)SCCN21 HODVQYQNLRXFNK-UHFFFAOYSA-N 0.000 claims description 3
• VYIFXMDXJZVGMQ-UHFFFAOYSA-N 10-(5-chlorofuran-2-yl)-1,3-dimethyl-5-phenyl-8,10-dihydro-7h-pyrimido[1,2]pyrrolo[4,5-a][1,4]thiazine-2,4-dione Chemical compound C=12C(=O)N(C)C(=O)N(C)C2=C2C(C=3OC(Cl)=CC=3)SCCN2C=1C1=CC=CC=C1 VYIFXMDXJZVGMQ-UHFFFAOYSA-N 0.000 claims description 3
• KGBBKIRQNQXTLL-UHFFFAOYSA-N 10-(5-chlorofuran-2-yl)-8-(hydroxymethyl)-1,3-dimethyl-5-phenyl-8,10-dihydro-7h-pyrimido[1,2]pyrrolo[4,5-a][1,4]thiazine-2,4-dione Chemical compound C=12C(=O)N(C)C(=O)N(C)C2=C2C(C=3OC(Cl)=CC=3)SC(CO)CN2C=1C1=CC=CC=C1 KGBBKIRQNQXTLL-UHFFFAOYSA-N 0.000 claims description 3
• QNTGLAAAZRVNMY-UHFFFAOYSA-N 10-(5-chlorofuran-2-yl)-8-(imidazol-1-ylmethyl)-1,3-dimethyl-5-(4-methyl-1,3-thiazol-2-yl)-8,10-dihydro-7h-pyrimido[1,2]pyrrolo[4,5-a][1,4]thiazine-2,4-dione Chemical compound CC1=CSC(C2=C3C(=O)N(C)C(=O)N(C)C3=C3C(C=4OC(Cl)=CC=4)SC(CN4C=NC=C4)CN32)=N1 QNTGLAAAZRVNMY-UHFFFAOYSA-N 0.000 claims description 3
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 3
• GQMRGCWPYIYAMA-UHFFFAOYSA-N 5-(3-fluorophenyl)-1,3-dimethyl-10-(5-methylfuran-2-yl)-7,8,9,10-tetrahydropyrimido[4,5-a]indolizine-2,4-dione Chemical compound O1C(C)=CC=C1C1C2=C(N(C)C(=O)N(C)C3=O)C3=C(C=3C=C(F)C=CC=3)N2CCC1 GQMRGCWPYIYAMA-UHFFFAOYSA-N 0.000 claims description 3
• XYTHAMQYSFXAAO-UHFFFAOYSA-N 9-(4-chloro-1,3-thiazol-2-yl)-1,3-dimethyl-5-phenyl-8,9-dihydro-7h-pyrimido[4,5-a]pyrrolizine-2,4-dione Chemical compound C=12C(=O)N(C)C(=O)N(C)C2=C2C(C=3SC=C(Cl)N=3)CCN2C=1C1=CC=CC=C1 XYTHAMQYSFXAAO-UHFFFAOYSA-N 0.000 claims description 3
• 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims description 3
• FCDNVZVJKPOBNM-UHFFFAOYSA-N 1,3-dimethyl-10-(3-methylphenyl)-5-phenyl-8,10-dihydro-7h-pyrimido[1,2]pyrrolo[4,5-a][1,4]thiazine-2,4-dione Chemical compound CC1=CC=CC(C2C=3N(C(=C4C(=O)N(C)C(=O)N(C)C4=3)C=3C=CC=CC=3)CCS2)=C1 FCDNVZVJKPOBNM-UHFFFAOYSA-N 0.000 claims description 2
• HNVVHZKLSMTISP-UHFFFAOYSA-N 1,3-dimethyl-10-(4-methyl-1,3-thiazol-2-yl)-5-phenyl-7,8,9,10-tetrahydropyrimido[4,5-a]indolizine-2,4-dione Chemical compound CC1=CSC(C2C=3N(C(=C4C(=O)N(C)C(=O)N(C)C4=3)C=3C=CC=CC=3)CCC2)=N1 HNVVHZKLSMTISP-UHFFFAOYSA-N 0.000 claims description 2
• PYTIQBNISILIGV-UHFFFAOYSA-N 1,3-dimethyl-5-(3-methylphenyl)-10-(4-methyl-1,3-thiazol-2-yl)-8,10-dihydro-7h-pyrimido[1,2]pyrrolo[4,5-a][1,4]thiazine-2,4-dione Chemical compound CC1=CSC(C2C=3N(C(=C4C(=O)N(C)C(=O)N(C)C4=3)C=3C=C(C)C=CC=3)CCS2)=N1 PYTIQBNISILIGV-UHFFFAOYSA-N 0.000 claims description 2
• ZVPBNWABGHQZNI-UHFFFAOYSA-N 1,3-dimethyl-9-(4-methyl-1,3-thiazol-2-yl)-5-phenyl-8,9-dihydro-7h-pyrimido[4,5-a]pyrrolizine-2,4-dione Chemical compound CC1=CSC(C2C=3N(C(=C4C(=O)N(C)C(=O)N(C)C4=3)C=3C=CC=CC=3)CC2)=N1 ZVPBNWABGHQZNI-UHFFFAOYSA-N 0.000 claims description 2
• IEFQSGOKISPRQO-UHFFFAOYSA-N 1,3-dimethyl-9-(5-methylfuran-2-yl)-5-phenyl-8,9-dihydro-7h-pyrimido[4,5-a]pyrrolizine-2,4-dione Chemical compound O1C(C)=CC=C1C1C2=C(N(C)C(=O)N(C)C3=O)C3=C(C=3C=CC=CC=3)N2CC1 IEFQSGOKISPRQO-UHFFFAOYSA-N 0.000 claims description 2
• HMVYYTRDXNKRBQ-UHFFFAOYSA-N 1,3-thiazole-4-carboxylic acid Chemical compound OC(=O)C1=CSC=N1 HMVYYTRDXNKRBQ-UHFFFAOYSA-N 0.000 claims description 2
• VPZFSXVQZXOITQ-UHFFFAOYSA-N 10-(2,3-difluorophenyl)-1,3-dimethyl-5-phenyl-7,8,9,10-tetrahydropyrimido[4,5-a]indolizine-2,4-dione Chemical compound C=12C(=O)N(C)C(=O)N(C)C2=C2C(C=3C(=C(F)C=CC=3)F)CCCN2C=1C1=CC=CC=C1 VPZFSXVQZXOITQ-UHFFFAOYSA-N 0.000 claims description 2
• QGKGPOZDMKIHPG-UHFFFAOYSA-N 10-(4-chloro-1,3-thiazol-2-yl)-5-[4-(hydroxymethyl)-1,3-thiazol-2-yl]-1,3-dimethyl-7,8,9,10-tetrahydropyrimido[4,5-a]indolizine-2,4-dione Chemical compound C=12C(=O)N(C)C(=O)N(C)C2=C2C(C=3SC=C(Cl)N=3)CCCN2C=1C1=NC(CO)=CS1 QGKGPOZDMKIHPG-UHFFFAOYSA-N 0.000 claims description 2
• YILZNBNKEXAKMX-UHFFFAOYSA-N 10-(5-chlorofuran-2-yl)-1,3-dimethyl-5-(4-methyl-1,3-thiazol-2-yl)-8-[(2-oxo-1,3-oxazolidin-3-yl)methyl]-8,10-dihydro-7h-pyrimido[1,2]pyrrolo[4,5-a][1,4]thiazine-2,4-dione Chemical compound CC1=CSC(C2=C3C(=O)N(C)C(=O)N(C)C3=C3C(C=4OC(Cl)=CC=4)SC(CN4C(OCC4)=O)CN32)=N1 YILZNBNKEXAKMX-UHFFFAOYSA-N 0.000 claims description 2
• LZVAAXNDLUJMFY-UHFFFAOYSA-N 10-(5-chlorofuran-2-yl)-5-[4-(1-hydroxyethyl)-1,3-thiazol-2-yl]-1,3-dimethyl-8,10-dihydro-7h-pyrimido[1,2]pyrrolo[4,5-a][1,4]thiazine-2,4-dione Chemical compound CC(O)C1=CSC(C2=C3C(=O)N(C)C(=O)N(C)C3=C3C(C=4OC(Cl)=CC=4)SCCN32)=N1 LZVAAXNDLUJMFY-UHFFFAOYSA-N 0.000 claims description 2
• ULTQGYQOQUFXDC-UHFFFAOYSA-N 10-(5-chlorofuran-2-yl)-8-(hydroxymethyl)-1,3-dimethyl-5-(1-methylpyrazol-3-yl)-8,10-dihydro-7h-pyrimido[1,2]pyrrolo[4,5-a][1,4]thiazine-2,4-dione Chemical compound CN1C=CC(C2=C3C(=O)N(C)C(=O)N(C)C3=C3C(C=4OC(Cl)=CC=4)SC(CO)CN32)=N1 ULTQGYQOQUFXDC-UHFFFAOYSA-N 0.000 claims description 2
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
• QMJHFPIQCRMUCS-UHFFFAOYSA-N 3-[10-(4-chloro-1,3-thiazol-2-yl)-1,3-dimethyl-2,4-dioxo-7,8,9,10-tetrahydropyrimido[4,5-a]indolizin-5-yl]benzonitrile Chemical compound C=12C(=O)N(C)C(=O)N(C)C2=C2C(C=3SC=C(Cl)N=3)CCCN2C=1C1=CC=CC(C#N)=C1 QMJHFPIQCRMUCS-UHFFFAOYSA-N 0.000 claims description 2
• RLVZCPZUJUJJHR-UHFFFAOYSA-N 3-[10-(4-chloro-1,3-thiazol-2-yl)-8-(hydroxymethyl)-1,3-dimethyl-2,4-dioxo-7,8,9,10-tetrahydropyrimido[4,5-a]indolizin-5-yl]benzonitrile Chemical compound C=12C(=O)N(C)C(=O)N(C)C2=C2C(C=3SC=C(Cl)N=3)CC(CO)CN2C=1C1=CC=CC(C#N)=C1 RLVZCPZUJUJJHR-UHFFFAOYSA-N 0.000 claims description 2
• PCJWLAMUOWWJEG-UHFFFAOYSA-N 3-[9-(4-chloro-1,3-thiazol-2-yl)-7-(hydroxymethyl)-1,3-dimethyl-2,4-dioxo-8,9-dihydro-7h-pyrimido[4,5-a]pyrrolizin-5-yl]benzonitrile Chemical compound C=12C(=O)N(C)C(=O)N(C)C2=C2C(C=3SC=C(Cl)N=3)CC(CO)N2C=1C1=CC=CC(C#N)=C1 PCJWLAMUOWWJEG-UHFFFAOYSA-N 0.000 claims description 2
• DDSJSTWPJIVJHW-UHFFFAOYSA-N 3-chloro-5-[10-(5-chlorofuran-2-yl)-1,3-dimethyl-2,4-dioxo-8,10-dihydro-7h-pyrimido[1,2]pyrrolo[4,5-a][1,4]thiazin-5-yl]benzonitrile Chemical compound C=12C(=O)N(C)C(=O)N(C)C2=C2C(C=3OC(Cl)=CC=3)SCCN2C=1C1=CC(Cl)=CC(C#N)=C1 DDSJSTWPJIVJHW-UHFFFAOYSA-N 0.000 claims description 2
• FJUCTSFLSKBGKB-UHFFFAOYSA-N 5-(3-fluorophenyl)-1,3,8-trimethyl-10-(5-methylfuran-2-yl)-7,8,9,10-tetrahydropyrimido[4,5-a]indolizine-2,4-dione Chemical compound C=1C=CC(F)=CC=1C1=C(C(N(C)C(=O)N2C)=O)C2=C2N1CC(C)CC2C1=CC=C(C)O1 FJUCTSFLSKBGKB-UHFFFAOYSA-N 0.000 claims description 2
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