TW201429974A - 三環化合物 - Google Patents
三環化合物 Download PDFInfo
- Publication number
- TW201429974A TW201429974A TW102147023A TW102147023A TW201429974A TW 201429974 A TW201429974 A TW 201429974A TW 102147023 A TW102147023 A TW 102147023A TW 102147023 A TW102147023 A TW 102147023A TW 201429974 A TW201429974 A TW 201429974A
- Authority
- TW
- Taiwan
- Prior art keywords
- dimethyl
- dione
- pyrrolo
- pyrimido
- dihydro
- Prior art date
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 307
- 150000003839 salts Chemical class 0.000 claims abstract description 64
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 21
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 288
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 90
- -1 Dimethyl-5-(4-methylthiazol-2-yl)-7,8-dihydro-1H-pyrimido[4',5':3,4]pyrrolo[2,1-c][ 1,4]thiazine-2,4(3H,10H)-dione Chemical compound 0.000 claims description 82
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 73
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 44
- 206010012735 Diarrhoea Diseases 0.000 claims description 42
- 125000005843 halogen group Chemical group 0.000 claims description 41
- 108010079245 Cystic Fibrosis Transmembrane Conductance Regulator Proteins 0.000 claims description 39
- 238000011282 treatment Methods 0.000 claims description 36
- 229910052739 hydrogen Inorganic materials 0.000 claims description 34
- 239000001257 hydrogen Substances 0.000 claims description 34
- 201000010099 disease Diseases 0.000 claims description 30
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 30
- 125000004941 pyridazin-5-yl group Chemical group N1=NC=CC(=C1)* 0.000 claims description 30
- 239000003814 drug Substances 0.000 claims description 26
- 125000001424 substituent group Chemical group 0.000 claims description 25
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 20
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 20
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 17
- 125000004432 carbon atom Chemical group C* 0.000 claims description 17
- 208000030761 polycystic kidney disease Diseases 0.000 claims description 17
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 16
- GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 claims description 16
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 claims description 14
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 claims description 14
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 14
- 229910052760 oxygen Inorganic materials 0.000 claims description 13
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- 230000000694 effects Effects 0.000 claims description 10
- HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 claims description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
- 229910052717 sulfur Inorganic materials 0.000 claims description 9
- 125000006526 (C1-C2) alkyl group Chemical group 0.000 claims description 8
- 125000003118 aryl group Chemical group 0.000 claims description 8
- 125000004429 atom Chemical group 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 8
- AGIJRRREJXSQJR-UHFFFAOYSA-N 2h-thiazine Chemical compound N1SC=CC=C1 AGIJRRREJXSQJR-UHFFFAOYSA-N 0.000 claims description 7
- PCNDJXKNXGMECE-UHFFFAOYSA-N Phenazine Natural products C1=CC=CC2=NC3=CC=CC=C3N=C21 PCNDJXKNXGMECE-UHFFFAOYSA-N 0.000 claims description 7
- 125000003282 alkyl amino group Chemical group 0.000 claims description 7
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 125000000623 heterocyclic group Chemical group 0.000 claims description 7
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 claims description 7
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 claims description 7
- 125000000335 thiazolyl group Chemical group 0.000 claims description 7
- 125000001544 thienyl group Chemical group 0.000 claims description 7
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 6
- 239000001301 oxygen Substances 0.000 claims description 6
- 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 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 5
- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 5
- 150000001412 amines Chemical class 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000002541 furyl group Chemical group 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 125000006536 (C1-C2)alkoxy group Chemical group 0.000 claims description 4
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 4
- 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 4
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 4
- 239000002671 adjuvant Substances 0.000 claims description 4
- 125000004434 sulfur atom Chemical group 0.000 claims description 4
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 3
- VEVARMXPPWZFND-UHFFFAOYSA-N 1,3-dimethyl-10-(4-methyl-1,3-thiazol-2-yl)-5-phenyl-7,8,9,10-tetrahydropyrimido[1,2]pyrrolo[4,5-b]pyridazine-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)NCC2)=N1 VEVARMXPPWZFND-UHFFFAOYSA-N 0.000 claims description 3
- HMVYYTRDXNKRBQ-UHFFFAOYSA-N 1,3-thiazole-4-carboxylic acid Chemical compound OC(=O)C1=CSC=N1 HMVYYTRDXNKRBQ-UHFFFAOYSA-N 0.000 claims description 3
- FMMKKYIEZSJODV-UHFFFAOYSA-N 10-(5-chlorofuran-2-yl)-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)SCCN32)=N1 FMMKKYIEZSJODV-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
- WZBSYUDTBIEPPK-UHFFFAOYSA-N 5-(3-chlorophenyl)-1,3-dimethyl-10-(4-methyl-1,3-thiazol-2-yl)-7,8,9,10-tetrahydropyrimido[1,2]pyrrolo[4,5-b]pyridazine-2,4-dione Chemical compound CC1=CSC(C2C=3N(C(=C4C(=O)N(C)C(=O)N(C)C4=3)C=3C=C(Cl)C=CC=3)NCC2)=N1 WZBSYUDTBIEPPK-UHFFFAOYSA-N 0.000 claims description 3
- ZYILWZGTSMNONG-UHFFFAOYSA-N 7-[(dimethylamino)methyl]-1,3-dimethyl-10-(5-methylfuran-2-yl)-5-phenyl-8,10-dihydro-7h-pyrimido[1,2]pyrrolo[4,5-a][1,4]thiazine-2,4-dione Chemical compound C=1C=CC=CC=1C1=C(C(N(C)C(=O)N2C)=O)C2=C2N1C(CN(C)C)CSC2C1=CC=C(C)O1 ZYILWZGTSMNONG-UHFFFAOYSA-N 0.000 claims description 3
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims description 3
- SCWJMTRWNKOOKE-UHFFFAOYSA-N 1,3,8-trimethyl-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 S1C(C)CN(C(=C2C(=O)N(C)C(=O)N(C)C2=2)C=3C=CC=CC=3)C=2C1C1=NC(C)=CS1 SCWJMTRWNKOOKE-UHFFFAOYSA-N 0.000 claims description 2
- OMKFKEYPKXLIDM-UHFFFAOYSA-N 1,3-dimethyl-10-(5-methylthiophen-2-yl)-5-phenyl-8,10-dihydro-7h-pyrimido[1,2]pyrrolo[4,5-a][1,4]thiazine-2,4-dione Chemical compound S1C(C)=CC=C1C1C2=C(N(C)C(=O)N(C)C3=O)C3=C(C=3C=CC=CC=3)N2CCS1 OMKFKEYPKXLIDM-UHFFFAOYSA-N 0.000 claims description 2
- KBXXSTGPDJDKPZ-UHFFFAOYSA-N 1,3-dimethyl-11-(4-methyl-1,3-thiazol-2-yl)-5-phenyl-8,9,10,11-tetrahydro-7h-pyrimido[1,2]pyrrolo[4,5-a]azepine-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)CCCC2)=N1 KBXXSTGPDJDKPZ-UHFFFAOYSA-N 0.000 claims description 2
- 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 2
- CTTIOMZLKYKEKX-UHFFFAOYSA-N 10-(5-chlorofuran-2-yl)-1,3-diethyl-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(CC)C(=O)N(CC)C2=C2C(C=3OC(Cl)=CC=3)SCCN2C=1C1=CC=CC=C1 CTTIOMZLKYKEKX-UHFFFAOYSA-N 0.000 claims description 2
- 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 2
- 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 2
- HGIIJMBAUDLRQN-UHFFFAOYSA-N 10-(5-chlorofuran-2-yl)-8-(hydroxymethyl)-1,3-dimethyl-5-(2-methyl-1,3-thiazol-4-yl)-8,10-dihydro-7h-pyrimido[1,2]pyrrolo[4,5-a][1,4]thiazine-2,4-dione Chemical compound S1C(C)=NC(C2=C3C(=O)N(C)C(=O)N(C)C3=C3C(C=4OC(Cl)=CC=4)SC(CO)CN32)=C1 HGIIJMBAUDLRQN-UHFFFAOYSA-N 0.000 claims description 2
- QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-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
- 229960002155 chlorothiazide Drugs 0.000 claims description 2
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 2
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 2
- 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 2
- BBKGYGFXPBKJAB-UHFFFAOYSA-N 10-(5-chlorofuran-2-yl)-5-(3-ethoxyphenyl)-1,3-dimethyl-8,10-dihydro-7h-pyrimido[1,2]pyrrolo[4,5-a][1,4]thiazine-2,4-dione Chemical compound CCOC1=CC=CC(C2=C3C(=O)N(C)C(=O)N(C)C3=C3C(C=4OC(Cl)=CC=4)SCCN32)=C1 BBKGYGFXPBKJAB-UHFFFAOYSA-N 0.000 claims 2
- YYMSODGVZHNXDE-UHFFFAOYSA-N 10-(4-chloro-1,3-thiazol-2-yl)-5-(3-fluorophenyl)-8-(hydroxymethyl)-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)SC(CO)CN2C=1C1=CC=CC(F)=C1 YYMSODGVZHNXDE-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- BSHCBORTLOSSJM-UHFFFAOYSA-N 10-(5-chlorofuran-2-yl)-5-(3-methoxyphenyl)-1,3-dimethyl-8,10-dihydro-7h-pyrimido[1,2]pyrrolo[4,5-a][1,4]thiazine-2,4-dione Chemical compound COC1=CC=CC(C2=C3C(=O)N(C)C(=O)N(C)C3=C3C(C=4OC(Cl)=CC=4)SCCN32)=C1 BSHCBORTLOSSJM-UHFFFAOYSA-N 0.000 claims 1
- RVXYBSFWYANPGV-UHFFFAOYSA-N 10-(5-chlorofuran-2-yl)-5-(cyclohexen-1-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=CCCCC1 RVXYBSFWYANPGV-UHFFFAOYSA-N 0.000 claims 1
- 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 1
- GGKFHMXFNJQQFD-UHFFFAOYSA-N 10-(5-chlorofuran-2-yl)-8-[(dimethylamino)methyl]-1,3-dimethyl-5-phenyl-8,10-dihydro-7h-pyrimido[1,2]pyrrolo[4,5-a][1,4]thiazine-2,4-dione Chemical compound S1C(CN(C)C)CN(C(=C2C(=O)N(C)C(=O)N(C)C2=2)C=3C=CC=CC=3)C=2C1C1=CC=C(Cl)O1 GGKFHMXFNJQQFD-UHFFFAOYSA-N 0.000 claims 1
- ZGVYRUCPMUAXAH-UHFFFAOYSA-N 11-(4-chloro-1,3-thiazol-2-yl)-5-(3-fluorophenyl)-1,3-dimethyl-8,9,10,11-tetrahydro-7h-pyrimido[1,2]pyrrolo[4,5-a]azepine-2,4-dione Chemical compound C=12C(=O)N(C)C(=O)N(C)C2=C2C(C=3SC=C(Cl)N=3)CCCCN2C=1C1=CC=CC(F)=C1 ZGVYRUCPMUAXAH-UHFFFAOYSA-N 0.000 claims 1
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- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 33
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- 229910017604 nitric acid Inorganic materials 0.000 description 1
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- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
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- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical class [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
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- NYBWUHOMYZZKOR-UHFFFAOYSA-N tes-adt Chemical class C1=C2C(C#C[Si](CC)(CC)CC)=C(C=C3C(SC=C3)=C3)C3=C(C#C[Si](CC)(CC)CC)C2=CC2=C1SC=C2 NYBWUHOMYZZKOR-UHFFFAOYSA-N 0.000 description 1
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- YLGRTLMDMVAFNI-UHFFFAOYSA-N tributyl(prop-2-enyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)CC=C YLGRTLMDMVAFNI-UHFFFAOYSA-N 0.000 description 1
- OTMIHZHASCPXNT-UHFFFAOYSA-N tributyl-(5-methylfuran-2-yl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C1=CC=C(C)O1 OTMIHZHASCPXNT-UHFFFAOYSA-N 0.000 description 1
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- AHZJKOKFZJYCLG-UHFFFAOYSA-K trifluoromethanesulfonate;ytterbium(3+) Chemical compound [Yb+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F AHZJKOKFZJYCLG-UHFFFAOYSA-K 0.000 description 1
- IIHPVYJPDKJYOU-UHFFFAOYSA-N triphenylcarbethoxymethylenephosphorane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=CC(=O)OCC)C1=CC=CC=C1 IIHPVYJPDKJYOU-UHFFFAOYSA-N 0.000 description 1
- JQZIKLPHXXBMCA-UHFFFAOYSA-N triphenylmethanethiol Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(S)C1=CC=CC=C1 JQZIKLPHXXBMCA-UHFFFAOYSA-N 0.000 description 1
- JUDXOKKZTISQDJ-UHFFFAOYSA-N triphenylphosphane;hydrochloride Chemical compound Cl.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 JUDXOKKZTISQDJ-UHFFFAOYSA-N 0.000 description 1
- NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains three hetero rings
- C07D513/14—Ortho-condensed systems
-
- 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
- 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
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/12—Antidiarrhoeals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
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- 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains three hetero rings
- C07D487/14—Ortho-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/22—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains four or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains three hetero rings
- C07D495/14—Ortho-condensed systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
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- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
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- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Urology & Nephrology (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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| US201261739335P | 2012-12-19 | 2012-12-19 | |
| US201361906141P | 2013-11-19 | 2013-11-19 |
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| TW201429974A true TW201429974A (zh) | 2014-08-01 |
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| US9056867B2 (en) | 2011-09-16 | 2015-06-16 | Novartis Ag | N-substituted heterocyclyl carboxamides |
| EP2935278B1 (en) | 2012-12-19 | 2017-03-15 | Novartis AG | Tricyclic compounds for inhibiting the cftr channel |
| KR20150095925A (ko) | 2012-12-19 | 2015-08-21 | 노파르티스 아게 | Cftr 억제제로서의 트리시클릭 화합물 |
| CN106715536B (zh) * | 2014-09-19 | 2021-06-01 | 莫门蒂夫性能材料股份有限公司 | 用于受控的硅氧烷交联的铂(ii)二烯配合物 |
| US9624233B2 (en) * | 2015-04-23 | 2017-04-18 | Trevi Therapeutics, Inc. | Compounds for treating pruritic conditions |
| CN106478558B (zh) * | 2016-10-17 | 2019-03-29 | 天津雅奥科技发展有限公司 | 一种4-羟甲基-二氢-呋喃-2(3h)-酮的合成方法 |
| US12319686B2 (en) | 2019-01-17 | 2025-06-03 | Hoffmann-La Roche Inc. | Process for the preparation of tetrahydropyridopyrimidines |
| CN114007623A (zh) * | 2019-06-12 | 2022-02-01 | 加利福尼亚大学董事会 | 治疗胆汁酸性腹泻的方法 |
| AU2022265718A1 (en) | 2021-04-29 | 2023-11-02 | Novartis Ag | Deubiquitinase-targeting chimeras and related methods |
| CN117654560B (zh) * | 2023-12-01 | 2024-06-04 | 安徽泽升科技股份有限公司 | 一种通过氧化氨基连续化制备硝基化合物的方法 |
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| CA2382528A1 (en) | 1999-08-25 | 2001-03-01 | Banyu Pharmaceutical Co., Ltd. | Novel isoindole derivatives |
| JP2002255967A (ja) | 2001-02-27 | 2002-09-11 | Banyu Pharmaceut Co Ltd | イソインドール誘導体を有効成分とする糖尿病の治療剤、糖尿病の慢性合併症の予防剤又は肥満の治療剤。 |
| JP2007524596A (ja) | 2003-02-28 | 2007-08-30 | トランスフォーム・ファーマシューティカルズ・インコーポレイテッド | 共結晶医薬組成物 |
| MX2009006228A (es) | 2006-12-12 | 2009-06-22 | Schering Corp | Inhibidores de aspartil proteasa. |
| US20110015137A1 (en) * | 2007-07-05 | 2011-01-20 | Trustees Of Boston University | Reca inhibitors and their uses as microbial inhibitors or potentiators of antibiotic activity |
| AU2008345225A1 (en) | 2007-12-21 | 2009-07-09 | University Of Rochester | Method for altering the lifespan of eukaryotic organisms |
| IN2012DN00719A (enExample) * | 2009-08-10 | 2015-06-19 | Univ California | |
| USRE48842E1 (en) * | 2011-05-27 | 2021-12-07 | The Regents Of The University Of California | Pyrimido-pyrrolo-oxazine-dione compound inhibitors of the cystic fibrosis transmembrane conductance regulator protein and uses therefor |
| EP2935278B1 (en) | 2012-12-19 | 2017-03-15 | Novartis AG | Tricyclic compounds for inhibiting the cftr channel |
| KR20150095925A (ko) | 2012-12-19 | 2015-08-21 | 노파르티스 아게 | Cftr 억제제로서의 트리시클릭 화합물 |
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| HK1209741A1 (en) | 2016-04-08 |
| US9359381B2 (en) | 2016-06-07 |
| KR20150097660A (ko) | 2015-08-26 |
| IL239389A0 (en) | 2015-07-30 |
| ES2628369T3 (es) | 2017-08-02 |
| WO2014097148A9 (en) | 2015-02-19 |
| EP2935278B1 (en) | 2017-03-15 |
| CN105143230A (zh) | 2015-12-09 |
| CL2015001730A1 (es) | 2015-08-28 |
| AU2013365739A1 (en) | 2015-07-09 |
| EP2935278A1 (en) | 2015-10-28 |
| TN2015000279A1 (en) | 2016-10-03 |
| CN105143230B (zh) | 2017-06-09 |
| CA2895660A1 (en) | 2014-06-26 |
| EA201591177A1 (ru) | 2015-11-30 |
| UY35211A (es) | 2014-07-31 |
| CR20150325A (es) | 2015-08-10 |
| JP2016509579A (ja) | 2016-03-31 |
| PH12015501386A1 (en) | 2015-09-02 |
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| US20140171417A1 (en) | 2014-06-19 |
| PE20151055A1 (es) | 2015-08-05 |
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| AP2015008539A0 (en) | 2015-06-30 |
| MX2015007939A (es) | 2016-03-11 |
| JP6284546B2 (ja) | 2018-02-28 |
| CU20150066A7 (es) | 2015-11-27 |
| US20150336986A1 (en) | 2015-11-26 |
| AR094122A1 (es) | 2015-07-08 |
| WO2014097148A1 (en) | 2014-06-26 |
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