HRP20120457T1 - 4-(4-cijano-2-tioaril)dihidropirimidinoni i njihova uporaba - Google Patents
4-(4-cijano-2-tioaril)dihidropirimidinoni i njihova uporaba Download PDFInfo
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- HRP20120457T1 HRP20120457T1 HRP20120457AT HRP20120457T HRP20120457T1 HR P20120457 T1 HRP20120457 T1 HR P20120457T1 HR P20120457A T HRP20120457A T HR P20120457AT HR P20120457 T HRP20120457 T HR P20120457T HR P20120457 T1 HRP20120457 T1 HR P20120457T1
- Authority
- HR
- Croatia
- Prior art keywords
- phenyl
- cyano
- alkyl
- trifluoromethyl
- methyl
- Prior art date
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- 150000001875 compounds Chemical class 0.000 claims abstract 35
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 43
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 43
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 42
- 239000001257 hydrogen Substances 0.000 claims 42
- 229910052739 hydrogen Inorganic materials 0.000 claims 42
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 40
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 35
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 34
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 33
- 239000011737 fluorine Substances 0.000 claims 27
- 229910052731 fluorine Inorganic materials 0.000 claims 27
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 26
- 150000003839 salts Chemical class 0.000 claims 26
- 239000012453 solvate Substances 0.000 claims 25
- 125000001424 substituent group Chemical group 0.000 claims 20
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims 17
- 239000000460 chlorine Substances 0.000 claims 17
- 229910052801 chlorine Inorganic materials 0.000 claims 17
- ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims 15
- 125000004093 cyano group Chemical group *C#N 0.000 claims 13
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 12
- -1 cyano, hydroxyl Chemical group 0.000 claims 11
- 125000000623 heterocyclic group Chemical group 0.000 claims 11
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims 10
- WCFAPJDPAPDDAQ-UHFFFAOYSA-N 1,2-dihydropyrimidine Chemical group C1NC=CC=N1 WCFAPJDPAPDDAQ-UHFFFAOYSA-N 0.000 claims 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims 9
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims 8
- 201000003883 Cystic fibrosis Diseases 0.000 claims 8
- 206010064911 Pulmonary arterial hypertension Diseases 0.000 claims 8
- 206010069351 acute lung injury Diseases 0.000 claims 8
- 208000006682 alpha 1-Antitrypsin Deficiency Diseases 0.000 claims 8
- 208000002815 pulmonary hypertension Diseases 0.000 claims 8
- 229940079593 drug Drugs 0.000 claims 7
- 239000003814 drug Substances 0.000 claims 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 7
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims 6
- 229910052757 nitrogen Inorganic materials 0.000 claims 6
- 229910052760 oxygen Inorganic materials 0.000 claims 6
- 125000004430 oxygen atom Chemical group O* 0.000 claims 6
- 230000002265 prevention Effects 0.000 claims 6
- 229910052717 sulfur Inorganic materials 0.000 claims 6
- 125000004043 oxo group Chemical group O=* 0.000 claims 5
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims 4
- 206010014561 Emphysema Diseases 0.000 claims 4
- 125000005842 heteroatom Chemical group 0.000 claims 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims 4
- 125000004076 pyridyl group Chemical group 0.000 claims 4
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 4
- YAJWYFPMASPAMM-HXUWFJFHSA-N (4s)-4-(4-cyano-2-methylsulfonylphenyl)-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-4h-pyrimidine-5-carbonitrile Chemical compound N#CC([C@H](N(C1=O)C)C=2C(=CC(=CC=2)C#N)S(C)(=O)=O)=C(C)N1C1=CC=CC(C(F)(F)F)=C1 YAJWYFPMASPAMM-HXUWFJFHSA-N 0.000 claims 3
- WQASVWJQEKONLG-LJQANCHMSA-N (6s)-6-(4-cyano-2-methylsulfonylphenyl)-4-methyl-2-oxo-3-[3-(trifluoromethyl)phenyl]-1,6-dihydropyrimidine-5-carbonitrile Chemical compound N([C@@H](C(C#N)=C1C)C=2C(=CC(=CC=2)C#N)S(C)(=O)=O)C(=O)N1C1=CC=CC(C(F)(F)F)=C1 WQASVWJQEKONLG-LJQANCHMSA-N 0.000 claims 3
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical group FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims 3
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims 3
- JJUJXMUTFGTNRO-OAQYLSRUSA-N (4s)-3-(cyanomethyl)-4-(4-cyano-2-methylsulfonylphenyl)-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-4h-pyrimidine-5-carbonitrile Chemical compound N#CCN([C@@H](C(C#N)=C1C)C=2C(=CC(=CC=2)C#N)S(C)(=O)=O)C(=O)N1C1=CC=CC(C(F)(F)F)=C1 JJUJXMUTFGTNRO-OAQYLSRUSA-N 0.000 claims 2
- GGNSKHNSFNMRLE-OAQYLSRUSA-N (4s)-4-(4-cyano-2-ethylsulfonylphenyl)-3,6-dimethyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-4h-pyrimidine-5-carbonitrile Chemical compound CCS(=O)(=O)C1=CC(C#N)=CC=C1[C@@H]1C(C#N)=C(C)N(C=2C=C(C=CC=2)C(F)(F)F)C(=O)N1C GGNSKHNSFNMRLE-OAQYLSRUSA-N 0.000 claims 2
- PFLBFZZQDYVNIM-JOCHJYFZSA-N (4s)-4-(4-cyano-2-methylsulfonylphenyl)-3-cyclopropylsulfonyl-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-4h-pyrimidine-5-carbonitrile Chemical compound C1CC1S(=O)(=O)N([C@@H](C(C#N)=C1C)C=2C(=CC(=CC=2)C#N)S(C)(=O)=O)C(=O)N1C1=CC=CC(C(F)(F)F)=C1 PFLBFZZQDYVNIM-JOCHJYFZSA-N 0.000 claims 2
- GZTFGXKIIHXIPY-HXUWFJFHSA-N (4s)-4-(4-cyano-2-methylsulfonylphenyl)-6-methyl-3-methylsulfonyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-4h-pyrimidine-5-carbonitrile Chemical compound CS(=O)(=O)N([C@@H](C(C#N)=C1C)C=2C(=CC(=CC=2)C#N)S(C)(=O)=O)C(=O)N1C1=CC=CC(C(F)(F)F)=C1 GZTFGXKIIHXIPY-HXUWFJFHSA-N 0.000 claims 2
- RPTJTTCMRUOZFG-HSZRJFAPSA-N (4s)-5-cyano-4-(4-cyano-2-methylsulfonylphenyl)-n',n'-bis(2-hydroxyethyl)-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-4h-pyrimidine-3-carbohydrazide Chemical compound OCCN(CCO)NC(=O)N([C@@H](C(C#N)=C1C)C=2C(=CC(=CC=2)C#N)S(C)(=O)=O)C(=O)N1C1=CC=CC(C(F)(F)F)=C1 RPTJTTCMRUOZFG-HSZRJFAPSA-N 0.000 claims 2
- RSAOXKQRVMUZJS-OAQYLSRUSA-N (4s)-5-cyano-4-(4-cyano-2-methylsulfonylphenyl)-n-(2-hydroxyethyl)-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-4h-pyrimidine-3-carboxamide Chemical compound OCCNC(=O)N([C@@H](C(C#N)=C1C)C=2C(=CC(=CC=2)C#N)S(C)(=O)=O)C(=O)N1C1=CC=CC(C(F)(F)F)=C1 RSAOXKQRVMUZJS-OAQYLSRUSA-N 0.000 claims 2
- YUDZKTXXZOBMQS-OAQYLSRUSA-N 2-hydroxyethyl (4s)-4-(4-cyano-2-methylsulfonylphenyl)-6-methyl-3-methylsulfonyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-4h-pyrimidine-5-carboxylate Chemical compound CS(=O)(=O)N([C@@H](C(=C1C)C(=O)OCCO)C=2C(=CC(=CC=2)C#N)S(C)(=O)=O)C(=O)N1C1=CC=CC(C(F)(F)F)=C1 YUDZKTXXZOBMQS-OAQYLSRUSA-N 0.000 claims 2
- CXQUELQTPOBOKG-HXUWFJFHSA-N 4-[(4s)-6-methyl-3-methylsulfonyl-2,5-dioxo-1-[3-(trifluoromethyl)phenyl]-4,7-dihydropyrrolo[3,4-d]pyrimidin-4-yl]-3-methylsulfonylbenzonitrile Chemical compound CS(=O)(=O)N([C@@H](C1=C2CN(C1=O)C)C=1C(=CC(=CC=1)C#N)S(C)(=O)=O)C(=O)N2C1=CC=CC(C(F)(F)F)=C1 CXQUELQTPOBOKG-HXUWFJFHSA-N 0.000 claims 2
- 125000006163 5-membered heteroaryl group Chemical group 0.000 claims 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims 2
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 2
- 239000002253 acid Substances 0.000 claims 2
- 201000009267 bronchiectasis Diseases 0.000 claims 2
- 125000004786 difluoromethoxy group Chemical group [H]C(F)(F)O* 0.000 claims 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 2
- 125000001072 heteroaryl group Chemical group 0.000 claims 2
- 238000000034 method Methods 0.000 claims 2
- DQUIWJMVVAZSHU-NTKDMRAZSA-N (4s)-3-[(3r)-3-aminopiperidine-1-carbonyl]-4-(4-cyano-2-methylsulfonylphenyl)-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-4h-pyrimidine-5-carbonitrile Chemical compound N1([C@@H](C(C#N)=C(N(C1=O)C=1C=C(C=CC=1)C(F)(F)F)C)C=1C(=CC(=CC=1)C#N)S(C)(=O)=O)C(=O)N1CCC[C@@H](N)C1 DQUIWJMVVAZSHU-NTKDMRAZSA-N 0.000 claims 1
- UEFMMWPBQMIVKU-OAQYLSRUSA-N (4s)-4-(4-cyano-2-ethylsulfonylphenyl)-6-methyl-3-methylsulfonyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-4h-pyrimidine-5-carbonitrile Chemical compound CCS(=O)(=O)C1=CC(C#N)=CC=C1[C@@H]1C(C#N)=C(C)N(C=2C=C(C=CC=2)C(F)(F)F)C(=O)N1S(C)(=O)=O UEFMMWPBQMIVKU-OAQYLSRUSA-N 0.000 claims 1
- BMBFPPKJIMEVLC-XMMPIXPASA-N (4s)-4-(4-cyano-2-methylsulfonylphenyl)-3-(1,2-dimethylimidazol-4-yl)sulfonyl-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-4h-pyrimidine-5-carbonitrile Chemical compound CN1C(C)=NC(S(=O)(=O)N2C(N(C(C)=C(C#N)[C@H]2C=2C(=CC(=CC=2)C#N)S(C)(=O)=O)C=2C=C(C=CC=2)C(F)(F)F)=O)=C1 BMBFPPKJIMEVLC-XMMPIXPASA-N 0.000 claims 1
- FTDGYSATFAMVGK-AREMUKBSSA-N (4s)-4-(4-cyano-2-methylsulfonylphenyl)-3-(2-cyanophenyl)sulfonyl-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-4h-pyrimidine-5-carbonitrile Chemical compound C=1C=CC=C(C#N)C=1S(=O)(=O)N([C@@H](C(C#N)=C1C)C=2C(=CC(=CC=2)C#N)S(C)(=O)=O)C(=O)N1C1=CC=CC(C(F)(F)F)=C1 FTDGYSATFAMVGK-AREMUKBSSA-N 0.000 claims 1
- XNFFHCDHZFYPMV-JOCHJYFZSA-N (4s)-4-(4-cyano-2-methylsulfonylphenyl)-3-(3-hydroxyazetidine-1-carbonyl)-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-4h-pyrimidine-5-carbonitrile Chemical compound N1([C@@H](C(C#N)=C(N(C1=O)C=1C=C(C=CC=1)C(F)(F)F)C)C=1C(=CC(=CC=1)C#N)S(C)(=O)=O)C(=O)N1CC(O)C1 XNFFHCDHZFYPMV-JOCHJYFZSA-N 0.000 claims 1
- KFVGYSFEGDEAQM-AREMUKBSSA-N (4s)-4-(4-cyano-2-methylsulfonylphenyl)-3-(4-cyanophenyl)-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-4h-pyrimidine-5-carbonitrile Chemical compound C=1C=C(C#N)C=CC=1N([C@@H](C(C#N)=C1C)C=2C(=CC(=CC=2)C#N)S(C)(=O)=O)C(=O)N1C1=CC=CC(C(F)(F)F)=C1 KFVGYSFEGDEAQM-AREMUKBSSA-N 0.000 claims 1
- MWBOAVDWAVUVPI-RUZDIDTESA-N (4s)-4-(4-cyano-2-methylsulfonylphenyl)-3-(4-fluorophenyl)sulfonyl-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-4h-pyrimidine-5-carbonitrile Chemical compound C=1C=C(F)C=CC=1S(=O)(=O)N([C@@H](C(C#N)=C1C)C=2C(=CC(=CC=2)C#N)S(C)(=O)=O)C(=O)N1C1=CC=CC(C(F)(F)F)=C1 MWBOAVDWAVUVPI-RUZDIDTESA-N 0.000 claims 1
- NQLZZTRTBMMPER-WMZHIEFXSA-N (4s)-4-(4-cyano-2-methylsulfonylphenyl)-3-[(3s)-3-hydroxypyrrolidine-1-carbonyl]-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-4h-pyrimidine-5-carbonitrile Chemical compound N1([C@@H](C(C#N)=C(N(C1=O)C=1C=C(C=CC=1)C(F)(F)F)C)C=1C(=CC(=CC=1)C#N)S(C)(=O)=O)C(=O)N1CC[C@H](O)C1 NQLZZTRTBMMPER-WMZHIEFXSA-N 0.000 claims 1
- ULBHGNNSNNKEOM-HSZRJFAPSA-N (4s)-4-(4-cyano-2-methylsulfonylphenyl)-3-[1-(difluoromethyl)-5-methylpyrazol-4-yl]sulfonyl-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-4h-pyrimidine-5-carbonitrile Chemical compound C1=NN(C(F)F)C(C)=C1S(=O)(=O)N1C(=O)N(C=2C=C(C=CC=2)C(F)(F)F)C(C)=C(C#N)[C@H]1C1=CC=C(C#N)C=C1S(C)(=O)=O ULBHGNNSNNKEOM-HSZRJFAPSA-N 0.000 claims 1
- GBKFWWXHEQLBCS-RUZDIDTESA-N (4s)-4-(4-cyano-2-methylsulfonylphenyl)-3-[4-(2-hydroxyethyl)piperazine-1-carbonyl]-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-4h-pyrimidine-5-carbonitrile Chemical compound N1([C@@H](C(C#N)=C(N(C1=O)C=1C=C(C=CC=1)C(F)(F)F)C)C=1C(=CC(=CC=1)C#N)S(C)(=O)=O)C(=O)N1CCN(CCO)CC1 GBKFWWXHEQLBCS-RUZDIDTESA-N 0.000 claims 1
- MCUBLIRBIFHIBH-OAQYLSRUSA-N (4s)-4-(4-cyano-2-methylsulfonylphenyl)-3-ethylsulfonyl-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-4h-pyrimidine-5-carbonitrile Chemical compound N#CC([C@H](N(C1=O)S(=O)(=O)CC)C=2C(=CC(=CC=2)C#N)S(C)(=O)=O)=C(C)N1C1=CC=CC(C(F)(F)F)=C1 MCUBLIRBIFHIBH-OAQYLSRUSA-N 0.000 claims 1
- UGKKSUGBIYNQEJ-RUZDIDTESA-N (4s)-4-(4-cyano-2-methylsulfonylphenyl)-6-methyl-2-oxo-1,3-bis[3-(trifluoromethyl)phenyl]-4h-pyrimidine-5-carbonitrile Chemical compound C=1C=CC(C(F)(F)F)=CC=1N([C@@H](C(C#N)=C1C)C=2C(=CC(=CC=2)C#N)S(C)(=O)=O)C(=O)N1C1=CC=CC(C(F)(F)F)=C1 UGKKSUGBIYNQEJ-RUZDIDTESA-N 0.000 claims 1
- IWZCCVFZHONFJG-MUUNZHRXSA-N (4s)-4-(4-cyano-2-methylsulfonylphenyl)-6-methyl-2-oxo-3-(4-pyridin-2-ylpiperazine-1-carbonyl)-1-[3-(trifluoromethyl)phenyl]-4h-pyrimidine-5-carbonitrile Chemical compound N1([C@@H](C(C#N)=C(N(C1=O)C=1C=C(C=CC=1)C(F)(F)F)C)C=1C(=CC(=CC=1)C#N)S(C)(=O)=O)C(=O)N(CC1)CCN1C1=CC=CC=N1 IWZCCVFZHONFJG-MUUNZHRXSA-N 0.000 claims 1
- SVJGCERDRAEQDU-RUZDIDTESA-N (4s)-4-(4-cyano-2-methylsulfonylphenyl)-6-methyl-2-oxo-3-[2-(trifluoromethoxy)phenyl]sulfonyl-1-[3-(trifluoromethyl)phenyl]-4h-pyrimidine-5-carbonitrile Chemical compound C=1C=CC=C(OC(F)(F)F)C=1S(=O)(=O)N([C@@H](C(C#N)=C1C)C=2C(=CC(=CC=2)C#N)S(C)(=O)=O)C(=O)N1C1=CC=CC(C(F)(F)F)=C1 SVJGCERDRAEQDU-RUZDIDTESA-N 0.000 claims 1
- YXUWIPAWIHQIPF-RUZDIDTESA-N (4s)-4-(4-cyano-2-methylsulfonylphenyl)-6-methyl-2-oxo-3-[2-oxo-2-(3-oxopiperazin-1-yl)ethyl]-1-[3-(trifluoromethyl)phenyl]-4h-pyrimidine-5-carbonitrile Chemical compound N1([C@@H](C(C#N)=C(N(C1=O)C=1C=C(C=CC=1)C(F)(F)F)C)C=1C(=CC(=CC=1)C#N)S(C)(=O)=O)CC(=O)N1CCNC(=O)C1 YXUWIPAWIHQIPF-RUZDIDTESA-N 0.000 claims 1
- JABTUTUSLVKUOZ-WFUJHSFVSA-N (4s)-5-cyano-4-(4-cyano-2-methylsulfonylphenyl)-n,n-bis(2-hydroxypropyl)-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-4h-pyrimidine-3-carboxamide Chemical compound N#CC([C@H](N(C1=O)C(=O)N(CC(C)O)CC(O)C)C=2C(=CC(=CC=2)C#N)S(C)(=O)=O)=C(C)N1C1=CC=CC(C(F)(F)F)=C1 JABTUTUSLVKUOZ-WFUJHSFVSA-N 0.000 claims 1
- XNIPVPACUCOMIK-HSZRJFAPSA-N (4s)-5-cyano-4-(4-cyano-2-methylsulfonylphenyl)-n-[2-(2-hydroxyethoxy)ethyl]-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-4h-pyrimidine-3-carboxamide Chemical compound OCCOCCNC(=O)N([C@@H](C(C#N)=C1C)C=2C(=CC(=CC=2)C#N)S(C)(=O)=O)C(=O)N1C1=CC=CC(C(F)(F)F)=C1 XNIPVPACUCOMIK-HSZRJFAPSA-N 0.000 claims 1
- CSBCCPAMYNFXKE-HXUWFJFHSA-N (6s)-6-(4-cyano-2-ethylsulfonylphenyl)-4-methyl-2-oxo-3-[3-(trifluoromethyl)phenyl]-1,6-dihydropyrimidine-5-carbonitrile Chemical compound CCS(=O)(=O)C1=CC(C#N)=CC=C1[C@@H]1C(C#N)=C(C)N(C=2C=C(C=CC=2)C(F)(F)F)C(=O)N1 CSBCCPAMYNFXKE-HXUWFJFHSA-N 0.000 claims 1
- DPLUIKAOFGLVPO-LJQANCHMSA-N (6s)-6-(4-cyano-2-methylsulfanylphenyl)-4-methyl-2-oxo-3-[3-(trifluoromethyl)phenyl]-1,6-dihydropyrimidine-5-carbonitrile Chemical compound CSC1=CC(C#N)=CC=C1[C@@H]1C(C#N)=C(C)N(C=2C=C(C=CC=2)C(F)(F)F)C(=O)N1 DPLUIKAOFGLVPO-LJQANCHMSA-N 0.000 claims 1
- WWEHNHMJNBCEJH-GOSISDBHSA-N (6s)-6-(4-cyano-2-methylsulfonylphenyl)-4-methyl-2-oxo-3-[3-(trifluoromethyl)phenyl]-1,6-dihydropyrimidine-5-carboxamide Chemical compound N([C@@H](C(=C1C)C(N)=O)C=2C(=CC(=CC=2)C#N)S(C)(=O)=O)C(=O)N1C1=CC=CC(C(F)(F)F)=C1 WWEHNHMJNBCEJH-GOSISDBHSA-N 0.000 claims 1
- HMVMFEGNIIGGET-XMMPIXPASA-N (6s)-6-[2-(benzenesulfonyl)-4-cyanophenyl]-4-methyl-2-oxo-3-[3-(trifluoromethyl)phenyl]-1,6-dihydropyrimidine-5-carbonitrile Chemical compound N([C@@H](C(C#N)=C1C)C=2C(=CC(=CC=2)C#N)S(=O)(=O)C=2C=CC=CC=2)C(=O)N1C1=CC=CC(C(F)(F)F)=C1 HMVMFEGNIIGGET-XMMPIXPASA-N 0.000 claims 1
- JUJDKQGAENKARI-KKIUXKEOSA-N (6s)-6-[4-cyano-2-[(s)-methylsulfinyl]phenyl]-4-methyl-2-oxo-3-[3-(trifluoromethyl)phenyl]-1,6-dihydropyrimidine-5-carbonitrile Chemical compound N([C@@H](C(C#N)=C1C)C=2C(=CC(=CC=2)C#N)[S@](C)=O)C(=O)N1C1=CC=CC(C(F)(F)F)=C1 JUJDKQGAENKARI-KKIUXKEOSA-N 0.000 claims 1
- GNAXRDJCJDRCQN-OAQYLSRUSA-N 2-[(4s)-5-cyano-4-(4-cyano-2-methylsulfonylphenyl)-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-4h-pyrimidin-3-yl]acetamide Chemical compound NC(=O)CN([C@@H](C(C#N)=C1C)C=2C(=CC(=CC=2)C#N)S(C)(=O)=O)C(=O)N1C1=CC=CC(C(F)(F)F)=C1 GNAXRDJCJDRCQN-OAQYLSRUSA-N 0.000 claims 1
- GMNWFCQKLMUHLC-UHFFFAOYSA-N 2-[4-(4-cyano-2-methylsulfonylphenyl)-2,5-dioxo-1-[3-(trifluoromethyl)phenyl]-4,7-dihydro-3h-pyrrolo[3,4-d]pyrimidin-6-yl]ethylurea Chemical compound CS(=O)(=O)C1=CC(C#N)=CC=C1C1C(C(=O)N(CCNC(N)=O)C2)=C2N(C=2C=C(C=CC=2)C(F)(F)F)C(=O)N1 GMNWFCQKLMUHLC-UHFFFAOYSA-N 0.000 claims 1
- SFVGRPFQOFTBOE-UHFFFAOYSA-N 4-(4-cyano-2-methylsulfonylphenyl)-n-(2-hydroxyethyl)-6-methyl-2,5-dioxo-1-[3-(trifluoromethyl)phenyl]-4,7-dihydropyrrolo[3,4-d]pyrimidine-3-carboxamide Chemical compound O=C1N(C)CC2=C1C(C=1C(=CC(=CC=1)C#N)S(C)(=O)=O)N(C(=O)NCCO)C(=O)N2C1=CC=CC(C(F)(F)F)=C1 SFVGRPFQOFTBOE-UHFFFAOYSA-N 0.000 claims 1
- FMVSDDAARUVXBX-HXUWFJFHSA-N 4-[(6s)-5-acetyl-4-methyl-2-oxo-3-[3-(trifluoromethyl)phenyl]-1,6-dihydropyrimidin-6-yl]-3-methylsulfonylbenzonitrile Chemical compound C1([C@H]2NC(=O)N(C(C)=C2C(=O)C)C=2C=C(C=CC=2)C(F)(F)F)=CC=C(C#N)C=C1S(C)(=O)=O FMVSDDAARUVXBX-HXUWFJFHSA-N 0.000 claims 1
- AQWWJOVOLJMMPP-UHFFFAOYSA-N 6-[4-cyano-2-(2-hydroxyethylsulfonyl)phenyl]-4-methyl-2-oxo-3-[3-(trifluoromethyl)phenyl]-1,6-dihydropyrimidine-5-carbonitrile Chemical compound CC1=C(C#N)C(C=2C(=CC(=CC=2)C#N)S(=O)(=O)CCO)NC(=O)N1C1=CC=CC(C(F)(F)F)=C1 AQWWJOVOLJMMPP-UHFFFAOYSA-N 0.000 claims 1
- 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 claims 1
- 101710095468 Cyclase Proteins 0.000 claims 1
- 229940118365 Endothelin receptor antagonist Drugs 0.000 claims 1
- 241001465754 Metazoa Species 0.000 claims 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 1
- 150000008065 acid anhydrides Chemical class 0.000 claims 1
- 150000007513 acids Chemical class 0.000 claims 1
- 239000012190 activator Substances 0.000 claims 1
- 239000000808 adrenergic beta-agonist Substances 0.000 claims 1
- 125000006598 aminocarbonylamino group Chemical group 0.000 claims 1
- 229940065524 anticholinergics inhalants for obstructive airway diseases Drugs 0.000 claims 1
- JMWPCMOFXMPUCC-UHFFFAOYSA-N benzyl 5-cyano-4-(4-cyano-2-methylsulfonylphenyl)-6-methyl-2-oxo-1-[3-(trifluoromethyl)phenyl]-4h-pyrimidine-3-carboxylate Chemical compound O=C1N(C=2C=C(C=CC=2)C(F)(F)F)C(C)=C(C#N)C(C=2C(=CC(=CC=2)C#N)S(C)(=O)=O)N1C(=O)OCC1=CC=CC=C1 JMWPCMOFXMPUCC-UHFFFAOYSA-N 0.000 claims 1
- 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 claims 1
- 239000000812 cholinergic antagonist Substances 0.000 claims 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims 1
- 230000006806 disease prevention Effects 0.000 claims 1
- 239000002308 endothelin receptor antagonist Substances 0.000 claims 1
- 125000001153 fluoro group Chemical group F* 0.000 claims 1
- 239000003862 glucocorticoid Substances 0.000 claims 1
- RQFCJASXJCIDSX-UUOKFMHZSA-N guanosine 5'-monophosphate Chemical compound C1=2NC(N)=NC(=O)C=2N=CN1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O RQFCJASXJCIDSX-UUOKFMHZSA-N 0.000 claims 1
- 229910052736 halogen Inorganic materials 0.000 claims 1
- 150000002367 halogens Chemical class 0.000 claims 1
- 229940043355 kinase inhibitor Drugs 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000011159 matrix material Substances 0.000 claims 1
- 239000003475 metalloproteinase inhibitor Substances 0.000 claims 1
- 231100000252 nontoxic Toxicity 0.000 claims 1
- 230000003000 nontoxic effect Effects 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 239000002571 phosphodiesterase inhibitor Substances 0.000 claims 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 claims 1
- 150000003815 prostacyclins Chemical class 0.000 claims 1
- 239000002904 solvent Substances 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 229940037128 systemic glucocorticoids Drugs 0.000 claims 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims 1
Classifications
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- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/06—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D239/08—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms directly attached in position 2
- C07D239/10—Oxygen or sulfur atoms
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- 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
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- 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
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
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- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- A61K31/535—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 oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
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- A61K31/541—Non-condensed thiazines containing further heterocyclic rings
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- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- C—CHEMISTRY; METALLURGY
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- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/20—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D239/22—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms directly attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
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- C—CHEMISTRY; METALLURGY
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- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
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- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
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- C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
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- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
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- Cardiology (AREA)
- Pulmonology (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
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Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE102007061766A DE102007061766A1 (de) | 2007-12-20 | 2007-12-20 | 4-(4-Cyano-2-thioaryl)-dihydropyrimidinone und ihre Verwendung |
| DE102008022521A DE102008022521A1 (de) | 2008-05-07 | 2008-05-07 | 1,4-Diaryl-pyrimidopyridazin-2,5-dione und ihre Verwendung |
| DE102008052013A DE102008052013A1 (de) | 2008-10-17 | 2008-10-17 | 4-(4-Cyano-2-thioaryl)-dihydropyrimidinone und ihre Verwendung |
| PCT/EP2008/010411 WO2009080199A1 (de) | 2007-12-20 | 2008-12-09 | 4- (4-cyano-2-thioaryl) -dihydropyrimidinone und ihre verwendung |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| HRP20120457T1 true HRP20120457T1 (hr) | 2012-06-30 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20120457AT HRP20120457T1 (hr) | 2007-12-20 | 2012-05-29 | 4-(4-cijano-2-tioaril)dihidropirimidinoni i njihova uporaba |
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| MX (1) | MX2010006033A (sr) |
| MY (1) | MY150285A (sr) |
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| PE (1) | PE20091429A1 (sr) |
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Families Citing this family (32)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2157092A4 (en) * | 2007-04-11 | 2011-04-13 | Ajinomoto Kk | MEANS FOR THE TREATMENT OF DIABETES |
| SG10201604819TA (en) * | 2007-12-20 | 2016-07-28 | Bayer Ip Gmbh | 4-(4-cyano-2-thioaryl)dihydropyrimidinones and use thereof |
| DE102009016553A1 (de) * | 2009-04-06 | 2010-10-07 | Bayer Schering Pharma Aktiengesellschaft | Sulfonamid- und Sulfoximin-substituierte Diaryldihydropyrimidinone und ihre Verwendung |
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