HUT67552A - Pyrido [2,3-d] pyrimidine derivatives as phosphodiesterase inhibitors, pharmaceutical compositions containing them and process for their production - Google Patents
Pyrido [2,3-d] pyrimidine derivatives as phosphodiesterase inhibitors, pharmaceutical compositions containing them and process for their production Download PDFInfo
- Publication number
- HUT67552A HUT67552A HU9402653A HU9402653A HUT67552A HU T67552 A HUT67552 A HU T67552A HU 9402653 A HU9402653 A HU 9402653A HU 9402653 A HU9402653 A HU 9402653A HU T67552 A HUT67552 A HU T67552A
- Authority
- HU
- Hungary
- Prior art keywords
- pyrido
- pyrimidine
- dione
- compound
- formula
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 81
- 239000008194 pharmaceutical composition Substances 0.000 title claims description 13
- 230000008569 process Effects 0.000 title claims description 13
- 238000004519 manufacturing process Methods 0.000 title description 4
- 239000002571 phosphodiesterase inhibitor Substances 0.000 title description 4
- 229940082638 cardiac stimulant phosphodiesterase inhibitors Drugs 0.000 title description 3
- 159000000018 pyrido[2,3-d]pyrimidines Chemical class 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 224
- -1 methylcarbamoyl Chemical group 0.000 claims description 186
- 238000002360 preparation method Methods 0.000 claims description 89
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 65
- 239000001257 hydrogen Substances 0.000 claims description 40
- 229910052739 hydrogen Inorganic materials 0.000 claims description 40
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 38
- DGYIJVNZSDYBOE-UHFFFAOYSA-N [CH2]C1=CC=NC=C1 Chemical group [CH2]C1=CC=NC=C1 DGYIJVNZSDYBOE-UHFFFAOYSA-N 0.000 claims description 35
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 27
- 125000000217 alkyl group Chemical group 0.000 claims description 27
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 26
- 150000003839 salts Chemical class 0.000 claims description 26
- 125000001072 heteroaryl group Chemical group 0.000 claims description 21
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 21
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 19
- 150000002431 hydrogen Chemical class 0.000 claims description 16
- 125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 claims description 15
- 239000003814 drug Substances 0.000 claims description 14
- 125000003118 aryl group Chemical group 0.000 claims description 13
- 150000002148 esters Chemical class 0.000 claims description 12
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 12
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 10
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 9
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 9
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 9
- 208000023275 Autoimmune disease Diseases 0.000 claims description 8
- 150000001204 N-oxides Chemical class 0.000 claims description 8
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- 208000006673 asthma Diseases 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 208000002193 Pain Diseases 0.000 claims description 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- 125000006216 methylsulfinyl group Chemical group [H]C([H])([H])S(*)=O 0.000 claims description 5
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 4
- 125000006479 2-pyridyl methyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 3
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 3
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 3
- ALZKIYWRMWPNAN-UHFFFAOYSA-N 1-(3-chlorophenyl)-3-(pyridin-3-ylmethyl)-4h-pyrido[2,3-d]pyrimidin-2-one Chemical compound ClC1=CC=CC(N2C3=NC=CC=C3CN(CC=3C=NC=CC=3)C2=O)=C1 ALZKIYWRMWPNAN-UHFFFAOYSA-N 0.000 claims description 2
- UUDZSOQPKQTJPR-UHFFFAOYSA-N 1-(3-chlorophenyl)-3-(pyridin-4-ylmethyl)-4h-pyrido[2,3-d]pyrimidin-2-one Chemical compound ClC1=CC=CC(N2C3=NC=CC=C3CN(CC=3C=CN=CC=3)C2=O)=C1 UUDZSOQPKQTJPR-UHFFFAOYSA-N 0.000 claims description 2
- 239000012458 free base Substances 0.000 claims description 2
- 206010029897 Obsessive thoughts Diseases 0.000 claims 4
- ULQHZYNDLXOCDR-UHFFFAOYSA-N 1-methylsulfanyl-2-phenylbenzene Chemical group CSC1=CC=CC=C1C1=CC=CC=C1 ULQHZYNDLXOCDR-UHFFFAOYSA-N 0.000 claims 1
- 125000001153 fluoro group Chemical group F* 0.000 claims 1
- 208000027866 inflammatory disease Diseases 0.000 claims 1
- DWLVWMUCHSLGSU-UHFFFAOYSA-M n,n-dimethylcarbamate Chemical compound CN(C)C([O-])=O DWLVWMUCHSLGSU-UHFFFAOYSA-M 0.000 claims 1
- 239000000243 solution Substances 0.000 description 82
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- 239000002904 solvent Substances 0.000 description 68
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- 125000004446 heteroarylalkyl group Chemical group 0.000 description 28
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 19
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- 239000002244 precipitate Substances 0.000 description 17
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 14
- 235000019341 magnesium sulphate Nutrition 0.000 description 14
- 238000010992 reflux Methods 0.000 description 14
- JQPYINKVAWEQDQ-UHFFFAOYSA-N 1h-pyrido[2,3-d]pyrimidine-2,4-dione Chemical compound C1=CC=C2C(=O)NC(=O)NC2=N1 JQPYINKVAWEQDQ-UHFFFAOYSA-N 0.000 description 13
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 13
- 241000699670 Mus sp. Species 0.000 description 13
- 230000003110 anti-inflammatory effect Effects 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 12
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- 229910052757 nitrogen Inorganic materials 0.000 description 12
- 238000000746 purification Methods 0.000 description 12
- 229940079593 drug Drugs 0.000 description 11
- 238000001914 filtration Methods 0.000 description 11
- 238000012746 preparative thin layer chromatography Methods 0.000 description 11
- XISPDDYROWQPHI-UHFFFAOYSA-N 3,4-dihydro-1h-pyrido[2,3-d]pyrimidin-2-one Chemical class C1=CN=C2NC(=O)NCC2=C1 XISPDDYROWQPHI-UHFFFAOYSA-N 0.000 description 10
- QGKGASXQTBQINX-UHFFFAOYSA-N 3,4-dihydro-1h-pyrimidin-2-one Chemical compound O=C1NCC=CN1 QGKGASXQTBQINX-UHFFFAOYSA-N 0.000 description 10
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- 230000001506 immunosuppresive effect Effects 0.000 description 10
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- 239000000126 substance Substances 0.000 description 10
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- 230000000202 analgesic effect Effects 0.000 description 8
- 238000003556 assay Methods 0.000 description 8
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 8
- 230000006870 function Effects 0.000 description 8
- 239000012312 sodium hydride Substances 0.000 description 8
- 229910000104 sodium hydride Inorganic materials 0.000 description 8
- DECBEECYBHUSOO-UHFFFAOYSA-N 3-(aminomethyl)-n-phenylpyridin-2-amine Chemical class NCC1=CC=CN=C1NC1=CC=CC=C1 DECBEECYBHUSOO-UHFFFAOYSA-N 0.000 description 7
- 229910052782 aluminium Inorganic materials 0.000 description 7
- 239000002775 capsule Substances 0.000 description 7
- OXAIIPJGBIWVIM-UHFFFAOYSA-M potassium;2-chloropyridine-3-carboxylate Chemical compound [K+].[O-]C(=O)C1=CC=CN=C1Cl OXAIIPJGBIWVIM-UHFFFAOYSA-M 0.000 description 7
- UDJFFSGCRRMVFH-UHFFFAOYSA-N pyrido[2,3-d]pyrimidine Chemical class N1=CN=CC2=CC=CN=C21 UDJFFSGCRRMVFH-UHFFFAOYSA-N 0.000 description 7
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- GUKZTMNMNAOZOX-UHFFFAOYSA-N 1-(3-chlorophenyl)-3,4-dihydropyrido[2,3-d]pyrimidin-2-one Chemical compound ClC1=CC=CC(N2C3=NC=CC=C3CNC2=O)=C1 GUKZTMNMNAOZOX-UHFFFAOYSA-N 0.000 description 3
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- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
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- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
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- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 description 1
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- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- WBYWAXJHAXSJNI-UHFFFAOYSA-N methyl p-hydroxycinnamate Natural products OC(=O)C=CC1=CC=CC=C1 WBYWAXJHAXSJNI-UHFFFAOYSA-N 0.000 description 1
- NQMRYBIKMRVZLB-UHFFFAOYSA-N methylamine hydrochloride Chemical compound [Cl-].[NH3+]C NQMRYBIKMRVZLB-UHFFFAOYSA-N 0.000 description 1
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- 239000003595 mist Substances 0.000 description 1
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- 210000005087 mononuclear cell Anatomy 0.000 description 1
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- 231100000150 mutagenicity / genotoxicity testing Toxicity 0.000 description 1
- JIAOUYONZMRJJD-UHFFFAOYSA-N n-benzylpyridine-3-carboxamide Chemical compound C=1C=CN=CC=1C(=O)NCC1=CC=CC=C1 JIAOUYONZMRJJD-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000005375 negative regulation of lymphocyte activation Effects 0.000 description 1
- 230000006213 negative regulation of lymphocyte proliferation Effects 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
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- 238000006053 organic reaction Methods 0.000 description 1
- 239000006179 pH buffering agent Substances 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
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- 230000000737 periodic effect Effects 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
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- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 description 1
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- IBBMAWULFFBRKK-UHFFFAOYSA-N picolinamide Chemical compound NC(=O)C1=CC=CC=N1 IBBMAWULFFBRKK-UHFFFAOYSA-N 0.000 description 1
- SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 1
- 239000003880 polar aprotic solvent Substances 0.000 description 1
- 229920000515 polycarbonate Polymers 0.000 description 1
- 239000004417 polycarbonate Substances 0.000 description 1
- 229920002523 polyethylene Glycol 1000 Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 1
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 1
- OKBMCNHOEMXPTM-UHFFFAOYSA-M potassium peroxymonosulfate Chemical compound [K+].OOS([O-])(=O)=O OKBMCNHOEMXPTM-UHFFFAOYSA-M 0.000 description 1
- 229910052939 potassium sulfate Inorganic materials 0.000 description 1
- OTYBMLCTZGSZBG-UHFFFAOYSA-L potassium sulfate Chemical compound [K+].[K+].[O-]S([O-])(=O)=O OTYBMLCTZGSZBG-UHFFFAOYSA-L 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
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- 238000002953 preparative HPLC Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
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- 150000008513 pyrimidine-2,4(1H,3H)-diones Chemical class 0.000 description 1
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- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- XMVJITFPVVRMHC-UHFFFAOYSA-N roxarsone Chemical group OC1=CC=C([As](O)(O)=O)C=C1[N+]([O-])=O XMVJITFPVVRMHC-UHFFFAOYSA-N 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
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- 239000003998 snake venom Substances 0.000 description 1
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- 229960004249 sodium acetate Drugs 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- RYYKJJJTJZKILX-UHFFFAOYSA-M sodium octadecanoate Chemical compound [Na+].CCCCCCCCCCCCCCCCCC([O-])=O RYYKJJJTJZKILX-UHFFFAOYSA-M 0.000 description 1
- 229940054269 sodium pyruvate Drugs 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
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- 125000001424 substituent group Chemical group 0.000 description 1
- 125000003107 substituted aryl group Chemical group 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
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- 239000012730 sustained-release form Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
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- 238000007910 systemic administration Methods 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- KFVSLSTULZVNPG-UHFFFAOYSA-N terbutaline sulfate Chemical compound [O-]S([O-])(=O)=O.CC(C)(C)[NH2+]CC(O)C1=CC(O)=CC(O)=C1.CC(C)(C)[NH2+]CC(O)C1=CC(O)=CC(O)=C1 KFVSLSTULZVNPG-UHFFFAOYSA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 229940104230 thymidine Drugs 0.000 description 1
- VYNCPPVQAZGELS-UHFFFAOYSA-N toluene;trimethylalumane Chemical compound C[Al](C)C.CC1=CC=CC=C1 VYNCPPVQAZGELS-UHFFFAOYSA-N 0.000 description 1
- 239000006208 topical dosage form Substances 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
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- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229910052727 yttrium Inorganic materials 0.000 description 1
- CZPRKINNVBONSF-UHFFFAOYSA-M zinc;dioxido(oxo)phosphanium Chemical compound [Zn+2].[O-][P+]([O-])=O CZPRKINNVBONSF-UHFFFAOYSA-M 0.000 description 1
Classifications
-
- 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
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Pain & Pain Management (AREA)
- Transplantation (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Rheumatology (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US07/855,179 US5264437A (en) | 1992-03-20 | 1992-03-20 | Optionally substituted pyrido[2,3-d]pyridine-2,4(1H,3H)-diones and pyrido[2,]pyrimidine-2(1H,3H)-ones |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| HU9402653D0 HU9402653D0 (en) | 1994-11-28 |
| HUT67552A true HUT67552A (en) | 1995-04-28 |
Family
ID=25320543
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HU9402653A HUT67552A (en) | 1992-03-20 | 1993-03-18 | Pyrido [2,3-d] pyrimidine derivatives as phosphodiesterase inhibitors, pharmaceutical compositions containing them and process for their production |
| HU95P/P00114P HU210873A9 (en) | 1992-03-20 | 1995-04-24 | Optionally substituted pyrido/2,3-d/pyrimidine-2,4(1h,3h)-diones and pyrido/2,3-d/ pyrimidine-2(1h,3h)-ones |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HU95P/P00114P HU210873A9 (en) | 1992-03-20 | 1995-04-24 | Optionally substituted pyrido/2,3-d/pyrimidine-2,4(1h,3h)-diones and pyrido/2,3-d/ pyrimidine-2(1h,3h)-ones |
Country Status (16)
| Country | Link |
|---|---|
| US (1) | US5264437A (enFirst) |
| EP (2) | EP1770093A1 (enFirst) |
| JP (1) | JP3241384B2 (enFirst) |
| KR (1) | KR100274104B1 (enFirst) |
| CN (1) | CN1040327C (enFirst) |
| AU (1) | AU669520B2 (enFirst) |
| CA (1) | CA2132297C (enFirst) |
| FI (1) | FI106960B (enFirst) |
| HU (2) | HUT67552A (enFirst) |
| IL (1) | IL105092A (enFirst) |
| MX (1) | MX9301530A (enFirst) |
| NO (1) | NO301763B1 (enFirst) |
| NZ (1) | NZ251525A (enFirst) |
| TW (1) | TW240226B (enFirst) |
| WO (1) | WO1993019068A1 (enFirst) |
| ZA (1) | ZA931945B (enFirst) |
Families Citing this family (38)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5672622A (en) * | 1994-04-21 | 1997-09-30 | Berlex Laboratories, Inc. | Treatment of multiple sclerosis |
| US6060501A (en) * | 1994-06-02 | 2000-05-09 | Schering Aktiengesellschaft | Combined treatment of multiple sclerosis |
| CA2197984A1 (en) * | 1994-08-29 | 1996-03-07 | Kazuhisa Takayama | Novel naphthyridine derivatives and pharmaceutical compositions thereof |
| CN1173818A (zh) * | 1995-02-10 | 1998-02-18 | 舍林股份公司 | 用于tnf抑制的药物制剂 |
| DE19540475A1 (de) * | 1995-10-20 | 1997-04-24 | Schering Ag | Chirale Methylphenyloxazolidinone |
| NZ322197A (en) * | 1995-11-21 | 1999-02-25 | Yamanouchi Pharma Co Ltd | Pyrido[2,3-d] pyrimidine derivatives and pharmaceutical compositions thereof |
| JP2000119272A (ja) | 1998-10-15 | 2000-04-25 | Nippon Zoki Pharmaceut Co Ltd | 新規７−アミノピリド〔２，３−ｄ〕ピリミジン誘導体 |
| US6455554B1 (en) | 1999-06-07 | 2002-09-24 | Targacept, Inc. | Oxopyridinyl pharmaceutical compositions and methods for use |
| ATE320800T1 (de) | 1999-08-21 | 2006-04-15 | Altana Pharma Ag | Synergistische kombination von roflumilast und salmeterol |
| TWI243055B (en) | 2000-04-13 | 2005-11-11 | Nippon Zoki Pharmaceutical Co | Pharmaceutical composition for use in treatment of dermatitis |
| US6825180B2 (en) * | 2001-05-18 | 2004-11-30 | Cell Therapeutics, Inc. | Pyridopyrimidine compounds and their uses |
| WO2003037869A1 (en) * | 2001-11-01 | 2003-05-08 | Janssen Pharmaceutica N.V. | Amide derivatives as glycogen synthase kinase 3-beta inhibitors |
| US7772188B2 (en) | 2003-01-28 | 2010-08-10 | Ironwood Pharmaceuticals, Inc. | Methods and compositions for the treatment of gastrointestinal disorders |
| EP1624893A2 (en) | 2003-04-01 | 2006-02-15 | Applied Research Systems ARS Holding N.V. | Inhibitors of phosphodiesterases in infertility |
| WO2006019965A2 (en) * | 2004-07-16 | 2006-02-23 | Takeda San Diego, Inc. | Dipeptidyl peptidase inhibitors |
| TW200726767A (en) * | 2005-07-04 | 2007-07-16 | Astrazeneca Ab | Chemical compounds 2 |
| TW200800997A (en) * | 2006-03-22 | 2008-01-01 | Astrazeneca Ab | Chemical compounds |
| HRP20110621T2 (hr) * | 2006-09-15 | 2013-12-06 | Pfizer Products Inc. | SPOJEVI PIRIDO[2,3-d]PIRIMIDINONA I NJIHOVA UPOTREBA KAO INHIBITORI PI3 |
| SA08280783B1 (ar) * | 2007-01-11 | 2011-04-24 | استرازينيكا ايه بي | مشتقات بيريدوبيريميدين كمثبطات pde4 |
| WO2008084236A1 (en) * | 2007-01-11 | 2008-07-17 | Astrazeneca Ab | Chemical compounds 635 : pyridopyrimidinediones as pde4 inhibitors |
| TW200835497A (en) * | 2007-01-11 | 2008-09-01 | Astrazeneca Ab | Chemical compounds 636 |
| AU2008261102B2 (en) | 2007-06-04 | 2013-11-28 | Bausch Health Ireland Limited | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| US8969514B2 (en) | 2007-06-04 | 2015-03-03 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
| FR2921926B1 (fr) * | 2007-10-03 | 2009-12-04 | Sanofi Aventis | Derives de quinazolinedione,leur preparation et leurs applications therapeutiques. |
| JP5607032B2 (ja) | 2008-05-27 | 2014-10-15 | アストラゼネカ・アクチエボラーグ | フェノキシピリジニルアミド誘導体およびｐｄｅ４仲介疾患状態におけるその使用 |
| EP3239170B1 (en) | 2008-06-04 | 2019-03-20 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal disorders, inflammation, cancer and other disorders |
| WO2010009319A2 (en) | 2008-07-16 | 2010-01-21 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase useful for the treatment of gastrointestinal, inflammation, cancer and other disorders |
| FR2944282B1 (fr) | 2009-04-09 | 2013-05-03 | Sanofi Aventis | Derives de quinazolinedione, leur preparation et leurs diverses applications therapeutiques |
| US9616097B2 (en) | 2010-09-15 | 2017-04-11 | Synergy Pharmaceuticals, Inc. | Formulations of guanylate cyclase C agonists and methods of use |
| CA3100941C (en) | 2011-03-01 | 2024-03-05 | Synergy Pharmaceuticals Inc. | Process of preparing guanylate cyclase c agonists |
| WO2014131024A2 (en) | 2013-02-25 | 2014-08-28 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase and their uses |
| WO2014151200A2 (en) | 2013-03-15 | 2014-09-25 | Synergy Pharmaceuticals Inc. | Compositions useful for the treatment of gastrointestinal disorders |
| EP2970384A1 (en) | 2013-03-15 | 2016-01-20 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase and their uses |
| HRP20240805T1 (hr) | 2013-06-05 | 2024-09-27 | Bausch Health Ireland Limited | Ultra-pročišćeni agonisti guanilat-ciklaze c, postupak njihove pripreme i uporabe |
| CN114404588A (zh) | 2013-08-09 | 2022-04-29 | 阿德利克斯公司 | 用于抑制磷酸盐转运的化合物和方法 |
| CN114340631A (zh) | 2019-05-21 | 2022-04-12 | 阿德利克斯股份有限公司 | 用于降低患者的血清磷酸盐的组合 |
| JPWO2023042879A1 (enFirst) * | 2021-09-17 | 2023-03-23 | ||
| CN113831491B (zh) * | 2021-09-30 | 2023-03-24 | 南昌大学 | 一种嘧啶唑共价有机框架的制备方法及吸附应用 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5649917B2 (enFirst) * | 1973-12-18 | 1981-11-25 | ||
| JPS58428B2 (ja) * | 1974-07-05 | 1983-01-06 | ヒサミツセイヤク カブシキガイシヤ | シンキナ ２− オキソ −１，２，３，４− テトラヒドロピリド （ ２，３−ｄ ） ピリミジンユウドウタイノ セイゾウホウ |
| DE2523730A1 (de) * | 1974-06-12 | 1976-02-12 | Hisamitsu Pharmaceutical Co | Pyrido eckige klammer auf 2,3-d eckige klammer zu pyrimidinonen |
| DE3770095D1 (de) * | 1986-08-21 | 1991-06-20 | Pfizer | Chinazolindione und pyridopyrimidindione. |
| DE69327312T2 (de) * | 1992-04-29 | 2000-07-13 | Sri International, Menlo Park | Deazaaminopterine für behandlung von entzündungen |
-
1992
- 1992-03-20 US US07/855,179 patent/US5264437A/en not_active Expired - Lifetime
-
1993
- 1993-03-18 IL IL105092A patent/IL105092A/en not_active IP Right Cessation
- 1993-03-18 CA CA002132297A patent/CA2132297C/en not_active Expired - Fee Related
- 1993-03-18 HU HU9402653A patent/HUT67552A/hu unknown
- 1993-03-18 MX MX9301530A patent/MX9301530A/es not_active IP Right Cessation
- 1993-03-18 ZA ZA931945A patent/ZA931945B/xx unknown
- 1993-03-18 KR KR1019940703294A patent/KR100274104B1/ko not_active Expired - Fee Related
- 1993-03-18 NZ NZ251525A patent/NZ251525A/en unknown
- 1993-03-18 AU AU39186/93A patent/AU669520B2/en not_active Ceased
- 1993-03-18 TW TW082101993A patent/TW240226B/zh active
- 1993-03-18 EP EP05023665A patent/EP1770093A1/en not_active Withdrawn
- 1993-03-18 EP EP93908322A patent/EP0631580A1/en not_active Ceased
- 1993-03-18 JP JP51663493A patent/JP3241384B2/ja not_active Expired - Fee Related
- 1993-03-18 CN CN93103352A patent/CN1040327C/zh not_active Expired - Fee Related
- 1993-03-18 WO PCT/US1993/002273 patent/WO1993019068A1/en not_active Ceased
-
1994
- 1994-09-16 NO NO943456A patent/NO301763B1/no not_active IP Right Cessation
- 1994-09-16 FI FI944305A patent/FI106960B/fi not_active IP Right Cessation
-
1995
- 1995-04-24 HU HU95P/P00114P patent/HU210873A9/hu unknown
Also Published As
| Publication number | Publication date |
|---|---|
| KR950700909A (ko) | 1995-02-20 |
| MX9301530A (es) | 1994-01-31 |
| JP3241384B2 (ja) | 2001-12-25 |
| EP1770093A1 (en) | 2007-04-04 |
| FI944305L (fi) | 1994-09-16 |
| AU669520B2 (en) | 1996-06-13 |
| HU9402653D0 (en) | 1994-11-28 |
| AU3918693A (en) | 1993-10-21 |
| CA2132297C (en) | 2006-01-03 |
| WO1993019068A1 (en) | 1993-09-30 |
| FI106960B (fi) | 2001-05-15 |
| CN1040327C (zh) | 1998-10-21 |
| CN1078470A (zh) | 1993-11-17 |
| NO943456D0 (no) | 1994-09-16 |
| KR100274104B1 (ko) | 2000-12-15 |
| US5264437A (en) | 1993-11-23 |
| ZA931945B (en) | 1994-09-18 |
| NO301763B1 (no) | 1997-12-08 |
| JPH07504676A (ja) | 1995-05-25 |
| NZ251525A (en) | 1996-09-25 |
| NO943456L (no) | 1994-09-16 |
| IL105092A (en) | 1998-06-15 |
| EP0631580A1 (en) | 1995-01-04 |
| CA2132297A1 (en) | 1993-09-30 |
| HU210873A9 (en) | 1995-08-28 |
| IL105092A0 (en) | 1993-07-08 |
| FI944305A0 (fi) | 1994-09-16 |
| TW240226B (enFirst) | 1995-02-11 |
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