CA2368460A1 - Derivatives of pyrimido¬6,1-a|isoquinolin-4-one - Google Patents
Derivatives of pyrimido¬6,1-a|isoquinolin-4-one Download PDFInfo
- Publication number
- CA2368460A1 CA2368460A1 CA002368460A CA2368460A CA2368460A1 CA 2368460 A1 CA2368460 A1 CA 2368460A1 CA 002368460 A CA002368460 A CA 002368460A CA 2368460 A CA2368460 A CA 2368460A CA 2368460 A1 CA2368460 A1 CA 2368460A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- group
- alkenyl
- alkynyl
- acyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- PVKCAQKXTLCSBC-UHFFFAOYSA-N 1h-isoquinolin-4-one Chemical compound C1=CC=C2C(=O)C=NCC2=C1 PVKCAQKXTLCSBC-UHFFFAOYSA-N 0.000 title claims description 19
- 150000001875 compounds Chemical class 0.000 claims abstract description 173
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 97
- 125000002252 acyl group Chemical group 0.000 claims abstract description 52
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 46
- 125000005843 halogen group Chemical group 0.000 claims abstract description 35
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims abstract description 33
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims abstract description 33
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 33
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 32
- 239000001257 hydrogen Substances 0.000 claims abstract description 32
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 32
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 32
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims abstract description 30
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 24
- 150000003839 salts Chemical class 0.000 claims abstract description 17
- 238000011282 treatment Methods 0.000 claims abstract description 16
- 208000006673 asthma Diseases 0.000 claims abstract description 11
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract 62
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims abstract 44
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract 28
- 125000004755 (C2-C7) acylamino group Chemical group 0.000 claims abstract 15
- 125000006593 (C2-C3) alkynyl group Chemical group 0.000 claims abstract 14
- 125000006592 (C2-C3) alkenyl group Chemical group 0.000 claims abstract 13
- 239000000203 mixture Substances 0.000 claims description 45
- -1 C1-6 alhylthio Chemical group 0.000 claims description 35
- 238000000034 method Methods 0.000 claims description 33
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 28
- 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 claims description 19
- 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 claims description 19
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 16
- 239000003112 inhibitor Substances 0.000 claims description 16
- 239000003814 drug Substances 0.000 claims description 15
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 13
- 125000003342 alkenyl group Chemical group 0.000 claims description 11
- 125000000304 alkynyl group Chemical group 0.000 claims description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 241000124008 Mammalia Species 0.000 claims description 9
- 201000010099 disease Diseases 0.000 claims description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
- 230000002265 prevention Effects 0.000 claims description 9
- 230000008569 process Effects 0.000 claims description 9
- CIVQDIGHVMGTPD-UHFFFAOYSA-N pyrimido[6,1-a]isoquinolin-4-one Chemical compound C1=CC=C2C=CN3C(=O)N=CC=C3C2=C1 CIVQDIGHVMGTPD-UHFFFAOYSA-N 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 9
- 108010044467 Isoenzymes Proteins 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 7
- 229940124630 bronchodilator Drugs 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- 230000003834 intracellular effect Effects 0.000 claims description 5
- 231100000252 nontoxic Toxicity 0.000 claims description 5
- 230000003000 nontoxic effect Effects 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 241001465754 Metazoa Species 0.000 claims description 4
- 239000000443 aerosol Substances 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 239000003862 glucocorticoid Substances 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 2
- 239000013543 active substance Substances 0.000 claims description 2
- 239000000048 adrenergic agonist Substances 0.000 claims description 2
- 230000001088 anti-asthma Effects 0.000 claims description 2
- 239000000924 antiasthmatic agent Substances 0.000 claims description 2
- 230000008901 benefit Effects 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims 1
- MCMSJVMUSBZUCN-YYDJUVGSSA-N chembl285913 Chemical compound C1=2C=C(OC)C(OC)=CC=2CCN(C(N2C)=O)C1=C\C2=N/C1=C(C)C=C(C)C=C1C MCMSJVMUSBZUCN-YYDJUVGSSA-N 0.000 abstract description 10
- 229950004127 trequinsin Drugs 0.000 abstract description 10
- 230000009471 action Effects 0.000 abstract description 6
- 208000023504 respiratory system disease Diseases 0.000 abstract description 5
- MCMSJVMUSBZUCN-UHFFFAOYSA-N 9,10-dimethoxy-3-methyl-2-(2,4,6-trimethylphenyl)imino-6,7-dihydropyrimido[6,1-a]isoquinolin-4-one Chemical compound C1=2C=C(OC)C(OC)=CC=2CCN(C(N2C)=O)C1=CC2=NC1=C(C)C=C(C)C=C1C MCMSJVMUSBZUCN-UHFFFAOYSA-N 0.000 abstract description 3
- 235000019658 bitter taste Nutrition 0.000 abstract description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 60
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 47
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 27
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 239000007787 solid Substances 0.000 description 21
- 230000000694 effects Effects 0.000 description 19
- 241000700199 Cavia porcellus Species 0.000 description 18
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
- 125000000217 alkyl group Chemical group 0.000 description 18
- 239000000243 solution Substances 0.000 description 17
- BIJWXQNMLKVZJM-UHFFFAOYSA-N 2-chloro-9,10-dimethoxy-6,7-dihydropyrimido[6,1-a]isoquinolin-4-one Chemical compound C1=2C=C(OC)C(OC)=CC=2CCN2C1=CC(Cl)=NC2=O BIJWXQNMLKVZJM-UHFFFAOYSA-N 0.000 description 16
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- 235000019439 ethyl acetate Nutrition 0.000 description 15
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 15
- 238000002360 preparation method Methods 0.000 description 14
- 125000004432 carbon atom Chemical group C* 0.000 description 13
- 230000000638 stimulation Effects 0.000 description 13
- 210000003437 trachea Anatomy 0.000 description 13
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
- 229910052799 carbon Inorganic materials 0.000 description 12
- 230000009989 contractile response Effects 0.000 description 12
- 229910052757 nitrogen Inorganic materials 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 11
- 230000005684 electric field Effects 0.000 description 11
- ZBYZWTDPATVYRA-UHFFFAOYSA-N C1=CC=C2C3=C(OC)C(OC)=NC(=O)N3C=CC2=C1 Chemical compound C1=CC=C2C3=C(OC)C(OC)=NC(=O)N3C=CC2=C1 ZBYZWTDPATVYRA-UHFFFAOYSA-N 0.000 description 10
- 125000003282 alkyl amino group Chemical group 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 10
- 238000004440 column chromatography Methods 0.000 description 10
- 238000001816 cooling Methods 0.000 description 10
- 239000000741 silica gel Substances 0.000 description 10
- 229910002027 silica gel Inorganic materials 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 238000001514 detection method Methods 0.000 description 9
- 239000000706 filtrate Substances 0.000 description 9
- 238000004128 high performance liquid chromatography Methods 0.000 description 9
- 239000000843 powder Substances 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- 101150041968 CDC13 gene Proteins 0.000 description 8
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 8
- 230000008602 contraction Effects 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 8
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 8
- 235000019341 magnesium sulphate Nutrition 0.000 description 8
- 210000005087 mononuclear cell Anatomy 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- 125000004442 acylamino group Chemical group 0.000 description 6
- 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 230000005764 inhibitory process Effects 0.000 description 6
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 6
- 230000035755 proliferation Effects 0.000 description 6
- 235000019640 taste Nutrition 0.000 description 6
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 229960004592 isopropanol Drugs 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 230000000144 pharmacologic effect Effects 0.000 description 5
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 5
- NBRRSNFRTBXBID-UHFFFAOYSA-N 2-[2,6-di(propan-2-yl)phenoxy]-9,10-dimethoxy-6,7-dihydropyrimido[6,1-a]isoquinolin-4-one Chemical compound C1=2C=C(OC)C(OC)=CC=2CCN(C(N=2)=O)C1=CC=2OC1=C(C(C)C)C=CC=C1C(C)C NBRRSNFRTBXBID-UHFFFAOYSA-N 0.000 description 4
- 206010006482 Bronchospasm Diseases 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 4
- 125000004423 acyloxy group Chemical group 0.000 description 4
- 125000004414 alkyl thio group Chemical group 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 230000001713 cholinergic effect Effects 0.000 description 4
- 229960001340 histamine Drugs 0.000 description 4
- 150000002430 hydrocarbons Chemical group 0.000 description 4
- 239000003380 propellant Substances 0.000 description 4
- 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 3
- 208000009079 Bronchial Spasm Diseases 0.000 description 3
- 208000014181 Bronchial disease Diseases 0.000 description 3
- 241000700198 Cavia Species 0.000 description 3
- IVOMOUWHDPKRLL-KQYNXXCUSA-N Cyclic adenosine monophosphate Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-KQYNXXCUSA-N 0.000 description 3
- 235000019502 Orange oil Nutrition 0.000 description 3
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- IVOMOUWHDPKRLL-UHFFFAOYSA-N UNPD107823 Natural products O1C2COP(O)(=O)OC2C(O)C1N1C(N=CN=C2N)=C2N=C1 IVOMOUWHDPKRLL-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 208000011341 adult acute respiratory distress syndrome Diseases 0.000 description 3
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 3
- 239000000556 agonist Substances 0.000 description 3
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- 239000000427 antigen Substances 0.000 description 3
- 102000036639 antigens Human genes 0.000 description 3
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- 239000008346 aqueous phase Substances 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 229940095074 cyclic amp Drugs 0.000 description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 239000012954 diazonium Substances 0.000 description 3
- 150000001989 diazonium salts Chemical class 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 230000004054 inflammatory process Effects 0.000 description 3
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- 239000010502 orange oil Substances 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
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- 229910052697 platinum Inorganic materials 0.000 description 3
- 239000011541 reaction mixture Substances 0.000 description 3
- 238000011084 recovery Methods 0.000 description 3
- 150000003431 steroids Chemical class 0.000 description 3
- 239000001117 sulphuric acid Substances 0.000 description 3
- 235000011149 sulphuric acid Nutrition 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- 125000006017 1-propenyl group Chemical group 0.000 description 2
- 125000000530 1-propynyl group Chemical group [H]C([H])([H])C#C* 0.000 description 2
- NXXYKOUNUYWIHA-UHFFFAOYSA-N 2,6-Dimethylphenol Chemical compound CC1=CC=CC(C)=C1O NXXYKOUNUYWIHA-UHFFFAOYSA-N 0.000 description 2
- NFIDBGJMFKNGGQ-UHFFFAOYSA-N 2-(2-methylpropyl)phenol Chemical compound CC(C)CC1=CC=CC=C1O NFIDBGJMFKNGGQ-UHFFFAOYSA-N 0.000 description 2
- IXQGCWUGDFDQMF-UHFFFAOYSA-N 2-Ethylphenol Chemical compound CCC1=CC=CC=C1O IXQGCWUGDFDQMF-UHFFFAOYSA-N 0.000 description 2
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- 206010012438 Dermatitis atopic Diseases 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- UIAYVIIHMORPSJ-UHFFFAOYSA-N N-cyclohexyl-N-methyl-4-[(2-oxo-1H-quinolin-6-yl)oxy]butanamide Chemical compound C=1C=C2NC(=O)C=CC2=CC=1OCCCC(=O)N(C)C1CCCCC1 UIAYVIIHMORPSJ-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- 229940123263 Phosphodiesterase 3 inhibitor Drugs 0.000 description 2
- 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 description 2
- 201000004681 Psoriasis Diseases 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 206010039085 Rhinitis allergic Diseases 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 229960000583 acetic acid Drugs 0.000 description 2
- UDMBCSSLTHHNCD-KQYNXXCUSA-N adenosine 5'-monophosphate Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](COP(O)(O)=O)[C@@H](O)[C@H]1O UDMBCSSLTHHNCD-KQYNXXCUSA-N 0.000 description 2
- 230000002411 adverse Effects 0.000 description 2
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- 201000009961 allergic asthma Diseases 0.000 description 2
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- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 2
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 2
- 230000004872 arterial blood pressure Effects 0.000 description 2
- 201000008937 atopic dermatitis Diseases 0.000 description 2
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- 229950002934 cilostamide Drugs 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 2
- 125000004663 dialkyl amino group Chemical group 0.000 description 2
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 2
- 238000003818 flash chromatography Methods 0.000 description 2
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- 238000000338 in vitro Methods 0.000 description 2
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- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 description 2
- 229910052759 nickel Inorganic materials 0.000 description 2
- 229910000510 noble metal Inorganic materials 0.000 description 2
- QWVGKYWNOKOFNN-UHFFFAOYSA-N o-cresol Chemical compound CC1=CC=CC=C1O QWVGKYWNOKOFNN-UHFFFAOYSA-N 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 239000002570 phosphodiesterase III inhibitor Substances 0.000 description 2
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 229910052703 rhodium Inorganic materials 0.000 description 2
- 239000010948 rhodium Substances 0.000 description 2
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 2
- HJORMJIFDVBMOB-UHFFFAOYSA-N rolipram Chemical compound COC1=CC=C(C2CC(=O)NC2)C=C1OC1CCCC1 HJORMJIFDVBMOB-UHFFFAOYSA-N 0.000 description 2
- 229950005741 rolipram Drugs 0.000 description 2
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- 210000002460 smooth muscle Anatomy 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 2
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 125000004001 thioalkyl group Chemical group 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- 210000005062 tracheal ring Anatomy 0.000 description 2
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- 239000003071 vasodilator agent Substances 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000000080 wetting agent Substances 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9907456.9A GB9907456D0 (en) | 1999-03-31 | 1999-03-31 | Compounds |
| GB9909803.0 | 1999-04-28 | ||
| GBGB9909803.0A GB9909803D0 (en) | 1999-04-28 | 1999-04-28 | Compounds |
| GB9907456.9 | 1999-04-28 | ||
| PCT/GB2000/001195 WO2000058309A1 (en) | 1999-03-31 | 2000-03-29 | Derivatives of pyrimido[6,1-a]isoquinolin-4-one |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2368460A1 true CA2368460A1 (en) | 2000-10-05 |
Family
ID=26315370
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002368460A Abandoned CA2368460A1 (en) | 1999-03-31 | 2000-03-29 | Derivatives of pyrimido¬6,1-a|isoquinolin-4-one |
Country Status (10)
| Country | Link |
|---|---|
| EP (1) | EP1165556A1 (es) |
| JP (1) | JP2002543046A (es) |
| CN (1) | CN1348452A (es) |
| AU (1) | AU3974700A (es) |
| BR (1) | BR0009449A (es) |
| CA (1) | CA2368460A1 (es) |
| MX (1) | MXPA01009847A (es) |
| NO (1) | NO20014729L (es) |
| NZ (1) | NZ514157A (es) |
| WO (1) | WO2000058309A1 (es) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR089284A1 (es) * | 2011-12-22 | 2014-08-13 | Galapagos Nv | Dihidropirimidinoisoquinolinonas y composiciones farmaceuticas de las mismas para el tratamiento de trastornos inflamatorios |
-
2000
- 2000-03-29 AU AU39747/00A patent/AU3974700A/en not_active Abandoned
- 2000-03-29 CA CA002368460A patent/CA2368460A1/en not_active Abandoned
- 2000-03-29 BR BR0009449-8A patent/BR0009449A/pt not_active IP Right Cessation
- 2000-03-29 JP JP2000608011A patent/JP2002543046A/ja active Pending
- 2000-03-29 NZ NZ514157A patent/NZ514157A/en unknown
- 2000-03-29 WO PCT/GB2000/001195 patent/WO2000058309A1/en not_active Application Discontinuation
- 2000-03-29 EP EP00918982A patent/EP1165556A1/en not_active Withdrawn
- 2000-03-29 MX MXPA01009847A patent/MXPA01009847A/es unknown
- 2000-03-29 CN CN00806771A patent/CN1348452A/zh active Pending
-
2001
- 2001-09-28 NO NO20014729A patent/NO20014729L/no not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| NO20014729L (no) | 2001-11-23 |
| NZ514157A (en) | 2003-08-29 |
| AU3974700A (en) | 2000-10-16 |
| WO2000058309A1 (en) | 2000-10-05 |
| NO20014729D0 (no) | 2001-09-28 |
| BR0009449A (pt) | 2002-01-08 |
| CN1348452A (zh) | 2002-05-08 |
| MXPA01009847A (es) | 2003-06-24 |
| JP2002543046A (ja) | 2002-12-17 |
| EP1165556A1 (en) | 2002-01-02 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Dead |