NO300925B1 - Xantinderivater - Google Patents
Xantinderivater Download PDFInfo
- Publication number
- NO300925B1 NO300925B1 NO934792A NO934792A NO300925B1 NO 300925 B1 NO300925 B1 NO 300925B1 NO 934792 A NO934792 A NO 934792A NO 934792 A NO934792 A NO 934792A NO 300925 B1 NO300925 B1 NO 300925B1
- Authority
- NO
- Norway
- Prior art keywords
- compound
- mmol
- lower alkyl
- methyl
- nmr
- Prior art date
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- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical class O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 title claims abstract description 14
- 229940083747 low-ceiling diuretics xanthine derivative Drugs 0.000 title abstract description 5
- 150000003839 salts Chemical class 0.000 claims abstract description 28
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 27
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 19
- 239000001257 hydrogen Substances 0.000 claims abstract description 19
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 12
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 9
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 5
- 150000002367 halogens Chemical class 0.000 claims abstract description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 4
- 150000001875 compounds Chemical class 0.000 claims description 145
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- UXRMZEGZDOIEMY-CSKARUKUSA-N 8-[(e)-2-(3-acetyl-4-fluorophenyl)ethenyl]-1,3-diethyl-7-methylpurine-2,6-dione Chemical compound CN1C=2C(=O)N(CC)C(=O)N(CC)C=2N=C1\C=C\C1=CC=C(F)C(C(C)=O)=C1 UXRMZEGZDOIEMY-CSKARUKUSA-N 0.000 claims description 2
- HTHWKSPTPFSIFK-ZHACJKMWSA-N 8-[(e)-2-(3-acetylphenyl)ethenyl]-1,3-diethyl-7-methylpurine-2,6-dione Chemical group CN1C=2C(=O)N(CC)C(=O)N(CC)C=2N=C1\C=C\C1=CC=CC(C(C)=O)=C1 HTHWKSPTPFSIFK-ZHACJKMWSA-N 0.000 claims description 2
- YIUNWZCYCKYJTA-PKNBQFBNSA-N 8-[(e)-2-(4-acetyl-3-methoxyphenyl)ethenyl]-1,3-diethyl-7-methylpurine-2,6-dione Chemical compound CN1C=2C(=O)N(CC)C(=O)N(CC)C=2N=C1\C=C\C1=CC=C(C(C)=O)C(OC)=C1 YIUNWZCYCKYJTA-PKNBQFBNSA-N 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 7
- 125000003118 aryl group Chemical group 0.000 abstract description 2
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 abstract 1
- 229910052760 oxygen Inorganic materials 0.000 abstract 1
- 239000001301 oxygen Substances 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 57
- 238000000034 method Methods 0.000 description 48
- 239000000203 mixture Substances 0.000 description 46
- 238000002844 melting Methods 0.000 description 44
- 230000008018 melting Effects 0.000 description 44
- 239000013078 crystal Substances 0.000 description 42
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 39
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 39
- 238000000921 elemental analysis Methods 0.000 description 36
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 36
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 34
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 32
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 30
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 28
- 239000002904 solvent Substances 0.000 description 28
- GCQNNBDLJOCODU-ZHACJKMWSA-N 1,3-diethyl-8-[(e)-2-(3-methoxyphenyl)ethenyl]-7-methylpurine-2,6-dione Chemical compound CN1C=2C(=O)N(CC)C(=O)N(CC)C=2N=C1\C=C\C1=CC=CC(OC)=C1 GCQNNBDLJOCODU-ZHACJKMWSA-N 0.000 description 27
- 239000000843 powder Substances 0.000 description 26
- 239000000243 solution Substances 0.000 description 25
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- 238000012360 testing method Methods 0.000 description 24
- -1 8-substituted xanthine Chemical class 0.000 description 23
- 238000006243 chemical reaction Methods 0.000 description 23
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 20
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 238000001816 cooling Methods 0.000 description 18
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 16
- 239000000725 suspension Substances 0.000 description 16
- 235000019441 ethanol Nutrition 0.000 description 14
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
- OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 12
- 239000007864 aqueous solution Substances 0.000 description 12
- 238000001914 filtration Methods 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
- 241000699670 Mus sp. Species 0.000 description 10
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 10
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
- 229940125904 compound 1 Drugs 0.000 description 10
- 238000002451 electron ionisation mass spectrometry Methods 0.000 description 10
- 238000001704 evaporation Methods 0.000 description 10
- 230000008020 evaporation Effects 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 229920006395 saturated elastomer Polymers 0.000 description 9
- 239000011780 sodium chloride Substances 0.000 description 9
- 229940124530 sulfonamide Drugs 0.000 description 9
- 239000003480 eluent Substances 0.000 description 8
- LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 8
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 7
- 208000009132 Catalepsy Diseases 0.000 description 7
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
- 206010047853 Waxy flexibility Diseases 0.000 description 7
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 7
- 229910052794 bromium Inorganic materials 0.000 description 7
- 239000011541 reaction mixture Substances 0.000 description 7
- 102000005962 receptors Human genes 0.000 description 7
- 108020003175 receptors Proteins 0.000 description 7
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 6
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- 208000018737 Parkinson disease Diseases 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 229960005305 adenosine Drugs 0.000 description 6
- 239000002775 capsule Substances 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 6
- 230000000694 effects Effects 0.000 description 6
- 150000002170 ethers Chemical class 0.000 description 6
- 239000011630 iodine Substances 0.000 description 6
- 229910052740 iodine Inorganic materials 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- UYSUETCFMBIADB-UHFFFAOYSA-N 5,6-diamino-1,3-diethylpyrimidine-2,4-dione Chemical compound CCN1C(N)=C(N)C(=O)N(CC)C1=O UYSUETCFMBIADB-UHFFFAOYSA-N 0.000 description 5
- JJUJLNZUNIJSHZ-MDZDMXLPSA-N 8-[(e)-2-(3-bromophenyl)ethenyl]-1,3-diethyl-7-methylpurine-2,6-dione Chemical compound CN1C=2C(=O)N(CC)C(=O)N(CC)C=2N=C1\C=C\C1=CC=CC(Br)=C1 JJUJLNZUNIJSHZ-MDZDMXLPSA-N 0.000 description 5
- 208000001132 Osteoporosis Diseases 0.000 description 5
- YNHIGQDRGKUECZ-UHFFFAOYSA-L bis(triphenylphosphine)palladium(ii) dichloride Chemical compound [Cl-].[Cl-].[Pd+2].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 YNHIGQDRGKUECZ-UHFFFAOYSA-L 0.000 description 5
- HGXJOXHYPGNVNK-UHFFFAOYSA-N butane;ethenoxyethane;tin Chemical compound CCCC[Sn](CCCC)(CCCC)C(=C)OCC HGXJOXHYPGNVNK-UHFFFAOYSA-N 0.000 description 5
- 239000012153 distilled water Substances 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 238000004519 manufacturing process Methods 0.000 description 5
- 239000012044 organic layer Substances 0.000 description 5
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 5
- 229920000053 polysorbate 80 Polymers 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 4
- KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 4
- WKTSODZKCLNEOY-UHFFFAOYSA-N 1,3-diethyl-7-methyl-2,6-dioxopurine-8-carbaldehyde Chemical compound O=C1N(CC)C(=O)N(CC)C2=C1N(C)C(C=O)=N2 WKTSODZKCLNEOY-UHFFFAOYSA-N 0.000 description 4
- ZWXNGZIWLGSANT-UHFFFAOYSA-N 1,3-diethyl-8-(hydroxymethyl)-7-methylpurine-2,6-dione Chemical compound O=C1N(CC)C(=O)N(CC)C2=C1N(C)C(CO)=N2 ZWXNGZIWLGSANT-UHFFFAOYSA-N 0.000 description 4
- HRMJJJDGACABJM-MDZDMXLPSA-N 1,3-diethyl-8-[(e)-2-(3-methoxyphenyl)ethenyl]-7h-purine-2,6-dione Chemical compound N1C=2C(=O)N(CC)C(=O)N(CC)C=2N=C1\C=C\C1=CC=CC(OC)=C1 HRMJJJDGACABJM-MDZDMXLPSA-N 0.000 description 4
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 4
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- MWFJUQNGMQBODH-CMDGGOBGSA-N 8-[(e)-2-(3-bromophenyl)ethenyl]-1,3-diethyl-7h-purine-2,6-dione Chemical compound N1C=2C(=O)N(CC)C(=O)N(CC)C=2N=C1\C=C\C1=CC=CC(Br)=C1 MWFJUQNGMQBODH-CMDGGOBGSA-N 0.000 description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
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- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
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- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 150000004714 phosphonium salts Chemical class 0.000 description 1
- UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- 239000002504 physiological saline solution Substances 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 235000019422 polyvinyl alcohol Nutrition 0.000 description 1
- 230000001242 postsynaptic effect Effects 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 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
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000003549 soybean oil Substances 0.000 description 1
- 235000012424 soybean oil Nutrition 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000000021 stimulant Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000005504 styryl group Chemical group 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 230000006103 sulfonylation Effects 0.000 description 1
- 238000005694 sulfonylation reaction Methods 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- UDYFLDICVHJSOY-UHFFFAOYSA-N sulfur trioxide-pyridine complex Substances O=S(=O)=O.C1=CC=NC=C1 UDYFLDICVHJSOY-UHFFFAOYSA-N 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000007910 systemic administration Methods 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229940095064 tartrate Drugs 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
- QEMXHQIAXOOASZ-UHFFFAOYSA-N tetramethylammonium Chemical class C[N+](C)(C)C QEMXHQIAXOOASZ-UHFFFAOYSA-N 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- DTQVDTLACAAQTR-DYCDLGHISA-N trifluoroacetic acid-d1 Chemical compound [2H]OC(=O)C(F)(F)F DTQVDTLACAAQTR-DYCDLGHISA-N 0.000 description 1
- GRGCWBWNLSTIEN-UHFFFAOYSA-N trifluoromethanesulfonyl chloride Chemical compound FC(F)(F)S(Cl)(=O)=O GRGCWBWNLSTIEN-UHFFFAOYSA-N 0.000 description 1
- 210000001364 upper extremity Anatomy 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D473/00—Heterocyclic compounds containing purine ring systems
- C07D473/02—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6
- C07D473/04—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms
- C07D473/06—Heterocyclic compounds containing purine ring systems with oxygen, sulphur, or nitrogen atoms directly attached in positions 2 and 6 two oxygen atoms with radicals containing only hydrogen and carbon atoms, attached in position 1 or 3
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP34411692 | 1992-12-24 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO934792D0 NO934792D0 (no) | 1993-12-23 |
| NO934792L NO934792L (no) | 1994-06-27 |
| NO300925B1 true NO300925B1 (no) | 1997-08-18 |
Family
ID=18366763
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO934792A NO300925B1 (no) | 1992-12-24 | 1993-12-23 | Xantinderivater |
Country Status (6)
| Country | Link |
|---|---|
| US (1) | US5670498A (de) |
| EP (1) | EP0607607B1 (de) |
| AT (1) | ATE143019T1 (de) |
| CA (1) | CA2112031A1 (de) |
| DE (1) | DE69304883T2 (de) |
| NO (1) | NO300925B1 (de) |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE69526822T2 (de) * | 1994-02-23 | 2003-01-23 | Kyowa Hakko Kogyo K.K., Tokio/Tokyo | Xanthin-derivate |
| WO1999012546A1 (fr) * | 1997-09-05 | 1999-03-18 | Kyowa Hakko Kogyo Co., Ltd. | Remede contre la degenerescence neurale |
| USRE47351E1 (en) | 1999-06-22 | 2019-04-16 | Gilead Sciences, Inc. | 2-(N-pyrazolo)adenosines with application as adenosine A2A receptor agonists |
| US6403567B1 (en) * | 1999-06-22 | 2002-06-11 | Cv Therapeutics, Inc. | N-pyrazole A2A adenosine receptor agonists |
| US6815446B1 (en) | 1999-08-31 | 2004-11-09 | Vanderbilt University | Selective antagonists of A2B adenosine receptors |
| EP1234576B1 (de) * | 1999-10-29 | 2006-03-08 | Kyowa Hakko Kogyo Co., Ltd. | Arzneimittel gegen essstörungen |
| CA2671940A1 (en) * | 2000-02-23 | 2001-08-30 | Cv Therapeutics, Inc. | Identification of partial agonists of the a2a adenosine receptor |
| JP2005538190A (ja) * | 2002-07-29 | 2005-12-15 | シーブイ・セラピューティクス・インコーポレイテッド | 心筋潅流イメージング |
| US8470801B2 (en) | 2002-07-29 | 2013-06-25 | Gilead Sciences, Inc. | Myocardial perfusion imaging methods and compositions |
| US20050020915A1 (en) * | 2002-07-29 | 2005-01-27 | Cv Therapeutics, Inc. | Myocardial perfusion imaging methods and compositions |
| US7148229B2 (en) * | 2003-02-19 | 2006-12-12 | Hoffman-La Roche Inc. | Sulfonamide substituted xanthine derivatives |
| TWI346114B (en) * | 2003-09-29 | 2011-08-01 | Method for stabilization of diarylvinylene compounds | |
| ES2532479T3 (es) * | 2004-01-28 | 2015-03-27 | Kyowa Hakko Kirin Co., Ltd. | Agentes para el tratamiento de la migraña |
| CA2583185A1 (en) | 2004-10-20 | 2006-04-27 | Cv Therapeutics, Inc. | Use of a2a adenosine receptor agonists |
| KR101494125B1 (ko) | 2006-02-03 | 2015-02-16 | 길리애드 사이언시즈, 인코포레이티드 | Ａ2ａ-아데노신 수용체 효능제 및 이의 다형체의 제조 방법 |
| RU2459626C2 (ru) * | 2006-09-01 | 2012-08-27 | Гайлид Сайэнсиз, Инк. | Способы и композиции, повышающие переносимость пациентом методов визуализации миокарда |
| US20090081120A1 (en) * | 2006-09-01 | 2009-03-26 | Cv Therapeutics, Inc. | Methods and Compositions for Increasing Patient Tolerability During Myocardial Imaging Methods |
| EP2066232A1 (de) * | 2006-09-29 | 2009-06-10 | Cv Therapeutics, Inc. | Verfahren zur myokardialen abbildung für patienten mit einer lungenerkrankungs-vorgeschichte |
| WO2008086096A2 (en) * | 2007-01-03 | 2008-07-17 | Cv Therapeutics, Inc. | Myocardial perfusion imaging |
| US8871751B2 (en) * | 2008-01-18 | 2014-10-28 | The Board Of Trustees Of The University Of Illinois | Compositions and methods relating to nuclear hormone and steroid hormone receptors including inhibitors of estrogen receptor alpha-mediated gene expression and inhibition of breast cancer |
| MX2011003168A (es) * | 2008-09-29 | 2011-05-19 | Gilead Sciences Inc | Combinaciones de un agente de control de cantidad y un antagonista del receptor a-2-alfa para utilizarse en metodos de tomografia computarizada de detectores multiples. |
| CN110981876B (zh) * | 2018-12-21 | 2021-10-01 | 广东东阳光药业有限公司 | 8-取代的苯乙烯基黄嘌呤衍生物及其用途 |
| CN111333648B (zh) * | 2019-04-24 | 2021-05-11 | 东莞市东阳光新药研发有限公司 | 8-取代的芳香环乙烯基黄嘌呤衍生物及其用途 |
| CN111072663B (zh) * | 2019-12-12 | 2021-10-01 | 广东东阳光药业有限公司 | 8-取代的苯乙烯基黄嘌呤衍生物及其用途 |
| CN111018856B (zh) * | 2019-12-12 | 2021-10-01 | 广东东阳光药业有限公司 | 8-取代的苯乙烯基黄嘌呤衍生物及其用途 |
| IL296215A (en) * | 2020-03-10 | 2022-11-01 | Marvel Biotechnology | Purine compounds for the treatment of diseases |
| CN113248505B (zh) * | 2021-06-09 | 2021-09-21 | 南京安杰新生物医药有限公司 | 伊曲茶碱去甲基杂质的制备方法 |
| WO2023097402A1 (en) * | 2021-12-03 | 2023-06-08 | Marvel Biotechnology | Purine compounds for treating disorders |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4452788A (en) * | 1982-04-21 | 1984-06-05 | Warner-Lambert Company | Substituted 8-phenylxanthines |
| GB8510758D0 (en) * | 1985-04-27 | 1985-06-05 | Wellcome Found | Compounds |
| ATE195739T1 (de) * | 1989-10-20 | 2000-09-15 | Kyowa Hakko Kogyo Kk | Kondensierte purinderivate |
| ATE176470T1 (de) * | 1990-10-18 | 1999-02-15 | Kyowa Hakko Kogyo Kk | Xanthinderivate |
-
1993
- 1993-12-21 CA CA002112031A patent/CA2112031A1/en not_active Abandoned
- 1993-12-23 NO NO934792A patent/NO300925B1/no not_active IP Right Cessation
- 1993-12-23 DE DE69304883T patent/DE69304883T2/de not_active Expired - Fee Related
- 1993-12-23 AT AT93120842T patent/ATE143019T1/de not_active IP Right Cessation
- 1993-12-23 EP EP93120842A patent/EP0607607B1/de not_active Expired - Lifetime
-
1995
- 1995-09-13 US US08/527,497 patent/US5670498A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| DE69304883D1 (de) | 1996-10-24 |
| EP0607607B1 (de) | 1996-09-18 |
| ATE143019T1 (de) | 1996-10-15 |
| NO934792L (no) | 1994-06-27 |
| NO934792D0 (no) | 1993-12-23 |
| CA2112031A1 (en) | 1994-06-25 |
| EP0607607A1 (de) | 1994-07-27 |
| DE69304883T2 (de) | 1997-05-15 |
| US5670498A (en) | 1997-09-23 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM1K | Lapsed by not paying the annual fees |