NO300925B1 - Xantinderivater - Google Patents

Xantinderivater Download PDF

Info

Publication number: NO300925B1
Authority: NO; Norway
Prior art keywords: compound; mmol; lower alkyl; methyl; nmr
Prior art date: 1992-12-24

Application number

NO934792A

Other languages

English (en)

Norwegian (no)

Other versions

NO934792L (no

NO934792D0 (no

Inventor

Fumio Suzuki

Junichi Shimada

Nobuaki Koike

Hiroshi Kase

Joji Nakamura

Shizuo Shiozaki

Hiromi Nonaka

Original Assignee

Kyowa Hakko Kogyo Kk

Priority date (The priority date 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 date listed.)

1992-12-24

Filing date

1993-12-23

Publication date

1997-08-18

1993-12-23 Application filed by Kyowa Hakko Kogyo Kk filed Critical Kyowa Hakko Kogyo Kk

1993-12-23 Publication of NO934792D0 publication Critical patent/NO934792D0/no

1994-06-27 Publication of NO934792L publication Critical patent/NO934792L/no

1997-08-18 Publication of NO300925B1 publication Critical patent/NO300925B1/no

Links

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
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
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
AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 4
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
150000001412 amines Chemical class 0.000 description 4
208000006673 asthma Diseases 0.000 description 4
239000000872 buffer Substances 0.000 description 4
239000000460 chlorine Substances 0.000 description 4
229910052801 chlorine Inorganic materials 0.000 description 4
XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 4
229960001760 dimethyl sulfoxide Drugs 0.000 description 4
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208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 4
150000008282 halocarbons Chemical class 0.000 description 4
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230000005764 inhibitory process Effects 0.000 description 4
239000006188 syrup Substances 0.000 description 4
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VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
UAOUIVVJBYDFKD-XKCDOFEDSA-N (1R,9R,10S,11R,12R,15S,18S,21R)-10,11,21-trihydroxy-8,8-dimethyl-14-methylidene-4-(prop-2-enylamino)-20-oxa-5-thia-3-azahexacyclo[9.7.2.112,15.01,9.02,6.012,18]henicosa-2(6),3-dien-13-one Chemical compound C([C@@H]1[C@@H](O)[C@@]23C(C1=C)=O)C[C@H]2[C@]12C(N=C(NCC=C)S4)=C4CC(C)(C)[C@H]1[C@H](O)[C@]3(O)OC2 UAOUIVVJBYDFKD-XKCDOFEDSA-N 0.000 description 3
WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 3
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 3
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CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
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241000699666 Mus <mouse, genus> Species 0.000 description 3
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
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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)

NO934792A 1992-12-24 1993-12-23 Xantinderivater NO300925B1 (no)

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 (fr)
EP (1)	EP0607607B1 (fr)
AT (1)	ATE143019T1 (fr)
CA (1)	CA2112031A1 (fr)
DE (1)	DE69304883T2 (fr)
NO (1)	NO300925B1 (fr)

Families Citing this family (28)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
AU1823895A (en) *	1994-02-23	1995-09-11	Kyowa Hakko Kogyo Co. Ltd.	Xanthine derivative
US6727259B2 (en)	1997-09-05	2004-04-27	Kyowa Hakko Kogyo Co., Ltd.	Remedial agent for neural degeneration
US6403567B1 (en)	1999-06-22	2002-06-11	Cv Therapeutics, Inc.	N-pyrazole A2A adenosine receptor agonists
USRE47351E1 (en)	1999-06-22	2019-04-16	Gilead Sciences, Inc.	2-(N-pyrazolo)adenosines with application as adenosine A2A receptor agonists
US6815446B1 (en)	1999-08-31	2004-11-09	Vanderbilt University	Selective antagonists of A2B adenosine receptors
EP1234576B1 (fr) *	1999-10-29	2006-03-08	Kyowa Hakko Kogyo Co., Ltd.	Remedes contre les troubles de l'alimentation
WO2001062979A2 (fr) *	2000-02-23	2001-08-30	Cv Therapeutics, Inc.	Procede permettant d'identifier des agonistes partiels du recepteur a¿2a?
US8470801B2 (en)	2002-07-29	2013-06-25	Gilead Sciences, Inc.	Myocardial perfusion imaging methods and compositions
US7683037B2 (en) *	2002-07-29	2010-03-23	Gilead Palo Alto, Inc.	Myocardial perfusion imaging method
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
AU2005295437B2 (en)	2004-10-20	2011-05-19	Gilead Palo Alto, Inc.	Use of A2A adenosine receptor agonists
ES2593028T3 (es)	2006-02-03	2016-12-05	Gilead Sciences, Inc.	Proceso para preparar un agonista de receptor de adenosina A2A y sus polimorfos
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 (fr) *	2006-09-29	2009-06-10	Cv Therapeutics, Inc.	Procédés d'imagerie myocardique chez des patients ayant un historique de maladie pulmonaire
US20080267861A1 (en) *	2007-01-03	2008-10-30	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
CA2737077A1 (fr) *	2008-09-29	2010-04-01	Gilead Sciences, Inc.	Combinaisons d'agent de regulation de la frequence cardiaque et d'antagoniste de recepteur a-2-alpha utilisees dans des procedes de tomographie a detecteurs multiples assistee par ordinateur
WO2020125779A1 (fr) *	2018-12-21	2020-06-25	Sunshine Lake Pharma Co., Ltd.	Dérivés de styryl xanthine substitués en position 8 et leurs utilisations
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
AU2021235803A1 (en) *	2020-03-10	2022-09-29	Marvel Biotechnology	Purine compounds for treating disorders
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 (fr) *	2021-12-03	2023-06-08	Marvel Biotechnology	Composés de purine pour le traitement de troubles

Family Cites Families (4)

* Cited by examiner, † Cited by third party
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
US5270316A (en) *	1989-10-20	1993-12-14	Kyowa Hakko Kogyo Co., Ltd.	Condensed purine derivatives
WO1992006976A1 (fr) *	1990-10-18	1992-04-30	Kyowa Hakko Kogyo Co., Ltd.	Derive de xanthine

1993
- 1993-12-21 CA CA002112031A patent/CA2112031A1/fr not_active Abandoned
- 1993-12-23 EP EP93120842A patent/EP0607607B1/fr not_active Expired - Lifetime
- 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
1995
- 1995-09-13 US US08/527,497 patent/US5670498A/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
ATE143019T1 (de)	1996-10-15
CA2112031A1 (fr)	1994-06-25
NO934792L (no)	1994-06-27
US5670498A (en)	1997-09-23
NO934792D0 (no)	1993-12-23
DE69304883D1 (de)	1996-10-24
EP0607607A1 (fr)	1994-07-27
EP0607607B1 (fr)	1996-09-18
DE69304883T2 (de)	1997-05-15

Publication	Publication Date	Title
NO300925B1 (no)	1997-08-18	Xantinderivater
EP1319003B1 (fr)	2009-06-10	Xanthines, inhibiteurs de la phosphodiesterase de type v
US7625881B2 (en)	2009-12-01	Prodrugs of A2B adenosine receptor antagonists
US7521554B2 (en)	2009-04-21	A2B adenosine receptor antagonists
WO1995023148A1 (fr)	1995-08-31	Derive de la xanthine
AU2001291022A1 (en)	2002-06-20	Xanthine phosphodiesterase v inhibitors
ES2218439T3 (es)	2004-11-16	Indoloquinazolinonas.
US7776868B2 (en)	2010-08-17	Substituted bicyclic and tricyclic thieno[2,3-d]pyrimidines as A2A adenosine receptor antagonists
EP0559893A1 (fr)	1993-09-15	Derive de xanthine
JPH0616559A (ja)	1994-01-25	パーキンソン病治療剤
US6187780B1 (en)	2001-02-13	Assymetrically substituted xanthine derivatives having adenosine A1 antagonistic activity
CN111303147B (zh)	2024-07-02	吡啶酮衍生物、其组合物及作为抗流感病毒药物的应用
EP0386722B1 (fr)	1995-07-26	Dérivés de l'imidazoquinolone
EP1440075B1 (fr)	2005-06-08	Nouveaux derives amides heteroaromatiques de 3beta-amino azabicyclooctane, leur procede de preparation et leurs applications en therapeutique
JP2002512246A (ja)	2002-04-23	非対称的に置換した新規キサンチン誘導体、その製造方法及びそのアデノシン拮抗作用を有する医薬としての使用
JP3165769B2 (ja)	2001-05-14	キサンチン誘導体
JP2988692B2 (ja)	1999-12-13	イミダゾキノロン誘導体
GB2107709A (en)	1983-05-05	Xanthines
JP2988683B2 (ja)	1999-12-13	イミダゾキノロン誘導体
CA2084669C (fr)	2001-10-30	[3h,7h]thiazolo[3,4-a]pyridines ayant une action anti-asthmatique et anti-inflammatoire sur les voies respiratoires
US20130096135A1 (en)	2013-04-18	Selected Inhibitors of Protein Tyrosine Kinase Activity
JP2843671B2 (ja)	1999-01-06	キサンチン誘導体
JPH01156978A (ja)	1989-06-20	新規なキサンチン誘導体

Legal Events

Date	Code	Title	Description
2005-09-12	MM1K	Lapsed by not paying the annual fees