CA1296001C - 1-hydroxyalkylxanthines, processes for their preparation and medicaments containing them - Google Patents
1-hydroxyalkylxanthines, processes for their preparation and medicaments containing themInfo
- Publication number
- CA1296001C CA1296001C CA000550244A CA550244A CA1296001C CA 1296001 C CA1296001 C CA 1296001C CA 000550244 A CA000550244 A CA 000550244A CA 550244 A CA550244 A CA 550244A CA 1296001 C CA1296001 C CA 1296001C
- Authority
- CA
- Canada
- Prior art keywords
- xanthine
- compound
- methyl
- propyl
- alkyl group
- 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.)
- Expired - Fee Related
Links
- 238000000034 method Methods 0.000 title claims abstract description 16
- 238000002360 preparation method Methods 0.000 title claims abstract description 6
- 239000003814 drug Substances 0.000 title abstract description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 35
- 150000003839 salts Chemical class 0.000 claims abstract description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 8
- -1 R8 is H Chemical group 0.000 claims abstract description 6
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 4
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract 4
- 239000002168 alkylating agent Substances 0.000 claims description 6
- 229940100198 alkylating agent Drugs 0.000 claims description 6
- 150000002148 esters Chemical class 0.000 claims description 4
- 230000002829 reductive effect Effects 0.000 claims description 4
- DQGDSGQAZDWEIB-UHFFFAOYSA-N 1-(3-hydroxybutyl)-3-(2-methylpropyl)-7h-purine-2,6-dione Chemical compound O=C1N(CCC(C)O)C(=O)N(CC(C)C)C2=C1NC=N2 DQGDSGQAZDWEIB-UHFFFAOYSA-N 0.000 claims description 3
- NWJJZOITSANPIZ-UHFFFAOYSA-N 1-(5-hydroxypentyl)-8-methyl-3-propyl-7h-purine-2,6-dione Chemical compound O=C1N(CCCCCO)C(=O)N(CCC)C2=C1NC(C)=N2 NWJJZOITSANPIZ-UHFFFAOYSA-N 0.000 claims description 3
- KXNKCLAMHGIOHR-UHFFFAOYSA-N 3-butyl-1-(4-hydroxybutyl)-7h-purine-2,6-dione Chemical compound O=C1N(CCCCO)C(=O)N(CCCC)C2=C1NC=N2 KXNKCLAMHGIOHR-UHFFFAOYSA-N 0.000 claims description 3
- 125000000217 alkyl group Chemical group 0.000 claims description 3
- PPKCADWHBHKMRY-UHFFFAOYSA-N 1-(2-hydroxyethyl)-3-propyl-7h-purine-2,6-dione Chemical compound O=C1N(CCO)C(=O)N(CCC)C2=C1NC=N2 PPKCADWHBHKMRY-UHFFFAOYSA-N 0.000 claims description 2
- RJTLNEGJDDHQFR-UHFFFAOYSA-N 1-(2-hydroxypropyl)-3-propyl-7h-purine-2,6-dione Chemical compound O=C1N(CC(C)O)C(=O)N(CCC)C2=C1NC=N2 RJTLNEGJDDHQFR-UHFFFAOYSA-N 0.000 claims description 2
- BCCWRHNOLDRMGF-UHFFFAOYSA-N 1-(3-hydroxybutyl)-3-methyl-7h-purine-2,6-dione Chemical compound O=C1N(CCC(O)C)C(=O)N(C)C2=C1NC=N2 BCCWRHNOLDRMGF-UHFFFAOYSA-N 0.000 claims description 2
- WJDXXRCYTRARFB-UHFFFAOYSA-N 1-(3-hydroxybutyl)-3-propyl-7h-purine-2,6-dione Chemical compound O=C1N(CCC(C)O)C(=O)N(CCC)C2=C1NC=N2 WJDXXRCYTRARFB-UHFFFAOYSA-N 0.000 claims description 2
- XYKCXIKMARUABR-UHFFFAOYSA-N 1-(3-hydroxypropyl)-3-(2-methylpropyl)-7h-purine-2,6-dione Chemical compound O=C1N(CCCO)C(=O)N(CC(C)C)C2=C1NC=N2 XYKCXIKMARUABR-UHFFFAOYSA-N 0.000 claims description 2
- MLQJLDJELAVLSY-UHFFFAOYSA-N 1-(3-hydroxypropyl)-3-propyl-7h-purine-2,6-dione Chemical compound O=C1N(CCCO)C(=O)N(CCC)C2=C1NC=N2 MLQJLDJELAVLSY-UHFFFAOYSA-N 0.000 claims description 2
- KQHIXQSIRSNUOB-UHFFFAOYSA-N 1-(3-hydroxypropyl)-8-methyl-3-(2-methylpropyl)-7h-purine-2,6-dione Chemical compound O=C1N(CCCO)C(=O)N(CC(C)C)C2=C1NC(C)=N2 KQHIXQSIRSNUOB-UHFFFAOYSA-N 0.000 claims description 2
- GTLSSMDMVGJFEQ-UHFFFAOYSA-N 1-(3-hydroxypropyl)-8-methyl-3-propyl-7h-purine-2,6-dione Chemical compound O=C1N(CCCO)C(=O)N(CCC)C2=C1NC(C)=N2 GTLSSMDMVGJFEQ-UHFFFAOYSA-N 0.000 claims description 2
- FEIKMJIHZWZNDO-UHFFFAOYSA-N 1-(4-hydroxybutyl)-3-propyl-7h-purine-2,6-dione Chemical compound O=C1N(CCCCO)C(=O)N(CCC)C2=C1NC=N2 FEIKMJIHZWZNDO-UHFFFAOYSA-N 0.000 claims description 2
- DDUPCWHWLADGGA-UHFFFAOYSA-N 1-(4-hydroxybutyl)-8-methyl-3-(2-methylpropyl)-7h-purine-2,6-dione Chemical compound O=C1N(CCCCO)C(=O)N(CC(C)C)C2=C1NC(C)=N2 DDUPCWHWLADGGA-UHFFFAOYSA-N 0.000 claims description 2
- JIBYCMGGUVOCQI-UHFFFAOYSA-N 1-(4-hydroxybutyl)-8-methyl-3-propyl-7h-purine-2,6-dione Chemical compound O=C1N(CCCCO)C(=O)N(CCC)C2=C1NC(C)=N2 JIBYCMGGUVOCQI-UHFFFAOYSA-N 0.000 claims description 2
- NDNNJYYEMVEBMY-UHFFFAOYSA-N 1-(4-hydroxypentyl)-3-methyl-7h-purine-2,6-dione Chemical compound O=C1N(CCCC(O)C)C(=O)N(C)C2=C1NC=N2 NDNNJYYEMVEBMY-UHFFFAOYSA-N 0.000 claims description 2
- OQWOQWAYOVAQBU-UHFFFAOYSA-N 1-(4-hydroxypentyl)-3-propyl-7h-purine-2,6-dione Chemical compound O=C1N(CCCC(C)O)C(=O)N(CCC)C2=C1NC=N2 OQWOQWAYOVAQBU-UHFFFAOYSA-N 0.000 claims description 2
- ARZCFOQRJQJLOL-UHFFFAOYSA-N 1-(5-hydroxypentyl)-3-methyl-7h-purine-2,6-dione Chemical compound O=C1N(CCCCCO)C(=O)N(C)C2=C1NC=N2 ARZCFOQRJQJLOL-UHFFFAOYSA-N 0.000 claims description 2
- XYNDWTKJLGSVIO-UHFFFAOYSA-N 3-butyl-1-(2-hydroxypropyl)-7h-purine-2,6-dione Chemical compound O=C1N(CC(C)O)C(=O)N(CCCC)C2=C1NC=N2 XYNDWTKJLGSVIO-UHFFFAOYSA-N 0.000 claims description 2
- DUIPGIVJYFFGRO-UHFFFAOYSA-N 3-butyl-1-(3-hydroxypropyl)-7h-purine-2,6-dione Chemical compound O=C1N(CCCO)C(=O)N(CCCC)C2=C1NC=N2 DUIPGIVJYFFGRO-UHFFFAOYSA-N 0.000 claims description 2
- PPVOZPCGSDKACI-UHFFFAOYSA-N 3-ethyl-1-(3-hydroxybutyl)-7h-purine-2,6-dione Chemical compound O=C1N(CCC(C)O)C(=O)N(CC)C2=C1NC=N2 PPVOZPCGSDKACI-UHFFFAOYSA-N 0.000 claims description 2
- SOPMHRXOQFAEMG-UHFFFAOYSA-N 3-ethyl-1-(3-hydroxybutyl)-8-methyl-7h-purine-2,6-dione Chemical compound O=C1N(CCC(C)O)C(=O)N(CC)C2=C1NC(C)=N2 SOPMHRXOQFAEMG-UHFFFAOYSA-N 0.000 claims description 2
- SNGZYEFKXPNBQB-UHFFFAOYSA-N 8-ethyl-1-(3-hydroxypropyl)-3-propyl-7h-purine-2,6-dione Chemical compound O=C1N(CCCO)C(=O)N(CCC)C2=C1NC(CC)=N2 SNGZYEFKXPNBQB-UHFFFAOYSA-N 0.000 claims description 2
- 238000007259 addition reaction Methods 0.000 claims description 2
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- VFNGKCDDZUSWLR-UHFFFAOYSA-L disulfate(2-) Chemical compound [O-]S(=O)(=O)OS([O-])(=O)=O VFNGKCDDZUSWLR-UHFFFAOYSA-L 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 2
- PKBQHRPGEFVUJP-UHFFFAOYSA-N 1-(5-hydroxypentyl)-3-propyl-7h-purine-2,6-dione Chemical compound O=C1N(CCCCCO)C(=O)N(CCC)C2=C1NC=N2 PKBQHRPGEFVUJP-UHFFFAOYSA-N 0.000 claims 1
- 229940065721 systemic for obstructive airway disease xanthines Drugs 0.000 abstract description 8
- 230000005792 cardiovascular activity Effects 0.000 abstract description 2
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 27
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical class O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 26
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
- 239000000243 solution Substances 0.000 description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
- 239000000047 product Substances 0.000 description 13
- 239000002904 solvent Substances 0.000 description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
- ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 10
- 229940075420 xanthine Drugs 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 239000000203 mixture Substances 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 230000000875 corresponding effect Effects 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 229940035893 uracil Drugs 0.000 description 5
- 238000005804 alkylation reaction Methods 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 4
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 3
- 239000000376 reactant Substances 0.000 description 3
- 239000000377 silicon dioxide Substances 0.000 description 3
- 125000001424 substituent group Chemical group 0.000 description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 229910010084 LiAlH4 Inorganic materials 0.000 description 2
- HFEFMUSTGZNOPY-UHFFFAOYSA-N OOOOOOOOOOOOOOOO Chemical compound OOOOOOOOOOOOOOOO HFEFMUSTGZNOPY-UHFFFAOYSA-N 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 230000000949 anxiolytic effect Effects 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 229940124461 cardiostimulant Drugs 0.000 description 2
- 230000003177 cardiotonic effect Effects 0.000 description 2
- 230000008602 contraction Effects 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 239000003480 eluent Substances 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 239000012280 lithium aluminium hydride Substances 0.000 description 2
- BRMYZIKAHFEUFJ-UHFFFAOYSA-L mercury diacetate Chemical compound CC(=O)O[Hg]OC(C)=O BRMYZIKAHFEUFJ-UHFFFAOYSA-L 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 229960000278 theophylline Drugs 0.000 description 2
- FQUJKOSQZZWJMY-UHFFFAOYSA-N 1-(2-hydroxyethyl)-3-(2-methylpropyl)-7h-purine-2,6-dione Chemical compound O=C1N(CCO)C(=O)N(CC(C)C)C2=C1NC=N2 FQUJKOSQZZWJMY-UHFFFAOYSA-N 0.000 description 1
- DMGPILXIKRESOB-UHFFFAOYSA-N 1-(2-hydroxyethyl)-8-methyl-3-(2-methylpropyl)-7h-purine-2,6-dione Chemical compound O=C1N(CCO)C(=O)N(CC(C)C)C2=C1NC(C)=N2 DMGPILXIKRESOB-UHFFFAOYSA-N 0.000 description 1
- RSGCBTHHNSSFPB-UHFFFAOYSA-N 1-(2-hydroxypropyl)-8-methyl-3-propyl-7h-purine-2,6-dione Chemical compound O=C1N(CC(C)O)C(=O)N(CCC)C2=C1NC(C)=N2 RSGCBTHHNSSFPB-UHFFFAOYSA-N 0.000 description 1
- DBCGVTTVZUPQEI-UHFFFAOYSA-N 3-ethyl-1-(4-hydroxybutyl)-7h-purine-2,6-dione Chemical compound O=C1N(CCCCO)C(=O)N(CC)C2=C1NC=N2 DBCGVTTVZUPQEI-UHFFFAOYSA-N 0.000 description 1
- DMAYBPBPEUFIHJ-UHFFFAOYSA-N 4-bromobut-1-ene Chemical compound BrCCC=C DMAYBPBPEUFIHJ-UHFFFAOYSA-N 0.000 description 1
- WJVQJXVMLRGNGA-UHFFFAOYSA-N 5-bromopentan-1-ol Chemical compound OCCCCCBr WJVQJXVMLRGNGA-UHFFFAOYSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical class [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 229910001854 alkali hydroxide Inorganic materials 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 229960001948 caffeine Drugs 0.000 description 1
- VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000009084 cardiovascular function Effects 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- XBPOBCXHALHJFP-UHFFFAOYSA-N ethyl 4-bromobutanoate Chemical compound CCOC(=O)CCCBr XBPOBCXHALHJFP-UHFFFAOYSA-N 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000036571 hydration Effects 0.000 description 1
- 238000006703 hydration reaction Methods 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 230000000297 inotrophic effect Effects 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- PZRHRDRVRGEVNW-UHFFFAOYSA-N milrinone Chemical compound N1C(=O)C(C#N)=CC(C=2C=CN=CC=2)=C1C PZRHRDRVRGEVNW-UHFFFAOYSA-N 0.000 description 1
- 229960003574 milrinone Drugs 0.000 description 1
- PYPVYGKAJIDXSX-UHFFFAOYSA-N n-(6-amino-1-butyl-2,4-dioxopyrimidin-5-yl)formamide Chemical compound CCCCN1C(N)=C(NC=O)C(=O)NC1=O PYPVYGKAJIDXSX-UHFFFAOYSA-N 0.000 description 1
- BTDMXPMYBOWGAG-UHFFFAOYSA-N n-(6-amino-2,4-dioxo-1-propylpyrimidin-5-yl)acetamide Chemical compound CCCN1C(N)=C(NC(C)=O)C(=O)NC1=O BTDMXPMYBOWGAG-UHFFFAOYSA-N 0.000 description 1
- JCMGISAKAKWXFX-UHFFFAOYSA-N n-[6-amino-1-(2-methylpropyl)-2,4-dioxopyrimidin-5-yl]formamide Chemical compound CC(C)CN1C(N)=C(NC=O)C(=O)NC1=O JCMGISAKAKWXFX-UHFFFAOYSA-N 0.000 description 1
- 239000003176 neuroleptic agent Substances 0.000 description 1
- 230000000701 neuroleptic effect Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 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
- 239000012429 reaction media Substances 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 238000011287 therapeutic dose Methods 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
- C07D473/08—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 with methyl radicals in positions 1 and 3, e.g. theophylline
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Heart & Thoracic Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH4253/86-8 | 1986-10-27 | ||
| CH4253/86A CH670090A5 (enrdf_load_stackoverflow) | 1986-10-27 | 1986-10-27 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1296001C true CA1296001C (en) | 1992-02-18 |
Family
ID=4272668
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000550244A Expired - Fee Related CA1296001C (en) | 1986-10-27 | 1987-10-26 | 1-hydroxyalkylxanthines, processes for their preparation and medicaments containing them |
Country Status (13)
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0570831A2 (de) * | 1992-05-20 | 1993-11-24 | Hoechst Aktiengesellschaft | Verwendung von Xanthinderivaten zur Behandlung von Nervenschädigungen nach Unterbrechung der Blutzirkulation |
| DE4316576A1 (de) * | 1993-05-18 | 1994-11-24 | Boehringer Ingelheim Kg | Verbessertes Verfahren zur Herstellung von 1,3-Dipropyl-8-(3-Oxocyclopentyl)-xanthin |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2517410A (en) * | 1947-08-15 | 1950-08-01 | Searle & Co | Hydroxy alkyl xanthines and the production thereof |
| FR1211333A (fr) * | 1955-10-19 | 1960-03-15 | Boehringer Sohn Ingelheim | Perfectionnements apportés aux procédés pour fabriquer des oxyalcoylxanthines |
| US4567183A (en) * | 1983-03-11 | 1986-01-28 | Analgesic Associates | Analgesic and anti-inflammatory compositions comprising xanthines and methods of using same |
| US4558051A (en) * | 1983-10-11 | 1985-12-10 | Richardson-Vicks, Inc. | Analgesic and anti-inflammatory compositions comprising xanthines and methods of using same |
-
1986
- 1986-10-27 CH CH4253/86A patent/CH670090A5/fr not_active IP Right Cessation
-
1987
- 1987-10-19 ZA ZA877851A patent/ZA877851B/xx unknown
- 1987-10-21 DK DK551487A patent/DK169336B1/da not_active IP Right Cessation
- 1987-10-21 AU AU79980/87A patent/AU604767B2/en not_active Ceased
- 1987-10-23 EP EP87115591A patent/EP0269841B1/fr not_active Expired - Lifetime
- 1987-10-23 ES ES87115591T patent/ES2043631T3/es not_active Expired - Lifetime
- 1987-10-23 DE DE8787115591T patent/DE3782619T2/de not_active Expired - Fee Related
- 1987-10-23 AT AT87115591T patent/ATE82289T1/de active
- 1987-10-25 IL IL84266A patent/IL84266A/xx not_active IP Right Cessation
- 1987-10-26 KR KR1019870011905A patent/KR930010559B1/ko not_active Expired - Fee Related
- 1987-10-26 CA CA000550244A patent/CA1296001C/en not_active Expired - Fee Related
- 1987-10-27 JP JP62271591A patent/JP2527769B2/ja not_active Expired - Lifetime
-
1992
- 1992-11-12 GR GR920402559T patent/GR3006223T3/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JPS63122683A (ja) | 1988-05-26 |
| IL84266A0 (en) | 1988-03-31 |
| GR3006223T3 (enrdf_load_stackoverflow) | 1993-06-21 |
| DK551487D0 (da) | 1987-10-21 |
| KR930010559B1 (ko) | 1993-10-28 |
| EP0269841A1 (fr) | 1988-06-08 |
| JP2527769B2 (ja) | 1996-08-28 |
| DK169336B1 (da) | 1994-10-10 |
| DE3782619D1 (de) | 1992-12-17 |
| EP0269841B1 (fr) | 1992-11-11 |
| ES2043631T3 (es) | 1994-01-01 |
| ATE82289T1 (de) | 1992-11-15 |
| AU7998087A (en) | 1988-04-28 |
| DK551487A (da) | 1988-04-28 |
| KR880005131A (ko) | 1988-06-28 |
| DE3782619T2 (de) | 1993-04-22 |
| CH670090A5 (enrdf_load_stackoverflow) | 1989-05-12 |
| AU604767B2 (en) | 1991-01-03 |
| ZA877851B (en) | 1988-04-22 |
| IL84266A (en) | 1992-02-16 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKLA | Lapsed |