IL93832A - 1,3,8-freshly-converted xanthines, their preparation and pharmaceutical preparations containing them - Google Patents

1,3,8-freshly-converted xanthines, their preparation and pharmaceutical preparations containing them

Info

Publication number: IL93832A
Authority: IL; Israel
Prior art keywords: group; formula; bis; compound; xanthine
Prior art date: 1989-03-23

Application number

IL9383290A

Other languages

English (en)

Hebrew (he)

Other versions

IL93832A0 (en

Original Assignee

Beecham Wuelfing Gmbh & Co Kg

Beecham Group Plc

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.)

1989-03-23

Filing date

1990-03-21

Publication date

1994-07-31

1990-03-21 Application filed by Beecham Wuelfing Gmbh & Co Kg, Beecham Group Plc filed Critical Beecham Wuelfing Gmbh & Co Kg

1990-12-23 Publication of IL93832A0 publication Critical patent/IL93832A0/xx

1994-07-31 Publication of IL93832A publication Critical patent/IL93832A/en

Links

238000002360 preparation method Methods 0.000 title claims description 32
239000008194 pharmaceutical composition Substances 0.000 title claims description 5
-1 1,3,8-trisubstituted xanthines Chemical class 0.000 title description 13
150000001875 compounds Chemical class 0.000 claims abstract description 117
238000000034 method Methods 0.000 claims abstract description 56
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 29
150000003839 salts Chemical class 0.000 claims abstract description 28
125000005843 halogen group Chemical group 0.000 claims abstract description 16
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 16
125000004448 alkyl carbonyl group Chemical group 0.000 claims abstract description 13
125000000217 alkyl group Chemical group 0.000 claims abstract description 13
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 13
239000001257 hydrogen Substances 0.000 claims abstract description 13
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 8
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 6
125000004435 hydrogen atom Chemical class [H]* 0.000 claims abstract description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 4
LRFVTYWOQMYALW-UHFFFAOYSA-N Xanthine Natural products O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 claims description 18
238000006243 chemical reaction Methods 0.000 claims description 17
230000008569 process Effects 0.000 claims description 14
229940075420 xanthine Drugs 0.000 claims description 13
125000003277 amino group Chemical group 0.000 claims description 10
239000003795 chemical substances by application Substances 0.000 claims description 9
239000003153 chemical reaction reagent Substances 0.000 claims description 8
125000006413 ring segment Chemical group 0.000 claims description 7
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 6
150000002431 hydrogen Chemical class 0.000 claims description 5
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
230000000802 nitrating effect Effects 0.000 claims description 4
125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 3
125000005842 heteroatom Chemical group 0.000 claims description 3
YWIDXLMXWUIXOJ-UHFFFAOYSA-N 1,3-bis(cyclohexylmethyl)-8-nitro-7h-purine-2,6-dione Chemical compound O=C1N(CC2CCCCC2)C(=O)C=2NC([N+](=O)[O-])=NC=2N1CC1CCCCC1 YWIDXLMXWUIXOJ-UHFFFAOYSA-N 0.000 claims description 2
125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
230000002152 alkylating effect Effects 0.000 claims 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 claims description 2
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
229910052717 sulfur Inorganic materials 0.000 claims description 2
125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims 4
125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 3
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims 2
KSPYMJJKQMWWNB-UHFFFAOYSA-N cipamfylline Chemical compound O=C1N(CC2CC2)C(=O)C=2NC(N)=NC=2N1CC1CC1 KSPYMJJKQMWWNB-UHFFFAOYSA-N 0.000 claims 1
125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 claims 1
125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 claims 1
125000002757 morpholinyl group Chemical group 0.000 claims 1
125000003386 piperidinyl group Chemical group 0.000 claims 1
239000000203 mixture Substances 0.000 abstract description 25
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 17
238000011282 treatment Methods 0.000 abstract description 12
230000002490 cerebral effect Effects 0.000 abstract description 6
208000026106 cerebrovascular disease Diseases 0.000 abstract description 2
231100000252 nontoxic Toxicity 0.000 abstract description 2
230000003000 nontoxic effect Effects 0.000 abstract description 2
239000007787 solid Substances 0.000 description 15
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 15
208000035475 disorder Diseases 0.000 description 14
239000000047 product Substances 0.000 description 14
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
238000005481 NMR spectroscopy Methods 0.000 description 11
239000002904 solvent Substances 0.000 description 9
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
239000003981 vehicle Substances 0.000 description 8
210000004369 blood Anatomy 0.000 description 7
239000008280 blood Substances 0.000 description 7
230000000694 effects Effects 0.000 description 7
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
229920005654 Sephadex Polymers 0.000 description 6
239000012507 Sephadex™ Substances 0.000 description 6
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
239000002253 acid Substances 0.000 description 6
239000002585 base Substances 0.000 description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
238000012360 testing method Methods 0.000 description 6
241001465754 Metazoa Species 0.000 description 5
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
125000004432 carbon atom Chemical group C* 0.000 description 5
229940079593 drug Drugs 0.000 description 5
239000003814 drug Substances 0.000 description 5
230000000302 ischemic effect Effects 0.000 description 5
230000000144 pharmacologic effect Effects 0.000 description 5
238000003756 stirring Methods 0.000 description 5
102000004861 Phosphoric Diester Hydrolases Human genes 0.000 description 4
108090001050 Phosphoric Diester Hydrolases Proteins 0.000 description 4
241000700159 Rattus Species 0.000 description 4
239000006071 cream Substances 0.000 description 4
210000003743 erythrocyte Anatomy 0.000 description 4
235000019441 ethanol Nutrition 0.000 description 4
238000009472 formulation Methods 0.000 description 4
239000000499 gel Substances 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
230000002062 proliferating effect Effects 0.000 description 4
238000011321 prophylaxis Methods 0.000 description 4
125000006239 protecting group Chemical group 0.000 description 4
210000002345 respiratory system Anatomy 0.000 description 4
208000017520 skin disease Diseases 0.000 description 4
JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 4
239000000243 solution Substances 0.000 description 4
238000005160 1H NMR spectroscopy Methods 0.000 description 3
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
206010014950 Eosinophilia Diseases 0.000 description 3
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
206010039966 Senile dementia Diseases 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
239000000443 aerosol Substances 0.000 description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
238000011049 filling Methods 0.000 description 3
230000002140 halogenating effect Effects 0.000 description 3
239000007788 liquid Substances 0.000 description 3
239000006210 lotion Substances 0.000 description 3
238000002156 mixing Methods 0.000 description 3
239000002674 ointment Substances 0.000 description 3
239000000546 pharmaceutical excipient Substances 0.000 description 3
239000000843 powder Substances 0.000 description 3
239000003755 preservative agent Substances 0.000 description 3
239000011780 sodium chloride Substances 0.000 description 3
229910052938 sodium sulfate Inorganic materials 0.000 description 3
235000011152 sodium sulphate Nutrition 0.000 description 3
239000000600 sorbitol Substances 0.000 description 3
235000010356 sorbitol Nutrition 0.000 description 3
239000000725 suspension Substances 0.000 description 3
235000020357 syrup Nutrition 0.000 description 3
239000006188 syrup Substances 0.000 description 3
239000003826 tablet Substances 0.000 description 3
239000012049 topical pharmaceutical composition Substances 0.000 description 3
KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 2
SVZORQBLCFZGBK-UHFFFAOYSA-N 1,3-bis(cyclohexylmethyl)urea Chemical compound C1CCCCC1CNC(=O)NCC1CCCCC1 SVZORQBLCFZGBK-UHFFFAOYSA-N 0.000 description 2
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
LNDZXOWGUAIUBG-UHFFFAOYSA-N 6-aminouracil Chemical compound NC1=CC(=O)NC(=O)N1 LNDZXOWGUAIUBG-UHFFFAOYSA-N 0.000 description 2
PKUFNWPSFCOSLU-UHFFFAOYSA-N 6-chloro-1h-pyrimidine-2,4-dione Chemical compound ClC1=CC(=O)NC(=O)N1 PKUFNWPSFCOSLU-UHFFFAOYSA-N 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
206010003645 Atopy Diseases 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
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 2
201000004624 Dermatitis Diseases 0.000 description 2
206010012438 Dermatitis atopic Diseases 0.000 description 2
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
108010010803 Gelatin Proteins 0.000 description 2
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
206010020649 Hyperkeratosis Diseases 0.000 description 2
208000001126 Keratosis Diseases 0.000 description 2
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 2
235000010643 Leucaena leucocephala Nutrition 0.000 description 2
240000007472 Leucaena leucocephala Species 0.000 description 2
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
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ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 2
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YVGVBKYNDBGWGY-UHFFFAOYSA-N [N].O=C1NC(=O)NC2=C1NC=N2 Chemical group [N].O=C1NC(=O)NC2=C1NC=N2 YVGVBKYNDBGWGY-UHFFFAOYSA-N 0.000 description 2
239000000654 additive Substances 0.000 description 2
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 2
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
208000006673 asthma Diseases 0.000 description 2
125000004429 atom Chemical group 0.000 description 2
201000008937 atopic dermatitis Diseases 0.000 description 2
208000010668 atopic eczema Diseases 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
229940124630 bronchodilator Drugs 0.000 description 2
239000002775 capsule Substances 0.000 description 2
238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
210000004027 cell Anatomy 0.000 description 2
238000001816 cooling Methods 0.000 description 2
239000013078 crystal Substances 0.000 description 2
229940095074 cyclic amp Drugs 0.000 description 2
125000000753 cycloalkyl group Chemical group 0.000 description 2
HXSNGAHNYZBZTH-UHFFFAOYSA-N cyclopropylmethanamine;hydrochloride Chemical compound Cl.NCC1CC1 HXSNGAHNYZBZTH-UHFFFAOYSA-N 0.000 description 2
239000002552 dosage form Substances 0.000 description 2
210000003979 eosinophil Anatomy 0.000 description 2
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239000000543 intermediate Substances 0.000 description 2
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239000008101 lactose Substances 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
230000003211 malignant effect Effects 0.000 description 2
239000000463 material Substances 0.000 description 2
230000002503 metabolic effect Effects 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
230000004770 neurodegeneration Effects 0.000 description 2
238000007911 parenteral administration Methods 0.000 description 2
239000002245 particle Substances 0.000 description 2
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
239000001267 polyvinylpyrrolidone Substances 0.000 description 2
229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
210000002027 skeletal muscle Anatomy 0.000 description 2
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 2
239000007921 spray Substances 0.000 description 2
229910021653 sulphate ion Inorganic materials 0.000 description 2
229940065721 systemic for obstructive airway disease xanthines Drugs 0.000 description 2
ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 2
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JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 1
ALSTYHKOOCGGFT-KTKRTIGZSA-N (9Z)-octadecen-1-ol Chemical compound CCCCCCCC\C=C/CCCCCCCCO ALSTYHKOOCGGFT-KTKRTIGZSA-N 0.000 description 1
ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
ONUJUMZNBLRIMY-UHFFFAOYSA-N 1,3-bis(cyclopropylmethyl)-7H-purine-2,6-dione Chemical compound C1(CC1)CN1C(=O)N(C=2N=CNC2C1=O)CC1CC1.C1(CC1)CN1C(=O)N(C=2N=CNC2C1=O)CC1CC1 ONUJUMZNBLRIMY-UHFFFAOYSA-N 0.000 description 1
UFAQFYMNIFOKGO-UHFFFAOYSA-N 1,3-bis(cyclopropylmethyl)-8-piperidin-1-yl-7h-purine-2,6-dione Chemical compound C1=2N=C(N3CCCCC3)NC=2C(=O)N(CC2CC2)C(=O)N1CC1CC1 UFAQFYMNIFOKGO-UHFFFAOYSA-N 0.000 description 1
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ZWBASWPKNUWUSZ-UHFFFAOYSA-N 1,3-dimethyl-8-nitro-7h-purine-2,6-dione Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC([N+]([O-])=O)=N2 ZWBASWPKNUWUSZ-UHFFFAOYSA-N 0.000 description 1
IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 1
JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
WWSJZGAPAVMETJ-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]-3-ethoxypyrazol-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C=1C(=NN(C=1)CC(=O)N1CC2=C(CC1)NN=N2)OCC WWSJZGAPAVMETJ-UHFFFAOYSA-N 0.000 description 1
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239000002571 phosphodiesterase inhibitor Substances 0.000 description 1
229910052698 phosphorus Inorganic materials 0.000 description 1
239000011574 phosphorus Substances 0.000 description 1
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
229960005205 prednisolone Drugs 0.000 description 1
OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 1
230000002335 preservative effect Effects 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
239000004405 propyl p-hydroxybenzoate Substances 0.000 description 1
235000013772 propylene glycol Nutrition 0.000 description 1
QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 1
210000004129 prosencephalon Anatomy 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
230000009467 reduction Effects 0.000 description 1
238000010992 reflux Methods 0.000 description 1
206010039083 rhinitis Diseases 0.000 description 1
229960002052 salbutamol Drugs 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
238000007789 sealing Methods 0.000 description 1
208000008742 seborrheic dermatitis Diseases 0.000 description 1
210000003491 skin Anatomy 0.000 description 1
AWUCVROLDVIAJX-GSVOUGTGSA-N sn-glycerol 3-phosphate Chemical compound OC[C@@H](O)COP(O)(O)=O AWUCVROLDVIAJX-GSVOUGTGSA-N 0.000 description 1
235000019333 sodium laurylsulphate Nutrition 0.000 description 1
235000010288 sodium nitrite Nutrition 0.000 description 1
229910000162 sodium phosphate Inorganic materials 0.000 description 1
159000000000 sodium salts Chemical class 0.000 description 1
229940080313 sodium starch Drugs 0.000 description 1
235000010199 sorbic acid Nutrition 0.000 description 1
239000004334 sorbic acid Substances 0.000 description 1
229940075582 sorbic acid Drugs 0.000 description 1
239000001593 sorbitan monooleate Substances 0.000 description 1
235000011069 sorbitan monooleate Nutrition 0.000 description 1
229940035049 sorbitan monooleate Drugs 0.000 description 1
238000012453 sprague-dawley rat model Methods 0.000 description 1
206010041823 squamous cell carcinoma Diseases 0.000 description 1
238000010186 staining Methods 0.000 description 1
239000008107 starch Substances 0.000 description 1
229940032147 starch Drugs 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
230000001954 sterilising effect Effects 0.000 description 1
238000004659 sterilization and disinfection Methods 0.000 description 1
239000000021 stimulant Substances 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
239000000758 substrate Substances 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000004094 surface-active agent Substances 0.000 description 1
238000001356 surgical procedure Methods 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
239000002278 tabletting lubricant Substances 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
229960000278 theophylline Drugs 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
238000011200 topical administration Methods 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
239000008009 topical excipient Substances 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
230000002110 toxicologic effect Effects 0.000 description 1
231100000759 toxicological effect Toxicity 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
230000001052 transient effect Effects 0.000 description 1
QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
LZGVDNRJCGPNDS-UHFFFAOYSA-N trinitromethane Chemical group [O-][N+](=O)C([N+]([O-])=O)[N+]([O-])=O LZGVDNRJCGPNDS-UHFFFAOYSA-N 0.000 description 1
238000009827 uniform distribution Methods 0.000 description 1
230000002792 vascular Effects 0.000 description 1
239000008215 water for injection Substances 0.000 description 1
238000005303 weighing Methods 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
- 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
- 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
- A61P25/00—Drugs for disorders of the nervous system
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
- 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
- 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
- A61P9/08—Vasodilators for multiple indications
- 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
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- 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

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Life Sciences & Earth Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Heart & Thoracic Surgery (AREA)
Biomedical Technology (AREA)
Cardiology (AREA)
Neurosurgery (AREA)
Neurology (AREA)
Pulmonology (AREA)
Immunology (AREA)
Vascular Medicine (AREA)
Urology & Nephrology (AREA)
Hospice & Palliative Care (AREA)
Psychiatry (AREA)
Epidemiology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Saccharide Compounds (AREA)
Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

IL9383290A 1989-03-23 1990-03-21 1,3,8-freshly-converted xanthines, their preparation and pharmaceutical preparations containing them IL93832A (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
GB898906792A GB8906792D0 (en)	1989-03-23	1989-03-23	Treatment and compounds

Publications (2)

Publication Number	Publication Date
IL93832A0 IL93832A0 (en)	1990-12-23
IL93832A true IL93832A (en)	1994-07-31

Family

ID=10653940

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
IL9383290A IL93832A (en)	1989-03-23	1990-03-21	1,3,8-freshly-converted xanthines, their preparation and pharmaceutical preparations containing them

Country Status (27)

Country	Link
US (4)	US5734051A (fr)
EP (2)	EP0389282B1 (fr)
JP (1)	JP2510889B2 (fr)
KR (1)	KR0160768B1 (fr)
CN (1)	CN1031641C (fr)
AT (1)	ATE213498T1 (fr)
AU (1)	AU629315B2 (fr)
CA (1)	CA2012686C (fr)
CZ (1)	CZ391891A3 (fr)
DE (1)	DE69033915T2 (fr)
DK (1)	DK0389282T3 (fr)
ES (1)	ES2173074T3 (fr)
FI (1)	FI95033C (fr)
GB (1)	GB8906792D0 (fr)
HK (1)	HK1040392A1 (fr)
HU (1)	HU207081B (fr)
IL (1)	IL93832A (fr)
MA (1)	MA21800A1 (fr)
MY (1)	MY109737A (fr)
NO (1)	NO175592C (fr)
NZ (1)	NZ233021A (fr)
PL (1)	PL164811B1 (fr)
PT (1)	PT93527B (fr)
SA (1)	SA90100215B1 (fr)
SK (1)	SK391891A3 (fr)
ZA (1)	ZA902170B (fr)
ZW (1)	ZW3690A1 (fr)

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1989
- 1989-03-23 GB GB898906792A patent/GB8906792D0/en active Pending
1990
- 1990-03-20 MA MA22044A patent/MA21800A1/fr unknown
- 1990-03-21 NO NO901300A patent/NO175592C/no unknown
- 1990-03-21 AU AU52083/90A patent/AU629315B2/en not_active Ceased
- 1990-03-21 NZ NZ233021A patent/NZ233021A/en unknown
- 1990-03-21 PT PT93527A patent/PT93527B/pt not_active IP Right Cessation
- 1990-03-21 IL IL9383290A patent/IL93832A/en unknown
- 1990-03-21 ZA ZA902170A patent/ZA902170B/xx unknown
- 1990-03-21 CA CA002012686A patent/CA2012686C/fr not_active Expired - Fee Related
- 1990-03-22 EP EP90303093A patent/EP0389282B1/fr not_active Expired - Lifetime
- 1990-03-22 DE DE69033915T patent/DE69033915T2/de not_active Expired - Fee Related
- 1990-03-22 ES ES90303093T patent/ES2173074T3/es not_active Expired - Lifetime
- 1990-03-22 EP EP00203905A patent/EP1120417A3/fr not_active Withdrawn
- 1990-03-22 AT AT90303093T patent/ATE213498T1/de not_active IP Right Cessation
- 1990-03-22 HU HU901792A patent/HU207081B/hu not_active IP Right Cessation
- 1990-03-22 KR KR1019900003902A patent/KR0160768B1/ko not_active Expired - Fee Related
- 1990-03-22 FI FI901447A patent/FI95033C/fi not_active IP Right Cessation
- 1990-03-22 ZW ZW36/90A patent/ZW3690A1/xx unknown
- 1990-03-22 DK DK90303093T patent/DK0389282T3/da active
- 1990-03-23 PL PL90284429A patent/PL164811B1/pl not_active IP Right Cessation
- 1990-03-23 MY MYPI90000465A patent/MY109737A/en unknown
- 1990-03-23 JP JP2075359A patent/JP2510889B2/ja not_active Expired - Fee Related
- 1990-03-23 CN CN90102240A patent/CN1031641C/zh not_active Expired - Fee Related
- 1990-05-08 SA SA90100215A patent/SA90100215B1/ar unknown
1991
- 1991-12-19 SK SK3918-91A patent/SK391891A3/sk unknown
- 1991-12-19 CZ CS913918A patent/CZ391891A3/cs unknown
1995
- 1995-06-07 US US08/477,157 patent/US5734051A/en not_active Expired - Fee Related
- 1995-06-07 US US08/474,093 patent/US5981535A/en not_active Expired - Fee Related
1998
- 1998-02-17 US US09/024,252 patent/US6180791B1/en not_active Expired - Fee Related
- 1998-12-15 HK HK02100617.1A patent/HK1040392A1/en unknown
2000
- 2000-11-08 US US09/708,338 patent/US6531600B1/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
FI95033C (fi)	1995-12-11
AU5208390A (en)	1990-09-27
FI901447A0 (fi)	1990-03-22
HU207081B (en)	1993-03-01
MY109737A (en)	1997-05-31
ES2173074T3 (es)	2002-10-16
GB8906792D0 (en)	1989-05-10
CN1047502A (zh)	1990-12-05
NO901300L (no)	1990-09-24
HK1040392A1 (en)	2002-06-07
IL93832A0 (en)	1990-12-23
US6531600B1 (en)	2003-03-11
EP0389282B1 (fr)	2002-02-20
MA21800A1 (fr)	1990-12-31
SK391891A3 (en)	2000-12-11
PT93527A (pt)	1990-11-07
KR900013962A (ko)	1990-10-22
CZ391891A3 (en)	1993-11-17
CN1031641C (zh)	1996-04-24
NO175592B (no)	1994-07-25
AU629315B2 (en)	1992-10-01
US5981535A (en)	1999-11-09
SA90100215B1 (ar)	2001-10-07
HUT54155A (en)	1991-01-28
EP0389282A3 (fr)	1992-07-01
HU901792D0 (en)	1990-06-28
DK0389282T3 (da)	2002-06-03
JPH02273676A (ja)	1990-11-08
US5734051A (en)	1998-03-31
PL164811B1 (pl)	1994-10-31
CA2012686A1 (fr)	1990-09-23
US6180791B1 (en)	2001-01-30
KR0160768B1 (ko)	1998-12-01
NO901300D0 (no)	1990-03-21
PT93527B (pt)	1996-08-30
ZW3690A1 (en)	1991-02-06
ZA902170B (en)	1991-03-27
NO175592C (no)	1994-11-02
DE69033915T2 (de)	2002-10-10
ATE213498T1 (de)	2002-03-15
EP0389282A2 (fr)	1990-09-26
JP2510889B2 (ja)	1996-06-26
FI95033B (fi)	1995-08-31
EP1120417A3 (fr)	2001-08-08
CA2012686C (fr)	1999-12-07
EP1120417A2 (fr)	2001-08-01
NZ233021A (en)	1993-12-23
DE69033915D1 (de)	2002-03-28

Legal Events

Date	Code	Title
1996-07-23	KB	Patent renewed
2000-08-13	KB	Patent renewed
2004-05-12	KB	Patent renewed
2009-05-03	KB	Patent renewed

Publication	Publication Date	Title
US5981535A (en)	1999-11-09	Substituted xanthines and their use in the treatment of cerebrovascular disorders and other diseases
US5409934A (en)	1995-04-25	Xanthine derivatives
AU653364B2 (en)	1994-09-29	Xanthine derivatives
CS203093B2 (en)	1981-02-27	Method of preparing substituted purines
EP0369744B1 (fr)	1994-09-21	Dérivés de Xanthine, procédé pour leur préparation et compositions pharmaceutiques les contenant
JPH0780882B2 (ja)	1995-08-30	６‐チオキサンチン誘導体
HK1004551B (en)	1998-11-27	Xanthine derivatives, process for their preparation and pharmaceutical compositions.
AU650679B2 (en)	1994-06-30	Xanthines
HK1012360B (en)	2002-12-27	Xanthinederivatives, process for their preparation and their pharmaceutical use
HK1012360A (en)	1999-07-30	Xanthinederivatives, process for their preparation and their pharmaceutical use
IE44708B1 (en)	1982-03-10	Esters of hydroxyalkoxylkyl purines, their preparation, and pharmaceutical compositions containing them