CA1142928A - 3-alkylxanthines, intermediaires, procedes de preparation, composition et methodes pour le traitement de l'obstruction chronique des voies respiratoires et des maladies cardiaques - Google Patents

3-alkylxanthines, intermediaires, procedes de preparation, composition et methodes pour le traitement de l'obstruction chronique des voies respiratoires et des maladies cardiaques

Info

Publication number: CA1142928A
Authority: CA; Canada
Prior art keywords: cyclopentyl; preparation; compound; dione; formula
Prior art date: 1978-10-20
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

Application number

CA000391134A

Other languages

English (en)

Inventor

Carl G. A. Persson

Per G. Kjellin

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Draco AB

Original Assignee

Draco AB

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.)

1978-10-20

Filing date

1981-11-27

Publication date

1983-03-15

1978-10-20 Priority claimed from SE7810947A external-priority patent/SE7810947L/xx

1981-11-27 Application filed by Draco AB filed Critical Draco AB

1981-11-27 Priority to CA000391134A priority Critical patent/CA1142928A/fr

1983-03-15 Application granted granted Critical

1983-03-15 Publication of CA1142928A publication Critical patent/CA1142928A/fr

Status Expired legal-status Critical Current

Links

238000000034 method Methods 0.000 title claims description 15
238000002360 preparation method Methods 0.000 title abstract description 39
208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 title abstract description 8
208000020446 Cardiac disease Diseases 0.000 title abstract description 5
208000019622 heart disease Diseases 0.000 title abstract description 5
239000000543 intermediate Substances 0.000 title abstract description 4
239000000203 mixture Substances 0.000 title description 5
150000001875 compounds Chemical class 0.000 claims abstract description 37
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims abstract description 7
125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 claims abstract description 6
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims abstract description 6
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims abstract description 6
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims abstract description 6
125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims abstract description 6
125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims abstract description 6
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 abstract description 5
MLIREBYILWEBDM-UHFFFAOYSA-N cyanoacetic acid Chemical compound OC(=O)CC#N MLIREBYILWEBDM-UHFFFAOYSA-N 0.000 claims description 7
229910019020 PtO2 Inorganic materials 0.000 claims description 4
YKIOKAURTKXMSB-UHFFFAOYSA-N adams's catalyst Chemical compound O=[Pt]=O YKIOKAURTKXMSB-UHFFFAOYSA-N 0.000 claims description 4
239000003054 catalyst Substances 0.000 claims description 4
239000002253 acid Substances 0.000 claims description 3
CBEYJGNJOCTQGW-UHFFFAOYSA-N cyclopentylurea Chemical compound NC(=O)NC1CCCC1 CBEYJGNJOCTQGW-UHFFFAOYSA-N 0.000 claims description 3
239000000126 substance Substances 0.000 claims description 3
LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 claims 4
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 3
LULQKPJRMIFLSW-UHFFFAOYSA-N 5,6-diamino-1-cyclopentylpyrimidine-2,4-dione Chemical compound NC1=C(N)C(=O)NC(=O)N1C1CCCC1 LULQKPJRMIFLSW-UHFFFAOYSA-N 0.000 claims 2
QHFVYQRCYOANIO-UHFFFAOYSA-N 6-amino-1-cyclopentyl-5-nitrosopyrimidine-2,4-dione Chemical compound NC1=C(N=O)C(=O)NC(=O)N1C1CCCC1 QHFVYQRCYOANIO-UHFFFAOYSA-N 0.000 claims 2
QQVPYWWVYAEKFS-UHFFFAOYSA-N 6-amino-1-cyclopentylpyrimidine-2,4-dione Chemical compound NC1=CC(=O)NC(=O)N1C1CCCC1 QQVPYWWVYAEKFS-UHFFFAOYSA-N 0.000 claims 2
238000004519 manufacturing process Methods 0.000 claims 2
150000002832 nitroso derivatives Chemical class 0.000 claims 2
235000010288 sodium nitrite Nutrition 0.000 claims 2
230000000694 effects Effects 0.000 abstract description 7
-1 3-substituted-3,7-dihydro-1H-purine-2,6-dione compounds Chemical class 0.000 abstract description 5
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 57
239000013078 crystal Substances 0.000 description 28
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 27
239000000243 solution Substances 0.000 description 24
ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 24
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
150000001408 amides Chemical class 0.000 description 13
229960000278 theophylline Drugs 0.000 description 12
239000013543 active substance Substances 0.000 description 11
229940079593 drug Drugs 0.000 description 10
239000003814 drug Substances 0.000 description 10
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 10
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 10
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 10
150000003839 salts Chemical class 0.000 description 10
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
241001465754 Metazoa Species 0.000 description 9
238000006243 chemical reaction Methods 0.000 description 8
229960001701 chloroform Drugs 0.000 description 8
238000001816 cooling Methods 0.000 description 8
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 8
206010010904 Convulsion Diseases 0.000 description 7
230000036461 convulsion Effects 0.000 description 7
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 7
239000011541 reaction mixture Substances 0.000 description 7
VOPWNXZWBYDODV-UHFFFAOYSA-N Chlorodifluoromethane Chemical compound FC(F)Cl VOPWNXZWBYDODV-UHFFFAOYSA-N 0.000 description 6
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
RYYVLZVUVIJVGH-UHFFFAOYSA-N caffeine Chemical compound CN1C(=O)N(C)C(=O)C2=C1N=CN2C RYYVLZVUVIJVGH-UHFFFAOYSA-N 0.000 description 6
235000019253 formic acid Nutrition 0.000 description 6
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235000019322 gelatine Nutrition 0.000 description 6
239000001257 hydrogen Substances 0.000 description 6
229910052739 hydrogen Inorganic materials 0.000 description 6
239000002904 solvent Substances 0.000 description 6
LRFVTYWOQMYALW-UHFFFAOYSA-N 9H-xanthine Chemical class O=C1NC(=O)NC2=C1NC=N2 LRFVTYWOQMYALW-UHFFFAOYSA-N 0.000 description 5
239000001828 Gelatine Substances 0.000 description 5
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 5
ISAKRJDGNUQOIC-UHFFFAOYSA-N Uracil Chemical compound O=C1C=CNC(=O)N1 ISAKRJDGNUQOIC-UHFFFAOYSA-N 0.000 description 5
239000004480 active ingredient Substances 0.000 description 5
238000002347 injection Methods 0.000 description 5
239000007924 injection Substances 0.000 description 5
239000008101 lactose Substances 0.000 description 5
239000007787 solid Substances 0.000 description 5
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 4
239000002775 capsule Substances 0.000 description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
239000011734 sodium Substances 0.000 description 4
239000003826 tablet Substances 0.000 description 4
NHFCELOARWLFPC-UHFFFAOYSA-N 3-cyclopropyl-7h-purine-2,6-dione Chemical compound O=C1NC(=O)C=2NC=NC=2N1C1CC1 NHFCELOARWLFPC-UHFFFAOYSA-N 0.000 description 3
229920002261 Corn starch Polymers 0.000 description 3
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 3
LPHGQDQBBGAPDZ-UHFFFAOYSA-N Isocaffeine Natural products CN1C(=O)N(C)C(=O)C2=C1N(C)C=N2 LPHGQDQBBGAPDZ-UHFFFAOYSA-N 0.000 description 3
241000699670 Mus sp. Species 0.000 description 3
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
206010043994 Tonic convulsion Diseases 0.000 description 3
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
125000000217 alkyl group Chemical group 0.000 description 3
239000002585 base Substances 0.000 description 3
229960001948 caffeine Drugs 0.000 description 3
VJEONQKOZGKCAK-UHFFFAOYSA-N caffeine Natural products CN1C(=O)N(C)C(=O)C2=C1C=CN2C VJEONQKOZGKCAK-UHFFFAOYSA-N 0.000 description 3
230000003177 cardiotonic effect Effects 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 3
239000003921 oil Substances 0.000 description 3
235000019198 oils Nutrition 0.000 description 3
229920001223 polyethylene glycol Polymers 0.000 description 3
239000000047 product Substances 0.000 description 3
229910052708 sodium Inorganic materials 0.000 description 3
239000000454 talc Substances 0.000 description 3
229910052623 talc Inorganic materials 0.000 description 3
238000012360 testing method Methods 0.000 description 3
230000001256 tonic effect Effects 0.000 description 3
210000003437 trachea Anatomy 0.000 description 3
VJDSUFIVURYZOJ-UHFFFAOYSA-N 3-cyclopentyl-7h-purine-2,6-dione Chemical compound O=C1NC(=O)C=2NC=NC=2N1C1CCCC1 VJDSUFIVURYZOJ-UHFFFAOYSA-N 0.000 description 2
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-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
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
241000700198 Cavia Species 0.000 description 2
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 2
FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 2
FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
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229930195725 Mannitol Natural products 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
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CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
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239000007788 liquid Substances 0.000 description 2
239000000314 lubricant 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
239000000594 mannitol Substances 0.000 description 2
235000010355 mannitol Nutrition 0.000 description 2
231100000252 nontoxic Toxicity 0.000 description 2
230000003000 nontoxic effect Effects 0.000 description 2
210000000056 organ Anatomy 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
239000001814 pectin Substances 0.000 description 2
235000010987 pectin Nutrition 0.000 description 2
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239000000825 pharmaceutical preparation Substances 0.000 description 2
239000001267 polyvinylpyrrolidone Substances 0.000 description 2
229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
229910052700 potassium Inorganic materials 0.000 description 2
239000011591 potassium Substances 0.000 description 2
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BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
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239000000843 powder Substances 0.000 description 2
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229940065721 systemic for obstructive airway disease xanthines Drugs 0.000 description 2
230000001225 therapeutic effect Effects 0.000 description 2
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
238000005303 weighing Methods 0.000 description 2
YHVGCAATIHTUFE-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;1-aminopropan-2-ol Chemical compound CC(O)CN.OCC(N)(CO)CO YHVGCAATIHTUFE-UHFFFAOYSA-N 0.000 description 1
FXQRJLXSYBQNMQ-UHFFFAOYSA-N 3-(cyclohexylmethyl)-7h-purine-2,6-dione Chemical compound O=C1NC(=O)C=2NC=NC=2N1CC1CCCCC1 FXQRJLXSYBQNMQ-UHFFFAOYSA-N 0.000 description 1
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GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
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125000004429 atom Chemical group 0.000 description 1
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CNWSQCLBDWYLAN-UHFFFAOYSA-N butylurea Chemical compound CCCCNC(N)=O CNWSQCLBDWYLAN-UHFFFAOYSA-N 0.000 description 1
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AIXAANGOTKPUOY-UHFFFAOYSA-N carbachol Chemical compound [Cl-].C[N+](C)(C)CCOC(N)=O AIXAANGOTKPUOY-UHFFFAOYSA-N 0.000 description 1
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125000004432 carbon atom Chemical group C* 0.000 description 1
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical class OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
150000004649 carbonic acid derivatives Chemical class 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
239000001768 carboxy methyl cellulose Substances 0.000 description 1
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239000000969 carrier Substances 0.000 description 1
OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 description 1
229960001231 choline Drugs 0.000 description 1
230000002057 chronotropic effect Effects 0.000 description 1
235000015165 citric acid Nutrition 0.000 description 1
235000020971 citrus fruits Nutrition 0.000 description 1
230000002566 clonic effect Effects 0.000 description 1
239000007931 coated granule Substances 0.000 description 1
238000000576 coating method Methods 0.000 description 1
230000008602 contraction Effects 0.000 description 1
PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
229940043237 diethanolamine Drugs 0.000 description 1
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
239000002270 dispersing agent Substances 0.000 description 1
238000006073 displacement reaction Methods 0.000 description 1
230000009429 distress Effects 0.000 description 1
239000008298 dragée Substances 0.000 description 1
239000003937 drug carrier Substances 0.000 description 1
239000007911 effervescent powder Substances 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
229940012017 ethylenediamine Drugs 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
210000003414 extremity Anatomy 0.000 description 1
230000002496 gastric effect Effects 0.000 description 1
239000008273 gelatin Substances 0.000 description 1
235000011852 gelatine desserts Nutrition 0.000 description 1
229940052308 general anesthetics halogenated hydrocarbons Drugs 0.000 description 1
229960002449 glycine Drugs 0.000 description 1
239000008187 granular material Substances 0.000 description 1
150000008282 halocarbons Chemical class 0.000 description 1
238000010438 heat treatment Methods 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
238000001802 infusion Methods 0.000 description 1
238000007914 intraventricular administration Methods 0.000 description 1
238000005342 ion exchange Methods 0.000 description 1
229940083747 low-ceiling diuretics xanthine derivative Drugs 0.000 description 1
210000003141 lower extremity Anatomy 0.000 description 1
239000011777 magnesium Substances 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
239000000463 material Substances 0.000 description 1
239000011159 matrix material Substances 0.000 description 1
GXHFUVWIGNLZSC-UHFFFAOYSA-N meldrum's acid Chemical compound CC1(C)OC(=O)CC(=O)O1 GXHFUVWIGNLZSC-UHFFFAOYSA-N 0.000 description 1
238000002156 mixing Methods 0.000 description 1
210000003205 muscle Anatomy 0.000 description 1
210000004165 myocardium Anatomy 0.000 description 1
230000008693 nausea Effects 0.000 description 1
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
235000008390 olive oil Nutrition 0.000 description 1
239000004006 olive oil Substances 0.000 description 1
238000007243 oxidative cyclization reaction Methods 0.000 description 1
230000001590 oxidative effect Effects 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
230000010412 perfusion Effects 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
230000000144 pharmacologic effect Effects 0.000 description 1
239000004014 plasticizer Substances 0.000 description 1
229920000573 polyethylene Polymers 0.000 description 1
239000011736 potassium bicarbonate Substances 0.000 description 1
235000015497 potassium bicarbonate Nutrition 0.000 description 1
229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
235000011181 potassium carbonates Nutrition 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
FAIAJSOSTNJZCI-UHFFFAOYSA-N purine-2,6-dione Chemical compound O=C1NC(=O)C2=NC=NC2=N1 FAIAJSOSTNJZCI-UHFFFAOYSA-N 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
230000002040 relaxant effect Effects 0.000 description 1
210000005241 right ventricle Anatomy 0.000 description 1
CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
231100000161 signs of toxicity Toxicity 0.000 description 1
210000002460 smooth muscle Anatomy 0.000 description 1
JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
239000003381 stabilizer Substances 0.000 description 1
239000008107 starch Substances 0.000 description 1
239000007858 starting material Substances 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000008223 sterile water Substances 0.000 description 1
239000006190 sub-lingual tablet Substances 0.000 description 1
239000002511 suppository base Substances 0.000 description 1
239000000725 suspension Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
238000011287 therapeutic dose Methods 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
239000004408 titanium dioxide Substances 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 0.000 description 1
UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
229960004418 trolamine Drugs 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
210000003462 vein Anatomy 0.000 description 1
238000005406 washing Methods 0.000 description 1
239000001993 wax Substances 0.000 description 1

Landscapes

Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA000391134A 1978-10-20 1981-11-27 3-alkylxanthines, intermediaires, procedes de preparation, composition et methodes pour le traitement de l'obstruction chronique des voies respiratoires et des maladies cardiaques Expired CA1142928A (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA000391134A CA1142928A (fr)	1978-10-20	1981-11-27	3-alkylxanthines, intermediaires, procedes de preparation, composition et methodes pour le traitement de l'obstruction chronique des voies respiratoires et des maladies cardiaques

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
SE7810947-7		1978-10-20
SE7810947A SE7810947L (sv)	1978-10-20	1978-10-20	3-alkylxanthines
CA337,077A CA1131632A (fr)	1978-10-20	1979-10-05	Procedes d'obtention de 3-alkylxanthines et de leurs derives, substances qui en contiennent et methode pour traiter les troubles respiratoires de forme obstructive et les deficiences cardiaques
CA000391134A CA1142928A (fr)	1978-10-20	1981-11-27	3-alkylxanthines, intermediaires, procedes de preparation, composition et methodes pour le traitement de l'obstruction chronique des voies respiratoires et des maladies cardiaques

Publications (1)

Publication Number	Publication Date
CA1142928A true CA1142928A (fr)	1983-03-15

Family

ID=27166435

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000391134A Expired CA1142928A (fr)	1978-10-20	1981-11-27	3-alkylxanthines, intermediaires, procedes de preparation, composition et methodes pour le traitement de l'obstruction chronique des voies respiratoires et des maladies cardiaques

Country Status (1)

Country	Link
CA (1)	CA1142928A (fr)

1981
- 1981-11-27 CA CA000391134A patent/CA1142928A/fr not_active Expired

Legal Events

Date	Code	Title	Description
2000-03-15	MKEX	Expiry

Publication	Publication Date	Title
CA1131632A (fr)	1982-09-14	Procedes d'obtention de 3-alkylxanthines et de leurs derives, substances qui en contiennent et methode pour traiter les troubles respiratoires de forme obstructive et les deficiences cardiaques
US4804664A (en)	1989-02-14	Method and pharmaceutical preparation for treating chronic obstructive airway disease and cardiac disease, and intermediates for the preparation of therapeutically active xanthine derivatives
AU683270B2 (en)	1997-11-06	Novel chemical compounds having PDE-IV inhibition activity
US4089959A (en)	1978-05-16	Long-acting xanthine bronchodilators and antiallergy agents
EP0435811B1 (fr)	1993-09-01	Dérivés de xanthine
CA1286666C (fr)	1991-07-23	Derives de substitution de la 8-phenylxanthine
US4120947A (en)	1978-10-17	Xanthine compounds and method of treating bronchospastic and allergic diseases
EP0163599B1 (fr)	1990-03-21	Dérivés de pyrimidopyrimidine, procédé pour leur préparation, compositions pharmaceutiques les contenant et leur utilisation comme agents antiallergiques
GB2135311A (en)	1984-08-30	Novel xanthine-type adenosine receptor antagonists
EP0267607B1 (fr)	1991-11-27	8-Arylxanthines
CA1077932A (fr)	1980-05-20	Composes de la xanthine pour le traitement des bronchospasmes et des affections allergiques
CA1156229A (fr)	1983-11-01	3,8-dialkylxanthines, methodes pour les preparer, composition et methodes pour le traitement de l'obstruction chronique des voies aeriennes et des maladies cardio-vasculaires
IE52872B1 (en)	1988-03-30	Derivatives of 2-piperazino-pyrimidine, methods for their preparation, medicaments containing them and their utilization as intermediates for the manufacture of medicaments
CA1142928A (fr)	1983-03-15	3-alkylxanthines, intermediaires, procedes de preparation, composition et methodes pour le traitement de l'obstruction chronique des voies respiratoires et des maladies cardiaques
EP0244352B1 (fr)	1993-03-31	Dérivés de pyrido[4,3-d]pyrimidine
KR830001654B1 (ko)	1983-08-22	만성장애 기도증과 심장병 치료를 위한 3-알킬 크산틴의 제조방법
JPH05262770A (ja)	1993-10-12	化学的製法
JPH0613518B2 (ja)	1994-02-23	新規ピリミドピリミジン誘導体、その製法並びに該化合物を含有する医薬組成物
JPH02255681A (ja)	1990-10-16	キサンチン誘導体