CA1288432C - Derives oxadiazole-alkyl-purine - Google Patents

Derives oxadiazole-alkyl-purine

Info

Publication number: CA1288432C
Authority: CA; Canada
Prior art keywords: methyl; general formula; pharmaceutically acceptable; oxadiazole; acceptable salt
Prior art date: 1986-10-09
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 - Lifetime

Application number

CA000548853A

Other languages

English (en)

Inventor

Gergely Heja

Zoltan Vargai

Emil Minker

Dezso Korbonits

Gabor Horvath

Sandor Virag

Sandor Antus

Gabor Kovacs

Agnes Gottsegen

Lorand Debreczeni

Laszlo Tardos

Peter Kormoczy

Andrea Bolehovszky

Jeno Marton

Katalin Marmarosi

Vera Gergely

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.)

Chinoin Private Co Ltd

Original Assignee

Chinoin Gyogyszer es Vegyeszeti Termekek Gyara Zrt

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.)

1986-10-09

Filing date

1987-10-08

Publication date

1991-09-03

1987-10-08 Application filed by Chinoin Gyogyszer es Vegyeszeti Termekek Gyara Zrt filed Critical Chinoin Gyogyszer es Vegyeszeti Termekek Gyara Zrt

1991-09-03 Application granted granted Critical

1991-09-03 Publication of CA1288432C publication Critical patent/CA1288432C/fr

2008-09-03 Anticipated expiration legal-status Critical

Status Expired - Lifetime legal-status Critical Current

Links

229940083251 peripheral vasodilators purine derivative Drugs 0.000 title abstract description 4
150000001875 compounds Chemical class 0.000 claims abstract description 72
150000003839 salts Chemical class 0.000 claims abstract description 33
-1 carboxyphenyl Chemical group 0.000 claims abstract description 24
238000000034 method Methods 0.000 claims abstract description 23
229940124584 antitussives Drugs 0.000 claims abstract description 11
239000003434 antitussive agent Substances 0.000 claims abstract description 10
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 8
125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 8
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 5
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 4
125000004103 aminoalkyl group Chemical group 0.000 claims abstract description 4
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 4
125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 claims abstract description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 3
125000005842 heteroatom Chemical group 0.000 claims abstract description 3
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 3
239000001257 hydrogen Substances 0.000 claims abstract description 3
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 3
125000004464 hydroxyphenyl group Chemical group 0.000 claims abstract description 3
125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 3
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract 2
125000002947 alkylene group Chemical group 0.000 claims abstract 2
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract 2
GMSNIKWWOQHZGF-UHFFFAOYSA-N 3-methyl-9H-xanthine Chemical compound O=C1NC(=O)N(C)C2=C1N=CN2 GMSNIKWWOQHZGF-UHFFFAOYSA-N 0.000 claims description 15
239000004480 active ingredient Substances 0.000 claims description 10
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 claims description 9
239000002253 acid Substances 0.000 claims description 9
SFZULDYEOVSIKM-UHFFFAOYSA-N chembl321317 Chemical compound C1=CC(C(=N)NO)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(=N)NO)O1 SFZULDYEOVSIKM-UHFFFAOYSA-N 0.000 claims description 8
229910052708 sodium Inorganic materials 0.000 claims description 8
239000011734 sodium Substances 0.000 claims description 8
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
239000008194 pharmaceutical composition Substances 0.000 claims description 6
239000003054 catalyst Substances 0.000 claims description 5
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 4
150000007529 inorganic bases Chemical class 0.000 claims description 4
238000002360 preparation method Methods 0.000 claims description 4
229910052736 halogen Inorganic materials 0.000 claims description 3
150000002367 halogens Chemical class 0.000 claims description 3
150000004866 oxadiazoles Chemical class 0.000 claims description 3
125000002130 sulfonic acid ester group Chemical group 0.000 claims description 3
125000002774 3,4-dimethoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 2
230000018044 dehydration Effects 0.000 claims description 2
238000006297 dehydration reaction Methods 0.000 claims description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims 1
RYQVRAILJXPCMZ-UHFFFAOYSA-N 3-methyl-7-[(5-methyl-1,2,4-oxadiazol-3-yl)methyl]purine-2,6-dione Chemical compound O1C(C)=NC(CN2C=3C(=O)NC(=O)N(C)C=3N=C2)=N1 RYQVRAILJXPCMZ-UHFFFAOYSA-N 0.000 claims 1
NXZSQVAOHWKDMV-UHFFFAOYSA-N 3-methyl-7-[2-(5-methyl-1,2,4-oxadiazol-3-yl)ethyl]purine-2,6-dione Chemical compound O1C(C)=NC(CCN2C=3C(=O)NC(=O)N(C)C=3N=C2)=N1 NXZSQVAOHWKDMV-UHFFFAOYSA-N 0.000 claims 1
ULZPUYUELWKFRH-UHFFFAOYSA-N 3-methyl-7-[2-[5-(2-piperidin-1-ylethyl)-1,2,4-oxadiazol-3-yl]ethyl]purine-2,6-dione Chemical compound C1=2C(=O)NC(=O)N(C)C=2N=CN1CCC(N=1)=NOC=1CCN1CCCCC1 ULZPUYUELWKFRH-UHFFFAOYSA-N 0.000 claims 1
SLVAMRGYTYECNM-UHFFFAOYSA-N 3-methyl-7-[3-(5-methyl-1,2,4-oxadiazol-3-yl)propyl]purine-2,6-dione Chemical compound O1C(C)=NC(CCCN2C=3C(=O)NC(=O)N(C)C=3N=C2)=N1 SLVAMRGYTYECNM-UHFFFAOYSA-N 0.000 claims 1
FBHOTLWINLXBFB-UHFFFAOYSA-N 7-[(5-benzyl-1,2,4-oxadiazol-3-yl)methyl]-3-methylpurine-2,6-dione Chemical compound C1=2C(=O)NC(=O)N(C)C=2N=CN1CC(N=1)=NOC=1CC1=CC=CC=C1 FBHOTLWINLXBFB-UHFFFAOYSA-N 0.000 claims 1
XISPUHUXJZHTFN-UHFFFAOYSA-N 7-[[5-(chloromethyl)-1,2,4-oxadiazol-3-yl]methyl]-3-methylpurine-2,6-dione Chemical compound C1=2C(=O)NC(=O)N(C)C=2N=CN1CC1=NOC(CCl)=N1 XISPUHUXJZHTFN-UHFFFAOYSA-N 0.000 claims 1
125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims 1
150000001336 alkenes Chemical class 0.000 claims 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 1
125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 claims 1
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 1
125000006264 diethylaminomethyl group Chemical group [H]C([H])([H])C([H])([H])N(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 claims 1
238000004519 manufacturing process Methods 0.000 claims 1
125000001064 morpholinomethyl group Chemical group [H]C([H])(*)N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 claims 1
JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 claims 1
125000001188 haloalkyl group Chemical group 0.000 abstract description 3
125000004181 carboxyalkyl group Chemical group 0.000 abstract 1
125000002768 hydroxyalkyl group Chemical group 0.000 abstract 1
238000002560 therapeutic procedure Methods 0.000 abstract 1
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 48
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
239000000203 mixture Substances 0.000 description 17
239000000243 solution Substances 0.000 description 17
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
230000000954 anitussive effect Effects 0.000 description 15
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
239000011541 reaction mixture Substances 0.000 description 11
OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 10
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
239000002904 solvent Substances 0.000 description 9
BBVIDBNAYOIXOE-UHFFFAOYSA-N 1,2,4-oxadiazole Chemical group C=1N=CON=1 BBVIDBNAYOIXOE-UHFFFAOYSA-N 0.000 description 8
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
238000009835 boiling Methods 0.000 description 8
239000003085 diluting agent Substances 0.000 description 7
238000003756 stirring Methods 0.000 description 7
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
CAZFYQLISAOCOV-UHFFFAOYSA-N n'-hydroxy-2-(3-methyl-2,6-dioxopurin-7-yl)ethanimidamide Chemical compound O=C1NC(=O)N(C)C2=C1N(CC(N)=NO)C=N2 CAZFYQLISAOCOV-UHFFFAOYSA-N 0.000 description 6
239000003960 organic solvent Substances 0.000 description 6
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 5
KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 5
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 5
125000000217 alkyl group Chemical group 0.000 description 5
229960004126 codeine Drugs 0.000 description 5
239000000306 component Substances 0.000 description 5
OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 5
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 5
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
239000011230 binding agent Substances 0.000 description 4
238000006243 chemical reaction Methods 0.000 description 4
238000002425 crystallisation Methods 0.000 description 4
230000008025 crystallization Effects 0.000 description 4
239000008298 dragée Substances 0.000 description 4
230000002349 favourable effect Effects 0.000 description 4
238000010438 heat treatment Methods 0.000 description 4
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 4
229910000041 hydrogen chloride Inorganic materials 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
230000029058 respiratory gaseous exchange Effects 0.000 description 4
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 4
239000000126 substance 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
230000001225 therapeutic effect Effects 0.000 description 4
230000001988 toxicity Effects 0.000 description 4
231100000419 toxicity Toxicity 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
206010011224 Cough Diseases 0.000 description 3
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
241000700159 Rattus Species 0.000 description 3
229910052784 alkaline earth metal Inorganic materials 0.000 description 3
150000008064 anhydrides Chemical class 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
230000000694 effects Effects 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical class O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 3
WCPAKWJPBJAGKN-UHFFFAOYSA-N oxadiazole Chemical compound C1=CON=N1 WCPAKWJPBJAGKN-UHFFFAOYSA-N 0.000 description 3
239000000047 product Substances 0.000 description 3
235000020374 simple syrup Nutrition 0.000 description 3
229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
235000017557 sodium bicarbonate Nutrition 0.000 description 3
229910000029 sodium carbonate Inorganic materials 0.000 description 3
239000007921 spray Substances 0.000 description 3
235000020357 syrup Nutrition 0.000 description 3
239000006188 syrup Substances 0.000 description 3
229940086542 triethylamine Drugs 0.000 description 3
ROTWYIYTFZNLQP-UHFFFAOYSA-N 2-(3-methyl-2,6-dioxopurin-7-yl)acetonitrile Chemical compound O=C1NC(=O)N(C)C2=C1N(CC#N)C=N2 ROTWYIYTFZNLQP-UHFFFAOYSA-N 0.000 description 2
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-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
239000005711 Benzoic acid Substances 0.000 description 2
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-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
WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
238000005481 NMR spectroscopy Methods 0.000 description 2
PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 2
241000283973 Oryctolagus cuniculus Species 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
235000021355 Stearic acid Nutrition 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
150000008065 acid anhydrides Chemical class 0.000 description 2
230000010933 acylation Effects 0.000 description 2
238000005917 acylation reaction Methods 0.000 description 2
239000003513 alkali Substances 0.000 description 2
150000004945 aromatic hydrocarbons Chemical class 0.000 description 2
238000010533 azeotropic distillation Methods 0.000 description 2
239000002585 base Substances 0.000 description 2
235000010233 benzoic acid Nutrition 0.000 description 2
230000000903 blocking effect Effects 0.000 description 2
239000000872 buffer Substances 0.000 description 2
235000010216 calcium carbonate Nutrition 0.000 description 2
239000001768 carboxy methyl cellulose Substances 0.000 description 2
235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
239000008112 carboxymethyl-cellulose Substances 0.000 description 2
229940105329 carboxymethylcellulose Drugs 0.000 description 2
239000000969 carrier Substances 0.000 description 2
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 2
201000010099 disease Diseases 0.000 description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 2
150000004820 halides Chemical class 0.000 description 2
238000001990 intravenous administration Methods 0.000 description 2
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 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
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
150000007522 mineralic acids Chemical class 0.000 description 2
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 2
210000000056 organ Anatomy 0.000 description 2
150000007524 organic acids Chemical class 0.000 description 2
150000007530 organic bases Chemical class 0.000 description 2
239000006187 pill Substances 0.000 description 2
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
PXZDWASDNFWKSD-UHFFFAOYSA-N prenoxdiazine Chemical compound C1CCCCN1CCC(ON=1)=NC=1CC(C=1C=CC=CC=1)C1=CC=CC=C1 PXZDWASDNFWKSD-UHFFFAOYSA-N 0.000 description 2
235000017550 sodium carbonate Nutrition 0.000 description 2
239000007858 starting material Substances 0.000 description 2
239000008117 stearic acid Substances 0.000 description 2
238000006467 substitution reaction Methods 0.000 description 2
YAPQBXQYLJRXSA-UHFFFAOYSA-N theobromine Chemical compound CN1C(=O)NC(=O)C2=C1N=CN2C YAPQBXQYLJRXSA-UHFFFAOYSA-N 0.000 description 2
229960000278 theophylline Drugs 0.000 description 2
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
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230000004071 biological effect Effects 0.000 description 1
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229910052791 calcium Inorganic materials 0.000 description 1
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239000001506 calcium phosphate Substances 0.000 description 1
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230000005923 long-lasting effect Effects 0.000 description 1
229910052749 magnesium Inorganic materials 0.000 description 1
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VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
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QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
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AEXITZJSLGALNH-UHFFFAOYSA-N n'-hydroxyethanimidamide Chemical compound CC(N)=NO AEXITZJSLGALNH-UHFFFAOYSA-N 0.000 description 1
239000011664 nicotinic acid Substances 0.000 description 1
235000001968 nicotinic acid Nutrition 0.000 description 1
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239000012454 non-polar solvent Substances 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
150000002894 organic compounds Chemical class 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
239000001267 polyvinylpyrrolidone Substances 0.000 description 1
229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
235000011181 potassium carbonates Nutrition 0.000 description 1
230000000063 preceeding effect Effects 0.000 description 1
238000002203 pretreatment Methods 0.000 description 1
230000004224 protection Effects 0.000 description 1
150000003212 purines Chemical group 0.000 description 1
238000000197 pyrolysis Methods 0.000 description 1
125000001453 quaternary ammonium group Chemical group 0.000 description 1
239000000376 reactant Substances 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
230000000241 respiratory effect Effects 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
230000000638 stimulation Effects 0.000 description 1
150000003460 sulfonic acids Chemical class 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000000725 suspension Substances 0.000 description 1
239000003826 tablet Substances 0.000 description 1
239000011975 tartaric acid Substances 0.000 description 1
235000002906 tartaric acid Nutrition 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
229960004559 theobromine Drugs 0.000 description 1
210000003437 trachea Anatomy 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
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
238000010792 warming Methods 0.000 description 1
229940100445 wheat starch Drugs 0.000 description 1
239000008096 xylene Substances 0.000 description 1

Landscapes

Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA000548853A 1986-10-09 1987-10-08 Derives oxadiazole-alkyl-purine Expired - Lifetime CA1288432C (fr)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
HU4320/86		1986-10-09
HU432086		1986-10-09

Publications (1)

Publication Number	Publication Date
CA1288432C true CA1288432C (fr)	1991-09-03

Family

ID=10967635

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000548853A Expired - Lifetime CA1288432C (fr)	1986-10-09	1987-10-08	Derives oxadiazole-alkyl-purine

Country Status (1)

Country	Link
CA (1)	CA1288432C (fr)

1987
- 1987-10-08 CA CA000548853A patent/CA1288432C/fr not_active Expired - Lifetime

Legal Events

Date	Code	Title	Description
2001-09-04	MKLA	Lapsed

Publication	Publication Date	Title
US4840949A (en)	1989-06-20	Oxadiazole-alkyl-purine derivatives useful as antitussive agents
GB1601195A (en)	1981-10-28	4-acylamino-or 4-acylaminoalkyl-benzoic acids derivatives thereof and processes for their manufacture
CN1042633C (zh)	1999-03-24	咪唑并(1,2－a)吡啶类的氨基甲酸烷氧基烷基酯
EP0045094A1 (fr)	1982-02-03	Intermédiaires pour la préparation de dérivés thérapeutiquement actifs de xanthine
JPS6230780A (ja)	1987-02-09	１，７−ナフチリジン誘導体及びこれを含有する薬剤
IE46918B1 (en)	1983-11-02	Novel antibacterial amide compounds and process means for producing the same
CA1288432C (fr)	1991-09-03	Derives oxadiazole-alkyl-purine
JPH045289A (ja)	1992-01-09	アミド化合物
AU2324400A (en)	2000-08-25	Benzamide derivatives and drugs containing the same
JPS58201764A (ja)	1983-11-24	ジヒドロピリジン誘導体
US3498992A (en)	1970-03-03	Substituted 1,2,3,6-tetrahydro-4-pyridine acetic acid amides
JPH05262770A (ja)	1993-10-12	化学的製法
HRP920559A2 (en)	1994-10-31	Oxadiazole-alkyl-purine derivatives
EP0025965A2 (fr)	1981-04-01	Composés d'organogermanium, procédé pour leur préparation et compositions pharmaceutiques les contenant
IE44948B1 (en)	1982-05-19	7h-thiazolo(and 1,3,4-thiadiazolo-)(3,2-alpha)pyrimidin-7-one-5-carboxylic acids,derivatives and medicaments thereof
IE54085B1 (en)	1989-06-07	New 1-furyl-3,4-dihydroisoquinolines, pharmaceutical compositions containing them and processes for the preparation thereof and the use thereof
CS241026B2 (en)	1986-03-13	Method of pyrazolo(1,5-c)-quinozoline derivatives production
EP0133259A2 (fr)	1985-02-20	Dérivés de benzène substitués par des groupes aminoalcoyle, procédé de leur production et leurs compositions pharmaceutiques
US3882127A (en)	1975-05-06	17-alkenyl-6{62 -azido-4,5{60 -epoxymorphinan-3-ols
IL99900A (en)	1995-07-31	Isoquinoline derivatives, pharmaceutical compositions containing them and process for preparing same
JPS5948450A (ja)	1984-03-19	新規なオキサミド酸誘導体、その製法及びそれを含有する医薬
KR790001270B1 (ko)	1979-09-20	알킬피리미도[4, 5-b]-퀴놀린-4-(3H)-온-2-카복실 레이트류의 제조방법
JPH0227345B2 (fr)	1990-06-15
EP1082304A1 (fr)	2001-03-14	Nouvelle forme cristalline polymorphe d'ester guaiacyle d'acide 1-methyl-5-p-toluoylpyrrole-2-acetamido-acetique
EP0043961A1 (fr)	1982-01-20	1,2-Benzothiazinopyrazoles à activité pharmacologique