AT390792B - Process for the preparation of novel imidazoquinoxalines and their salts - Google Patents
Process for the preparation of novel imidazoquinoxalines and their salts Download PDFInfo
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- AT390792B AT390792B AT298486A AT298486A AT390792B AT 390792 B AT390792 B AT 390792B AT 298486 A AT298486 A AT 298486A AT 298486 A AT298486 A AT 298486A AT 390792 B AT390792 B AT 390792B
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- 150000003839 salts Chemical class 0.000 title claims abstract description 9
- 238000000034 method Methods 0.000 title claims abstract description 7
- 238000002360 preparation method Methods 0.000 title claims abstract description 6
- YELMWJNXDALKFE-UHFFFAOYSA-N 3h-imidazo[4,5-f]quinoxaline Chemical class N1=CC=NC2=C(NC=N3)C3=CC=C21 YELMWJNXDALKFE-UHFFFAOYSA-N 0.000 title claims abstract description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 29
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 24
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 8
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 4
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 15
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims description 3
- 239000002904 solvent Substances 0.000 claims description 3
- 229910052717 sulfur Inorganic materials 0.000 claims 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 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 claims description 2
- 125000005843 halogen group Chemical group 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 150000007529 inorganic bases Chemical class 0.000 claims description 2
- 239000003960 organic solvent Substances 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 239000011593 sulfur Substances 0.000 claims description 2
- -1 methoxy, ethoxy, propoxy, isopropoxy Chemical group 0.000 description 6
- 239000002253 acid Substances 0.000 description 5
- 239000003814 drug Substances 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 125000004494 ethyl ester group Chemical group 0.000 description 3
- 239000000825 pharmaceutical preparation Substances 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound 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
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 208000006673 asthma Diseases 0.000 description 2
- ISAOCJYIOMOJEB-UHFFFAOYSA-N benzoin Chemical compound C=1C=CC=CC=1C(O)C(=O)C1=CC=CC=C1 ISAOCJYIOMOJEB-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
- 239000000203 mixture Substances 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 description 1
- 235000005979 Citrus limon Nutrition 0.000 description 1
- 244000131522 Citrus pyriformis Species 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 241000257303 Hymenoptera Species 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 244000028419 Styrax benzoin Species 0.000 description 1
- 235000000126 Styrax benzoin Nutrition 0.000 description 1
- 235000008411 Sumatra benzointree Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 201000009961 allergic asthma Diseases 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000003266 anti-allergic effect Effects 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- 235000003704 aspartic acid Nutrition 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 150000008107 benzenesulfonic acids Chemical class 0.000 description 1
- 229960002130 benzoin Drugs 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- OQFSQFPPLPISGP-UHFFFAOYSA-N beta-carboxyaspartic acid Natural products OC(=O)C(N)C(C(O)=O)C(O)=O OQFSQFPPLPISGP-UHFFFAOYSA-N 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 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 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- FTSSQTHHNUYTHG-UHFFFAOYSA-N ethyl 4,5-dihydroimidazo[1,2-a]quinoxaline-2-carboxylate Chemical compound C1=CC=C2N3C=C(C(=O)OCC)N=C3CNC2=C1 FTSSQTHHNUYTHG-UHFFFAOYSA-N 0.000 description 1
- NHBJABCFROJKSV-UHFFFAOYSA-N ethyl 5-(2-chloroacetyl)-4h-imidazo[1,2-a]quinoxaline-2-carboxylate Chemical compound C1=CC=C2N3C=C(C(=O)OCC)N=C3CN(C(=O)CCl)C2=C1 NHBJABCFROJKSV-UHFFFAOYSA-N 0.000 description 1
- BMSIQDJIBASORO-UHFFFAOYSA-N ethyl 5-(2-piperidin-1-ylacetyl)-4h-imidazo[1,2-a]quinoxaline-2-carboxylate Chemical compound N=1C(C(=O)OCC)=CN(C2=CC=CC=C22)C=1CN2C(=O)CN1CCCCC1 BMSIQDJIBASORO-UHFFFAOYSA-N 0.000 description 1
- FVPNTAOFROJSCG-UHFFFAOYSA-N ethyl 5-[2-(diethylamino)acetyl]-4h-imidazo[1,2-a]quinoxaline-2-carboxylate Chemical compound C1=CC=C2N3C=C(C(=O)OCC)N=C3CN(C(=O)CN(CC)CC)C2=C1 FVPNTAOFROJSCG-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 235000019197 fats Nutrition 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 235000019382 gum benzoic Nutrition 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 235000013311 vegetables Nutrition 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
- 235000021419 vinegar Nutrition 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Nr. 390 792No. 390 792
Die Erfindung betrifft ein Verfahren zur Herstellung von neuen Imidazochinoxalinen der allgemeinen Formel 1 2^C°-R1 9The invention relates to a process for the preparation of new imidazoquinoxalines of the general formula 1 2 ^ C ° -R1 9
.(I) worin Rj eine Alkoxygruppe mit 1 bis 5 C-Atomen bedeutet und R2 eine Gruppe -A-(CH9)m-Y darstellt, worin A eine Gruppe -CO- oder -C02-, m eine ganze Zahl von 1 bis 3 und Y eine Gruppe. (I) in which Rj is an alkoxy group having 1 to 5 carbon atoms and R2 is a group -A- (CH9) mY, in which A is a group -CO- or -C02-, m is an integer from 1 to 3 and Y a group
-N-N
bedeuten, in der und R4, die gleich oder verschieden sein können, ein Wasserstoffatom, eine geradkettige oder verzweigte Alkylgruppe mit 1 bis 5 C-Atomen, eine Cycloalkylgruppe mit 3 bis 7 C-Atomen, eine Aryl- oder Aralkylgruppe mit 6 bis 8 C-Atomen bedeuten, oder R3 und R4 zusammen mit dem N-Atom, an das sie gebunden sind, einen gesättigten Heterocyclus mit 4 bis 8 C-Atomen bilden, der ein Sauerstoff-, Schwefel- oder ein weiteres Stickstoffatom enthalten kann, wobei dieses Stickstoffatom seinerseits durch eine Alkylgruppe mit 1 bis 3 C-Atomen oder durch eine Alkoxycarbonylgruppe mit 2 bis 5 C-Atomen substituiert sein kann, sowie von deren Salzen, welches dadurch gekennzeichnet ist, daß man eine Verbindung der Formelmean in which and R4, which may be the same or different, a hydrogen atom, a straight-chain or branched alkyl group having 1 to 5 carbon atoms, a cycloalkyl group having 3 to 7 carbon atoms, an aryl or aralkyl group having 6 to 8 carbon atoms -Atoms mean, or R3 and R4 together with the N atom to which they are attached form a saturated heterocycle with 4 to 8 C atoms, which may contain an oxygen, sulfur or another nitrogen atom, this nitrogen atom may in turn be substituted by an alkyl group having 1 to 3 carbon atoms or by an alkoxycarbonyl group having 2 to 5 carbon atoms, and by their salts, which is characterized in that a compound of the formula
HH
.cm worin Ale eine Alkylgruppe mit 1 bis 5 C-Atomen bedeutet, mit einer Verbindung der Formel.cm in which ale is an alkyl group having 1 to 5 carbon atoms, with a compound of the formula
Q-A-(CH2)m-Q -2- 5Q-A- (CH2) m-Q -2- 5
Nr. 390 792 worin A und m die angeführte Bedeutung haben und Q ein Halogenatom bedeutet, umsetzt, und die erhaltene Verbindung der FormelNo. 390 792 wherein A and m have the meaning given and Q represents a halogen atom, and the compound of the formula obtained
10 15 20 worin A, Ale, m und Q die angeführte Bedeutung haben, mit einer Verbindung der Formel10 15 20 wherein A, Ale, m and Q have the meaning given, with a compound of the formula
H-Y 25 ,(X) worin Y die angeführte Bedeutung hat, umsetzt, und die erhaltene Verbindung der Formel 30 35 40H-Y 25, (X) in which Y has the meaning given, and the compound of the formula 30 35 40 obtained
ÖD> 45 worin A, Ale, m und Y die angeführte Bedeutung haben, gewünschtenfalls in ein Salz überführtÖD > 45 where A, Ale, m and Y have the meaning given, if desired converted into a salt
Bevorzugte Ausführungsformen des erfindungsgemäßen Verfahrens bestehen darin, daß man die Umsetzung der Verbindung der Formel (1^) mit der Verbindung der Formel (VII) in einem organischen, wasserfreien 50 Lösungsmittel, wie Dimethylformamid, Toluol, Tetrahydrofuran, oder in einem Chlorkohlenwasserstoff, wie Dichlormethan, Chloroform oder Dichloräthan, gegebenenfalls in Anwesenheit einer anorganischen Base, wie Natrium- oder Kaliumcarbonat durchführt; und daß man die Umsetzung der Verbindung der Formel (IX) mit der Verbindung der Formel (X) in einem wasserfreien, organischen Lösungsmittel, wie Toluol, Tetrahydrofuran, Dichlormethan oder Dichloräthan, durchführt 55 In der allgemeinen Formel (I) und in den folgenden bedeutet: - der Ausdruck Alkoxygruppe mit 1 - 5 C-Atomen z. B. eine Methoxy-, Äthoxy-, Propoxy-, Isopropoxy- oder Butoxy-Gruppe; - der Ausdruck Alkylgruppe mit 1 - 5 C-Atomen z. B. eine Methyl-, Äthyl-, n-Propyl-, Isopropyl-, n-Butyl-, Isobutyl-, tertButyi-, n-Pentyl-, Isopentyl-Gruppe; 60 - der Ausdruck Cycloalkylgruppe mit 3 - 7 C-Atomen z. B. eine Cyclopropyl-, Cyclobutyl-, Cyclopentyl-,Preferred embodiments of the process according to the invention consist in reacting the compound of formula (1 ^) with the compound of formula (VII) in an organic, anhydrous solvent, such as dimethylformamide, toluene, tetrahydrofuran, or in a chlorinated hydrocarbon, such as dichloromethane , Chloroform or dichloroethane, optionally in the presence of an inorganic base, such as sodium or potassium carbonate; and that one carries out the reaction of the compound of formula (IX) with the compound of formula (X) in an anhydrous organic solvent such as toluene, tetrahydrofuran, dichloromethane or dichloroethane 55 In the general formula (I) and in the following means : - the expression alkoxy group with 1-5 carbon atoms z. B. a methoxy, ethoxy, propoxy, isopropoxy or butoxy group; - The expression alkyl group with 1-5 carbon atoms z. B. a methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl group; 60 - the expression cycloalkyl group with 3 - 7 C atoms z. B. a cyclopropyl, cyclobutyl, cyclopentyl,
Cyclohexyl-, oder Cycloheptyl-Gruppe; -3-Cyclohexyl or cycloheptyl group; -3-
Nr. 390 792 - der Ausdruck Alkoxycarbonylgruppe mit 2-5 C-Atomen z. B. eine Methoxycarbonyl- oder Äthoxycarbonyl-Gruppe; - der Ausdruck Aryl- oder Aralkylgruppe mit 6-8 C-Atomen z. B. eine Phenyl-, Benzyl- oder Phenäthylgruppe; - der Ausdruck gesättigter Heterocyclus mit 4 - 8 C-Atomen, der ein Sauerstoffatom, Schwefelatom oder ein anderes Stickstoffatom enthalten kann, bezeichnet z. B. eine Gruppe wie die Pyrrolidino-, Piperidino-2,3,4,5,6,7-Hexahydroazepino-, Tropanyl-, Morpholino- oder Piperazin-l-yl-Gruppe.No. 390 792 - the expression alkoxycarbonyl group with 2-5 C atoms z. B. a methoxycarbonyl or ethoxycarbonyl group; - The expression aryl or aralkyl group with 6-8 C atoms z. B. a phenyl, benzyl or phenethyl group; - The expression saturated heterocycle with 4 - 8 C atoms, which may contain an oxygen atom, sulfur atom or another nitrogen atom, denotes e.g. B. a group such as the pyrrolidino, piperidino-2,3,4,5,6,7-hexahydroazepino, tropanyl, morpholino or piperazin-l-yl group.
Die Verbindungen der Formel (I) besitzen basischen Charakter; in diesem Falle können die gebildeten Salze z. B. jene sein, die mit Hilfe von Salzsäure, Bromwasserstoffsäure, Jodwasserstoffsäure, Salpeter-, Schwefel-, Phosphor-, Essig-, Ameisen-, Benzoe-, Malein-, Fumar-, Bernstein-, Wein-, Zitronen-, Oxal-, Asparaginsäure, Alkansulfonsäuren, wie Methansulfonsäure und Arylsulfonsäuren, wie Benzolsulfonsäuren, gebildet sind.The compounds of formula (I) have a basic character; in this case the salts formed z. B. be those using hydrochloric acid, hydrobromic acid, hydroiodic acid, nitric acid, sulfuric acid, phosphoric acid, vinegar, ants, benzoin, maleic, fumaric, amber, wine, lemon, oxalic , Aspartic acid, alkanesulfonic acids such as methanesulfonic acid and arylsulfonic acids such as benzenesulfonic acids.
Die erfindungsgemäß erhaltenen Verbindungen besitzen sehr interessante pharmakologische Eigenschaften; sie sind besonders durch bemerkenswerte antiallergische Eigenschaften ausgezeichnetThe compounds obtained according to the invention have very interesting pharmacological properties; they are particularly characterized by remarkable anti-allergic properties
Diese Eigenschaften worden im experimentellen Teil erläutertThese properties were explained in the experimental section
Diese Eigenschaften begründen die Verwendbarkeit der neuen Imidazochinoxaline sowie ihrer pharmazeutisch annehmbaren Salze als Medikamente.These properties justify the use of the new imidazoquinoxalines and their pharmaceutically acceptable salts as medicines.
Diese Medikamente vorwendet man z. B. bei der Behandlung von allergischem Asthma und asthmatischer Bronchitis allergischer Herkunft.These drugs are used e.g. B. in the treatment of allergic asthma and asthmatic bronchitis of allergic origin.
Die Medikation richtet sich nach dem verwendeten Produkt, dem zu behandelnden Patienten und der jeweiligen Krankheit und beträgt z. B. 0,25 mg bis 100 mg pro Tag auf oralem Wege beim Erwachsenen.The medication depends on the product used, the patient to be treated and the respective disease. B. 0.25 mg to 100 mg per day orally in adults.
Die Verbindungen gemäß Formel I sowie ihre pharmazeutisch annehmbaren Salze können in pharmazeutische Zubereitungen einverleibt werden, die zur Verabreichung über den Verdauungstrakt, parenteral oder lokal bestimmt sind.The compounds of the formula I and their pharmaceutically acceptable salts can be incorporated into pharmaceutical preparations which are intended for administration via the digestive tract, parenterally or locally.
Die pharmazeutischen Zubereitungen können z. B. fest oder flüssig sein und in all jenen Formen vorliegen, die man stets in der Humanmedizin verwendet, wie z. B. als einfache oder umhüllte Tabletten, Kapseln, Granalien, Suppositorien, Sirupe, Aerosole, Cremen, Pommaden, injizierbare Zubereitungen; sie werden nach üblichen Methoden bereitet. Der oder die Wirkstoff(e) können in übliche Exzipienten einverleibt werden, die man in pharmazeutischen Zubereitungen verwendet, wie Talk, Gummi arabicum, Milchzucker, Stärke, Magnesiumstearat, Kakaobutter, wässerige oder nichtwässerige Vehikel, Fette tierischer oder pflanzlicher Herkunft, Paraffinderivate, Glykole, verschiedene Netz-, Dispergier-, Emulgier- und Konservierungsmittel.The pharmaceutical preparations can e.g. B. be solid or liquid and exist in all those forms that are always used in human medicine, such as. B. as simple or coated tablets, capsules, granules, suppositories, syrups, aerosols, creams, fries, injectable preparations; they are prepared using standard methods. The active ingredient (s) can be incorporated into conventional excipients used in pharmaceutical preparations, such as talc, gum arabic, milk sugar, starch, magnesium stearate, cocoa butter, aqueous or non-aqueous vehicles, fats of animal or vegetable origin, paraffin derivatives, glycols, various wetting, dispersing, emulsifying and preserving agents.
Die folgenden, nicht einschränkenden Beispiele dienen der Erfindungserläuterung.The following non-limiting examples serve to explain the invention.
Beispiel 1: 4,5-Dihydio-5-(diäthylaminoacetyl)imidazo [1,2-a] chinoxalin-2-caibonsäureäthylester.Example 1: 4,5-Dihydio-5- (diethylaminoacetyl) imidazo [1,2-a] quinoxaline-2-caibonic acid ethyl ester.
Stufe A: 4.5-Dihvdro-5-chloracetvlimidazo [1,2-a] chinoxalin-2-caibonsäureäthylester.Step A: 4.5-Dihvdro-5-chloroacetvlimidazo [1,2-a] quinoxaline-2-caibonic acid ethyl ester.
Man löst 2 g 4,5-Dihydroimidazo [1,2-a] chinoxalin-2-carbonsäureäthylester in 20 cm^ Dimethylformamid, fügt dann 2 cm^ Chloracetylchlorid zu und rührt über Nacht. Man filtriert die gebildeten weißen Kristalle ab und kristallisiert sie aus Äthanol um. Man erhält 2,27 g erwartete Verbindung. F = 178 -183°C.2 g of 4,5-dihydroimidazo [1,2-a] quinoxaline-2-carboxylic acid ethyl ester are dissolved in 20 cm ^ dimethylformamide, then 2 cm ^ chloroacetyl chloride is added and the mixture is stirred overnight. The white crystals formed are filtered off and recrystallized from ethanol. 2.27 g of expected compound are obtained. F = 178-183 ° C.
Stufe B: 4,5-Dihydro-5-(diäthylaminoacetyl)imidazo [1,2-a] chinoxalin-2-carbonsäureäthylesler.Step B: 4,5-Dihydro-5- (diethylaminoacetyl) imidazo [1,2-a] quinoxaline-2-carboxylic acid ethyl ester.
Man löst 0,8 g 4,5-Dihydro-5-chloracetylimidazo [1,2-a] chinoxalin-2-carbonsäureäthylester in 40 cmr*0.8 g of 4,5-dihydro-5-chloroacetylimidazo [1,2-a] quinoxaline-2-carboxylic acid ethyl ester is dissolved in 40 cm *
Toluol, fügt dann 10 cm^ Diäthylamin zu, rührt über Nacht bei Raumtemperatur, bringt sodann auf 60°C während 6 Stunden. Man gießt die Mischung in Wasser, extrahiert mit Äthylacetat, dekantiert, wäscht die organische Phase mit Wasser, trocknet sie und verdampft das Lösungsmittel. Den Rückstand Chromatographien man an Siliziumdioxid, wobei man mit Chloroform eluiert und so das erwartete Produkt erhält. F = 116 - 118°C.Toluene, then add 10 cm ^ of diethylamine, stir overnight at room temperature, then bring to 60 ° C for 6 hours. The mixture is poured into water, extracted with ethyl acetate, decanted, the organic phase is washed with water, dried and the solvent is evaporated off. The residue was chromatographed on silica, eluting with chloroform to give the expected product. F = 116-118 ° C.
Man verwendet für die Herstellung der folgenden Verbindungen eine analoge Methode wie in Beispiel 1 beschrieben, wobei man aber von der entsprechenden Verbindung der Formel 1^ ausgehtAn analogous method as described in Example 1 is used for the preparation of the following compounds, but starting from the corresponding compound of the formula 1 ^
Beispiel 2:4,5-Dihydro-5-(piperidinoacetyl)imidazo [1,2-a] chinoxalin-2-carbonsäureäthylesterExample 2: 4,5-Dihydro-5- (piperidinoacetyl) imidazo [1,2-a] quinoxaline-2-carboxylic acid ethyl ester
Beispiel 3B: Chlorhydrat des 4,5-Dihydro-5-(2-morpholinoäthoxycarbonyl)imidazo [1,2-a] chmoxalin-2-caibonsäuieäthylestersExample 3B: Chlorohydrate of 4,5-dihydro-5- (2-morpholinoethoxycarbonyl) imidazo [1,2-a] chmoxalin-2-caibonic acid ethyl ester
Beispiel 4: Dichlorhvdrat des 4,5-Dihydro-5-(2-methylpiperazinoäthoxycarbonyl)imidazo [1,2-a] chinoxalin-2-carbonsäureäthylestersExample 4: Dichlorohydrate of 4,5-dihydro-5- (2-methylpiperazinoethoxycarbonyl) imidazo [1,2-a] quinoxaline-2-carboxylic acid ethyl ester
Beispiel 5: Chlorhydrat des 4,5-Dihydro-5-(2-piperidinoäthoxycarbonyl)imidazo [1,2-a] chinoxalm-2-carbonsäureäthylesters. -4-Example 5: Chlorohydrate of 4,5-dihydro-5- (2-piperidinoethoxycarbonyl) imidazo [1,2-a] quinoxalm-2-carboxylic acid ethyl ester. -4-
Nr. 390 792No. 390 792
Tabelle 1Table 1
Os Os © Ό vo o o 2; VO VO r- cs S; CO in CS © f—1 cd mh *-H 1—1 *“· f-H mH c <D T3 oo CO CO co 00 i m 00 Ό o r- •s- VC) vd ’S-’ n vd in o cs cs r* in in in cj CO 00 CO Os ri* rp OS vd co cd ö vd MH* in VO n n rr η cs mH VO VO m in r- r- VO co Os in Z CO wo cs o MM CS mh mm mH -mm <U c ,_M Os co Os co CS CO fä Tf VO o co in Tr vd vd τί in vd vo 0) CQ n co 00 «η in r* CS CO o Γ-* 00 vo o cj vd s TT oo o vd cs* in in TT in 'T in o CS 33 O cs X cs o cs 33 CO | Tp CJ co CJ Formel co O CO z co o u 33 <rs O cf € S cs in O jjf O* in Z cs X cs -½ O u z Z m z u z •rf CS sO Os vo MH CS cs CS CS cs 33 33 33 33 T4 MM 33 33 WO Os o VO O MH MH ^H mH cs |-M CS CS CS cj u cj CJ CJ CJ CJ co u 0 00 MH oo 00 VO Zers. . CS 3 0 O 144 cs 1 c £Ih r- mH 05 O VO CS O mh »M «_ Se!§ So s· £?·§ u g ? 03 03 <3 03 33 03 MH mm mH x: o Λ s Λ u 33 cs ) HCl cs 1¾ cs o u 03 cs 33 CJ V cs 33 CJ z^ cs 33 CJ Q cs 33 o o CS CS cs CS cs cs cs 33 33 33 Mm 33 33 33 CJ CJ CJ CJ u c; u CS CS CS CS o o o o o o o u CJ CJ u CJ CJ u in m in n in in m ä 33 33 33 333 33 33 mH cs CS CS CS CS cs cs 04 cj u u u u CJ U o o o o o O O 1 mm •δ .h c 33 < 03 CQ G, ^ V5 MH cs co CO m o wo o in © MH mH CS cs co CS-5-Os Os © Ό vo o o 2; VO VO r- cs S; CO in CS © f — 1 cd mh * -H 1—1 * “· fH mH c < D T3 oo CO CO co 00 in 00 Ό o r- • s- VC) vd 'S-' n vd in o cs cs r * in in in cj CO 00 CO Os ri * rp OS vd co cd ö vd MH * in VO nn rr η cs mH VO VO m in r- r- VO co Os in Z CO wo cs o MM CS mh mm mH -mm < U c, _M Os co Os co CS CO fä Tf VO o co in Tr vd vd τί in vd vo 0) CQ n co 00 «η in r * CS CO o Γ- * 00 vo o cj vd s TT oo o vd cs * in in TT in 'T in o CS 33 O cs X cs o cs 33 CO | Tp CJ co CJ formula co O CO z co ou 33 < rs O cf € S cs in O jjf O * in Z cs X cs -½ O uz Z mzuz • rf CS sO Os vo MH CS cs CS CS cs 33 33 33 33 T4 MM 33 33 WO Os o VO O MH MH ^ H mH cs | -M CS CS CS cj u cj CJ CJ CJ CJ co u 0 00 MH oo 00 VO Zers. . CS 3 0 O 144 cs 1 c £ Ih r- mH 05 O VO CS O mh "M" _ Se! § So s · £? · § u g? 03 03 < 3 03 33 03 MH mm mH x: o Λ s Λ u 33 cs) HCl cs 1¾ cs ou 03 cs 33 CJ V cs 33 CJ z ^ cs 33 CJ Q cs 33 oo CS CS cs CS cs cs cs 33 33 33 mm 33 33 33 CJ CJ CJ CJ uc; u CS CS CS CS o o o o o o o CJ CJ u CJ CJ u in m in n in in m ä 33 33 33 333 33 33 mH cs CS CS CS CS cs cs 04 cj u u u u CJ U o o o o o O O 1 mm • δ .h c 33 < 03 CQ G, ^ V5 MH cs co CO m o wo o in © MH mH CS cs co CS-5-
Claims (2)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AT298486A AT390792B (en) | 1982-04-28 | 1986-11-10 | Process for the preparation of novel imidazoquinoxalines and their salts |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB8212325 | 1982-04-28 | ||
| AT0154183A AT390063B (en) | 1982-04-28 | 1983-04-28 | METHOD FOR PRODUCING NEW IMIDAZOCHINOXALINES AND THEIR SALTS |
| AT298486A AT390792B (en) | 1982-04-28 | 1986-11-10 | Process for the preparation of novel imidazoquinoxalines and their salts |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| ATA298486A ATA298486A (en) | 1989-12-15 |
| AT390792B true AT390792B (en) | 1990-06-25 |
Family
ID=27147630
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AT298486A AT390792B (en) | 1982-04-28 | 1986-11-10 | Process for the preparation of novel imidazoquinoxalines and their salts |
Country Status (1)
| Country | Link |
|---|---|
| AT (1) | AT390792B (en) |
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1986
- 1986-11-10 AT AT298486A patent/AT390792B/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
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| ATA298486A (en) | 1989-12-15 |
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