NO169437B - 3-amino-kinoliner. - Google Patents
3-amino-kinoliner. Download PDFInfo
- Publication number
- NO169437B NO169437B NO890825A NO890825A NO169437B NO 169437 B NO169437 B NO 169437B NO 890825 A NO890825 A NO 890825A NO 890825 A NO890825 A NO 890825A NO 169437 B NO169437 B NO 169437B
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- Prior art keywords
- carbon atoms
- compounds
- amino
- alkyl
- formula
- Prior art date
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- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 17
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 3
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 3
- 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 3
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 3
- 150000002367 halogens Chemical class 0.000 claims abstract description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 3
- 239000001257 hydrogen Substances 0.000 claims abstract description 3
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 3
- 125000001424 substituent group Chemical group 0.000 claims abstract description 3
- 150000005014 3-aminoquinolines Chemical class 0.000 claims description 2
- 125000004990 dihydroxyalkyl group Chemical group 0.000 claims description 2
- 150000001875 compounds Chemical class 0.000 abstract description 19
- 239000000543 intermediate Substances 0.000 abstract description 4
- ITIRVXDSMXFTPW-UHFFFAOYSA-N 1H-imidazo[4,5-c]quinoline Chemical class C1=CC=CC2=C(NC=N3)C3=CN=C21 ITIRVXDSMXFTPW-UHFFFAOYSA-N 0.000 abstract 1
- 230000015572 biosynthetic process Effects 0.000 abstract 1
- 238000003786 synthesis reaction Methods 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 238000001914 filtration Methods 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 238000000034 method Methods 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 239000013067 intermediate product Substances 0.000 description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- ZRFUZDDJSQVQBY-UHFFFAOYSA-N 4-chloro-3-nitroquinoline Chemical compound C1=CC=CC2=C(Cl)C([N+](=O)[O-])=CN=C21 ZRFUZDDJSQVQBY-UHFFFAOYSA-N 0.000 description 3
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000000908 ammonium hydroxide Substances 0.000 description 3
- KDSNLYIMUZNERS-UHFFFAOYSA-N 2-methylpropanamine Chemical compound CC(C)CN KDSNLYIMUZNERS-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- QGJOPFRUJISHPQ-UHFFFAOYSA-N Carbon disulfide Chemical compound S=C=S QGJOPFRUJISHPQ-UHFFFAOYSA-N 0.000 description 2
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- 229940124630 bronchodilator Drugs 0.000 description 2
- 239000000168 bronchodilator agent Substances 0.000 description 2
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- CDUWBBGUDMBQDE-UHFFFAOYSA-N n-(2-methylpropyl)-3-nitroquinolin-4-amine Chemical compound C1=CC=C2C(NCC(C)C)=C([N+]([O-])=O)C=NC2=C1 CDUWBBGUDMBQDE-UHFFFAOYSA-N 0.000 description 2
- LWIDZOGTVKRTBL-UHFFFAOYSA-N n-(cyclohexylmethyl)-3-nitroquinolin-4-amine Chemical compound [O-][N+](=O)C1=CN=C2C=CC=CC2=C1NCC1CCCCC1 LWIDZOGTVKRTBL-UHFFFAOYSA-N 0.000 description 2
- 150000002905 orthoesters Chemical class 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- NDQXKKFRNOPRDW-UHFFFAOYSA-N 1,1,1-triethoxyethane Chemical compound CCOC(C)(OCC)OCC NDQXKKFRNOPRDW-UHFFFAOYSA-N 0.000 description 1
- OUTIRSSPHAPPPQ-UHFFFAOYSA-N 1,2-dimethylimidazo[4,5-c]quinoline Chemical compound C1=CC=CC2=C(N(C(C)=N3)C)C3=CN=C21 OUTIRSSPHAPPPQ-UHFFFAOYSA-N 0.000 description 1
- QLVBTVZLMBLWSG-UHFFFAOYSA-N 1-(cyclohexylmethyl)imidazo[4,5-c]quinoline Chemical compound C1=NC2=CN=C3C=CC=CC3=C2N1CC1CCCCC1 QLVBTVZLMBLWSG-UHFFFAOYSA-N 0.000 description 1
- BHKKSKOHRFHHIN-MRVPVSSYSA-N 1-[[2-[(1R)-1-aminoethyl]-4-chlorophenyl]methyl]-2-sulfanylidene-5H-pyrrolo[3,2-d]pyrimidin-4-one Chemical compound N[C@H](C)C1=C(CN2C(NC(C3=C2C=CN3)=O)=S)C=CC(=C1)Cl BHKKSKOHRFHHIN-MRVPVSSYSA-N 0.000 description 1
- 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 1
- UXHQLGLGLZKHTC-CUNXSJBXSA-N 4-[(3s,3ar)-3-cyclopentyl-7-(4-hydroxypiperidine-1-carbonyl)-3,3a,4,5-tetrahydropyrazolo[3,4-f]quinolin-2-yl]-2-chlorobenzonitrile Chemical compound C1CC(O)CCN1C(=O)C1=CC=C(C=2[C@@H]([C@H](C3CCCC3)N(N=2)C=2C=C(Cl)C(C#N)=CC=2)CC2)C2=N1 UXHQLGLGLZKHTC-CUNXSJBXSA-N 0.000 description 1
- NARMRWUULYDZIS-UHFFFAOYSA-N 4-n-(cyclohexylmethyl)quinoline-3,4-diamine Chemical compound NC1=CN=C2C=CC=CC2=C1NCC1CCCCC1 NARMRWUULYDZIS-UHFFFAOYSA-N 0.000 description 1
- OGAYBYZECXWINC-UHFFFAOYSA-N 4-n-methylquinoline-3,4-diamine Chemical compound C1=CC=C2C(NC)=C(N)C=NC2=C1 OGAYBYZECXWINC-UHFFFAOYSA-N 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- XTUVJUMINZSXGF-UHFFFAOYSA-N N-methylcyclohexylamine Chemical compound CNC1CCCCC1 XTUVJUMINZSXGF-UHFFFAOYSA-N 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 229940111121 antirheumatic drug quinolines Drugs 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- IRUNKQSGDBYUDC-UHFFFAOYSA-N diethoxymethyl acetate Chemical compound CCOC(OCC)OC(C)=O IRUNKQSGDBYUDC-UHFFFAOYSA-N 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 230000002363 herbicidal effect Effects 0.000 description 1
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- HAAYRLITTXBZOP-UHFFFAOYSA-N n-methyl-3-nitroquinolin-4-amine Chemical compound C1=CC=C2C(NC)=C([N+]([O-])=O)C=NC2=C1 HAAYRLITTXBZOP-UHFFFAOYSA-N 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000010183 spectrum analysis Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- 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
- A61P11/08—Bronchodilators
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/38—Nitrogen atoms
- C07D215/42—Nitrogen atoms attached in position 4
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Oncology (AREA)
- Communicable Diseases (AREA)
- Virology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pulmonology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Physical Water Treatments (AREA)
- Plural Heterocyclic Compounds (AREA)
- Macromonomer-Based Addition Polymer (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Alarm Systems (AREA)
- Quinoline Compounds (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
- Luminescent Compositions (AREA)
- Lubricants (AREA)
Description
Foreliggende oppfinnelse angår 3-aminokinoliner. Forbindelsene er anvendbare som utgangsmaterialer for fremstilling av forbindelser som anvendes som bronchodilatorer og/eller som antivirale midler.
Fremstilling av de terapeutisk aktive forbindelser er beskrevet i norsk patent 163 819.
US patentskrift 3 700 6 74 (Diehl et al.) beskriver visse 4-alkylamino-3-:nitrokinoliner. som herbicide forbindelser.
Oppfinnelsen angår i særdeleshet nye forbindelser, hvilke forbindelser er kjennetegnet ved at de har formel
hvori hver gruppe R5 uavhengig er valgt fra alkyl med 1 til 4 carbonatomer, alkoxy med 1 til 4 carbonatomer og halogen, og n er et helt tall 0-2, forutsatt at hvis n er 2, inneholder R5-substituentene til sammen ikke mer enn 6 carbonatomer; R6 er valgt fra hydroxyalkyl eller dihydroksyalkyl med 1 til 6 carbonatomer og cyclohexylmethyl; og R7 er valgt fra alkyl med 1 til 4 carbonatomer og hydrogen.
Forbindelsene fremstilles som vist i det etter-følgende reaksjonsskjerna:
Forbindelser av formel V reduseres katalytisk under anvendelse av en platinakatalysator slik som platina-på-carbon, under dannelse av forbindelser I. Reduksjonen utføres hensiktsmessig i en Parr-apparatur i et ikke-reaktivt løs-ningsmiddel slik som toluen eller en lavere alkanol.
Mellomproduktene I anvendes som beskrevet i norsk patent nr. 163 819 til fremstilling av farmasøytisk aktive forbindelser etter følgende reaksjonsskjerna:
hvor R2 har den i stamsøknaden angitte betydning.
I denne reaksjon omsettes mellomproduktene av formel I med et dialkoxyalkylalkanoat slik som diethoxymethylacetat, eller en carboxylsyre som kan innføre den ønskede R2-gruppe eller en trialkylorthoester av formel R2C(Oalkyl)3, hvor alkyl-gruppen inneholder 1-4 carbonatomer, eller kombinasjonen av en slik trialkylorthoester og en slik carboxylsyre under dannelse av en hittil ukjent forbindelse. Reaksjonen utføres ved oppvarming, for eksempel til 130°C i nærvær av en syre, fortrinnsvis en alkansyre med 1 carbonatom mer enn R2. Egnede syrer innbefatter også halogenalkansyrer, aminoalkansyrer, hydroxyalkansyrer og lignende. Carbondisulfid kan også anvendes i nærvær av en sterk base under dannelse av forbindelser hvori R2 er -SH. De fremstilte forbindelser er som nevnt aktive som bronchodilatorer.
Oppfinnelsen illustreres nærmere i de etterfølgende eksempler, fremstillingen og anvendelsen av mellomproduktene.
Eksempel 1
Fremstilling av en forbindelse av formel V
Til en løsning av 50,0 g (0,24 mol) 4-klor-3-nitrokinolin i 300 ml tetrahydrofuran ble tilsatt i små porsjoner 52,7 g (0,72 mol) isobutylamin. Blandingen ble oppvarmet til tilbakeløpstemperaturen i 1 time og ble deretter inndampet i vakuum. Vann ble tilsatt til residuet, og det faste stoff ble fraskilt ved filtrering. Det faste stoff ble suspendert i 1 liter vann og oppløst ved gradvis tilsetning av konsentrert saltsyre (til pH 3 - 4) etterfulgt av filtrering av oppløsningen. Filtratet ble gjort basisk
(til pH 9 - 10) ved tilsetning av konsentrert ammoniumhydroxyd under dannelse av lysegult 4-(isobutylamino)-3-nitro-kinolin, sra.p. 119 - 121° C> Den strukturelle bekreftelse ble understøttet av infrarød spektralanalyse.
Eksempel 2
Alternativ fremstilling av en forbindelse av formel V
Til en omrørt oppløsning av 40 % vandig methylamin ble i små porsjoner tilsatt 30,0 g (0,144 mol) 4-klor-3-nitrokinolin. Reaksjonsblandingen ble deretter oppvarmet til tilbakeløpstemperaturen i 0,75 timer. Etter avkjøling ble blandingen helt over i 300 ml vann. Det faste stoff ble fraskilt ved filtrering og ble deretter suspendert i 300 ml vann. Surgjøring med 6N saltsyre til pH 3 - 4 ga oppløsning av størstedelen av det faste stoff. Etter filtrering ble filtratet gjort basisk med konsentrert ammoniumhydroxyd til pH 8 - 10 under dannelse av et gult bunnfall. Det faste stoff ble fraskilt ved filtrering, vasket med vann og omkrystallisert fra ethanol under dannelse av gult 4-methylamino-3-nitrokinolin, sm.p. 168 - 170° C.
Analyse for C^<Hg>N^O,,:
Beregnet: C 59,1 H4,5 N 20,7 I
Funnet : C 59,0 H 4,2 N 20,8 %
Under anvendelse av de metoder som er beskrevet i eksempel 1 og 2 ut fra de angitte substituerte kinoliner og primære aminer ble følgende forbindelse- av formel V fremstilt (tabell I) .
Eksempel 7
Fremstilling av en forbindelse av formel I
Til en oppløsning av 57,3 g (0,23 mol) 4-(isobutyl-amino) -3-nitrokinolin (fra eksempel 1) i 600 ml ethanol ble tilsatt 2 g platina-på-carbon, og den resulterende blanding ble hydrogenert i en Parr-apparatur i 3 timer. Filtrering etterfulgt av inndampning i vakuum ga et residuum som gradvis størket til et gult fast stoff, 3-amino-4-(isobutyl-amino). -kinolin .
Under anvendelse av metoden beskrevet i eksempel 7 ut fra de angitte mellomprodukter av formel V ble fremstilt de mellomprodukter av formel I som er angitt i tabell II. I de tilfeller hvor hydrokloridet er angitt, ble dette oppnådd ved først å boblehydrogenklorid gjennom en ethan-oppløsning av det frie amin hvorpå det faste produkt ble fraskilt ved filtrering.
5
Eksempel - 12
Anvendelse av mellomproduktet
0,207 mol urent 3-amino-4-(methylamino)kinolin erholdt ved fremgangsmåten ifølge eksempel 26 ble blandet med 500 ml iseddik og 76 ml triethylorthoacetat, og den resulterende blanding ble oppvarmet under tilbakeløpskjøling i 2 timer. Inndampning ga et residuum som ble oppløst i 800 ml vann. Oppløsningen ble gjort basisk med konsentrert ammoniumhydroxyd. Det faste stoff ble fraskilt ved filtrering og vasket med vann under dannelse av 1,2-dimethyl-lH-imidazo [4 ,5-c ]kinolin. Når en prøve av dette produkt ble omkrystallisert med diethylether hadde den et smeltepunkt på 194 - 196° c.
Analyse for C12<H>11<N3:>
Beregnet: C 73,1 H 5,6 N 21,3 %
Funnet : C 73,4 H 5,7 N 21,5
Under anvendelse av metoden beskrevet i eksempel 12 ut fra de angitte mellomprodukter, carboxylsyrer og tri-alkylorthoestere ble de sluttprodukter, SOm er angitt i tabell III, fremstilt.
Eksempel 17-
Del A
En blanding av 26,1 g (0,125 mol) 4-klor-3-nitrokinolin, 16,4 g (0,1275 mol) 95 % cyclohexylmethylamin og 16,5 g (0,125 mol) 95 % diisopropylethylamin i 300 ml tetrahydrofuran ble oppvarmet på et dampbad i 1/2 time. Oppløs-ningen ble inndampet og resten ble oppslemmet i methanol,
ble filtrert og vasket med methanol. Omkrystallisering fra methanol ga gule plaster av 4-cyclohexylmethylamino-3-nitro-kinolin, sm.p. 140 - 142° C.
Analyse for ci6H]_9<N>3°<2:>
Beregnet: C 67,3 H 6,7 N 14, 7 %
Funnet : C 67,3 H6,6 N 14,7 %
Del B
Under anvendelse av metoden ifølge eksempel 7 ble 17 g (0,60 mol) 4-cyclohexylmethylamino-3-nitrokinolin redu-sert til 3-amino-4-cyclohexylmethylaminokinolin.
Del C
Det urene produkt fra del B ble oppvarmet under tilbakeløpskjøling i 2 1/2 time i 250 ml 98 % maursyre under dannelse av 1-cyclohexylmethyl-lH-imidazo[4,5-c]kinolin som et blek gult fast stoff.
Claims (1)
- 3-aminokinoliner,karakterisert ved at de har formelhvori hver gruppe R5 uavhengig er valgt fra alkyl med 1 til 4 carbonatomer, alkoxy med 1 til 4 carbonatomer og halogen, og n er et helt tall 0-2, forutsatt at hvis n er 2, inneholder R5-substituentene til sammen ikke mer enn 6 carbonatomer; R6 er valgt fra hydroxyalkyl eller dihydroxyalkyl med 1 til 6 carbonatomer og cyclohexylmethyl; og R7 er valgt fra alkyl med 1 til 4 carbonatomer og hydrogen.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NO890825A NO169437C (no) | 1983-11-18 | 1989-02-27 | 3-amino-kinoliner. |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US55315783A | 1983-11-18 | 1983-11-18 | |
| US55315883A | 1983-11-18 | 1983-11-18 | |
| NO844565A NO163819C (no) | 1983-11-18 | 1984-11-15 | Analogifremgangsmaate for fremstilling av terapeutisk aktive 1h-imidazo(4,5-c)kinolin og derivater derav. |
| NO890825A NO169437C (no) | 1983-11-18 | 1989-02-27 | 3-amino-kinoliner. |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| NO890825L NO890825L (no) | 1985-05-20 |
| NO890825D0 NO890825D0 (no) | 1989-02-27 |
| NO169437B true NO169437B (no) | 1992-03-16 |
| NO169437C NO169437C (no) | 1992-06-24 |
Family
ID=27070262
Family Applications (7)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO844565A NO163819C (no) | 1983-11-18 | 1984-11-15 | Analogifremgangsmaate for fremstilling av terapeutisk aktive 1h-imidazo(4,5-c)kinolin og derivater derav. |
| NO890825A NO169437C (no) | 1983-11-18 | 1989-02-27 | 3-amino-kinoliner. |
| NO890826A NO168705C (no) | 1983-11-18 | 1989-02-27 | 3-nitro-kinoliner. |
| NO890824A NO165147C (no) | 1983-11-18 | 1989-02-27 | 1h-imidazo(4,5-c)-kinolin-5-oxydforbindelser. |
| NO890823A NO165146C (no) | 1983-11-18 | 1989-02-27 | 1h-imidazo-(4,5-c)-kinolin-4-klorforbindelser. |
| NO890822A NO165145C (no) | 1983-11-18 | 1989-02-27 | Analogifremgangsmaate for fremstilling av terapeutisk aktive 1h-imidazo-(4,5-c)-kinolin-4-aminderivater. |
| NO1999015C NO1999015I1 (no) | 1983-11-18 | 1999-07-08 | Imiquimod |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO844565A NO163819C (no) | 1983-11-18 | 1984-11-15 | Analogifremgangsmaate for fremstilling av terapeutisk aktive 1h-imidazo(4,5-c)kinolin og derivater derav. |
Family Applications After (5)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO890826A NO168705C (no) | 1983-11-18 | 1989-02-27 | 3-nitro-kinoliner. |
| NO890824A NO165147C (no) | 1983-11-18 | 1989-02-27 | 1h-imidazo(4,5-c)-kinolin-5-oxydforbindelser. |
| NO890823A NO165146C (no) | 1983-11-18 | 1989-02-27 | 1h-imidazo-(4,5-c)-kinolin-4-klorforbindelser. |
| NO890822A NO165145C (no) | 1983-11-18 | 1989-02-27 | Analogifremgangsmaate for fremstilling av terapeutisk aktive 1h-imidazo-(4,5-c)-kinolin-4-aminderivater. |
| NO1999015C NO1999015I1 (no) | 1983-11-18 | 1999-07-08 | Imiquimod |
Country Status (15)
| Country | Link |
|---|---|
| EP (2) | EP0310950B1 (no) |
| JP (1) | JPS60123488A (no) |
| KR (1) | KR900005657B1 (no) |
| AT (2) | ATE84525T1 (no) |
| AU (2) | AU581190B2 (no) |
| CA (1) | CA1271477A (no) |
| DE (3) | DE3486043T2 (no) |
| DK (6) | DK164280C (no) |
| ES (1) | ES8603477A1 (no) |
| IE (1) | IE57874B1 (no) |
| IL (2) | IL84537A (no) |
| NL (2) | NL980041I2 (no) |
| NO (7) | NO163819C (no) |
| NZ (1) | NZ210228A (no) |
| PH (1) | PH22338A (no) |
Families Citing this family (72)
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| CA1306260C (en) * | 1985-10-18 | 1992-08-11 | Shionogi & Co., Ltd. | Condensed imidazopyridine derivatives |
| US4942168A (en) * | 1987-07-13 | 1990-07-17 | Hoechst-Roussel Pharmaceuticals Inc. | Hydroxyquinoline amines, and method of enhancing memory in mammals |
| CA1335996C (en) * | 1988-02-16 | 1995-06-20 | Susumu Takada | 2-substituted carbonylimidazo¬4,5-c|quinolines |
| EP0361489A3 (en) * | 1988-09-30 | 1991-06-12 | Chugai Seiyaku Kabushiki Kaisha | Novel 3,4-diaminoquinoline and pyridine compounds |
| EP0385630B1 (en) * | 1989-02-27 | 1996-11-27 | Riker Laboratories, Inc. | 1H-imidazo(4,5-c)Quinolin-4-amines as antivirals |
| US4994468A (en) * | 1989-03-07 | 1991-02-19 | Kyowa Hakko Kogyo Co., Ltd. | Imidazoquinolone derivatives |
| US4929624A (en) * | 1989-03-23 | 1990-05-29 | Minnesota Mining And Manufacturing Company | Olefinic 1H-imidazo(4,5-c)quinolin-4-amines |
| CA2021338C (en) * | 1989-07-18 | 1996-07-16 | Fumio Suzuki | Imidazoquinolone derivatives |
| US4988815A (en) * | 1989-10-26 | 1991-01-29 | Riker Laboratories, Inc. | 3-Amino or 3-nitro quinoline compounds which are intermediates in preparing 1H-imidazo[4,5-c]quinolines |
| FR2654021B1 (fr) * | 1989-11-07 | 1992-02-28 | Simond Jacques | Procede de vitrification de cendres volantes et dispositif pour sa mise en óoeuvre. |
| GB8928281D0 (en) * | 1989-12-14 | 1990-02-21 | Smith Kline French Lab | Compounds |
| EP0459505B1 (en) * | 1990-06-01 | 1996-10-02 | Kyowa Hakko Kogyo Co., Ltd. | Imidazonaphthyridine derivatives |
| WO1992015582A1 (en) * | 1991-03-01 | 1992-09-17 | Minnesota Mining And Manufacturing Company | 1-SUBSTITUTED, 2-SUBSTITUTED 1H-IMIDAZO[4,5-c]QUINOLIN-4-AMINES |
| US5266575A (en) * | 1991-11-06 | 1993-11-30 | Minnesota Mining And Manufacturing Company | 2-ethyl 1H-imidazo[4,5-ciquinolin-4-amines |
| IL105325A (en) * | 1992-04-16 | 1996-11-14 | Minnesota Mining & Mfg | Immunogen/vaccine adjuvant composition |
| US5395937A (en) * | 1993-01-29 | 1995-03-07 | Minnesota Mining And Manufacturing Company | Process for preparing quinoline amines |
| US5693811A (en) * | 1996-06-21 | 1997-12-02 | Minnesota Mining And Manufacturing Company | Process for preparing tetrahdroimidazoquinolinamines |
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| JP2000119271A (ja) * | 1998-08-12 | 2000-04-25 | Hokuriku Seiyaku Co Ltd | １ｈ―イミダゾピリジン誘導体 |
| EP2332922A1 (en) * | 2001-10-23 | 2011-06-15 | Merck Serono S.A. | N-substituted azoles and their use as MEK-1 and/or ERK-2 modulators |
| GB0211649D0 (en) * | 2002-05-21 | 2002-07-03 | Novartis Ag | Organic compounds |
| MXPA05000893A (es) | 2002-07-23 | 2005-09-30 | Biogal Gyogyszergyar | Preparacion de 1h-imidazo[4,5-c]quinolin-4-aminas a traves de compuestos intermedios 1h-imidazo [4,5-c] quinolin-4-ftalimida. |
| SI1539752T1 (sl) | 2002-07-26 | 2007-08-31 | Teva Gyogyszergyar Zartkoruen Mukodo Reszvenytarsasag | Priprava 1H-imidazo(4,5-c)kinolin-4-aminov preko novih imidazo(4,5-c)kinolin-4-ciano in 1H-imidazo(4,5-c)kinolin-4- karboksamidnih intermediatov |
| MXPA06001674A (es) | 2003-08-12 | 2006-05-12 | 3M Innovative Properties Co | Compuestos que contienen imidazo hidroxilamina-sustituidos. |
| EP1658076B1 (en) * | 2003-08-27 | 2013-03-06 | 3M Innovative Properties Company | Aryloxy and arylalkyleneoxy substituted imidazoquinolines |
| EP1660026A4 (en) | 2003-09-05 | 2008-07-16 | 3M Innovative Properties Co | TREATMENT FOR CD5 + B CELL LYMPHOMA |
| WO2005033049A2 (en) | 2003-10-01 | 2005-04-14 | Taro Pharmaceuticals U.S.A., Inc. | METHOD OF PREPARING 4-AMINO-1H-IMIDAZO(4,5-c)QUINOLINES AND ACID ADDITION SALTS THEREOF |
| US7544697B2 (en) | 2003-10-03 | 2009-06-09 | Coley Pharmaceutical Group, Inc. | Pyrazolopyridines and analogs thereof |
| AU2004278014B2 (en) | 2003-10-03 | 2011-04-28 | 3M Innovative Properties Company | Alkoxy substituted imidazoquinolines |
| ITMI20032121A1 (it) * | 2003-11-04 | 2005-05-05 | Dinamite Dipharma Spa In Forma Abbr Eviata Dipharm | Procedimento per la preparazione di imiquimod e suoi intermedi |
| EP1685129A4 (en) | 2003-11-14 | 2008-10-22 | 3M Innovative Properties Co | OXIMSUBSTITUTED IMIDAZORING CONNECTIONS |
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| AR046781A1 (es) | 2003-11-25 | 2005-12-21 | 3M Innovative Properties Co | Derivados de imidazoquinolinas. composiciones farmaceuticas. |
| WO2005066170A1 (en) | 2003-12-29 | 2005-07-21 | 3M Innovative Properties Company | Arylalkenyl and arylalkynyl substituted imidazoquinolines |
| CA2551399A1 (en) | 2003-12-30 | 2005-07-21 | 3M Innovative Properties Company | Imidazoquinolinyl, imidazopyridinyl, and imidazonaphthyridinyl sulfonamides |
| WO2005094531A2 (en) | 2004-03-24 | 2005-10-13 | 3M Innovative Properties Company | Amide substituted imidazopyridines, imidazoquinolines, and imidazonaphthyridines |
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| EP1831221B1 (en) | 2004-12-30 | 2012-08-08 | 3M Innovative Properties Company | Substituted chiral fused 1,2 imidazo 4,5-c ring compounds |
| AU2005322898B2 (en) | 2004-12-30 | 2011-11-24 | 3M Innovative Properties Company | Chiral fused (1,2)imidazo(4,5-c) ring compounds |
| JP2008530022A (ja) | 2005-02-04 | 2008-08-07 | コーリー ファーマシューティカル グループ，インコーポレイテッド | 免疫反応調節物質を含む水性ゲル処方物 |
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| JP2008535832A (ja) | 2005-04-01 | 2008-09-04 | コーリー ファーマシューティカル グループ，インコーポレイテッド | ピラゾロピリジン−１，４−ジアミン、およびそのアナログ |
| US7943636B2 (en) | 2005-04-01 | 2011-05-17 | 3M Innovative Properties Company | 1-substituted pyrazolo (3,4-C) ring compounds as modulators of cytokine biosynthesis for the treatment of viral infections and neoplastic diseases |
| JP2009504803A (ja) | 2005-08-22 | 2009-02-05 | ザ リージェンツ オブ ザ ユニバーシティ オブ カリフォルニア | Ｔｌｒアゴニスト |
| WO2007142755A2 (en) | 2006-05-31 | 2007-12-13 | The Regents Of The University Of California | Purine analogs |
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| CN101790380B (zh) | 2007-02-07 | 2013-07-10 | 加利福尼亚大学董事会 | 合成tlr激动剂的缀合物及其应用 |
| EP2009002A1 (en) * | 2007-06-21 | 2008-12-31 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | New process for the manufacture of 1H-imidazo [4,5-c]-quinoline ring systems |
| WO2010088924A1 (en) | 2009-02-06 | 2010-08-12 | Telormedix Sa | Pharmaceutical compositions comprising imidazoquinolin(amines) and derivatives thereof suitable for local administration |
| BRPI1008383A2 (pt) | 2009-02-11 | 2016-02-23 | Univ California | composto, composição farmacêutica, método para prevenir, inibir ou tratar uma condição, e, uso de um composto |
| CN105294684B (zh) * | 2010-08-17 | 2018-04-06 | 3M创新有限公司 | 脂质化免疫反应调节剂化合物的组合物、制剂及方法 |
| US8728486B2 (en) | 2011-05-18 | 2014-05-20 | University Of Kansas | Toll-like receptor-7 and -8 modulatory 1H imidazoquinoline derived compounds |
| IN2014KN00948A (no) | 2011-10-04 | 2015-08-21 | Janus Biotherapeutics Inc | |
| MX369611B (es) * | 2013-02-01 | 2019-11-14 | Wellstat Therapeutics Corp | Compuestos de amina que tienen actividad anti-inflamatoria, antifungica, antiparasitaria y anticancer. |
| AR095604A1 (es) | 2013-03-15 | 2015-10-28 | Syngenta Participations Ag | Derivados de imidazopiridina útiles como microbicidas |
| ES2538880B1 (es) * | 2013-12-24 | 2016-09-08 | Laboratorios Viñas S.A. | Un procedimiento para obtener 4-amino-1-isobutil-1H-imidazo[4,5-c]quinoleína |
| US10548985B2 (en) | 2014-01-10 | 2020-02-04 | Birdie Biopharmaceuticals, Inc. | Compounds and compositions for treating EGFR expressing tumors |
| EP3166976B1 (en) | 2014-07-09 | 2022-02-23 | Birdie Biopharmaceuticals Inc. | Anti-pd-l1 combinations for treating tumors |
| WO2017046675A1 (en) * | 2015-09-14 | 2017-03-23 | Pfizer Inc. | Novel imidazo [4,5-c] quinoline and imidazo [4,5-c][1,5] naphthyridine derivatives as lrrk2 inhibitors |
| CN115554406A (zh) | 2016-01-07 | 2023-01-03 | 博笛生物科技有限公司 | 用于治疗肿瘤的抗-cd20组合 |
| CN106943597A (zh) | 2016-01-07 | 2017-07-14 | 博笛生物科技（北京）有限公司 | 用于治疗肿瘤的抗-egfr组合 |
| US10533007B2 (en) | 2016-04-19 | 2020-01-14 | Innate Tumor Immunity, Inc. | NLRP3 modulators |
| WO2017184746A1 (en) | 2016-04-19 | 2017-10-26 | Ifm Therapeutics, Inc | Nlrp3 modulators |
| US11697851B2 (en) | 2016-05-24 | 2023-07-11 | The Regents Of The University Of California | Early ovarian cancer detection diagnostic test based on mRNA isoforms |
| TWI674261B (zh) | 2017-02-17 | 2019-10-11 | 美商英能腫瘤免疫股份有限公司 | Nlrp3 調節劑 |
| CN108794467A (zh) | 2017-04-27 | 2018-11-13 | 博笛生物科技有限公司 | 2-氨基-喹啉衍生物 |
| US11517567B2 (en) | 2017-06-23 | 2022-12-06 | Birdie Biopharmaceuticals, Inc. | Pharmaceutical compositions |
| FR3113287B1 (fr) | 2020-08-07 | 2023-06-23 | Phv Pharma | Procédé industriel de synthèse de l’imiquimod à partir de la quinolèine-2,4-diol applicable à son utilisation pharmaceutique |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3700674A (en) * | 1969-04-30 | 1972-10-24 | American Cyanamid Co | 4-alkylamino-3-nitroquinolines |
| RO86850B (ro) * | 1982-05-03 | 1985-05-31 | Eli Lilly And Company | Procedeu pentru prepararea unor 2-fenilimidazo [4,5 c] piridine |
-
1984
- 1984-11-13 CA CA000467706A patent/CA1271477A/en not_active Expired - Lifetime
- 1984-11-14 AU AU35402/84A patent/AU581190B2/en not_active Expired
- 1984-11-15 NO NO844565A patent/NO163819C/no not_active IP Right Cessation
- 1984-11-15 ES ES537677A patent/ES8603477A1/es not_active Expired
- 1984-11-15 DK DK542684A patent/DK164280C/da not_active IP Right Cessation
- 1984-11-16 EP EP88116137A patent/EP0310950B1/en not_active Expired - Lifetime
- 1984-11-16 PH PH31451A patent/PH22338A/en unknown
- 1984-11-16 DE DE8888116137T patent/DE3486043T2/de not_active Expired - Lifetime
- 1984-11-16 IE IE2952/84A patent/IE57874B1/en not_active IP Right Cessation
- 1984-11-16 AT AT88116137T patent/ATE84525T1/de not_active IP Right Cessation
- 1984-11-16 IL IL84537A patent/IL84537A/xx not_active IP Right Cessation
- 1984-11-16 NZ NZ210228A patent/NZ210228A/xx unknown
- 1984-11-16 DE DE1999175027 patent/DE19975027I2/de active Active
- 1984-11-16 EP EP84307974A patent/EP0145340B1/en not_active Expired - Lifetime
- 1984-11-16 AT AT84307974T patent/ATE49763T1/de active
- 1984-11-16 DE DE8484307974T patent/DE3481124D1/de not_active Expired - Lifetime
- 1984-11-17 KR KR1019840007224A patent/KR900005657B1/ko not_active IP Right Cessation
- 1984-11-17 JP JP59243142A patent/JPS60123488A/ja active Granted
-
1987
- 1987-11-19 IL IL84537A patent/IL84537A0/xx unknown
-
1989
- 1989-02-14 AU AU29911/89A patent/AU611997B2/en not_active Expired
- 1989-02-27 NO NO890825A patent/NO169437C/no not_active IP Right Cessation
- 1989-02-27 NO NO890826A patent/NO168705C/no not_active IP Right Cessation
- 1989-02-27 NO NO890824A patent/NO165147C/no not_active IP Right Cessation
- 1989-02-27 NO NO890823A patent/NO165146C/no not_active IP Right Cessation
- 1989-02-27 NO NO890822A patent/NO165145C/no not_active IP Right Cessation
-
1991
- 1991-07-16 DK DK135791A patent/DK169179B1/da not_active IP Right Cessation
- 1991-07-16 DK DK135991A patent/DK165921C/da not_active IP Right Cessation
- 1991-07-16 DK DK136091A patent/DK164451C/da not_active IP Right Cessation
- 1991-07-16 DK DK136191A patent/DK164452C/da not_active IP Right Cessation
- 1991-07-16 DK DK135891A patent/DK164455C/da not_active IP Right Cessation
-
1998
- 1998-12-14 NL NL980041C patent/NL980041I2/nl unknown
- 1998-12-14 NL NL980043C patent/NL980043I1/nl unknown
-
1999
- 1999-07-08 NO NO1999015C patent/NO1999015I1/no unknown
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