NO833541L - Ortosubstituerte dihydroksy-2(1h)kinazolinon-1-alkansyrer og fremgangsmaate for deres fremstilling - Google Patents
Ortosubstituerte dihydroksy-2(1h)kinazolinon-1-alkansyrer og fremgangsmaate for deres fremstillingInfo
- Publication number
- NO833541L NO833541L NO833541A NO833541A NO833541L NO 833541 L NO833541 L NO 833541L NO 833541 A NO833541 A NO 833541A NO 833541 A NO833541 A NO 833541A NO 833541 L NO833541 L NO 833541L
- Authority
- NO
- Norway
- Prior art keywords
- methyl
- quinazolinone
- hydrogen
- dihydroxy
- propionic acid
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 29
- 238000002360 preparation method Methods 0.000 title claims description 12
- 239000002253 acid Substances 0.000 title claims description 9
- 150000007513 acids Chemical class 0.000 title 1
- -1 amine salt Chemical class 0.000 claims abstract description 38
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 35
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 19
- 150000003839 salts Chemical class 0.000 claims abstract description 19
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 10
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 9
- 125000003118 aryl group Chemical group 0.000 claims abstract description 8
- 150000001602 bicycloalkyls Chemical group 0.000 claims abstract description 8
- 125000001188 haloalkyl group Chemical group 0.000 claims abstract description 8
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims abstract description 7
- 125000003435 aroyl group Chemical group 0.000 claims abstract description 6
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 6
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims abstract description 5
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 4
- 125000001589 carboacyl group Chemical group 0.000 claims abstract 3
- 150000001350 alkyl halides Chemical class 0.000 claims abstract 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 63
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 56
- 150000001875 compounds Chemical class 0.000 claims description 45
- 239000001257 hydrogen Substances 0.000 claims description 34
- 229910052739 hydrogen Inorganic materials 0.000 claims description 34
- 150000002431 hydrogen Chemical group 0.000 claims description 27
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 17
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 16
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 claims description 10
- 235000019260 propionic acid Nutrition 0.000 claims description 10
- 239000003085 diluting agent Substances 0.000 claims description 7
- 229910000042 hydrogen bromide Inorganic materials 0.000 claims description 7
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 150000001336 alkenes Chemical class 0.000 claims description 6
- 125000005518 carboxamido group Chemical group 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 6
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 claims description 6
- 229920006395 saturated elastomer Polymers 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- 125000003107 substituted aryl group Chemical group 0.000 claims description 6
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 5
- XRZJCCJKHICMRD-UHFFFAOYSA-N 5,6-dimethoxy-4-methyl-3,4-dihydro-1h-quinazolin-2-one Chemical compound N1C(=O)NC(C)C2=C(OC)C(OC)=CC=C21 XRZJCCJKHICMRD-UHFFFAOYSA-N 0.000 claims description 5
- 230000037396 body weight Effects 0.000 claims description 5
- CCRCUPLGCSFEDV-UHFFFAOYSA-N cinnamic acid methyl ester Natural products COC(=O)C=CC1=CC=CC=C1 CCRCUPLGCSFEDV-UHFFFAOYSA-N 0.000 claims description 5
- CCRCUPLGCSFEDV-BQYQJAHWSA-N methyl trans-cinnamate Chemical compound COC(=O)\C=C\C1=CC=CC=C1 CCRCUPLGCSFEDV-BQYQJAHWSA-N 0.000 claims description 5
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 229910052783 alkali metal Inorganic materials 0.000 claims description 4
- WVNXGAOAWSQPAL-UHFFFAOYSA-N 5,6-dimethoxy-4-methyl-3h-quinazolin-2-one Chemical compound O=C1NC(C)=C2C(OC)=C(OC)C=CC2=N1 WVNXGAOAWSQPAL-UHFFFAOYSA-N 0.000 claims description 3
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 claims description 3
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 3
- 150000001340 alkali metals Chemical class 0.000 claims description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical group IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 claims description 3
- 210000003734 kidney Anatomy 0.000 claims description 3
- MCVVUJPXSBQTRZ-ONEGZZNKSA-N methyl (e)-but-2-enoate Chemical compound COC(=O)\C=C\C MCVVUJPXSBQTRZ-ONEGZZNKSA-N 0.000 claims description 3
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 3
- UXFQFBNBSPQBJW-UHFFFAOYSA-N 2-amino-2-methylpropane-1,3-diol Chemical class OCC(N)(C)CO UXFQFBNBSPQBJW-UHFFFAOYSA-N 0.000 claims description 2
- KQIGMPWTAHJUMN-UHFFFAOYSA-N 3-aminopropane-1,2-diol Chemical class NCC(O)CO KQIGMPWTAHJUMN-UHFFFAOYSA-N 0.000 claims description 2
- IDKXKBBJERCUMF-UHFFFAOYSA-N 5,6-dimethoxy-1h-quinazolin-2-one Chemical compound N1C(=O)N=CC2=C(OC)C(OC)=CC=C21 IDKXKBBJERCUMF-UHFFFAOYSA-N 0.000 claims description 2
- 230000017531 blood circulation Effects 0.000 claims description 2
- 230000003177 cardiotonic effect Effects 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 208000024172 Cardiovascular disease Diseases 0.000 claims 2
- 206010020772 Hypertension Diseases 0.000 claims 1
- 230000003276 anti-hypertensive effect Effects 0.000 claims 1
- 239000002585 base Substances 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
- 235000001014 amino acid Nutrition 0.000 abstract description 4
- 150000001414 amino alcohols Chemical class 0.000 abstract description 3
- 239000000543 intermediate Substances 0.000 abstract description 3
- 239000002327 cardiovascular agent Substances 0.000 abstract description 2
- 229940125692 cardiovascular agent Drugs 0.000 abstract description 2
- IMCGHZIGRANKHV-AJNGGQMLSA-N tert-butyl (3s,5s)-2-oxo-5-[(2s,4s)-5-oxo-4-propan-2-yloxolan-2-yl]-3-propan-2-ylpyrrolidine-1-carboxylate Chemical compound O1C(=O)[C@H](C(C)C)C[C@H]1[C@H]1N(C(=O)OC(C)(C)C)C(=O)[C@H](C(C)C)C1 IMCGHZIGRANKHV-AJNGGQMLSA-N 0.000 abstract description 2
- PUAQLLVFLMYYJJ-UHFFFAOYSA-N 2-aminopropiophenone Chemical compound CC(N)C(=O)C1=CC=CC=C1 PUAQLLVFLMYYJJ-UHFFFAOYSA-N 0.000 abstract 2
- 239000003513 alkali Substances 0.000 abstract 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 abstract 1
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 abstract 1
- 239000000496 cardiotonic agent Substances 0.000 abstract 1
- 239000002184 metal Substances 0.000 abstract 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Natural products C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 abstract 1
- 229940124550 renal vasodilator Drugs 0.000 abstract 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 126
- 239000000243 solution Substances 0.000 description 66
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 63
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 42
- 239000000203 mixture Substances 0.000 description 41
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 39
- 239000007787 solid Substances 0.000 description 38
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 32
- 239000000047 product Substances 0.000 description 31
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 29
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 28
- 239000002244 precipitate Substances 0.000 description 26
- AVRPFRMDMNDIDH-UHFFFAOYSA-N 1h-quinazolin-2-one Chemical class C1=CC=CC2=NC(O)=NC=C21 AVRPFRMDMNDIDH-UHFFFAOYSA-N 0.000 description 25
- 239000002904 solvent Substances 0.000 description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 21
- 239000000725 suspension Substances 0.000 description 20
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 18
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 239000011541 reaction mixture Substances 0.000 description 17
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 16
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 15
- NDKBVBUGCNGSJJ-UHFFFAOYSA-M benzyltrimethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)CC1=CC=CC=C1 NDKBVBUGCNGSJJ-UHFFFAOYSA-M 0.000 description 14
- 125000004432 carbon atom Chemical group C* 0.000 description 14
- 229910052757 nitrogen Inorganic materials 0.000 description 14
- 238000003756 stirring Methods 0.000 description 14
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- 229960000583 acetic acid Drugs 0.000 description 11
- 235000019441 ethanol Nutrition 0.000 description 11
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 11
- 238000010992 reflux Methods 0.000 description 11
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 239000005457 ice water Substances 0.000 description 10
- 238000001953 recrystallisation Methods 0.000 description 10
- SXUFERDRAFUQGD-UHFFFAOYSA-N 6,7-dimethoxy-4-methyl-3h-quinazolin-2-one Chemical compound N1C(=O)N=C(C)C2=C1C=C(OC)C(OC)=C2 SXUFERDRAFUQGD-UHFFFAOYSA-N 0.000 description 9
- 238000006243 chemical reaction Methods 0.000 description 9
- 238000001816 cooling Methods 0.000 description 9
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 239000012043 crude product Substances 0.000 description 8
- 239000000741 silica gel Substances 0.000 description 8
- 229910002027 silica gel Inorganic materials 0.000 description 8
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 7
- 238000001035 drying Methods 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical class C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 6
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical class C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 6
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 5
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 239000012362 glacial acetic acid Substances 0.000 description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 5
- 229920000137 polyphosphoric acid Polymers 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 229910021529 ammonia Inorganic materials 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
- 239000012264 purified product Substances 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical class CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 3
- NYTBFFZQIRSGLL-UHFFFAOYSA-N 4-isocyanato-1,2-dimethoxybenzene Chemical compound COC1=CC=C(N=C=O)C=C1OC NYTBFFZQIRSGLL-UHFFFAOYSA-N 0.000 description 3
- KZYAZTMEIATJLJ-UHFFFAOYSA-N 6,7-dimethoxy-4-methyl-1-(3-phenylpropyl)quinazolin-2-one Chemical compound C1=2C=C(OC)C(OC)=CC=2C(C)=NC(=O)N1CCCC1=CC=CC=C1 KZYAZTMEIATJLJ-UHFFFAOYSA-N 0.000 description 3
- GOCVVZNBHHLTJX-UHFFFAOYSA-N 6,7-dimethoxy-4-methyl-5-nitro-3h-quinazolin-2-one Chemical compound N1C(=O)N=C(C)C2=C1C=C(OC)C(OC)=C2[N+]([O-])=O GOCVVZNBHHLTJX-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical class CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 3
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 3
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- IQZLUWLMQNGTIW-UHFFFAOYSA-N acetoveratrone Chemical compound COC1=CC=C(C(C)=O)C=C1OC IQZLUWLMQNGTIW-UHFFFAOYSA-N 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 238000010586 diagram Methods 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 3
- 235000019341 magnesium sulphate Nutrition 0.000 description 3
- 229960003194 meglumine Drugs 0.000 description 3
- 229910017604 nitric acid Inorganic materials 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- NUADXLCTIFJIAU-UHFFFAOYSA-N 1-hydroxyquinazoline-2,4-dione Chemical class C1=CC=C2C(O)=NC(=O)N(O)C2=C1 NUADXLCTIFJIAU-UHFFFAOYSA-N 0.000 description 2
- KWXFQMHMUVDCGC-UHFFFAOYSA-N 2,3-dimethoxy-6-nitrobenzaldehyde Chemical compound COC1=CC=C([N+]([O-])=O)C(C=O)=C1OC KWXFQMHMUVDCGC-UHFFFAOYSA-N 0.000 description 2
- AJPGVZKKXPZOGL-UHFFFAOYSA-N 2-(1,3-dioxolan-2-yl)-3,4-dimethoxyaniline Chemical compound COC1=CC=C(N)C(C2OCCO2)=C1OC AJPGVZKKXPZOGL-UHFFFAOYSA-N 0.000 description 2
- ATQBICRSZXLNBU-UHFFFAOYSA-N 2-(2,3-dimethoxy-6-nitrophenyl)-1,3-dioxolane Chemical compound COC1=CC=C([N+]([O-])=O)C(C2OCCO2)=C1OC ATQBICRSZXLNBU-UHFFFAOYSA-N 0.000 description 2
- KJJPLEZQSCZCKE-UHFFFAOYSA-N 2-aminopropane-1,3-diol Chemical compound OCC(N)CO KJJPLEZQSCZCKE-UHFFFAOYSA-N 0.000 description 2
- LPUYRRFGCOZEEK-UHFFFAOYSA-N 2-hydroxy-3-methoxy-6-nitrobenzaldehyde Chemical compound COC1=CC=C([N+]([O-])=O)C(C=O)=C1O LPUYRRFGCOZEEK-UHFFFAOYSA-N 0.000 description 2
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 2
- KGIGUEBEKRSTEW-UHFFFAOYSA-N 2-vinylpyridine Chemical compound C=CC1=CC=CC=N1 KGIGUEBEKRSTEW-UHFFFAOYSA-N 0.000 description 2
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 description 2
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 2
- WSZGBWYGRXQNED-UHFFFAOYSA-N 5,6-dimethoxy-4-(trifluoromethyl)-3h-quinazolin-2-one Chemical compound N1C(=O)N=C(C(F)(F)F)C2=C(OC)C(OC)=CC=C21 WSZGBWYGRXQNED-UHFFFAOYSA-N 0.000 description 2
- VMWCTBKJVZEMRW-UHFFFAOYSA-N 6-methoxy-4-methyl-3h-quinazolin-2-one Chemical compound N1C(=O)N=C(C)C2=CC(OC)=CC=C21 VMWCTBKJVZEMRW-UHFFFAOYSA-N 0.000 description 2
- LYZUHKSZLAMHPX-UHFFFAOYSA-N 7-methoxy-1h-quinazolin-2-one Chemical compound C1=NC(O)=NC2=CC(OC)=CC=C21 LYZUHKSZLAMHPX-UHFFFAOYSA-N 0.000 description 2
- IUOLSQXLCXVPMZ-UHFFFAOYSA-N 7-methoxy-4-methyl-3h-quinazolin-2-one Chemical compound CC1=NC(=O)NC2=CC(OC)=CC=C21 IUOLSQXLCXVPMZ-UHFFFAOYSA-N 0.000 description 2
- HGINCPLSRVDWNT-UHFFFAOYSA-N Acrolein Chemical compound C=CC=O HGINCPLSRVDWNT-UHFFFAOYSA-N 0.000 description 2
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
- 239000005695 Ammonium acetate Substances 0.000 description 2
- 239000004475 Arginine Substances 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- 238000006418 Brown reaction Methods 0.000 description 2
- 241000282472 Canis lupus familiaris Species 0.000 description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 2
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- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- IIBXQGYKZKOORG-QPJJXVBHSA-N methyl (e)-3-(4-chlorophenyl)prop-2-enoate Chemical compound COC(=O)\C=C\C1=CC=C(Cl)C=C1 IIBXQGYKZKOORG-QPJJXVBHSA-N 0.000 description 1
- RZAWURAEJZIPGT-UHFFFAOYSA-N methyl 2-(2,4-difluorophenyl)prop-2-enoate Chemical compound COC(=O)C(=C)C1=CC=C(F)C=C1F RZAWURAEJZIPGT-UHFFFAOYSA-N 0.000 description 1
- BJWLCWXTWGETFJ-UHFFFAOYSA-N methyl 2-(4-chlorophenyl)prop-2-enoate Chemical compound COC(=O)C(=C)C1=CC=C(Cl)C=C1 BJWLCWXTWGETFJ-UHFFFAOYSA-N 0.000 description 1
- CBPNSZGBDCGGFR-UHFFFAOYSA-N methyl 2-(4-methoxyphenyl)prop-2-enoate Chemical compound COC(=O)C(=C)C1=CC=C(OC)C=C1 CBPNSZGBDCGGFR-UHFFFAOYSA-N 0.000 description 1
- VEZIKIAGFYZTCI-VMPITWQZSA-N methyl 4-methoxycinnamate Chemical compound COC(=O)\C=C\C1=CC=C(OC)C=C1 VEZIKIAGFYZTCI-VMPITWQZSA-N 0.000 description 1
- VEZIKIAGFYZTCI-UHFFFAOYSA-N methyl ester of p-methoxycinnamic acid Natural products COC(=O)C=CC1=CC=C(OC)C=C1 VEZIKIAGFYZTCI-UHFFFAOYSA-N 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- KAQGUAVUISEXHF-UHFFFAOYSA-N n-[(3-methoxyphenyl)carbamoyl]acetamide Chemical compound COC1=CC=CC(NC(=O)NC(C)=O)=C1 KAQGUAVUISEXHF-UHFFFAOYSA-N 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 1
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229910003446 platinum oxide Inorganic materials 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 description 1
- 239000011698 potassium fluoride Substances 0.000 description 1
- 235000003270 potassium fluoride Nutrition 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical compound CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 description 1
- 229940080818 propionamide Drugs 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 210000002254 renal artery Anatomy 0.000 description 1
- 230000008327 renal blood flow Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000011775 sodium fluoride Substances 0.000 description 1
- 235000013024 sodium fluoride Nutrition 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- QSUJAUYJBJRLKV-UHFFFAOYSA-M tetraethylazanium;fluoride Chemical compound [F-].CC[N+](CC)(CC)CC QSUJAUYJBJRLKV-UHFFFAOYSA-M 0.000 description 1
- DLYUQMMRRRQYAE-UHFFFAOYSA-N tetraphosphorus decaoxide Chemical compound O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 238000000844 transformation Methods 0.000 description 1
- 230000024883 vasodilation Effects 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/78—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 2
- C07D239/80—Oxygen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicinal Preparation (AREA)
- Manufacture Of Tobacco Products (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Cosmetics (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US06/430,552 US4490374A (en) | 1982-09-30 | 1982-09-30 | 5,6-Dialkoxy-3,4-optionally substituted-2(1H)quinazolinones, composition and method of use |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO833541L true NO833541L (no) | 1984-04-02 |
Family
ID=23708017
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO833541A NO833541L (no) | 1982-09-30 | 1983-09-29 | Ortosubstituerte dihydroksy-2(1h)kinazolinon-1-alkansyrer og fremgangsmaate for deres fremstilling |
Country Status (13)
| Country | Link |
|---|---|
| KR (1) | KR840006218A (ro) |
| AT (2) | ATE58531T1 (ro) |
| DE (2) | DE3382013D1 (ro) |
| ES (4) | ES8503671A1 (ro) |
| HU (1) | HU192242B (ro) |
| IL (1) | IL69849A (ro) |
| NO (1) | NO833541L (ro) |
| NZ (1) | NZ205685A (ro) |
| PH (2) | PH19508A (ro) |
| RO (2) | RO87466B (ro) |
| SG (1) | SG31887G (ro) |
| YU (2) | YU196983A (ro) |
| ZW (1) | ZW20883A1 (ro) |
-
1983
- 1983-09-21 NZ NZ205685A patent/NZ205685A/en unknown
- 1983-09-28 PH PH29609A patent/PH19508A/en unknown
- 1983-09-28 IL IL69849A patent/IL69849A/xx unknown
- 1983-09-29 DE DE8686201912T patent/DE3382013D1/de not_active Expired - Lifetime
- 1983-09-29 AT AT86201912T patent/ATE58531T1/de not_active IP Right Cessation
- 1983-09-29 ZW ZW208/83A patent/ZW20883A1/xx unknown
- 1983-09-29 RO RO112200A patent/RO87466B/ro unknown
- 1983-09-29 NO NO833541A patent/NO833541L/no unknown
- 1983-09-29 RO RO83116473A patent/RO89787A/ro unknown
- 1983-09-29 ES ES526133A patent/ES8503671A1/es not_active Expired
- 1983-09-29 AT AT83305895T patent/ATE34979T1/de active
- 1983-09-29 DE DE8383305895T patent/DE3376978D1/de not_active Expired
- 1983-09-29 HU HU833392A patent/HU192242B/hu unknown
- 1983-09-30 KR KR1019830004638A patent/KR840006218A/ko not_active Ceased
- 1983-09-30 YU YU01969/83A patent/YU196983A/xx unknown
-
1984
- 1984-05-29 ES ES532920A patent/ES532920A0/es active Granted
- 1984-05-29 ES ES532918A patent/ES8507510A1/es not_active Expired
- 1984-05-29 ES ES532919A patent/ES8507511A1/es not_active Expired
-
1985
- 1985-05-24 PH PH32313A patent/PH21757A/en unknown
- 1985-12-11 YU YU01922/85A patent/YU192285A/xx unknown
-
1987
- 1987-03-31 SG SG318/87A patent/SG31887G/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| KR840006218A (ko) | 1984-11-22 |
| DE3376978D1 (en) | 1988-07-14 |
| PH19508A (en) | 1986-05-14 |
| RO87466A (ro) | 1985-08-31 |
| ZW20883A1 (en) | 1985-05-01 |
| ATE58531T1 (de) | 1990-12-15 |
| IL69849A0 (en) | 1983-12-30 |
| PH21757A (en) | 1988-02-18 |
| SG31887G (en) | 1987-07-17 |
| IL69849A (en) | 1987-11-30 |
| ES526133A0 (es) | 1985-03-16 |
| RO87466B (ro) | 1985-08-31 |
| ES532919A0 (es) | 1985-09-01 |
| YU192285A (en) | 1987-12-31 |
| ES532918A0 (es) | 1985-09-01 |
| ES8507512A1 (es) | 1985-09-01 |
| ES8507510A1 (es) | 1985-09-01 |
| ES8507511A1 (es) | 1985-09-01 |
| ES8503671A1 (es) | 1985-03-16 |
| HU192242B (en) | 1988-10-28 |
| YU196983A (en) | 1987-02-28 |
| ES532920A0 (es) | 1985-09-01 |
| DE3382013D1 (de) | 1991-01-03 |
| ATE34979T1 (de) | 1988-06-15 |
| NZ205685A (en) | 1987-03-31 |
| RO89787A (ro) | 1986-07-30 |
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