CA1224468A - Derives de substitution en ortho d'acides dihydroxy-2(1h)quinazolinone-1-alcanoiques - Google Patents

Derives de substitution en ortho d'acides dihydroxy-2(1h)quinazolinone-1-alcanoiques

Info

Publication number: CA1224468A
Authority: CA; Canada
Prior art keywords: methyl; quinazolinone; dimethoxy; carbon atoms; substituted
Prior art date: 1982-09-30
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired

Application number

CA000509685A

Other languages

English (en)

Inventor

Victor T. Bandurco

Dennis M. Mulvey

Seymour D. Levine

Alfonso J. Tobia

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

Ortho Pharmaceutical Corp

Original Assignee

Ortho Pharmaceutical Corp

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1982-09-30

Filing date

1986-05-21

Publication date

1987-07-21

1982-09-30 Priority claimed from US06/430,552 external-priority patent/US4490374A/en

1986-05-21 Application filed by Ortho Pharmaceutical Corp filed Critical Ortho Pharmaceutical Corp

1986-05-21 Priority to CA000509685A priority Critical patent/CA1224468A/fr

1987-07-21 Application granted granted Critical

1987-07-21 Publication of CA1224468A publication Critical patent/CA1224468A/fr

Status Expired legal-status Critical Current

Links

239000002253 acid Substances 0.000 title claims abstract description 11
150000007513 acids Chemical class 0.000 title abstract description 3
-1 p-hydroxyphenyl Chemical group 0.000 claims abstract description 36
125000000217 alkyl group Chemical group 0.000 claims abstract description 23
AVRPFRMDMNDIDH-UHFFFAOYSA-N 1h-quinazolin-2-one Chemical class C1=CC=CC2=NC(O)=NC=C21 AVRPFRMDMNDIDH-UHFFFAOYSA-N 0.000 claims abstract description 22
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 22
239000001257 hydrogen Substances 0.000 claims abstract description 21
150000001875 compounds Chemical class 0.000 claims abstract description 16
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 58
238000000034 method Methods 0.000 claims description 28
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 14
238000002360 preparation method Methods 0.000 claims description 10
229910021529 ammonia Inorganic materials 0.000 claims description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
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 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 4
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 4
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 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
HSGQCWJKQPAHHO-UHFFFAOYSA-N ethyl n-(2-formyl-3,4-dimethoxyphenyl)carbamate Chemical compound CCOC(=O)NC1=CC=C(OC)C(OC)=C1C=O HSGQCWJKQPAHHO-UHFFFAOYSA-N 0.000 claims description 3
GBTVBGKXLYNYRJ-UHFFFAOYSA-N ethyl n-[2-(1,3-dioxolan-2-yl)-3,4-dimethoxyphenyl]carbamate Chemical compound CCOC(=O)NC1=CC=C(OC)C(OC)=C1C1OCCO1 GBTVBGKXLYNYRJ-UHFFFAOYSA-N 0.000 claims description 2
NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 claims description 2
QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 claims description 2
239000012286 potassium permanganate Substances 0.000 claims description 2
239000000126 substance Substances 0.000 claims 4
239000007800 oxidant agent Substances 0.000 claims 3
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 2
239000003638 chemical reducing agent Substances 0.000 claims 2
229910052500 inorganic mineral Inorganic materials 0.000 claims 2
239000011707 mineral Substances 0.000 claims 2
IAWUUJITIDANOQ-UHFFFAOYSA-N 2-(1,3-dioxolan-2-yl)aniline Chemical compound NC1=CC=CC=C1C1OCCO1 IAWUUJITIDANOQ-UHFFFAOYSA-N 0.000 claims 1
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims 1
239000005977 Ethylene Substances 0.000 claims 1
125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
229910001623 magnesium bromide Inorganic materials 0.000 claims 1
238000004519 manufacturing process Methods 0.000 claims 1
125000004432 carbon atom Chemical group C* 0.000 abstract description 22
150000003839 salts Chemical group 0.000 abstract description 13
150000002431 hydrogen Chemical group 0.000 abstract description 11
125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 11
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 9
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 abstract description 9
125000001424 substituent group Chemical group 0.000 abstract description 7
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 abstract description 5
125000000753 cycloalkyl group Chemical group 0.000 abstract description 5
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 abstract description 4
125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 abstract description 4
125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 abstract description 4
125000003545 alkoxy group Chemical group 0.000 abstract description 4
125000003118 aryl group Chemical group 0.000 abstract description 4
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 abstract description 4
125000001246 bromo group Chemical group Br* 0.000 abstract description 4
125000001309 chloro group Chemical group Cl* 0.000 abstract description 4
150000001602 bicycloalkyls Chemical group 0.000 abstract description 3
125000005518 carboxamido group Chemical group 0.000 abstract description 3
125000004093 cyano group Chemical group *C#N 0.000 abstract description 3
125000001153 fluoro group Chemical group F* 0.000 abstract description 3
125000002485 formyl group Chemical group [H]C(*)=O 0.000 abstract description 3
125000001188 haloalkyl group Chemical group 0.000 abstract description 3
150000002466 imines Chemical class 0.000 abstract description 3
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract description 3
125000003107 substituted aryl group Chemical group 0.000 abstract description 3
125000004215 2,4-difluorophenyl group Chemical group [H]C1=C([H])C(*)=C(F)C([H])=C1F 0.000 abstract description 2
125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 abstract description 2
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 abstract description 2
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 abstract description 2
125000005036 alkoxyphenyl group Chemical group 0.000 abstract description 2
125000005037 alkyl phenyl group Chemical group 0.000 abstract description 2
125000003435 aroyl group Chemical group 0.000 abstract description 2
YFNONBGXNFCTMM-UHFFFAOYSA-N butoxybenzene Chemical group CCCCOC1=CC=CC=C1 YFNONBGXNFCTMM-UHFFFAOYSA-N 0.000 abstract description 2
239000002327 cardiovascular agent Substances 0.000 abstract description 2
229940125692 cardiovascular agent Drugs 0.000 abstract description 2
125000001316 cycloalkyl alkyl group Chemical group 0.000 abstract description 2
229910052736 halogen Inorganic materials 0.000 abstract description 2
125000005843 halogen group Chemical group 0.000 abstract description 2
150000002367 halogens Chemical class 0.000 abstract description 2
125000005059 halophenyl group Chemical group 0.000 abstract description 2
125000001072 heteroaryl group Chemical group 0.000 abstract description 2
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 abstract description 2
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 abstract description 2
125000002868 norbornyl group Chemical group C12(CCC(CC1)C2)* 0.000 abstract description 2
125000002924 primary amino group Chemical group [H]N([H])* 0.000 abstract description 2
230000008327 renal blood flow Effects 0.000 abstract description 2
229940124550 renal vasodilator 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
125000001113 thiadiazolyl group Chemical group 0.000 abstract description 2
230000015572 biosynthetic process Effects 0.000 abstract 1
125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 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 123
239000000243 solution Substances 0.000 description 64
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 60
239000007787 solid Substances 0.000 description 52
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 40
239000000203 mixture Substances 0.000 description 37
XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 35
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 34
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 34
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 30
229910001868 water Inorganic materials 0.000 description 30
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 28
238000003756 stirring Methods 0.000 description 27
239000002244 precipitate Substances 0.000 description 25
239000011541 reaction mixture Substances 0.000 description 25
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
239000000047 product Substances 0.000 description 23
239000002904 solvent Substances 0.000 description 23
230000000875 corresponding effect Effects 0.000 description 20
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 18
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 16
238000001914 filtration Methods 0.000 description 16
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
229910052757 nitrogen Inorganic materials 0.000 description 15
229960005419 nitrogen Drugs 0.000 description 15
XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 14
238000006243 chemical reaction Methods 0.000 description 14
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 13
NDKBVBUGCNGSJJ-UHFFFAOYSA-M benzyltrimethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)CC1=CC=CC=C1 NDKBVBUGCNGSJJ-UHFFFAOYSA-M 0.000 description 13
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
239000000725 suspension Substances 0.000 description 11
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 10
238000001816 cooling Methods 0.000 description 9
239000003921 oil Substances 0.000 description 9
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 8
OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-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
239000002002 slurry Substances 0.000 description 8
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
239000000284 extract Substances 0.000 description 7
239000005457 ice water Substances 0.000 description 7
238000001953 recrystallisation Methods 0.000 description 7
BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 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
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238000001035 drying Methods 0.000 description 6
239000000706 filtrate Substances 0.000 description 6
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 6
235000011121 sodium hydroxide Nutrition 0.000 description 6
HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 5
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239000007864 aqueous solution Substances 0.000 description 5
239000012362 glacial acetic acid Substances 0.000 description 5
229910000042 hydrogen bromide Inorganic materials 0.000 description 5
235000011118 potassium hydroxide Nutrition 0.000 description 5
229940083608 sodium hydroxide Drugs 0.000 description 5
239000007858 starting material Substances 0.000 description 5
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 4
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
239000007832 Na2SO4 Substances 0.000 description 4
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
239000003054 catalyst Substances 0.000 description 4
238000004587 chromatography analysis Methods 0.000 description 4
238000002425 crystallisation Methods 0.000 description 4
230000008025 crystallization Effects 0.000 description 4
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 4
229920000137 polyphosphoric acid Polymers 0.000 description 4
235000019260 propionic acid Nutrition 0.000 description 4
239000012264 purified product Substances 0.000 description 4
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 description 4
229920006395 saturated elastomer Polymers 0.000 description 4
229910052938 sodium sulfate Inorganic materials 0.000 description 4
235000011152 sodium sulphate Nutrition 0.000 description 4
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-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
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
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GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 3
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229910052783 alkali metal Inorganic materials 0.000 description 3
230000017531 blood circulation Effects 0.000 description 3
238000009835 boiling Methods 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
CCRCUPLGCSFEDV-UHFFFAOYSA-N cinnamic acid methyl ester Natural products COC(=O)C=CC1=CC=CC=C1 CCRCUPLGCSFEDV-UHFFFAOYSA-N 0.000 description 3
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229940079593 drug Drugs 0.000 description 3
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RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 3
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
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239000010410 layer Substances 0.000 description 3
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CCRCUPLGCSFEDV-BQYQJAHWSA-N methyl trans-cinnamate Chemical compound COC(=O)\C=C\C1=CC=CC=C1 CCRCUPLGCSFEDV-BQYQJAHWSA-N 0.000 description 3
229940113083 morpholine Drugs 0.000 description 3
125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 3
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 3
229910017604 nitric acid Inorganic materials 0.000 description 3
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
238000010992 reflux Methods 0.000 description 3
210000002254 renal artery Anatomy 0.000 description 3
238000001665 trituration Methods 0.000 description 3
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
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238000006418 Brown reaction Methods 0.000 description 2
241000282472 Canis lupus familiaris Species 0.000 description 2
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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
ZYZMFAILUWTEQK-UHFFFAOYSA-N n-[(3,4-dimethoxyphenyl)carbamoyl]propanamide Chemical compound CCC(=O)NC(=O)NC1=CC=C(OC)C(OC)=C1 ZYZMFAILUWTEQK-UHFFFAOYSA-N 0.000 description 1
RYVLOOXFFIFQEN-UHFFFAOYSA-N n-[4-(1-oxo-3,4-dihydro-2h-pyrido[4,3-b]indol-5-yl)butyl]acetamide Chemical compound C12=CC=CC=C2N(CCCCNC(=O)C)C2=C1C(=O)NCC2 RYVLOOXFFIFQEN-UHFFFAOYSA-N 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
229910052759 nickel Inorganic materials 0.000 description 1
235000019198 oils Nutrition 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
230000020477 pH reduction 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
235000011181 potassium carbonates Nutrition 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
239000003755 preservative agent Substances 0.000 description 1
GYPZFDNQZCSGND-UHFFFAOYSA-N propanoic acid;hydrate Chemical compound O.CCC(O)=O GYPZFDNQZCSGND-UHFFFAOYSA-N 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
FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 1
230000004043 responsiveness Effects 0.000 description 1
229910052703 rhodium Inorganic materials 0.000 description 1
239000010948 rhodium Substances 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
235000017550 sodium carbonate Nutrition 0.000 description 1
239000011775 sodium fluoride Substances 0.000 description 1
235000013024 sodium fluoride Nutrition 0.000 description 1
239000008279 sol Substances 0.000 description 1
238000010561 standard procedure Methods 0.000 description 1
235000019698 starch Nutrition 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
150000008163 sugars Chemical class 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000003826 tablet Substances 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
238000012360 testing method Methods 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
BNSCQVNQJGLJQV-UHFFFAOYSA-K tripotassium propanoate hydrate Chemical compound O.[K+].[K+].[K+].C(CC)(=O)[O-].C(CC)(=O)[O-].C(CC)(=O)[O-] BNSCQVNQJGLJQV-UHFFFAOYSA-K 0.000 description 1
GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 description 1
230000024883 vasodilation Effects 0.000 description 1
239000003039 volatile agent Substances 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1

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Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA000509685A 1982-09-30 1986-05-21 Derives de substitution en ortho d'acides dihydroxy-2(1h)quinazolinone-1-alcanoiques Expired CA1224468A (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA000509685A CA1224468A (fr)	1982-09-30	1986-05-21	Derives de substitution en ortho d'acides dihydroxy-2(1h)quinazolinone-1-alcanoiques

Applications Claiming Priority (5)

Application Number	Priority Date	Filing Date	Title
US430,552		1982-09-30
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
CA000437876A CA1215712A (fr)	1982-09-30	1983-09-29	Acides dihydroxy-2(1h) quinazolinone-1-alcanoiques substitues en position ortho
JP59058527A JPS60204770A (ja)	1982-09-30	1984-03-28	ジヒドロキシ−２（１ｈ）キナゾリノン−１−アルカン酸類
CA000509685A CA1224468A (fr)	1982-09-30	1986-05-21	Derives de substitution en ortho d'acides dihydroxy-2(1h)quinazolinone-1-alcanoiques

Related Parent Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000437876A Division CA1215712A (fr)	1982-09-30	1983-09-29	Acides dihydroxy-2(1h) quinazolinone-1-alcanoiques substitues en position ortho

Publications (1)

Publication Number	Publication Date
CA1224468A true CA1224468A (fr)	1987-07-21

Family

ID=27167383

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000509685A Expired CA1224468A (fr)	1982-09-30	1986-05-21	Derives de substitution en ortho d'acides dihydroxy-2(1h)quinazolinone-1-alcanoiques

Country Status (1)

Country	Link
CA (1)	CA1224468A (fr)

1986
- 1986-05-21 CA CA000509685A patent/CA1224468A/fr not_active Expired

Legal Events

Date	Code	Title	Description
2004-07-21	MKEX	Expiry

Publication	Publication Date	Title
CA1215712A (fr)	1986-12-23	Acides dihydroxy-2(1h) quinazolinone-1-alcanoiques substitues en position ortho
DE3834204C2 (fr)	1992-04-23
CA2012628C (fr)	2000-08-29	Nouveaux derives fluoro-4 benzoiques, leurs procedes de preparation et les compositions pharmaceutiques qui les contiennent
CA1066282A (fr)	1979-11-13	Agents bloquants des recepteurs adrenergiques
JP2002534508A (ja)	2002-10-15	Ｐｅｄ−ｉｖ阻害作用を有するフェニルフェナントリジン
DE69015541T2 (de)	1995-06-01	Chinolinderivate, deren Herstellung und Verwendung.
AU2003215678A1 (en)	2003-10-13	Quinoline and isoquinoline derivatives, method for the production thereof and use thereof as anti-inflammatory agents
CH644112A5 (de)	1984-07-13	3-aromatischsubstituierte-4(3h)chinazolinone und verfahren zu ihrer herstellung.
JPH0471914B2 (fr)	1992-11-16
JP2003502278A (ja)	2003-01-21	新規のｎ−オキシド
US4639518A (en)	1987-01-27	Substituted quinazolinediones
US4656267A (en)	1987-04-07	Substituted 2(1H)-quinazolinone-1-alkanoic acids and esters
US4556739A (en)	1985-12-03	3,4-Dialkoxy-2-alkylcarbonyl analino compounds
US4631283A (en)	1986-12-23	Ortho substituted dihydroxy-2(1H)quinazolinone-1-alkanoic acids
US4771047A (en)	1988-09-13	Benzazepine derivatives
US4555571A (en)	1985-11-26	Substituted 2(1H)-quinazolinone-1-alkanoic acids and esters
CA1099712A (fr)	1981-04-21	Carbostyriles de polyfluorohydroxyisopropyle bicycliques ou tricycliques comme antihypertenseurs
JPH01224364A (ja)	1989-09-07	除草性ｏ―カルボキシアリ―ルイミダゾリノン類の製法
US4617392A (en)	1986-10-14	4-alkyl-5,6-methylenedioxy-2-1[H]-quinazolinones useful as cardiotonic agents
CA1138871A (fr)	1983-01-04	Quinazol in-2-ones
US4302458A (en)	1981-11-24	Phthalidyl-isoquinoline derivatives
NZ205685A (en)	1987-03-31	Dihydroxy-2(1h)-quinazolinone-1-alkanoic acids and pharmaceutical compositions
JP2003506358A (ja)	2003-02-18	イソキノリン誘導体、該誘導体を含有する医薬組成物及び活性物質の製法
CA1125170A (fr)	1982-06-08	Quinazolin-2-ones
KR840000152B1 (ko)	1984-02-22	2-아자에리스리난 유도체 및 그 산부가염의 제조방법