NO853730L - Substituerte kinazolindioner og fremgangsm¨te for deres fr emstilling. - Google Patents
Substituerte kinazolindioner og fremgangsm¨te for deres fr emstilling.Info
- Publication number
- NO853730L NO853730L NO853730A NO853730A NO853730L NO 853730 L NO853730 L NO 853730L NO 853730 A NO853730 A NO 853730A NO 853730 A NO853730 A NO 853730A NO 853730 L NO853730 L NO 853730L
- Authority
- NO
- Norway
- Prior art keywords
- hydrogen
- formula
- compound
- alkyl
- amino
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 23
- 238000002360 preparation method Methods 0.000 title claims description 11
- 150000001875 compounds Chemical class 0.000 claims description 57
- -1 methylenedioxy Chemical group 0.000 claims description 48
- 239000001257 hydrogen Substances 0.000 claims description 28
- 229910052739 hydrogen Inorganic materials 0.000 claims description 28
- 125000000217 alkyl group Chemical group 0.000 claims description 27
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 claims description 14
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical group [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 13
- 239000000460 chlorine Substances 0.000 claims description 12
- 125000005518 carboxamido group Chemical group 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- 125000006310 cycloalkyl amino group Chemical group 0.000 claims description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 9
- 150000002367 halogens Chemical class 0.000 claims description 9
- GKKCIDNWFBPDBW-UHFFFAOYSA-M potassium cyanate Chemical group [K]OC#N GKKCIDNWFBPDBW-UHFFFAOYSA-M 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 claims description 8
- 125000003282 alkyl amino group Chemical group 0.000 claims description 8
- 150000001412 amines Chemical class 0.000 claims description 8
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
- 239000003638 chemical reducing agent Substances 0.000 claims description 7
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 7
- 229910052736 halogen Inorganic materials 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical group ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- SDQJTWBNWQABLE-UHFFFAOYSA-N 1h-quinazoline-2,4-dione Chemical compound C1=CC=C2C(=O)NC(=O)NC2=C1 SDQJTWBNWQABLE-UHFFFAOYSA-N 0.000 claims description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 4
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 4
- 150000004820 halides Chemical class 0.000 claims description 4
- 125000001188 haloalkyl group Chemical group 0.000 claims description 4
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 4
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 3
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 3
- 229960004050 aminobenzoic acid Drugs 0.000 claims description 3
- 239000003054 catalyst Substances 0.000 claims description 3
- XLJMAIOERFSOGZ-UHFFFAOYSA-M cyanate Chemical compound [O-]C#N XLJMAIOERFSOGZ-UHFFFAOYSA-M 0.000 claims description 3
- 239000012948 isocyanate Substances 0.000 claims description 3
- 150000002513 isocyanates Chemical class 0.000 claims description 3
- 229910017604 nitric acid Inorganic materials 0.000 claims description 3
- 239000007800 oxidant agent Substances 0.000 claims description 3
- 239000012286 potassium permanganate Substances 0.000 claims description 3
- SLAMLWHELXOEJZ-UHFFFAOYSA-N 2-nitrobenzoic acid Chemical compound OC(=O)C1=CC=CC=C1[N+]([O-])=O SLAMLWHELXOEJZ-UHFFFAOYSA-N 0.000 claims description 2
- UUKWKUSGGZNXGA-UHFFFAOYSA-N 3,5-dinitrobenzamide Chemical compound NC(=O)C1=CC([N+]([O-])=O)=CC([N+]([O-])=O)=C1 UUKWKUSGGZNXGA-UHFFFAOYSA-N 0.000 claims description 2
- ALYNCZNDIQEVRV-UHFFFAOYSA-N 4-aminobenzoic acid Chemical compound NC1=CC=C(C(O)=O)C=C1 ALYNCZNDIQEVRV-UHFFFAOYSA-N 0.000 claims description 2
- 125000001246 bromo group Chemical group Br* 0.000 claims description 2
- 239000003153 chemical reaction reagent Substances 0.000 claims description 2
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 claims description 2
- 150000002828 nitro derivatives Chemical class 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 229910052763 palladium Inorganic materials 0.000 claims description 2
- 150000003839 salts Chemical class 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 15
- 239000012320 chlorinating reagent Substances 0.000 claims 2
- 150000001408 amides Chemical class 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 75
- 239000007787 solid Substances 0.000 description 57
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 37
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 36
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 32
- 239000000243 solution Substances 0.000 description 29
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 26
- 239000000047 product Substances 0.000 description 24
- 239000002904 solvent Substances 0.000 description 21
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 20
- 238000002844 melting Methods 0.000 description 20
- 230000008018 melting Effects 0.000 description 20
- 239000000203 mixture Substances 0.000 description 19
- 150000008515 quinazolinediones Chemical class 0.000 description 19
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 17
- 239000011541 reaction mixture Substances 0.000 description 16
- 239000000725 suspension Substances 0.000 description 16
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 15
- 239000012043 crude product Substances 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- 229960000583 acetic acid Drugs 0.000 description 13
- 125000004432 carbon atom Chemical group C* 0.000 description 13
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- NDKBVBUGCNGSJJ-UHFFFAOYSA-M benzyltrimethylammonium hydroxide Chemical compound [OH-].C[N+](C)(C)CC1=CC=CC=C1 NDKBVBUGCNGSJJ-UHFFFAOYSA-M 0.000 description 11
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical class NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 10
- 238000002425 crystallisation Methods 0.000 description 9
- 230000008025 crystallization Effects 0.000 description 9
- 150000002431 hydrogen Chemical class 0.000 description 8
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 8
- 235000019341 magnesium sulphate Nutrition 0.000 description 8
- 239000012265 solid product Substances 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 7
- 239000000284 extract Substances 0.000 description 6
- 238000001953 recrystallisation Methods 0.000 description 6
- 238000001035 drying Methods 0.000 description 5
- FXHZMWOXUYSDQS-UHFFFAOYSA-N ethyl 6-amino-2,3-dimethoxybenzoate Chemical compound CCOC(=O)C1=C(N)C=CC(OC)=C1OC FXHZMWOXUYSDQS-UHFFFAOYSA-N 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- 239000012362 glacial acetic acid Substances 0.000 description 5
- 239000000843 powder Substances 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 238000001665 trituration Methods 0.000 description 5
- HJVAVGOPTDJYOJ-UHFFFAOYSA-N 2-amino-4,5-dimethoxybenzoic acid Chemical compound COC1=CC(N)=C(C(O)=O)C=C1OC HJVAVGOPTDJYOJ-UHFFFAOYSA-N 0.000 description 4
- JIHPDNGIVBWQEH-UHFFFAOYSA-N 5,6-dimethoxy-1h-quinazoline-2,4-dione Chemical compound N1=C(O)N=C(O)C2=C(OC)C(OC)=CC=C21 JIHPDNGIVBWQEH-UHFFFAOYSA-N 0.000 description 4
- ACWQMWNMSYEQCI-UHFFFAOYSA-N 5,6-dimethoxy-3-methyl-1h-quinazoline-2,4-dione Chemical compound N1C(=O)N(C)C(=O)C2=C(OC)C(OC)=CC=C21 ACWQMWNMSYEQCI-UHFFFAOYSA-N 0.000 description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 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 3
- MSEFOJHLQKTCGQ-UHFFFAOYSA-N 2,3-dimethoxy-6-nitrobenzoic acid Chemical compound COC1=CC=C([N+]([O-])=O)C(C(O)=O)=C1OC MSEFOJHLQKTCGQ-UHFFFAOYSA-N 0.000 description 3
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 3
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 3
- GOVSYZLYUYSKTR-UHFFFAOYSA-N 5-nitro-1,3-benzodioxole-4-carboxylic acid Chemical compound C1=C([N+]([O-])=O)C(C(=O)O)=C2OCOC2=C1 GOVSYZLYUYSKTR-UHFFFAOYSA-N 0.000 description 3
- LPDRGWOTVNVWNE-UHFFFAOYSA-N 6-amino-2,3-dimethoxybenzoic acid Chemical compound COC1=CC=C(N)C(C(O)=O)=C1OC LPDRGWOTVNVWNE-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 235000019441 ethanol Nutrition 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- RWZYAGGXGHYGMB-WGGUOBTBSA-N 2-aminobenzoic acid Chemical class NC1=CC=CC=C1[14C](O)=O RWZYAGGXGHYGMB-WGGUOBTBSA-N 0.000 description 2
- QHXOMESNWZGYIK-UHFFFAOYSA-N 3-(2-hydroxyethyl)-5,6-dimethoxy-1h-quinazoline-2,4-dione Chemical compound N1C(=O)N(CCO)C(=O)C2=C(OC)C(OC)=CC=C21 QHXOMESNWZGYIK-UHFFFAOYSA-N 0.000 description 2
- LDIYEGBGOOMPHV-UHFFFAOYSA-N 3-(4-chlorophenyl)-5,6-dimethoxy-1h-quinazoline-2,4-dione Chemical compound O=C1C2=C(OC)C(OC)=CC=C2NC(=O)N1C1=CC=C(Cl)C=C1 LDIYEGBGOOMPHV-UHFFFAOYSA-N 0.000 description 2
- BXRFQSNOROATLV-UHFFFAOYSA-N 4-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=C(C=O)C=C1 BXRFQSNOROATLV-UHFFFAOYSA-N 0.000 description 2
- KELUBQVVFZERLN-UHFFFAOYSA-N 5-nitro-6h-[1,3]dioxolo[4,5-f]quinazoline-7,9-dione Chemical compound N1C(=O)NC(=O)C2=C1C([N+](=O)[O-])=CC1=C2OCO1 KELUBQVVFZERLN-UHFFFAOYSA-N 0.000 description 2
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- JOYRKODLDBILNP-UHFFFAOYSA-N Ethyl urethane Chemical compound CCOC(N)=O JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- 125000005037 alkyl phenyl group Chemical group 0.000 description 2
- 230000004872 arterial blood pressure Effects 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000000496 cardiotonic agent Substances 0.000 description 2
- 230000003177 cardiotonic effect Effects 0.000 description 2
- 239000003610 charcoal Substances 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 125000000753 cycloalkyl group Chemical group 0.000 description 2
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- SXAWVGMHRUWXGG-UHFFFAOYSA-N ethyl 2,3-dimethoxy-6-nitrobenzoate Chemical compound CCOC(=O)C1=C(OC)C(OC)=CC=C1[N+]([O-])=O SXAWVGMHRUWXGG-UHFFFAOYSA-N 0.000 description 2
- ZFXJUEMMMJLPGY-UHFFFAOYSA-N ethyl 2-amino-3-chloro-5,6-dimethoxybenzoate Chemical compound CCOC(=O)C1=C(N)C(Cl)=CC(OC)=C1OC ZFXJUEMMMJLPGY-UHFFFAOYSA-N 0.000 description 2
- VALHWOAAZODCIG-UHFFFAOYSA-N ethyl 5-amino-1,3-benzodioxole-4-carboxylate Chemical compound C1=C(N)C(C(=O)OCC)=C2OCOC2=C1 VALHWOAAZODCIG-UHFFFAOYSA-N 0.000 description 2
- CZKNIXHEGVEHTH-UHFFFAOYSA-N ethyl 5-amino-6-bromo-1,3-benzodioxole-4-carboxylate Chemical compound BrC1=C(N)C(C(=O)OCC)=C2OCOC2=C1 CZKNIXHEGVEHTH-UHFFFAOYSA-N 0.000 description 2
- JHWCPERCBJKSDM-UHFFFAOYSA-N ethyl 5-nitro-1,3-benzodioxole-4-carboxylate Chemical compound C1=C([N+]([O-])=O)C(C(=O)OCC)=C2OCOC2=C1 JHWCPERCBJKSDM-UHFFFAOYSA-N 0.000 description 2
- 235000019439 ethyl acetate Nutrition 0.000 description 2
- 239000012065 filter cake Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 125000005843 halogen group Chemical group 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- HAMGRBXTJNITHG-UHFFFAOYSA-N methyl isocyanate Chemical compound CN=C=O HAMGRBXTJNITHG-UHFFFAOYSA-N 0.000 description 2
- 230000002107 myocardial effect Effects 0.000 description 2
- 230000000802 nitrating effect Effects 0.000 description 2
- 239000008024 pharmaceutical diluent Substances 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 235000000346 sugar Nutrition 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 2
- GECPWPFXXLLQTQ-UHFFFAOYSA-N (2-formyl-6-methoxy-3-nitrophenyl) benzenesulfonate Chemical compound COC1=CC=C([N+]([O-])=O)C(C=O)=C1OS(=O)(=O)C1=CC=CC=C1 GECPWPFXXLLQTQ-UHFFFAOYSA-N 0.000 description 1
- ZTOPOAYZSNYYTB-UHFFFAOYSA-N (3-amino-6-formyl-2-methoxyphenyl) benzenesulfonate Chemical compound COC1=C(N)C=CC(C=O)=C1OS(=O)(=O)C1=CC=CC=C1 ZTOPOAYZSNYYTB-UHFFFAOYSA-N 0.000 description 1
- WTGWWIQICMWYGM-UHFFFAOYSA-N (6-formyl-2-methoxy-3-nitrophenyl) benzenesulfonate Chemical compound O=CC1=CC=C([N+]([O-])=O)C(OC)=C1OS(=O)(=O)C1=CC=CC=C1 WTGWWIQICMWYGM-UHFFFAOYSA-N 0.000 description 1
- ADAKRBAJFHTIEW-UHFFFAOYSA-N 1-chloro-4-isocyanatobenzene Chemical compound ClC1=CC=C(N=C=O)C=C1 ADAKRBAJFHTIEW-UHFFFAOYSA-N 0.000 description 1
- NPOVTGVGOBJZPY-UHFFFAOYSA-N 1-isocyanato-3-methoxybenzene Chemical compound COC1=CC=CC(N=C=O)=C1 NPOVTGVGOBJZPY-UHFFFAOYSA-N 0.000 description 1
- TYMSDNUGIDMTRY-UHFFFAOYSA-N 2-(benzenesulfonyl)-3-methoxybenzaldehyde;(2-formyl-6-methoxy-3-nitrophenyl) benzenesulfonate Chemical compound COC1=CC=CC(C=O)=C1S(=O)(=O)C1=CC=CC=C1.COC1=CC=C([N+]([O-])=O)C(C=O)=C1OS(=O)(=O)C1=CC=CC=C1 TYMSDNUGIDMTRY-UHFFFAOYSA-N 0.000 description 1
- XMNBWADULMTFHS-UHFFFAOYSA-N 2-amino-3-ethyl-5,6-dimethoxybenzoic acid Chemical compound CCC1=CC(OC)=C(OC)C(C(O)=O)=C1N XMNBWADULMTFHS-UHFFFAOYSA-N 0.000 description 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
- 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 1
- CMWKITSNTDAEDT-UHFFFAOYSA-N 2-nitrobenzaldehyde Chemical class [O-][N+](=O)C1=CC=CC=C1C=O CMWKITSNTDAEDT-UHFFFAOYSA-N 0.000 description 1
- MUQZZRLOXQWEMH-UHFFFAOYSA-N 3-(2-chloroethyl)-5,6-dimethoxy-1h-quinazoline-2,4-dione Chemical compound N1C(=O)N(CCCl)C(=O)C2=C(OC)C(OC)=CC=C21 MUQZZRLOXQWEMH-UHFFFAOYSA-N 0.000 description 1
- WEIOIJISOJUDBB-UHFFFAOYSA-N 3-[2-(2-hydroxyethylamino)ethyl]-5,6-dimethoxy-1h-quinazoline-2,4-dione Chemical compound N1C(=O)N(CCNCCO)C(=O)C2=C(OC)C(OC)=CC=C21 WEIOIJISOJUDBB-UHFFFAOYSA-N 0.000 description 1
- UBVVFHIBABJQNO-UHFFFAOYSA-N 3-benzyl-5,6-dimethoxy-1h-quinazoline-2,4-dione Chemical compound O=C1C2=C(OC)C(OC)=CC=C2NC(=O)N1CC1=CC=CC=C1 UBVVFHIBABJQNO-UHFFFAOYSA-N 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- HHSLNSYEEBBNOY-UHFFFAOYSA-N 5,6-dimethoxy-1,3-dimethylquinazoline-2,4-dione Chemical compound CN1C(=O)N(C)C(=O)C2=C(OC)C(OC)=CC=C21 HHSLNSYEEBBNOY-UHFFFAOYSA-N 0.000 description 1
- GNBSCEPBQCOJBF-UHFFFAOYSA-N 5,6-dimethoxy-3-(3-methoxyphenyl)-1h-quinazoline-2,4-dione Chemical compound COC1=CC=CC(N2C(C3=C(OC)C(OC)=CC=C3NC2=O)=O)=C1 GNBSCEPBQCOJBF-UHFFFAOYSA-N 0.000 description 1
- FXZZGXSKHPCBCX-UHFFFAOYSA-N 5-chloro-6h-[1,3]dioxolo[4,5-f]quinazoline-7,9-dione Chemical compound N1C(=O)NC(=O)C2=C1C(Cl)=CC1=C2OCO1 FXZZGXSKHPCBCX-UHFFFAOYSA-N 0.000 description 1
- NFIMAKMUYBBCOI-UHFFFAOYSA-N 5-nitro-1,3-benzodioxole-4-carbaldehyde Chemical compound [O-][N+](=O)C1=CC=C2OCOC2=C1C=O NFIMAKMUYBBCOI-UHFFFAOYSA-N 0.000 description 1
- WCZPODXCOWJPBL-UHFFFAOYSA-N 6h-[1,3]dioxolo[4,5-f]quinazoline-7,9-dione Chemical compound C1=CC2=NC(O)=NC(O)=C2C2=C1OCO2 WCZPODXCOWJPBL-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- LQWNJJRGVCUNDC-UHFFFAOYSA-N 8-chloro-5,6-dimethoxy-3-methyl-1h-quinazoline-2,4-dione Chemical compound N1C(=O)N(C)C(=O)C2=C(OC)C(OC)=CC(Cl)=C21 LQWNJJRGVCUNDC-UHFFFAOYSA-N 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- ZKQDCIXGCQPQNV-UHFFFAOYSA-N Calcium hypochlorite Chemical compound [Ca+2].Cl[O-].Cl[O-] ZKQDCIXGCQPQNV-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- CERQOIWHTDAKMF-UHFFFAOYSA-M Methacrylate Chemical compound CC(=C)C([O-])=O CERQOIWHTDAKMF-UHFFFAOYSA-M 0.000 description 1
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 1
- 229910003204 NH2 Inorganic materials 0.000 description 1
- QGMRQYFBGABWDR-UHFFFAOYSA-M Pentobarbital sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)[N-]C1=O QGMRQYFBGABWDR-UHFFFAOYSA-M 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 235000006040 Prunus persica var persica Nutrition 0.000 description 1
- 240000006413 Prunus persica var. persica Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 125000005036 alkoxyphenyl group Chemical group 0.000 description 1
- 150000001351 alkyl iodides Chemical class 0.000 description 1
- 229940064734 aminobenzoate Drugs 0.000 description 1
- 150000005415 aminobenzoic acids Chemical class 0.000 description 1
- LHIJANUOQQMGNT-UHFFFAOYSA-N aminoethylethanolamine Chemical compound NCCNCCO LHIJANUOQQMGNT-UHFFFAOYSA-N 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000001174 ascending effect Effects 0.000 description 1
- CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 229940117975 chromium trioxide Drugs 0.000 description 1
- WGLPBDUCMAPZCE-UHFFFAOYSA-N chromium trioxide Inorganic materials O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 1
- GAMDZJFZMJECOS-UHFFFAOYSA-N chromium(6+);oxygen(2-) Chemical compound [O-2].[O-2].[O-2].[Cr+6] GAMDZJFZMJECOS-UHFFFAOYSA-N 0.000 description 1
- CCRCUPLGCSFEDV-UHFFFAOYSA-N cinnamic acid methyl ester Natural products COC(=O)C=CC1=CC=CC=C1 CCRCUPLGCSFEDV-UHFFFAOYSA-N 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 229940125773 compound 10 Drugs 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 150000008050 dialkyl sulfates Chemical class 0.000 description 1
- 125000001891 dimethoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- WSBNEASPDYUGRV-UHFFFAOYSA-N dimethyl sulfate;hydrate Chemical compound O.COS(=O)(=O)OC WSBNEASPDYUGRV-UHFFFAOYSA-N 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- SMICMEHDDWELMR-UHFFFAOYSA-N ethyl 2-amino-4,5-dimethoxybenzoate Chemical compound CCOC(=O)C1=CC(OC)=C(OC)C=C1N SMICMEHDDWELMR-UHFFFAOYSA-N 0.000 description 1
- NTBNYQBLABBJND-UHFFFAOYSA-N ethyl 5-amino-6-chloro-1,3-benzodioxole-4-carboxylate Chemical compound ClC1=C(N)C(C(=O)OCC)=C2OCOC2=C1 NTBNYQBLABBJND-UHFFFAOYSA-N 0.000 description 1
- UKWULRWYEWFJPZ-UHFFFAOYSA-N ethyl 6-(ethoxycarbonylamino)-2,3-dimethoxybenzoate Chemical compound CCOC(=O)NC1=CC=C(OC)C(OC)=C1C(=O)OCC UKWULRWYEWFJPZ-UHFFFAOYSA-N 0.000 description 1
- WUDNUHPRLBTKOJ-UHFFFAOYSA-N ethyl isocyanate Chemical compound CCN=C=O WUDNUHPRLBTKOJ-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 210000001105 femoral artery Anatomy 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 239000003979 granulating agent Substances 0.000 description 1
- 230000002140 halogenating effect Effects 0.000 description 1
- 230000026030 halogenation Effects 0.000 description 1
- 238000005658 halogenation reaction Methods 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 239000011872 intimate mixture Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- JEIPFZHSYJVQDO-UHFFFAOYSA-N iron(III) oxide Inorganic materials O=[Fe]O[Fe]=O JEIPFZHSYJVQDO-UHFFFAOYSA-N 0.000 description 1
- SUKKCZLQUGPISF-UHFFFAOYSA-N isocyanatobenzene hydrate Chemical compound C1(=CC=CC=C1)N=C=O.O SUKKCZLQUGPISF-UHFFFAOYSA-N 0.000 description 1
- YDNLNVZZTACNJX-UHFFFAOYSA-N isocyanatomethylbenzene Chemical compound O=C=NCC1=CC=CC=C1 YDNLNVZZTACNJX-UHFFFAOYSA-N 0.000 description 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 238000010907 mechanical stirring Methods 0.000 description 1
- MCVVUJPXSBQTRZ-ONEGZZNKSA-N methyl (e)-but-2-enoate Chemical compound COC(=O)\C=C\C MCVVUJPXSBQTRZ-ONEGZZNKSA-N 0.000 description 1
- ULWSYWRNOXBHSV-UHFFFAOYSA-N methyl 5-amino-1,3-benzodioxole-4-carboxylate Chemical compound C1=C(N)C(C(=O)OC)=C2OCOC2=C1 ULWSYWRNOXBHSV-UHFFFAOYSA-N 0.000 description 1
- CCRCUPLGCSFEDV-BQYQJAHWSA-N methyl trans-cinnamate Chemical compound COC(=O)\C=C\C1=CC=CC=C1 CCRCUPLGCSFEDV-BQYQJAHWSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- JCXJVPUVTGWSNB-UHFFFAOYSA-N nitrogen dioxide Inorganic materials O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- JJVNINGBHGBWJH-UHFFFAOYSA-N ortho-vanillin Chemical compound COC1=CC=CC(C=O)=C1O JJVNINGBHGBWJH-UHFFFAOYSA-N 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- XELRMPRLCPFTBH-UHFFFAOYSA-N quinazoline-2,4-diamine Chemical class C1=CC=CC2=NC(N)=NC(N)=C21 XELRMPRLCPFTBH-UHFFFAOYSA-N 0.000 description 1
- 229940124550 renal vasodilator Drugs 0.000 description 1
- 210000005241 right ventricle Anatomy 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- ZVCDLGYNFYZZOK-UHFFFAOYSA-M sodium cyanate Chemical compound [Na]OC#N ZVCDLGYNFYZZOK-UHFFFAOYSA-M 0.000 description 1
- BAZAXWOYCMUHIX-UHFFFAOYSA-M sodium perchlorate Chemical compound [Na+].[O-]Cl(=O)(=O)=O BAZAXWOYCMUHIX-UHFFFAOYSA-M 0.000 description 1
- 229910001488 sodium perchlorate Inorganic materials 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- NASFKTWZWDYFER-UHFFFAOYSA-N sodium;hydrate Chemical compound O.[Na] NASFKTWZWDYFER-UHFFFAOYSA-N 0.000 description 1
- CRWJEUDFKNYSBX-UHFFFAOYSA-N sodium;hypobromite Chemical compound [Na+].Br[O-] CRWJEUDFKNYSBX-UHFFFAOYSA-N 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
- 150000008163 sugars Chemical class 0.000 description 1
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 230000002861 ventricular Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/12—Antihypertensives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/44—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by —CHO groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C205/00—Compounds containing nitro groups bound to a carbon skeleton
- C07C205/49—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups
- C07C205/57—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton
- C07C205/59—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton the carbon skeleton being further substituted by singly-bound oxygen atoms
- C07C205/60—Compounds containing nitro groups bound to a carbon skeleton the carbon skeleton being further substituted by carboxyl groups having nitro groups and carboxyl groups bound to carbon atoms of six-membered aromatic rings of the carbon skeleton the carbon skeleton being further substituted by singly-bound oxygen atoms in ortho-position to the carboxyl group, e.g. nitro-salicylic acids
-
- 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
- C07D239/95—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in positions 2 and 4
- C07D239/96—Two oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/62—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring 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 atoms of the carbocyclic ring
- C07D317/68—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicinal Chemistry (AREA)
- Cardiology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Heart & Thoracic Surgery (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Compounds Of Unknown Constitution (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US06/653,620 US4639518A (en) | 1984-09-24 | 1984-09-24 | Substituted quinazolinediones |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO853730L true NO853730L (no) | 1986-03-25 |
Family
ID=24621636
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO853730A NO853730L (no) | 1984-09-24 | 1985-09-23 | Substituerte kinazolindioner og fremgangsm¨te for deres fr emstilling. |
Country Status (17)
| Country | Link |
|---|---|
| US (1) | US4639518A (ru) |
| EP (1) | EP0176333A3 (ru) |
| KR (1) | KR900001181B1 (ru) |
| AU (1) | AU578491B2 (ru) |
| DK (1) | DK431185A (ru) |
| ES (2) | ES8701737A1 (ru) |
| FI (1) | FI853639L (ru) |
| GR (1) | GR852324B (ru) |
| HU (1) | HU196188B (ru) |
| IL (1) | IL76467A0 (ru) |
| NO (1) | NO853730L (ru) |
| NZ (1) | NZ213474A (ru) |
| PL (1) | PL255499A1 (ru) |
| PT (1) | PT81182B (ru) |
| SU (1) | SU1409129A3 (ru) |
| ZA (1) | ZA857302B (ru) |
| ZW (1) | ZW16785A1 (ru) |
Families Citing this family (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4711883A (en) * | 1985-09-30 | 1987-12-08 | Ortho Pharmaceutical Corporation | Substituted 3-(4-phenyl-1-piperazinyl)alkylquinazolin-2,4-(1H,3H) diones, methods of preparation, compositions and method of use |
| US4703120A (en) * | 1986-04-28 | 1987-10-27 | Ortho Pharmaceutical Corporation | Furo(3,4-d)pyrimidine-2,4-dione derivatives and intermediates thereof |
| DE3929589A1 (de) * | 1989-09-06 | 1991-03-07 | Basf Ag | Verfahren zur herstellung von 3,7-dialkylxanthinen |
| JPH06509115A (ja) * | 1991-07-15 | 1994-10-13 | メルク エンド カンパニー インコーポレーテッド | 新規な芳香族臭素化方法 |
| DE4339209A1 (de) * | 1993-11-17 | 1995-05-18 | Hoechst Ag | Verfahren zur Herstellung von substituierten Chinazolin-2,4-dionen |
| DE4429978A1 (de) * | 1994-08-24 | 1996-02-29 | Bayer Ag | Verfahren zur Herstellung von Chinazolin-2,4-dionen |
| EP0742213A1 (de) * | 1995-05-10 | 1996-11-13 | Hoechst Aktiengesellschaft | Verfahren zur Herstellung von substituierten 3-Arylchinazolin-2,4-dionen |
| DE19532052C2 (de) * | 1995-08-31 | 1998-11-19 | Clariant Gmbh | Verfahren zur Herstellung von Chinazolinderivaten |
| WO1997029079A1 (fr) * | 1996-02-06 | 1997-08-14 | Japan Tobacco Inc. | Composes chimiques et utilisation pharmaceutique |
| EP3180318B1 (en) * | 2014-08-11 | 2019-02-20 | Hydra Biosciences, Inc. | Quinazoline-2,4(1h,3h)-dione derivatives as trcp5 modulators for the treatment of neuropsychiatric disorders |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4202895A (en) * | 1971-06-04 | 1980-05-13 | Sumitomo Chemical Company, Limited | 1-Polyhaloalkyl-2(1H)-quinazolinone derivatives |
| US4146717A (en) * | 1972-04-07 | 1979-03-27 | Sumitomo Chemical Company, Limited | Nitroquinazolinone compounds having antiviral properties |
| US3879393A (en) * | 1973-06-18 | 1975-04-22 | Miles Lab | Derivatives of 1,3-disubstituted 2,4(1h,3h)-quinazolinediones |
| US3983120A (en) * | 1974-11-06 | 1976-09-28 | Bristol-Myers Company | Process for the preparation of optionally substituted 1,2,3,5-tetrahydroimidazo[2,1-b]quinazolin-2-ones |
| US3988340A (en) * | 1975-01-23 | 1976-10-26 | Bristol-Myers Company | 6-Alkoxymethyl-1,2,3,5-tetrahydroimidazo[2,1-b]quinazolin-2-ones and 7-alkoxymethyl-6-[H]-1,2,3,4-tetrahydropyrimido[2,1-b]quinazolin-2-ones |
| EP0035619B1 (fr) * | 1980-03-10 | 1984-07-25 | BERRI-BALZAC Société dite: | Dérivés d'amino-3 (1H,3H) quinazolinedione-2,4 |
| US4634769A (en) * | 1984-09-25 | 1987-01-06 | Ortho Pharmaceutical Corporation | Process for the preparation of 8-halo-5,6-dialkoxyquinazoline-2,4-diones and their salts |
-
1984
- 1984-09-24 US US06/653,620 patent/US4639518A/en not_active Expired - Lifetime
-
1985
- 1985-09-13 NZ NZ213474A patent/NZ213474A/xx unknown
- 1985-09-23 ZA ZA857302A patent/ZA857302B/xx unknown
- 1985-09-23 SU SU853957506A patent/SU1409129A3/ru active
- 1985-09-23 FI FI853639A patent/FI853639L/fi not_active IP Right Cessation
- 1985-09-23 KR KR1019850006949A patent/KR900001181B1/ko active IP Right Grant
- 1985-09-23 EP EP85306739A patent/EP0176333A3/en not_active Withdrawn
- 1985-09-23 HU HU853576A patent/HU196188B/hu unknown
- 1985-09-23 IL IL76467A patent/IL76467A0/xx unknown
- 1985-09-23 AU AU47698/85A patent/AU578491B2/en not_active Ceased
- 1985-09-23 NO NO853730A patent/NO853730L/no unknown
- 1985-09-23 GR GR852324A patent/GR852324B/el unknown
- 1985-09-23 DK DK431185A patent/DK431185A/da not_active Application Discontinuation
- 1985-09-23 ES ES547205A patent/ES8701737A1/es not_active Expired
- 1985-09-23 ZW ZW167/85A patent/ZW16785A1/xx unknown
- 1985-09-24 PL PL25549985A patent/PL255499A1/xx unknown
- 1985-09-24 PT PT81182A patent/PT81182B/pt unknown
-
1986
- 1986-04-01 ES ES553602A patent/ES8800910A1/es not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| AU578491B2 (en) | 1988-10-27 |
| AU4769885A (en) | 1986-04-10 |
| PT81182B (en) | 1987-03-30 |
| GR852324B (ru) | 1986-01-24 |
| PT81182A (en) | 1985-10-01 |
| HUT40087A (en) | 1986-11-28 |
| ZW16785A1 (en) | 1987-04-15 |
| US4639518A (en) | 1987-01-27 |
| IL76467A0 (en) | 1986-01-31 |
| HU196188B (en) | 1988-10-28 |
| ES8800910A1 (es) | 1987-12-01 |
| FI853639L (fi) | 1986-03-25 |
| ES547205A0 (es) | 1986-12-01 |
| DK431185A (da) | 1986-03-25 |
| DK431185D0 (da) | 1985-09-23 |
| FI853639A0 (fi) | 1985-09-23 |
| ES553602A0 (es) | 1987-12-01 |
| KR900001181B1 (ko) | 1990-02-27 |
| EP0176333A3 (en) | 1987-03-18 |
| ES8701737A1 (es) | 1986-12-01 |
| SU1409129A3 (ru) | 1988-07-07 |
| KR860002478A (ko) | 1986-04-26 |
| PL255499A1 (en) | 1987-06-15 |
| ZA857302B (en) | 1987-05-27 |
| NZ213474A (en) | 1988-10-28 |
| EP0176333A2 (en) | 1986-04-02 |
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