DE3011994A1 - Chinolonverbindungen, verfahren zu deren herstellung und arzneimittelzubereitungen, enthaltend diese chinolonverbindungen - Google Patents
Chinolonverbindungen, verfahren zu deren herstellung und arzneimittelzubereitungen, enthaltend diese chinolonverbindungenInfo
- Publication number
- DE3011994A1 DE3011994A1 DE19803011994 DE3011994A DE3011994A1 DE 3011994 A1 DE3011994 A1 DE 3011994A1 DE 19803011994 DE19803011994 DE 19803011994 DE 3011994 A DE3011994 A DE 3011994A DE 3011994 A1 DE3011994 A1 DE 3011994A1
- Authority
- DE
- Germany
- Prior art keywords
- group
- quinolone
- methyl
- groups
- general formula
- Prior art date
- 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.)
- Granted
Links
- 150000001875 compounds Chemical class 0.000 title claims description 65
- 238000002360 preparation method Methods 0.000 title claims description 25
- 238000000034 method Methods 0.000 title claims description 17
- 239000003814 drug Substances 0.000 title claims description 5
- 238000004519 manufacturing process Methods 0.000 title description 5
- GSDSWSVVBLHKDQ-UHFFFAOYSA-N 9-fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid Chemical class FC1=CC(C(C(C(O)=O)=C2)=O)=C3N2C(C)COC3=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-UHFFFAOYSA-N 0.000 title 1
- 150000007660 quinolones Chemical class 0.000 claims description 36
- 125000000217 alkyl group Chemical group 0.000 claims description 32
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 26
- 239000004480 active ingredient Substances 0.000 claims description 22
- 125000003545 alkoxy group Chemical group 0.000 claims description 21
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
- -1 quinolone compound Chemical class 0.000 claims description 18
- 239000002775 capsule Substances 0.000 claims description 13
- 125000005843 halogen group Chemical group 0.000 claims description 11
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 0.000 claims description 9
- 229910052799 carbon Inorganic materials 0.000 claims description 9
- 125000004414 alkyl thio group Chemical group 0.000 claims description 8
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
- 150000001252 acrylic acid derivatives Chemical class 0.000 claims description 7
- 125000002252 acyl group Chemical group 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 claims description 4
- 239000000829 suppository Substances 0.000 claims description 4
- UZWAHQKAIZUPJV-UHFFFAOYSA-N 1-methyl-3-methylsulfinylquinolin-4-one Chemical compound C1=CC=C2N(C)C=C(S(C)=O)C(=O)C2=C1 UZWAHQKAIZUPJV-UHFFFAOYSA-N 0.000 claims description 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 239000000463 material Substances 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 229940030600 antihypertensive agent Drugs 0.000 claims description 2
- 239000002220 antihypertensive agent Substances 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims description 2
- UYGONJYYUKVHDD-UHFFFAOYSA-N flosequinan Chemical compound C1=C(F)C=C2N(C)C=C(S(C)=O)C(=O)C2=C1 UYGONJYYUKVHDD-UHFFFAOYSA-N 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- BLTJRWXGRSTNCR-UHFFFAOYSA-N 2-methylsulfinyl-3h-quinolin-4-one Chemical compound C1=CC=C2C(=O)CC(S(=O)C)=NC2=C1 BLTJRWXGRSTNCR-UHFFFAOYSA-N 0.000 claims 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims 1
- 125000000547 substituted alkyl group Chemical group 0.000 claims 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 113
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 70
- 238000002844 melting Methods 0.000 description 56
- 230000008018 melting Effects 0.000 description 56
- 239000000203 mixture Substances 0.000 description 39
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 36
- 239000000243 solution Substances 0.000 description 28
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 27
- 239000000047 product Substances 0.000 description 25
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 20
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 17
- 239000007787 solid Substances 0.000 description 16
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 description 16
- 239000011541 reaction mixture Substances 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 13
- 239000000725 suspension Substances 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N dimethyl sulfoxide Natural products CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 10
- 230000036772 blood pressure Effects 0.000 description 10
- 239000000543 intermediate Substances 0.000 description 10
- 238000007254 oxidation reaction Methods 0.000 description 10
- 241000700159 Rattus Species 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- 230000003647 oxidation Effects 0.000 description 9
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 8
- 238000000354 decomposition reaction Methods 0.000 description 8
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 8
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- 125000001309 chloro group Chemical group Cl* 0.000 description 7
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- 235000019198 oils Nutrition 0.000 description 7
- 239000000825 pharmaceutical preparation Substances 0.000 description 7
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- TZIHFWKZFHZASV-UHFFFAOYSA-N methyl formate Chemical compound COC=O TZIHFWKZFHZASV-UHFFFAOYSA-N 0.000 description 6
- 229910000027 potassium carbonate Inorganic materials 0.000 description 6
- 239000002244 precipitate Substances 0.000 description 6
- 159000000000 sodium salts Chemical class 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 5
- 229960000583 acetic acid Drugs 0.000 description 5
- 239000007800 oxidant agent Substances 0.000 description 5
- 238000007363 ring formation reaction Methods 0.000 description 5
- 239000000741 silica gel Substances 0.000 description 5
- 229910002027 silica gel Inorganic materials 0.000 description 5
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 5
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical class NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 4
- 150000001721 carbon Chemical group 0.000 description 4
- 239000000460 chlorine Substances 0.000 description 4
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 229910052736 halogen Inorganic materials 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 150000003568 thioethers Chemical class 0.000 description 4
- DBVVBYBNNNDCHK-UHFFFAOYSA-N 3-methylsulfinyl-3h-quinolin-4-one Chemical compound C1=CC=C2C(=O)C(S(=O)C)C=NC2=C1 DBVVBYBNNNDCHK-UHFFFAOYSA-N 0.000 description 3
- BACOFPPVBVJWHF-UHFFFAOYSA-N 6,7-dimethoxy-1-methyl-3-methylsulfinylquinolin-4-one Chemical compound CN1C=C(S(C)=O)C(=O)C2=C1C=C(OC)C(OC)=C2 BACOFPPVBVJWHF-UHFFFAOYSA-N 0.000 description 3
- GEMDGXXVKPNXOV-UHFFFAOYSA-N 7-bromo-3-methylsulfinyl-3h-quinolin-4-one Chemical compound BrC1=CC=C2C(=O)C(S(=O)C)C=NC2=C1 GEMDGXXVKPNXOV-UHFFFAOYSA-N 0.000 description 3
- GZQHWCULMKQPMV-UHFFFAOYSA-N 7-chloro-1-methyl-3-methylsulfinylquinolin-4-one Chemical compound C1=C(Cl)C=C2N(C)C=C(S(C)=O)C(=O)C2=C1 GZQHWCULMKQPMV-UHFFFAOYSA-N 0.000 description 3
- ZGFPFJNYSUVWHB-UHFFFAOYSA-N 7-fluoro-3-methylsulfinyl-3h-quinolin-4-one Chemical compound FC1=CC=C2C(=O)C(S(=O)C)C=NC2=C1 ZGFPFJNYSUVWHB-UHFFFAOYSA-N 0.000 description 3
- ZCTAXXJVBDEDEK-UHFFFAOYSA-N 7-methoxy-1,3-dimethylquinoline-4-thione Chemical compound CN1C=C(C)C(=S)C=2C1=CC(OC)=CC=2 ZCTAXXJVBDEDEK-UHFFFAOYSA-N 0.000 description 3
- 229920000623 Cellulose acetate phthalate Polymers 0.000 description 3
- 239000002168 alkylating agent Substances 0.000 description 3
- 229940100198 alkylating agent Drugs 0.000 description 3
- 150000005130 benzoxazines Chemical class 0.000 description 3
- 239000001506 calcium phosphate Substances 0.000 description 3
- 229910000389 calcium phosphate Inorganic materials 0.000 description 3
- 235000011010 calcium phosphates Nutrition 0.000 description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 description 3
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 238000011835 investigation Methods 0.000 description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 3
- 150000004967 organic peroxy acids Chemical class 0.000 description 3
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 238000011699 spontaneously hypertensive rat Methods 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 3
- ZXNFYHLFPXEBGY-UHFFFAOYSA-N 1,7-dimethyl-3-methylsulfinylquinolin-4-one Chemical compound CN1C=C(S(C)=O)C(=O)C=2C1=CC(C)=CC=2 ZXNFYHLFPXEBGY-UHFFFAOYSA-N 0.000 description 2
- AKNVDMJCVKFYSB-UHFFFAOYSA-N 1-methyl-3-methylsulfanyl-7-propan-2-ylquinolin-4-one Chemical compound CC(C)C1=CC=C2C(=O)C(SC)=CN(C)C2=C1 AKNVDMJCVKFYSB-UHFFFAOYSA-N 0.000 description 2
- FCLWUYJURISLKH-UHFFFAOYSA-N 1-methyl-3-methylsulfinyl-7-(trifluoromethyl)quinolin-4-one Chemical compound C1=C(C(F)(F)F)C=C2N(C)C=C(S(C)=O)C(=O)C2=C1 FCLWUYJURISLKH-UHFFFAOYSA-N 0.000 description 2
- BGDOLELXXPTPFX-UHFFFAOYSA-N 3,4-dihydro-2h-1,2-benzoxazine Chemical compound C1=CC=C2ONCCC2=C1 BGDOLELXXPTPFX-UHFFFAOYSA-N 0.000 description 2
- SCWPCJKOXRPFCD-UHFFFAOYSA-N 3-ethylsulfanyl-1-methylquinolin-4-one Chemical compound C1=CC=C2C(=O)C(SCC)=CN(C)C2=C1 SCWPCJKOXRPFCD-UHFFFAOYSA-N 0.000 description 2
- PNSCZWXWBWBHSF-UHFFFAOYSA-N 7-chloro-6-methoxy-1,3-dimethylquinoline-4-thione Chemical compound CN1C=C(C)C(=S)C2=C1C=C(Cl)C(OC)=C2 PNSCZWXWBWBHSF-UHFFFAOYSA-N 0.000 description 2
- KUFYVZBJMBNICU-UHFFFAOYSA-N 7-chloro-6-methoxy-1-methyl-3-methylsulfinylquinolin-4-one Chemical compound CN1C=C(S(C)=O)C(=O)C2=C1C=C(Cl)C(OC)=C2 KUFYVZBJMBNICU-UHFFFAOYSA-N 0.000 description 2
- YTPAZJSGIQSNME-UHFFFAOYSA-N 7-chloro-6-methoxy-3-methyl-3h-quinoline-4-thione Chemical compound S=C1C(C)C=NC2=C1C=C(OC)C(Cl)=C2 YTPAZJSGIQSNME-UHFFFAOYSA-N 0.000 description 2
- ZKTQPDBLGNGCBO-UHFFFAOYSA-N 7-ethyl-1,3-dimethylquinoline-4-thione Chemical compound CN1C=C(C)C(=S)C=2C1=CC(CC)=CC=2 ZKTQPDBLGNGCBO-UHFFFAOYSA-N 0.000 description 2
- AANRGFUCQKJETA-UHFFFAOYSA-N 7-ethyl-1-methyl-3-methylsulfinylquinolin-4-one Chemical compound CN1C=C(S(C)=O)C(=O)C=2C1=CC(CC)=CC=2 AANRGFUCQKJETA-UHFFFAOYSA-N 0.000 description 2
- KVGQFTUVCDHXBT-UHFFFAOYSA-N 7-fluoro-1,3-dimethylquinoline-4-thione Chemical compound FC1=CC=C2C(=S)C(C)=CN(C)C2=C1 KVGQFTUVCDHXBT-UHFFFAOYSA-N 0.000 description 2
- LIHRHGSHVXLIOB-UHFFFAOYSA-N 7-tert-butyl-1-methyl-3-methylsulfinylquinolin-4-one Chemical compound C1=C(C(C)(C)C)C=C2N(C)C=C(S(C)=O)C(=O)C2=C1 LIHRHGSHVXLIOB-UHFFFAOYSA-N 0.000 description 2
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- 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 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- HZYCAKGEXXKCDM-UHFFFAOYSA-N Methyl 2-(methylthio)acetate Chemical compound COC(=O)CSC HZYCAKGEXXKCDM-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 239000006286 aqueous extract Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- 230000005540 biological transmission Effects 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 2
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 210000001198 duodenum Anatomy 0.000 description 2
- 239000002702 enteric coating Substances 0.000 description 2
- 238000009505 enteric coating Methods 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 239000013067 intermediate product Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000012299 nitrogen atmosphere Substances 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000003208 petroleum Substances 0.000 description 2
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- 239000012312 sodium hydride Substances 0.000 description 2
- 229910000104 sodium hydride Inorganic materials 0.000 description 2
- 150000003462 sulfoxides Chemical class 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- ITTYVMKWMLPYAT-UHFFFAOYSA-N 1,3-dimethylquinoline-4-thione 1-ethyl-3-methylsulfinylquinolin-4-one 1-methyl-3-methylsulfinylquinolin-4-one 1-methyl-3-methylsulfonylquinolin-4-one Chemical compound CN1C=C(C(C2=CC=CC=C12)=O)S(=O)(=O)C.CN1C=C(C(C2=CC=CC=C12)=S)C.C(C)N1C=C(C(C2=CC=CC=C12)=O)S(=O)C.CN1C=C(C(C2=CC=CC=C12)=O)S(=O)C ITTYVMKWMLPYAT-UHFFFAOYSA-N 0.000 description 1
- HAZYXTYCLOYJIL-UHFFFAOYSA-N 1,5,7-trimethyl-3-methylsulfinylquinolin-4-one Chemical compound CN1C=C(S(C)=O)C(=O)C=2C1=CC(C)=CC=2C HAZYXTYCLOYJIL-UHFFFAOYSA-N 0.000 description 1
- FCSWOQDHAURNPI-UHFFFAOYSA-N 1,7-dimethyl-3-methylsulfinylquinoline-4-thione Chemical compound CN1C=C(S(C)=O)C(=S)C=2C1=CC(C)=CC=2 FCSWOQDHAURNPI-UHFFFAOYSA-N 0.000 description 1
- VHBJGBWEWWARRW-UHFFFAOYSA-N 1,8-dimethyl-3-methylsulfinylquinolin-4-one Chemical compound CN1C=C(S(C)=O)C(=O)C2=C1C(C)=CC=C2 VHBJGBWEWWARRW-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/04—1,3-Oxazines; Hydrogenated 1,3-oxazines
- C07D265/12—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems
- C07D265/14—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D265/24—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with hetero atoms directly attached in positions 2 and 4
- C07D265/26—Two oxygen atoms, e.g. isatoic anhydride
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/36—Sulfur atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (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)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB7910558 | 1979-03-27 | ||
| GB7939505 | 1979-11-15 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE3011994A1 true DE3011994A1 (de) | 1980-10-16 |
| DE3011994C2 DE3011994C2 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1991-06-27 |
Family
ID=26271029
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19803011994 Granted DE3011994A1 (de) | 1979-03-27 | 1980-03-27 | Chinolonverbindungen, verfahren zu deren herstellung und arzneimittelzubereitungen, enthaltend diese chinolonverbindungen |
| DE19803051205 Expired - Lifetime DE3051205C2 (de) | 1979-03-27 | 1980-03-27 | Pharmazeutische Zubereitung mit antihypartensiver Wirkung, enthaltend eine Chinolonverbindung |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19803051205 Expired - Lifetime DE3051205C2 (de) | 1979-03-27 | 1980-03-27 | Pharmazeutische Zubereitung mit antihypartensiver Wirkung, enthaltend eine Chinolonverbindung |
Country Status (34)
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3138121A1 (de) * | 1980-09-26 | 1982-04-15 | The Boots Co. Ltd., Nottingham | Chinolone, verfahren zur ihrer herstellung und ihre verwendung in therapeutischen zubereitungen |
Families Citing this family (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PT79031B (en) * | 1983-08-20 | 1986-08-22 | Boots Co Plc | Therapeutic agents |
| DE3578374D1 (de) * | 1984-01-13 | 1990-08-02 | Boots Co Ltd | Verwendung von chinolonen fuer die herstellung eines arzneimittels zur behandlung von herzerkrankungen. |
| DE3576686D1 (de) * | 1984-08-15 | 1990-04-26 | Boots Co Ltd | Chinolinone, verfahren zu ihrer herstellung und die sie enthaltenden pharmazeutischen praeparate. |
| GB8515207D0 (en) * | 1985-06-15 | 1985-07-17 | Boots Co Plc | Therapeutic agents |
| GB8515209D0 (en) * | 1985-06-15 | 1985-07-17 | Boots Co Plc | Therapeutic agents |
| GB8627698D0 (en) * | 1986-11-20 | 1986-12-17 | Boots Co Plc | Therapeutic agents |
| GB8726950D0 (en) * | 1987-11-18 | 1987-12-23 | Boots Co Plc | Chemical process |
| GB8804016D0 (en) * | 1988-02-22 | 1988-03-23 | Boots Co Plc | Therapeutic agents |
| GB8918952D0 (en) * | 1989-08-19 | 1989-10-04 | Boots Co Plc | Therapeutic agents |
| FR2680511B1 (fr) * | 1991-08-20 | 1995-05-19 | Roussel Uclaf | Derives n-substitues de la quinoleine, leur procede de preparation, intermediaires obtenus, leur application comme medicaments et les compositions les renfermant. |
| FR2672597B1 (fr) * | 1991-02-07 | 1995-05-19 | Roussel Uclaf | Nouveaux derives n-substitues de la quinoleine, leur procede de preparation, les nouveaux intermediaires obtenus, leur application a titre de medicaments et les compositions pharmaceutiques les renfermant. |
| IL100555A (en) * | 1991-02-07 | 2000-08-31 | Hoechst Marion Roussel Inc | N-substituted quinoline derivatives their preparation their use for the preparation of medicaments and the pharmaceutical compositions containing them |
| FR2684671B1 (fr) * | 1991-11-20 | 1995-05-19 | Roussel Uclaf | Nouveaux derives de la quinoleine, leur procede de preparation et intermediaires et leur application a titre de medicaments. |
| WO2000007595A1 (en) * | 1998-08-03 | 2000-02-17 | Basf Corporation | Pyridinones for the treatment of sexual dysfunction |
| US6307050B1 (en) * | 2000-08-29 | 2001-10-23 | R. T. Alamo Venture I Llc | Method of synthesizing flosequinan from 4-fluoroanthranilic acid |
| US6458804B1 (en) * | 2001-01-26 | 2002-10-01 | R.T. Alamo Venturesi, Llc | Methods for the treatment of central nervous system disorders in certain patient groups |
| US6451813B1 (en) | 2001-01-26 | 2002-09-17 | R. T. Alamo Ventures I, Llc | Treatment of gastroparesis in certain patient groups |
| US6562838B2 (en) * | 2001-01-26 | 2003-05-13 | R. T. Alamo Ventures I, L.L.C. | Treatment of cardiovascular disease with quinolinone enantiomers |
| US6649764B2 (en) * | 2001-10-25 | 2003-11-18 | R. T. Alamo Ventures I, Llc | Stereospecific enrichment of heterocyclic enantiomers |
| US6730790B2 (en) * | 2002-03-01 | 2004-05-04 | R.T. Alamo Ventures I. Llc | Chlorinated heterocyclic compounds and methods of synthesis |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4048177A (en) * | 1975-01-16 | 1977-09-13 | John Wyeth & Brother Limited | Certain 2-substituted 4-phenylquinoline-4-ols |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3178348A (en) * | 1961-02-08 | 1965-04-13 | Norwich Pharma Co | Hypotensive quinolines |
| BE661965A (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1964-04-03 | 1965-10-04 | ||
| DE1770482A1 (de) * | 1968-05-22 | 1971-11-11 | Basf Ag | Verfahren zur Herstellung von 2,4-Dioxychinolinen |
| US3798219A (en) * | 1971-10-18 | 1974-03-19 | Warner Lambert Co | 3-(methylsulfinyl)cinnolinones and their derivatives |
| US3772301A (en) * | 1971-11-22 | 1973-11-13 | Warner Lambert Co | (4-substituted)4-(methylsulfinyl)methylcarbostyrils |
| CH607848A5 (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) * | 1974-06-04 | 1978-11-30 | Bayer Ag | |
| US4124587A (en) * | 1976-03-01 | 1978-11-07 | Sandoz, Inc. | 4-Hydroxy-3-sulfinyl-quinolin-2(1H)-ones |
| US4127574A (en) * | 1976-03-01 | 1978-11-28 | Sandoz, Inc. | 4-Hydroxy-3-sulfonyl-quinolin-2(1H)-ones |
| DE2616991A1 (de) | 1976-04-17 | 1977-10-27 | Bayer Ag | Heterocyclisch-substituierte schwefelhaltige dihydropyridine, mehrere verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel |
| DE2616995A1 (de) | 1976-04-17 | 1977-10-27 | Bayer Ag | 1.4-dihydropyridine mit schwefelhaltigen substituenten mehrere verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel |
| DE2639257A1 (de) | 1976-09-01 | 1978-03-02 | Bayer Ag | Aminoalkylidenamino-1,4-dihydropyridine, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel |
| DE2639498A1 (de) | 1976-09-02 | 1978-03-09 | Bayer Ag | Neue schwefelhaltige amino-dihydropyridine, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel |
| DE2641746C2 (de) | 1976-09-16 | 1986-11-06 | Bayer Ag, 5090 Leverkusen | 1,4-Dihydropyridin-Zuckerderivate, Verfahren zu ihrer Herstellung sowie ihre Verwendung als Arzneimittel |
| DE2658183A1 (de) | 1976-12-22 | 1978-07-06 | Bayer Ag | In 2-position substituierte 1,4- dihydropyridin-derivate, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel |
| DE2658804A1 (de) | 1976-12-24 | 1978-07-06 | Bayer Ag | Kreislaufbeeinflussende mittel |
| DE2715182A1 (de) | 1977-04-05 | 1978-10-19 | Bayer Ag | 2-alkylenaminodihydropyridine, verfahren zu ihrer herstellung sowie ihre verwendung als arzneimittel |
| US4177278A (en) * | 1977-04-05 | 1979-12-04 | Bayer Aktiengesellschaft | 2-Alkyleneaminodihydropyridines compounds, their production and their medicinal use |
| JPS5424882A (en) | 1977-07-22 | 1979-02-24 | Yamanouchi Pharmaceut Co Ltd | Novel heterocyclic compounds and their preparation |
| DE2747513A1 (de) | 1977-10-22 | 1979-05-03 | Bayer Ag | Dihydropyridine mit schwefelhaltigen estergruppierungen |
-
1980
- 1980-03-18 NZ NZ193167A patent/NZ193167A/en unknown
- 1980-03-19 IE IE567/80A patent/IE49562B1/en not_active IP Right Cessation
- 1980-03-21 AU AU56702/80A patent/AU536616B2/en not_active Ceased
- 1980-03-22 GR GR61514A patent/GR68007B/el unknown
- 1980-03-24 PH PH23802A patent/PH16758A/en unknown
- 1980-03-24 US US06/133,310 patent/US4302460A/en not_active Expired - Lifetime
- 1980-03-25 IL IL59710A patent/IL59710A/xx not_active IP Right Cessation
- 1980-03-25 LU LU82295A patent/LU82295A1/fr unknown
- 1980-03-25 RO RO80100611A patent/RO79397A/ro unknown
- 1980-03-25 FI FI800923A patent/FI77026C/fi not_active IP Right Cessation
- 1980-03-25 PT PT71006A patent/PT71006A/pt not_active IP Right Cessation
- 1980-03-26 CH CH237680A patent/CH644366A5/fr not_active IP Right Cessation
- 1980-03-26 DK DK130180A patent/DK151252C/da not_active IP Right Cessation
- 1980-03-26 NL NL8001771A patent/NL191306C/xx not_active IP Right Cessation
- 1980-03-26 NO NO800881A patent/NO156787C/no unknown
- 1980-03-26 BG BG066170A patent/BG37993A3/xx unknown
- 1980-03-26 CA CA000348520A patent/CA1151652A/en not_active Expired
- 1980-03-26 BG BG047135A patent/BG37836A3/xx unknown
- 1980-03-26 IT IT48262/80A patent/IT1188916B/it active
- 1980-03-26 KR KR1019800001266A patent/KR840001612B1/ko not_active Expired
- 1980-03-26 YU YU849/80A patent/YU42332B/xx unknown
- 1980-03-26 HU HU8080713A patent/HU179845B/hu not_active IP Right Cessation
- 1980-03-26 AT AT0161880A patent/AT379390B/de not_active IP Right Cessation
- 1980-03-26 SE SE8002345A patent/SE455422B/sv not_active IP Right Cessation
- 1980-03-27 DD DD80219973A patent/DD149608A5/de not_active IP Right Cessation
- 1980-03-27 CS CS802156A patent/CS221906B2/cs unknown
- 1980-03-27 DE DE19803011994 patent/DE3011994A1/de active Granted
- 1980-03-27 PL PL1980223050A patent/PL124037B1/pl unknown
- 1980-03-27 MX MX808725U patent/MX6816E/es unknown
- 1980-03-27 DE DE19803051205 patent/DE3051205C2/de not_active Expired - Lifetime
- 1980-03-27 FR FR8006811A patent/FR2452484A1/fr active Granted
- 1980-03-29 EG EG188/80A patent/EG16606A/xx active
- 1980-10-02 FR FR8021107A patent/FR2468367A1/fr active Granted
-
1986
- 1986-07-08 KE KE3649BD patent/KE3649D/xx unknown
- 1986-07-10 SG SG608/86A patent/SG60886G/en unknown
- 1986-12-04 HK HK949/86A patent/HK94986A/xx not_active IP Right Cessation
- 1986-12-30 MY MY668/86A patent/MY8600668A/xx unknown
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4048177A (en) * | 1975-01-16 | 1977-09-13 | John Wyeth & Brother Limited | Certain 2-substituted 4-phenylquinoline-4-ols |
Non-Patent Citations (2)
| Title |
|---|
| Chemical Abstracts, Bd. 88, 1978, 105172 c * |
| EHRHART-RUSCHIG: Arzneimittel, Bd. 2, 1972, S.284 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE3138121A1 (de) * | 1980-09-26 | 1982-04-15 | The Boots Co. Ltd., Nottingham | Chinolone, verfahren zur ihrer herstellung und ihre verwendung in therapeutischen zubereitungen |
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| 8128 | New person/name/address of the agent |
Representative=s name: SCHWABE, H., DIPL.-ING. SANDMAIR, K., DIPL.-CHEM. |
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| D2 | Grant after examination | ||
| 8364 | No opposition during term of opposition |