JPS6348268B2 - - Google Patents
Info
- Publication number
- JPS6348268B2 JPS6348268B2 JP56151895A JP15189581A JPS6348268B2 JP S6348268 B2 JPS6348268 B2 JP S6348268B2 JP 56151895 A JP56151895 A JP 56151895A JP 15189581 A JP15189581 A JP 15189581A JP S6348268 B2 JPS6348268 B2 JP S6348268B2
- Authority
- JP
- Japan
- Prior art keywords
- methyl
- quinolone
- chloro
- fluoro
- compound
- 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.)
- Expired
Links
- 150000001875 compounds Chemical class 0.000 claims description 86
- -1 quinolone compound Chemical class 0.000 claims description 25
- 238000004519 manufacturing process Methods 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 11
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 claims description 10
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 150000001450 anions Chemical class 0.000 claims description 5
- PMZDQRJGMBOQBF-UHFFFAOYSA-N quinolin-4-ol Chemical compound C1=CC=C2C(O)=CC=NC2=C1 PMZDQRJGMBOQBF-UHFFFAOYSA-N 0.000 claims description 5
- IWWMWAAPKDZCIG-UHFFFAOYSA-N 7-chloro-1-methyl-3-(methylsulfonylmethyl)quinolin-4-one Chemical compound C1=C(Cl)C=C2N(C)C=C(CS(C)(=O)=O)C(=O)C2=C1 IWWMWAAPKDZCIG-UHFFFAOYSA-N 0.000 claims description 4
- XDTQCQCYYCBTDO-UHFFFAOYSA-N 7-fluoro-1-methyl-3-(methylsulfonylmethyl)quinolin-4-one Chemical compound C1=C(F)C=C2N(C)C=C(CS(C)(=O)=O)C(=O)C2=C1 XDTQCQCYYCBTDO-UHFFFAOYSA-N 0.000 claims description 4
- 230000008707 rearrangement Effects 0.000 claims description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 claims description 2
- 230000002152 alkylating effect Effects 0.000 claims 1
- 230000003301 hydrolyzing effect Effects 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 75
- 239000000203 mixture Substances 0.000 description 50
- 238000002844 melting Methods 0.000 description 39
- 230000008018 melting Effects 0.000 description 39
- 239000000243 solution Substances 0.000 description 34
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 30
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 27
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- 239000000047 product Substances 0.000 description 18
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 238000012360 testing method Methods 0.000 description 14
- 238000006243 chemical reaction Methods 0.000 description 12
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 12
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 239000002775 capsule Substances 0.000 description 9
- 238000010992 reflux Methods 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 8
- 241000700159 Rattus Species 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 8
- 230000036772 blood pressure Effects 0.000 description 8
- LYPGDCWPTHTUDO-UHFFFAOYSA-M sodium;methanesulfinate Chemical compound [Na+].CS([O-])=O LYPGDCWPTHTUDO-UHFFFAOYSA-M 0.000 description 8
- 239000007787 solid Substances 0.000 description 8
- 239000012265 solid product Substances 0.000 description 8
- 235000015096 spirit Nutrition 0.000 description 8
- GENAIPOCRXECKE-UHFFFAOYSA-N 1-methyl-3-(methylsulfonylmethyl)quinolin-4-one Chemical compound C1=CC=C2N(C)C=C(CS(C)(=O)=O)C(=O)C2=C1 GENAIPOCRXECKE-UHFFFAOYSA-N 0.000 description 7
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 7
- 230000003647 oxidation Effects 0.000 description 7
- 238000007254 oxidation reaction Methods 0.000 description 7
- 150000007660 quinolones Chemical class 0.000 description 7
- RMBAVIFYHOYIFM-UHFFFAOYSA-M sodium methanethiolate Chemical compound [Na+].[S-]C RMBAVIFYHOYIFM-UHFFFAOYSA-M 0.000 description 7
- 230000001225 therapeutic effect Effects 0.000 description 7
- CSJAXRKDCCWCSJ-UHFFFAOYSA-N Echinopsine Chemical compound C1=CC=C2N(C)C=CC(=O)C2=C1 CSJAXRKDCCWCSJ-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 206010020772 Hypertension Diseases 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 239000001506 calcium phosphate Substances 0.000 description 5
- 229910000389 calcium phosphate Inorganic materials 0.000 description 5
- 235000011010 calcium phosphates Nutrition 0.000 description 5
- 230000001631 hypertensive effect Effects 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 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 5
- 238000009835 boiling Methods 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 229920002261 Corn starch Polymers 0.000 description 3
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- 241001465754 Metazoa Species 0.000 description 3
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical class N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 3
- 239000008120 corn starch Substances 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 239000007903 gelatin capsule Substances 0.000 description 3
- 239000008101 lactose Substances 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 150000004965 peroxy acids Chemical class 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 150000003462 sulfoxides Chemical class 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 150000003568 thioethers Chemical class 0.000 description 3
- WHMKOLHSNXZCAV-UHFFFAOYSA-N 1,7-dimethyl-3-(methylsulfonylmethyl)quinolin-4-one Chemical compound CN1C=C(CS(C)(=O)=O)C(=O)C=2C1=CC(C)=CC=2 WHMKOLHSNXZCAV-UHFFFAOYSA-N 0.000 description 2
- HGYSLLDCNCCEHQ-UHFFFAOYSA-N 1-methyl-3-(methylsulfanylmethyl)quinolin-4-one Chemical compound C1=CC=C2C(=O)C(CSC)=CN(C)C2=C1 HGYSLLDCNCCEHQ-UHFFFAOYSA-N 0.000 description 2
- CQKLDECUWZDOAW-UHFFFAOYSA-N 3-(chloromethyl)-1-methyl-7-(trifluoromethyl)quinolin-4-one;hydrochloride Chemical compound Cl.C1=C(C(F)(F)F)C=C2N(C)C=C(CCl)C(=O)C2=C1 CQKLDECUWZDOAW-UHFFFAOYSA-N 0.000 description 2
- DJIDIYHFTRCMAZ-UHFFFAOYSA-N 3-(hydroxymethyl)-1-methylquinolin-4-one Chemical compound C1=CC=C2N(C)C=C(CO)C(=O)C2=C1 DJIDIYHFTRCMAZ-UHFFFAOYSA-N 0.000 description 2
- HRBXHHMSBOWGSY-UHFFFAOYSA-N 3-(methylsulfonylmethyl)-1h-quinolin-4-one Chemical class C1=CC=CC2=C(O)C(CS(=O)(=O)C)=CN=C21 HRBXHHMSBOWGSY-UHFFFAOYSA-N 0.000 description 2
- KAGQRUNOAPAMCZ-UHFFFAOYSA-N 4-chloro-3-(chloromethyl)quinoline Chemical compound C1=CC=CC2=C(Cl)C(CCl)=CN=C21 KAGQRUNOAPAMCZ-UHFFFAOYSA-N 0.000 description 2
- HDPVRRZTNQXTJR-UHFFFAOYSA-N 7-chloro-1-methyl-3-(methylsulfanylmethyl)quinolin-4-one Chemical compound ClC1=CC=C2C(=O)C(CSC)=CN(C)C2=C1 HDPVRRZTNQXTJR-UHFFFAOYSA-N 0.000 description 2
- 229920000623 Cellulose acetate phthalate Polymers 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
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 229940081734 cellulose acetate phthalate Drugs 0.000 description 2
- 239000003610 charcoal Substances 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- 238000004440 column chromatography Methods 0.000 description 2
- FLKPEMZONWLCSK-UHFFFAOYSA-N diethyl phthalate Chemical compound CCOC(=O)C1=CC=CC=C1C(=O)OCC FLKPEMZONWLCSK-UHFFFAOYSA-N 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 235000019198 oils Nutrition 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 150000003457 sulfones Chemical class 0.000 description 2
- 150000003512 tertiary amines Chemical class 0.000 description 2
- HMUNWXXNJPVALC-UHFFFAOYSA-N 1-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-2-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)C(CN1CC2=C(CC1)NN=N2)=O HMUNWXXNJPVALC-UHFFFAOYSA-N 0.000 description 1
- AGEVWYPZSUUXCB-UHFFFAOYSA-N 1-methyl-3-(methylsulfinylmethyl)-7-(trifluoromethyl)quinolin-4-one Chemical compound C1=C(C(F)(F)F)C=C2N(C)C=C(CS(C)=O)C(=O)C2=C1 AGEVWYPZSUUXCB-UHFFFAOYSA-N 0.000 description 1
- XVVNYAOJFHUUJU-UHFFFAOYSA-N 1-methyl-3-(methylsulfonylmethyl)-7-(trifluoromethyl)quinolin-4-one Chemical compound C1=C(C(F)(F)F)C=C2N(C)C=C(CS(C)(=O)=O)C(=O)C2=C1 XVVNYAOJFHUUJU-UHFFFAOYSA-N 0.000 description 1
- FITARACUDZLEAW-UHFFFAOYSA-N 2-(trifluoromethyl)-3h-quinolin-4-one Chemical compound C1=CC=C2C(=O)CC(C(F)(F)F)=NC2=C1 FITARACUDZLEAW-UHFFFAOYSA-N 0.000 description 1
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 1
- PHXZYTOVHGFBGV-UHFFFAOYSA-N 2-methyl-3-(methylsulfinylmethyl)-3H-quinolin-4-one Chemical compound CC1=NC2=CC=CC=C2C(C1CS(=O)C)=O PHXZYTOVHGFBGV-UHFFFAOYSA-N 0.000 description 1
- NLKAGOBCXYMVBL-UHFFFAOYSA-N 2-methyl-7-(trifluoromethyl)-3H-quinolin-4-one Chemical compound CC1=NC2=CC(=CC=C2C(=O)C1)C(F)(F)F NLKAGOBCXYMVBL-UHFFFAOYSA-N 0.000 description 1
- GQVBDXKXBACRJS-UHFFFAOYSA-N 3-(chloromethyl)-1-methylquinolin-4-one;hydrochloride Chemical compound Cl.C1=CC=C2N(C)C=C(CCl)C(=O)C2=C1 GQVBDXKXBACRJS-UHFFFAOYSA-N 0.000 description 1
- YOGIENHSLIMXBF-UHFFFAOYSA-N 3-(hydroxymethyl)-7-(trifluoromethyl)-1h-quinolin-4-one Chemical compound FC(F)(F)C1=CC=C2C(=O)C(CO)=CNC2=C1 YOGIENHSLIMXBF-UHFFFAOYSA-N 0.000 description 1
- ZRILLKPLFRVBPV-UHFFFAOYSA-N 3-(methylsulfonylmethyl)-3h-quinolin-4-one Chemical compound C1=CC=C2C(=O)C(CS(=O)(=O)C)C=NC2=C1 ZRILLKPLFRVBPV-UHFFFAOYSA-N 0.000 description 1
- UVBNWRMZMQJLKE-UHFFFAOYSA-N 4-chloro-3-(methylsulfonylmethyl)quinoline Chemical compound C1=CC=CC2=C(Cl)C(CS(=O)(=O)C)=CN=C21 UVBNWRMZMQJLKE-UHFFFAOYSA-N 0.000 description 1
- WPYDKPOTLBKLRR-UHFFFAOYSA-N 4-methoxy-3-(methylsulfonylmethyl)quinoline Chemical compound C1=CC=C2C(OC)=C(CS(C)(=O)=O)C=NC2=C1 WPYDKPOTLBKLRR-UHFFFAOYSA-N 0.000 description 1
- ZJGHSMMIYGZJJV-UHFFFAOYSA-N 6-fluoro-1-methyl-3-(methylsulfanylmethyl)quinolin-4-one Chemical class C1=C(F)C=C2C(=O)C(CSC)=CN(C)C2=C1 ZJGHSMMIYGZJJV-UHFFFAOYSA-N 0.000 description 1
- CIFBUMABMXYVGU-UHFFFAOYSA-N 6-fluoro-1-methyl-3-(methylsulfinylmethyl)quinolin-4-one Chemical compound FC1=CC=C2N(C)C=C(CS(C)=O)C(=O)C2=C1 CIFBUMABMXYVGU-UHFFFAOYSA-N 0.000 description 1
- HKZNZSVDBFVUFL-UHFFFAOYSA-N 6-fluoro-1-methyl-3-(methylsulfonylmethyl)quinolin-4-one Chemical compound FC1=CC=C2N(C)C=C(CS(C)(=O)=O)C(=O)C2=C1 HKZNZSVDBFVUFL-UHFFFAOYSA-N 0.000 description 1
- BYZXOYSEYWCLOK-UHFFFAOYSA-N 6-fluoro-1h-quinolin-4-one Chemical compound C1=C(F)C=C2C(O)=CC=NC2=C1 BYZXOYSEYWCLOK-UHFFFAOYSA-N 0.000 description 1
- WZWHUBIVAMSGGX-UHFFFAOYSA-N 6-fluoro-3-(hydroxymethyl)-1h-quinolin-4-one Chemical compound C1=CC(F)=CC2=C(O)C(CO)=CN=C21 WZWHUBIVAMSGGX-UHFFFAOYSA-N 0.000 description 1
- OWPLFJSQLPTCHS-UHFFFAOYSA-N 7-(trifluoromethyl)-1H-quinolin-4-one Chemical compound FC(F)(F)C1=CC=C2C(O)=CC=NC2=C1 OWPLFJSQLPTCHS-UHFFFAOYSA-N 0.000 description 1
- GGCBEWNXEGDQAP-UHFFFAOYSA-N 7-bromo-1h-quinolin-4-one Chemical compound N1C=CC(=O)C=2C1=CC(Br)=CC=2 GGCBEWNXEGDQAP-UHFFFAOYSA-N 0.000 description 1
- NHXDXHBIMREAMF-UHFFFAOYSA-N 7-chloro-1-methyl-3-(methylsulfinylmethyl)quinolin-4-one Chemical compound C1=C(Cl)C=C2N(C)C=C(CS(C)=O)C(=O)C2=C1 NHXDXHBIMREAMF-UHFFFAOYSA-N 0.000 description 1
- AXZHIJAIXQIFBT-UHFFFAOYSA-N 7-chloro-3-(hydroxymethyl)-1-methylquinolin-4-one Chemical compound C1=C(Cl)C=C2N(C)C=C(CO)C(=O)C2=C1 AXZHIJAIXQIFBT-UHFFFAOYSA-N 0.000 description 1
- CKYFKKNREGWYNK-UHFFFAOYSA-N 7-chloro-3-(hydroxymethyl)-1h-quinolin-4-one Chemical compound ClC1=CC=C2C(=O)C(CO)=CNC2=C1 CKYFKKNREGWYNK-UHFFFAOYSA-N 0.000 description 1
- BXSQVPSEMPXLGL-UHFFFAOYSA-N 7-ethyl-1-methyl-3-(methylsulfonylmethyl)quinolin-4-one Chemical compound CN1C=C(CS(C)(=O)=O)C(=O)C=2C1=CC(CC)=CC=2 BXSQVPSEMPXLGL-UHFFFAOYSA-N 0.000 description 1
- KFODGYUZXRZUCQ-UHFFFAOYSA-N 7-fluoro-1-methyl-3-(methylsulfanylmethyl)quinolin-4-one Chemical compound FC1=CC=C2C(=O)C(CSC)=CN(C)C2=C1 KFODGYUZXRZUCQ-UHFFFAOYSA-N 0.000 description 1
- ZLHGUGJJHJJVHV-UHFFFAOYSA-N 7-fluoro-1h-quinolin-4-one Chemical compound N1C=CC(=O)C=2C1=CC(F)=CC=2 ZLHGUGJJHJJVHV-UHFFFAOYSA-N 0.000 description 1
- JPVTWKDGBWUNBQ-UHFFFAOYSA-N 7-methyl-1h-quinolin-4-one Chemical compound OC1=CC=NC2=CC(C)=CC=C21 JPVTWKDGBWUNBQ-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 1
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 238000004949 mass spectrometry Methods 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- JZMJDSHXVKJFKW-UHFFFAOYSA-M methyl sulfate(1-) Chemical compound COS([O-])(=O)=O JZMJDSHXVKJFKW-UHFFFAOYSA-M 0.000 description 1
- 238000003801 milling Methods 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 150000004967 organic peroxy acids Chemical class 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 238000010298 pulverizing process Methods 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 238000012306 spectroscopic technique Methods 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- 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
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
- C07D215/233—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 4
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/04—Immunostimulants
-
- 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
- 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
- C07D215/18—Halogen atoms or nitro radicals
-
- 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
- C07D215/20—Oxygen atoms
- C07D215/24—Oxygen atoms attached in position 8
- C07D215/26—Alcohols; Ethers thereof
-
- 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
-
- 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
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D215/54—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3
- C07D215/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen attached in position 3 with oxygen atoms in position 4
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Immunology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Quinoline Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB8031106 | 1980-09-26 |
Publications (2)
Publication Number | Publication Date |
---|---|
JPS5785369A JPS5785369A (en) | 1982-05-28 |
JPS6348268B2 true JPS6348268B2 (enrdf_load_stackoverflow) | 1988-09-28 |
Family
ID=10516302
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP56151895A Granted JPS5785369A (en) | 1980-09-26 | 1981-09-25 | Quinolone, therapeutical composition containing same and manufacture |
Country Status (4)
Country | Link |
---|---|
JP (1) | JPS5785369A (enrdf_load_stackoverflow) |
BE (1) | BE890477A (enrdf_load_stackoverflow) |
HU (1) | HU184968B (enrdf_load_stackoverflow) |
ZA (1) | ZA816352B (enrdf_load_stackoverflow) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH03196382A (ja) * | 1989-12-26 | 1991-08-27 | Nec Home Electron Ltd | 携帯型情報処理装置 |
-
1981
- 1981-09-14 ZA ZA816352A patent/ZA816352B/xx unknown
- 1981-09-24 BE BE0/206048A patent/BE890477A/fr not_active IP Right Cessation
- 1981-09-25 HU HU812775A patent/HU184968B/hu unknown
- 1981-09-25 JP JP56151895A patent/JPS5785369A/ja active Granted
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPH03196382A (ja) * | 1989-12-26 | 1991-08-27 | Nec Home Electron Ltd | 携帯型情報処理装置 |
Also Published As
Publication number | Publication date |
---|---|
JPS5785369A (en) | 1982-05-28 |
ZA816352B (en) | 1982-09-29 |
BE890477A (fr) | 1982-03-24 |
HU184968B (en) | 1984-11-28 |
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