JPH02174784A - Isothiazoloquinoline derivative - Google Patents
Isothiazoloquinoline derivativeInfo
- Publication number
- JPH02174784A JPH02174784A JP63327761A JP32776188A JPH02174784A JP H02174784 A JPH02174784 A JP H02174784A JP 63327761 A JP63327761 A JP 63327761A JP 32776188 A JP32776188 A JP 32776188A JP H02174784 A JPH02174784 A JP H02174784A
- Authority
- JP
- Japan
- Prior art keywords
- acid
- formula
- present
- derivative
- 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.)
- Pending
Links
- VRRISJNZQGMTND-UHFFFAOYSA-N [1,2]thiazolo[3,4-h]quinoline Chemical class C1=CN=C2C3=CSN=C3C=CC2=C1 VRRISJNZQGMTND-UHFFFAOYSA-N 0.000 title 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 4
- 150000003839 salts Chemical class 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 7
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 12
- -1 cyclic amine compound Chemical class 0.000 abstract description 12
- 239000002904 solvent Substances 0.000 abstract description 11
- 125000000217 alkyl group Chemical group 0.000 abstract description 10
- 239000003242 anti bacterial agent Substances 0.000 abstract description 7
- 241000894006 Bacteria Species 0.000 abstract description 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 3
- 125000005843 halogen group Chemical group 0.000 abstract description 2
- 238000002360 preparation method Methods 0.000 abstract description 2
- 241000192125 Firmicutes Species 0.000 abstract 1
- 229910052736 halogen Inorganic materials 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 239000013078 crystal Substances 0.000 description 16
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- 238000006243 chemical reaction Methods 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- 238000000034 method Methods 0.000 description 7
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-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
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 238000000921 elemental analysis Methods 0.000 description 6
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 239000000203 mixture Substances 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 239000003814 drug 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
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 230000000844 anti-bacterial effect Effects 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000000354 decomposition reaction Methods 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- FLBAYUMRQUHISI-UHFFFAOYSA-N 1,8-naphthyridine Chemical group N1=CC=CC2=CC=CN=C21 FLBAYUMRQUHISI-UHFFFAOYSA-N 0.000 description 2
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-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
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 239000002168 alkylating agent Substances 0.000 description 2
- 229940100198 alkylating agent Drugs 0.000 description 2
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 2
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N butyric aldehyde Natural products CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 1
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- MPPPKRYCTPRNTB-UHFFFAOYSA-N 1-bromobutane Chemical compound CCCCBr MPPPKRYCTPRNTB-UHFFFAOYSA-N 0.000 description 1
- RJTGXTZXSYLWEY-VOTSOKGWSA-N 1-fluoro-4-[(e)-2-(4-methylphenyl)ethenyl]benzene Chemical compound C1=CC(C)=CC=C1\C=C\C1=CC=C(F)C=C1 RJTGXTZXSYLWEY-VOTSOKGWSA-N 0.000 description 1
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 1
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
- VMUXSMXIQBNMGZ-UHFFFAOYSA-N 3,4-dihydrocoumarin Chemical group C1=CC=C2OC(=O)CCC2=C1 VMUXSMXIQBNMGZ-UHFFFAOYSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- CYDGTBLZSKGNQS-UHFFFAOYSA-N 4-oxo-2-sulfanylidene-1H-quinoline-3-carboxylic acid Chemical compound C1=CC=C2C(=O)C(C(=O)O)C(=S)NC2=C1 CYDGTBLZSKGNQS-UHFFFAOYSA-N 0.000 description 1
- 108010054814 DNA Gyrase Proteins 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- IKHGUXGNUITLKF-XPULMUKRSA-N acetaldehyde Chemical compound [14CH]([14CH3])=O IKHGUXGNUITLKF-XPULMUKRSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229940111121 antirheumatic drug quinolines Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 239000008098 formaldehyde solution Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 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
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- LULAYUGMBFYYEX-UHFFFAOYSA-N metachloroperbenzoic acid Natural products OC(=O)C1=CC=CC(Cl)=C1 LULAYUGMBFYYEX-UHFFFAOYSA-N 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- MHWLWQUZZRMNGJ-UHFFFAOYSA-N nalidixic acid Chemical compound C1=C(C)N=C2N(CC)C=C(C(O)=O)C(=O)C2=C1 MHWLWQUZZRMNGJ-UHFFFAOYSA-N 0.000 description 1
- 229960000210 nalidixic acid Drugs 0.000 description 1
- 239000007923 nasal drop Substances 0.000 description 1
- 229940100662 nasal drops Drugs 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- OGJPXUAPXNRGGI-UHFFFAOYSA-N norfloxacin Chemical compound C1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCNCC1 OGJPXUAPXNRGGI-UHFFFAOYSA-N 0.000 description 1
- 229960001180 norfloxacin Drugs 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- SIRSTRHGFGFVME-UHFFFAOYSA-N piperazin-2-ylmethanol Chemical compound OCC1CNCCN1 SIRSTRHGFGFVME-UHFFFAOYSA-N 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- HYHCSLBZRBJJCH-UHFFFAOYSA-M sodium hydrosulfide Chemical compound [Na+].[SH-] HYHCSLBZRBJJCH-UHFFFAOYSA-M 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 208000019206 urinary tract infection Diseases 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Landscapes
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
【発明の詳細な説明】
−の１
本発明は優れた抗菌作用を仔し医薬品として有用な新規
なインチアゾロキノリン誘導体及びその薬理学的に許容
しつる酸付加塩に関するものである。DETAILED DESCRIPTION OF THE INVENTION (1) The present invention relates to novel inthiazoloquinoline derivatives that have excellent antibacterial activity and are useful as pharmaceuticals, and their pharmacologically acceptable phosphoric acid addition salts.
従」ＬＯ丑」【
ナリジクス酸からの流れを受けついで発展して来た合成
抗菌剤はナフチリジン環、ベンゾオキサノン環あるいは
キノリン環を母核とする合成抗菌剤が主流であり、本発
明に係るインチアゾロキノリン誘導体については全く知
られていない。Synthetic antibacterial agents that have been developed following the trend from nalidixic acid are mainly synthetic antibacterial agents that have a naphthyridine ring, benzoxanone ring, or quinoline ring as their core, and the present invention Nothing is known about inthiazoloquinoline derivatives.
ナフチリジン環及びキノリン系の合成抗菌剤は、ノルフ
ロキサシンの発見以来、画期的な進歩をもたらし、その
適応症は***症にとどまらずあらゆる感染症に有効
であることが示されている。Synthetic antibacterial agents based on naphthyridine rings and quinolines have brought breakthroughs since the discovery of norfloxacin, and have been shown to be effective for all kinds of infections, not just urinary tract infections.
又、その作用機序は、ＤＮＡ立体化酵素であるＤＮＡジ
ャイレースの阻害作用であり、抗生物質の如きプラスミ
ドによる耐性の伝達が起こらないことも知られている。It is also known that its mechanism of action is the inhibition of DNA gyrase, a DNA stericase, and that transmission of resistance by plasmids, such as with antibiotics, does not occur.
しかしながら、近年臨床の場では着実に非感受性閑の増
加が見られてきていることも事実である。これらのこと
から、既存の合成抗菌剤が完成された薬物であるとは言
い難く、臨床上での必要性からより優れた抗菌剤の登場
が強く望まれている。However, it is also true that in recent years there has been a steady increase in the number of non-susceptible patients in the clinical setting. For these reasons, it is difficult to say that existing synthetic antibacterial agents are perfect drugs, and the emergence of better antibacterial agents is strongly desired due to clinical necessity.
の
本発明者らは、前述の事情を鑑み鋭意研究した結果、本
発明に係る新規なインチアゾロキノリン誘導体及びその
薬理学的に許容しつる酸付加塩が優れた抗菌作用を有す
ることを見い出し、本発明を完成させた。As a result of intensive research in view of the above-mentioned circumstances, the present inventors have discovered that the novel inthiazoloquinoline derivative and its pharmacologically acceptable acid addition salt thereof according to the present invention have excellent antibacterial activity, The present invention has been completed.
即ち、本発明は次の一般式（Ｉ）
（式中、Ｒ１は低級アルキル基又はヒドロキシ低級アル
キル基を、Ｒ２及びＲ３は同一もしくは異なって水素原
子又は低級アルキル基を表わし、ｎは２又は３の整数を
表わす。ただし、Ｒ１がメチル基を表わす時、Ｒ２及び
Ｒ３は同時に水素原子を表わさない。）
で示されるインチアゾロキノリン誘導体及びその薬理学
的に許容しうる酸付加塩に関するものである。That is, the present invention relates to the following general formula (I) (wherein R1 represents a lower alkyl group or a hydroxy lower alkyl group, R2 and R3 are the same or different and represent a hydrogen atom or a lower alkyl group, and n is 2 or 3 (However, when R1 represents a methyl group, R2 and R3 do not represent a hydrogen atom at the same time.) and its pharmacologically acceptable acid addition salts. .
本発明の前記一般式（Ｉ）中、Ｒ工、Ｒ２及びＲ３で示
される低級アルキル基としては、たとえば、メチル基、
エチル基、ｎ−プロピル基、イソプロピル基、ｎ−ブチ
ル基、 ５ｅｃ−ブチル基、 ｔｅｒｔ−ブチル基等が
Ｘ Ｒ１で示されるヒドロキシ低級アルキル基としては
、たとえば、ヒドロキシメチル基。In the general formula (I) of the present invention, the lower alkyl group represented by R, R2 and R3 includes, for example, a methyl group,
An example of the hydroxy lower alkyl group represented by R1 is a hydroxymethyl group.
２−ヒドロキシエチル基、３−ヒドロキシプロピル基、
４−ヒドロキシブチル基等が挙げられる。2-hydroxyethyl group, 3-hydroxypropyl group,
Examples include 4-hydroxybutyl group.
本発明の前記一般式（Ｉ）で示される化合物の薬理学的
に許容しつる酸付加塩としては、たとえば、塩酸、臭化
水素酸、ヨウ化水素酸、硝酸、硫酸、燐酸等の鉱酸塩、
あるいは、酢酸、マレイン酸、フマル酸、クエン酸、リ
ンゴ酸、シュウ酸。Examples of the pharmacologically acceptable acid addition salts of the compound represented by the general formula (I) of the present invention include mineral acids such as hydrochloric acid, hydrobromic acid, hydroiodic acid, nitric acid, sulfuric acid, and phosphoric acid. salt,
Or acetic acid, maleic acid, fumaric acid, citric acid, malic acid, oxalic acid.
酒石酸、 メタンスルホン酸、 １０−カンファース
ルホン酸、マンデル酸等の有機酸塩が挙げられる。Examples include organic acid salts such as tartaric acid, methanesulfonic acid, 10-camphorsulfonic acid, and mandelic acid.
本発明の前記一般式（Ｉ）で示される化合物は７位環状
アミン基に不斉炭素原子を有しており、これらは光学活
性体として存在し得るため、これらの光学活性体も本発
明の化合物に包含される。The compound represented by the general formula (I) of the present invention has an asymmetric carbon atom in the 7-position cyclic amine group, and these can exist as optically active forms. Therefore, these optically active forms are also included in the present invention. Included in compounds.
本発明の前記一般式（Ｉ）で示されるインチアゾロキノ
リン誘導体は種々の方法により製造することができる。The inthiazoloquinoline derivative represented by the general formula (I) of the present invention can be produced by various methods.
本発明に係る化合物の製造方法の第一の様式によれば、
前記一般式（Ｉ）で示される化合物は、次の一般式（Ｉ
Ｉ）
（式中、Ｘはハロゲン原子を表わす。）で示される７−
バロゲンイソチアゾロキノリン誘導体と、次の一般式（
ＩＩＩ）
（式中、Ｒ工
Ｒ２、Ｒ３及びｎは前述と同意義
を表わす。）
でボされる環伏アミン化合物を、溶媒中塩基の存在下又
は非存在下で反応させることにより製造することができ
る。According to the first mode of the method for producing a compound according to the present invention,
The compound represented by the general formula (I) is represented by the following general formula (I).
I) 7- represented by (wherein, X represents a halogen atom)
A balogen isothiazoquinoline derivative and the following general formula (
III) (In the formula, R2, R3 and n represent the same meanings as above.) Produced by reacting a cyclic amine compound represented by the formula in the presence or absence of a base in a solvent. Can be done.
本発明の方法において使用される溶媒としては、反応を
阻害しない限りいかなるものでもよく、たとえば、アセ
トニトリル、Ｎ、Ｎ−ジメチルホルムアミド、Ｎ−メチ
ル−２−ピロリドン、ジメチルスルホキシド、ヘキサメ
チルフォスポリツクトリアミド等の非プロトン性極性溶
媒、ベンゼン。Any solvent may be used in the method of the present invention as long as it does not inhibit the reaction, such as acetonitrile, N,N-dimethylformamide, N-methyl-2-pyrrolidone, dimethylsulfoxide, hexamethylphosphoric acid, etc. Aprotic polar solvents such as amides, benzene.
トルエン等の芳香族炭化水素系溶媒、ピリノン。Aromatic hydrocarbon solvents such as toluene, pyrinone.
ピコリン、ルチジン、コリジン等の有機塩基あるいはこ
れらの混合溶媒が挙げられる。Examples include organic bases such as picoline, lutidine, and collidine, and mixed solvents thereof.
本発明の方法において使用される塩基としては、たとえ
ば、トリエチルアミン、１，８−ジアザビシクロ［：５
．４．０］−７−ウンデセン、炭酸ナトリウム、炭酸カ
リウム等が挙げられ、又、反応は水冷下から溶媒の還流
温度までの範囲で行われる。Bases used in the method of the invention include, for example, triethylamine, 1,8-diazabicyclo[:5
．． 4.0]-7-undecene, sodium carbonate, potassium carbonate, etc., and the reaction is carried out at a temperature ranging from water cooling to the reflux temperature of the solvent.
本発明の方法において出発原料となった前記−般式（ｎ
）で示される７−バロゲノイソチアゾロキノリン誘導体
もまた新規な化合物であり、以下の図に示す様にして製
造され、それらを参考例に記載した。In the method of the present invention, the starting material is the general formula (n
The 7-valogenoisothiazoloquinoline derivatives represented by ) are also new compounds, and were produced as shown in the figures below, and are described in Reference Examples.
（式中、Ｘは前述と同意義を表わす。）本発明に係る化
合物の製造方法の第二の様式によれば、前記一般式ＣＩ
）で示される化合物のうち、Ｒ２が低級アルキル基であ
る化合物は、前記一般式（Ｉ）中、Ｒ２が水素原子であ
る化合物をアルキル化することにより製造することがで
きる。(In the formula, X represents the same meaning as defined above.) According to the second mode of the method for producing a compound according to the present invention,
) Among the compounds represented by formula (1), a compound in which R2 is a lower alkyl group can be produced by alkylating a compound in which R2 is a hydrogen atom in the general formula (I).
本発明の方法において使用されるアルキル化剤としては
、ハロゲン化低級アルキルもしくはアルデヒド化合物が
挙げられ、ハロゲン化低級アルキルを用いる場合は、溶
媒中、脱酸剤としての塩基の存在下又は非存在下で反応
させ、又、アルデヒド化合物を用いる場合はギ酸の存在
下に反応させることにより製造することができる。The alkylating agent used in the method of the present invention includes a halogenated lower alkyl or an aldehyde compound, and when a halogenated lower alkyl is used, the alkylating agent is used in a solvent, in the presence or absence of a base as a deoxidizing agent. Alternatively, when an aldehyde compound is used, it can be produced by reacting it in the presence of formic acid.
本発明の方法において用いられるハロゲン化低級アルキ
ルとしては、たとえば、ヨウ化メチル。Examples of the lower alkyl halide used in the method of the present invention include methyl iodide.
ヨウ化エチル、臭化エチル、臭化ブチル等が、溶媒とし
ては、たとえば、Ｎ、Ｎ−ジメチルホルムアミド、アセ
トン、エタノール、テトラヒドロフラン、ベンゼン、ク
ロロホルム等が挙げられ、脱酸剤としての塩基としては
、たとえば、トリエチルアミン、炭酸カリウム等が挙げ
られる。Examples of solvents include ethyl iodide, ethyl bromide, butyl bromide, etc.; examples of solvents include N,N-dimethylformamide, acetone, ethanol, tetrahydrofuran, benzene, and chloroform; examples of bases as deoxidizers include: Examples include triethylamine, potassium carbonate, and the like.
又、本発明の方法のうち、アルデヒド化合物を用いる場
合のアルデヒド化合物としては、たとえば、ホルムアル
デヒド、アセトアルデヒド、プロピオンアルデヒド等が
挙げられ、ホルムアルデヒドはホルムアルデヒド水溶液
（ホルマリン）として使用することが好ましく、又、ア
セトアルデヒド及びプロピオンアルデヒドを使用する時
は、ニトロベンゼンを溶媒として用いることが好ましい
。Further, in the method of the present invention, when an aldehyde compound is used, examples of the aldehyde compound include formaldehyde, acetaldehyde, propionaldehyde, etc., and formaldehyde is preferably used as an aqueous formaldehyde solution (formalin); When using propionaldehyde, it is preferable to use nitrobenzene as a solvent.
又、反応は室ｌ」から２００’の範囲で行われる。Further, the reaction is carried out in a range from 1' to 200'.
この様にして製造される前記一般式（Ｉ）で示される新
規なインチアゾロキノリン誘導体及びその薬理学的に許
容しつる酸付加塩は、医薬品として一般に用いられる製
剤添加物を用いて、常法により錠剤、散剤、カプセル剤
、注射剤１点眼剤。The novel inthiazoloquinoline derivative represented by the general formula (I) and its pharmacologically acceptable acid addition salt produced in this way can be prepared by a conventional method using formulation additives commonly used as pharmaceuticals. Tablets, powders, capsules, injections and 1 eye drop.
点鼻剤又は外用剤等の製剤とすることができ、経口又は
非経口投与することにより臨床に供される。It can be made into formulations such as nasal drops or external preparations, and is clinically administered by oral or parenteral administration.
Ｌ胤■
以下、本発明を参考例及び実施例によって説明するが、
本発明はこれらの実施例の特定の細部に限定されるもの
ではない。Ltane ■ The present invention will be explained below by reference examples and examples.
The invention is not limited to the specific details of these examples.
参考例１
１−７クロプロピルー６．７−ジフルオロ−１４−ジヒ
ドロ−２−メチルスルフィニル−４−オキソキノリン−
３−カルボン酸エチル１−シクロプロピル−８，７−ジ
フルオロ−１４−ジヒドロ−２−メチルチオ−４−オキ
ソキノリン−３−カルボン酸エチル１．ＯＯｇの塩化メ
チレン１００ｍ１溶液に、８０％メタクロロ過安息香酸
０．７０ｇを加え室温で５．５時間撹拌する。反応液に
水を加え、水洗、乾燥後溶媒を減圧留去する。残渣にエ
ーテルを加え析出結晶をろ取し、無色結晶０．７１ｇを
得る。ベンゼンより再結晶して融点２１３〜２１４°の
無色針状晶を得る。Reference example 1 1-7 clopropyl-6,7-difluoro-14-dihydro-2-methylsulfinyl-4-oxoquinoline-
Ethyl 3-carboxylate 1-cyclopropyl-8,7-difluoro-14-dihydro-2-methylthio-4-oxoquinoline-3-carboxylate 1. 0.70 g of 80% metachloroperbenzoic acid was added to a solution of OOg in 100 ml of methylene chloride, and the mixture was stirred at room temperature for 5.5 hours. Water is added to the reaction solution, washed with water, and after drying, the solvent is distilled off under reduced pressure. Ether was added to the residue and the precipitated crystals were collected by filtration to obtain 0.71 g of colorless crystals. Recrystallization from benzene gives colorless needle crystals with a melting point of 213-214°.
元素分析値 Ｃ工。Ｈ工、Ｆ２Ｎ０４Ｓ理論値 Ｃ，５
４，０８； Ｈ、４，２５； Ｎ 、 ３．９４実験値
Ｃ，５４，８７； Ｈ、４，３９； Ｎ 、 ３．９
１参考例２
１−７りロプロピルー６．７−ジフルオロ−１４−ジヒ
ドロ−２−メルカプト−４−オキソキノリン−３−カル
ボン酸エチル
１−シクロプロピル−６，７−ジフルオロ−１４−ノヒ
ドロー２−メチルスルフイニル−４−オキソキノリン−
３−カルボン酸エチル０．７１ｇのテトラヒドロフラン
１０−１懸濁液に、ＩＮ水硫化ナトリウム水／８液２．
２１を加え３時間室温撹拌する。反応液を減圧濃縮し、
残渣を炭酸水素ナトリウム０．２５ｇ及び水２０−１に
溶解する。Elemental analysis value C engineering. H engineering, F2N04S theoretical value C, 5
4,08; H, 4,25; N, 3.94 Experimental value C, 54,87; H, 4,39; N, 3.9
1 Reference Example 2 Ethyl 1-7-difluoro-14-dihydro-2-mercapto-4-oxoquinoline-3-carboxylate 1-cyclopropyl-6,7-difluoro-14-nohydro-2-methyl Sulfinyl-4-oxoquinoline-
To a suspension of 0.71 g of ethyl 3-carboxylate in tetrahydrofuran 10-1, IN sodium hydrogen sulfide water/8 solution 2.
Add 21 and stir at room temperature for 3 hours. Concentrate the reaction solution under reduced pressure,
The residue is dissolved in 0.25 g of sodium bicarbonate and 20 parts of water.
水溶液をエーテル洗浄後、水層に希塩酸を加えｐＨ３と
し、析出結晶をろ取して融点９１〜９３″の赤色結晶０
．５０ｇを得る。After washing the aqueous solution with ether, dilute hydrochloric acid was added to the aqueous layer to adjust the pH to 3, and the precipitated crystals were collected by filtration.
．． Obtain 50g.
元素分析値 Ｃ１５Ｈ１３Ｆ ２ ＮＯ３Ｓ理論値 Ｃ
，５５，３８； Ｈ、４，０３； Ｎ 、 ４．３１実
験値 Ｃ，５５，２３； Ｈ、４，３５； Ｎ 、 ４
．３２参考例３
９−シクロプロピル−６，７−ジフルオロイソチアゾロ
［５，４−ｂ］キノリン−３，４（２８９Ｈ）−ジオン
１−シクロプロピル−６，７−ジフルオロ−１４−ジヒ
ドロ−２−メルカプト−４−オキソキノリン−３−カル
ボン酸０．４５ｇ、炭酸水素ナトリウム０．８７ｇ及び
テトラヒドロフラン５１の水２０■１溶液に、ヒドロキ
シルアミン−〇−スルホン酸０．３６ｇを加え２時間室
温撹拌する。Elemental analysis value C15H13F 2 NO3S theoretical value C
,55,38; H,4,03; N,4.31 Experimental value C,55,23; H,4,35; N,4
．． 32 Reference Example 3 9-Cyclopropyl-6,7-difluoroisothiazolo[5,4-b]quinoline-3,4(289H)-dione 1-cyclopropyl-6,7-difluoro-14-dihydro-2- To a solution of 0.45 g of mercapto-4-oxoquinoline-3-carboxylic acid, 0.87 g of sodium hydrogen carbonate, and 51 parts of tetrahydrofuran in 20 parts of water was added 0.36 g of hydroxylamine-〇-sulfonic acid, and the mixture was stirred at room temperature for 2 hours.
反応液に希塩酸を加えｐＨ３とし析出結晶をろ取する。Dilute hydrochloric acid is added to the reaction solution to adjust the pH to 3, and the precipitated crystals are collected by filtration.
得られた結晶をメタノール洗浄して融点２８２〜２８７
° （分解）の淡黄色結晶０．２４ｇを得る。The obtained crystals were washed with methanol to give a melting point of 282 to 287.
0.24 g of pale yellow crystals (decomposition) are obtained.
元素分析値 Ｃ１３Ｈ８Ｆ２ Ｎ ２０２ Ｓ理論値
Ｃ，５３，０８； Ｈ、２，７４； Ｎ 、 ９．５２
実験値 Ｃ，５３，０４； Ｈ、３，０９ｉ Ｎ 、
９．３４実施例１
９−シクロプロピル−６−フルオロ−７−（３−ヒトロ
キシメチルーｌ−ピペラジニル）−イソチアゾロ［５，
４−ｂコキノリン−３，４（２Ｈ９Ｈ）−ジオン
９−シクロプロピル−６，７−ジフルオロインチアゾロ
［５，４−ｂコキノリン−３，４（２Ｈ９Ｈ）−ジオン
０．５０ｇのピリジン８．５１Ｍ１＆！液に、２−ヒド
ロキシメチルピペラジン０゜３９ｇ、１．８−ジアザビ
シクロ［５，４，Ｏコー７−ウンデセン０．５２ｇを加
え３時間還流し、さらに２−ヒドロキシメチルピペラジ
ン０．１０ｇを加えて１時間還流する。反応液の溶媒を
留去し、残渣に酢酸エチルを加え析出結晶をろ取する。Elemental analysis value C13H8F2 N 202 S theoretical value
C, 53,08; H, 2,74; N, 9.52
Experimental value C, 53,04; H, 3,09i N,
9.34 Example 1 9-Cyclopropyl-6-fluoro-7-(3-hydroxymethyl-l-piperazinyl)-isothiazolo[5,
4-b coquinoline-3,4(2H9H)-dione 9-cyclopropyl-6,7-difluorothiazolo[5,4-b coquinoline-3,4(2H9H)-dione 0.50 g of pyridine 8.51 M1 &! To the solution, 0.39 g of 2-hydroxymethylpiperazine and 0.52 g of 1,8-diazabicyclo[5,4,O-7-undecene were added, and the mixture was refluxed for 3 hours. Reflux for an hour. The solvent of the reaction solution was distilled off, ethyl acetate was added to the residue, and the precipitated crystals were collected by filtration.
結晶を水に懸濁させ、１０％水酸化ナトリウム水溶液に
てｐＨ１１とした後、１０％塩酸でｐＨ８〜９とし、析
出結晶をろ取する。結晶をメタノールに懸濁させ、エタ
ノール性塩酸を加えてｐＨ１〜２とする。析出結晶をろ
取し、水及び１０％塩酸に加熱溶解し、１０％水酸化ナ
トリウム水溶液でｐＨ８〜９とする。析出結晶をろ取し
、融点２７５〜２８０° （分解）の淡褐色結晶を得る
。The crystals are suspended in water, the pH is adjusted to 11 with a 10% aqueous sodium hydroxide solution, the pH is adjusted to 8 to 9 with 10% hydrochloric acid, and the precipitated crystals are collected by filtration. The crystals are suspended in methanol and ethanolic hydrochloric acid is added to adjust the pH to 1-2. The precipitated crystals are collected by filtration, heated and dissolved in water and 10% hydrochloric acid, and adjusted to pH 8-9 with a 10% aqueous sodium hydroxide solution. The precipitated crystals are collected by filtration to obtain pale brown crystals with a melting point of 275-280° (decomposed).
元素分析値 Ｃ工。Ｈ工、ＦＮ４０３Ｓ＠Ｈ２０理論値
Ｃ，５２，９３；Ｈ、５，１８；Ｎ 、１３．７２実
験値 Ｃ，５３，２２； Ｈ、５，３０； Ｎ 、１３
．５９実施例１と同様にして実施例２〜３の化合物を得
る。Elemental analysis value C engineering. H Engineering, FN403S@H20 Theoretical value C, 52,93; H, 5, 18; N, 13.72 Experimental value C, 53, 22; H, 5, 30; N, 13
．． 59 Compounds of Examples 2 and 3 are obtained in the same manner as in Example 1.
実施例２
９−シクロプロピル−７−（３，５−ジメチル１−ピペ
ラジニル）−６−フルオロイソチアゾロ［５，４−ｂ］
キノリン−３，４（２Ｈ，９Ｈ）−ジオン働塩酸塩
性状 無色結晶（Ｆ２０）
融点 ２８８〜２９３＠ （分解）
元素分析値 Ｃ工９Ｈ２□ＦＮ４０２Ｓ・ＨＣＩ・Ｆ２
０
理論値 Ｃ，５１，５２； Ｈ，５，４Ｇ； Ｎ、１２
．６５実験値 Ｃ，５１，Ｇ３； Ｈ、５，３１； Ｎ
、１２．５８実施例３
９−７クロプロピルー６−フルオロー７−（１−ホモピ
ペラジニル）−インチアゾロ［５，４−ｂコキノリン−
３，４（２Ｈ，９Ｈ）−ジオン性状 淡黄色結晶（Ｆ２
０）
融点 ２９０〜２９５° （分解）
元素分析値 Ｃ，、Ｈ，、ＦＮ４０□Ｓ ＃ Ｈ２０理
論値 Ｃ，５５，０９； Ｈ、５，３９； Ｎ 、１４
．２８実験値 Ｃ，５５，０３； Ｈ、５，４２； Ｎ
、１４．０５光」ＩＱ」Ｌ呆−
この様にして製造される前記一般式（１）で示される新
規なインチアゾロキノリン誘導体、及びその薬理学的に
許容しろる酸付加塩は、グラム陽
性菌、
ダラム陰性菌に対して広い抗菌作用を存し、医薬として
極めて有用である。Example 2 9-cyclopropyl-7-(3,5-dimethyl 1-piperazinyl)-6-fluoroisothiazolo[5,4-b]
Quinoline-3,4(2H,9H)-dione hydrochloride Properties Colorless crystals (F20) Melting point 288-293@ (decomposition) Elemental analysis values C-9H2□FN402S・HCI・F2
0 Theoretical value C, 51, 52; H, 5, 4G; N, 12
．． 65 experimental value C, 51, G3; H, 5, 31; N
, 12.58 Example 3 9-7 clopropyl-6-fluoro-7-(1-homopiperazinyl)-inthiazolo[5,4-b coquinoline-
3,4(2H,9H)-dione Properties Pale yellow crystals (F2
0) Melting point 290-295° (decomposition) Elemental analysis value C,, H,, FN40□S # H20 theoretical value C, 55,09; H, 5,39; N, 14
．． 28 Experimental value C, 55,03; H, 5,42; N
, 14.05 Hikari'IQ'L - The novel inthiazoloquinoline derivative represented by the general formula (1) and its pharmacologically acceptable acid addition salt produced in this manner are Gram-positive. It has a wide range of antibacterial effects against bacteria and Durham-negative bacteria, making it extremely useful as a medicine.
Claims (1)
ルキル基を、Ｒ＿２及びＲ＿３は同一もしくは異なって
水素原子又は低級アルキル基を表わし、ｎは２又は３の
整数を表わす。ただし、Ｒ＿１がメチル基を表わす時、
Ｒ＿２及びＲ＿３は同時に水素原子を表わさない。） で示されるイソチアゾロキノリン誘導体及びその薬理学
的に許容しうる酸付加塩。[Claims] General formula ▲ Numerical formula, chemical formula, table, etc. , n represents an integer of 2 or 3. However, when R_1 represents a methyl group,
R_2 and R_3 do not represent hydrogen atoms at the same time. ) isothiazoquinoline derivatives and pharmacologically acceptable acid addition salts thereof.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63327761A JPH02174784A (en) | 1988-12-27 | 1988-12-27 | Isothiazoloquinoline derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP63327761A JPH02174784A (en) | 1988-12-27 | 1988-12-27 | Isothiazoloquinoline derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH02174784A true JPH02174784A (en) | 1990-07-06 |
Family
ID=18202694
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP63327761A Pending JPH02174784A (en) | 1988-12-27 | 1988-12-27 | Isothiazoloquinoline derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH02174784A (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7199128B2 (en) | 2005-02-02 | 2007-04-03 | Achillion Pharmaceuticals, Inc. | 8-N-substituted-2H-isothiazolo[5,4-b]quinolizine-3,4-diones and related compounds as antiinfective agents |
| US7659399B2 (en) | 2005-01-05 | 2010-02-09 | Achillion Pharmaceuticals, Inc. | 1-thia-2,4a-diaza-cyclopenta[b]napththalene-3,4-diones and related compounds as anti-infective agents |
| US8044204B2 (en) | 2005-07-27 | 2011-10-25 | Achillion Pharmaceuticals, Inc. | 8-methoxy-9H-isothiazolo[5,4-b]quinoline-3,4-diones and related compounds as anti-infective agents |
| US8114888B2 (en) | 2005-02-16 | 2012-02-14 | Achillion Pharmaceuticals, Inc. | Isothiazoloquinolones and related compounds as anti-infective agents |
| US8173636B2 (en) | 2009-04-03 | 2012-05-08 | Achillion Pharmaceuticals, Inc. | Hydroxylthienoquinolones and related compounds as anti-infective agents |
-
1988
- 1988-12-27 JP JP63327761A patent/JPH02174784A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7659399B2 (en) | 2005-01-05 | 2010-02-09 | Achillion Pharmaceuticals, Inc. | 1-thia-2,4a-diaza-cyclopenta[b]napththalene-3,4-diones and related compounds as anti-infective agents |
| US7199128B2 (en) | 2005-02-02 | 2007-04-03 | Achillion Pharmaceuticals, Inc. | 8-N-substituted-2H-isothiazolo[5,4-b]quinolizine-3,4-diones and related compounds as antiinfective agents |
| US8114888B2 (en) | 2005-02-16 | 2012-02-14 | Achillion Pharmaceuticals, Inc. | Isothiazoloquinolones and related compounds as anti-infective agents |
| US8044204B2 (en) | 2005-07-27 | 2011-10-25 | Achillion Pharmaceuticals, Inc. | 8-methoxy-9H-isothiazolo[5,4-b]quinoline-3,4-diones and related compounds as anti-infective agents |
| US8946422B2 (en) | 2005-07-27 | 2015-02-03 | Achillion Pharmaceuticals, Inc. | 8-methoxy-9H-isothiazolo[5,4-B]quinoline-3,4-diones and related compounds as anti-infective agents |
| US8173636B2 (en) | 2009-04-03 | 2012-05-08 | Achillion Pharmaceuticals, Inc. | Hydroxylthienoquinolones and related compounds as anti-infective agents |
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