JPS63196579A - Quinoline-3-carboxylic acid derivative - Google Patents
Quinoline-3-carboxylic acid derivativeInfo
- Publication number
- JPS63196579A JPS63196579A JP2631087A JP2631087A JPS63196579A JP S63196579 A JPS63196579 A JP S63196579A JP 2631087 A JP2631087 A JP 2631087A JP 2631087 A JP2631087 A JP 2631087A JP S63196579 A JPS63196579 A JP S63196579A
- Authority
- JP
- Japan
- Prior art keywords
- carboxylic acid
- formula
- acid derivative
- quinoline
- 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
- DJXNJVFEFSWHLY-UHFFFAOYSA-N quinoline-3-carboxylic acid Chemical class C1=CC=CC2=CC(C(=O)O)=CN=C21 DJXNJVFEFSWHLY-UHFFFAOYSA-N 0.000 title claims abstract description 7
- 150000003839 salts Chemical class 0.000 claims abstract description 12
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 9
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 2
- 230000000144 pharmacologic effect Effects 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 11
- 239000002904 solvent Substances 0.000 abstract description 9
- 241000894006 Bacteria Species 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 3
- 125000005843 halogen group Chemical group 0.000 abstract description 3
- 150000004050 homopiperazines Chemical class 0.000 abstract description 2
- 238000002360 preparation method Methods 0.000 abstract description 2
- 230000000845 anti-microbial effect Effects 0.000 abstract 1
- 230000001747 exhibiting effect Effects 0.000 abstract 1
- 229910052736 halogen Inorganic materials 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 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
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 238000000034 method Methods 0.000 description 6
- 239000003242 anti bacterial agent Substances 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- NBBJYMSMWIIQGU-UHFFFAOYSA-N Propionic aldehyde Chemical compound CCC=O NBBJYMSMWIIQGU-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- -1 Alternatively Chemical compound 0.000 description 3
- 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
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-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
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-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
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- ZTQSAGDEMFDKMZ-UHFFFAOYSA-N butyric aldehyde Natural products CCCC=O ZTQSAGDEMFDKMZ-UHFFFAOYSA-N 0.000 description 2
- 150000001728 carbonyl compounds Chemical class 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000002329 infrared spectrum Methods 0.000 description 2
- PHTQWCKDNZKARW-UHFFFAOYSA-N isoamylol Chemical compound CC(C)CCO PHTQWCKDNZKARW-UHFFFAOYSA-N 0.000 description 2
- 238000001819 mass spectrum Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 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
- 150000007530 organic bases Chemical class 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000001228 spectrum Methods 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
- YFNKIDBQEZZDLK-UHFFFAOYSA-N triglyme Chemical compound COCCOCCOCCOC YFNKIDBQEZZDLK-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 description 1
- FXHRAKUEZPSMLJ-UHFFFAOYSA-N 1-methyl-1,4-diazepane Chemical compound CN1CCCNCC1 FXHRAKUEZPSMLJ-UHFFFAOYSA-N 0.000 description 1
- BSKHPKMHTQYZBB-UHFFFAOYSA-N 2-methylpyridine Chemical compound CC1=CC=CC=N1 BSKHPKMHTQYZBB-UHFFFAOYSA-N 0.000 description 1
- JSGVZVOGOQILFM-UHFFFAOYSA-N 3-methoxy-1-butanol Chemical compound COC(C)CCO JSGVZVOGOQILFM-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
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 239000005973 Carvone Substances 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
- 101100136092 Drosophila melanogaster peng gene Proteins 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-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
- 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
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-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
- 150000001298 alcohols Chemical class 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 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
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 description 1
- 239000004020 conductor Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- HPYNZHMRTTWQTB-UHFFFAOYSA-N dimethylpyridine Natural products CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 239000008098 formaldehyde solution Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 229910000042 hydrogen bromide Inorganic materials 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
- 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
- 229910001389 inorganic alkali salt Inorganic materials 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000002386 leaching Methods 0.000 description 1
- 239000011133 lead Substances 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
- 230000010534 mechanism of action Effects 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 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
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- LOAUVZALPPNFOQ-UHFFFAOYSA-N quinaldic acid Chemical group C1=CC=CC2=NC(C(=O)O)=CC=C21 LOAUVZALPPNFOQ-UHFFFAOYSA-N 0.000 description 1
- 229910052709 silver Inorganic materials 0.000 description 1
- 239000004332 silver Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000007858 starting material 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
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 208000019206 urinary tract infection Diseases 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Landscapes
- Plural Heterocyclic Compounds (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有し医薬品として有用な新規
なキノリン−３−カルボン酸誘導体、及びその薬理学的
に許容しうる塩に関するものである。DETAILED DESCRIPTION OF THE INVENTION Part 1 The present invention relates to a novel quinoline-3-carboxylic acid derivative that has excellent antibacterial activity and is useful as a pharmaceutical, and a pharmacologically acceptable salt thereof.
ｌ１ＡａＵ【
キノリンカルボン酸骨格を有する抗菌剤はノルフロキサ
シンをはじめとして数多く知られているが、本発明に係
るキノリン−３−カルボン酸誘導体は全く知られていな
い。l1AaU [ Many antibacterial agents having a quinoline carboxylic acid skeleton are known, including norfloxacin, but the quinoline-3-carboxylic acid derivative according to the present invention is completely unknown.
」 く、ｌ ″ 。” く、l ″
合成抗菌剤は、国内外で活発に研究されており、その成
果は臨床の場に対して画期的な進歩をもたらし、適応症
は***症にとどまらずあらゆる感染症に仔効である
ことが示されている。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。しかしながら合成抗菌剤が完成された
薬物であるとは言い難く、その有用性から新しい抗菌剤
の登場が強く望まれている。Synthetic antibacterial agents are being actively researched both domestically and internationally, and the results have brought ground-breaking progress to the clinical field, and are effective against all kinds of infections, not just urinary tract infections. It has been shown that It is also known that its mechanism of action is the inhibition of DNA gyrase, which is a DNA steric enzyme, and that transmission of resistance by plasmids such as antibiotics does not occur. However, it is difficult to say that synthetic antibacterial agents are perfect drugs, and the emergence of new antibacterial agents is strongly desired due to their usefulness.
ｍの
本発明者らは、前述の事情を鑑み鋭意研究した結果、キ
・ノリソー３−カルボン酸誘導体、及びその薬理学的に
許容しうる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 circumstances, the present inventors of m. completed.
ト
（式中、Ｒは水素原子又は低級アルキル基を表わす。）
で示されるキノリン−３−カルボン酸誘導体、及びその
薬理学的に許容しつる塩に関するものである。The present invention relates to a quinoline-3-carboxylic acid derivative represented by the following formula (wherein R represents a hydrogen atom or a lower alkyl group) and a pharmacologically acceptable salt thereof.
本発明の前記一般式（Ｉ）中、Ｒで示される低級アルキ
ル基としては、たとえば、メチル、エチル、ｎ−プロピ
ル、イソプロピル、ｎ−ブチル、 ５ｅｃ−ブチル、
ｔｅｒｔ−ブチル基等が挙げられる。In the general formula (I) of the present invention, examples of the lower alkyl group represented by R include methyl, ethyl, n-propyl, isopropyl, n-butyl, 5ec-butyl,
Examples include tert-butyl group.
本発明の前記一般式（Ｉ）で示へれる化合物の薬理学的
に許容しうる塩としては、酸付加塩又はアルカリ付加塩
が挙げられ、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、フマール酸、クエン酸、
シュウ酸、酒石酸等の有機酸塩が、アルカリ付加塩とし
ては、たとえば、ナトリウム、カリウム、カルシウム。Examples of the pharmacologically acceptable salts of the compound represented by the general formula (I) of the present invention include acid addition salts and alkali addition salts; examples of the acid addition salts include hydrochloric acid, hydrogen bromide, acids, mineral acid salts such as hydroiodic acid, nitric acid, sulfuric acid, phosphoric acid,
Alternatively, acetic acid, maleic acid, fumaric acid, citric acid,
Organic acid salts such as oxalic acid and tartaric acid are used as alkali addition salts such as sodium, potassium, and calcium.
銀、亜鉛、鉛、アンモニウム等の無機アルカリ塩、ある
いはエタノールアミン、Ｎ、Ｎ−ジアルキルエタノール
アミン等の有機塩基の塩等が挙げられる。Examples include inorganic alkali salts such as silver, zinc, lead, and ammonium, and salts of organic bases such as ethanolamine and N,N-dialkylethanolamine.
本発明の前記一般式（Ｉ）で示される新規なキノリン−
３−カルボン酸現導体は、種々の方法により製造するこ
とができる。A novel quinoline represented by the general formula (I) of the present invention
The 3-carboxylic acid current conductor 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ＣＩ）で示される化合物は、（式中、Ｘはハ
ロゲン原子を表わす。）で示される７−ハロゲノキノリ
ン−３−カルボン酸誘導体と、次の一般式（ＩＩＩ）
（式中、Ｒは前述と同意義を表わす。）で示されるホモ
ピペラジン誘導体とを、無溶媒下あるいは溶媒下におい
て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 CI) includes a 7-halogenoquinoline-3-carboxylic acid derivative represented by (wherein, X represents a halogen atom) and the following general formula (III) (wherein, R has the same meaning as above.) It can be produced by reacting the homopiperazine derivatives shown in (1) in the absence of a solvent or in the presence of a solvent.
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、水、
メタノール、エタノール、ｎ−プロパツール、ｎ−ブタ
ノール、３−メトキシブタノール。Any solvent may be used in the method of the present invention as long as it does not inhibit the reaction, such as water,
Methanol, ethanol, n-propanol, n-butanol, 3-methoxybutanol.
イソアミルアルコール等のアルコール類、エチレングリ
コールジメチルエーテル（モノグライム）。Alcohols such as isoamyl alcohol, ethylene glycol dimethyl ether (monoglyme).
ジエチレングリコールジメチルエーテル（ジグラ“イム
）、トリエチレングリコールジメチルエーテル（トリグ
ライム）等のエーテル類、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
サメチルフォスホリフクトリアミド等の非プロトン性極
性溶媒、ベンゼン。Ethers such as diethylene glycol dimethyl ether (ziglyme), triethylene glycol dimethyl ether (triglyme), dimethylformamide, N-
Aprotic polar solvents such as methyl-2-pyrrolidone, dimethyl sulfoxide, hexamethylphosphorifuctriamide, benzene.
トルエン等の芳香族炭化水素系溶媒、あるいは、ピリジ
ン、ピコリン、ルチジン、コリジン、トリエチルアミン
等の有機塩基が挙げられる。Examples include aromatic hydrocarbon solvents such as toluene, and organic bases such as pyridine, picoline, lutidine, collidine, and triethylamine.
又、反応は室温から２００＠の範囲で行われる。Further, the reaction is carried out at a temperature ranging from room temperature to 200°C.
本発明の製造方法において出発原料となった前記一般式
（ＩＩ）で示される７−ハロゲノキノリン−３−カルボ
ン酸誘導体は、たとえば、特開昭６０−１８３８８６号
に既に開示されている公知の物質である。The 7-halogenoquinoline-3-carboxylic acid derivative represented by the general formula (II) that is the starting material in the production method of the present invention is, for example, a known substance already disclosed in JP-A-60-183886. It is.
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（Ｉ）で示される化合物のうちＲが低級アル
キル基である化合物は、前記一般で示される７−ホモビ
ペラジノキノリンー３−カルボン酸誘導体と次の一般式
（Ｖ）
、 Ｒ１−ｙ （Ｖ ）（式
中、Ｒ１は低１級アルキル基を、Ｙはハロゲン原子を表
わす。）
で示されるハロゲン化アルキルとを、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ることによ
り製造することができる。According to the second mode of the method for producing a compound according to the present invention,
Among the compounds represented by the above general formula (I), the compound in which R is a lower alkyl group is a compound represented by the above general 7-homobiperazinoquinoline-3-carboxylic acid derivative and the following general formula (V), R1- A halogenated alkyl represented by y (V) (wherein R1 represents a lower primary alkyl group and Y represents a halogen atom) in a solvent in the presence or absence of a base as a deoxidizing agent. It can be produced by reacting with
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
トン、エタノール、エーテル、テトラヒドロフラン、ジ
メチルホルムアミド、ジオキサン、ベンゼン、トルエン
、クロロホルム等カ挙げられる。Any solvent may be used in the method of the present invention as long as it does not inhibit the reaction, and examples thereof include acetone, ethanol, ether, tetrahydrofuran, dimethylformamide, dioxane, benzene, toluene, and chloroform.
本発明の方法において使用される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。Examples of the base used as a deoxidizing agent in the method of the present invention include triethylamine.
ピリジン、炭酸カリウム等が挙げられる。Examples include pyridine and potassium carbonate.
又、反応は室温から使用される溶媒の加熱還流温度下に
おいて行われる。Further, the reaction is carried out at a temperature ranging from room temperature to the reflux temperature of the solvent used.
本発明に係る化合物の製造方法の第三の様式によれば、
前記一般式（Ｉ）で示される化合物のうちＲが低級アル
キル基である化合物は、前記一般式（ＩＶ）で示される
７−ホモビペラジノキノリンー３−カルボン酸誘導体と
、次の一般式（Ｖｌ）Ｒ２−仁−Ｈ（Ｖｌ）
（式中、Ｒ２は水素原子又は低級アルキル基を表わす。According to the third mode of the method for producing a compound according to the present invention,
Among the compounds represented by the general formula (I), the compound in which R is a lower alkyl group is a 7-homobiperazinoquinoline-3-carboxylic acid derivative represented by the general formula (IV) and the following general formula ( Vl) R2-H (Vl) (wherein, R2 represents a hydrogen atom or a lower alkyl group.
）
で示されるカルボニル化合物とを、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。) can be produced by reacting the carbonyl compound shown in the following in the presence of formic acid.
本発明の方法において使用される前記一般式（Ｖｌ）で
示されるカルボニル化合物としては、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。Examples of the carbonyl compound represented by the general formula (Vl) used in the method of the present invention include formaldehyde, acetaldehyde, propionaldehyde, etc. Formaldehyde is preferably used as an aqueous formaldehyde solution (formalin), and acetaldehyde When using propionaldehyde, it is preferable to use nitrobenzene as a solvent.
又、反応は１００〜２００°の範囲で行われる。Moreover, the reaction is carried out in the range of 100 to 200°.
支敷肚
以下、本発明を実施例によって説明するが、本発明はこ
の実施例の特定の細部に限定されるものではない。In the following, the present invention will be explained by way of examples, but the present invention is not limited to the specific details of these examples.
実施例１
６．８−ジフルオロ−１−（２，４−ジフルオロフェニ
ル）−７−（１−ホモピペラジニル）−１，４−ジヒド
ロ−４−オキソキノリン−３−カルボン酸
１−（２，４−ジフルオロフェニル）−８，７゜８−ト
リフルオロ−１，４−ジヒドロ−４−オキソキノリン−
３−カルボン酸０−０−５Ｏホモピペラジン０．４３ｇ
及びエタノール１０１の混合物を２０時間加熱還流する
。冷浸析出結晶をろ取し、得られた結晶を水及び１０％
水酸化ナトリウム水溶液に溶解する。水溶液をろ過後１
０％塩酸にてｐＨ８とする。析出結晶をろ取し、融点２
４８〜２５４” （分解）の微黄色粉末品０．１９ｇ
を得る。Example 1 6.8-difluoro-1-(2,4-difluorophenyl)-7-(1-homopiperazinyl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid 1-(2,4- difluorophenyl)-8,7゜8-trifluoro-1,4-dihydro-4-oxoquinoline-
3-carboxylic acid 0-0-5O homopiperazine 0.43g
A mixture of 101 and ethanol is heated under reflux for 20 hours. The cold leaching precipitated crystals were collected by filtration, and the obtained crystals were mixed with water and 10%
Dissolve in aqueous sodium hydroxide solution. After filtering the aqueous solution 1
Adjust the pH to 8 with 0% hydrochloric acid. The precipitated crystals were collected by filtration, and the melting point was 2.
48-254” (decomposed) slightly yellow powder product 0.19g
get.
マススペクトル 園／ｚ ： ４３５ （Ｍ ）ＩＲス
ペクトル ｖ （ＫＢｒ） Ｃｍ 、 ｌＧ２４Ｎ
ＭＲスペクトル δ （ＤＭＳＯ−ｄ６） ｐｐＨ’１
、ＧＯ−１，９２（２Ｈ，ｓ）、２．７７−２．９６（
４Ｈ，ｍ）、３．３０−３．４９（４Ｈ，ｍ）、フ、ｔ
ｓ−ｓ、ｏ７（４■、■）、８．６０（１１１，Ｓ）実
施例２
６．８−ジフルオロ−１−（２，４−ジフルオロフェニ
ル）−７−（４−メチル−１−ホモピペラジニル）−１
，４−ジヒドロ−４−オキソキノリン−３−カルボン酸
・塩酸塩
１−（２，４−ジフルオロフェニル）−８，７゜８−ト
リフルオロ−１，４−ジヒドロ−４−オキソキノリン−
３−カルボンＭ０．８０ｇ、Ｎ−メチルホモピペラジン
０．７７ｇ及びエタノール１６１の混合物を２０時間加
熱還流する。冷浸エタノールを留去し、水及び１０％水
酸化ナトリウム水溶液に溶解する。水溶液をろ過後１０
％塩酸にてｐＨＥＩとする。析出結晶をろ取し、メタノ
ールより再結晶すると融点２４９〜２６０° （分解）
の淡黄色粉末品０．１８ｇを得る。Mass spectrum Sono/z: 435 (M) IR spectrum v (KBr) Cm, lG24N
MR spectrum δ (DMSO-d6) ppH'1
, GO-1,92(2H,s), 2.77-2.96(
4H, m), 3.30-3.49 (4H, m), F, t
s-s, o7 (4■, ■), 8.60 (111,S) Example 2 6.8-difluoro-1-(2,4-difluorophenyl)-7-(4-methyl-1-homopiperazinyl )-1
,4-dihydro-4-oxoquinoline-3-carboxylic acid hydrochloride 1-(2,4-difluorophenyl)-8,7°8-trifluoro-1,4-dihydro-4-oxoquinoline-
A mixture of 0.80 g of 3-carvone M, 0.77 g of N-methylhomopiperazine, and 161 g of ethanol is heated under reflux for 20 hours. The cold soaked ethanol is distilled off and dissolved in water and 10% aqueous sodium hydroxide solution. After filtering the aqueous solution 10
Adjust to pHEI with % hydrochloric acid. When the precipitated crystals are filtered and recrystallized from methanol, the melting point is 249-260° (decomposition).
0.18 g of pale yellow powder was obtained.
マススペクトル ■／ｚ ： ４４９ （Ｍ”）ＩＲス
ペクトル ｖ （ＫＢｒ） ａｍ 、１７３０．ｌ
Ｉｌｉ２２ＮＭＲスペクトル δ （ＤＭＳＯ−ｄ６）
Ｐｐ■：１．８Ｇ−２，２８（２ｔｌ、ｍ）、２．６
８（３旺、ｓ）、３．ＩＴ−３，７８（８Ｌｉｌ）、７
．１９−８．１９（４１１，鵬）、８Ｊ４（ＩＨ，ｓ）
元素分析値 Ｃ２２Ｈ工９ Ｆ４Ｎ３０３・ＨＣｌ −
１／４Ｈ２０理論値 Ｃ，５３，８９； Ｈ，４，２１
； Ｎ、 ８．５７実験値 Ｃ，５３，５７； Ｈ，４
，１０； Ｎ、 ８．１５主朋１１Ｕ先
この様にして製造される前記一般式（Ｉ）で示される新
規なキノリン−３−カルボン酸誘導体、及びその薬理学
的に許容しうる塩は、ダラム陽性菌、ダラム陰性菌に対
し広い抗菌作用を有し、医薬として極めて有用である。Mass spectrum ■/z: 449 (M”) IR spectrum v (KBr) am, 1730.l
Ili22NMR spectrum δ (DMSO-d6)
Pp ■: 1.8G-2,28 (2tl, m), 2.6
8 (3-o, s), 3. IT-3, 78 (8Lil), 7
．． 19-8.19 (411, Peng), 8J4 (IH, s)
Elemental analysis value C22H engineering 9 F4N303・HCl −
1/4H20 theoretical value C, 53,89; H, 4,21
; N, 8.57 experimental value C, 53,57; H, 4
,10; It has a wide range of antibacterial effects against Durham-positive bacteria and Durham-negative bacteria, and is extremely useful as a medicine.
この様にして製造される前記一般式（Ｉ）で示される新
規なキノリン−３−カルボン酸誘導体、及びその薬理学
的に許容しろる塩は、常法により、錠剤、散剤、カプセ
ル剤、注射剤９点眼剤９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。投与量は治療すべき症杖及び投与方法によ
り左右されるが成人に経口投与する場合で、通常１回５
０〜１６００ｍｇである。The novel quinoline-3-carboxylic acid derivative represented by the general formula (I) and its pharmacologically acceptable salts produced in this way can be prepared into tablets, powders, capsules, injections, etc. by conventional methods. It can be made into formulations such as eye drops, nasal drops, or external preparations, and is clinically administered by oral or parenteral administration. The dosage depends on the disease to be treated and the method of administration, but when administered orally to adults, it is usually 5 times a day.
It is 0-1600 mg.
Claims (1)
薬理学的に許容しうる塩。[Claims] A quinoline-3-carboxylic acid derivative represented by the general formula ▲ Numerical formula, chemical formula, table, etc. ▼ (In the formula, R represents a hydrogen atom or a lower alkyl group), and its pharmacological Tolerable salt.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2631087A JPS63196579A (en) | 1987-02-09 | 1987-02-09 | Quinoline-3-carboxylic acid derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2631087A JPS63196579A (en) | 1987-02-09 | 1987-02-09 | Quinoline-3-carboxylic acid derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPS63196579A true JPS63196579A (en) | 1988-08-15 |
Family
ID=12189800
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2631087A Pending JPS63196579A (en) | 1987-02-09 | 1987-02-09 | Quinoline-3-carboxylic acid derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS63196579A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008045673A3 (en) * | 2006-10-06 | 2008-05-29 | Bausch & Lomb | Quinolone carboxylic acids, derivatives thereof, processes for its preparation and its use as antibacterial agents |
| WO2008091752A3 (en) * | 2007-01-24 | 2008-10-16 | Bausch & Lomb | Quinolone carboxylic acids, derivatives thereof, processes for their preparation and their use as antibacterial agents |
| US8252783B2 (en) | 2007-01-24 | 2012-08-28 | Bausch & Lomb Incorporated | Quinolone carboxylic acids, derivatives thereof, and methods of making and using same |
-
1987
- 1987-02-09 JP JP2631087A patent/JPS63196579A/en active Pending
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008045673A3 (en) * | 2006-10-06 | 2008-05-29 | Bausch & Lomb | Quinolone carboxylic acids, derivatives thereof, processes for its preparation and its use as antibacterial agents |
| JP2010505861A (en) * | 2006-10-06 | 2010-02-25 | ボーシュ アンド ローム インコーポレイティド | Quinolone carboxylic acid, its derivatives, and methods for producing and using them |
| US8227597B2 (en) | 2006-10-06 | 2012-07-24 | Bausch & Lomb Incorporated | Quinolone carboxylic acids, derivatives thereof, and methods of making and using same |
| TWI383978B (en) * | 2006-10-06 | 2013-02-01 | Bausch & Lomb | Quinolone carboxylic acids, derivatives thereof, and methods of making and using same |
| WO2008091752A3 (en) * | 2007-01-24 | 2008-10-16 | Bausch & Lomb | Quinolone carboxylic acids, derivatives thereof, processes for their preparation and their use as antibacterial agents |
| US7632944B2 (en) | 2007-01-24 | 2009-12-15 | Bausch & Lomb Incorporated | Quinolone carboxylic acids, derivatives thereof, and methods of making and using same |
| US8252783B2 (en) | 2007-01-24 | 2012-08-28 | Bausch & Lomb Incorporated | Quinolone carboxylic acids, derivatives thereof, and methods of making and using same |
| AU2008209416B2 (en) * | 2007-01-24 | 2013-05-09 | Bausch & Lomb Incorporated | Quinolone carboxylic acids, derivatives thereof, processes for their preparation and their use as antibacterial agents |
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