KR900001547B1 - 벤조퀴놀리진 카르복실산 유도체의 제조방법 - Google Patents
벤조퀴놀리진 카르복실산 유도체의 제조방법 Download PDFInfo
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- KR900001547B1 KR900001547B1 KR1019840000865A KR840000865A KR900001547B1 KR 900001547 B1 KR900001547 B1 KR 900001547B1 KR 1019840000865 A KR1019840000865 A KR 1019840000865A KR 840000865 A KR840000865 A KR 840000865A KR 900001547 B1 KR900001547 B1 KR 900001547B1
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- carboxylic acid
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- piperazinyl
- preparing
- acid derivative
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- 238000004519 manufacturing process Methods 0.000 title claims 2
- SWWBKIRNVOWLRS-UHFFFAOYSA-N 4h-benzo[a]quinolizine-1-carboxylic acid Chemical class C1=CC=C2C3=C(C(=O)O)C=CCN3C=CC2=C1 SWWBKIRNVOWLRS-UHFFFAOYSA-N 0.000 title description 2
- 239000002253 acid Substances 0.000 claims description 8
- 150000003839 salts Chemical class 0.000 claims description 5
- YCWRFIYBUQBHJI-UHFFFAOYSA-N 2-(4-aminophenyl)acetonitrile Chemical group NC1=CC=C(CC#N)C=C1 YCWRFIYBUQBHJI-UHFFFAOYSA-N 0.000 claims description 2
- ZSMCRJGGFUPQRE-UHFFFAOYSA-N 2-methyl-4-oxo-1-azatricyclo[7.3.1.05,13]trideca-2,5,7,9(13),10-pentaene-3-carboxylic acid Chemical compound C1=CCN2C(C)=C(C(O)=O)C(=O)C3=CC=CC1=C32 ZSMCRJGGFUPQRE-UHFFFAOYSA-N 0.000 claims 1
- JPKYTPDTKVYDNM-UHFFFAOYSA-N [N+](=O)([O-])C1=CC=C(CN2CCN(CC2)C2=C(C=C3C(C=CN4C(CCC2=C34)C)=O)F)C=C1 Chemical compound [N+](=O)([O-])C1=CC=C(CN2CCN(CC2)C2=C(C=C3C(C=CN4C(CCC2=C34)C)=O)F)C=C1 JPKYTPDTKVYDNM-UHFFFAOYSA-N 0.000 claims 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
- 150000001875 compounds Chemical class 0.000 description 9
- 241001148470 aerobic bacillus Species 0.000 description 8
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 230000000844 anti-bacterial effect Effects 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 4
- 239000003242 anti bacterial agent Substances 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- -1 p-nitrobenzyl halide Chemical class 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- 241001148471 unidentified anaerobic bacterium Species 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 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 3
- 229960001180 norfloxacin Drugs 0.000 description 3
- 229910052763 palladium Inorganic materials 0.000 description 3
- 230000003389 potentiating effect Effects 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 238000006722 reduction reaction Methods 0.000 description 3
- 238000001228 spectrum Methods 0.000 description 3
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 2
- CWYNVVGOOAEACU-UHFFFAOYSA-N Fe2+ Chemical compound [Fe+2] CWYNVVGOOAEACU-UHFFFAOYSA-N 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 238000010531 catalytic reduction reaction Methods 0.000 description 2
- 239000013078 crystal Substances 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000000921 elemental analysis Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 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 2
- 229960000210 nalidixic acid Drugs 0.000 description 2
- 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- VOLRSQPSJGXRNJ-UHFFFAOYSA-N 4-nitrobenzyl bromide Chemical compound [O-][N+](=O)C1=CC=C(CBr)C=C1 VOLRSQPSJGXRNJ-UHFFFAOYSA-N 0.000 description 1
- IAKNLKLKKBPMHN-UHFFFAOYSA-N 4h-quinolizine-2-carboxylic acid Chemical compound C1=CC=CC2=CC(C(=O)O)=CCN21 IAKNLKLKKBPMHN-UHFFFAOYSA-N 0.000 description 1
- AQBHJEQDRFIAFI-UHFFFAOYSA-N 7-fluoro-12-methyl-4-oxo-8-piperazin-1-yl-1-azatricyclo[7.3.1.05,13]trideca-2,5,7,9(13)-tetraene-3-carboxylic acid Chemical class FC1=CC(C(C(C(O)=O)=C2)=O)=C3N2C(C)CCC3=C1N1CCNCC1 AQBHJEQDRFIAFI-UHFFFAOYSA-N 0.000 description 1
- GPQKXWVKDHIOCH-UHFFFAOYSA-N 8-[4-[(4-aminophenyl)methyl]piperazin-1-yl]-7-fluoro-12-methyl-4-oxo-1-azatricyclo[7.3.1.05,13]trideca-2,5,7,9(13)-tetraene-3-carboxylic acid Chemical compound FC1=CC(C(C(C(O)=O)=C2)=O)=C3N2C(C)CCC3=C1N(CC1)CCN1CC1=CC=C(N)C=C1 GPQKXWVKDHIOCH-UHFFFAOYSA-N 0.000 description 1
- 241000251468 Actinopterygii Species 0.000 description 1
- 229910000761 Aluminium amalgam Inorganic materials 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 238000002814 agar dilution Methods 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000004440 column chromatography Methods 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
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 229910001448 ferrous ion Inorganic materials 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000012264 purified product Substances 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 229910052718 tin Inorganic materials 0.000 description 1
- 239000011135 tin Substances 0.000 description 1
- 229910001432 tin ion Inorganic materials 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D455/00—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
- C07D455/03—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing quinolizine ring systems directly condensed with at least one six-membered carbocyclic ring, e.g. protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine
- C07D455/04—Heterocyclic compounds containing quinolizine ring systems, e.g. emetine alkaloids, protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing quinolizine ring systems directly condensed with at least one six-membered carbocyclic ring, e.g. protoberberine; Alkylenedioxy derivatives of dibenzo [a, g] quinolizines, e.g. berberine containing a quinolizine ring system condensed with only one six-membered carbocyclic ring, e.g. julolidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
내용 없음.
Description
본 발명은 신규하고 유용한 벤조퀴놀리진 카르복실산 유도체, 상기 화합물의 항박테리아제로서의 용도 및 제조방법에 관한 것이다.
1962년 레서 등에 의해 개발된 날리디시 산(Nalidixic acid)은 그림-음성의 호기성 박테리아에 대해서 강력한 활성을 갖는 항박테리아제로 널리 공지되어 있다. 날리디산과 관련된, 많은 새로운 퀴놀린 화합물은 최근 수년동안 개발되기 시작하였다. 그리고 상기 유도체들 가운데 하나로 개발된 노르플록사신(norfloxacin)은 그람-음성뿐 아니라 그람-양성의 호기성 박테리아에 대해서도 우수한 활성을 갖는다.
본 발명자들은 호기성 박테리아 뿐만 아니라 편성 혐기성 박테리아에 대해서도 강력한 항박테리아 활성을 갖는 화합물을 개발하기 위해 광범위한 연구를 수행한 결과, 날리디시산 및 노르플록사신과 같은 종래의 화합물에 비해 호기성 박테랑 및 편성 혐기성 박테리아에 대해 보다 넓은 항박테리아 스펙트럼 및 더 큰 효능을 갖는 새로운 화합물을 발견하게 되었다.
즉, 본 발명에 따른 신규의 화합물은 하기 화학식(Ⅰ)의 8-[4-(4-아미노벤질)-1-피페라지닐]-9-플루오로-6,7-디히드로-5-메틸-1-옥소-1H,5H-벤조[ij]퀴놀리진-2-카르복실산(이하 화학식(Ⅰ)로 약칭한다), 그 수화물 및 그의 산 부가염이다 :
본 발명의 화학식(Ⅰ)은 그람-음성 및 그람-양성 호기성 박테리아와 그람-음성 및 그람-양성 편성 혐기성 박테리아에 대해 매우 넓은 항박테리아 활성 스펙트럼을 나타낸다. 따라서, 화학식(Ⅰ)은 항박테리아제로서 실제적으로 유효할 뿐만 아니라 사람의 질병에 대한 치료제로서 또한 물고기 및 동물에 대한 치료약과 농업용 화학 약품용의 신규의 의약에 사용할 수 있다. 본 발명의 화합물은 8-[4-(4-니트로벤질)-1-피페라지닐]-9-플루오로-6,7-디히드로-5-메틸-1-옥소-1H,5H-벤조[ij] 퀴놀리진-2-카르복실산 (이하 화학식 Ⅱ로 약칭한다)의 환원반응 (예컨대, 팔라듐, 니켈 및 플라티늄과 같은 촉매의 존재하에서 수소에 의한 촉매성 환원반응이나, 아연, 주석, 철 및 알루미늄 아말감과 같은 금속에 의한 환원반응이나, 염형태로 존재하는 제1주석 이온, 제1철 이온과 같은 금속 이온에 의한 환원반응)에 의해 제조되는데, 이중 실온 및 상압하에서, 아세트산내에서 차콜상의 팔라듐 존재하에서의 수소에 의한 촉매성 환원반응에 의해 제조되는 것이 바람직하다.
또한, 출발물질인 화학식(Ⅱ)도 또한 신규의 화합물로서 하기의 방법에 의해 제조된다. 즉, 화학식(Ⅱ)는 9-플로오로-6, 7-디히드로-5-메틸-1-옥소-8-( 1-피페라지닐)-1H, 5H-벤조[ij] 퀴놀리진 -2-카르복실산(이하 화학식(Ⅲ)으로 약칭한다)이나 그의 산 부가염을 p-니트로벤질 할라이드(이하 화학식(Ⅳ)로 약칭한다. 바람직하기로는 브로마이드, 클로라이드이다)와 적합한 용매(예 : N, N-디메틸포름아미드), 실온 내지 사용된 용매의 비점까지의 온도 범위에서, 바람직하게는 산수용체(예 : 트리에틸아민)의 존재하에서 반응시킴으로써 제조된다.
하기의 바람직한 구체예를 들어 본 발명에 대해 보다 상세히 설명한다.
[실시예 1]
8-[4-(4-피페라지닐)-1-피페라지닐]-9 플루오로-6, 7-디히드로-5-메틸 -1-옥소-1H, 5H-벤조[ij]퀴놀리진-2-카르복실산(화합물 Ⅱ)의 제조.
N,N-디메틸포름아미드(50㎖)내의 9-플루오로-6,7-디히드로-5-메틸-8-(1-피페라지닐)-1-옥소-1N,5N-벤조[ij]퀴놀리진-2-카르복실산(화합물 Ⅲ), 히드로클로라이드(1.1g), p-니트로벤질브로미이드(화학식(Ⅳ)(1.87g) 및 트리에틸아민(1.46g)의 혼합물을 80∼90℃의 온도에서 10시간 동안 교반하면서 가열한다. 용매를 증발시킨후, 물을 잔류물에 부가하고 수용성 혼합물을 클로로포름으로 추출한다. 클로로포름 층을 무수 황산나트륨으로 탈수시키고, 건조할때까지 증발시킨다. 잔류물을 N, N-디메틸포름아미드와 에탄올의 혼합물(2 : 1)로 재결정화시켜 0.83g(수득율 : 60%)의 8-[ 4-(4-니트로벤질) -1-피페라지닐]-9-플루오로-6, 7-디히드로-5-메틸-1-옥소-1H, 5H-벤조[ij]퀴놀리진-2-카르복실산(화합물 Ⅱ)을 얻는다. (엷은 황색의 침상 결정체, 융점 = 230∼233℃ (분해).
원소분석 C25H25FN4O5
계산치 : C : 62, 49, H : 5. 24 N : 11, 66
설측치 : C : 62, 59, H : 5, 11, N : 11, 82
[실시예 2]
8-[4-(4-아미노벤질)-1-피페라지닐]-9-플루오로-6,7-디히드로-5-메틸-1-옥소-1H, 5H-벤조[ij]퀴놀리진-2-카르복실산(화학식 1)의 제조.
아세트산(25ml)과 차콜상의 10% 팔라듐(0.2g)이 혼합된 화학식 (2) (0.71g)을 실온 및 상압하에서 일정한 (계산된) 부피의 수소로 수소화시킨다. 이 일정한 부피를 갖는 수소가 완전히 포화된 후, 차콜상의 팔라듐을 여과하고 여액을 농축시켜 건조상태로 한다. 잔류물을 소량의 물에 용해시키고 10%의 수산화나트륨 용액으로 중화시킨다. 생성된 침전물을 수집하여 건조시키고 전개용매로 클로로포름과 에탄올의 혼합물(10 : 1)을 사용하여 실리카겔상의 컬럼 크로마토그래피로 정제한다. 정제된 생성물은 에탄올로 재결정화시켜 0.25g(수득율 : 37.1 %)의 8-[4-(4-아미노벤질)-1-피페라지닐]-9-플루오로-6, 7-디히드로 -5-메틸 -1-옥소-1H, 5H-벤조[ij]퀴놀리진-2-카르복실산(화합물 Ⅰ)을 얻는다. (엷은 황색의 침상 결정체, 융점 = 215. 5 ∼ 217.5℃(분해).
원소분석 C25H27FN4O3ㆍ1/3H2O
계산치 : C : 65, 77, H : 6. 11, N : 12, 27
설측치 : C : 65, 92, H : 5. 93, N 12. 21
[실험예 1]
본 발명의 화학식(Ⅰ)에 대한 항박테리아 활성은 호기성 박테리아 및 편성 혐기성 박테리아에 대한 표준 아가 희석액 스트리크 방법( standard agar dilution streak method)에 의해 분석한다(Chemotherapy Vol. 22, No. 6. pp. 1126 ∼ 1128(1974) : Vol. 27, No. 3, pp. 559 ∼ 560(1979), 결과는 하기 표 1과 2에 기재되어 있다.
[표 1]
[표 2]
상기 표 1 및 표 2로부터, 화학식(Ⅰ)의 활성은 그람-음성 및 그람-양성의 편성 혐기성 박테리아와 그람-양성 호기성 박테리아에 대한 날리디시 산과 노르플록사신의 활성 그리고 그람-양성의 호기성 박테리아에 대한 날리디시 산의 활성보다 크다는 것을 알 수 있다. 상기에 기재한 것처럼, 본 발명의 화합물은 양호기성 박테리아 및 편성 혐기성 박테리아에 대해 보다 넓은 강력한 항박테리아 스펙트럼을 나타내며, 특히
항박테리아제로서 보다 유효하다.
Claims (1)
- 8-[4-(4-니트로벤질)-1-피페라지닐]-9-플루오로-6, 7-디히드로-5-메틸-1-옥소-1H, 5H-벤조[ij]퀴놀리진-2-카르복실산이나 그의 산부가염을 환원시킴을 특징으로 하는, 8-[4-(4-아미노벤질)-1-피페라지닐]-9-플루오르-6, 7-디히드로-5-메틸-1-옥소-1H, 5H-벤조[ij]퀴놀리진 -2-카르복실산, 그의 수화물 및 그의 산부가염을 제조하는 방법.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP58028135A JPS59155381A (ja) | 1983-02-22 | 1983-02-22 | ベンゾキノリジンカルボン酸誘導体及びその製造法 |
| JP28135 | 1983-02-22 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| KR840007878A KR840007878A (ko) | 1984-12-11 |
| KR900001547B1 true KR900001547B1 (ko) | 1990-03-12 |
Family
ID=12240322
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1019840000865A Expired KR900001547B1 (ko) | 1983-02-22 | 1984-02-22 | 벤조퀴놀리진 카르복실산 유도체의 제조방법 |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US4599418A (ko) |
| JP (1) | JPS59155381A (ko) |
| KR (1) | KR900001547B1 (ko) |
| AU (2) | AU2457884A (ko) |
| CA (1) | CA1225091A (ko) |
| DE (1) | DE3406235C2 (ko) |
| ES (1) | ES8600274A1 (ko) |
| FR (1) | FR2541278B1 (ko) |
| GB (2) | GB8404223D0 (ko) |
| IT (1) | IT1173336B (ko) |
| SE (1) | SE459809B (ko) |
Families Citing this family (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4472405A (en) * | 1982-11-12 | 1984-09-18 | Riker Laboratories, Inc. | Antimicrobial 6,7-dihydro-5,8-dimethyl-9 fluoro-1-oxo-1H, 5H-benzo (ij) quinolizine-2-carboxylic acid and derivatives |
| JPH08775B2 (ja) * | 1986-05-22 | 1996-01-10 | 協和醗酵工業株式会社 | 魚類のパスツレラ属細菌性類結節症治療剤 |
| US7247642B2 (en) | 1999-05-07 | 2007-07-24 | Wockhardt Limited | Antibacterial optically pure benzoquinolizine carboxylic acids, processes, compositions and methods of treatment |
| US6750224B1 (en) | 1999-05-07 | 2004-06-15 | Wockhardt Limited | Antibacterial optically pure benzoquinolizine carboxylic acids, processes, compositions and methods of treatment |
| US6514986B2 (en) | 2000-11-22 | 2003-02-04 | Wockhardt Limited | Chiral fluoroquinolone arginine salt forms |
| US6608078B2 (en) | 2000-05-08 | 2003-08-19 | Wockhardt Limited | Antibacterial chiral 8-(substituted piperidino)-benzo [i,j] quinolizines, processes, compositions and methods of treatment |
| US7098219B2 (en) | 2000-08-01 | 2006-08-29 | Wockhart Limited | Inhibitors of cellular efflux pumps of microbes |
| US6878713B2 (en) | 2001-04-25 | 2005-04-12 | Wockhardt Limited | Generation triple-targeting, chiral, broad-spectrum antimicrobial 7-substituted piperidino-quinolone carboxylic acid derivatives, their preparation, compositions and use as medicaments |
| US6964966B2 (en) | 2001-04-25 | 2005-11-15 | Wockhardt Limited | Generation triple-targeting, chiral, broad-spectrum antimicrobial 7-substituted piperidino-quinolone carboxylic acid derivatives, their preparation, compositions and use as medicaments |
| EP1487460A2 (en) * | 2002-02-28 | 2004-12-22 | A & D Bioscience, Inc. | Glycuronamides, glycosides and orthoester glycosides of fluoxetine, analogs and uses thereof |
| US20050107310A1 (en) * | 2002-03-19 | 2005-05-19 | Holick Michael F. | Carboxylic acid glycuronides, glycosamides and glycosides of quinolones, penicillins, analogs, and uses thereof |
| WO2003086475A1 (en) * | 2002-04-12 | 2003-10-23 | A & D Bioscience, Inc. | Conjugates comprising cancer cell specific ligands, a sugar and diagnostic agents, and uses thereof |
| EP1549323A2 (en) * | 2002-05-07 | 2005-07-06 | A & D Bioscience, Inc. | Conjugates comprising central nervous system active drug |
| WO2003099815A1 (en) * | 2002-05-28 | 2003-12-04 | Wockhardt Limited | Crystalline fluoroquinolone arginine salt form |
| US20050215487A1 (en) * | 2002-06-27 | 2005-09-29 | Holick Michael F | Conjugates comprising an nsaid and a sugar and uses thereof |
| BR0318460A (pt) | 2003-09-04 | 2006-09-12 | Wockhardt Ltd | sal de arginina de ácido benzoquinolizina-2-carboxìlico tetrahidratado |
| CN108349968A (zh) * | 2015-07-28 | 2018-07-31 | 维奥梅生物科学私人有限公司 | 抗菌治疗剂和预防剂 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4416884A (en) * | 1978-04-12 | 1983-11-22 | Otsuka Pharmaceutical Co., Ltd. | Piperazinylbenzoheterocyclic compounds |
| JPS6019910B2 (ja) * | 1979-10-11 | 1985-05-18 | 大塚製薬株式会社 | ベンゾ〔ｉｊ〕キノリジン−２−カルボン酸誘導体及びその製造法 |
| JPS5630964A (en) * | 1979-08-22 | 1981-03-28 | Kyorin Pharmaceut Co Ltd | Novel substituted quinolinecarboxylic acid and its preparation |
| NO156828C (no) * | 1980-11-10 | 1987-12-02 | Otsuka Pharma Co Ltd | Analogifremgangsm te for fremstilling av antibakterielt virksomme benzoheterocykliske forbindelser. |
| AT380250B (de) * | 1980-12-18 | 1986-04-25 | Otsuka Pharma Co Ltd | Verfahren zur herstellung benzoheterocyclischer verbindungen |
| JPS57145862A (en) * | 1981-03-06 | 1982-09-09 | Kyorin Pharmaceut Co Ltd | Quinolinecarboxylic acid derivative |
-
1983
- 1983-02-22 JP JP58028135A patent/JPS59155381A/ja active Granted
-
1984
- 1984-02-14 AU AU24578/84A patent/AU2457884A/en not_active Abandoned
- 1984-02-17 GB GB848404223A patent/GB8404223D0/en active Pending
- 1984-02-17 SE SE8400853A patent/SE459809B/sv not_active IP Right Cessation
- 1984-02-20 FR FR8402530A patent/FR2541278B1/fr not_active Expired
- 1984-02-21 US US06/581,957 patent/US4599418A/en not_active Expired - Lifetime
- 1984-02-21 CA CA000447876A patent/CA1225091A/en not_active Expired
- 1984-02-21 DE DE3406235A patent/DE3406235C2/de not_active Expired - Lifetime
- 1984-02-22 GB GB08404691A patent/GB2138806B/en not_active Expired
- 1984-02-22 ES ES529962A patent/ES8600274A1/es not_active Expired
- 1984-02-22 IT IT19740/84A patent/IT1173336B/it active
- 1984-02-22 KR KR1019840000865A patent/KR900001547B1/ko not_active Expired
- 1984-02-22 AU AU24832/84A patent/AU559156B2/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| GB2138806B (en) | 1986-05-21 |
| JPH0412268B2 (ko) | 1992-03-04 |
| US4599418A (en) | 1986-07-08 |
| FR2541278B1 (fr) | 1986-09-26 |
| GB8404691D0 (en) | 1984-03-28 |
| GB8404223D0 (en) | 1984-03-21 |
| JPS59155381A (ja) | 1984-09-04 |
| SE8400853D0 (sv) | 1984-02-17 |
| SE8400853L (sv) | 1984-08-23 |
| IT8419740A0 (it) | 1984-02-22 |
| DE3406235C2 (de) | 1994-12-22 |
| DE3406235A1 (de) | 1984-10-11 |
| SE459809B (sv) | 1989-08-07 |
| ES529962A0 (es) | 1985-10-01 |
| AU559156B2 (en) | 1987-02-26 |
| FR2541278A1 (fr) | 1984-08-24 |
| AU2457884A (en) | 1984-08-30 |
| KR840007878A (ko) | 1984-12-11 |
| AU2483284A (en) | 1984-08-30 |
| CA1225091A (en) | 1987-08-04 |
| IT1173336B (it) | 1987-06-24 |
| ES8600274A1 (es) | 1985-10-01 |
| GB2138806A (en) | 1984-10-31 |
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