CA2443307C - Derives d'acides quinolone-carboxyliques et naphtyridone-carboxyliques - Google Patents

Derives d'acides quinolone-carboxyliques et naphtyridone-carboxyliques Download PDF

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Publication number: CA2443307C
Authority: CA; Canada
Prior art keywords: diazabicyclo; cyclopropyl; oxo; nonane; dihydro
Prior art date: 1992-01-10
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Expired - Lifetime

Application number

CA002443307A

Other languages

English (en)

Other versions

CA2443307A1 (fr

Inventor

Uwe Petersen

Andreas Krebs

Thomas Schenke

Thomas Philipps

Klaus Grohe

Klaus-Dieter Bremm

Rainer Endermann

Karl-Georg Metzger

Ingo Haller

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Bayer Pharma AG

Original Assignee

Bayer Healthcare AG

Priority date (The priority date 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 date listed.)

1992-01-10

Filing date

1993-01-07

Publication date

2007-03-20

1992-01-10 Priority claimed from DE4200414A external-priority patent/DE4200414A1/de

1992-03-19 Priority claimed from DE4208789A external-priority patent/DE4208789A1/de

1992-03-19 Priority claimed from DE4208792A external-priority patent/DE4208792A1/de

1993-01-07 Application filed by Bayer Healthcare AG filed Critical Bayer Healthcare AG

1993-01-07 Priority claimed from CA002086914A external-priority patent/CA2086914C/fr

1993-07-11 Publication of CA2443307A1 publication Critical patent/CA2443307A1/fr

2007-03-20 Application granted granted Critical

2007-03-20 Publication of CA2443307C publication Critical patent/CA2443307C/fr

2013-01-07 Anticipated expiration legal-status Critical

Status Expired - Lifetime legal-status Critical Current

Links

150000001875 compounds Chemical class 0.000 claims abstract description 62
125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 9
238000002360 preparation method Methods 0.000 abstract description 8
239000000543 intermediate Substances 0.000 abstract description 6
FABPRXSRWADJSP-MEDUHNTESA-N moxifloxacin Chemical compound COC1=C(N2C[C@H]3NCCC[C@H]3C2)C(F)=CC(C(C(C(O)=O)=C2)=O)=C1N2C1CC1 FABPRXSRWADJSP-MEDUHNTESA-N 0.000 abstract description 3
229960003702 moxifloxacin Drugs 0.000 abstract 1
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 154
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 103
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 100
238000002844 melting Methods 0.000 description 97
230000008018 melting Effects 0.000 description 95
238000000354 decomposition reaction Methods 0.000 description 72
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239000000203 mixture Substances 0.000 description 69
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 63
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239000000243 solution Substances 0.000 description 61
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125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 38
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 38
-1 bicyclic amine radical Chemical class 0.000 description 37
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239000000047 product Substances 0.000 description 36
238000006243 chemical reaction Methods 0.000 description 35
238000000034 method Methods 0.000 description 34
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 33
XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 32
239000002244 precipitate Substances 0.000 description 28
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
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238000010992 reflux Methods 0.000 description 23
150000003839 salts Chemical class 0.000 description 22
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 20
239000002253 acid Substances 0.000 description 20
239000013078 crystal Substances 0.000 description 19
239000000706 filtrate Substances 0.000 description 18
238000009835 boiling Methods 0.000 description 17
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FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 16
235000011167 hydrochloric acid Nutrition 0.000 description 16
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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 13
238000001816 cooling Methods 0.000 description 13
238000001212 derivatisation Methods 0.000 description 13
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
150000001412 amines Chemical class 0.000 description 12
239000000460 chlorine Substances 0.000 description 12
IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 12
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238000004817 gas chromatography Methods 0.000 description 11
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238000004128 high performance liquid chromatography Methods 0.000 description 10
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
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ZCYXXKJEDCHMGH-UHFFFAOYSA-N nonane Chemical compound CCCC[CH]CCCC ZCYXXKJEDCHMGH-UHFFFAOYSA-N 0.000 description 9
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239000000741 silica gel Substances 0.000 description 9
229910002027 silica gel Inorganic materials 0.000 description 9
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
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150000001340 alkali metals Chemical class 0.000 description 8
239000003153 chemical reaction reagent Substances 0.000 description 8
238000004587 chromatography analysis Methods 0.000 description 8
229910052739 hydrogen Inorganic materials 0.000 description 8
229910052943 magnesium sulfate Inorganic materials 0.000 description 8
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 8
229910052763 palladium Inorganic materials 0.000 description 8
230000003134 recirculating effect Effects 0.000 description 8
238000001953 recrystallisation Methods 0.000 description 8
239000007858 starting material Substances 0.000 description 8
RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 8
RRBLNPCNHNHAFW-NEPJUHHUSA-N (4ar,7as)-6-benzyl-1,2,3,4,4a,7a-hexahydropyrrolo[3,4-b]pyridine-5,7-dione Chemical compound O=C([C@H]1NCCC[C@H]1C1=O)N1CC1=CC=CC=C1 RRBLNPCNHNHAFW-NEPJUHHUSA-N 0.000 description 7
AFYZAHZKOFBVLE-UONOGXRCSA-N (4as,7as)-6-benzyl-1,2,3,4,4a,5,7,7a-octahydropyrrolo[3,4-b]pyridine Chemical compound C([C@H]1NCCC[C@H]1C1)N1CC1=CC=CC=C1 AFYZAHZKOFBVLE-UONOGXRCSA-N 0.000 description 7
KIUPCUCGVCGPPA-UHFFFAOYSA-N (5-methyl-2-propan-2-ylcyclohexyl) carbonochloridate Chemical compound CC(C)C1CCC(C)CC1OC(Cl)=O KIUPCUCGVCGPPA-UHFFFAOYSA-N 0.000 description 7
KWIUHFFTVRNATP-UHFFFAOYSA-O N,N,N-trimethylglycinium Chemical compound C[N+](C)(C)CC(O)=O KWIUHFFTVRNATP-UHFFFAOYSA-O 0.000 description 7
229960003237 betaine Drugs 0.000 description 7
239000003054 catalyst Substances 0.000 description 7
239000012043 crude product Substances 0.000 description 7
QUPDWYMUPZLYJZ-UHFFFAOYSA-N ethyl Chemical compound C[CH2] QUPDWYMUPZLYJZ-UHFFFAOYSA-N 0.000 description 7
FEWJPZIEWOKRBE-LWMBPPNESA-N levotartaric acid Chemical compound OC(=O)[C@@H](O)[C@H](O)C(O)=O FEWJPZIEWOKRBE-LWMBPPNESA-N 0.000 description 7
238000000926 separation method Methods 0.000 description 7
229920002554 vinyl polymer Polymers 0.000 description 7
GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 6
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WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
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235000011002 L(+)-tartaric acid Nutrition 0.000 description 6
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
229910052783 alkali metal Inorganic materials 0.000 description 6
229910052784 alkaline earth metal Inorganic materials 0.000 description 6
239000011230 binding agent Substances 0.000 description 6
FUSUHKVFWTUUBE-UHFFFAOYSA-N buten-2-one Chemical compound CC(=O)C=C FUSUHKVFWTUUBE-UHFFFAOYSA-N 0.000 description 6
MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 6
239000001257 hydrogen Substances 0.000 description 6
235000019341 magnesium sulphate Nutrition 0.000 description 6
244000005700 microbiome Species 0.000 description 6
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 6
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
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RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 5
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229910052736 halogen Inorganic materials 0.000 description 5
150000002367 halogens Chemical class 0.000 description 5
AUONNNVJUCSETH-UHFFFAOYSA-N icosanoyl icosanoate Chemical compound CCCCCCCCCCCCCCCCCCCC(=O)OC(=O)CCCCCCCCCCCCCCCCCCC AUONNNVJUCSETH-UHFFFAOYSA-N 0.000 description 5
208000015181 infectious disease Diseases 0.000 description 5
239000012074 organic phase Substances 0.000 description 5
229910000027 potassium carbonate Inorganic materials 0.000 description 5
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150000003254 radicals Chemical group 0.000 description 5
239000000126 substance Substances 0.000 description 5
229940095064 tartrate Drugs 0.000 description 5
OCKGFTQIICXDQW-ZEQRLZLVSA-N 5-[(1r)-1-hydroxy-2-[4-[(2r)-2-hydroxy-2-(4-methyl-1-oxo-3h-2-benzofuran-5-yl)ethyl]piperazin-1-yl]ethyl]-4-methyl-3h-2-benzofuran-1-one Chemical compound C1=C2C(=O)OCC2=C(C)C([C@@H](O)CN2CCN(CC2)C[C@H](O)C2=CC=C3C(=O)OCC3=C2C)=C1 OCKGFTQIICXDQW-ZEQRLZLVSA-N 0.000 description 4
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KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
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VHILMKFSCRWWIJ-UHFFFAOYSA-N dimethyl acetylenedicarboxylate Chemical compound COC(=O)C#CC(=O)OC VHILMKFSCRWWIJ-UHFFFAOYSA-N 0.000 description 3
238000004821 distillation Methods 0.000 description 3
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125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
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DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 1
239000006187 pill Substances 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
230000003389 potentiating effect Effects 0.000 description 1
239000000843 powder Substances 0.000 description 1
230000001376 precipitating effect Effects 0.000 description 1
230000002265 prevention Effects 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
238000011321 prophylaxis Methods 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
239000013557 residual solvent Substances 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
150000003378 silver Chemical class 0.000 description 1
229910001961 silver nitrate Inorganic materials 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
239000012279 sodium borohydride Substances 0.000 description 1
229910000033 sodium borohydride Inorganic materials 0.000 description 1
239000011775 sodium fluoride Substances 0.000 description 1
235000013024 sodium fluoride Nutrition 0.000 description 1
GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 description 1
241000894007 species Species 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
239000007921 spray Substances 0.000 description 1
238000012916 structural analysis Methods 0.000 description 1
ADNPLDHMAVUMIW-CUZNLEPHSA-N substance P Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CCCN=C(N)N)C1=CC=CC=C1 ADNPLDHMAVUMIW-CUZNLEPHSA-N 0.000 description 1
150000003456 sulfonamides Chemical class 0.000 description 1
229910021653 sulphate ion Inorganic materials 0.000 description 1
239000000829 suppository Substances 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
150000003892 tartrate salts Chemical class 0.000 description 1
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 1
235000019364 tetracycline Nutrition 0.000 description 1
150000003522 tetracyclines Chemical class 0.000 description 1
229940040944 tetracyclines Drugs 0.000 description 1
GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 description 1
239000002023 wood Substances 0.000 description 1
239000010457 zeolite Substances 0.000 description 1

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Nitrogen Condensed Heterocyclic Rings (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA002443307A 1992-01-10 1993-01-07 Derives d'acides quinolone-carboxyliques et naphtyridone-carboxyliques Expired - Lifetime CA2443307C (fr)

Applications Claiming Priority (7)

Application Number	Priority Date	Filing Date	Title
DE4200414A DE4200414A1 (de)	1992-01-10	1992-01-10	Chinolon- und naphthyridon-carbonsaeure-derivate
DEP4200414.4		1992-01-10
DE4208789A DE4208789A1 (de)	1992-03-19	1992-03-19	Enantiomerenreine chinolincarbonsaeure-derivate
DEP4208789.9		1992-03-19
DEP4208792.9		1992-03-19
DE4208792A DE4208792A1 (de)	1992-03-19	1992-03-19	Enantiomerenreine chinolincarbonsaeure-derivate
CA002086914A CA2086914C (fr)	1992-01-10	1993-01-07	Derives d'acides quinolone-carboxyliques et naphtyridone-carboxyliques

Related Parent Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002086914A Division CA2086914C (fr)	1992-01-10	1993-01-07	Derives d'acides quinolone-carboxyliques et naphtyridone-carboxyliques

Publications (2)

Publication Number	Publication Date
CA2443307A1 CA2443307A1 (fr)	1993-07-11
CA2443307C true CA2443307C (fr)	2007-03-20

Family

ID=29554282

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA002443307A Expired - Lifetime CA2443307C (fr)	1992-01-10	1993-01-07	Derives d'acides quinolone-carboxyliques et naphtyridone-carboxyliques

Country Status (1)

Country	Link
CA (1)	CA2443307C (fr)

1993
- 1993-01-07 CA CA002443307A patent/CA2443307C/fr not_active Expired - Lifetime

Also Published As

Publication number	Publication date
CA2443307A1 (fr)	1993-07-11

Legal Events

Date	Code	Title	Description
2003-10-08	EEER	Examination request
2013-03-12	MKEX	Expiry	Effective date: 20130107

Publication	Publication Date	Title
CA2086914C (fr)	2005-03-15	Derives d'acides quinolone-carboxyliques et naphtyridone-carboxyliques
AU671386B2 (en)	1996-08-22	Quinolone carboxylic acid derivatives and pharmaceutical formulations containing them
EP0159174B1 (fr)	1991-10-23	Acides carboxyliques substitués de la naphtyridine, quinoléine et benzoxazine comme agents bactéricides et procédés pour leur préparation
AU674272B2 (en)	1996-12-12	Intermediates for the manufacture of 6-fluoro-1,4-dihydro-4-oxo-3-quinoline carboxylic acids
AU666772B2 (en)	1996-02-22	Quinolone carboxylic acids
SK99093A3 (en)	1994-04-06	7-isoindolinyl-quinolone derivatives and 7-isoindolinyl- -naphthyridone derivatives
IE80557B1 (en)	1998-09-23	8-vinyl- and 8-ethinyl-quinolone-carboxylic acids
JPH06228154A (ja)	1994-08-16	キノロンカルボン酸
JPH08225567A (ja)	1996-09-03	キノロン−及びナフチリドンカルボン酸誘導体
RU2105770C1 (ru)	1998-02-27	Производные хинолон- и нафтиридонкарбоновой кислоты в виде смеси изомеров или отдельных изомеров, их гидраты и соли, фармацевтическая композиция
KR100266888B1 (ko)	2000-09-15	퀴놀론- 및 나프티리돈-카르복실산 유도체의 전구체
SK137194A3 (en)	1995-06-07	1-(2-fluorinecyclopropyl)-quinoline-carboxylic) and 1-(2- -florinecyclopropyl)-naphthyridonecarboxylic acid derivatives, method of their producing and their using in medicines
AU668286B2 (en)	1996-04-26	Diazabicyclo(4.3.0)nonane and (3.3.0)octane heterocycles
JPH0859656A (ja)	1996-03-05	キノロン−及びナフチリドンカルボン酸誘導体
IE19970856A1 (en)	2000-02-23	7-(1-Pyrrolidinyl)-3-quinolone and naphthyridone carboxylic acid derivatives, method for their preparation and for substituted mono- and bicyclic pyrrolidine intermediates, and their antibacterial and feed additive compositions