CS94391A2 - Carbapenemic compounds and method of their production - Google Patents

Carbapenemic compounds and method of their production Download PDF

Info

Publication number: CS94391A2
Authority: CS; Czechoslovakia
Prior art keywords: group; hydrogen; methyl; oxo; formula
Prior art date: 1990-04-09

Application number

CS91943A

Other languages

Czech (cs)

English (en)

Inventor

Scott Louis Dax

Dennis Dalton Keith

Pamela Loreen Rossman

Original Assignee

Hoffmann La Roche

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.)

1990-04-09

Filing date

1991-04-05

Publication date

1991-11-12

1991-04-05 Application filed by Hoffmann La Roche filed Critical Hoffmann La Roche

1991-11-12 Publication of CS94391A2 publication Critical patent/CS94391A2/cs

Links

150000001875 compounds Chemical class 0.000 title claims description 106
238000004519 manufacturing process Methods 0.000 title claims 2
238000000034 method Methods 0.000 title description 21
-1 carbapenem compound Chemical class 0.000 claims description 146
239000001257 hydrogen Substances 0.000 claims description 118
229910052739 hydrogen Inorganic materials 0.000 claims description 118
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 106
125000000217 alkyl group Chemical group 0.000 claims description 88
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 78
150000002148 esters Chemical class 0.000 claims description 62
125000004193 piperazinyl group Chemical group 0.000 claims description 62
150000003839 salts Chemical class 0.000 claims description 55
125000004432 carbon atom Chemical group C* 0.000 claims description 54
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 53
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 47
229910052736 halogen Inorganic materials 0.000 claims description 45
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 43
150000002367 halogens Chemical class 0.000 claims description 39
229910052757 nitrogen Inorganic materials 0.000 claims description 37
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 36
150000004677 hydrates Chemical class 0.000 claims description 35
125000003545 alkoxy group Chemical group 0.000 claims description 29
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 28
229910052760 oxygen Inorganic materials 0.000 claims description 28
239000001301 oxygen Substances 0.000 claims description 28
125000000719 pyrrolidinyl group Chemical group 0.000 claims description 27
125000006239 protecting group Chemical group 0.000 claims description 26
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 25
229910052717 sulfur Chemical group 0.000 claims description 25
239000011593 sulfur Chemical group 0.000 claims description 25
BSIMZHVOQZIAOY-SCSAIBSYSA-N 1-carbapenem-3-carboxylic acid Chemical class OC(=O)C1=CC[C@@H]2CC(=O)N12 BSIMZHVOQZIAOY-SCSAIBSYSA-N 0.000 claims description 24
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 24
125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 claims description 23
125000005843 halogen group Chemical group 0.000 claims description 23
125000000753 cycloalkyl group Chemical group 0.000 claims description 21
125000002947 alkylene group Chemical group 0.000 claims description 20
GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 19
125000003277 amino group Chemical group 0.000 claims description 17
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 17
125000004433 nitrogen atom Chemical group N* 0.000 claims description 17
125000003342 alkenyl group Chemical group 0.000 claims description 15
125000006244 carboxylic acid protecting group Chemical group 0.000 claims description 14
125000002768 hydroxyalkyl group Chemical group 0.000 claims description 14
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 14
125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 13
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
239000002253 acid Substances 0.000 claims description 12
125000004414 alkyl thio group Chemical group 0.000 claims description 12
125000001153 fluoro group Chemical group F* 0.000 claims description 11
125000005842 heteroatom Chemical group 0.000 claims description 11
FYZUENZXIZCLAZ-UHFFFAOYSA-N 2-methylhept-2-enoic acid Chemical compound CCCCC=C(C)C(O)=O FYZUENZXIZCLAZ-UHFFFAOYSA-N 0.000 claims description 10
150000007970 thio esters Chemical group 0.000 claims description 10
KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical group NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 claims description 9
150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 8
125000004185 ester group Chemical group 0.000 claims description 8
125000000623 heterocyclic group Chemical group 0.000 claims description 8
238000002360 preparation method Methods 0.000 claims description 8
125000001424 substituent group Chemical group 0.000 claims description 8
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 7
125000005530 alkylenedioxy group Chemical group 0.000 claims description 7
125000001309 chloro group Chemical group Cl* 0.000 claims description 7
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 7
125000001453 quaternary ammonium group Chemical group 0.000 claims description 7
229910052799 carbon Inorganic materials 0.000 claims description 6
150000001733 carboxylic acid esters Chemical class 0.000 claims description 6
238000003776 cleavage reaction Methods 0.000 claims description 6
125000003784 fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 claims description 6
125000001207 fluorophenyl group Chemical group 0.000 claims description 6
125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 claims description 6
230000007017 scission Effects 0.000 claims description 6
125000004149 thio group Chemical group *S* 0.000 claims description 6
229910052731 fluorine Inorganic materials 0.000 claims description 5
ZLTPDFXIESTBQG-UHFFFAOYSA-N isothiazole Chemical compound C=1C=NSC=1 ZLTPDFXIESTBQG-UHFFFAOYSA-N 0.000 claims description 5
150000002545 isoxazoles Chemical class 0.000 claims description 5
125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 4
125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 3
229910052801 chlorine Inorganic materials 0.000 claims description 3
239000011737 fluorine Substances 0.000 claims description 3
OTTZHAVKAVGASB-UHFFFAOYSA-N hept-2-ene Chemical compound CCCCC=CC OTTZHAVKAVGASB-UHFFFAOYSA-N 0.000 claims description 3
125000004430 oxygen atom Chemical group O* 0.000 claims description 3
125000004434 sulfur atom Chemical group 0.000 claims description 3
ZFRUGZMCGCYBRC-UHFFFAOYSA-N 1h-1,8-naphthyridin-2-one Chemical compound C1=CC=NC2=NC(O)=CC=C21 ZFRUGZMCGCYBRC-UHFFFAOYSA-N 0.000 claims description 2
125000003118 aryl group Chemical group 0.000 claims description 2
125000005059 halophenyl group Chemical group 0.000 claims description 2
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 2
SMWDFEZZVXVKRB-UHFFFAOYSA-O hydron;quinoline Chemical compound [NH+]1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-O 0.000 claims description 2
125000004159 quinolin-2-yl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C([H])C(*)=NC2=C1[H] 0.000 claims description 2
238000006798 ring closing metathesis reaction Methods 0.000 claims description 2
238000001149 thermolysis Methods 0.000 claims description 2
125000005708 carbonyloxy group Chemical group [*:2]OC([*:1])=O 0.000 claims 3
239000007795 chemical reaction product Substances 0.000 claims 3
238000011321 prophylaxis Methods 0.000 claims 3
238000011282 treatment Methods 0.000 claims 3
208000035473 Communicable disease Diseases 0.000 claims 2
201000010099 disease Diseases 0.000 claims 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
239000003814 drug Substances 0.000 claims 1
150000003254 radicals Chemical class 0.000 claims 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 57
239000000243 solution Substances 0.000 description 42
239000000203 mixture Substances 0.000 description 36
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 30
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 27
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 24
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
238000006243 chemical reaction Methods 0.000 description 19
239000003960 organic solvent Substances 0.000 description 17
239000003795 chemical substances by application Substances 0.000 description 16
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 14
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 14
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 14
239000012300 argon atmosphere Substances 0.000 description 14
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 13
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 12
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 12
229910052938 sodium sulfate Inorganic materials 0.000 description 11
235000011152 sodium sulphate Nutrition 0.000 description 11
239000002904 solvent Substances 0.000 description 11
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
239000002585 base Substances 0.000 description 10
239000011541 reaction mixture Substances 0.000 description 10
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical compound [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 9
239000003480 eluent Substances 0.000 description 9
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 8
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
239000000284 extract Substances 0.000 description 8
LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 8
239000000741 silica gel Substances 0.000 description 8
229910002027 silica gel Inorganic materials 0.000 description 8
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 7
MSPCIZMDDUQPGJ-UHFFFAOYSA-N N-methyl-N-(trimethylsilyl)trifluoroacetamide Chemical group C[Si](C)(C)N(C)C(=O)C(F)(F)F MSPCIZMDDUQPGJ-UHFFFAOYSA-N 0.000 description 7
229910052786 argon Inorganic materials 0.000 description 7
FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 7
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 6
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
150000002170 ethers Chemical class 0.000 description 6
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
239000007787 solid Substances 0.000 description 6
229910019142 PO4 Inorganic materials 0.000 description 5
239000012267 brine Substances 0.000 description 5
125000002843 carboxylic acid group Chemical group 0.000 description 5
125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
150000004702 methyl esters Chemical class 0.000 description 5
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 5
235000021317 phosphate Nutrition 0.000 description 5
AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 4
108090000371 Esterases Proteins 0.000 description 4
241000124008 Mammalia Species 0.000 description 4
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical class [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
230000000844 anti-bacterial effect Effects 0.000 description 4
239000000872 buffer Substances 0.000 description 4
150000001735 carboxylic acids Chemical class 0.000 description 4
IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 4
239000000706 filtrate Substances 0.000 description 4
150000007530 organic bases Chemical class 0.000 description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 4
239000010452 phosphate Substances 0.000 description 4
239000000047 product Substances 0.000 description 4
238000003756 stirring Methods 0.000 description 4
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
150000003952 β-lactams Chemical class 0.000 description 4
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 3
229940126062 Compound A Drugs 0.000 description 3
NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 3
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group 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 3
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
230000001476 alcoholic effect Effects 0.000 description 3
239000012298 atmosphere Substances 0.000 description 3
JXLHNMVSKXFWAO-UHFFFAOYSA-N azane;7-fluoro-2,1,3-benzoxadiazole-4-sulfonic acid Chemical compound N.OS(=O)(=O)C1=CC=C(F)C2=NON=C12 JXLHNMVSKXFWAO-UHFFFAOYSA-N 0.000 description 3
238000010511 deprotection reaction Methods 0.000 description 3
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 3
239000012074 organic phase Substances 0.000 description 3
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 3
239000011734 sodium Substances 0.000 description 3
229910052708 sodium Inorganic materials 0.000 description 3
229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
235000017557 sodium bicarbonate Nutrition 0.000 description 3
159000000000 sodium salts Chemical class 0.000 description 3
DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 3
125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 3
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
DDFHBQSCUXNBSA-UHFFFAOYSA-N 5-(5-carboxythiophen-2-yl)thiophene-2-carboxylic acid Chemical compound S1C(C(=O)O)=CC=C1C1=CC=C(C(O)=O)S1 DDFHBQSCUXNBSA-UHFFFAOYSA-N 0.000 description 2
208000035143 Bacterial infection Diseases 0.000 description 2
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
241000192125 Firmicutes Species 0.000 description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical group [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical group [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
125000005041 acyloxyalkyl group Chemical group 0.000 description 2
125000003158 alcohol group Chemical group 0.000 description 2
125000004453 alkoxycarbonyl group Chemical group 0.000 description 2
125000005205 alkoxycarbonyloxyalkyl group Chemical group 0.000 description 2
125000004849 alkoxymethyl group Chemical group 0.000 description 2
239000004599 antimicrobial Substances 0.000 description 2
239000006286 aqueous extract Substances 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
MNFORVFSTILPAW-UHFFFAOYSA-N azetidin-2-one Chemical compound O=C1CCN1 MNFORVFSTILPAW-UHFFFAOYSA-N 0.000 description 2
208000022362 bacterial infectious disease Diseases 0.000 description 2
150000001720 carbohydrates Chemical class 0.000 description 2
150000001721 carbon Chemical group 0.000 description 2
FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical class OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 description 2
229940106681 chloroacetic acid Drugs 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
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 2
239000012043 crude product Substances 0.000 description 2
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Substances CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 2
238000003818 flash chromatography Methods 0.000 description 2
JEGUKCSWCFPDGT-UHFFFAOYSA-N h2o hydrate Chemical compound O.O JEGUKCSWCFPDGT-UHFFFAOYSA-N 0.000 description 2
230000002140 halogenating effect Effects 0.000 description 2
238000000338 in vitro Methods 0.000 description 2
239000000543 intermediate Substances 0.000 description 2
229910052744 lithium Chemical group 0.000 description 2
210000004185 liver Anatomy 0.000 description 2
125000005699 methyleneoxy group Chemical group [H]C([H])([*:1])O[*:2] 0.000 description 2
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
150000007524 organic acids Chemical class 0.000 description 2
239000008363 phosphate buffer Substances 0.000 description 2
239000011591 potassium Chemical group 0.000 description 2
229910052700 potassium Inorganic materials 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 2
229910000105 potassium hydride Inorganic materials 0.000 description 2
238000001556 precipitation Methods 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
SIOVKLKJSOKLIF-HJWRWDBZSA-N trimethylsilyl (1z)-n-trimethylsilylethanimidate Chemical compound C[Si](C)(C)OC(/C)=N\[Si](C)(C)C SIOVKLKJSOKLIF-HJWRWDBZSA-N 0.000 description 2
125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
CSRZQMIRAZTJOY-UHFFFAOYSA-N trimethylsilyl iodide Chemical compound C[Si](C)(C)I CSRZQMIRAZTJOY-UHFFFAOYSA-N 0.000 description 2
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 2
239000003643 water by type Substances 0.000 description 2
OKBVVJOGVLARMR-QMTHXVAHSA-N (6R,7R)-7-[[2-(2-amino-4-thiazolyl)-2-(carboxymethoxyimino)-1-oxoethyl]amino]-3-ethenyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound S1C(N)=NC(C(=NOCC(O)=O)C(=O)N[C@@H]2C(N3C(=C(C=C)CS[C@@H]32)C(O)=O)=O)=C1 OKBVVJOGVLARMR-QMTHXVAHSA-N 0.000 description 1
PXHHIBMOFPCBJQ-UHFFFAOYSA-N 1,2-dimethylpyrrolidine Chemical compound CC1CCCN1C PXHHIBMOFPCBJQ-UHFFFAOYSA-N 0.000 description 1
RXYPXQSKLGGKOL-UHFFFAOYSA-N 1,4-dimethylpiperazine Chemical compound CN1CCN(C)CC1 RXYPXQSKLGGKOL-UHFFFAOYSA-N 0.000 description 1
PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
AVFZOVWCLRSYKC-UHFFFAOYSA-N 1-methylpyrrolidine Chemical compound CN1CCCC1 AVFZOVWCLRSYKC-UHFFFAOYSA-N 0.000 description 1
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KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical class NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 1
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241000219470 Mirabilis Species 0.000 description 1
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 1
AHVYPIQETPWLSZ-UHFFFAOYSA-N N-methyl-pyrrolidine Natural products CN1CC=CC1 AHVYPIQETPWLSZ-UHFFFAOYSA-N 0.000 description 1
101100030361 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) pph-3 gene Proteins 0.000 description 1
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KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
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150000001558 benzoic acid derivatives Chemical class 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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150000001768 cations Chemical class 0.000 description 1
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239000000460 chlorine Substances 0.000 description 1
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239000012230 colorless oil Substances 0.000 description 1
239000013078 crystal Substances 0.000 description 1
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239000012895 dilution Substances 0.000 description 1
239000012971 dimethylpiperazine Substances 0.000 description 1
ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
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238000000605 extraction Methods 0.000 description 1
239000012467 final product Substances 0.000 description 1
XBJBPGROQZJDOJ-UHFFFAOYSA-N fleroxacin Chemical compound C1CN(C)CCN1C1=C(F)C=C2C(=O)C(C(O)=O)=CN(CCF)C2=C1F XBJBPGROQZJDOJ-UHFFFAOYSA-N 0.000 description 1
229960003306 fleroxacin Drugs 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
239000000499 gel Substances 0.000 description 1
125000001188 haloalkyl group Chemical group 0.000 description 1
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 1
239000008240 homogeneous mixture Substances 0.000 description 1
150000002430 hydrocarbons Chemical group 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
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238000007918 intramuscular administration Methods 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
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WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
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 1
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239000008194 pharmaceutical composition Substances 0.000 description 1
239000012071 phase Substances 0.000 description 1
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
150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
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239000003495 polar organic solvent Substances 0.000 description 1
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DCKIEHUEZQBPSD-UHFFFAOYSA-M potassium;6,8-difluoro-1-(2-fluoroethyl)-7-(4-methylpiperazin-1-yl)-4-oxoquinoline-3-carboxylate Chemical compound [K+].C1CN(C)CCN1C1=C(F)C=C2C(=O)C(C([O-])=O)=CN(CCF)C2=C1F DCKIEHUEZQBPSD-UHFFFAOYSA-M 0.000 description 1
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
229960004919 procaine Drugs 0.000 description 1
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BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
238000000746 purification Methods 0.000 description 1
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208000020029 respiratory tract infectious disease Diseases 0.000 description 1
150000003902 salicylic acid esters Chemical class 0.000 description 1
239000012266 salt solution Substances 0.000 description 1
229930195734 saturated hydrocarbon Natural products 0.000 description 1
239000012047 saturated solution Substances 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
239000012312 sodium hydride Substances 0.000 description 1
229910000104 sodium hydride Inorganic materials 0.000 description 1
239000011877 solvent mixture Substances 0.000 description 1
238000004611 spectroscopical analysis Methods 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 1
125000001273 sulfonato group Chemical class [O-]S(*)(=O)=O 0.000 description 1
150000003461 sulfonyl halides Chemical class 0.000 description 1
150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
239000000829 suppository Substances 0.000 description 1
150000003899 tartaric acid esters Chemical class 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
230000001225 therapeutic effect Effects 0.000 description 1
238000004809 thin layer chromatography Methods 0.000 description 1
239000001585 thymus vulgaris Substances 0.000 description 1
LBLYYCQCTBFVLH-UHFFFAOYSA-M toluenesulfonate group Chemical group C=1(C(=CC=CC1)S(=O)(=O)[O-])C LBLYYCQCTBFVLH-UHFFFAOYSA-M 0.000 description 1
GRGCWBWNLSTIEN-UHFFFAOYSA-N trifluoromethanesulfonyl chloride Chemical compound FC(F)(F)S(Cl)(=O)=O GRGCWBWNLSTIEN-UHFFFAOYSA-N 0.000 description 1
239000005051 trimethylchlorosilane Substances 0.000 description 1
210000001635 urinary tract Anatomy 0.000 description 1
208000019206 urinary tract infection Diseases 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
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239000011701 zinc Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D477/00—Heterocyclic compounds containing 1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbapenicillins, thienamycins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulphur-containing hetero ring
- C07D477/10—Heterocyclic compounds containing 1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbapenicillins, thienamycins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulphur-containing hetero ring with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 4, and with a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2
- C07D477/12—Heterocyclic compounds containing 1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbapenicillins, thienamycins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulphur-containing hetero ring with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 4, and with a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2 with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached in position 6
- C07D477/14—Heterocyclic compounds containing 1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbapenicillins, thienamycins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulphur-containing hetero ring with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 4, and with a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2 with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached in position 6 with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached in position 3
- 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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D477/00—Heterocyclic compounds containing 1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbapenicillins, thienamycins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulphur-containing hetero ring
- C07D477/26—Heterocyclic compounds containing 1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbapenicillins, thienamycins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulphur-containing hetero ring with hetero atoms or carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 4
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Landscapes

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)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)

CS91943A 1990-04-09 1991-04-05 Carbapenemic compounds and method of their production CS94391A2 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US50613590A	1990-04-09	1990-04-09

Publications (1)

Publication Number	Publication Date
CS94391A2 true CS94391A2 (en)	1991-11-12

Family

ID=24013339

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CS91943A CS94391A2 (en)	1990-04-09	1991-04-05	Carbapenemic compounds and method of their production

Country Status (17)

Country	Link
EP (1)	EP0451764A1 (fr)
JP (1)	JPH04234884A (fr)
AU (1)	AU7420591A (fr)
BR (1)	BR9101418A (fr)
CA (1)	CA2039987A1 (fr)
CS (1)	CS94391A2 (fr)
FI (1)	FI911666A7 (fr)
HU (1)	HUT57769A (fr)
IE (1)	IE911161A1 (fr)
IL (1)	IL97797A0 (fr)
MC (1)	MC2262A1 (fr)
MX (1)	MX25231A (fr)
NO (1)	NO911357L (fr)
PT (1)	PT97287A (fr)
TW (1)	TW216420B (fr)
YU (1)	YU62991A (fr)
ZA (1)	ZA912279B (fr)

Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CA2001203C (fr) *	1988-10-24	2001-02-13	Thomas P. Demuth, Jr.	Dithiocarbamoyl quinolones antimicrobiens
US5328908A (en) *	1988-10-24	1994-07-12	Procter & Gamble Pharmaceuticals, Inc.	Antimicrobial quinolone thioureas
US5180719A (en) *	1988-10-24	1993-01-19	Norwich Eaton Pharmaceuticals, Inc.	Antimicrobial quinolonyl lactam esters
EP0366189A3 (fr) *	1988-10-24	1992-01-02	Norwich Eaton Pharmaceuticals, Inc.	Lactames-quinolones antimicrobiennes
US5273973A (en) *	1988-10-24	1993-12-28	Norwich Eaton Pharmaceuticals, Inc.	Antimicrobial quinolonyl esters
US5491139A (en) *	1988-10-24	1996-02-13	The Procter & Gamble Company	Antimicrobial quinolonyl lactams
WO1991016327A1 (fr) *	1990-04-18	1991-10-31	Norwich Eaton Pharmaceuticals, Inc.	Quinolonyle lactames anti-microbiens
CZ73194A3 (en) *	1991-10-01	1994-11-16	Procter & Gamble Pharma	Process for preparing anti-microbial quinolonyl-lactams
DE4234078A1 (de) *	1992-10-09	1994-04-14	Bayer Ag	Chinoloncarbonsäuren
DE4234330A1 (de) *	1992-10-12	1994-04-14	Bayer Ag	Chinoloncarbonsäuren
BR9508513A (pt) *	1994-08-02	1998-06-02	Procter & Gamble	Processo para a produção de antimicrobianos de quinolonil lactama e novos compostos intermediários
MX9700871A (es) *	1994-08-02	1997-05-31	Procter & Gamble	Procedimiento para hacer compuestos antimicrobianos.
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1991
- 1991-03-26 ZA ZA912279A patent/ZA912279B/xx unknown
- 1991-04-05 MC MC932182A patent/MC2262A1/fr unknown
- 1991-04-05 CS CS91943A patent/CS94391A2/cs unknown
- 1991-04-05 MX MX2523191A patent/MX25231A/es unknown
- 1991-04-05 JP JP3099750A patent/JPH04234884A/ja active Pending
- 1991-04-08 NO NO91911357A patent/NO911357L/no unknown
- 1991-04-08 EP EP91105550A patent/EP0451764A1/fr not_active Withdrawn
- 1991-04-08 TW TW080102600A patent/TW216420B/zh active
- 1991-04-08 FI FI911666A patent/FI911666A7/fi not_active Application Discontinuation
- 1991-04-08 CA CA002039987A patent/CA2039987A1/fr not_active Abandoned
- 1991-04-08 IE IE116191A patent/IE911161A1/en unknown
- 1991-04-08 AU AU74205/91A patent/AU7420591A/en not_active Abandoned
- 1991-04-08 YU YU62991A patent/YU62991A/sh unknown
- 1991-04-08 HU HU911132A patent/HUT57769A/hu unknown
- 1991-04-08 IL IL97797A patent/IL97797A0/xx unknown
- 1991-04-08 PT PT97287A patent/PT97287A/pt not_active Application Discontinuation
- 1991-04-09 BR BR919101418A patent/BR9101418A/pt unknown

Also Published As

Publication number	Publication date
NO911357L (no)	1991-10-10
MX25231A (es)	1993-10-01
MC2262A1 (fr)	1993-04-26
YU62991A (sh)	1994-04-05
TW216420B (fr)	1993-11-21
HU911132D0 (en)	1991-10-28
CA2039987A1 (fr)	1991-10-10
PT97287A (pt)	1992-01-31
EP0451764A1 (fr)	1991-10-16
IL97797A0 (en)	1992-06-21
BR9101418A (pt)	1991-11-26
ZA912279B (en)	1992-02-26
JPH04234884A (ja)	1992-08-24
HUT57769A (en)	1991-12-30
AU7420591A (en)	1991-10-10
FI911666A0 (fi)	1991-04-08
NO911357D0 (no)	1991-04-08
IE911161A1 (en)	1991-10-09
FI911666A7 (fi)	1991-10-10

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JP2010001315A (ja)	2010-01-07	キノロン類及びナフチリジン類の製造方法における環化工程
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US5328904A (en)	1994-07-12	2-phenanthridinyl carbapenem antibacterial agents
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JPH0559052A (ja)	1993-03-09	新規三環性化合物又はその塩及びこれを含有する抗菌剤
WO1994014819A1 (fr)	1994-07-07	Derive d'acide carboxyquinolinique et procede d'obtention de ce derive
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JPH0413355B2 (fr)	1992-03-09