CA1117948A - Derives de l'acide clavulanique - Google Patents

Derives de l'acide clavulanique

Info

Publication number: CA1117948A
Authority: CA; Canada
Prior art keywords: group; formula; lower alkyl; compound; ester
Prior art date: 1977-04-27
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

Application number

CA000302012A

Other languages

English (en)

Inventor

John B. Harbridge

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.)

Beecham Group PLC

Original Assignee

Beecham Group PLC

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.)

1977-04-27

Filing date

1978-04-26

Publication date

1982-02-09

1977-04-27 Priority claimed from GB17660/77A external-priority patent/GB1603208A/en

1977-10-20 Priority claimed from GB43794/77A external-priority patent/GB1559356A/en

1978-04-26 Application filed by Beecham Group PLC filed Critical Beecham Group PLC

1982-02-09 Application granted granted Critical

1982-02-09 Publication of CA1117948A publication Critical patent/CA1117948A/fr

Status Expired legal-status Critical Current

Links

HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical class OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 title claims description 18
150000001875 compounds Chemical class 0.000 claims abstract description 163
238000000034 method Methods 0.000 claims abstract description 97
230000008569 process Effects 0.000 claims abstract description 92
150000003839 salts Chemical class 0.000 claims abstract description 80
150000002148 esters Chemical class 0.000 claims abstract description 73
125000000217 alkyl group Chemical group 0.000 claims abstract description 64
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 55
125000003118 aryl group Chemical group 0.000 claims abstract description 53
125000002877 alkyl aryl group Chemical group 0.000 claims abstract description 39
125000003342 alkenyl group Chemical group 0.000 claims abstract description 37
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 36
125000002843 carboxylic acid group Chemical group 0.000 claims abstract description 29
238000002360 preparation method Methods 0.000 claims abstract description 28
101100134927 Gallus gallus COR8 gene Proteins 0.000 claims abstract description 25
125000003545 alkoxy group Chemical group 0.000 claims abstract description 16
101100295741 Gallus gallus COR4 gene Proteins 0.000 claims abstract description 15
229910052731 fluorine Inorganic materials 0.000 claims abstract description 14
239000011737 fluorine Substances 0.000 claims abstract description 14
125000002373 5 membered heterocyclic group Chemical group 0.000 claims abstract description 12
125000004070 6 membered heterocyclic group Chemical group 0.000 claims abstract description 12
125000003341 7 membered heterocyclic group Chemical group 0.000 claims abstract description 12
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract description 8
125000001309 chloro group Chemical group Cl* 0.000 claims abstract description 7
101100134925 Gallus gallus COR6 gene Proteins 0.000 claims abstract description 5
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 85
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 62
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 61
238000005984 hydrogenation reaction Methods 0.000 claims description 45
239000002253 acid Substances 0.000 claims description 43
-1 methoxyphenyl Chemical group 0.000 claims description 41
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 40
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 40
239000000047 product Substances 0.000 claims description 39
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 39
239000000706 filtrate Substances 0.000 claims description 35
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 33
239000002904 solvent Substances 0.000 claims description 32
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 31
238000006243 chemical reaction Methods 0.000 claims description 29
239000003054 catalyst Substances 0.000 claims description 27
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 25
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 23
229910052744 lithium Inorganic materials 0.000 claims description 23
238000001914 filtration Methods 0.000 claims description 21
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 18
125000004432 carbon atom Chemical group C* 0.000 claims description 18
HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 claims description 17
239000003610 charcoal Substances 0.000 claims description 15
238000006460 hydrolysis reaction Methods 0.000 claims description 14
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 13
230000007062 hydrolysis Effects 0.000 claims description 13
TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 claims description 12
239000001257 hydrogen Substances 0.000 claims description 12
229910052739 hydrogen Inorganic materials 0.000 claims description 12
125000004185 ester group Chemical group 0.000 claims description 11
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical group [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 10
229960003324 clavulanic acid Drugs 0.000 claims description 10
239000000460 chlorine Chemical group 0.000 claims description 9
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 9
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 7
229910052801 chlorine Inorganic materials 0.000 claims description 7
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
229910052794 bromium Inorganic materials 0.000 claims description 6
125000001153 fluoro group Chemical group F* 0.000 claims description 6
238000007327 hydrogenolysis reaction Methods 0.000 claims description 6
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 6
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 6
239000003960 organic solvent Substances 0.000 claims description 6
238000011084 recovery Methods 0.000 claims description 6
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 5
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 4
RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 claims description 4
QARVLSVVCXYDNA-UHFFFAOYSA-N bromobenzene Chemical compound BrC1=CC=CC=C1 QARVLSVVCXYDNA-UHFFFAOYSA-N 0.000 claims description 4
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 4
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 4
229910052763 palladium Inorganic materials 0.000 claims description 4
125000005633 phthalidyl group Chemical group 0.000 claims description 4
229910052723 transition metal Inorganic materials 0.000 claims description 4
150000003624 transition metals Chemical class 0.000 claims description 4
BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 claims description 4
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
125000004122 cyclic group Chemical group 0.000 claims description 3
239000000376 reactant Substances 0.000 claims description 3
CYTQBVOFDCPGCX-UHFFFAOYSA-N trimethyl phosphite Chemical compound COP(OC)OC CYTQBVOFDCPGCX-UHFFFAOYSA-N 0.000 claims description 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
125000004423 acyloxy group Chemical group 0.000 claims description 2
239000003153 chemical reaction reagent Substances 0.000 claims description 2
239000003795 chemical substances by application Substances 0.000 claims description 2
150000008049 diazo compounds Chemical class 0.000 claims description 2
238000005886 esterification reaction Methods 0.000 claims description 2
150000004820 halides Chemical class 0.000 claims description 2
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 claims description 2
PYLWMHQQBFSUBP-UHFFFAOYSA-N monofluorobenzene Chemical compound FC1=CC=CC=C1 PYLWMHQQBFSUBP-UHFFFAOYSA-N 0.000 claims description 2
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
239000000126 substance Substances 0.000 claims 10
238000004448 titration Methods 0.000 claims 4
239000012895 dilution Substances 0.000 claims 3
238000010790 dilution Methods 0.000 claims 3
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims 2
230000032050 esterification Effects 0.000 claims 1
125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims 1
230000000844 anti-bacterial effect Effects 0.000 abstract description 3
230000002401 inhibitory effect Effects 0.000 abstract description 2
239000000243 solution Substances 0.000 description 64
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 53
239000000203 mixture Substances 0.000 description 48
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 43
LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 description 27
229940093499 ethyl acetate Drugs 0.000 description 27
229960003022 amoxicillin Drugs 0.000 description 22
LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 description 22
239000007787 solid Substances 0.000 description 21
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 20
AZUFHGGGPUUXKI-FLFDDASRSA-N benzyl (2r,3z,5r)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]heptane-2-carboxylate Chemical compound O=C([C@@H]1N2C(=O)C[C@H]2O\C1=C/CO)OCC1=CC=CC=C1 AZUFHGGGPUUXKI-FLFDDASRSA-N 0.000 description 20
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 18
239000000463 material Substances 0.000 description 18
239000000741 silica gel Substances 0.000 description 17
229910002027 silica gel Inorganic materials 0.000 description 17
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 16
230000002829 reductive effect Effects 0.000 description 16
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 15
FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 15
101150041968 CDC13 gene Proteins 0.000 description 14
229930182555 Penicillin Natural products 0.000 description 14
JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 14
239000011734 sodium Substances 0.000 description 13
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 12
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 12
229910052708 sodium Inorganic materials 0.000 description 12
229930186147 Cephalosporin Natural products 0.000 description 11
229940124587 cephalosporin Drugs 0.000 description 11
150000001780 cephalosporins Chemical class 0.000 description 11
229940090805 clavulanate Drugs 0.000 description 11
239000007858 starting material Substances 0.000 description 11
238000004809 thin layer chromatography Methods 0.000 description 11
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 10
239000003480 eluent Substances 0.000 description 10
239000000543 intermediate Substances 0.000 description 10
NOTFZGFABLVTIG-UHFFFAOYSA-N Cyclohexylethyl acetate Chemical compound CC(=O)OCCC1CCCCC1 NOTFZGFABLVTIG-UHFFFAOYSA-N 0.000 description 9
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 9
229960000723 ampicillin Drugs 0.000 description 9
FPPNZSSZRUTDAP-UWFZAAFLSA-N carbenicillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)C(C(O)=O)C1=CC=CC=C1 FPPNZSSZRUTDAP-UWFZAAFLSA-N 0.000 description 9
229960003669 carbenicillin Drugs 0.000 description 9
239000002198 insoluble material Substances 0.000 description 9
OHKOGUYZJXTSFX-KZFFXBSXSA-N ticarcillin Chemical compound C=1([C@@H](C(O)=O)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)C=CSC=1 OHKOGUYZJXTSFX-KZFFXBSXSA-N 0.000 description 9
229960004659 ticarcillin Drugs 0.000 description 9
IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 8
150000002960 penicillins Chemical class 0.000 description 8
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 7
238000004440 column chromatography Methods 0.000 description 7
150000001993 dienes Chemical class 0.000 description 7
WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
238000001704 evaporation Methods 0.000 description 6
230000008020 evaporation Effects 0.000 description 6
208000015181 infectious disease Diseases 0.000 description 6
229910003002 lithium salt Inorganic materials 0.000 description 6
159000000002 lithium salts Chemical class 0.000 description 6
235000019359 magnesium stearate Nutrition 0.000 description 6
229940049954 penicillin Drugs 0.000 description 6
KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 6
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 5
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 5
241000588724 Escherichia coli Species 0.000 description 5
241000699670 Mus sp. Species 0.000 description 5
WACQKHWOTAEEFS-UHFFFAOYSA-N cyclohexane;ethyl acetate Chemical compound CCOC(C)=O.C1CCCCC1 WACQKHWOTAEEFS-UHFFFAOYSA-N 0.000 description 5
238000004019 gradient elution chromatography Methods 0.000 description 5
239000008187 granular material Substances 0.000 description 5
150000003949 imides Chemical class 0.000 description 5
238000001727 in vivo Methods 0.000 description 5
239000007972 injectable composition Substances 0.000 description 5
229920005989 resin Polymers 0.000 description 5
239000011347 resin Substances 0.000 description 5
159000000000 sodium salts Chemical class 0.000 description 5
239000006188 syrup Substances 0.000 description 5
235000020357 syrup Nutrition 0.000 description 5
229920000168 Microcrystalline cellulose Polymers 0.000 description 4
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 4
239000003242 anti bacterial agent Substances 0.000 description 4
229940106164 cephalexin Drugs 0.000 description 4
239000013078 crystal Substances 0.000 description 4
238000010828 elution Methods 0.000 description 4
125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 4
150000002576 ketones Chemical class 0.000 description 4
239000011777 magnesium Substances 0.000 description 4
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
229940016286 microcrystalline cellulose Drugs 0.000 description 4
235000019813 microcrystalline cellulose Nutrition 0.000 description 4
239000008108 microcrystalline cellulose Substances 0.000 description 4
235000019371 penicillin G benzathine Nutrition 0.000 description 4
229940056360 penicillin g Drugs 0.000 description 4
239000011591 potassium Substances 0.000 description 4
229910052700 potassium Inorganic materials 0.000 description 4
229940002612 prodrug Drugs 0.000 description 4
239000000651 prodrug Substances 0.000 description 4
235000011121 sodium hydroxide Nutrition 0.000 description 4
239000000725 suspension Substances 0.000 description 4
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
229930195708 Penicillin V Natural products 0.000 description 3
229960003311 ampicillin trihydrate Drugs 0.000 description 3
229940088710 antibiotic agent Drugs 0.000 description 3
239000007864 aqueous solution Substances 0.000 description 3
239000003849 aromatic solvent Substances 0.000 description 3
230000003115 biocidal effect Effects 0.000 description 3
230000036765 blood level Effects 0.000 description 3
239000002775 capsule Substances 0.000 description 3
229960002588 cefradine Drugs 0.000 description 3
ZAIPMKNFIOOWCQ-UEKVPHQBSA-N cephalexin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=CC=C1 ZAIPMKNFIOOWCQ-UEKVPHQBSA-N 0.000 description 3
RDLPVSKMFDYCOR-UEKVPHQBSA-N cephradine Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CCC=CC1 RDLPVSKMFDYCOR-UEKVPHQBSA-N 0.000 description 3
238000002425 crystallisation Methods 0.000 description 3
229960004244 cyclacillin Drugs 0.000 description 3
HGBLNBBNRORJKI-WCABBAIRSA-N cyclacillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)C1(N)CCCCC1 HGBLNBBNRORJKI-WCABBAIRSA-N 0.000 description 3
239000002552 dosage form Substances 0.000 description 3
239000003814 drug Substances 0.000 description 3
229960002457 epicillin Drugs 0.000 description 3
RPBAFSBGYDKNRG-NJBDSQKTSA-N epicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CCC=CC1 RPBAFSBGYDKNRG-NJBDSQKTSA-N 0.000 description 3
CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 3
239000010410 layer Substances 0.000 description 3
238000012544 monitoring process Methods 0.000 description 3
238000006386 neutralization reaction Methods 0.000 description 3
229940056367 penicillin v Drugs 0.000 description 3
239000008194 pharmaceutical composition Substances 0.000 description 3
BPLBGHOLXOTWMN-MBNYWOFBSA-N phenoxymethylpenicillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)COC1=CC=CC=C1 BPLBGHOLXOTWMN-MBNYWOFBSA-N 0.000 description 3
239000011541 reaction mixture Substances 0.000 description 3
230000002441 reversible effect Effects 0.000 description 3
229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
229960002317 succinimide Drugs 0.000 description 3
210000001635 urinary tract Anatomy 0.000 description 3
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 3
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XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 description 1
239000002798 polar solvent Substances 0.000 description 1
229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
159000000001 potassium salts Chemical class 0.000 description 1
239000000843 powder Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000001737 promoting effect Effects 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
230000009467 reduction Effects 0.000 description 1
238000010992 reflux Methods 0.000 description 1
230000007017 scission Effects 0.000 description 1
238000006748 scratching Methods 0.000 description 1
230000002393 scratching effect Effects 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
235000017550 sodium carbonate Nutrition 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
239000008279 sol Substances 0.000 description 1
238000001179 sorption measurement Methods 0.000 description 1
UUCCCPNEFXQJEL-UHFFFAOYSA-L strontium dihydroxide Chemical compound [OH-].[OH-].[Sr+2] UUCCCPNEFXQJEL-UHFFFAOYSA-L 0.000 description 1
229910001866 strontium hydroxide Inorganic materials 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
238000010254 subcutaneous injection Methods 0.000 description 1
239000007929 subcutaneous injection Substances 0.000 description 1
230000002195 synergetic effect Effects 0.000 description 1
210000001519 tissue Anatomy 0.000 description 1
125000003944 tolyl group Chemical group 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
125000005490 tosylate group Chemical group 0.000 description 1
ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
JFALSRSLKYAFGM-UHFFFAOYSA-N uranium(0) Chemical compound [U] JFALSRSLKYAFGM-UHFFFAOYSA-N 0.000 description 1
238000007738 vacuum evaporation Methods 0.000 description 1
238000010792 warming Methods 0.000 description 1

Landscapes

Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA000302012A 1977-04-27 1978-04-26 Derives de l'acide clavulanique Expired CA1117948A (fr)

Applications Claiming Priority (8)

Application Number	Priority Date	Filing Date	Title
GB17660/77A GB1603208A (en)	1977-04-27	1977-04-27	Aminodeoxyclavulanic acid and acyl derivatives threreof
GB3283577		1977-08-05
GB43794/77A GB1559356A (en)	1976-10-22	1977-10-20	Display cabinet for deep frozen foodstuffs
GB4739477		1977-11-15
GB47394/77		1977-11-15
GB32835/77		1978-04-18
GB43794/77		1978-04-18
GB17660/77		1978-04-18

Publications (1)

Publication Number	Publication Date
CA1117948A true CA1117948A (fr)	1982-02-09

Family

ID=27448399

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000302012A Expired CA1117948A (fr)	1977-04-27	1978-04-26	Derives de l'acide clavulanique

Country Status (1)

Country	Link
CA (1)	CA1117948A (fr)

1978
- 1978-04-26 CA CA000302012A patent/CA1117948A/fr not_active Expired

Legal Events

Date	Code	Title	Description
1999-02-09	MKEX	Expiry

Publication	Publication Date	Title
US4256638A (en)	1981-03-17	Process for manufacture of 9-amino-9-deoxyclavulanates
US4435565A (en)	1984-03-06	9-Deoxy-9-amino-clavulanate antibacterial agents
US4244965A (en)	1981-01-13	Azetidinoyl ethers
US4258050A (en)	1981-03-24	Antibacterial agents
US4215128A (en)	1980-07-29	Clavulanic acid derivatives their preparation and use
US4228174A (en)	1980-10-14	Clavulanic acid ethers
IE45559B1 (en)	1982-09-22	Lactam antibiotics
US4609495A (en)	1986-09-02	Clavulanic acid ethers as antibacterial agents
EP0002312B1 (fr)	1982-02-03	Dérivés de l'acide clavulanique et compositions pharmaceutiques les contenant
EP0025271B1 (fr)	1984-03-14	Dérivés de l'acide clavulanique, leur préparation et compositions pharmaceutiques les contenant
GB1603208A (en)	1981-11-18	Aminodeoxyclavulanic acid and acyl derivatives threreof
US4571392A (en)	1986-02-18	6-Substituted derivatives of clavulanic acid
CA1149390A (fr)	1983-07-05	Derives d'acide clavulanique; methode pour les preparer, et applications
NZ199200A (en)	1984-07-31	Clavulanic acid derivatives and pharmaceutical compositions
EP0023093B1 (fr)	1983-09-28	Dérivés de l'acide pénicillanique, leur préparation et leurs compositions pharmaceutiques avec une pénicilline ou céphalosporine
EP0008884B1 (fr)	1983-08-17	Dérivés de l'acide clavulanique, un procédé pour leur préparation et leurs compositions
IE46742B1 (en)	1983-09-07	9-aminodeoxyclavulanic acid and acyl derivatives thereof
CA1105467A (fr)	1981-07-21	COMPOSES .beta.-LACTAM, PREPARATION ET UTILISATION
US4427689A (en)	1984-01-24	Clavulanic acid 9-deoxy-9-thia derivatives their preparation and use
EP0027323B1 (fr)	1984-03-14	Dérivés de l'acide clavulanique, procédés pour leur préparation et compositions pharmaceutiques les contenant
IE46100B1 (en)	1983-02-23	Clavulanic acid ethers
EP0021836B1 (fr)	1983-05-11	Dérivés de l'acide clavulanique, procédé pour leur préparation et compositions pharmaceutiques les contenant
GB2052981A (en)	1981-02-04	Penicillanic acid derivatives as beta -lactamase inhibitors
EP0028083B1 (fr)	1984-02-08	Dérivés de l'acide clavulanique, procédé pour leur préparation et compositions pharmaceutiques les contenant
CA1118349A (fr)	1982-02-16	Agent anti-bacterien