CA1121821A - COMPOSES CONTENANT DU .beta.-LACTAM, PREPARATION ET UTILISATION - Google Patents

COMPOSES CONTENANT DU .beta.-LACTAM, PREPARATION ET UTILISATION

Info

Publication number: CA1121821A
Authority: CA; Canada
Prior art keywords: clavulanate; ethyl; benzyl; obvious chemical; whenever prepared
Prior art date: 1977-09-16
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

CA000311405A

Other languages

English (en)

Inventor

Brian C. Gasson

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.)

1977-09-16

Filing date

1978-09-15

Publication date

1982-04-13

1978-09-15 Application filed by Beecham Group PLC filed Critical Beecham Group PLC

1982-04-13 Application granted granted Critical

1982-04-13 Publication of CA1121821A publication Critical patent/CA1121821A/fr

Status Expired legal-status Critical Current

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 99
238000002360 preparation method Methods 0.000 title claims abstract description 26
238000000034 method Methods 0.000 claims abstract description 94
230000008569 process Effects 0.000 claims abstract description 90
HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 claims abstract description 55
150000003839 salts Chemical class 0.000 claims abstract description 48
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 47
150000002148 esters Chemical class 0.000 claims abstract description 45
HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical compound OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 claims abstract description 44
229960003324 clavulanic acid Drugs 0.000 claims abstract description 38
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 18
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 18
125000000217 alkyl group Chemical group 0.000 claims abstract description 6
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 6
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 4
101100295741 Gallus gallus COR4 gene Chemical group 0.000 claims abstract 6
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 105
229940090805 clavulanate Drugs 0.000 claims description 95
239000000243 solution Substances 0.000 claims description 81
239000000203 mixture Substances 0.000 claims description 69
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 64
KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 claims description 56
239000000126 substance Substances 0.000 claims description 40
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 32
-1 dimethylaminocarbonyl group Chemical group 0.000 claims description 31
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 30
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 23
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 claims description 22
239000011734 sodium Substances 0.000 claims description 22
229910052708 sodium Inorganic materials 0.000 claims description 22
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 claims description 16
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 14
WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 12
238000006243 chemical reaction Methods 0.000 claims description 12
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical group [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 11
239000007864 aqueous solution Substances 0.000 claims description 11
229910052744 lithium Inorganic materials 0.000 claims description 11
239000003054 catalyst Substances 0.000 claims description 9
238000005984 hydrogenation reaction Methods 0.000 claims description 8
238000001727 in vivo Methods 0.000 claims description 7
239000002253 acid Substances 0.000 claims description 6
229910052784 alkaline earth metal Inorganic materials 0.000 claims description 6
239000002585 base Substances 0.000 claims description 6
125000006281 4-bromobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Br)C([H])([H])* 0.000 claims description 5
125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims description 5
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 5
238000007327 hydrogenolysis reaction Methods 0.000 claims description 5
230000007062 hydrolysis Effects 0.000 claims description 5
238000006460 hydrolysis reaction Methods 0.000 claims description 5
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 4
PFXWAZGPFWJKBF-UHFFFAOYSA-N benzyl aziridine-1-carboxylate Chemical compound C1CN1C(=O)OCC1=CC=CC=C1 PFXWAZGPFWJKBF-UHFFFAOYSA-N 0.000 claims description 4
125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 claims description 4
239000011591 potassium Substances 0.000 claims description 4
229910052700 potassium Inorganic materials 0.000 claims description 4
COGMUSQFBKEIPS-UHFFFAOYSA-N (2,2-dimethylaziridin-1-yl)-phenylmethanone Chemical compound CC1(C)CN1C(=O)C1=CC=CC=C1 COGMUSQFBKEIPS-UHFFFAOYSA-N 0.000 claims description 3
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 3
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
239000003513 alkali Substances 0.000 claims description 3
229910052791 calcium Inorganic materials 0.000 claims description 3
239000011575 calcium Substances 0.000 claims description 3
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 3
159000000003 magnesium salts Chemical class 0.000 claims description 3
125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 3
125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 claims description 3
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 3
YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical class CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 claims description 3
OTIXUSNHAKOJBX-UHFFFAOYSA-N 1-(aziridin-1-yl)ethanone Chemical compound CC(=O)N1CC1 OTIXUSNHAKOJBX-UHFFFAOYSA-N 0.000 claims description 2
HGBCPYMIZWPKMI-UHFFFAOYSA-N aziridin-1-yl(phenyl)methanone Chemical compound C=1C=CC=CC=1C(=O)N1CC1 HGBCPYMIZWPKMI-UHFFFAOYSA-N 0.000 claims description 2
150000001541 aziridines Chemical class 0.000 claims description 2
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
MXZWPNNJPGRZSH-UHFFFAOYSA-N benzyl 2,2-dimethylaziridine-1-carboxylate Chemical compound CC1(C)CN1C(=O)OCC1=CC=CC=C1 MXZWPNNJPGRZSH-UHFFFAOYSA-N 0.000 claims description 2
238000009903 catalytic hydrogenation reaction Methods 0.000 claims description 2
IPZJQDSFZGZEOY-UHFFFAOYSA-N dimethylmethylene Chemical group C[C]C IPZJQDSFZGZEOY-UHFFFAOYSA-N 0.000 claims description 2
159000000001 potassium salts Chemical class 0.000 claims description 2
238000001816 cooling Methods 0.000 claims 14
238000010792 warming Methods 0.000 claims 11
230000003301 hydrolyzing effect Effects 0.000 claims 2
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims 2
PZFRYCITLDECIX-UHFFFAOYSA-N 1-(2,2-dimethylaziridin-1-yl)ethanone Chemical compound CC(=O)N1CC1(C)C PZFRYCITLDECIX-UHFFFAOYSA-N 0.000 claims 1
CFMHHZPHSCJOGO-UHFFFAOYSA-N 1-(aziridin-1-yl)-2-phenylethanone Chemical compound C(C1=CC=CC=C1)C(=O)N1CC1 CFMHHZPHSCJOGO-UHFFFAOYSA-N 0.000 claims 1
235000009434 Actinidia chinensis Nutrition 0.000 claims 1
244000298697 Actinidia deliciosa Species 0.000 claims 1
235000009436 Actinidia deliciosa Nutrition 0.000 claims 1
150000001342 alkaline earth metals Chemical class 0.000 claims 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 1
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims 1
230000002485 urinary effect Effects 0.000 abstract description 6
230000036765 blood level Effects 0.000 abstract description 5
150000002170 ethers Chemical class 0.000 abstract description 4
239000008194 pharmaceutical composition Substances 0.000 abstract description 4
238000011084 recovery Methods 0.000 abstract description 4
230000002401 inhibitory effect Effects 0.000 abstract description 3
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 80
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 34
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 26
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 26
229940093499 ethyl acetate Drugs 0.000 description 25
235000019439 ethyl acetate Nutrition 0.000 description 25
239000012074 organic phase Substances 0.000 description 23
229940073584 methylene chloride Drugs 0.000 description 20
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 19
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
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 19
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 17
229930182555 Penicillin Natural products 0.000 description 17
229960003022 amoxicillin Drugs 0.000 description 17
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 17
235000017557 sodium bicarbonate Nutrition 0.000 description 17
229910000030 sodium bicarbonate Inorganic materials 0.000 description 17
239000012267 brine Substances 0.000 description 16
239000000047 product Substances 0.000 description 16
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 16
101150041968 CDC13 gene Proteins 0.000 description 14
229930186147 Cephalosporin 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
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 14
229940124587 cephalosporin Drugs 0.000 description 14
150000001780 cephalosporins Chemical class 0.000 description 14
229910052943 magnesium sulfate Inorganic materials 0.000 description 13
235000019341 magnesium sulphate Nutrition 0.000 description 13
239000008346 aqueous phase Substances 0.000 description 12
238000004440 column chromatography Methods 0.000 description 12
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 11
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 10
229940049954 penicillin Drugs 0.000 description 10
239000002904 solvent Substances 0.000 description 10
229960000723 ampicillin Drugs 0.000 description 9
208000015181 infectious disease Diseases 0.000 description 9
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
239000007787 solid Substances 0.000 description 8
230000002195 synergetic effect Effects 0.000 description 8
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
150000002960 penicillins Chemical class 0.000 description 7
239000011541 reaction mixture Substances 0.000 description 7
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
229940022663 acetate Drugs 0.000 description 6
WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 6
238000010828 elution Methods 0.000 description 6
238000001704 evaporation Methods 0.000 description 6
230000008020 evaporation Effects 0.000 description 6
239000012065 filter cake Substances 0.000 description 6
239000000706 filtrate Substances 0.000 description 6
DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 6
241000699670 Mus sp. Species 0.000 description 5
238000004458 analytical method Methods 0.000 description 5
YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 5
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
239000003242 anti bacterial agent Substances 0.000 description 4
235000011089 carbon dioxide Nutrition 0.000 description 4
239000003480 eluent Substances 0.000 description 4
125000002485 formyl group Chemical class [H]C(*)=O 0.000 description 4
238000002347 injection Methods 0.000 description 4
239000007924 injection Substances 0.000 description 4
150000002576 ketones Chemical class 0.000 description 4
NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 description 3
229910015900 BF3 Inorganic materials 0.000 description 3
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
101000599862 Homo sapiens Intercellular adhesion molecule 3 Proteins 0.000 description 3
102100037871 Intercellular adhesion molecule 3 Human genes 0.000 description 3
229940088710 antibiotic agent Drugs 0.000 description 3
RBHJBMIOOPYDBQ-UHFFFAOYSA-N carbon dioxide;propan-2-one Chemical compound O=C=O.CC(C)=O RBHJBMIOOPYDBQ-UHFFFAOYSA-N 0.000 description 3
230000000875 corresponding effect Effects 0.000 description 3
239000003814 drug Substances 0.000 description 3
239000003937 drug carrier Substances 0.000 description 3
239000000284 extract Substances 0.000 description 3
229910052739 hydrogen Inorganic materials 0.000 description 3
239000001257 hydrogen Substances 0.000 description 3
229910052763 palladium Inorganic materials 0.000 description 3
238000007920 subcutaneous administration Methods 0.000 description 3
229940124597 therapeutic agent Drugs 0.000 description 3
125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 description 2
241000283690 Bos taurus Species 0.000 description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
241000124008 Mammalia Species 0.000 description 2
241001465754 Metazoa Species 0.000 description 2
229930195708 Penicillin V Natural products 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
230000000844 anti-bacterial effect Effects 0.000 description 2
TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 2
HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 2
229960003669 carbenicillin Drugs 0.000 description 2
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 2
229960004424 carbon dioxide Drugs 0.000 description 2
229950004030 cefaloglycin Drugs 0.000 description 2
FUBBGQLTSCSAON-PBFPGSCMSA-N cefaloglycin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)COC(=O)C)C(O)=O)=CC=CC=C1 FUBBGQLTSCSAON-PBFPGSCMSA-N 0.000 description 2
229960001139 cefazolin Drugs 0.000 description 2
MLYYVTUWGNIJIB-BXKDBHETSA-N cefazolin Chemical class S1C(C)=NN=C1SCC1=C(C(O)=O)N2C(=O)[C@@H](NC(=O)CN3N=NN=C3)[C@H]2SC1 MLYYVTUWGNIJIB-BXKDBHETSA-N 0.000 description 2
229960002588 cefradine Drugs 0.000 description 2
229940106164 cephalexin Drugs 0.000 description 2
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 2
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 2
238000004587 chromatography analysis Methods 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
229960004244 cyclacillin Drugs 0.000 description 2
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 2
230000000994 depressogenic effect Effects 0.000 description 2
229960002457 epicillin Drugs 0.000 description 2
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 2
238000001802 infusion Methods 0.000 description 2
150000002500 ions Chemical class 0.000 description 2
239000007788 liquid Substances 0.000 description 2
229910052749 magnesium Inorganic materials 0.000 description 2
239000011777 magnesium Substances 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
208000004396 mastitis Diseases 0.000 description 2
239000000463 material Substances 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
235000019371 penicillin G benzathine Nutrition 0.000 description 2
229940056360 penicillin g Drugs 0.000 description 2
229940056367 penicillin v Drugs 0.000 description 2
239000012071 phase Substances 0.000 description 2
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 2
125000005633 phthalidyl group Chemical group 0.000 description 2
229960003672 propicillin Drugs 0.000 description 2
HOCWPKXKMNXINF-XQERAMJGSA-N propicillin Chemical compound N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C(O)=O)=O)C(=O)C(CC)OC1=CC=CC=C1 HOCWPKXKMNXINF-XQERAMJGSA-N 0.000 description 2
238000001953 recrystallisation Methods 0.000 description 2
239000008227 sterile water for injection Substances 0.000 description 2
239000012258 stirred mixture Substances 0.000 description 2
229910021653 sulphate ion Inorganic materials 0.000 description 2
229960004659 ticarcillin Drugs 0.000 description 2
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 2
238000001665 trituration Methods 0.000 description 2
238000005406 washing Methods 0.000 description 2
DNXHEGUUPJUMQT-UHFFFAOYSA-N (+)-estrone Natural products OC1=CC=C2C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 DNXHEGUUPJUMQT-UHFFFAOYSA-N 0.000 description 1
FGRJGEWVJCCOJJ-UHFFFAOYSA-N 2,2-dimethylaziridine Chemical compound CC1(C)CN1 FGRJGEWVJCCOJJ-UHFFFAOYSA-N 0.000 description 1
MROVZCRMXJZHCN-UHFFFAOYSA-N 3-[4-(aminomethyl)-6-(trifluoromethyl)pyridin-2-yl]oxy-N-(2-hydroxyethyl)benzamide Chemical compound NCC1=CC(=NC(=C1)C(F)(F)F)OC=1C=C(C(=O)NCCO)C=CC=1 MROVZCRMXJZHCN-UHFFFAOYSA-N 0.000 description 1
208000035143 Bacterial infection Diseases 0.000 description 1
UQLLWWBDSUHNEB-CZUORRHYSA-N Cefaprin Chemical class N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)COC(=O)C)C(O)=O)C(=O)CSC1=CC=NC=C1 UQLLWWBDSUHNEB-CZUORRHYSA-N 0.000 description 1
OPFTUNCRGUEPRZ-QLFBSQMISA-N Cyclohexane Natural products CC(=C)[C@@H]1CC[C@@](C)(C=C)[C@H](C(C)=C)C1 OPFTUNCRGUEPRZ-QLFBSQMISA-N 0.000 description 1
101100096703 Drosophila melanogaster mtSSB gene Proteins 0.000 description 1
241000588724 Escherichia coli Species 0.000 description 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
229960003311 ampicillin trihydrate Drugs 0.000 description 1
208000022362 bacterial infectious disease Diseases 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
230000003115 biocidal effect Effects 0.000 description 1
230000015572 biosynthetic process Effects 0.000 description 1
239000006172 buffering agent Substances 0.000 description 1
239000002775 capsule Substances 0.000 description 1
125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 description 1
229960003972 cefacetrile Drugs 0.000 description 1
RRYMAQUWDLIUPV-BXKDBHETSA-N cefacetrile Chemical class S1CC(COC(=O)C)=C(C(O)=O)N2C(=O)[C@@H](NC(=O)CC#N)[C@@H]12 RRYMAQUWDLIUPV-BXKDBHETSA-N 0.000 description 1
229960003866 cefaloridine Drugs 0.000 description 1
CZTQZXZIADLWOZ-CRAIPNDOSA-N cefaloridine Chemical class O=C([C@@H](NC(=O)CC=1SC=CC=1)[C@H]1SC2)N1C(C(=O)[O-])=C2C[N+]1=CC=CC=C1 CZTQZXZIADLWOZ-CRAIPNDOSA-N 0.000 description 1
229960000603 cefalotin Drugs 0.000 description 1
229960003012 cefamandole Drugs 0.000 description 1
OLVCFLKTBJRLHI-AXAPSJFSSA-N cefamandole Chemical class CN1N=NN=C1SCC1=C(C(O)=O)N2C(=O)[C@@H](NC(=O)[C@H](O)C=3C=CC=CC=3)[C@H]2SC1 OLVCFLKTBJRLHI-AXAPSJFSSA-N 0.000 description 1
229960004350 cefapirin Drugs 0.000 description 1
VUFGUVLLDPOSBC-XRZFDKQNSA-M cephalothin sodium Chemical class [Na+].N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)COC(=O)C)C([O-])=O)C(=O)CC1=CC=CS1 VUFGUVLLDPOSBC-XRZFDKQNSA-M 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
239000003245 coal Substances 0.000 description 1
238000004040 coloring Methods 0.000 description 1
238000006482 condensation reaction Methods 0.000 description 1
239000006071 cream Substances 0.000 description 1
230000009089 cytolysis Effects 0.000 description 1
230000008021 deposition Effects 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
230000000694 effects Effects 0.000 description 1
239000002702 enteric coating Substances 0.000 description 1
238000009505 enteric coating Methods 0.000 description 1
IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
235000019634 flavors Nutrition 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
210000004051 gastric juice Anatomy 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
229960003884 hetacillin Drugs 0.000 description 1
DXVUYOAEDJXBPY-NFFDBFGFSA-N hetacillin Chemical compound C1([C@@H]2C(=O)N(C(N2)(C)C)[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 DXVUYOAEDJXBPY-NFFDBFGFSA-N 0.000 description 1
239000008240 homogeneous mixture Substances 0.000 description 1
238000000338 in vitro Methods 0.000 description 1
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
230000005764 inhibitory process Effects 0.000 description 1
239000007972 injectable composition Substances 0.000 description 1
239000008101 lactose Substances 0.000 description 1
239000000314 lubricant Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
229960003806 metampicillin Drugs 0.000 description 1
FZECHKJQHUVANE-MCYUEQNJSA-N metampicillin Chemical compound C1([C@@H](N=C)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 FZECHKJQHUVANE-MCYUEQNJSA-N 0.000 description 1
229910000510 noble metal Inorganic materials 0.000 description 1
235000014571 nuts Nutrition 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
239000000843 powder Substances 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
210000002345 respiratory system Anatomy 0.000 description 1
210000004872 soft tissue Anatomy 0.000 description 1
239000011343 solid material Substances 0.000 description 1
239000006228 supernatant Substances 0.000 description 1
239000000725 suspension Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
239000003826 tablet Substances 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
238000004809 thin layer chromatography Methods 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
210000001635 urinary tract Anatomy 0.000 description 1
239000008215 water for injection Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D203/00—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom
- C07D203/04—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D203/06—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
- C07D203/16—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with acylated ring nitrogen atoms
- C07D203/20—Heterocyclic compounds containing three-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members with acylated ring nitrogen atoms by carbonic acid, or by sulfur or nitrogen analogues thereof, e.g. carbamates
- 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
- C07D503/00—Heterocyclic compounds containing 4-oxa-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. oxapenicillins, clavulanic acid derivatives; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Life Sciences & Earth Sciences (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Communicable Diseases (AREA)
Pharmacology & Pharmacy (AREA)
Oncology (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 And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Saccharide Compounds (AREA)

CA000311405A 1977-09-16 1978-09-15 COMPOSES CONTENANT DU .beta.-LACTAM, PREPARATION ET UTILISATION Expired CA1121821A (fr)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
GB38649/77		1977-09-16
GB3864977		1977-09-16
GB24047/78		1978-05-30
GB2404778		1978-05-30

Publications (1)

Publication Number	Publication Date
CA1121821A true CA1121821A (fr)	1982-04-13

Family

ID=26256866

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000311405A Expired CA1121821A (fr)	1977-09-16	1978-09-15	COMPOSES CONTENANT DU .beta.-LACTAM, PREPARATION ET UTILISATION

Country Status (19)

Country	Link
JP (1)	JPS5452093A (fr)
AR (1)	AR218504A1 (fr)
AT (1)	ATA664078A (fr)
AU (1)	AU3974778A (fr)
CA (1)	CA1121821A (fr)
CH (1)	CH640536A5 (fr)
DE (1)	DE2839426A1 (fr)
DK (1)	DK410378A (fr)
ES (1)	ES473414A1 (fr)
FI (1)	FI782791A7 (fr)
FR (1)	FR2403343A1 (fr)
GB (1)	GB2004541B (fr)
GR (1)	GR65657B (fr)
IT (1)	IT7851089A0 (fr)
LU (1)	LU80244A1 (fr)
NL (1)	NL7809400A (fr)
NO (1)	NO783132L (fr)
PT (1)	PT68513A (fr)
SE (1)	SE7809747L (fr)

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
IL51267A (en) *	1976-01-31	1979-12-30	Beecham Group Ltd	Clavulanic acid thioethers their preparation and pharmaceutical compositions containing them
GB1587612A (en) *	1976-10-30	1981-04-08	Beecham Group Ltd	Isoclavulanic acid derivatives
GB1595176A (en) *	1976-12-03	1981-08-12	Beecham Group Ltd	Clavulanic acid ethers

1978
- 1978-08-23 GB GB7834334A patent/GB2004541B/en not_active Expired
- 1978-09-05 PT PT68513A patent/PT68513A/pt unknown
- 1978-09-07 AR AR273614A patent/AR218504A1/es active
- 1978-09-11 AU AU39747/78A patent/AU3974778A/en active Pending
- 1978-09-11 GR GR57194A patent/GR65657B/el unknown
- 1978-09-11 DE DE19782839426 patent/DE2839426A1/de not_active Withdrawn
- 1978-09-12 FR FR7826106A patent/FR2403343A1/fr active Granted
- 1978-09-12 FI FI782791A patent/FI782791A7/fi unknown
- 1978-09-14 AT AT0664078A patent/ATA664078A/de not_active Application Discontinuation
- 1978-09-14 JP JP11400778A patent/JPS5452093A/ja active Pending
- 1978-09-14 IT IT7851089A patent/IT7851089A0/it unknown
- 1978-09-15 CA CA000311405A patent/CA1121821A/fr not_active Expired
- 1978-09-15 SE SE7809747A patent/SE7809747L/xx unknown
- 1978-09-15 CH CH967178A patent/CH640536A5/de not_active IP Right Cessation
- 1978-09-15 LU LU80244A patent/LU80244A1/fr unknown
- 1978-09-15 NO NO783132A patent/NO783132L/no unknown
- 1978-09-15 NL NL7809400A patent/NL7809400A/xx not_active Application Discontinuation
- 1978-09-15 DK DK410378A patent/DK410378A/da unknown
- 1978-09-15 ES ES473414A patent/ES473414A1/es not_active Expired

Also Published As

Publication number	Publication date
SE7809747L (sv)	1979-03-17
JPS5452093A (en)	1979-04-24
NO783132L (no)	1979-03-19
FI782791A7 (fi)	1979-03-17
FR2403343A1 (fr)	1979-04-13
CH640536A5 (de)	1984-01-13
LU80244A1 (fr)	1979-03-07
NL7809400A (nl)	1979-03-20
ATA664078A (de)	1982-06-15
AR218504A1 (es)	1980-06-13
ES473414A1 (es)	1979-11-01
PT68513A (en)	1978-10-01
DE2839426A1 (de)	1979-03-29
AU3974778A (en)	1980-03-20
FR2403343B1 (fr)	1980-06-13
GB2004541A (en)	1979-04-04
GB2004541B (en)	1982-05-12
DK410378A (da)	1979-03-17
GR65657B (en)	1980-10-16
IT7851089A0 (it)	1978-09-14

Legal Events

Date	Code	Title	Description
1999-04-13	MKEX	Expiry

Publication	Publication Date	Title
US4526783A (en)	1985-07-02	Antibiotic from S. clavuligerus
US6218380B1 (en)	2001-04-17	Pharmaceutical compositions
US6048977A (en)	2000-04-11	Clavulanic acid and salts thereof
US4529720A (en)	1985-07-16	Antibiotic from Streptomyces clavulicerus
NO802686L (no)	1978-10-24	Fremgangsmaate for fremstilling av en ester av et klavulansyreamin
US4258050A (en)	1981-03-24	Antibacterial agents
US4652560A (en)	1987-03-24	A-deoxy-a-aza derivatives of clavulanic acid, a process for their preparation and their use
EP0055062B1 (fr)	1984-05-23	Composés contenant des bêta-lactames
EP0008884B1 (fr)	1983-08-17	Dérivés de l'acide clavulanique, un procédé pour leur préparation et leurs compositions
EP0002319B1 (fr)	1981-11-18	Dérivés de l'acide clavulanique, procédé pour leur préparation et compositions les contenant
CA1149390A (fr)	1983-07-05	Derives d'acide clavulanique; methode pour les preparer, et applications
US4426389A (en)	1984-01-17	Derivatives of clavulanic acid, a process for their preparation and their use
KR20000076288A (ko)	2000-12-26	항균성 치환 7-아실아미노-3-(메틸히드라조노)메틸-세팔로스포린 및 중간체
US4314941A (en)	1982-02-09	Aminocarbonylmethyl ethers of clavulanic acid, a process for their preparation and use
EP0046596B1 (fr)	1984-06-27	Antibiotique PA-39504-X3, procédé pour sa préparation et compositions pharmaceutiques
NO783132L (no)	1979-03-19	Fremgangsmaate for fremstilling av clavulansyreaminoetere
EP0028083B1 (fr)	1984-02-08	Dérivés de l'acide clavulanique, procédé pour leur préparation et compositions pharmaceutiques les contenant
CA1117948A (fr)	1982-02-09	Derives de l'acide clavulanique
EP0027323B1 (fr)	1984-03-14	Dérivés de l'acide clavulanique, procédés pour leur préparation et compositions pharmaceutiques les contenant
US4539202A (en)	1985-09-03	Derivatives of clavulanic acid, a process for their preparation and their use
US4342749A (en)	1982-08-03	Clavulanic acid derivatives a process for their preparation and their use in pharmaceutical compositions
EP0112685B1 (fr)	1986-04-23	Composés contenant des bêta-lactames
EP0021836B1 (fr)	1983-05-11	Dérivés de l'acide clavulanique, procédé pour leur préparation et compositions pharmaceutiques les contenant
GB1582884A (en)	1981-01-14	Clavulanic acid derivatives their preparation and use
EP0013790B1 (fr)	1982-09-22	Dérivés de l'acide clavulanique, leur préparation et compositions pharmaceutiques les contenant