CA1148085A - Derives de l'acide clavulanique, procede de preparation et utilisation - Google Patents

Derives de l'acide clavulanique, procede de preparation et utilisation

Info

Publication number: CA1148085A
Authority: CA; Canada
Prior art keywords: formula; pharmaceutical composition; beta; carbon atoms; compound
Prior art date: 1978-07-29
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

CA000399886A

Other languages

English (en)

Inventor

Irene Stirling

Brian P. Clarke

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.)

1978-07-29

Filing date

1982-03-30

Publication date

1983-06-14

1979-07-30 Priority claimed from CA000332788A external-priority patent/CA1149390A/fr

1982-03-30 Application filed by Beecham Group PLC filed Critical Beecham Group PLC

1982-03-30 Priority to CA000399886A priority Critical patent/CA1148085A/fr

1983-06-14 Application granted granted Critical

1983-06-14 Publication of CA1148085A publication Critical patent/CA1148085A/fr

Status Expired legal-status Critical Current

Links

238000000034 method Methods 0.000 title description 14
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 description 8
238000002360 preparation method Methods 0.000 title description 5
150000001875 compounds Chemical class 0.000 claims abstract description 95
150000003839 salts Chemical class 0.000 claims abstract description 38
150000002148 esters Chemical class 0.000 claims abstract description 35
239000002253 acid Substances 0.000 claims abstract description 34
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 25
125000000217 alkyl group Chemical group 0.000 claims abstract description 22
229930182555 Penicillin Natural products 0.000 claims abstract description 17
230000002195 synergetic effect Effects 0.000 claims abstract description 17
229930186147 Cephalosporin Natural products 0.000 claims abstract description 15
229940124587 cephalosporin Drugs 0.000 claims abstract description 15
150000001780 cephalosporins Chemical class 0.000 claims abstract description 15
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 15
230000003115 biocidal effect Effects 0.000 claims abstract description 13
125000003545 alkoxy group Chemical group 0.000 claims abstract description 12
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 12
239000000460 chlorine Substances 0.000 claims abstract description 11
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 8
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract description 8
229910052801 chlorine Inorganic materials 0.000 claims abstract description 8
239000011737 fluorine Substances 0.000 claims abstract description 8
229910052731 fluorine Inorganic materials 0.000 claims abstract description 8
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 8
150000002960 penicillins Chemical class 0.000 claims abstract description 8
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 7
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 6
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 6
229910052794 bromium Inorganic materials 0.000 claims abstract description 6
125000003342 alkenyl group Chemical group 0.000 claims abstract description 4
239000003937 drug carrier Substances 0.000 claims abstract description 4
125000004423 acyloxy group Chemical group 0.000 claims abstract description 3
125000000304 alkynyl group Chemical group 0.000 claims abstract description 3
239000000203 mixture Substances 0.000 claims description 67
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 claims description 15
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 claims description 14
229960003022 amoxicillin Drugs 0.000 claims description 11
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 claims 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 claims description 10
229960000723 ampicillin Drugs 0.000 claims description 6
238000002347 injection Methods 0.000 claims description 6
239000007924 injection Substances 0.000 claims description 6
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 claims description 6
229960004659 ticarcillin Drugs 0.000 claims description 6
239000007864 aqueous solution Substances 0.000 claims description 4
229960003866 cefaloridine Drugs 0.000 claims description 4
CZTQZXZIADLWOZ-CRAIPNDOSA-N cefaloridine Chemical compound 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 claims description 4
238000001802 infusion Methods 0.000 claims description 3
235000019371 penicillin G benzathine Nutrition 0.000 claims description 3
229940056360 penicillin g Drugs 0.000 claims description 3
229960003623 azlocillin Drugs 0.000 claims description 2
JTWOMNBEOCYFNV-NFFDBFGFSA-N azlocillin Chemical compound N([C@@H](C(=O)N[C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C=1C=CC=CC=1)C(=O)N1CCNC1=O JTWOMNBEOCYFNV-NFFDBFGFSA-N 0.000 claims description 2
229960001139 cefazolin Drugs 0.000 claims description 2
MLYYVTUWGNIJIB-BXKDBHETSA-N cefazolin Chemical compound 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 claims description 2
229960000198 mezlocillin Drugs 0.000 claims description 2
YPBATNHYBCGSSN-VWPFQQQWSA-N mezlocillin Chemical compound N([C@@H](C(=O)N[C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C=1C=CC=CC=1)C(=O)N1CCN(S(C)(=O)=O)C1=O YPBATNHYBCGSSN-VWPFQQQWSA-N 0.000 claims description 2
150000004684 trihydrates Chemical class 0.000 claims 1
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 80
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 61
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 48
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 37
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical group [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 35
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 32
-1 CH2-C--CH Chemical group 0.000 description 27
239000003921 oil Substances 0.000 description 27
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 20
229940093499 ethyl acetate Drugs 0.000 description 20
235000019439 ethyl acetate Nutrition 0.000 description 20
239000000047 product Substances 0.000 description 18
239000003054 catalyst Substances 0.000 description 17
239000000377 silicon dioxide Substances 0.000 description 16
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 15
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 12
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 12
238000005984 hydrogenation reaction Methods 0.000 description 12
229910052943 magnesium sulfate Inorganic materials 0.000 description 12
239000007787 solid Substances 0.000 description 12
239000000243 solution Substances 0.000 description 12
239000002904 solvent Substances 0.000 description 12
238000006243 chemical reaction Methods 0.000 description 11
229910052681 coesite Inorganic materials 0.000 description 11
229910052906 cristobalite Inorganic materials 0.000 description 11
WACQKHWOTAEEFS-UHFFFAOYSA-N cyclohexane;ethyl acetate Chemical compound CCOC(C)=O.C1CCCCC1 WACQKHWOTAEEFS-UHFFFAOYSA-N 0.000 description 11
229910052682 stishovite Inorganic materials 0.000 description 11
229910052905 tridymite Inorganic materials 0.000 description 11
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
235000012239 silicon dioxide Nutrition 0.000 description 10
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
238000007792 addition Methods 0.000 description 9
229910052763 palladium Inorganic materials 0.000 description 9
229940049954 penicillin Drugs 0.000 description 9
101150041968 CDC13 gene Proteins 0.000 description 8
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
239000001257 hydrogen Substances 0.000 description 8
229910052739 hydrogen Inorganic materials 0.000 description 8
239000011541 reaction mixture Substances 0.000 description 8
239000007921 spray Substances 0.000 description 8
HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 description 7
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 7
229940090805 clavulanate Drugs 0.000 description 7
238000001514 detection method Methods 0.000 description 7
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
239000000706 filtrate Substances 0.000 description 6
208000015181 infectious disease Diseases 0.000 description 6
235000019341 magnesium sulphate Nutrition 0.000 description 6
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
150000001412 amines Chemical class 0.000 description 5
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 5
229960003669 carbenicillin Drugs 0.000 description 5
229960003324 clavulanic acid Drugs 0.000 description 5
238000001704 evaporation Methods 0.000 description 5
239000012286 potassium permanganate Substances 0.000 description 5
238000005406 washing Methods 0.000 description 5
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
239000001913 cellulose Substances 0.000 description 4
229920002678 cellulose Polymers 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
239000013078 crystal Substances 0.000 description 4
230000008020 evaporation Effects 0.000 description 4
238000001914 filtration Methods 0.000 description 4
239000012458 free base Substances 0.000 description 4
229960004592 isopropanol Drugs 0.000 description 4
239000010410 layer Substances 0.000 description 4
125000005394 methallyl group Chemical group 0.000 description 4
239000012074 organic phase Substances 0.000 description 4
239000003960 organic solvent Substances 0.000 description 4
229940002612 prodrug Drugs 0.000 description 4
239000000651 prodrug Substances 0.000 description 4
LJXPWUAAAAXJBX-UHFFFAOYSA-N 2-methylallyl radical Chemical compound [CH2]C(C)=C LJXPWUAAAAXJBX-UHFFFAOYSA-N 0.000 description 3
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 3
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
241000283690 Bos taurus Species 0.000 description 3
241000588724 Escherichia coli Species 0.000 description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
239000012267 brine Substances 0.000 description 3
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
238000004440 column chromatography Methods 0.000 description 3
238000001035 drying Methods 0.000 description 3
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
238000007327 hydrogenolysis reaction Methods 0.000 description 3
238000001727 in vivo Methods 0.000 description 3
239000000543 intermediate Substances 0.000 description 3
208000004396 mastitis Diseases 0.000 description 3
239000000463 material Substances 0.000 description 3
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
159000000000 sodium salts Chemical class 0.000 description 3
239000008223 sterile water Substances 0.000 description 3
238000003756 stirring Methods 0.000 description 3
238000001665 trituration Methods 0.000 description 3
LDCWGVLBCJEQMT-UHFFFAOYSA-N 2-methyl-n-(2-methylprop-2-enyl)prop-2-en-1-amine Chemical compound CC(=C)CNCC(C)=C LDCWGVLBCJEQMT-UHFFFAOYSA-N 0.000 description 2
KDSNLYIMUZNERS-UHFFFAOYSA-N 2-methylpropanamine Chemical compound CC(C)CN KDSNLYIMUZNERS-UHFFFAOYSA-N 0.000 description 2
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 2
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 2
101000599862 Homo sapiens Intercellular adhesion molecule 3 Proteins 0.000 description 2
102100037871 Intercellular adhesion molecule 3 Human genes 0.000 description 2
241000124008 Mammalia Species 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
XAKBSHICSHRJCL-UHFFFAOYSA-N [CH2]C(=O)C1=CC=CC=C1 Chemical class [CH2]C(=O)C1=CC=CC=C1 XAKBSHICSHRJCL-UHFFFAOYSA-N 0.000 description 2
229960003311 ampicillin trihydrate Drugs 0.000 description 2
239000003242 anti bacterial agent Substances 0.000 description 2
125000004429 atom Chemical group 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
230000036765 blood level Effects 0.000 description 2
DADQTDAEJJZHDV-UHFFFAOYSA-N butan-1-ol;propan-2-ol;hydrate Chemical compound O.CC(C)O.CCCCO DADQTDAEJJZHDV-UHFFFAOYSA-N 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
238000009833 condensation Methods 0.000 description 2
230000005494 condensation Effects 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
FBCCMZVIWNDFMO-UHFFFAOYSA-N dichloroacetyl chloride Chemical compound ClC(Cl)C(Cl)=O FBCCMZVIWNDFMO-UHFFFAOYSA-N 0.000 description 2
239000003814 drug Substances 0.000 description 2
238000010828 elution Methods 0.000 description 2
125000000219 ethylidene group Chemical group [H]C(=[*])C([H])([H])[H] 0.000 description 2
210000001035 gastrointestinal tract Anatomy 0.000 description 2
229960003884 hetacillin Drugs 0.000 description 2
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 2
150000002431 hydrogen Chemical class 0.000 description 2
239000007972 injectable composition Substances 0.000 description 2
238000005342 ion exchange Methods 0.000 description 2
150000002500 ions Chemical class 0.000 description 2
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
150000002576 ketones Chemical class 0.000 description 2
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 2
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
125000006502 nitrobenzyl group Chemical group 0.000 description 2
239000012044 organic layer Substances 0.000 description 2
238000007911 parenteral administration Methods 0.000 description 2
125000005633 phthalidyl group Chemical group 0.000 description 2
229910052700 potassium Inorganic materials 0.000 description 2
239000011591 potassium Substances 0.000 description 2
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
210000002345 respiratory system Anatomy 0.000 description 2
239000012047 saturated solution Substances 0.000 description 2
239000000741 silica gel Substances 0.000 description 2
229910002027 silica gel Inorganic materials 0.000 description 2
229960001866 silicon dioxide Drugs 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
239000011734 sodium Substances 0.000 description 2
239000011780 sodium chloride Substances 0.000 description 2
238000001228 spectrum Methods 0.000 description 2
238000007920 subcutaneous administration Methods 0.000 description 2
229940124597 therapeutic agent Drugs 0.000 description 2
238000011200 topical administration Methods 0.000 description 2
WRFCGBVLTRJBKN-QSNWEANLSA-N (2s,5r,6r)-6-[[(2r)-2-[[2-[[amino(pyridin-4-yl)methylidene]amino]acetyl]amino]-2-phenylacetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound N([C@@H](C(=O)N[C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C=1C=CC=CC=1)C(=O)CN=C(N)C1=CC=NC=C1 WRFCGBVLTRJBKN-QSNWEANLSA-N 0.000 description 1
SBUCDZYLTRYMFG-PBFPGSCMSA-N (6r,7r)-7-[[(2r)-2-amino-2-(4-hydroxyphenyl)acetyl]amino]-3-[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound S1C(C)=NN=C1SCC1=C(C(O)=O)N2C(=O)[C@@H](NC(=O)[C@H](N)C=3C=CC(O)=CC=3)[C@H]2SC1 SBUCDZYLTRYMFG-PBFPGSCMSA-N 0.000 description 1
125000002030 1,2-phenylene group Chemical group [H]C1=C([H])C([*:1])=C([*:2])C([H])=C1[H] 0.000 description 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
DQECFVGMGBQCPA-GLCLSGQWSA-N 2,2-dimethylpropanoyloxymethyl (2s,5r,6r)-6-[[(2r)-2-amino-2-phenylacetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate;hydron;chloride Chemical compound Cl.C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)[C@H](C(S3)(C)C)C(=O)OCOC(=O)C(C)(C)C)=CC=CC=C1 DQECFVGMGBQCPA-GLCLSGQWSA-N 0.000 description 1
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
ONPGOSVDVDPBCY-CQSZACIVSA-N 6-amino-5-[(1r)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-n-[4-(4-methylpiperazine-1-carbonyl)phenyl]pyridazine-3-carboxamide Chemical compound O([C@H](C)C=1C(=C(F)C=CC=1Cl)Cl)C(C(=NN=1)N)=CC=1C(=O)NC(C=C1)=CC=C1C(=O)N1CCN(C)CC1 ONPGOSVDVDPBCY-CQSZACIVSA-N 0.000 description 1
208000035143 Bacterial infection Diseases 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
102100038916 Caspase-5 Human genes 0.000 description 1
UQLLWWBDSUHNEB-CZUORRHYSA-N Cefaprin Chemical compound 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
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
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229960002457 epicillin Drugs 0.000 description 1
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JBTWLSYIZRCDFO-UHFFFAOYSA-N ethyl methyl carbonate Chemical compound CCOC(=O)OC JBTWLSYIZRCDFO-UHFFFAOYSA-N 0.000 description 1
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150000004820 halides Chemical class 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
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
125000002768 hydroxyalkyl group Chemical group 0.000 description 1
239000012535 impurity Substances 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
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INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
239000007788 liquid Substances 0.000 description 1
229910003002 lithium salt Inorganic materials 0.000 description 1
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210000005075 mammary gland Anatomy 0.000 description 1
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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
150000007522 mineralic acids Chemical class 0.000 description 1
ZELJLECFTLYULH-UHFFFAOYSA-N n-benzyl-2-methylpropan-1-amine Chemical compound CC(C)CNCC1=CC=CC=C1 ZELJLECFTLYULH-UHFFFAOYSA-N 0.000 description 1
238000006386 neutralization reaction Methods 0.000 description 1
230000003472 neutralizing effect Effects 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
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239000012454 non-polar solvent Substances 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
125000000962 organic group Chemical group 0.000 description 1
229950004791 pirbenicillin Drugs 0.000 description 1
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239000003495 polar organic solvent Substances 0.000 description 1
239000004175 ponceau 4R Substances 0.000 description 1
239000000843 powder Substances 0.000 description 1
230000001376 precipitating effect Effects 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
230000001737 promoting effect Effects 0.000 description 1
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 1
229960003672 propicillin Drugs 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
208000020029 respiratory tract infectious disease Diseases 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000009518 sodium iodide Nutrition 0.000 description 1
PAYGMRRPBHYIMA-UHFFFAOYSA-N sodium;trihydrate Chemical compound O.O.O.[Na] PAYGMRRPBHYIMA-UHFFFAOYSA-N 0.000 description 1
210000004872 soft tissue Anatomy 0.000 description 1
238000001179 sorption measurement Methods 0.000 description 1
230000003595 spectral effect Effects 0.000 description 1
239000000126 substance Substances 0.000 description 1
229910021653 sulphate ion Inorganic materials 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
239000003826 tablet Substances 0.000 description 1
229960002780 talampicillin Drugs 0.000 description 1
SOROUYSPFADXSN-SUWVAFIASA-N talampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(=O)OC2C3=CC=CC=C3C(=O)O2)(C)C)=CC=CC=C1 SOROUYSPFADXSN-SUWVAFIASA-N 0.000 description 1
125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
229910052723 transition metal Inorganic materials 0.000 description 1
150000003624 transition metals Chemical class 0.000 description 1
210000001635 urinary tract Anatomy 0.000 description 1
208000019206 urinary tract infection Diseases 0.000 description 1
239000008215 water for injection Substances 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1

Landscapes

Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA000399886A 1978-07-29 1982-03-30 Derives de l'acide clavulanique, procede de preparation et utilisation Expired CA1148085A (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA000399886A CA1148085A (fr)	1978-07-29	1982-03-30	Derives de l'acide clavulanique, procede de preparation et utilisation

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
GB31624/78		1978-07-29
GB7831624		1978-07-29
CA000332788A CA1149390A (fr)	1978-07-29	1979-07-30	Derives d'acide clavulanique; methode pour les preparer, et applications
CA000399886A CA1148085A (fr)	1978-07-29	1982-03-30	Derives de l'acide clavulanique, procede de preparation et utilisation

Publications (1)

Publication Number	Publication Date
CA1148085A true CA1148085A (fr)	1983-06-14

Family

ID=27166347

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000399886A Expired CA1148085A (fr)	1978-07-29	1982-03-30	Derives de l'acide clavulanique, procede de preparation et utilisation

Country Status (1)

Country	Link
CA (1)	CA1148085A (fr)

1982
- 1982-03-30 CA CA000399886A patent/CA1148085A/fr not_active Expired

Legal Events

Date	Code	Title	Description
2000-06-14	MKEX	Expiry

Publication	Publication Date	Title
US4438101A (en)	1984-03-20	Antibiotics
IE46623B1 (en)	1983-08-10	N-monosubstituted-9-amino-9-deoxyclavulanic acid derivatives
US4426377A (en)	1984-01-17	Clavulanic acid derivatives their preparation and use
CA1148085A (fr)	1983-06-14	Derives de l'acide clavulanique, procede de preparation et utilisation
US4444754A (en)	1984-04-24	Derivatives of clavulanic acid, a process for their preparation and their use
IE45559B1 (en)	1982-09-22	Lactam antibiotics
US4258050A (en)	1981-03-24	Antibacterial agents
CA1167042A (fr)	1984-05-08	COMPOSES RENFERMANT DES .beta.-LACTAMES
CA1149390A (fr)	1983-07-05	Derives d'acide clavulanique; methode pour les preparer, et applications
CA1117532A (fr)	1982-02-02	Obtention et emploi de derives de l'acide clavulanique
US4426389A (en)	1984-01-17	Derivatives of clavulanic acid, a process for their preparation and their use
EP0008884B1 (fr)	1983-08-17	Dérivés de l'acide clavulanique, un procédé pour leur préparation et leurs compositions
US4388300A (en)	1983-06-14	Clavulanic acid derivatives, a process for their preparation and their use in pharmaceutical compositions
EP0021836B1 (fr)	1983-05-11	Dérivés de l'acide clavulanique, procédé pour leur préparation et compositions pharmaceutiques les contenant
CA1132548A (fr)	1982-09-28	Derives de l'acide clavulanique; methode pour les preparer et leur utilisation
EP0027323B1 (fr)	1984-03-14	Dérivés de l'acide clavulanique, procédés pour leur préparation et compositions pharmaceutiques les contenant
US4242262A (en)	1980-12-30	9-Nitromethyldeoxyclavulanic acid derivatives preparation and compositions
US4427689A (en)	1984-01-24	Clavulanic acid 9-deoxy-9-thia derivatives their preparation and use
US4342749A (en)	1982-08-03	Clavulanic acid derivatives a process for their preparation and their use in pharmaceutical compositions
US4359473A (en)	1982-11-16	α-Amino deoxy clavulanic acid antibacterial agents
US4145430A (en)	1979-03-20	Beta-lactam compounds, preparation and use
EP0023093B1 (fr)	1983-09-28	Dérivés de l'acide pénicillanique, leur préparation et leurs compositions pharmaceutiques avec une pénicilline ou céphalosporine
CA1118349A (fr)	1982-02-16	Agent anti-bacterien
US4314941A (en)	1982-02-09	Aminocarbonylmethyl ethers of clavulanic acid, a process for their preparation and use
EP0112685A1 (fr)	1984-07-04	Composés contenant des bêta-lactames