SE455702B - 2 beta-klormetyl-2alfa-metylpenam-3alfa-karboxsylsyrasulfon dess salter och fysiologiskt hydrolyserbara estrar med betalaktamasinhiberande verkan, forfarande for framstellning derav samt farmaceutiska kompositioner dera - Google Patents

2 beta-klormetyl-2alfa-metylpenam-3alfa-karboxsylsyrasulfon dess salter och fysiologiskt hydrolyserbara estrar med betalaktamasinhiberande verkan, forfarande for framstellning derav samt farmaceutiska kompositioner dera

Info

Publication number: SE455702B
Authority: SE; Sweden
Prior art keywords: acid; mixture; solution; added; chloromethyl
Prior art date: 1980-01-21

Application number

SE8100339A

Other languages

English (en)

Swedish (sv)

Other versions

SE8100339L (sv

Inventor

W J Gottstein

Original Assignee

Bristol Myers Co

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.)

1980-01-21

Filing date

1981-01-21

Publication date

1988-08-01

1980-12-11 Priority claimed from US06/214,833 external-priority patent/US4340539A/en

1981-01-21 Application filed by Bristol Myers Co filed Critical Bristol Myers Co

1981-09-01 Publication of SE8100339L publication Critical patent/SE8100339L/xx

1988-08-01 Publication of SE455702B publication Critical patent/SE455702B/sv

Links

238000002360 preparation method Methods 0.000 title claims description 13
230000002401 inhibitory effect Effects 0.000 title 1
230000035479 physiological effects, processes and functions Effects 0.000 title 1
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 98
239000000243 solution Substances 0.000 claims description 74
150000001875 compounds Chemical class 0.000 claims description 53
239000002253 acid Substances 0.000 claims description 51
-1 acetoxymethyl Chemical group 0.000 claims description 45
239000007864 aqueous solution Substances 0.000 claims description 33
150000003839 salts Chemical class 0.000 claims description 29
150000002148 esters Chemical class 0.000 claims description 28
238000000034 method Methods 0.000 claims description 19
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 17
239000001257 hydrogen Substances 0.000 claims description 14
229910052739 hydrogen Inorganic materials 0.000 claims description 14
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 13
239000003782 beta lactam antibiotic agent Substances 0.000 claims description 12
238000006243 chemical reaction Methods 0.000 claims description 12
239000002132 β-lactam antibiotic Substances 0.000 claims description 12
229940124586 β-lactam antibiotics Drugs 0.000 claims description 12
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 10
125000000217 alkyl group Chemical group 0.000 claims description 8
102000006635 beta-lactamase Human genes 0.000 claims description 8
239000003054 catalyst Substances 0.000 claims description 8
229910052763 palladium Inorganic materials 0.000 claims description 8
108090000204 Dipeptidase 1 Proteins 0.000 claims description 7
229960000583 acetic acid Drugs 0.000 claims description 7
125000003118 aryl group Chemical group 0.000 claims description 7
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
241000894006 Bacteria Species 0.000 claims description 5
125000003710 aryl alkyl group Chemical group 0.000 claims description 5
238000005984 hydrogenation reaction Methods 0.000 claims description 5
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 4
239000004480 active ingredient Substances 0.000 claims description 4
239000003085 diluting agent Substances 0.000 claims description 4
239000012362 glacial acetic acid Substances 0.000 claims description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
229910052783 alkali metal Inorganic materials 0.000 claims description 3
150000002431 hydrogen Chemical class 0.000 claims description 3
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
229910052751 metal Inorganic materials 0.000 claims description 3
239000002184 metal Substances 0.000 claims description 3
239000003960 organic solvent Substances 0.000 claims description 3
229910052725 zinc Inorganic materials 0.000 claims description 3
239000011701 zinc Substances 0.000 claims description 3
XAKBSHICSHRJCL-UHFFFAOYSA-N [CH2]C(=O)C1=CC=CC=C1 Chemical group [CH2]C(=O)C1=CC=CC=C1 XAKBSHICSHRJCL-UHFFFAOYSA-N 0.000 claims description 2
150000001340 alkali metals Chemical class 0.000 claims description 2
125000004104 aryloxy group Chemical group 0.000 claims description 2
150000004967 organic peroxy acids Chemical class 0.000 claims description 2
150000002978 peroxides Chemical class 0.000 claims description 2
150000004965 peroxy acids Chemical class 0.000 claims description 2
239000008194 pharmaceutical composition Substances 0.000 claims description 2
125000003545 alkoxy group Chemical group 0.000 claims 1
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims 1
230000003647 oxidation Effects 0.000 claims 1
238000007254 oxidation reaction Methods 0.000 claims 1
125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 174
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 95
239000000203 mixture Substances 0.000 description 83
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 70
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 66
239000000047 product Substances 0.000 description 38
238000001914 filtration Methods 0.000 description 36
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical class [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 31
229910052938 sodium sulfate Inorganic materials 0.000 description 28
235000011152 sodium sulphate Nutrition 0.000 description 28
238000003756 stirring Methods 0.000 description 28
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 23
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 23
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 23
239000000706 filtrate Substances 0.000 description 23
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 20
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 18
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 18
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 18
239000007787 solid Substances 0.000 description 18
239000010410 layer Substances 0.000 description 15
229920006395 saturated elastomer Polymers 0.000 description 15
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 14
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 14
238000004458 analytical method Methods 0.000 description 14
150000003462 sulfoxides Chemical class 0.000 description 13
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 12
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical class [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 11
239000011591 potassium Chemical class 0.000 description 11
229910052700 potassium Inorganic materials 0.000 description 11
239000002002 slurry Substances 0.000 description 11
JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 10
238000002844 melting Methods 0.000 description 10
230000008018 melting Effects 0.000 description 10
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 9
229960000723 ampicillin Drugs 0.000 description 9
235000017557 sodium bicarbonate Nutrition 0.000 description 9
229910000030 sodium bicarbonate Inorganic materials 0.000 description 9
239000002904 solvent Substances 0.000 description 9
239000000725 suspension Substances 0.000 description 9
239000013078 crystal Substances 0.000 description 8
238000002329 infrared spectrum Methods 0.000 description 8
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 8
239000000843 powder Substances 0.000 description 8
239000011541 reaction mixture Substances 0.000 description 8
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
229910000147 aluminium phosphate Inorganic materials 0.000 description 7
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 7
229960003022 amoxicillin Drugs 0.000 description 7
239000008346 aqueous phase Substances 0.000 description 7
229910052757 nitrogen Inorganic materials 0.000 description 7
239000012074 organic phase Substances 0.000 description 7
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 7
239000011734 sodium Substances 0.000 description 7
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
239000005909 Kieselgur Substances 0.000 description 6
KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 6
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
150000003863 ammonium salts Chemical class 0.000 description 6
229910052799 carbon Inorganic materials 0.000 description 6
238000000354 decomposition reaction Methods 0.000 description 6
239000002024 ethyl acetate extract Substances 0.000 description 6
239000002244 precipitate Substances 0.000 description 6
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 5
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 5
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 5
229940125898 compound 5 Drugs 0.000 description 5
238000001816 cooling Methods 0.000 description 5
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239000000284 extract Substances 0.000 description 5
239000012071 phase Substances 0.000 description 5
239000012286 potassium permanganate Substances 0.000 description 5
238000001953 recrystallisation Methods 0.000 description 5
238000007790 scraping Methods 0.000 description 5
239000012258 stirred mixture Substances 0.000 description 5
VOLRSQPSJGXRNJ-UHFFFAOYSA-N 4-nitrobenzyl bromide Chemical compound [O-][N+](=O)C1=CC=C(CBr)C=C1 VOLRSQPSJGXRNJ-UHFFFAOYSA-N 0.000 description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
101100298295 Drosophila melanogaster flfl gene Proteins 0.000 description 4
241000588724 Escherichia coli Species 0.000 description 4
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical class 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 4
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
ATTZFSUZZUNHBP-UHFFFAOYSA-N Piperonyl sulfoxide Chemical compound CCCCCCCCS(=O)C(C)CC1=CC=C2OCOC2=C1 ATTZFSUZZUNHBP-UHFFFAOYSA-N 0.000 description 4
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 4
230000000844 anti-bacterial effect Effects 0.000 description 4
TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 4
239000003781 beta lactamase inhibitor Substances 0.000 description 4
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230000036765 blood level Effects 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
GGRHYQCXXYLUTL-UHFFFAOYSA-N chloromethyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OCCl GGRHYQCXXYLUTL-UHFFFAOYSA-N 0.000 description 4
239000012065 filter cake Substances 0.000 description 4
239000000463 material Substances 0.000 description 4
230000007935 neutral effect Effects 0.000 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 description 4
ZUFQCVZBBNZMKD-UHFFFAOYSA-M potassium 2-ethylhexanoate Chemical compound [K+].CCCCC(CC)C([O-])=O ZUFQCVZBBNZMKD-UHFFFAOYSA-M 0.000 description 4
XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 4
238000010992 reflux Methods 0.000 description 4
229910052708 sodium Inorganic materials 0.000 description 4
235000009518 sodium iodide Nutrition 0.000 description 4
VYPDUQYOLCLEGS-UHFFFAOYSA-M sodium;2-ethylhexanoate Chemical compound [Na+].CCCCC(CC)C([O-])=O VYPDUQYOLCLEGS-UHFFFAOYSA-M 0.000 description 4
239000000126 substance Substances 0.000 description 4
238000005406 washing Methods 0.000 description 4
HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 3
238000005160 1H NMR spectroscopy Methods 0.000 description 3
CLMSHAWYULIVFQ-UHFFFAOYSA-N 3-bromo-3h-2-benzofuran-1-one Chemical compound C1=CC=C2C(Br)OC(=O)C2=C1 CLMSHAWYULIVFQ-UHFFFAOYSA-N 0.000 description 3
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 3
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 3
208000035143 Bacterial infection Diseases 0.000 description 3
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 3
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
241000699670 Mus sp. Species 0.000 description 3
238000005481 NMR spectroscopy Methods 0.000 description 3
102100026459 POU domain, class 3, transcription factor 2 Human genes 0.000 description 3
208000022362 bacterial infectious disease Diseases 0.000 description 3
PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 3
MTRNNCLQPVCDLF-UHFFFAOYSA-N benzyl-[2-(benzylazaniumyl)ethyl]azanium;diacetate Chemical compound CC(O)=O.CC(O)=O.C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 MTRNNCLQPVCDLF-UHFFFAOYSA-N 0.000 description 3
238000009835 boiling Methods 0.000 description 3
238000010790 dilution Methods 0.000 description 3
239000012895 dilution Substances 0.000 description 3
230000000694 effects Effects 0.000 description 3
238000001727 in vivo Methods 0.000 description 3
238000001990 intravenous administration Methods 0.000 description 3
229910052943 magnesium sulfate Inorganic materials 0.000 description 3
235000019341 magnesium sulphate Nutrition 0.000 description 3
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 3
239000012044 organic layer Substances 0.000 description 3
239000003208 petroleum Substances 0.000 description 3
QMWWAEFYIXXXQW-UHFFFAOYSA-M potassium;2-[(4-ethoxy-4-oxobut-2-en-2-yl)amino]-2-phenylacetate Chemical compound [K+].CCOC(=O)C=C(C)NC(C([O-])=O)C1=CC=CC=C1 QMWWAEFYIXXXQW-UHFFFAOYSA-M 0.000 description 3
229940002612 prodrug Drugs 0.000 description 3
239000000651 prodrug Substances 0.000 description 3
125000006239 protecting group Chemical group 0.000 description 3
239000000741 silica gel Substances 0.000 description 3
229910002027 silica gel Inorganic materials 0.000 description 3
239000011780 sodium chloride Substances 0.000 description 3
150000003457 sulfones Chemical class 0.000 description 3
239000003826 tablet Substances 0.000 description 3
238000004809 thin layer chromatography Methods 0.000 description 3
108010072897 transcription factor Brn-2 Proteins 0.000 description 3
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WNZQDUSMALZDQF-UHFFFAOYSA-N 2-benzofuran-1(3H)-one Chemical compound C1=CC=C2C(=O)OCC2=C1 WNZQDUSMALZDQF-UHFFFAOYSA-N 0.000 description 2
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241000606124 Bacteroides fragilis Species 0.000 description 2
UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
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235000010005 Catalpa ovata Nutrition 0.000 description 2
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WRQNANDWMGAFTP-UHFFFAOYSA-N Methylacetoacetic acid Chemical compound COC(=O)CC(C)=O WRQNANDWMGAFTP-UHFFFAOYSA-N 0.000 description 2
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
229930182555 Penicillin Natural products 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
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229920005654 Sephadex Polymers 0.000 description 2
239000012507 Sephadex™ Substances 0.000 description 2
DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 2
241000191967 Staphylococcus aureus Species 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
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238000010521 absorption reaction Methods 0.000 description 2
YRKCREAYFQTBPV-UHFFFAOYSA-N acetylacetone Chemical compound CC(=O)CC(C)=O YRKCREAYFQTBPV-UHFFFAOYSA-N 0.000 description 2
150000001412 amines Chemical class 0.000 description 2
239000003242 anti bacterial agent Substances 0.000 description 2
239000006286 aqueous extract Substances 0.000 description 2
239000007900 aqueous suspension Substances 0.000 description 2
230000003115 biocidal effect Effects 0.000 description 2
230000037396 body weight Effects 0.000 description 2
239000000872 buffer Substances 0.000 description 2
239000011575 calcium Chemical class 0.000 description 2
239000001110 calcium chloride Substances 0.000 description 2
229910001628 calcium chloride Inorganic materials 0.000 description 2
239000002775 capsule Substances 0.000 description 2
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
239000000969 carrier Substances 0.000 description 2
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PJGJQVRXEUVAFT-UHFFFAOYSA-N chloroiodomethane Chemical compound ClCI PJGJQVRXEUVAFT-UHFFFAOYSA-N 0.000 description 2
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229940125773 compound 10 Drugs 0.000 description 2
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150000002170 ethers Chemical class 0.000 description 2
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125000005633 phthalidyl group Chemical group 0.000 description 1
SHUZOJHMOBOZST-UHFFFAOYSA-N phylloquinone Natural products CC(C)CCCCC(C)CCC(C)CCCC(=CCC1=C(C)C(=O)c2ccccc2C1=O)C SHUZOJHMOBOZST-UHFFFAOYSA-N 0.000 description 1
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MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
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UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
229910052703 rhodium Inorganic materials 0.000 description 1
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MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
238000000926 separation method Methods 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
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229910001961 silver nitrate Inorganic materials 0.000 description 1
229910001923 silver oxide Inorganic materials 0.000 description 1
URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
239000001509 sodium citrate Substances 0.000 description 1
NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
239000004289 sodium hydrogen sulphite Substances 0.000 description 1
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AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
235000019345 sodium thiosulphate Nutrition 0.000 description 1
MZQCFPABNHFYAT-UHFFFAOYSA-M sodium;propan-2-one;iodide Chemical compound [Na+].[I-].CC(C)=O MZQCFPABNHFYAT-UHFFFAOYSA-M 0.000 description 1
239000011343 solid material Substances 0.000 description 1
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FKENQMMABCRJMK-RITPCOANSA-N sulbactam Chemical compound O=S1(=O)C(C)(C)[C@H](C(O)=O)N2C(=O)C[C@H]21 FKENQMMABCRJMK-RITPCOANSA-N 0.000 description 1
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239000000454 talc Substances 0.000 description 1
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235000012222 talc Nutrition 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; 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)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Steroid Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
Cephalosporin Compounds (AREA)

SE8100339A 1980-01-21 1981-01-21 2 beta-klormetyl-2alfa-metylpenam-3alfa-karboxsylsyrasulfon dess salter och fysiologiskt hydrolyserbara estrar med betalaktamasinhiberande verkan, forfarande for framstellning derav samt farmaceutiska kompositioner dera SE455702B (sv)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
US11389480A	1980-01-21	1980-01-21
US21483180A	1980-12-11	1980-12-11
US06/214,833 US4340539A (en)	1980-01-21	1980-12-11	Derivatives of 6-bromo penicillanic acid

Publications (2)

Publication Number	Publication Date
SE8100339L SE8100339L (sv)	1981-09-01
SE455702B true SE455702B (sv)	1988-08-01

Family

ID=27381401

Family Applications (5)

Application Number	Title	Priority Date	Filing Date
SE8100339A SE455702B (sv)	1980-01-21	1981-01-21	2 beta-klormetyl-2alfa-metylpenam-3alfa-karboxsylsyrasulfon dess salter och fysiologiskt hydrolyserbara estrar med betalaktamasinhiberande verkan, forfarande for framstellning derav samt farmaceutiska kompositioner dera
SE8502286A SE466203B (sv)	1980-01-21	1985-05-08	Estrar foer framstaellning av en beta-laktamas-inhibitor
SE8502285A SE8502285D0 (sv)	1980-01-21	1985-05-08	Antibakteriell komposition
SE9000189A SE9000189L (sv)	1980-01-21	1990-01-19	Estrar foer framstaellning av en beta-laktamasinhibitor
SE9000190A SE9000190L (sv)	1980-01-21	1990-01-19	Ester foer framstaellning av en beta-laktamasinhibitor

Family Applications After (4)

Application Number	Title	Priority Date	Filing Date
SE8502286A SE466203B (sv)	1980-01-21	1985-05-08	Estrar foer framstaellning av en beta-laktamas-inhibitor
SE8502285A SE8502285D0 (sv)	1980-01-21	1985-05-08	Antibakteriell komposition
SE9000189A SE9000189L (sv)	1980-01-21	1990-01-19	Estrar foer framstaellning av en beta-laktamasinhibitor
SE9000190A SE9000190L (sv)	1980-01-21	1990-01-19	Ester foer framstaellning av en beta-laktamasinhibitor

Country Status (12)

Country	Link
KR (1)	KR850001066B1 (fr)
CA (1)	CA1175807A (fr)
CH (2)	CH651571A5 (fr)
DE (1)	DE3101527A1 (fr)
DK (3)	DK162717C (fr)
GB (1)	GB2070592B (fr)
HU (2)	HU184380B (fr)
IL (1)	IL61880A (fr)
NL (1)	NL8100209A (fr)
NO (5)	NO160298C (fr)
OA (1)	OA06748A (fr)
SE (5)	SE455702B (fr)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ZA826687B (en) *	1981-09-14	1983-07-27	Pfizer	Beta-lactamase inhibiting 2-beta-substituted-2-alpha-methyl 5(r)penam-3-alpha-carboxylic acid 1,1-dioxides and intermediates therefor
DE3372068D1 (en) *	1983-09-15	1987-07-23	Bristol Myers Co	Pharmaceutical compositions for treating resistant bacteria including anaerobes
GB2157286B (en) *	1984-04-12	1987-12-31	Leo Pharm Prod Ltd	B-lactam antibiotic potentiators

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE2912511C2 (de) *	1977-06-07	1982-06-24	Pfizer Inc., 10017 New York, N.Y.	Pharmazeutische Zusammensetzung, enthaltend Penicillansäure
IN149747B (fr) *	1977-06-07	1982-04-03	Pfizer
IE49881B1 (en) *	1979-02-13	1986-01-08	Leo Pharm Prod Ltd	B-lactam intermediates
GB2045236A (en) *	1979-03-26	1980-10-29	Hoechst Uk Ltd	Oxapenem derivatives
US4244951A (en) *	1979-05-16	1981-01-13	Pfizer Inc.	Bis-esters of methanediol with penicillins and penicillanic acid 1,1-dioxide

1981
- 1981-01-08 IL IL61880A patent/IL61880A/xx unknown
- 1981-01-15 CA CA000368537A patent/CA1175807A/fr not_active Expired
- 1981-01-16 GB GB8101365A patent/GB2070592B/en not_active Expired
- 1981-01-16 NL NL8100209A patent/NL8100209A/xx not_active Application Discontinuation
- 1981-01-19 DK DK021881A patent/DK162717C/da not_active IP Right Cessation
- 1981-01-19 DE DE19813101527 patent/DE3101527A1/de not_active Withdrawn
- 1981-01-20 NO NO810166A patent/NO160298C/no unknown
- 1981-01-20 HU HU81115A patent/HU184380B/hu not_active IP Right Cessation
- 1981-01-20 HU HU833171A patent/HU188606B/hu not_active IP Right Cessation
- 1981-01-21 CH CH374/81A patent/CH651571A5/de not_active IP Right Cessation
- 1981-01-21 CH CH1284/84A patent/CH649087A5/de not_active IP Right Cessation
- 1981-01-21 SE SE8100339A patent/SE455702B/sv not_active IP Right Cessation
- 1981-02-19 OA OA57331A patent/OA06748A/fr unknown
1984
- 1984-07-21 KR KR1019840004326A patent/KR850001066B1/ko not_active Expired
1985
- 1985-05-08 SE SE8502286A patent/SE466203B/sv not_active IP Right Cessation
- 1985-05-08 SE SE8502285A patent/SE8502285D0/xx not_active Application Discontinuation
- 1985-09-03 NO NO85853450A patent/NO161677C/no unknown
1986
- 1986-05-16 NO NO86861945A patent/NO164299C/no unknown
- 1986-05-16 NO NO86861946A patent/NO164300C/no unknown
- 1986-05-16 NO NO86861944A patent/NO164298C/no unknown
1990
- 1990-01-19 SE SE9000189A patent/SE9000189L/xx not_active Application Discontinuation
- 1990-01-19 SE SE9000190A patent/SE9000190L/xx not_active Application Discontinuation
- 1990-11-30 DK DK285790A patent/DK162769C/da not_active IP Right Cessation
- 1990-11-30 DK DK285890A patent/DK164938C/da not_active IP Right Cessation

Also Published As

Publication number	Publication date
SE466203B (sv)	1992-01-13
SE9000190D0 (sv)	1990-01-19
DK162717B (da)	1991-12-02
NO861944L (no)	1981-07-22
IL61880A (en)	1984-11-30
GB2070592B (en)	1983-05-11
DK285890D0 (da)	1990-11-30
SE8502285L (sv)	1985-05-08
DK162717C (da)	1992-04-21
NO161677B (no)	1989-06-05
NO853450L (no)	1981-07-22
CA1175807A (fr)	1984-10-09
DE3101527A1 (de)	1982-02-18
DK285890A (da)	1990-11-30
DK164938C (da)	1993-02-01
NO160298C (no)	1989-04-05
SE9000189D0 (sv)	1990-01-19
NO861946L (no)	1981-07-22
SE9000190L (sv)	1991-07-20
NO164300C (no)	1990-09-19
NO164298C (no)	1990-09-19
HU184380B (en)	1984-08-28
SE8100339L (sv)	1981-09-01
DK164938B (da)	1992-09-14
SE8502285D0 (sv)	1985-05-08
KR850001066B1 (ko)	1985-07-25
NO164298B (no)	1990-06-11
NL8100209A (nl)	1981-08-17
NO861945L (no)	1981-07-22
CH651571A5 (de)	1985-09-30
DK285790A (da)	1990-11-30
CH649087A5 (de)	1985-04-30
SE8502286D0 (sv)	1985-05-08
OA06748A (fr)	1982-06-30
DK21881A (da)	1981-07-22
SE9000189L (sv)	1991-07-20
NO161677C (no)	1989-09-13
SE8502286L (sv)	1985-05-08
NO160298B (no)	1988-12-27
NO164300B (no)	1990-06-11
KR850001465A (ko)	1985-03-18
DK162769C (da)	1992-04-27
HU188606B (en)	1986-04-28
NO164299B (no)	1990-06-11
NO164299C (no)	1990-09-19
DK285790D0 (da)	1990-11-30
DK162769B (da)	1991-12-09
GB2070592A (en)	1981-09-09
NO810166L (no)	1981-07-22

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1995-01-31

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Publication	Publication Date	Title
CA1230113A (fr)	1987-12-08	Production de composes chimiques
SE449749B (sv)	1987-05-18	Bis-estrar av metandiol med penicilliner och penicillansyra-1,1-dioxid
EP0061313B1 (fr)	1985-01-16	Bis-esters de 1,1-alcane-diols avec le 1,1-dioxyde de l'acide 6-béta-hydroxy-méthylpénicillanique et les antibiotiques bêta-lactames
KR920005829B1 (ko)	1992-07-20	2β-치환된 티오메틸페니실린 유도체 및 그의 염의 제조방법
FR2579597A1 (fr)	1986-10-03	Esters d'alceneamidocephalosporines
SE455702B (sv)	1988-08-01	2 beta-klormetyl-2alfa-metylpenam-3alfa-karboxsylsyrasulfon dess salter och fysiologiskt hydrolyserbara estrar med betalaktamasinhiberande verkan, forfarande for framstellning derav samt farmaceutiska kompositioner dera
SE449103B (sv)	1987-04-06	Sett att framstella penicillansyra-1,1-dioxid samt estrar derav
US4340539A (en)	1982-07-20	Derivatives of 6-bromo penicillanic acid
EP0000645A1 (fr)	1979-02-07	Isopénicillines, procédés pour leur préparation et compositions qui les contiennent
US4380512A (en)	1983-04-19	2β-Chloromethyl-2α-methylpenam-3α-carboxylic acid sulfone and salts and esters thereof
US5321020A (en)	1994-06-14	Antibacterial 2-carbapenem derivatives
JPS61109791A (ja)	1986-05-28	６−（置換）メチレンペニシラン酸および６−（置換）ヒドロキシメチルペニシラン酸およびそれらの誘導体
KR840002214B1 (ko)	1984-12-03	2β-클로로메틸-2α-메틸페남-3α-카르복실산 술폰, 염 또는 그의 에스테르의 제조방법
US4325960A (en)	1982-04-20	6-Amidinopenicillanic acid derivatives including the radical of a β-lactamase inhibitor
US3928336A (en)	1975-12-23	7-{8 D-({60 -amino{60 -phenyl-, 2-thienyl- and 3-thienyl-acetamido){9 -3-(3-methyl-1,2,5-oxadiazol-4-yl)carbonylthiomethyl-3-cephem-4-carboxylic acids
US3316273A (en)	1967-04-25	Penicillin aldehydes
JPS63146886A (ja)	1988-06-18	６−（２−アミノ−２−フェニルアセタミド）ペニシラン酸１，１−ジオキソペニシラノイルオキシメチル製造のための中間体
JPS58128387A (ja)	1983-07-30	新規β−ラクタム化合物およびその製法と用途
CA1175809A (fr)	1984-10-09	2.beta.-CHLOROMETHYL-2.alpha.-METHYLPENAM-3.alpha.-ACIDE CARBOXYLIQUE SULFONE ET SELS, AINSI QUE LEURS ESTERS
US4081441A (en)	1978-03-28	Antibacterial agents
US4502990A (en)	1985-03-05	Process for 6-(aminomethyl)penicillanic acid 1,1-dioxide and derivatives thereof
US4444687A (en)	1984-04-24	2β-Chloromethyl-2α-methylpenam-3α-carboxylic acid sulfone methylene diol mixed esters
KR830001902B1 (ko)	1983-09-19	폐니실란산유도체의 제조방법
US4093807A (en)	1978-06-06	Tricyclic β-lactams
JPH02286681A (ja)	1990-11-26	抗菌性化合物