CA1076120A - Esters de l'acide clavulanique - Google Patents

Esters de l'acide clavulanique

Info

Publication number: CA1076120A
Authority: CA; Canada
Prior art keywords: clavulanate; clavulanic acid; ester; methyl; recovering
Prior art date: 1974-04-20
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

CA314,882A

Other languages

English (en)

Inventor

Martin Cole

Thomas T. Howarth

Christopher Reading

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.)

1974-04-20

Filing date

1978-10-30

Publication date

1980-04-22

1974-04-20 Priority claimed from GB17410/74A external-priority patent/GB1508977A/en

1975-04-18 Priority claimed from CA224,970A external-priority patent/CA1059050A/fr

1978-10-30 Application filed by Beecham Group PLC filed Critical Beecham Group PLC

1978-10-30 Priority to CA314,882A priority Critical patent/CA1076120A/fr

1980-04-22 Application granted granted Critical

1980-04-22 Publication of CA1076120A publication Critical patent/CA1076120A/fr

Status Expired legal-status Critical Current

Links

HZZVJAQRINQKSD-PBFISZAISA-N clavulanic acid Chemical class OC(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 HZZVJAQRINQKSD-PBFISZAISA-N 0.000 title claims abstract description 197
HZZVJAQRINQKSD-UHFFFAOYSA-N Clavulanic acid Natural products OC(=O)C1C(=CCO)OC2CC(=O)N21 HZZVJAQRINQKSD-UHFFFAOYSA-N 0.000 claims abstract description 212
229960003324 clavulanic acid Drugs 0.000 claims abstract description 178
150000002148 esters Chemical class 0.000 claims abstract description 86
150000003839 salts Chemical class 0.000 claims abstract description 76
150000001875 compounds Chemical class 0.000 claims abstract description 26
241000187433 Streptomyces clavuligerus Species 0.000 claims abstract description 19
238000000034 method Methods 0.000 claims description 88
-1 methoxyphenyl Chemical group 0.000 claims description 84
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 68
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 64
238000002360 preparation method Methods 0.000 claims description 55
230000008569 process Effects 0.000 claims description 52
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 49
238000006243 chemical reaction Methods 0.000 claims description 37
239000002904 solvent Substances 0.000 claims description 35
229940090805 clavulanate Drugs 0.000 claims description 34
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 24
239000000126 substance Substances 0.000 claims description 22
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
WOGMLDNCNBLDCA-JSYANWSFSA-M sodium;(2r,3z,5r)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]heptane-2-carboxylate Chemical compound [Na+].[O-]C(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 WOGMLDNCNBLDCA-JSYANWSFSA-M 0.000 claims description 20
239000003795 chemical substances by application Substances 0.000 claims description 18
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical group CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 17
125000004432 carbon atom Chemical group C* 0.000 claims description 17
125000000217 alkyl group Chemical group 0.000 claims description 16
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 15
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 15
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 14
AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 claims description 14
239000011734 sodium Substances 0.000 claims description 14
125000003944 tolyl group Chemical group 0.000 claims description 14
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 13
125000000068 chlorophenyl group Chemical group 0.000 claims description 13
229910052708 sodium Inorganic materials 0.000 claims description 13
125000003710 aryl alkyl group Chemical group 0.000 claims description 11
125000006501 nitrophenyl group Chemical group 0.000 claims description 11
239000003960 organic solvent Substances 0.000 claims description 11
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 9
229910052760 oxygen Inorganic materials 0.000 claims description 9
239000011541 reaction mixture Substances 0.000 claims description 9
239000012442 inert solvent Substances 0.000 claims description 8
150000004702 methyl esters Chemical class 0.000 claims description 8
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 7
125000003545 alkoxy group Chemical group 0.000 claims description 7
125000003118 aryl group Chemical group 0.000 claims description 7
229910052736 halogen Inorganic materials 0.000 claims description 7
150000002367 halogens Chemical group 0.000 claims description 7
GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical group [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 claims description 7
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 7
239000000460 chlorine Substances 0.000 claims description 6
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 5
125000000962 organic group Chemical group 0.000 claims description 5
229910052717 sulfur Inorganic materials 0.000 claims description 5
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
150000001718 carbodiimides Chemical class 0.000 claims description 4
229910052801 chlorine Inorganic materials 0.000 claims description 4
238000010438 heat treatment Methods 0.000 claims description 4
125000003342 alkenyl group Chemical group 0.000 claims description 3
125000000304 alkynyl group Chemical group 0.000 claims description 3
229910052794 bromium Inorganic materials 0.000 claims description 3
229960004132 diethyl ether Drugs 0.000 claims description 3
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 3
OGSJMFCWOUHXHN-UHFFFAOYSA-N 1-iodononane Chemical compound CCCCCCCCCI OGSJMFCWOUHXHN-UHFFFAOYSA-N 0.000 claims description 2
LJCZNYWLQZZIOS-UHFFFAOYSA-N 2,2,2-trichlorethoxycarbonyl chloride Chemical compound ClC(=O)OCC(Cl)(Cl)Cl LJCZNYWLQZZIOS-UHFFFAOYSA-N 0.000 claims description 2
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 claims description 2
VOLRSQPSJGXRNJ-UHFFFAOYSA-N 4-nitrobenzyl bromide Chemical compound [O-][N+](=O)C1=CC=C(CBr)C=C1 VOLRSQPSJGXRNJ-UHFFFAOYSA-N 0.000 claims description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 claims description 2
ACBDNFPUXYGKPT-UHFFFAOYSA-N bromomethyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OCBr ACBDNFPUXYGKPT-UHFFFAOYSA-N 0.000 claims description 2
125000004185 ester group Chemical group 0.000 claims description 2
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 claims description 2
125000001183 hydrocarbyl group Chemical group 0.000 claims 5
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 claims 2
JMRXTGCDVQLAFM-JSYANWSFSA-M lithium;(2r,3z,5r)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]heptane-2-carboxylate Chemical compound [Li+].[O-]C(=O)[C@H]1C(=C/CO)/O[C@@H]2CC(=O)N21 JMRXTGCDVQLAFM-JSYANWSFSA-M 0.000 claims 1
HNPPKZRZKDKXDO-UHFFFAOYSA-N n,n-dimethylformamide;propan-2-one Chemical group CC(C)=O.CN(C)C=O HNPPKZRZKDKXDO-UHFFFAOYSA-N 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
125000002130 sulfonic acid ester group Chemical group 0.000 claims 1
230000003115 biocidal effect Effects 0.000 abstract description 8
241000894006 Bacteria Species 0.000 abstract description 6
239000003782 beta lactam antibiotic agent Substances 0.000 abstract description 3
239000013543 active substance Substances 0.000 abstract 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 73
239000002253 acid Substances 0.000 description 63
239000000203 mixture Substances 0.000 description 50
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 47
239000002609 medium Substances 0.000 description 46
239000000706 filtrate Substances 0.000 description 44
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 38
238000003556 assay Methods 0.000 description 36
239000000243 solution Substances 0.000 description 34
230000005764 inhibitory process Effects 0.000 description 33
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 31
235000019441 ethanol Nutrition 0.000 description 31
239000007787 solid Substances 0.000 description 30
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 29
230000000844 anti-bacterial effect Effects 0.000 description 28
230000002401 inhibitory effect Effects 0.000 description 28
239000000741 silica gel Substances 0.000 description 28
229910002027 silica gel Inorganic materials 0.000 description 28
229960000723 ampicillin Drugs 0.000 description 25
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 24
229940093499 ethyl acetate Drugs 0.000 description 24
235000019439 ethyl acetate Nutrition 0.000 description 24
229930182555 Penicillin Natural products 0.000 description 23
230000000694 effects Effects 0.000 description 22
239000003921 oil Substances 0.000 description 21
235000019198 oils Nutrition 0.000 description 21
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 20
239000011780 sodium chloride Substances 0.000 description 19
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 17
238000010790 dilution Methods 0.000 description 17
239000012895 dilution Substances 0.000 description 17
159000000000 sodium salts Chemical class 0.000 description 17
229930186147 Cephalosporin Natural products 0.000 description 16
229940124587 cephalosporin Drugs 0.000 description 16
150000001780 cephalosporins Chemical class 0.000 description 16
239000003153 chemical reaction reagent Substances 0.000 description 15
239000012071 phase Substances 0.000 description 15
239000011347 resin Substances 0.000 description 15
229920005989 resin Polymers 0.000 description 15
150000002960 penicillins Chemical class 0.000 description 14
239000007921 spray Substances 0.000 description 14
244000068988 Glycine max Species 0.000 description 12
235000010469 Glycine max Nutrition 0.000 description 12
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
239000000284 extract Substances 0.000 description 12
235000019371 penicillin G benzathine Nutrition 0.000 description 12
241000588724 Escherichia coli Species 0.000 description 11
238000000855 fermentation Methods 0.000 description 11
230000004151 fermentation Effects 0.000 description 11
229940056360 penicillin g Drugs 0.000 description 11
VWDWKYIASSYTQR-UHFFFAOYSA-N sodium nitrate Chemical compound [Na+].[O-][N+]([O-])=O VWDWKYIASSYTQR-UHFFFAOYSA-N 0.000 description 11
238000012360 testing method Methods 0.000 description 11
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 10
108090000790 Enzymes Proteins 0.000 description 10
102000004190 Enzymes Human genes 0.000 description 10
239000008367 deionised water Substances 0.000 description 10
125000004435 hydrogen atom Chemical group [H]* 0.000 description 10
239000007788 liquid Substances 0.000 description 10
239000000463 material Substances 0.000 description 10
239000000725 suspension Substances 0.000 description 10
PKDBCJSWQUOKDO-UHFFFAOYSA-M 2,3,5-triphenyltetrazolium chloride Chemical compound [Cl-].C1=CC=CC=C1C(N=[N+]1C=2C=CC=CC=2)=NN1C1=CC=CC=C1 PKDBCJSWQUOKDO-UHFFFAOYSA-M 0.000 description 9
241000191967 Staphylococcus aureus Species 0.000 description 9
241000187747 Streptomyces Species 0.000 description 9
229960003866 cefaloridine Drugs 0.000 description 9
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 description 9
238000000605 extraction Methods 0.000 description 9
230000012010 growth Effects 0.000 description 9
239000003112 inhibitor Substances 0.000 description 9
229940049954 penicillin Drugs 0.000 description 9
239000000047 product Substances 0.000 description 9
229920001817 Agar Polymers 0.000 description 8
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
241000588915 Klebsiella aerogenes Species 0.000 description 8
RVGRUAULSDPKGF-UHFFFAOYSA-N Poloxamer Chemical compound C1CO1.CC1CO1 RVGRUAULSDPKGF-UHFFFAOYSA-N 0.000 description 8
239000008272 agar Substances 0.000 description 8
210000000078 claw Anatomy 0.000 description 8
230000007062 hydrolysis Effects 0.000 description 8
238000006460 hydrolysis reaction Methods 0.000 description 8
238000004519 manufacturing process Methods 0.000 description 8
239000008363 phosphate buffer Substances 0.000 description 8
238000005507 spraying Methods 0.000 description 8
229910001220 stainless steel Inorganic materials 0.000 description 8
239000010935 stainless steel Substances 0.000 description 8
238000004809 thin layer chromatography Methods 0.000 description 8
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical class [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 7
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 7
238000005119 centrifugation Methods 0.000 description 7
239000002054 inoculum Substances 0.000 description 7
HTABQNQMGKGBDT-NDFJAXRBSA-N methyl (2r,3z,5r)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]heptane-2-carboxylate Chemical compound O1\C(=C/CO)[C@H](C(=O)OC)N2C(=O)C[C@H]21 HTABQNQMGKGBDT-NDFJAXRBSA-N 0.000 description 7
230000002829 reductive effect Effects 0.000 description 7
NOJNFULGOQGBKB-UHFFFAOYSA-M sodium;3-[3-tert-butylsulfanyl-1-[[4-(6-ethoxypyridin-3-yl)phenyl]methyl]-5-[(5-methylpyridin-2-yl)methoxy]indol-2-yl]-2,2-dimethylpropanoate Chemical compound [Na+].C1=NC(OCC)=CC=C1C(C=C1)=CC=C1CN1C2=CC=C(OCC=3N=CC(C)=CC=3)C=C2C(SC(C)(C)C)=C1CC(C)(C)C([O-])=O NOJNFULGOQGBKB-UHFFFAOYSA-M 0.000 description 7
150000003573 thiols Chemical class 0.000 description 7
229910052721 tungsten Inorganic materials 0.000 description 7
101150041968 CDC13 gene Proteins 0.000 description 6
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
238000010521 absorption reaction Methods 0.000 description 6
229960003022 amoxicillin Drugs 0.000 description 6
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 6
239000003242 anti bacterial agent Substances 0.000 description 6
239000008346 aqueous phase Substances 0.000 description 6
230000001580 bacterial effect Effects 0.000 description 6
229910052799 carbon Inorganic materials 0.000 description 6
238000009833 condensation Methods 0.000 description 6
239000000499 gel Substances 0.000 description 6
239000008103 glucose Substances 0.000 description 6
208000015181 infectious disease Diseases 0.000 description 6
238000002955 isolation Methods 0.000 description 6
238000000746 purification Methods 0.000 description 6
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
239000004375 Dextrin Substances 0.000 description 5
229920001353 Dextrin Polymers 0.000 description 5
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 5
229940123930 Lactamase inhibitor Drugs 0.000 description 5
241000212749 Zesius chrysomallus Species 0.000 description 5
239000003957 anion exchange resin Substances 0.000 description 5
239000006286 aqueous extract Substances 0.000 description 5
125000004429 atom Chemical group 0.000 description 5
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
229910000019 calcium carbonate Inorganic materials 0.000 description 5
229940041514 candida albicans extract Drugs 0.000 description 5
239000003054 catalyst Substances 0.000 description 5
229920001429 chelating resin Polymers 0.000 description 5
230000005494 condensation Effects 0.000 description 5
235000019425 dextrin Nutrition 0.000 description 5
239000003814 drug Substances 0.000 description 5
235000015097 nutrients Nutrition 0.000 description 5
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 5
238000004816 paper chromatography Methods 0.000 description 5
235000010344 sodium nitrate Nutrition 0.000 description 5
239000012138 yeast extract Substances 0.000 description 5
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical class N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 4
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
241000588748 Klebsiella Species 0.000 description 4
NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 4
UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 4
229920002472 Starch Polymers 0.000 description 4
150000001412 amines Chemical class 0.000 description 4
229940088710 antibiotic agent Drugs 0.000 description 4
239000002518 antifoaming agent Substances 0.000 description 4
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
210000004369 blood Anatomy 0.000 description 4
239000008280 blood Substances 0.000 description 4
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 4
229960003669 carbenicillin Drugs 0.000 description 4
238000004587 chromatography analysis Methods 0.000 description 4
230000000994 depressogenic effect Effects 0.000 description 4
238000001514 detection method Methods 0.000 description 4
239000012153 distilled water Substances 0.000 description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 4
238000001914 filtration Methods 0.000 description 4
238000007327 hydrogenolysis reaction Methods 0.000 description 4
239000000543 intermediate Substances 0.000 description 4
238000004949 mass spectrometry Methods 0.000 description 4
229940043265 methyl isobutyl ketone Drugs 0.000 description 4
230000007935 neutral effect Effects 0.000 description 4
239000001301 oxygen Substances 0.000 description 4
230000001737 promoting effect Effects 0.000 description 4
SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 4
239000008107 starch Substances 0.000 description 4
235000019698 starch Nutrition 0.000 description 4
125000001424 substituent group Chemical group 0.000 description 4
230000002195 synergetic effect Effects 0.000 description 4
239000008399 tap water Substances 0.000 description 4
235000020679 tap water Nutrition 0.000 description 4
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 3
241001517488 Clavus Species 0.000 description 3
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
238000005481 NMR spectroscopy Methods 0.000 description 3
PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 3
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical group [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
239000001888 Peptone Substances 0.000 description 3
108010080698 Peptones Proteins 0.000 description 3
241000588770 Proteus mirabilis Species 0.000 description 3
241000589516 Pseudomonas Species 0.000 description 3
108091006629 SLC13A2 Proteins 0.000 description 3
229920005654 Sephadex Polymers 0.000 description 3
239000012507 Sephadex™ Substances 0.000 description 3
238000004458 analytical method Methods 0.000 description 3
230000000721 bacterilogical effect Effects 0.000 description 3
239000002585 base Substances 0.000 description 3
238000004440 column chromatography Methods 0.000 description 3
IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 3
ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 3
230000032050 esterification Effects 0.000 description 3
238000005886 esterification reaction Methods 0.000 description 3
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 3
235000013312 flour Nutrition 0.000 description 3
239000011521 glass Substances 0.000 description 3
238000001727 in vivo Methods 0.000 description 3
238000011081 inoculation Methods 0.000 description 3
229910052500 inorganic mineral Chemical class 0.000 description 3
150000003951 lactams Chemical group 0.000 description 3
244000005700 microbiome Species 0.000 description 3
239000011707 mineral Chemical class 0.000 description 3
235000010755 mineral Nutrition 0.000 description 3
238000002156 mixing Methods 0.000 description 3
239000012074 organic phase Substances 0.000 description 3
235000019319 peptone Nutrition 0.000 description 3
159000000001 potassium salts Chemical class 0.000 description 3
239000000651 prodrug Substances 0.000 description 3
229940002612 prodrug Drugs 0.000 description 3
235000017557 sodium bicarbonate Nutrition 0.000 description 3
229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
238000001228 spectrum Methods 0.000 description 3
239000008223 sterile water Substances 0.000 description 3
238000003756 stirring Methods 0.000 description 3
239000000758 substrate Substances 0.000 description 3
229940124597 therapeutic agent Drugs 0.000 description 3
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 3
229960004659 ticarcillin Drugs 0.000 description 3
210000001519 tissue Anatomy 0.000 description 3
LNOBZXNCABUBKK-UHFFFAOYSA-N 2,3,5-triphenyltetrazolium Chemical compound C1=CC=CC=C1C(N=[N+]1C=2C=CC=CC=2)=NN1C1=CC=CC=C1 LNOBZXNCABUBKK-UHFFFAOYSA-N 0.000 description 2
NKBWMBRPILTCRD-UHFFFAOYSA-N 2-Methylheptanoic acid Chemical compound CCCCCC(C)C(O)=O NKBWMBRPILTCRD-UHFFFAOYSA-N 0.000 description 2
SLRMQYXOBQWXCR-UHFFFAOYSA-N 2154-56-5 Chemical class [CH2]C1=CC=CC=C1 SLRMQYXOBQWXCR-UHFFFAOYSA-N 0.000 description 2
HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 2
241000203809 Actinomycetales Species 0.000 description 2
GUBGYTABKSRVRQ-WFVLMXAXSA-N DEAE-cellulose Chemical compound OC1C(O)C(O)C(CO)O[C@H]1O[C@@H]1C(CO)OC(O)C(O)C1O GUBGYTABKSRVRQ-WFVLMXAXSA-N 0.000 description 2
241000588914 Enterobacter Species 0.000 description 2
LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
241000282412 Homo Species 0.000 description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 2
RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 description 2
PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical class OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical group C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 description 2
241000607720 Serratia Species 0.000 description 2
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
241000191940 Staphylococcus Species 0.000 description 2
241001655322 Streptomycetales Species 0.000 description 2
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
229930006000 Sucrose Natural products 0.000 description 2
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
239000005864 Sulphur Chemical group 0.000 description 2
241000030538 Thecla Species 0.000 description 2
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
230000009603 aerobic growth Effects 0.000 description 2
150000001298 alcohols Chemical class 0.000 description 2
150000001450 anions Chemical class 0.000 description 2
238000012474 bioautography Methods 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
239000002021 butanolic extract Substances 0.000 description 2
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
239000001569 carbon dioxide Substances 0.000 description 2
229910002092 carbon dioxide Inorganic materials 0.000 description 2
150000001732 carboxylic acid derivatives Chemical group 0.000 description 2
230000015556 catabolic process Effects 0.000 description 2
239000001913 cellulose Substances 0.000 description 2
229920002678 cellulose Polymers 0.000 description 2
239000012141 concentrate Substances 0.000 description 2
235000008504 concentrate Nutrition 0.000 description 2
239000000287 crude extract Substances 0.000 description 2
238000006731 degradation reaction Methods 0.000 description 2
229910021641 deionized water Inorganic materials 0.000 description 2
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 2
229910000396 dipotassium phosphate Inorganic materials 0.000 description 2
229940116441 divinylbenzene Drugs 0.000 description 2
MYRTYDVEIRVNKP-UHFFFAOYSA-N divinylbenzene Substances C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 description 2
229940079593 drug Drugs 0.000 description 2
238000010828 elution Methods 0.000 description 2
239000004744 fabric Substances 0.000 description 2
IPCSVZSSVZVIGE-UHFFFAOYSA-N hexadecanoic acid Chemical compound CCCCCCCCCCCCCCCC(O)=O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 2
239000001257 hydrogen Substances 0.000 description 2
229910052739 hydrogen Inorganic materials 0.000 description 2
238000005984 hydrogenation reaction Methods 0.000 description 2
230000002779 inactivation Effects 0.000 description 2
238000011534 incubation Methods 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
238000004255 ion exchange chromatography Methods 0.000 description 2
230000014759 maintenance of location Effects 0.000 description 2
239000011159 matrix material Substances 0.000 description 2
230000007246 mechanism Effects 0.000 description 2
239000012528 membrane Substances 0.000 description 2
239000002207 metabolite Substances 0.000 description 2
WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical class [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 description 2
229960003085 meticillin Drugs 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
239000006916 nutrient agar Substances 0.000 description 2
230000000050 nutritive effect Effects 0.000 description 2
230000036961 partial effect Effects 0.000 description 2
239000008194 pharmaceutical composition Substances 0.000 description 2
230000005855 radiation Effects 0.000 description 2
238000001953 recrystallisation Methods 0.000 description 2
239000012266 salt solution Substances 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
230000035945 sensitivity Effects 0.000 description 2
238000000926 separation method Methods 0.000 description 2
229910001961 silver nitrate Inorganic materials 0.000 description 2
235000009518 sodium iodide Nutrition 0.000 description 2
239000004317 sodium nitrate Substances 0.000 description 2
239000012064 sodium phosphate buffer Substances 0.000 description 2
238000000638 solvent extraction Methods 0.000 description 2
239000005720 sucrose Substances 0.000 description 2
239000006228 supernatant Substances 0.000 description 2
RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 2
238000012546 transfer Methods 0.000 description 2
239000012137 tryptone Substances 0.000 description 2
238000000108 ultra-filtration Methods 0.000 description 2
XJRIDJAGAYGJCK-UHFFFAOYSA-N (1-acetyl-5-bromoindol-3-yl) acetate Chemical compound C1=C(Br)C=C2C(OC(=O)C)=CN(C(C)=O)C2=C1 XJRIDJAGAYGJCK-UHFFFAOYSA-N 0.000 description 1
OPEGYZAATHKDEM-HCWXCVPCSA-N (2r,4s)-2-[(r)-carboxy(formamido)methyl]-5,5-dimethyl-1,3-thiazolidine-4-carboxylic acid Chemical compound CC1(C)S[C@H]([C@H](NC=O)C(O)=O)N[C@H]1C(O)=O OPEGYZAATHKDEM-HCWXCVPCSA-N 0.000 description 1
WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 1
KPWDGTGXUYRARH-UHFFFAOYSA-N 2,2,2-trichloroethanol Chemical compound OCC(Cl)(Cl)Cl KPWDGTGXUYRARH-UHFFFAOYSA-N 0.000 description 1
125000000453 2,2,2-trichloroethyl group Chemical group [H]C([H])(*)C(Cl)(Cl)Cl 0.000 description 1
125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 description 1
125000003006 2-dimethylaminoethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
RCEFMOGVOYEGJN-UHFFFAOYSA-N 3-(2-hydroxyphenyl)-6-(3-nitrophenyl)-1,4-dihydropyrimidin-2-one Chemical compound OC1=CC=CC=C1N1C(=O)NC(C=2C=C(C=CC=2)[N+]([O-])=O)=CC1 RCEFMOGVOYEGJN-UHFFFAOYSA-N 0.000 description 1
125000003852 3-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(Cl)=C1[H])C([H])([H])* 0.000 description 1
BGNGWHSBYQYVRX-UHFFFAOYSA-N 4-(dimethylamino)benzaldehyde Chemical compound CN(C)C1=CC=C(C=O)C=C1 BGNGWHSBYQYVRX-UHFFFAOYSA-N 0.000 description 1
125000006281 4-bromobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Br)C([H])([H])* 0.000 description 1
125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 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
LQLQRFGHAALLLE-UHFFFAOYSA-N 5-bromouracil Chemical compound BrC1=CNC(=O)NC1=O LQLQRFGHAALLLE-UHFFFAOYSA-N 0.000 description 1
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
BUNGCZLFHHXKBX-UHFFFAOYSA-N 8-methoxypsoralen Natural products C1=CC(=O)OC2=C1C=C1CCOC1=C2OC BUNGCZLFHHXKBX-UHFFFAOYSA-N 0.000 description 1
QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
241000251468 Actinopterygii Species 0.000 description 1
241000478345 Afer Species 0.000 description 1
GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
DCXYFEDJOCDNAF-UHFFFAOYSA-N Asparagine Natural products OC(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-N 0.000 description 1
241000304886 Bacilli Species 0.000 description 1
241000193830 Bacillus <bacterium> Species 0.000 description 1
241000283690 Bos taurus Species 0.000 description 1
238000009631 Broth culture Methods 0.000 description 1
DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
OSYMQQBMLQYBLR-NQPNHJOESA-N COC1[C@@H]2N(C(=CCS2)C(=O)O)C1=O Chemical compound COC1[C@@H]2N(C(=CCS2)C(=O)O)C1=O OSYMQQBMLQYBLR-NQPNHJOESA-N 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
241000237074 Centris Species 0.000 description 1
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 description 1
241001478240 Coccus Species 0.000 description 1
208000003322 Coinfection Diseases 0.000 description 1
241000518994 Conta Species 0.000 description 1
241000065675 Cyclops Species 0.000 description 1
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 1
SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
241000588697 Enterobacter cloacae Species 0.000 description 1
241000588722 Escherichia Species 0.000 description 1
PLUBXMRUUVWRLT-UHFFFAOYSA-N Ethyl methanesulfonate Chemical compound CCOS(C)(=O)=O PLUBXMRUUVWRLT-UHFFFAOYSA-N 0.000 description 1
244000166102 Eucalyptus leucoxylon Species 0.000 description 1
235000004694 Eucalyptus leucoxylon Nutrition 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
MIFYHUACUWQUKT-UHFFFAOYSA-N Isopenicillin N Natural products OC(=O)C1C(C)(C)SC2C(NC(=O)CCCC(N)C(O)=O)C(=O)N21 MIFYHUACUWQUKT-UHFFFAOYSA-N 0.000 description 1
DCXYFEDJOCDNAF-REOHCLBHSA-N L-asparagine Chemical compound OC(=O)[C@@H](N)CC(N)=O DCXYFEDJOCDNAF-REOHCLBHSA-N 0.000 description 1
COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 1
125000000174 L-prolyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])([H])[C@@]1([H])C(*)=O 0.000 description 1
KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 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
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
PWHULOQIROXLJO-UHFFFAOYSA-N Manganese Chemical compound [Mn] PWHULOQIROXLJO-UHFFFAOYSA-N 0.000 description 1
241001465754 Metazoa Species 0.000 description 1
QXKHYNVANLEOEG-UHFFFAOYSA-N Methoxsalen Chemical compound C1=CC(=O)OC2=C1C=C1C=COC1=C2OC QXKHYNVANLEOEG-UHFFFAOYSA-N 0.000 description 1
102000014171 Milk Proteins Human genes 0.000 description 1
108010011756 Milk Proteins Proteins 0.000 description 1
241000219470 Mirabilis Species 0.000 description 1
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
GXCLVBGFBYZDAG-UHFFFAOYSA-N N-[2-(1H-indol-3-yl)ethyl]-N-methylprop-2-en-1-amine Chemical compound CN(CCC1=CNC2=C1C=CC=C2)CC=C GXCLVBGFBYZDAG-UHFFFAOYSA-N 0.000 description 1
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
IOVCWXUNBOPUCH-UHFFFAOYSA-N Nitrous acid Chemical compound ON=O IOVCWXUNBOPUCH-UHFFFAOYSA-N 0.000 description 1
239000005642 Oleic acid Substances 0.000 description 1
ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
235000021314 Palmitic acid Nutrition 0.000 description 1
229930195708 Penicillin V Natural products 0.000 description 1
239000004698 Polyethylene Substances 0.000 description 1
239000004743 Polypropylene Substances 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
108010009736 Protein Hydrolysates Proteins 0.000 description 1
241000588769 Proteus <enterobacteria> Species 0.000 description 1
241000589517 Pseudomonas aeruginosa Species 0.000 description 1
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
240000004808 Saccharomyces cerevisiae Species 0.000 description 1
241000607760 Shigella sonnei Species 0.000 description 1
241000219289 Silene Species 0.000 description 1
229910000831 Steel Inorganic materials 0.000 description 1
241000194017 Streptococcus Species 0.000 description 1
241000193996 Streptococcus pyogenes Species 0.000 description 1
241000424942 Streptomyces clavuligerus ATCC 27064 Species 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
XSTXAVWGXDQKEL-UHFFFAOYSA-N Trichloroethylene Chemical group ClC=C(Cl)Cl XSTXAVWGXDQKEL-UHFFFAOYSA-N 0.000 description 1
RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 1
KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
240000008042 Zea mays Species 0.000 description 1
235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
235000002017 Zea mays subsp mays Nutrition 0.000 description 1
JIAARYAFYJHUJI-UHFFFAOYSA-L Zinc chloride Inorganic materials [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 1
MZVQCMJNVPIDEA-UHFFFAOYSA-N [CH2]CN(CC)CC Chemical group [CH2]CN(CC)CC MZVQCMJNVPIDEA-UHFFFAOYSA-N 0.000 description 1
CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical class [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 description 1
238000000862 absorption spectrum Methods 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
150000001251 acridines Chemical class 0.000 description 1
230000009471 action Effects 0.000 description 1
125000004423 acyloxy group Chemical group 0.000 description 1
229950008644 adicillin Drugs 0.000 description 1
238000012459 agar diffusion assay Methods 0.000 description 1
125000001931 aliphatic group Chemical group 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
125000003282 alkyl amino group Chemical group 0.000 description 1
125000005907 alkyl ester group Chemical group 0.000 description 1
239000002168 alkylating agent Substances 0.000 description 1
229940100198 alkylating agent Drugs 0.000 description 1
239000004411 aluminium Substances 0.000 description 1
229910052782 aluminium Inorganic materials 0.000 description 1
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
229910000147 aluminium phosphate Inorganic materials 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
235000001014 amino acid Nutrition 0.000 description 1
229940024606 amino acid Drugs 0.000 description 1
150000001413 amino acids Chemical class 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
BFNBIHQBYMNNAN-UHFFFAOYSA-N ammonium sulfate Chemical compound N.N.OS(O)(=O)=O BFNBIHQBYMNNAN-UHFFFAOYSA-N 0.000 description 1
229910052921 ammonium sulfate Inorganic materials 0.000 description 1
239000001166 ammonium sulphate Substances 0.000 description 1
235000011130 ammonium sulphate Nutrition 0.000 description 1
238000005349 anion exchange Methods 0.000 description 1
125000000129 anionic group Chemical group 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
239000003125 aqueous solvent Substances 0.000 description 1
229960001230 asparagine Drugs 0.000 description 1
235000009582 asparagine Nutrition 0.000 description 1
239000007613 bennett's agar Substances 0.000 description 1
JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
239000011230 binding agent Substances 0.000 description 1
238000004166 bioassay Methods 0.000 description 1
238000002306 biochemical method Methods 0.000 description 1
QKSKPIVNLNLAAV-UHFFFAOYSA-N bis(2-chloroethyl) sulfide Chemical compound ClCCSCCCl QKSKPIVNLNLAAV-UHFFFAOYSA-N 0.000 description 1
230000036765 blood level Effects 0.000 description 1
239000000872 buffer Substances 0.000 description 1
230000003139 buffering effect Effects 0.000 description 1
125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
229940043232 butyl acetate Drugs 0.000 description 1
229910001424 calcium ion Inorganic materials 0.000 description 1
238000004364 calculation method Methods 0.000 description 1
239000002775 capsule Substances 0.000 description 1
239000004202 carbamide Substances 0.000 description 1
150000001720 carbohydrates Chemical class 0.000 description 1
235000014633 carbohydrates Nutrition 0.000 description 1
150000001735 carboxylic acids Chemical class 0.000 description 1
NZDASSHFKWDBBU-KVMCETHSSA-N carfecillin Chemical group N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)C(C=1C=CC=CC=1)C(=O)OC1=CC=CC=C1 NZDASSHFKWDBBU-KVMCETHSSA-N 0.000 description 1
229960002543 carfecillin Drugs 0.000 description 1
RRYMAQUWDLIUPV-BXKDBHETSA-N cefacetrile Chemical compound 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
229960003972 cefacetrile Drugs 0.000 description 1
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 1
229950004030 cefaloglycin Drugs 0.000 description 1
229960000603 cefalotin Drugs 0.000 description 1
OLVCFLKTBJRLHI-AXAPSJFSSA-N cefamandole Chemical compound 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
229960003012 cefamandole Drugs 0.000 description 1
229960004350 cefapirin Drugs 0.000 description 1
229960001139 cefazolin Drugs 0.000 description 1
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 description 1
229960002588 cefradine Drugs 0.000 description 1
239000006285 cell suspension Substances 0.000 description 1
229940106164 cephalexin Drugs 0.000 description 1
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 1
VUFGUVLLDPOSBC-XRZFDKQNSA-M cephalothin sodium Chemical compound [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
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 1
238000001311 chemical methods and process Methods 0.000 description 1
238000002512 chemotherapy Methods 0.000 description 1
125000001309 chloro group Chemical group Cl* 0.000 description 1
QSKWJTXWJJOJFP-UHFFFAOYSA-N chloroform;ethoxyethane Chemical compound ClC(Cl)Cl.CCOCC QSKWJTXWJJOJFP-UHFFFAOYSA-N 0.000 description 1
SKCNIGRBPJIUBQ-UHFFFAOYSA-N chloroform;ethyl acetate Chemical compound ClC(Cl)Cl.CCOC(C)=O SKCNIGRBPJIUBQ-UHFFFAOYSA-N 0.000 description 1
230000009194 climbing Effects 0.000 description 1
210000003555 cloaca Anatomy 0.000 description 1
239000011248 coating agent Substances 0.000 description 1
238000000576 coating method Methods 0.000 description 1
239000010941 cobalt Substances 0.000 description 1
229910017052 cobalt Inorganic materials 0.000 description 1
GUTLYIVDDKVIGB-UHFFFAOYSA-N cobalt atom Chemical compound [Co] GUTLYIVDDKVIGB-UHFFFAOYSA-N 0.000 description 1
239000003086 colorant Substances 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
238000001816 cooling Methods 0.000 description 1
235000005822 corn Nutrition 0.000 description 1
230000002596 correlated effect Effects 0.000 description 1
239000006071 cream Substances 0.000 description 1
239000012043 crude product Substances 0.000 description 1
239000012531 culture fluid Substances 0.000 description 1
229960004244 cyclacillin Drugs 0.000 description 1
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 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000003678 cyclohexadienyl group Chemical group C1(=CC=CCC1)* 0.000 description 1
WACQKHWOTAEEFS-UHFFFAOYSA-N cyclohexane;ethyl acetate Chemical compound CCOC(C)=O.C1CCCCC1 WACQKHWOTAEEFS-UHFFFAOYSA-N 0.000 description 1
125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
230000003247 decreasing effect Effects 0.000 description 1
125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
238000007257 deesterification reaction Methods 0.000 description 1
238000011161 development Methods 0.000 description 1
239000008121 dextrose Substances 0.000 description 1
125000004663 dialkyl amino group Chemical group 0.000 description 1
150000008049 diazo compounds Chemical class 0.000 description 1
238000009792 diffusion process Methods 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
AIUDWMLXCFRVDR-UHFFFAOYSA-N dimethyl 2-(3-ethyl-3-methylpentyl)propanedioate Chemical class CCC(C)(CC)CCC(C(=O)OC)C(=O)OC AIUDWMLXCFRVDR-UHFFFAOYSA-N 0.000 description 1
229960001760 dimethyl sulfoxide Drugs 0.000 description 1
ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 description 1
235000019797 dipotassium phosphate Nutrition 0.000 description 1
201000010099 disease Diseases 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
239000007884 disintegrant Substances 0.000 description 1
238000006073 displacement reaction Methods 0.000 description 1
125000003438 dodecyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
239000002552 dosage form Substances 0.000 description 1
238000001035 drying Methods 0.000 description 1
229940096118 ella Drugs 0.000 description 1
239000003480 eluent Substances 0.000 description 1
229940092559 enterobacter aerogenes Drugs 0.000 description 1
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 1
229960002457 epicillin Drugs 0.000 description 1
239000000469 ethanolic extract Substances 0.000 description 1
239000004210 ether based solvent Substances 0.000 description 1
IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
238000002270 exclusion chromatography Methods 0.000 description 1
239000003925 fat Substances 0.000 description 1
230000002349 favourable effect Effects 0.000 description 1
239000000796 flavoring agent Substances 0.000 description 1
235000019634 flavors Nutrition 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
239000006260 foam Substances 0.000 description 1
238000005187 foaming Methods 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
210000004051 gastric juice Anatomy 0.000 description 1
230000002068 genetic effect Effects 0.000 description 1
150000002314 glycerols Chemical class 0.000 description 1
230000005484 gravity Effects 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
125000005843 halogen group Chemical group 0.000 description 1
125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 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
FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
230000036571 hydration Effects 0.000 description 1
238000006703 hydration reaction Methods 0.000 description 1
150000002430 hydrocarbons Chemical group 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 description 1
OLKGTKIYKWXMOZ-UHFFFAOYSA-N hydroxymethyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OCO OLKGTKIYKWXMOZ-UHFFFAOYSA-N 0.000 description 1
JYVNDCLJHKQUHE-UHFFFAOYSA-N hydroxymethyl acetate Chemical compound CC(=O)OCO JYVNDCLJHKQUHE-UHFFFAOYSA-N 0.000 description 1
150000002460 imidazoles Chemical class 0.000 description 1
239000012535 impurity Substances 0.000 description 1
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
230000001524 infective effect Effects 0.000 description 1
238000002329 infrared spectrum Methods 0.000 description 1
238000001802 infusion Methods 0.000 description 1
229910052740 iodine Inorganic materials 0.000 description 1
238000005342 ion exchange Methods 0.000 description 1
239000003456 ion exchange resin Substances 0.000 description 1
229920003303 ion-exchange polymer Polymers 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
229910000359 iron(II) sulfate Inorganic materials 0.000 description 1
WNZQDUSMALZDQF-UHFFFAOYSA-N isobenzofuranone Natural products C1=CC=C2C(=O)OCC2=C1 WNZQDUSMALZDQF-UHFFFAOYSA-N 0.000 description 1
QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000008101 lactose Substances 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
230000001320 lysogenic effect Effects 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
229910052748 manganese Inorganic materials 0.000 description 1
239000011572 manganese Substances 0.000 description 1
239000003550 marker Substances 0.000 description 1
238000001819 mass spectrum Methods 0.000 description 1
208000004396 mastitis Diseases 0.000 description 1
235000013372 meat Nutrition 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
229960003806 metampicillin Drugs 0.000 description 1
WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
229960004469 methoxsalen Drugs 0.000 description 1
SQBBOVROCFXYBN-UHFFFAOYSA-N methoxypsoralen Natural products C1=C2OC(=O)C(OC)=CC2=CC2=C1OC=C2 SQBBOVROCFXYBN-UHFFFAOYSA-N 0.000 description 1
235000021239 milk protein Nutrition 0.000 description 1
LPUQAYUQRXPFSQ-DFWYDOINSA-M monosodium L-glutamate Chemical compound [Na+].[O-]C(=O)[C@@H](N)CCC(O)=O LPUQAYUQRXPFSQ-DFWYDOINSA-M 0.000 description 1
235000013923 monosodium glutamate Nutrition 0.000 description 1
239000004223 monosodium glutamate Substances 0.000 description 1
WQEPLUUGTLDZJY-UHFFFAOYSA-N n-Pentadecanoic acid Natural products CCCCCCCCCCCCCCC(O)=O WQEPLUUGTLDZJY-UHFFFAOYSA-N 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
229910052759 nickel Inorganic materials 0.000 description 1
229910017604 nitric acid Inorganic materials 0.000 description 1
239000012038 nucleophile Substances 0.000 description 1
125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
238000011017 operating method Methods 0.000 description 1
239000011368 organic material Substances 0.000 description 1
125000001477 organic nitrogen group Chemical group 0.000 description 1
125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 1
238000007911 parenteral administration Methods 0.000 description 1
MIFYHUACUWQUKT-GPUHXXMPSA-N penicillin N Chemical compound OC(=O)[C@H]1C(C)(C)S[C@@H]2[C@H](NC(=O)CCC[C@@H](N)C(O)=O)C(=O)N21 MIFYHUACUWQUKT-GPUHXXMPSA-N 0.000 description 1
229940056367 penicillin v Drugs 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
229940066779 peptones Drugs 0.000 description 1
150000002989 phenols Chemical class 0.000 description 1
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 1
COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 0.000 description 1
125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
125000005633 phthalidyl group Chemical group 0.000 description 1
239000004033 plastic Substances 0.000 description 1
229920003023 plastic Polymers 0.000 description 1
239000002798 polar solvent Substances 0.000 description 1
229920001983 poloxamer Polymers 0.000 description 1
229920000768 polyamine Polymers 0.000 description 1
229920000573 polyethylene Polymers 0.000 description 1
229920000642 polymer Polymers 0.000 description 1
229920001155 polypropylene Polymers 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229960003975 potassium Drugs 0.000 description 1
235000015497 potassium bicarbonate Nutrition 0.000 description 1
239000011736 potassium bicarbonate Substances 0.000 description 1
229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
239000000843 powder Substances 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
229960004919 procaine Drugs 0.000 description 1
230000002035 prolonged effect Effects 0.000 description 1
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
229960003672 propicillin Drugs 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
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
239000003531 protein hydrolysate Substances 0.000 description 1
235000018102 proteins Nutrition 0.000 description 1
102000004169 proteins and genes Human genes 0.000 description 1
108090000623 proteins and genes Proteins 0.000 description 1
JUJWROOIHBZHMG-RALIUCGRSA-N pyridine-d5 Chemical compound [2H]C1=NC([2H])=C([2H])C([2H])=C1[2H] JUJWROOIHBZHMG-RALIUCGRSA-N 0.000 description 1
125000000719 pyrrolidinyl group Chemical group 0.000 description 1
125000001453 quaternary ammonium group Chemical group 0.000 description 1
239000012429 reaction media Substances 0.000 description 1
238000005215 recombination Methods 0.000 description 1
230000006798 recombination Effects 0.000 description 1
238000011084 recovery Methods 0.000 description 1
239000012088 reference solution Substances 0.000 description 1
230000001172 regenerating effect Effects 0.000 description 1
238000011160 research Methods 0.000 description 1
210000002345 respiratory system Anatomy 0.000 description 1
239000012465 retentate Substances 0.000 description 1
IOVGROKTTNBUGK-SJCJKPOMSA-N ritodrine Chemical compound N([C@@H](C)[C@H](O)C=1C=CC(O)=CC=1)CCC1=CC=C(O)C=C1 IOVGROKTTNBUGK-SJCJKPOMSA-N 0.000 description 1
238000005185 salting out Methods 0.000 description 1
150000003335 secondary amines Chemical class 0.000 description 1
238000013207 serial dilution Methods 0.000 description 1
229940115939 shigella sonnei Drugs 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
RBWSWDPRDBEWCR-RKJRWTFHSA-N sodium;(2r)-2-[(2r)-3,4-dihydroxy-5-oxo-2h-furan-2-yl]-2-hydroxyethanolate Chemical compound [Na+].[O-]C[C@@H](O)[C@H]1OC(=O)C(O)=C1O RBWSWDPRDBEWCR-RKJRWTFHSA-N 0.000 description 1
BNRLJJXPMKKGJR-UHFFFAOYSA-M sodium;2-methylheptanoate Chemical compound [Na+].CCCCCC(C)C([O-])=O BNRLJJXPMKKGJR-UHFFFAOYSA-M 0.000 description 1
GGCZERPQGJTIQP-UHFFFAOYSA-N sodium;9,10-dioxoanthracene-2-sulfonic acid Chemical compound [Na+].C1=CC=C2C(=O)C3=CC(S(=O)(=O)O)=CC=C3C(=O)C2=C1 GGCZERPQGJTIQP-UHFFFAOYSA-N 0.000 description 1
210000004872 soft tissue Anatomy 0.000 description 1
239000007790 solid phase Substances 0.000 description 1
238000001179 sorption measurement Methods 0.000 description 1
235000012424 soybean oil Nutrition 0.000 description 1
239000003549 soybean oil Substances 0.000 description 1
241000894007 species Species 0.000 description 1
230000002269 spontaneous effect Effects 0.000 description 1
238000001694 spray drying Methods 0.000 description 1
239000010959 steel Substances 0.000 description 1
238000004659 sterilization and disinfection Methods 0.000 description 1
238000007920 subcutaneous administration Methods 0.000 description 1
235000000346 sugar Nutrition 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
BDHFUVZGWQCTTF-UHFFFAOYSA-N sulfonic acid Chemical class OS(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-N 0.000 description 1
235000011149 sulphuric acid Nutrition 0.000 description 1
239000012747 synergistic agent Substances 0.000 description 1
239000006188 syrup Substances 0.000 description 1
235000020357 syrup Nutrition 0.000 description 1
230000009897 systematic effect Effects 0.000 description 1
230000009885 systemic effect Effects 0.000 description 1
239000003826 tablet Substances 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
230000000699 topical effect Effects 0.000 description 1
239000011573 trace mineral Substances 0.000 description 1
235000013619 trace mineral Nutrition 0.000 description 1
230000026683 transduction Effects 0.000 description 1
238000010361 transduction Methods 0.000 description 1
230000009466 transformation Effects 0.000 description 1
229910052723 transition metal Inorganic materials 0.000 description 1
150000003624 transition metals Chemical class 0.000 description 1
UBOXGVDOUJQMTN-UHFFFAOYSA-N trichloroethylene Natural products ClCC(Cl)Cl UBOXGVDOUJQMTN-UHFFFAOYSA-N 0.000 description 1
ZBZJXHCVGLJWFG-UHFFFAOYSA-N trichloromethyl(.) Chemical group Cl[C](Cl)Cl ZBZJXHCVGLJWFG-UHFFFAOYSA-N 0.000 description 1
UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 1
125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
OOLLAFOLCSJHRE-ZHAKMVSLSA-N ulipristal acetate Chemical compound C1=CC(N(C)C)=CC=C1[C@@H]1C2=C3CCC(=O)C=C3CC[C@H]2[C@H](CC[C@]2(OC(C)=O)C(C)=O)[C@]2(C)C1 OOLLAFOLCSJHRE-ZHAKMVSLSA-N 0.000 description 1
241001446247 uncultured actinomycete Species 0.000 description 1
125000002948 undecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
210000001635 urinary tract Anatomy 0.000 description 1
239000004474 valine Substances 0.000 description 1
229910052720 vanadium Inorganic materials 0.000 description 1
235000015112 vegetable and seed oil Nutrition 0.000 description 1
239000008158 vegetable oil Substances 0.000 description 1
235000013311 vegetables Nutrition 0.000 description 1
125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
229920002554 vinyl polymer Polymers 0.000 description 1
235000013343 vitamin Nutrition 0.000 description 1
239000011782 vitamin Substances 0.000 description 1
229940088594 vitamin Drugs 0.000 description 1
229930003231 vitamin Natural products 0.000 description 1
238000010792 warming Methods 0.000 description 1
238000005406 washing Methods 0.000 description 1
239000002699 waste material Substances 0.000 description 1
238000009736 wetting Methods 0.000 description 1

Landscapes

Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)

CA314,882A 1974-04-20 1978-10-30 Esters de l'acide clavulanique Expired CA1076120A (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA314,882A CA1076120A (fr)	1974-04-20	1978-10-30	Esters de l'acide clavulanique

Applications Claiming Priority (6)

Application Number	Priority Date	Filing Date	Title
GB17410/74A GB1508977A (en)	1974-04-20	1974-04-20	Beta-lactam antibiotic from streptomyces clavuligerus
GB2771574		1974-06-21
GB4365174		1974-10-09
GB5352574		1974-12-11
CA224,970A CA1059050A (fr)	1974-04-20	1975-04-18	Acide clavulanique isole a partir du streptomyces clavuligerus
CA314,882A CA1076120A (fr)	1974-04-20	1978-10-30	Esters de l'acide clavulanique

Publications (1)

Publication Number	Publication Date
CA1076120A true CA1076120A (fr)	1980-04-22

Family

ID=27543273

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA314,882A Expired CA1076120A (fr)	1974-04-20	1978-10-30	Esters de l'acide clavulanique

Country Status (1)

Country	Link
CA (1)	CA1076120A (fr)

1978
- 1978-10-30 CA CA314,882A patent/CA1076120A/fr not_active Expired

Legal Events

Date	Code	Title	Description
1997-04-22	MKEX	Expiry

Publication	Publication Date	Title
US4110165A (en)	1978-08-29	Process for the production of clavulanic acid
CA1059050A (fr)	1979-07-24	Acide clavulanique isole a partir du streptomyces clavuligerus
US4529720A (en)	1985-07-16	Antibiotic from Streptomyces clavulicerus
US6218380B1 (en)	2001-04-17	Pharmaceutical compositions
US6051703A (en)	2000-04-18	Purified clavulanic acid and salts thereof
EP0182522B1 (fr)	1991-06-19	Préparation de l'acide clavulanique et de ses sels et esters
US4141986A (en)	1979-02-27	Antibiotics 890A2 and 890A5
CA1049532A (fr)	1979-02-27	Antibiotiques
US4189473A (en)	1980-02-19	Antibiotic MM 13902
US4162324A (en)	1979-07-24	Antibiotics 890A1 and 890A3
US4525353A (en)	1985-06-25	Antibiotics
EP0017246B1 (fr)	1984-04-11	L'antibiotique PA-31088-IV, ses sels avec des bases, procédé pour sa préparation, compositions pharmaceutiques le contenant, streptomyces tokunonensis PA-31088 et ses mutants
US4060530A (en)	1977-11-29	Clavulanic acid amides
RU2077534C1 (ru)	1997-04-20	Тиомаринол, обладающий антибактериальными свойствами, штамм микроорганизма alteromonas rava sank-73390 - продуцент тиомаринола и способ получения антибиотика тиомаринола
US4140764A (en)	1979-02-20	β-Lactamase inhibitors and process for their preparation
US4146610A (en)	1979-03-27	Antibiotics mm13902
JPH10508033A (ja)	1998-08-04	新規なアミノオリゴ糖誘導体およびその製造方法
CA1076120A (fr)	1980-04-22	Esters de l'acide clavulanique
US4172129A (en)	1979-10-23	Antibiotics
US4113856A (en)	1978-09-12	Antibiotic mm 13902
US4061649A (en)	1977-12-06	Clavulanic acid sulphates
US4123540A (en)	1978-10-31	Isoclavulanic acid as an antibacterial and a β-lactamase inhibitor
CA1074325A (fr)	1980-03-25	L'acide clavulanique et ses sels
US4181716A (en)	1980-01-01	Antibiotics
CA1055395A (fr)	1979-05-29	Antibiotiques