JPH0534336B2 - - Google Patents
Info
- Publication number
- JPH0534336B2 JPH0534336B2 JP1235475A JP23547589A JPH0534336B2 JP H0534336 B2 JPH0534336 B2 JP H0534336B2 JP 1235475 A JP1235475 A JP 1235475A JP 23547589 A JP23547589 A JP 23547589A JP H0534336 B2 JPH0534336 B2 JP H0534336B2
- Authority
- JP
- Japan
- Prior art keywords
- oxide
- dioxide
- compound
- acid
- ethyl acetate
- Prior art date
- 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 - Lifetime
Links
- 150000001875 compounds Chemical class 0.000 claims description 150
- 239000000203 mixture Substances 0.000 claims description 71
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 41
- 239000001257 hydrogen Substances 0.000 claims description 41
- 229910052739 hydrogen Inorganic materials 0.000 claims description 41
- 239000002253 acid Substances 0.000 claims description 40
- -1 3-phthalidyl Chemical group 0.000 claims description 26
- 150000003839 salts Chemical class 0.000 claims description 26
- 125000004432 carbon atom Chemical group C* 0.000 claims description 25
- 238000001727 in vivo Methods 0.000 claims description 25
- 230000000844 anti-bacterial effect Effects 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000005643 gamma-butyrolacton-4-yl group Chemical group 0.000 claims description 4
- 125000005042 acyloxymethyl group Chemical group 0.000 claims description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
- 125000005206 alkoxycarbonyloxymethyl group Chemical group 0.000 claims description 3
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
- 125000005847 1-methyl-1-(alkanoyloxy)-ethyl group Chemical group 0.000 claims description 2
- 125000005850 N-(alkoxycarbonyl)aminomethyl group Chemical group 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 229
- 239000000243 solution Substances 0.000 description 65
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 61
- RBKMMJSQKNKNEV-RITPCOANSA-N penicillanic acid Chemical class OC(=O)[C@H]1C(C)(C)S[C@@H]2CC(=O)N21 RBKMMJSQKNKNEV-RITPCOANSA-N 0.000 description 42
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 41
- 238000000034 method Methods 0.000 description 37
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 36
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
- 239000000047 product Substances 0.000 description 32
- 239000010410 layer Substances 0.000 description 26
- 238000001704 evaporation Methods 0.000 description 25
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- 241000699670 Mus sp. Species 0.000 description 24
- 239000002904 solvent Substances 0.000 description 24
- 238000003756 stirring Methods 0.000 description 24
- 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 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 21
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 21
- 239000011541 reaction mixture Substances 0.000 description 21
- 230000009102 absorption Effects 0.000 description 19
- 238000010521 absorption reaction Methods 0.000 description 19
- 230000008020 evaporation Effects 0.000 description 19
- NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 18
- 241000700159 Rattus Species 0.000 description 18
- 239000008346 aqueous phase Substances 0.000 description 18
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 17
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- 238000012360 testing method Methods 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 13
- 238000004519 manufacturing process Methods 0.000 description 12
- 238000007254 oxidation reaction Methods 0.000 description 12
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 12
- 239000007787 solid Substances 0.000 description 12
- 229940126062 Compound A Drugs 0.000 description 11
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 11
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- 230000003647 oxidation Effects 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 10
- 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 10
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 10
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 10
- 150000002148 esters Chemical class 0.000 description 10
- 239000011734 sodium Substances 0.000 description 10
- 159000000000 sodium salts Chemical class 0.000 description 10
- 239000007864 aqueous solution Substances 0.000 description 9
- 239000003153 chemical reaction reagent Substances 0.000 description 9
- 150000004820 halides Chemical class 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 239000012044 organic layer Substances 0.000 description 9
- 239000000126 substance Substances 0.000 description 9
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
- 229930182555 Penicillin Natural products 0.000 description 8
- 239000012298 atmosphere Substances 0.000 description 8
- 239000003054 catalyst Substances 0.000 description 8
- 238000001990 intravenous administration Methods 0.000 description 8
- 239000007788 liquid Substances 0.000 description 8
- 238000002844 melting Methods 0.000 description 8
- 230000008018 melting Effects 0.000 description 8
- 244000005700 microbiome Species 0.000 description 8
- 239000003921 oil Substances 0.000 description 8
- 235000019198 oils Nutrition 0.000 description 8
- 239000012286 potassium permanganate Substances 0.000 description 8
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- 229930186147 Cephalosporin Natural products 0.000 description 7
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical class [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 7
- 239000004480 active ingredient Substances 0.000 description 7
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 7
- 229940124587 cephalosporin Drugs 0.000 description 7
- 150000001780 cephalosporins Chemical class 0.000 description 7
- 238000007327 hydrogenolysis reaction Methods 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 230000001590 oxidative effect Effects 0.000 description 7
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 7
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 6
- 230000000845 anti-microbial effect Effects 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 239000003782 beta lactam antibiotic agent Substances 0.000 description 6
- 102000006635 beta-lactamase Human genes 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- 238000002329 infrared spectrum Methods 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 6
- 125000005846 1-(alkanoyloxy)ethyl group Chemical group 0.000 description 5
- ULQQGOGMQRGFFR-UHFFFAOYSA-N 2-chlorobenzenecarboperoxoic acid Chemical compound OOC(=O)C1=CC=CC=C1Cl ULQQGOGMQRGFFR-UHFFFAOYSA-N 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 230000001154 acute effect Effects 0.000 description 5
- 229910052783 alkali metal Inorganic materials 0.000 description 5
- 239000003242 anti bacterial agent Substances 0.000 description 5
- 230000037396 body weight Effects 0.000 description 5
- 229910000019 calcium carbonate Inorganic materials 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 229960003750 ethyl chloride Drugs 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 238000007912 intraperitoneal administration Methods 0.000 description 5
- 150000002960 penicillins Chemical class 0.000 description 5
- 238000010561 standard procedure Methods 0.000 description 5
- 125000001424 substituent group Chemical group 0.000 description 5
- 239000002132 β-lactam antibiotic Substances 0.000 description 5
- 229940124586 β-lactam antibiotics Drugs 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
- 229920001817 Agar Polymers 0.000 description 4
- 108020004256 Beta-lactamase Proteins 0.000 description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical class [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical class CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 4
- 229960000583 acetic acid Drugs 0.000 description 4
- 239000008272 agar Substances 0.000 description 4
- 125000002619 bicyclic group Chemical group 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 238000007256 debromination reaction Methods 0.000 description 4
- 239000003085 diluting agent Substances 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 239000002054 inoculum Substances 0.000 description 4
- 239000007800 oxidant agent Substances 0.000 description 4
- 229940049954 penicillin Drugs 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
- 235000011152 sodium sulphate Nutrition 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 238000007920 subcutaneous administration Methods 0.000 description 4
- 125000005848 1-(alkoxycarbonyloxy)ethyl group Chemical group 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 208000035143 Bacterial infection Diseases 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- XLYOFNOQVPJJNP-ZSJDYOACSA-N Heavy water Chemical compound [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 3
- 241000699666 Mus <mouse, genus> Species 0.000 description 3
- 229930195708 Penicillin V Natural products 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 150000001340 alkali metals Chemical class 0.000 description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 3
- 150000001342 alkaline earth metals Chemical class 0.000 description 3
- 150000004703 alkoxides Chemical class 0.000 description 3
- 238000009635 antibiotic susceptibility testing Methods 0.000 description 3
- 239000004599 antimicrobial Substances 0.000 description 3
- 239000007900 aqueous suspension Substances 0.000 description 3
- 208000022362 bacterial infectious disease Diseases 0.000 description 3
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 229910052801 chlorine Inorganic materials 0.000 description 3
- GGRHYQCXXYLUTL-UHFFFAOYSA-N chloromethyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OCCl GGRHYQCXXYLUTL-UHFFFAOYSA-N 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 238000010790 dilution Methods 0.000 description 3
- 239000012895 dilution Substances 0.000 description 3
- 150000002170 ethers Chemical class 0.000 description 3
- 239000002024 ethyl acetate extract Substances 0.000 description 3
- 150000004678 hydrides Chemical class 0.000 description 3
- 239000012442 inert solvent Substances 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 238000011081 inoculation Methods 0.000 description 3
- 238000007918 intramuscular administration Methods 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 229940056360 penicillin g Drugs 0.000 description 3
- 229940056367 penicillin v Drugs 0.000 description 3
- 150000004965 peroxy acids Chemical class 0.000 description 3
- 239000008194 pharmaceutical composition Substances 0.000 description 3
- OSORMYZMWHVFOZ-UHFFFAOYSA-N phenethyl benzoate Chemical compound C=1C=CC=CC=1C(=O)OCCC1=CC=CC=C1 OSORMYZMWHVFOZ-UHFFFAOYSA-N 0.000 description 3
- BPLBGHOLXOTWMN-MBNYWOFBSA-N phenoxymethylpenicillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)COC1=CC=CC=C1 BPLBGHOLXOTWMN-MBNYWOFBSA-N 0.000 description 3
- 239000000843 powder Substances 0.000 description 3
- 230000035484 reaction time Effects 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 3
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 238000007738 vacuum evaporation Methods 0.000 description 3
- YVRGKFXJZCTTRB-UHFFFAOYSA-N 1-chloroethyl ethyl carbonate Chemical compound CCOC(=O)OC(C)Cl YVRGKFXJZCTTRB-UHFFFAOYSA-N 0.000 description 2
- ODQLAECNMKXOBI-UHFFFAOYSA-N 2-bromo-2h-furan-5-one Chemical compound BrC1OC(=O)C=C1 ODQLAECNMKXOBI-UHFFFAOYSA-N 0.000 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 description 2
- NGHVIOIJCVXTGV-ALEPSDHESA-N 6-aminopenicillanic acid Chemical compound [O-]C(=O)[C@H]1C(C)(C)S[C@@H]2[C@H]([NH3+])C(=O)N21 NGHVIOIJCVXTGV-ALEPSDHESA-N 0.000 description 2
- NGHVIOIJCVXTGV-UHFFFAOYSA-N 6beta-amino-penicillanic acid Natural products OC(=O)C1C(C)(C)SC2C(N)C(=O)N21 NGHVIOIJCVXTGV-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 2
- 108090000204 Dipeptidase 1 Proteins 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 239000005909 Kieselgur Substances 0.000 description 2
- 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 2
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 2
- JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 2
- HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- 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 2
- 229960000723 ampicillin Drugs 0.000 description 2
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- 239000001488 sodium phosphate Substances 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- LVCJBUWIZQQMSU-IBTYICNHSA-M sodium;(2s,5r)-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate Chemical compound [Na+].[O-]C(=O)[C@H]1C(C)(C)S[C@@H]2CC(=O)N21 LVCJBUWIZQQMSU-IBTYICNHSA-M 0.000 description 1
- HWEXKRHYVOGVDA-UHFFFAOYSA-M sodium;3-trimethylsilylpropane-1-sulfonate Chemical compound [Na+].C[Si](C)(C)CCCS([O-])(=O)=O HWEXKRHYVOGVDA-UHFFFAOYSA-M 0.000 description 1
- 238000000935 solvent evaporation Methods 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000002769 thiazolinyl group Chemical group 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- NRTLTGGGUQIRRT-UHFFFAOYSA-N triethylazanium;bromide Chemical compound [Br-].CC[NH+](CC)CC NRTLTGGGUQIRRT-UHFFFAOYSA-N 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
- 150000003952 β-lactams Chemical group 0.000 description 1
- 229940126085 β‑Lactamase Inhibitor Drugs 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US96376378A | 1978-11-27 | 1978-11-27 | |
| US963763 | 1978-11-27 | ||
| US06/017,807 US4276285A (en) | 1977-06-07 | 1979-03-05 | Combinations of penicillanic acid 1,1-dioxide with 7-(D-2-[4-ethylpiperazin-2,3-dione-1-carboxamido]-2-[4-hydroxyphenyl]acetamido)-3-([1-methyl-5-tetrazolyl]thiomethyl)-3-desacetoxymethylcephalosporanic acid |
| US17807 | 1979-03-05 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPH02191284A JPH02191284A (ja) | 1990-07-27 |
| JPH0534336B2 true JPH0534336B2 (sv) | 1993-05-21 |
Family
ID=26690335
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP1235475A Granted JPH02191284A (ja) | 1978-11-27 | 1989-09-11 | 抗菌用組成物 |
Country Status (8)
| Country | Link |
|---|---|
| JP (1) | JPH02191284A (sv) |
| DD (1) | DD146790A6 (sv) |
| EG (1) | EG14169A (sv) |
| GR (1) | GR73837B (sv) |
| IN (1) | IN154073B (sv) |
| IT (1) | IT1188790B (sv) |
| MX (1) | MX5956E (sv) |
| PH (1) | PH15581A (sv) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6056160A (ja) * | 1983-09-06 | 1985-04-01 | Toyota Motor Corp | ディ−ゼル機関の吸気加熱用ヒ−タの制御方法 |
-
1979
- 1979-06-26 GR GR59445A patent/GR73837B/el unknown
- 1979-07-17 IT IT24438/79A patent/IT1188790B/it active
- 1979-11-13 IN IN809/DEL/79A patent/IN154073B/en unknown
- 1979-11-16 DD DD79216959A patent/DD146790A6/de unknown
- 1979-11-16 MX MX798492U patent/MX5956E/es unknown
- 1979-11-16 PH PH23287A patent/PH15581A/en unknown
- 1979-11-19 EG EG689/79A patent/EG14169A/xx active
-
1989
- 1989-09-11 JP JP1235475A patent/JPH02191284A/ja active Granted
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS6056160A (ja) * | 1983-09-06 | 1985-04-01 | Toyota Motor Corp | ディ−ゼル機関の吸気加熱用ヒ−タの制御方法 |
Also Published As
| Publication number | Publication date |
|---|---|
| EG14169A (en) | 1983-12-31 |
| GR73837B (sv) | 1984-05-04 |
| JPH02191284A (ja) | 1990-07-27 |
| IT1188790B (it) | 1988-01-28 |
| IT7924438A0 (it) | 1979-07-17 |
| PH15581A (en) | 1983-02-17 |
| MX5956E (es) | 1984-09-06 |
| IN154073B (sv) | 1984-09-15 |
| DD146790A6 (de) | 1981-03-04 |
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