JP5920601B2 - 蛍光性カルバペネム - Google Patents
蛍光性カルバペネム Download PDFInfo
- Publication number
- JP5920601B2 JP5920601B2 JP2013517098A JP2013517098A JP5920601B2 JP 5920601 B2 JP5920601 B2 JP 5920601B2 JP 2013517098 A JP2013517098 A JP 2013517098A JP 2013517098 A JP2013517098 A JP 2013517098A JP 5920601 B2 JP5920601 B2 JP 5920601B2
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- JP
- Japan
- Prior art keywords
- carbapenemase
- diluent
- compound
- bacterial
- inhibitor
- 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.)
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- YZBQHRLRFGPBSL-RXMQYKEDSA-N carbapenem Chemical compound C1C=CN2C(=O)C[C@H]21 YZBQHRLRFGPBSL-RXMQYKEDSA-N 0.000 title claims 4
- 108010068385 carbapenemase Proteins 0.000 claims description 67
- -1 amino, hydroxy Chemical group 0.000 claims description 63
- 150000001875 compounds Chemical class 0.000 claims description 46
- 230000001580 bacterial effect Effects 0.000 claims description 41
- 238000000034 method Methods 0.000 claims description 32
- 238000001514 detection method Methods 0.000 claims description 30
- 239000003112 inhibitor Substances 0.000 claims description 21
- 238000012360 testing method Methods 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 18
- 125000001424 substituent group Chemical group 0.000 claims description 17
- 238000011835 investigation Methods 0.000 claims description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 13
- 239000000203 mixture Substances 0.000 claims description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- 125000002252 acyl group Chemical group 0.000 claims description 12
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 239000003085 diluting agent Substances 0.000 claims description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 241000894007 species Species 0.000 claims description 10
- 239000003054 catalyst Substances 0.000 claims description 8
- 235000015097 nutrients Nutrition 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 8
- 125000006239 protecting group Chemical group 0.000 claims description 8
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 7
- 239000003599 detergent Substances 0.000 claims description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 125000000319 biphenyl-4-yl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 6
- 125000006269 biphenyl-2-yl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1=C(*)C([H])=C([H])C([H])=C1[H] 0.000 claims description 5
- 238000006880 cross-coupling reaction Methods 0.000 claims description 5
- 125000002950 monocyclic group Chemical group 0.000 claims description 5
- 125000002619 bicyclic group Chemical group 0.000 claims description 4
- 230000009089 cytolysis Effects 0.000 claims description 4
- 238000010511 deprotection reaction Methods 0.000 claims description 4
- 238000011161 development Methods 0.000 claims description 4
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 150000007530 organic bases Chemical class 0.000 claims description 4
- 125000004043 oxo group Chemical group O=* 0.000 claims description 4
- 239000008024 pharmaceutical diluent Substances 0.000 claims description 4
- 125000005118 N-alkylcarbamoyl group Chemical group 0.000 claims description 3
- 125000004442 acylamino group Chemical group 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 3
- 239000007864 aqueous solution Substances 0.000 claims description 3
- 125000001246 bromo group Chemical group Br* 0.000 claims description 3
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 125000005842 heteroatom Chemical group 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims description 3
- 230000001939 inductive effect Effects 0.000 claims description 3
- 150000007529 inorganic bases Chemical class 0.000 claims description 3
- 239000003475 metalloproteinase inhibitor Substances 0.000 claims description 3
- 125000005208 trialkylammonium group Chemical group 0.000 claims description 3
- OSDBTCRHLMWVSB-UHFFFAOYSA-N 2-(6-oxo-1,7-dihydropurin-2-yl)guanidine Chemical compound C(N)(=N)NC=1NC(C=2NC=NC=2N=1)=O OSDBTCRHLMWVSB-UHFFFAOYSA-N 0.000 claims description 2
- 241000233866 Fungi Species 0.000 claims description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 2
- 101000998548 Yersinia ruckeri Alkaline proteinase inhibitor Proteins 0.000 claims description 2
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
- 229910052760 oxygen Inorganic materials 0.000 claims description 2
- 239000001301 oxygen Substances 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 2
- 229910052717 sulfur Chemical group 0.000 claims description 2
- 239000011593 sulfur Chemical group 0.000 claims description 2
- 239000012351 deprotecting agent Substances 0.000 claims 2
- 230000002194 synthesizing effect Effects 0.000 claims 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims 1
- 102000012479 Serine Proteases Human genes 0.000 claims 1
- 108010022999 Serine Proteases Proteins 0.000 claims 1
- 230000005693 optoelectronics Effects 0.000 claims 1
- BSIMZHVOQZIAOY-SCSAIBSYSA-N 1-carbapenem-3-carboxylic acid Chemical compound OC(=O)C1=CC[C@@H]2CC(=O)N12 BSIMZHVOQZIAOY-SCSAIBSYSA-N 0.000 description 44
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 27
- 239000000243 solution Substances 0.000 description 26
- 102000004190 Enzymes Human genes 0.000 description 23
- 108090000790 Enzymes Proteins 0.000 description 23
- 102000006635 beta-lactamase Human genes 0.000 description 19
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 241000894006 Bacteria Species 0.000 description 13
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 13
- 108090000204 Dipeptidase 1 Proteins 0.000 description 12
- 241000588724 Escherichia coli Species 0.000 description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 12
- 108020004256 Beta-lactamase Proteins 0.000 description 11
- 241000588747 Klebsiella pneumoniae Species 0.000 description 10
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 10
- 229940041011 carbapenems Drugs 0.000 description 10
- 238000002329 infrared spectrum Methods 0.000 description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 230000008034 disappearance Effects 0.000 description 9
- 238000006460 hydrolysis reaction Methods 0.000 description 9
- 102000020235 metallo-beta-lactamase Human genes 0.000 description 9
- 108060004734 metallo-beta-lactamase Proteins 0.000 description 9
- 230000007062 hydrolysis Effects 0.000 description 8
- FYQBQWCKCPLPFC-UHFFFAOYSA-M potassium;2-methylhept-2-enoate Chemical compound [K+].CCCCC=C(C)C([O-])=O FYQBQWCKCPLPFC-UHFFFAOYSA-M 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- WKDDRNSBRWANNC-UHFFFAOYSA-N Thienamycin Natural products C1C(SCCN)=C(C(O)=O)N2C(=O)C(C(O)C)C21 WKDDRNSBRWANNC-UHFFFAOYSA-N 0.000 description 7
- 239000003242 anti bacterial agent Substances 0.000 description 7
- 229940088710 antibiotic agent Drugs 0.000 description 7
- 238000001914 filtration Methods 0.000 description 7
- ZSKVGTPCRGIANV-ZXFLCMHBSA-N imipenem Chemical compound C1C(SCC\N=C\N)=C(C(O)=O)N2C(=O)[C@H]([C@H](O)C)[C@H]21 ZSKVGTPCRGIANV-ZXFLCMHBSA-N 0.000 description 7
- 229960002182 imipenem Drugs 0.000 description 7
- 238000011534 incubation Methods 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- DMJNNHOOLUXYBV-PQTSNVLCSA-N meropenem Chemical compound C=1([C@H](C)[C@@H]2[C@H](C(N2C=1C(O)=O)=O)[C@H](O)C)S[C@@H]1CN[C@H](C(=O)N(C)C)C1 DMJNNHOOLUXYBV-PQTSNVLCSA-N 0.000 description 7
- 229960002260 meropenem Drugs 0.000 description 7
- 238000000527 sonication Methods 0.000 description 7
- XHIQSYLMJAVDLM-UHFFFAOYSA-N (4-nitrophenyl)methyl 2-methylhept-2-enoate Chemical compound CCCCC=C(C)C(=O)OCC1=CC=C([N+]([O-])=O)C=C1 XHIQSYLMJAVDLM-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 230000008859 change Effects 0.000 description 6
- 229920001971 elastomer Polymers 0.000 description 6
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 6
- 235000019341 magnesium sulphate Nutrition 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 6
- 150000003952 β-lactams Chemical class 0.000 description 6
- 101100026178 Caenorhabditis elegans egl-3 gene Proteins 0.000 description 5
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 125000002837 carbocyclic group Chemical group 0.000 description 5
- 230000007071 enzymatic hydrolysis Effects 0.000 description 5
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 5
- 239000002609 medium Substances 0.000 description 5
- 239000011591 potassium Substances 0.000 description 5
- 229910052700 potassium Inorganic materials 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 4
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 4
- 239000012267 brine Substances 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- DCFKHNIGBAHNSS-UHFFFAOYSA-N chloro(triethyl)silane Chemical compound CC[Si](Cl)(CC)CC DCFKHNIGBAHNSS-UHFFFAOYSA-N 0.000 description 4
- 230000021615 conjugation Effects 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- OAMZXMDZZWGPMH-UHFFFAOYSA-N ethyl acetate;toluene Chemical compound CCOC(C)=O.CC1=CC=CC=C1 OAMZXMDZZWGPMH-UHFFFAOYSA-N 0.000 description 4
- 229940071106 ethylenediaminetetraacetate Drugs 0.000 description 4
- 125000000623 heterocyclic group Chemical group 0.000 description 4
- 229910052763 palladium Inorganic materials 0.000 description 4
- 238000010898 silica gel chromatography Methods 0.000 description 4
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 4
- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 description 3
- FYZUENZXIZCLAZ-UHFFFAOYSA-N 2-methylhept-2-enoic acid Chemical compound CCCCC=C(C)C(O)=O FYZUENZXIZCLAZ-UHFFFAOYSA-N 0.000 description 3
- 229920001817 Agar Polymers 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 3
- 229930186147 Cephalosporin Natural products 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 108010087702 Penicillinase Proteins 0.000 description 3
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 239000008272 agar Substances 0.000 description 3
- 239000012062 aqueous buffer Substances 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- 230000003115 biocidal effect Effects 0.000 description 3
- 235000011089 carbon dioxide Nutrition 0.000 description 3
- 210000002421 cell wall Anatomy 0.000 description 3
- 229940124587 cephalosporin Drugs 0.000 description 3
- 150000001780 cephalosporins Chemical class 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 3
- 125000006575 electron-withdrawing group Chemical group 0.000 description 3
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 3
- 239000006260 foam Substances 0.000 description 3
- 238000004108 freeze drying Methods 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 239000002054 inoculum Substances 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 238000013048 microbiological method Methods 0.000 description 3
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 3
- 229950009506 penicillinase Drugs 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 230000001954 sterilising effect Effects 0.000 description 3
- 238000004659 sterilization and disinfection Methods 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- LHNIIDJCEODSHA-OQRUQETBSA-N (6r,7r)-3-[(e)-2-(2,4-dinitrophenyl)ethenyl]-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound N([C@H]1[C@H]2SCC(=C(N2C1=O)C(=O)O)\C=C\C=1C(=CC(=CC=1)[N+]([O-])=O)[N+]([O-])=O)C(=O)CC1=CC=CS1 LHNIIDJCEODSHA-OQRUQETBSA-N 0.000 description 2
- HPYNZHMRTTWQTB-UHFFFAOYSA-N 2,3-dimethylpyridine Chemical compound CC1=CC=CN=C1C HPYNZHMRTTWQTB-UHFFFAOYSA-N 0.000 description 2
- 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 description 2
- 241000589291 Acinetobacter Species 0.000 description 2
- GNWUOVJNSFPWDD-XMZRARIVSA-M Cefoxitin sodium Chemical compound [Na+].N([C@]1(OC)C(N2C(=C(COC(N)=O)CS[C@@H]21)C([O-])=O)=O)C(=O)CC1=CC=CS1 GNWUOVJNSFPWDD-XMZRARIVSA-M 0.000 description 2
- 241000588923 Citrobacter Species 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 102000005744 Glycoside Hydrolases Human genes 0.000 description 2
- 108010031186 Glycoside Hydrolases Proteins 0.000 description 2
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical class NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 description 2
- 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 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- 241000588653 Neisseria Species 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- 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 2
- 108010093965 Polymyxin B Proteins 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 241000588769 Proteus <enterobacteria> Species 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 2
- 239000011324 bead Substances 0.000 description 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 2
- 125000003460 beta-lactamyl group Chemical group 0.000 description 2
- 239000007853 buffer solution Substances 0.000 description 2
- 239000006172 buffering agent Substances 0.000 description 2
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 2
- 125000004623 carbolinyl group Chemical group 0.000 description 2
- 229960002682 cefoxitin Drugs 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000007327 hydrogenolysis reaction Methods 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 125000001041 indolyl group Chemical group 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 125000005956 isoquinolyl group Chemical group 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- 229910052749 magnesium Inorganic materials 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 229940049954 penicillin Drugs 0.000 description 2
- 125000004625 phenanthrolinyl group Chemical group N1=C(C=CC2=CC=C3C=CC=NC3=C12)* 0.000 description 2
- 125000005561 phenanthryl group Chemical group 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 238000003752 polymerase chain reaction Methods 0.000 description 2
- 229920000024 polymyxin B Polymers 0.000 description 2
- 229960005266 polymyxin b Drugs 0.000 description 2
- IKPPIDRDTJORBM-UHFFFAOYSA-M potassium 1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound [K+].N12C(=CCC2CC1)C(=O)[O-] IKPPIDRDTJORBM-UHFFFAOYSA-M 0.000 description 2
- 229910000160 potassium phosphate Inorganic materials 0.000 description 2
- 235000011009 potassium phosphates Nutrition 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 2
- 125000005493 quinolyl group Chemical group 0.000 description 2
- 230000009257 reactivity Effects 0.000 description 2
- 230000002829 reductive effect Effects 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 229910052703 rhodium Inorganic materials 0.000 description 2
- 239000010948 rhodium Substances 0.000 description 2
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- 239000003001 serine protease inhibitor Substances 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
- 238000003860 storage Methods 0.000 description 2
- 150000003751 zinc Chemical class 0.000 description 2
- OBQRODBYVNIZJU-UHFFFAOYSA-N (4-acetylphenyl)boronic acid Chemical compound CC(=O)C1=CC=C(B(O)O)C=C1 OBQRODBYVNIZJU-UHFFFAOYSA-N 0.000 description 1
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
- WIKBZUXHNPONPP-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoro-2-iodo-2-(trifluoromethyl)propane Chemical compound FC(F)(F)C(I)(C(F)(F)F)C(F)(F)F WIKBZUXHNPONPP-UHFFFAOYSA-N 0.000 description 1
- CMCBDXRRFKYBDG-UHFFFAOYSA-N 1-dodecoxydodecane Chemical compound CCCCCCCCCCCCOCCCCCCCCCCCC CMCBDXRRFKYBDG-UHFFFAOYSA-N 0.000 description 1
- WZPBZJONDBGPKJ-VEHQQRBSSA-L 2-[(z)-[1-(2-amino-1,3-thiazol-4-yl)-2-[[(2s,3s)-2-methyl-4-oxo-1-sulfonatoazetidin-3-yl]amino]-2-oxoethylidene]amino]oxy-2-methylpropanoate Chemical compound O=C1N(S([O-])(=O)=O)[C@@H](C)[C@@H]1NC(=O)C(=N/OC(C)(C)C([O-])=O)\C1=CSC(N)=N1 WZPBZJONDBGPKJ-VEHQQRBSSA-L 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- 241000607534 Aeromonas Species 0.000 description 1
- WZPBZJONDBGPKJ-UHFFFAOYSA-N Antibiotic SQ 26917 Natural products O=C1N(S(O)(=O)=O)C(C)C1NC(=O)C(=NOC(C)(C)C(O)=O)C1=CSC(N)=N1 WZPBZJONDBGPKJ-UHFFFAOYSA-N 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- GENOCZNUSQQKKW-UHFFFAOYSA-M C1CC2C1CC=C2C(=O)[O-].[K+] Chemical compound C1CC2C1CC=C2C(=O)[O-].[K+] GENOCZNUSQQKKW-UHFFFAOYSA-M 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 241000985973 Castilla ulei Species 0.000 description 1
- GHXZTYHSJHQHIJ-UHFFFAOYSA-N Chlorhexidine Chemical compound C=1C=C(Cl)C=CC=1NC(N)=NC(N)=NCCCCCCN=C(N)N=C(N)NC1=CC=C(Cl)C=C1 GHXZTYHSJHQHIJ-UHFFFAOYSA-N 0.000 description 1
- 206010011409 Cross infection Diseases 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 108010043121 Green Fluorescent Proteins Proteins 0.000 description 1
- 102000004144 Green Fluorescent Proteins Human genes 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- JUZNIMUFDBIJCM-ANEDZVCMSA-N Invanz Chemical compound O=C([C@H]1NC[C@H](C1)SC=1[C@H](C)[C@@H]2[C@H](C(N2C=1C(O)=O)=O)[C@H](O)C)NC1=CC=CC(C(O)=O)=C1 JUZNIMUFDBIJCM-ANEDZVCMSA-N 0.000 description 1
- 238000002768 Kirby-Bauer method Methods 0.000 description 1
- 241000588749 Klebsiella oxytoca Species 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 241000588655 Moraxella catarrhalis Species 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 206010029803 Nosocomial infection Diseases 0.000 description 1
- 206010034133 Pathogen resistance Diseases 0.000 description 1
- 108700020474 Penicillin-Binding Proteins Proteins 0.000 description 1
- 241000589516 Pseudomonas Species 0.000 description 1
- 241000607142 Salmonella Species 0.000 description 1
- 229940122055 Serine protease inhibitor Drugs 0.000 description 1
- 101710102218 Serine protease inhibitor Proteins 0.000 description 1
- 241000607715 Serratia marcescens Species 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- 241000219793 Trifolium Species 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- IOFXKDJCGBMXBT-UHFFFAOYSA-N [2-(4-acetylphenyl)phenyl]boronic acid Chemical compound C1=CC(C(=O)C)=CC=C1C1=CC=CC=C1B(O)O IOFXKDJCGBMXBT-UHFFFAOYSA-N 0.000 description 1
- 125000001539 acetonyl group Chemical group [H]C([H])([H])C(=O)C([H])([H])* 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000010306 acid treatment Methods 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- 150000001351 alkyl iodides Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 125000000909 amidinium group Chemical group 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 238000012443 analytical study Methods 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- 229960003644 aztreonam Drugs 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 244000052616 bacterial pathogen Species 0.000 description 1
- 239000003782 beta lactam antibiotic agent Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical group 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 229960003260 chlorhexidine Drugs 0.000 description 1
- 239000008139 complexing agent Substances 0.000 description 1
- 230000001086 cytosolic effect Effects 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- GSVLCKASFMVUSW-UHFFFAOYSA-N decyl(dimethyl)phosphine oxide Chemical compound CCCCCCCCCCP(C)(C)=O GSVLCKASFMVUSW-UHFFFAOYSA-N 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 229940039227 diagnostic agent Drugs 0.000 description 1
- 239000000032 diagnostic agent Substances 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 230000003292 diminished effect Effects 0.000 description 1
- 229960002770 ertapenem Drugs 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 229930182478 glucoside Natural products 0.000 description 1
- 150000008131 glucosides Chemical class 0.000 description 1
- 239000005090 green fluorescent protein Substances 0.000 description 1
- 239000003966 growth inhibitor Substances 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 125000001072 heteroaryl group Chemical group 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 239000000076 hypertonic saline solution Substances 0.000 description 1
- 239000000815 hypotonic solution Substances 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 159000000014 iron salts Chemical class 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- PYIDGJJWBIBVIA-UYTYNIKBSA-N lauryl glucoside Chemical compound CCCCCCCCCCCCO[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O PYIDGJJWBIBVIA-UYTYNIKBSA-N 0.000 description 1
- 231100001231 less toxic Toxicity 0.000 description 1
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 229960003085 meticillin Drugs 0.000 description 1
- 230000002906 microbiologic effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- YYELLDKEOUKVIQ-UHFFFAOYSA-N octaethyleneglycol monododecyl ether Chemical compound CCCCCCCCCCCCOCCOCCOCCOCCOCCOCCOCCOCCO YYELLDKEOUKVIQ-UHFFFAOYSA-N 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
- 230000001575 pathological effect Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 230000008823 permeabilization Effects 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 150000003141 primary amines Chemical class 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
- 230000000644 propagated effect Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 239000006152 selective media Substances 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- NRHMKIHPTBHXPF-TUJRSCDTSA-M sodium cholate Chemical class [Na+].C([C@H]1C[C@H]2O)[C@H](O)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@@H](CCC([O-])=O)C)[C@@]2(C)[C@@H](O)C1 NRHMKIHPTBHXPF-TUJRSCDTSA-M 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 235000010265 sodium sulphite Nutrition 0.000 description 1
- 238000011895 specific detection Methods 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 238000010257 thawing Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 238000002211 ultraviolet spectrum Methods 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 description 1
- 229960001763 zinc sulfate Drugs 0.000 description 1
- 229910000368 zinc sulfate Inorganic materials 0.000 description 1
- 239000002132 β-lactam antibiotic Substances 0.000 description 1
- 229940124586 β-lactam antibiotics Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D477/00—Heterocyclic compounds containing 1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbapenicillins, thienamycins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulphur-containing hetero ring
- C07D477/10—Heterocyclic compounds containing 1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbapenicillins, thienamycins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulphur-containing hetero ring with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 4, and with a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2
- C07D477/12—Heterocyclic compounds containing 1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbapenicillins, thienamycins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulphur-containing hetero ring with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 4, and with a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2 with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached in position 6
- C07D477/14—Heterocyclic compounds containing 1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. carbapenicillins, thienamycins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulphur-containing hetero ring with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached in position 4, and with a carbon atom having three bonds to hetero atoms with at the most one bond to halogen, e.g. an ester or nitrile radical, directly attached in position 2 with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached in position 6 with hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached in position 3
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/34—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving hydrolase
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/90—Enzymes; Proenzymes
- G01N2333/914—Hydrolases (3)
- G01N2333/948—Hydrolases (3) acting on peptide bonds (3.4)
- G01N2333/968—Plasmin, i.e. fibrinolysin
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/90—Enzymes; Proenzymes
- G01N2333/914—Hydrolases (3)
- G01N2333/978—Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5)
- G01N2333/986—Hydrolases (3) acting on carbon to nitrogen bonds other than peptide bonds (3.5) acting on amide bonds in cyclic amides (3.5.2), e.g. beta-lactamase (penicillinase, 3.5.2.6), creatinine amidohydrolase (creatininase, EC 3.5.2.10), N-methylhydantoinase (3.5.2.6)
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2500/00—Screening for compounds of potential therapeutic value
Description
これらの細菌酵素は、不活性代謝物質の形成を伴ってβ−ラクタム部分の加水分解を触媒する(Chemother.J.2004,3,206)。2001年には、340を超える種々のベータラクタマーゼが知られていた(Clin.Infect.Dis.2001,32,1085)。
臨床検査室における定型調査にはほとんど有用でない。
実施例1
(4S,5R,6S)−3−(4−アセチル−フェニル)−6−((1’R)−ヒドロキシ−エチル)−4−メチル−7−オキソ−1−アザ−ビシクロ[3.2.0]ヘプタ−2−エン−2−カルボン酸カリウムの調製
(4S,5R,6S)−3−(4−アセチル−フェニル)−4−メチル−7−オキソ−6−((1’R)−ヒドロキシ−エチル)−1−アザ−ビシクロ[3.2.0]ヘプタ−2−エン−2−カルボキシル酸4−ニトロ−ベンジルエステル
(4S,5R,6S)−3−(4−アセチル−フェニル)−6−((1’R)−ヒドロキシ−エチル)−4−メチル−7−オキソ−1−アザ−ビシクロ[3.2.0]ヘプタ−2−エン−2−カルボン酸カリウム
実施例2
(4S,5R,6S)−6−[(1’R)−ヒドロキシ−エチル]−4−メチル−7−オキソ−3−(4−アミノ−フェニル)−1−アザ−ビシクロ[3.2.0]ヘプタ−2−エン−2−カルボン酸カリウムの調製
(4S,5R,6S)−6−((1’R)−ヒドロキシエチル)−4−メチル−3−(4−ニトロ−フェニル)−7−オキソ−1−アザ−ビシクロ[3.2.0]ヘプタ−2−エン−2−カルボキシル酸4−ニトロ−ベンジルエステル
(4S,5R.6S)−6−[(1’R)−ヒドロキシ−エチル]−4−メチル−7−オキソ−3−(4−アミノ−フェニル)−1−アザ−ビシクロ[3.2.0]ヘプタ−2−エン−2−カルボン酸カリウム
実施例3
(4S,5R,6S)−3−(4’−アセチル−ビフェニル−4−イル)−6−[(1’R)−ヒドロキシエチル]−4−メチル−7−オキソ−1−アザ−ビシクロ[3.2.0]ヘプタ−2−エン−2−カルボン酸カリウムの調製
(4S,5R,6S)−3−(4’−アセチル−ビフェニル−4−イル)−6−((1’R)−ヒドロキシ−エチル)−4−メチル−7−オキソ−1−アザ−ビシクロ[3.2.0]ヘプタ−2−エン−2−カルボン酸4−ニトロ−ベンジルエステル
(4S,5R,6S)−3−(4’−アセチル−ビフェニル−4−イル)−6−[(1’R)−ヒドロキシエチル]−4−メチル−7−オキソ−1−アザ−ビシクロ[3.2.0]ヘプタ−2−エン−2−カルボン酸カリウム
実施例4
(4S,5R,6S)−3−(4−アセチル−フェニル)−6−[(1’R)−アセトキシエチル]−4−メチル−7−オキソ−1−アザ−ビシクロ[3.2.0]ヘプタ−2−エン−2−カルボン酸カリウムの調製
実施例5
超音波処理による物理的破壊後の蛍光性(4S,5R,6S)−3−(4−アセチル−フェニル)−6−((1’R)−ヒドロキシ−エチル)−4−メチル−7−オキソ−1−アザ−ビシクロ[3.2.0]ヘプタ−2−エン−2−カルボン酸カリウムによる肺炎杆菌カルバペネマーゼ(KPC)の検出
実施例6
ガラスビーズを含む超音波処理による物理的破壊の間の蛍光性(4S,5R,6S)−3−(4−アセチル−フェニル)−6−((1’R)−ヒドロキシ−エチル)−4−メチル−7−オキソ−1−アザ−ビシクロ[3.2.0]ヘプタ−2−エン−2−カルボン酸カリウムによる肺炎杆菌カルバペネマーゼ(KPC)の検出
実施例7
超音波処理による物理的破壊後の蛍光性(4S,5R,6S)−3−(4−アセチル−フェニル)−6−((1’R)−ヒドロキシ−エチル)−4−メチル−7−オキソ−1−アザ−ビシクロ[3.2.0]ヘプタ−2−エン−2−カルボン酸カリウムによる大腸菌の誘発性(Qxa−タイプ)カルバペネマーゼの検出
実施例8
インキュベーションの間のPBS中の蛍光性(4S,5R,6S)−3−(4−アセチル−フェニル)−6−((1’R)−ヒドロキシ−エチル)−4−メチル−7−オキソ−1−アザ−ビシクロ[3.2.0]ヘプタ−2−エン−2−カルボン酸カリウムによるメタロカルバペネマーゼの検出
実施例9
インキュベーションの間の蛍光性(4S,5R,6S)−3−(4−アセチル−フェニル)−6−((1’R)−ヒドロキシ−エチル)−4−メチル−7−オキソ−1−アザ−ビシクロ[3.2.0]ヘプタ−2−エン−2−カルボン酸カリウムによるカルバペネマーゼの検出
実施例10
最適化したインキュベーションの間の蛍光性(4S,5R,6S)−3−(4−アセチル−フェニル)−6−((1’R)−ヒドロキシ−エチル)−4−メチル−7−オキソ−1−アザ−ビシクロ[3.2.0]ヘプタ−2−エン−2−カルボン酸カリウムによるカルバペネマーゼの検出
実施例11
化学的溶解の間の蛍光性(4S,5R,6S)−3−(4−アセチル−フェニル)−6−((1’R)−ヒドロキシ−エチル)−4−メチル−7−オキソ−1−アザ−ビシクロ[3.2.0]ヘプタ−2−エン−2−カルボン酸カリウムによるカルバペネマーゼの検出
Claims (19)
- 菌のカルバペネムへの抵抗を検知するために用いられる、式Iの蛍光性もしくは発色性カルバペネムおよび/またはその塩。
[式中、R1は、水素、または1から6の炭素原子をそれぞれ有するアルキルおよびアシルから選択され、ここで、Arは、モノもしくはジ置換炭素環式芳香族、または場合によってモノもしくはジ置換ヘテロ環式芳香族基であり、ここで、炭素環式芳香族部分は、6から14の炭素原子を有する単環式、二環式または三環式であり、ヘテロ環式芳香族部分は、単環式、二環式または三環式であり、1から13の炭素原子を含み、かつ互いに独立して酸素、窒素または硫黄から選択される1から5のヘテロ原子を含み、ここで、芳香族部分Arの置換基R2およびR3は、互いに独立して、水素、アミノ、ヒドロキシ、オキソ、フルオロ、クロロ、ブロモ、ニトロ、シアノ、カルボキシ、カルバモイル、スルファモイル、アミジノ、グアニジノ、スルホ、またはそれぞれ1から6の炭素原子を有するアルキル、アルコキシ、アシル、アシルアミノ、モノアルキルアミノ、ジアルキルアミノ、トリアルキルアンモニウム、Ν,Ν−ジアルキルカルバモイル、N−アルキルカルバモイルおよびアルコキシカルボニルから選択される。]。
- 細菌性カルバペネマーゼの調査および/または検出のための方法であって、請求項1に記載の化合物、栄養培地および少なくとも1種の細菌種が希釈剤中に組み込まれていることを特徴とする方法。
- 細菌性カルバペネマーゼの調査および/または検出のための方法であって、請求項1に記載の化合物、イオン性または非イオン性清浄剤および少なくとも1種の細菌種が希釈剤に組み込まれていることを特徴とする方法。
- 細菌性カルバペネマーゼの調査および/または検出のための方法であって、請求項1に記載の化合物、および少なくとも1種の細菌種の溶解によって得られた調製物が希釈剤に組み込まれていることを特徴とする方法。
- 細菌性カルバペネマーゼの調査および/または検出のための方法であって、請求項1に記載の化合物の発色または蛍光の強度が、視覚によってまたは光電子装置によって希釈剤中でモニターされることを特徴とする方法。
- カルバペネマーゼ阻害薬を試験するための請求項1に記載の化合物の使用。
- カルバペネマーゼ阻害薬の調査および/または検出のための方法であって、既知または疑わしい阻害薬、請求項1に記載の化合物、栄養培地および少なくとも1種のカルバペネマーゼ産生細菌種が希釈剤に組み込まれていることを特徴とする方法。
- カルバペネマーゼ阻害薬の調査および/または検出のための方法であって、既知または疑わしい阻害薬、請求項1に記載の化合物、およびカルバペネマーゼ産生細菌種の溶解によって得られた調製物が希釈剤に組み込まれていることを特徴とする方法。
- 阻害薬がセリンプロテアーゼまたはメタロプロテアーゼ阻害薬である、請求項7または8に記載の方法。
- カルバペネマーゼ誘発の阻害薬を試験するための請求項1に記載の化合物の使用。
- カルバペネマーゼ誘発の阻害薬の調査および/または検出のための方法であって、請求項1に記載の化合物、既知または疑わしい阻害薬、カルバペネマーゼ促進剤、栄養培地、および誘発性カルバペネマーゼを産生することができる少なくとも1種の細菌種が希釈剤に組み込まれていることを特徴とする方法。
- カルバペネマーゼ誘発の阻害薬の調査および/または検出のための方法であって、請求項1に記載の化合物、既知または疑わしい阻害薬、栄養培地および少なくとも1種のカルバペネマーゼ産生細菌種が希釈剤に組み込まれていることを特徴とする方法。
- 請求項1に記載の化合物が水溶液中で疑わしいまたは立証された細菌性カルバペネマーゼによって加水分解されることを特徴とする方法。
- 請求項1に記載の化合物、イオン性もしくは非イオン性清浄剤およびそのための医薬品担体または希釈剤、ならびに使用説明書を1つもしくは複数の容器内に含む、細菌のカルバペネム耐性を検出するためのキット。
- 請求項1に記載の化合物および/またはその塩であって、R1は、水素または1から6の炭素原子をそれぞれ有するアルキルおよびアシルから選択され、ここで、Arは、モノもしくはジ置換フェニル、2−ビフェニルもしくは4−ビフェニル、または場合によってモノもしくはジ置換2−ピリジル、4−ピリジルもしくは2−ピリミジニルであり、ここで、芳香族部分Arの置換基R2およびR3は、互いに独立して、水素、アミノ、ヒドロキシ、オキソ、フルオロ、クロロ、ブロモ、ニトロ、シアノ、カルボキシ、カルバモイル、スルファモイル、アミジノ、グアニジノ、スルホ、またはそれぞれ1から6の炭素原子を有するアルキル、アルコキシ、アシル、アシルアミノ、モノアルキルアミノ、ジアルキルアミノ、トリアルキルアンモニウム、Ν,Ν−ジアルキルカルバモイル、N−アルキルカルバモイルおよびアルコキシカルボニルから選択される、化合物。
- 請求項15に記載の化合物を合成する方法であって、
a)式
b)式
- 請求項15に記載の化合物を合成する方法であって、
a)式
b)式
- 請求項15による化合物およびイオンもしくは非イオン性清浄剤ならびにそのための医薬品担体または希釈剤を含む組成物。
- 請求項15に記載の化合物、栄養培地およびそのための医薬品担体または希釈剤を含む組成物。
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