NO310684B1 - 1-metylkarbapenemderivater og farmasöytisk preparat inneholdende disse - Google Patents

Info

Publication number

NO310684B1

NO310684B1 NO19982873A NO982873A NO310684B1 NO 310684 B1 NO310684 B1 NO 310684B1 NO 19982873 A NO19982873 A NO 19982873A NO 982873 A NO982873 A NO 982873A NO 310684 B1 NO310684 B1 NO 310684B1

Authority

NO

Norway

Prior art keywords

nitrobenzyloxycarbonyl

methyl

denotes

pyrrolidin

ylcarbonyl

Prior art date

1995-12-21

Links

• Espacenet
• Global Dossier
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• YKMONJZIUAOVEM-GDVGLLTNSA-N (5S)-4-methyl-1-azabicyclo[3.2.0]hept-2-en-7-one Chemical class CC1C=CN2[C@H]1CC2=O YKMONJZIUAOVEM-GDVGLLTNSA-N 0.000 title claims description 7
• 239000008194 pharmaceutical composition Substances 0.000 title 1
• -1 phenylene- Chemical class 0.000 claims description 112
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 37
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 34
• 150000003839 salts Chemical class 0.000 claims description 29
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 21
• 125000001424 substituent group Chemical group 0.000 claims description 12
• 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 11
• 125000000217 alkyl group Chemical group 0.000 claims description 9
• 150000002148 esters Chemical group 0.000 claims description 9
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 7
• 208000035473 Communicable disease Diseases 0.000 claims description 7
• 238000001727 in vivo Methods 0.000 claims description 7
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
• 239000004615 ingredient Substances 0.000 claims description 6
• 230000002265 prevention Effects 0.000 claims description 6
• 238000004519 manufacturing process Methods 0.000 claims description 5
• NARVIWMVBMUEOG-UHFFFAOYSA-N prop-1-en-2-ol Chemical group CC(O)=C NARVIWMVBMUEOG-UHFFFAOYSA-N 0.000 claims description 4
• 239000003814 drug Substances 0.000 claims description 3
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
• AURGXAAPSXABQV-VZRURGHZSA-N (5S)-3-[5-[3-[2-(diaminomethylideneamino)propanoylamino]azetidine-1-carbonyl]pyrrolidin-3-yl]sulfanyl-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound CC(O)C1[C@H]2C(C)C(SC3CNC(C3)C(=O)N3CC(C3)NC(=O)C(C)NC(N)=N)=C(N2C1=O)C(O)=O AURGXAAPSXABQV-VZRURGHZSA-N 0.000 claims description 2
• SIOTXAXQMYMRSW-XRKGJLGJSA-N (5S)-3-[5-[3-[[2-(diaminomethylideneamino)acetyl]-methylamino]pyrrolidine-1-carbonyl]pyrrolidin-3-yl]sulfanyl-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound N(C(=N)N)CC(=O)N(C)C1CN(CC1)C(=O)C1NCC(C1)SC=1C([C@H]2N(C=1C(=O)O)C(C2C(C)O)=O)C SIOTXAXQMYMRSW-XRKGJLGJSA-N 0.000 claims description 2
• KEDAXBWZURNCHS-XRKGJLGJSA-N (5S)-3-[5-[3-[[2-(diaminomethylideneamino)acetyl]amino]pyrrolidine-1-carbonyl]-1-methylpyrrolidin-3-yl]sulfanyl-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound CC(O)C1[C@H]2C(C)C(SC3CC(N(C)C3)C(=O)N3CCC(C3)NC(=O)CNC(N)=N)=C(N2C1=O)C(O)=O KEDAXBWZURNCHS-XRKGJLGJSA-N 0.000 claims description 2
• VSVDGUIRMVQXNP-BOFZDKAQSA-N (5S)-3-[5-[3-[[2-(diaminomethylideneamino)acetyl]amino]pyrrolidine-1-carbonyl]pyrrolidin-3-yl]sulfanyl-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical group CC(O)C1[C@H]2C(C)C(SC3CNC(C3)C(=O)N3CCC(C3)NC(=O)CNC(N)=N)=C(N2C1=O)C(O)=O VSVDGUIRMVQXNP-BOFZDKAQSA-N 0.000 claims description 2
• QKIOFYJUUDPEND-XRKGJLGJSA-N (5S)-3-[5-[3-[[2-[carbamimidoyl(methyl)amino]acetyl]amino]pyrrolidine-1-carbonyl]pyrrolidin-3-yl]sulfanyl-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound CN(C(=N)N)CC(=O)NC1CN(CC1)C(=O)C1NCC(C1)SC=1C([C@H]2N(C=1C(=O)O)C(C2C(C)O)=O)C QKIOFYJUUDPEND-XRKGJLGJSA-N 0.000 claims description 2
• CAOOCJBOEODUAN-CIFATLAASA-N (5S)-3-[5-[3-[[4-(diaminomethylideneamino)-3-hydroxybutanoyl]amino]azetidine-1-carbonyl]pyrrolidin-3-yl]sulfanyl-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound N(C(=N)N)CC(CC(=O)NC1CN(C1)C(=O)C1NCC(C1)SC=1C([C@H]2N(C=1C(=O)O)C(C2C(C)O)=O)C)O CAOOCJBOEODUAN-CIFATLAASA-N 0.000 claims description 2
• 125000000783 acetimidoyl group Chemical group C(C)(=N)* 0.000 claims description 2
• 239000003242 anti bacterial agent Substances 0.000 claims description 2
• 125000004956 cyclohexylene group Chemical group 0.000 claims description 2
• 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 2
• 125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 claims description 2
• 239000000825 pharmaceutical preparation Substances 0.000 claims description 2
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 2
• 150000001875 compounds Chemical class 0.000 description 355
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 283
• 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 249
• 238000000862 absorption spectrum Methods 0.000 description 241
• RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 230
• 239000000243 solution Substances 0.000 description 193
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 192
• 239000000203 mixture Substances 0.000 description 187
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 171
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 164
• 239000011541 reaction mixture Substances 0.000 description 163
• 101150041968 CDC13 gene Proteins 0.000 description 149
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 126
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 118
• 238000003756 stirring Methods 0.000 description 98
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 91
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 88
• 230000002829 reductive effect Effects 0.000 description 85
• 239000000126 substance Substances 0.000 description 85
• 238000001816 cooling Methods 0.000 description 82
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 82
• 238000001704 evaporation Methods 0.000 description 80
• 230000008020 evaporation Effects 0.000 description 80
• 238000006243 chemical reaction Methods 0.000 description 79
• 239000000843 powder Substances 0.000 description 72
• RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 68
• 238000000746 purification Methods 0.000 description 65
• 239000002904 solvent Substances 0.000 description 55
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 52
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 49
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 48
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 42
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 42
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 39
• 238000004587 chromatography analysis Methods 0.000 description 39
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 37
• 239000000741 silica gel Substances 0.000 description 36
• 229910002027 silica gel Inorganic materials 0.000 description 36
• 239000003054 catalyst Substances 0.000 description 34
• UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 34
• ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 34
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 32
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 32
• 238000005984 hydrogenation reaction Methods 0.000 description 30
• UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 28
• 238000000034 method Methods 0.000 description 28
• JQWUEVPNOSPHNN-OALUTQOASA-N (2s,4s)-4-[(4-methoxyphenyl)methylsulfanyl]-1-[(4-nitrophenyl)methoxycarbonyl]pyrrolidine-2-carboxylic acid Chemical compound C1=CC(OC)=CC=C1CS[C@@H]1CN(C(=O)OCC=2C=CC(=CC=2)[N+]([O-])=O)[C@H](C(O)=O)C1 JQWUEVPNOSPHNN-OALUTQOASA-N 0.000 description 27
• 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 description 24
• YLXDRUQODCBMGR-BWGZFRQBSA-N (4R,5R,6S)-3-diphenylphosphoryloxy-6-[(1R)-1-hydroxyethyl]-4-methyl-4-[(4-nitrophenyl)methyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound C[C@H]([C@@H]1[C@@H]2[C@@](C(=C(N2C1=O)C(=O)O)OP(=O)(C3=CC=CC=C3)C4=CC=CC=C4)(C)CC5=CC=C(C=C5)[N+](=O)[O-])O YLXDRUQODCBMGR-BWGZFRQBSA-N 0.000 description 23
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 22
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 22
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 22
• 239000001257 hydrogen Substances 0.000 description 22
• 229910052739 hydrogen Inorganic materials 0.000 description 22
• 125000006239 protecting group Chemical group 0.000 description 21
• IXHQGIFAPSNAKV-UHFFFAOYSA-N (4-nitrophenyl)methyl n-[n'-[3-(azetidin-3-ylamino)-3-oxopropyl]-n-[(4-nitrophenyl)methoxycarbonyl]carbamimidoyl]carbamate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CC([N+](=O)[O-])=CC=C1COC(=O)NC(NC(=O)OCC=1C=CC(=CC=1)[N+]([O-])=O)=NCCC(=O)NC1CNC1 IXHQGIFAPSNAKV-UHFFFAOYSA-N 0.000 description 19
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 18
• 239000012267 brine Substances 0.000 description 18
• 239000007864 aqueous solution Substances 0.000 description 17
• 239000000047 product Substances 0.000 description 17
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
• 238000002955 isolation Methods 0.000 description 14
• 239000010410 layer Substances 0.000 description 14
• 239000007788 liquid Substances 0.000 description 13
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 13
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 12
• XLYOFNOQVPJJNP-ZSJDYOACSA-N Heavy water Chemical compound [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 12
• 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 11
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
• 235000017557 sodium bicarbonate Nutrition 0.000 description 11
• DMKZERWLEGTECU-PIYXRGFCSA-N (4-nitrophenyl)methyl (4r,5r,6s)-3-diphenylphosphoryloxy-6-[(1r)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound C=1([C@H](C)[C@@H]2[C@H](C(N2C=1C(=O)OCC=1C=CC(=CC=1)[N+]([O-])=O)=O)[C@H](O)C)OP(=O)(C=1C=CC=CC=1)C1=CC=CC=C1 DMKZERWLEGTECU-PIYXRGFCSA-N 0.000 description 10
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 10
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 10
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 9
• UREBWPXBXRYXRJ-UHFFFAOYSA-N ethyl acetate;methanol Chemical compound OC.CCOC(C)=O UREBWPXBXRYXRJ-UHFFFAOYSA-N 0.000 description 9
• 238000000605 extraction Methods 0.000 description 9
• ZZMUNSYAVBLAPC-UHFFFAOYSA-N (4-nitrophenyl)methyl n-[[(4-nitrophenyl)methoxycarbonylamino]-pyrazol-1-ylmethylidene]carbamate Chemical compound C1=CC([N+](=O)[O-])=CC=C1COC(=O)NC(N1N=CC=C1)=NC(=O)OCC1=CC=C([N+]([O-])=O)C=C1 ZZMUNSYAVBLAPC-UHFFFAOYSA-N 0.000 description 8
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 8
• 108090000204 Dipeptidase 1 Proteins 0.000 description 8
• 230000000844 anti-bacterial effect Effects 0.000 description 8
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 8
• 239000003795 chemical substances by application Substances 0.000 description 8
• 229920006395 saturated elastomer Polymers 0.000 description 8
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 7
• WKDDRNSBRWANNC-ATRFCDNQSA-N Thienamycin Chemical class C1C(SCCN)=C(C(O)=O)N2C(=O)[C@H]([C@H](O)C)[C@H]21 WKDDRNSBRWANNC-ATRFCDNQSA-N 0.000 description 7
• 239000002585 base Substances 0.000 description 7
• ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 7
• 239000000706 filtrate Substances 0.000 description 7
• 239000003960 organic solvent Substances 0.000 description 7
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 6
• PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 6
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 6
• 238000010908 decantation Methods 0.000 description 6
• 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 6
• 239000000725 suspension Substances 0.000 description 6
• CMIBWIAICVBURI-ZETCQYMHSA-N tert-butyl (3s)-3-aminopyrrolidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CC[C@H](N)C1 CMIBWIAICVBURI-ZETCQYMHSA-N 0.000 description 6
• 102000003850 Dipeptidase 1 Human genes 0.000 description 5
• 239000003638 chemical reducing agent Substances 0.000 description 5
• 238000004821 distillation Methods 0.000 description 5
• IIEWJVIFRVWJOD-UHFFFAOYSA-N ethyl cyclohexane Natural products CCC1CCCCC1 IIEWJVIFRVWJOD-UHFFFAOYSA-N 0.000 description 5
• 238000009472 formulation Methods 0.000 description 5
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
• 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 5
• 239000000546 pharmaceutical excipient Substances 0.000 description 5
• 230000035484 reaction time Effects 0.000 description 5
• 238000001953 recrystallisation Methods 0.000 description 5
• 238000004366 reverse phase liquid chromatography Methods 0.000 description 5
• 229910000029 sodium carbonate Inorganic materials 0.000 description 5
• 238000005406 washing Methods 0.000 description 5
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 4
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 4
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 4
• FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 4
• 241000894006 Bacteria Species 0.000 description 4
• IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
• 206010029155 Nephropathy toxic Diseases 0.000 description 4
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
• QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 4
• 150000002170 ethers Chemical class 0.000 description 4
• 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 4
• 238000004108 freeze drying Methods 0.000 description 4
• 230000007694 nephrotoxicity Effects 0.000 description 4
• 231100000417 nephrotoxicity Toxicity 0.000 description 4
• 231100000989 no adverse effect Toxicity 0.000 description 4
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
• 239000002244 precipitate Substances 0.000 description 4
• 238000011084 recovery Methods 0.000 description 4
• 229910052708 sodium Inorganic materials 0.000 description 4
• 239000011734 sodium Substances 0.000 description 4
• 239000003826 tablet Substances 0.000 description 4
• AHSQPICSVCRVKP-NRAUDTLTSA-N (4-nitrophenyl)methyl (2s,4s)-2-[3-[[(2s)-2-[bis[(4-nitrophenyl)methoxycarbonylamino]methylideneamino]propanoyl]amino]azetidine-1-carbonyl]-4-sulfanylpyrrolidine-1-carboxylate Chemical compound N([C@@H](C)C(=O)NC1CN(C1)C(=O)[C@H]1N(C[C@@H](S)C1)C(=O)OCC=1C=CC(=CC=1)[N+]([O-])=O)C(=NC(=O)OCC=1C=CC(=CC=1)[N+]([O-])=O)NC(=O)OCC1=CC=C([N+]([O-])=O)C=C1 AHSQPICSVCRVKP-NRAUDTLTSA-N 0.000 description 3
• BSIMZHVOQZIAOY-SCSAIBSYSA-N 1-carbapenem-3-carboxylic acid Chemical class OC(=O)C1=CC[C@@H]2CC(=O)N12 BSIMZHVOQZIAOY-SCSAIBSYSA-N 0.000 description 3
• LVGIUOZGDVZIMK-UHFFFAOYSA-N 1-sulfanylpyrrolidine Chemical class SN1CCCC1 LVGIUOZGDVZIMK-UHFFFAOYSA-N 0.000 description 3
• JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 3
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
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