FI103046B - Menetelmä lääkeaineina käyttökelpoisten pyrrolidinyylitiokarbapeneemij ohdannaisten valmistamiseksi - Google Patents
Menetelmä lääkeaineina käyttökelpoisten pyrrolidinyylitiokarbapeneemij ohdannaisten valmistamiseksi Download PDFInfo
- Publication number
- FI103046B FI103046B FI931079A FI931079A FI103046B FI 103046 B FI103046 B FI 103046B FI 931079 A FI931079 A FI 931079A FI 931079 A FI931079 A FI 931079A FI 103046 B FI103046 B FI 103046B
- Authority
- FI
- Finland
- Prior art keywords
- multiplet
- methyl
- group
- ylcarbonyl
- hydroxyethyl
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims description 81
- 238000000034 method Methods 0.000 title claims description 75
- 239000003814 drug Substances 0.000 title claims description 3
- 229940079593 drug Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 251
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 39
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 3
- -1 sulfonyloxy Chemical group 0.000 claims description 186
- 238000006243 chemical reaction Methods 0.000 claims description 75
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 74
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 54
- 125000004432 carbon atom Chemical group C* 0.000 claims description 53
- 125000000217 alkyl group Chemical group 0.000 claims description 46
- 150000003839 salts Chemical class 0.000 claims description 45
- 239000003153 chemical reaction reagent Substances 0.000 claims description 36
- 229910052757 nitrogen Inorganic materials 0.000 claims description 26
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 23
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 20
- 125000001424 substituent group Chemical group 0.000 claims description 20
- 125000006239 protecting group Chemical group 0.000 claims description 15
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 claims description 13
- 125000004429 atom Chemical group 0.000 claims description 13
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 12
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 10
- 150000002148 esters Chemical group 0.000 claims description 10
- 125000005843 halogen group Chemical group 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- 150000002500 ions Chemical class 0.000 claims description 10
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 9
- 125000001188 haloalkyl group Chemical group 0.000 claims description 7
- 125000005117 dialkylcarbamoyl group Chemical group 0.000 claims description 6
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 5
- 150000001450 anions Chemical class 0.000 claims description 4
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 4
- QIYOCWUXNNXYCG-YIRPQJDUSA-N (5S)-3-[5-[3-[2-fluoroethyl(dimethyl)azaniumyl]pyrrolidine-1-carbonyl]pyrrolidin-3-yl]sulfanyl-6-(1-hydroxyethyl)-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound FCC[N+](C)(C)C1CN(CC1)C(=O)C1NCC(C1)SC=1C([C@H]2N(C=1C(=O)[O-])C(C2C(C)O)=O)C QIYOCWUXNNXYCG-YIRPQJDUSA-N 0.000 claims description 3
- SNTWKPAKVQFCCF-UHFFFAOYSA-N 2,3-dihydro-1h-triazole Chemical compound N1NC=CN1 SNTWKPAKVQFCCF-UHFFFAOYSA-N 0.000 claims description 3
- FKCMADOPPWWGNZ-YUMQZZPRSA-N [(2r)-1-[(2s)-2-amino-3-methylbutanoyl]pyrrolidin-2-yl]boronic acid Chemical compound CC(C)[C@H](N)C(=O)N1CCC[C@H]1B(O)O FKCMADOPPWWGNZ-YUMQZZPRSA-N 0.000 claims description 3
- 125000003118 aryl group Chemical group 0.000 claims description 3
- 229910052736 halogen Chemical group 0.000 claims description 3
- MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 claims description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 2
- 229910052744 lithium Inorganic materials 0.000 claims description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 2
- FQWGQNPNUJXRHN-IDWKVMDRSA-N (5S)-3-[5-(4-carbamimidoyl-1,4-diazepane-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 C(N)(=N)N1CCN(CCC1)C(=O)C1NCC(C1)SC=1C([C@H]2N(C=1C(=O)O)C(C2C(C)O)=O)C FQWGQNPNUJXRHN-IDWKVMDRSA-N 0.000 claims 1
- OYKCJGFQXFBOFS-QCYUVGAGSA-N (5S)-3-[5-(4-carbamimidoylpiperazine-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 C(N)(=N)N1CCN(CC1)C(=O)C1NCC(C1)SC=1C([C@H]2N(C=1C(=O)O)C(C2C(C)O)=O)C OYKCJGFQXFBOFS-QCYUVGAGSA-N 0.000 claims 1
- IUICOVQHLKWNIU-DCTVEYNDSA-N (5S)-4-[(1R)-1-hydroxyethyl]-4-methyl-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound O[C@H](C)C1(C=C(N2[C@H]1CC2=O)C(=O)O)C IUICOVQHLKWNIU-DCTVEYNDSA-N 0.000 claims 1
- XLJMOHKQRRPBDS-IENPIDJESA-N (5S)-4-pyrrolidin-1-ylsulfanyl-1-azabicyclo[3.2.0]hept-2-en-7-one Chemical class N1(CCCC1)SC1C=CN2[C@H]1CC2=O XLJMOHKQRRPBDS-IENPIDJESA-N 0.000 claims 1
- MLVMAXSBBGIUKW-ASUKBFJSSA-N (5S)-6-(1-hydroxyethyl)-4-methyl-7-oxo-3-[5-[3-(trimethylazaniumyl)pyrrolidine-1-carbonyl]pyrrolidin-3-yl]sulfanyl-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound OC(C)C1[C@@H]2N(C(=C(C2C)SC2CC(NC2)C(=O)N2CC(CC2)[N+](C)(C)C)C(=O)[O-])C1=O MLVMAXSBBGIUKW-ASUKBFJSSA-N 0.000 claims 1
- 125000000913 palmityl 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])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims 1
- 229910052739 hydrogen Inorganic materials 0.000 abstract description 38
- 239000001257 hydrogen Substances 0.000 abstract description 24
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 22
- 239000003242 anti bacterial agent Substances 0.000 abstract description 7
- 108090000204 Dipeptidase 1 Proteins 0.000 abstract description 6
- 102000003850 Dipeptidase 1 Human genes 0.000 abstract description 5
- 229940088710 antibiotic agent Drugs 0.000 abstract description 5
- 125000004185 ester group Chemical group 0.000 abstract description 3
- 150000002431 hydrogen Chemical class 0.000 abstract description 3
- 238000011282 treatment Methods 0.000 abstract description 3
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 abstract 1
- 208000015181 infectious disease Diseases 0.000 abstract 1
- 230000000813 microbial effect Effects 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 321
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 201
- 239000000203 mixture Substances 0.000 description 188
- 230000002829 reductive effect Effects 0.000 description 177
- 239000000243 solution Substances 0.000 description 157
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 138
- 238000000862 absorption spectrum Methods 0.000 description 131
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 121
- 238000001704 evaporation Methods 0.000 description 120
- 230000008020 evaporation Effects 0.000 description 120
- 239000000843 powder Substances 0.000 description 114
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 102
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 93
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 86
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 82
- 239000002904 solvent Substances 0.000 description 81
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 69
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 66
- 238000001816 cooling Methods 0.000 description 59
- 239000011541 reaction mixture Substances 0.000 description 56
- 238000004821 distillation Methods 0.000 description 54
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 52
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 43
- 239000011780 sodium chloride Substances 0.000 description 41
- 238000003756 stirring Methods 0.000 description 41
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 40
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 39
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 36
- 238000010898 silica gel chromatography Methods 0.000 description 36
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 33
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 33
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 32
- 239000003054 catalyst Substances 0.000 description 32
- 239000010410 layer Substances 0.000 description 32
- NFUHGQVNWQOHQB-UHFFFAOYSA-N sodium;trimethylsilyl propanoate Chemical class [Na].CCC(=O)O[Si](C)(C)C NFUHGQVNWQOHQB-UHFFFAOYSA-N 0.000 description 31
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- 239000007858 starting material Substances 0.000 description 21
- 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 20
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 20
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 20
- 235000017557 sodium bicarbonate Nutrition 0.000 description 20
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 20
- 238000004440 column chromatography Methods 0.000 description 19
- 238000010828 elution Methods 0.000 description 19
- 239000000706 filtrate Substances 0.000 description 19
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
- 239000002253 acid Substances 0.000 description 18
- 239000003480 eluent Substances 0.000 description 18
- 238000001914 filtration Methods 0.000 description 18
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 18
- 239000000047 product Substances 0.000 description 18
- 229920006395 saturated elastomer Polymers 0.000 description 18
- 239000012298 atmosphere Substances 0.000 description 17
- 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 15
- 239000012071 phase Substances 0.000 description 15
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 description 15
- 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 14
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 13
- 230000002441 reversible effect Effects 0.000 description 13
- 238000005984 hydrogenation reaction Methods 0.000 description 12
- 239000000725 suspension Substances 0.000 description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 10
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- 239000000460 chlorine Substances 0.000 description 9
- 239000012043 crude product Substances 0.000 description 9
- OIRDBPQYVWXNSJ-UHFFFAOYSA-N methyl trifluoromethansulfonate Chemical compound COS(=O)(=O)C(F)(F)F OIRDBPQYVWXNSJ-UHFFFAOYSA-N 0.000 description 9
- 239000012074 organic phase Substances 0.000 description 9
- 229920001467 poly(styrenesulfonates) Polymers 0.000 description 9
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 9
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 8
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 7
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 7
- BHIIGRBMZRSDRI-UHFFFAOYSA-N [chloro(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(Cl)OC1=CC=CC=C1 BHIIGRBMZRSDRI-UHFFFAOYSA-N 0.000 description 7
- 239000008346 aqueous phase Substances 0.000 description 7
- 238000010908 decantation Methods 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- GUGYCHHWTVUBLV-MSECNUKYSA-N (4-nitrophenyl)methyl (4r,5r,6s)-6-[(1r)-1-hydroxyethyl]-4-methyl-3,7-dioxo-1-azabicyclo[3.2.0]heptane-2-carboxylate Chemical compound O=C([C@H](C)[C@@H]1[C@H](C(N11)=O)[C@H](O)C)C1C(=O)OCC1=CC=C([N+]([O-])=O)C=C1 GUGYCHHWTVUBLV-MSECNUKYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 230000003115 biocidal effect Effects 0.000 description 6
- 239000013078 crystal Substances 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- 238000005406 washing Methods 0.000 description 6
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 5
- 238000007796 conventional method Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 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 4
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
- 241000894006 Bacteria Species 0.000 description 4
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
- ZSIAANIILFGLQH-UHFFFAOYSA-N C1(=CC=CC=C1)[ClH]P(=O)(Cl)[ClH]C1=CC=CC=C1 Chemical compound C1(=CC=CC=C1)[ClH]P(=O)(Cl)[ClH]C1=CC=CC=C1 ZSIAANIILFGLQH-UHFFFAOYSA-N 0.000 description 4
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- 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 4
- 230000000844 anti-bacterial effect Effects 0.000 description 4
- 125000003460 beta-lactamyl group Chemical group 0.000 description 4
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 4
- 229910052801 chlorine Inorganic materials 0.000 description 4
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 229910052740 iodine Inorganic materials 0.000 description 4
- 238000004255 ion exchange chromatography Methods 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 231100000989 no adverse effect Toxicity 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- SSUBBXZBKKWORU-SFTDATJTSA-N (4-nitrophenyl)methyl (2s,4s)-2-[3-[(4-nitrophenyl)methoxycarbonylamino]azetidine-1-carbonyl]-4-sulfanylpyrrolidine-1-carboxylate Chemical compound C1=CC([N+](=O)[O-])=CC=C1COC(=O)NC1CN(C(=O)[C@H]2N(C[C@@H](S)C2)C(=O)OCC=2C=CC(=CC=2)[N+]([O-])=O)C1 SSUBBXZBKKWORU-SFTDATJTSA-N 0.000 description 3
- MXPDNPAIJIFTDY-HOTGVXAUSA-N (4-nitrophenyl)methyl (ne)-n-[amino-[4-[(2s,4s)-1-methyl-4-sulfanylpyrrolidine-2-carbonyl]piperazin-1-yl]methylidene]carbamate Chemical compound CN1C[C@@H](S)C[C@H]1C(=O)N1CCN(C(=N)NC(=O)OCC=2C=CC(=CC=2)[N+]([O-])=O)CC1 MXPDNPAIJIFTDY-HOTGVXAUSA-N 0.000 description 3
- FMIOOGWLBUDLOZ-RZBMREITSA-N (5S)-3-[5-(4-carbamimidoyl-1,4-diazepane-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 C(N)(=N)N1CCN(CCC1)C(=O)C1N(CC(C1)SC=1C([C@H]2N(C=1C(=O)O)C(C2C(C)O)=O)C)C FMIOOGWLBUDLOZ-RZBMREITSA-N 0.000 description 3
- WOUBUYGESDHYER-ZPKSRCETSA-N (5S)-3-[5-[3-(1-aminoethylideneamino)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 C(C)(=N)NC1CN(C1)C(=O)C1NCC(C1)SC=1C([C@H]2N(C=1C(=O)O)C(C2C(C)O)=O)C WOUBUYGESDHYER-ZPKSRCETSA-N 0.000 description 3
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- CKNYWTABPYGPEX-UHFFFAOYSA-N pyrrolidin-1-ium;2,2,2-trifluoroacetate Chemical compound C1CC[NH2+]C1.[O-]C(=O)C(F)(F)F CKNYWTABPYGPEX-UHFFFAOYSA-N 0.000 description 1
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- 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 1
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- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
-
- 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
- C07D477/16—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 hetero atoms or carbon atoms 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 3
- C07D477/20—Sulfur atoms
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- 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
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Materials For Medical Uses (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP5216392 | 1992-03-11 | ||
| JP5216392 | 1992-03-11 | ||
| JP24495392 | 1992-09-14 | ||
| JP24495392 | 1992-09-14 | ||
| JP24657892 | 1992-09-16 | ||
| JP24657892 | 1992-09-16 |
Publications (4)
| Publication Number | Publication Date |
|---|---|
| FI931079A0 FI931079A0 (fi) | 1993-03-10 |
| FI931079L FI931079L (fi) | 1993-09-12 |
| FI103046B1 FI103046B1 (fi) | 1999-04-15 |
| FI103046B true FI103046B (fi) | 1999-04-15 |
Family
ID=27294566
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| FI931079A FI103046B (fi) | 1992-03-11 | 1993-03-10 | Menetelmä lääkeaineina käyttökelpoisten pyrrolidinyylitiokarbapeneemij ohdannaisten valmistamiseksi |
Country Status (18)
| Country | Link |
|---|---|
| EP (1) | EP0560613B1 (enExample) |
| KR (1) | KR100258225B1 (enExample) |
| CN (1) | CN1037180C (enExample) |
| AT (1) | ATE173733T1 (enExample) |
| AU (1) | AU664422B2 (enExample) |
| CA (1) | CA2091486A1 (enExample) |
| CZ (1) | CZ290002B6 (enExample) |
| DE (1) | DE69322188T2 (enExample) |
| DK (1) | DK0560613T3 (enExample) |
| ES (1) | ES2125945T3 (enExample) |
| FI (1) | FI103046B (enExample) |
| HU (1) | HU218676B (enExample) |
| IL (1) | IL105020A (enExample) |
| MX (1) | MX9301361A (enExample) |
| NO (1) | NO303730B1 (enExample) |
| NZ (1) | NZ247129A (enExample) |
| RU (1) | RU2097383C1 (enExample) |
| TW (1) | TW249803B (enExample) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FI101226B1 (fi) * | 1991-06-04 | 1998-05-15 | Sankyo Co | Menetelmä lääkeaineena käyttökelpoisten 2-[2-(karbonyyli)pyrrolidin-4-yylitio]-6-(1-hydroksietyyli)-1-metyylikarbapen-2-eemi-3-karboksyylihappojohdannaisten valmistamiseksi |
| GB9515975D0 (en) | 1995-08-04 | 1995-10-04 | Zeneca Ltd | Chemical compounds |
| EP0882728B1 (en) * | 1995-12-21 | 2002-09-04 | Sankyo Company Limited | 1-methylcarbapenem derivatives |
| WO1997041123A1 (en) * | 1996-04-26 | 1997-11-06 | Sankyo Company, Limited | 1-methylcarbapenem derivatives |
| AU4020897A (en) | 1996-08-17 | 1998-03-06 | Zeneca Limited | 3-mercaptopyrrolidines as farnesyl protein transferase inhibitors |
| WO2000034282A1 (en) * | 1998-12-07 | 2000-06-15 | Sankyo Company, Limited | 1-methylcarbapenem derivatives |
| US7041660B2 (en) | 1999-07-06 | 2006-05-09 | Sankyo Company, Limited | Crystalline 1-methylcarbapenem derivatives |
| GB9930318D0 (en) | 1999-12-22 | 2000-02-09 | Zeneca Ltd | Novel compounds |
| GB9930317D0 (en) | 1999-12-22 | 2000-02-09 | Zeneca Ltd | Novel compounds |
| KR100628676B1 (ko) * | 2001-09-26 | 2006-09-27 | 머크 앤드 캄파니 인코포레이티드 | 카바페넴 화합물의 제조방법 |
| WO2005063704A1 (ja) * | 2003-12-25 | 2005-07-14 | Ono Pharmaceutical Co., Ltd. | アゼチジン環化合物およびその医薬 |
| CN101367814B (zh) * | 2007-06-28 | 2010-12-15 | 山东轩竹医药科技有限公司 | 被巯基吡咯烷甲酰哌啶取代的培南衍生物 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1283906C (en) * | 1983-05-09 | 1991-05-07 | Makoto Sunagawa | .beta.-LACTAM COMPOUNDS AND PRODUCTION THEREOF |
| DE3780344T2 (de) * | 1986-03-27 | 1993-01-28 | Sumitomo Pharma | Beta-lactam-verbindungen und deren herstellung. |
| CA2036163C (en) * | 1990-02-14 | 2001-06-19 | Makoto Sunagawa | Novel beta-lactam compounds and their production |
| CA2036941A1 (en) * | 1990-02-23 | 1991-08-24 | Isao Kawamoto | Carbapenem derivatives having antibiotic activity, their preparation and their use |
| GB9107363D0 (en) * | 1991-04-08 | 1991-05-22 | Ici Plc | Antibiotic compounds |
| FI101226B1 (fi) * | 1991-06-04 | 1998-05-15 | Sankyo Co | Menetelmä lääkeaineena käyttökelpoisten 2-[2-(karbonyyli)pyrrolidin-4-yylitio]-6-(1-hydroksietyyli)-1-metyylikarbapen-2-eemi-3-karboksyylihappojohdannaisten valmistamiseksi |
| US5608056A (en) * | 1992-04-13 | 1997-03-04 | Fujisawa Pharmaceutical Co., Ltd. | Substituted 3-pyrrolidinylthio-carbapenems as antimicrobial agents |
-
1993
- 1993-03-10 CZ CZ1993393A patent/CZ290002B6/cs not_active IP Right Cessation
- 1993-03-10 FI FI931079A patent/FI103046B/fi active IP Right Grant
- 1993-03-10 HU HU9300677A patent/HU218676B/hu not_active IP Right Cessation
- 1993-03-11 CA CA002091486A patent/CA2091486A1/en not_active Abandoned
- 1993-03-11 DE DE69322188T patent/DE69322188T2/de not_active Expired - Fee Related
- 1993-03-11 RU RU9393004678A patent/RU2097383C1/ru not_active IP Right Cessation
- 1993-03-11 NZ NZ247129A patent/NZ247129A/en unknown
- 1993-03-11 IL IL105020A patent/IL105020A/xx not_active IP Right Cessation
- 1993-03-11 NO NO930884A patent/NO303730B1/no not_active IP Right Cessation
- 1993-03-11 ES ES93301872T patent/ES2125945T3/es not_active Expired - Lifetime
- 1993-03-11 KR KR1019930003664A patent/KR100258225B1/ko not_active Expired - Fee Related
- 1993-03-11 AU AU35151/93A patent/AU664422B2/en not_active Ceased
- 1993-03-11 AT AT93301872T patent/ATE173733T1/de not_active IP Right Cessation
- 1993-03-11 MX MX9301361A patent/MX9301361A/es not_active IP Right Cessation
- 1993-03-11 DK DK93301872T patent/DK0560613T3/da active
- 1993-03-11 CN CN93104412A patent/CN1037180C/zh not_active Expired - Fee Related
- 1993-03-11 TW TW082101810A patent/TW249803B/zh active
- 1993-03-11 EP EP93301872A patent/EP0560613B1/en not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| HU218676B (hu) | 2000-10-28 |
| FI103046B1 (fi) | 1999-04-15 |
| NO930884L (no) | 1993-09-13 |
| ATE173733T1 (de) | 1998-12-15 |
| EP0560613B1 (en) | 1998-11-25 |
| TW249803B (enExample) | 1995-06-21 |
| KR100258225B1 (ko) | 2000-08-01 |
| IL105020A (en) | 1997-04-15 |
| ES2125945T3 (es) | 1999-03-16 |
| DE69322188D1 (de) | 1999-01-07 |
| HUT64071A (en) | 1993-11-29 |
| CZ39393A3 (en) | 1993-12-15 |
| RU2097383C1 (ru) | 1997-11-27 |
| HK1011976A1 (en) | 1999-07-23 |
| CA2091486A1 (en) | 1993-09-12 |
| HU9300677D0 (en) | 1993-05-28 |
| NO303730B1 (no) | 1998-08-24 |
| NO930884D0 (no) | 1993-03-11 |
| FI931079A0 (fi) | 1993-03-10 |
| AU3515193A (en) | 1993-09-16 |
| EP0560613A1 (en) | 1993-09-15 |
| KR930019674A (ko) | 1993-10-18 |
| IL105020A0 (en) | 1993-07-08 |
| CN1079472A (zh) | 1993-12-15 |
| CN1037180C (zh) | 1998-01-28 |
| DK0560613T3 (da) | 1999-08-09 |
| AU664422B2 (en) | 1995-11-16 |
| DE69322188T2 (de) | 1999-07-29 |
| NZ247129A (en) | 1994-09-27 |
| CZ290002B6 (cs) | 2002-05-15 |
| FI931079L (fi) | 1993-09-12 |
| MX9301361A (es) | 1994-01-31 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FG | Patent granted |
Owner name: SANKYO COMPANY LIMITED |