CA2217885A1 - Esters of carbapenems - Google Patents
Esters of carbapenems Download PDFInfo
- Publication number
- CA2217885A1 CA2217885A1 CA002217885A CA2217885A CA2217885A1 CA 2217885 A1 CA2217885 A1 CA 2217885A1 CA 002217885 A CA002217885 A CA 002217885A CA 2217885 A CA2217885 A CA 2217885A CA 2217885 A1 CA2217885 A1 CA 2217885A1
- Authority
- CA
- Canada
- Prior art keywords
- group
- alkyl
- formula
- compound
- hydrogen
- 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.)
- Abandoned
Links
- 150000002148 esters Chemical class 0.000 title claims abstract description 7
- 229940041011 carbapenems Drugs 0.000 title description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 79
- 239000001257 hydrogen Substances 0.000 claims abstract description 29
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 29
- 125000006239 protecting group Chemical group 0.000 claims abstract description 20
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 19
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 17
- 125000003118 aryl group Chemical group 0.000 claims abstract description 13
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 12
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 10
- 125000003107 substituted aryl group Chemical group 0.000 claims abstract description 10
- 125000003277 amino group Chemical group 0.000 claims abstract description 8
- 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 7
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 7
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 6
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims abstract description 4
- 125000005843 halogen group Chemical group 0.000 claims abstract description 4
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims abstract description 3
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract 19
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims abstract 4
- 241001334141 Rugopharynx alpha Species 0.000 claims abstract 4
- 150000002431 hydrogen Chemical class 0.000 claims abstract 4
- 208000035143 Bacterial infection Diseases 0.000 claims abstract 3
- 208000022362 bacterial infectious disease Diseases 0.000 claims abstract 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract 2
- 125000003342 alkenyl group Chemical group 0.000 claims abstract 2
- 125000000000 cycloalkoxy group Chemical group 0.000 claims abstract 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract 2
- -1 2-Ethoxycarbonyl-E-but-2-enyl Chemical group 0.000 claims description 37
- 238000000034 method Methods 0.000 claims description 31
- 230000008569 process Effects 0.000 claims description 15
- 238000002360 preparation method Methods 0.000 claims description 13
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 10
- 239000003242 anti bacterial agent Substances 0.000 claims description 7
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 239000001301 oxygen Substances 0.000 claims description 7
- 230000003115 biocidal effect Effects 0.000 claims description 5
- 238000006880 cross-coupling reaction Methods 0.000 claims description 5
- 150000003839 salts Chemical class 0.000 claims description 4
- 229910052783 alkali metal Inorganic materials 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 241001465754 Metazoa Species 0.000 claims description 2
- 239000007809 chemical reaction catalyst Substances 0.000 claims description 2
- WOOJGEPTXCJIFB-ATZDWAIDSA-N (1-methylcyclohexyl)oxycarbonyloxymethyl (5r,6s)-3-(1-ethyl-5-methylpyrazol-3-yl)-6-[(1r)-1-hydroxyethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound C1=C(C)N(CC)N=C1C1=C(C(=O)OCOC(=O)OC2(C)CCCCC2)N2C(=O)[C@H]([C@@H](C)O)[C@H]2C1 WOOJGEPTXCJIFB-ATZDWAIDSA-N 0.000 claims 1
- UUBNUFNJFVNNJS-DAXOMENPSA-N (2-methoxy-2-methylpropanoyl)oxymethyl (5R,6S)-3-(1-ethyl-5-methylpyrazol-3-yl)-6-[(1R)-1-hydroxyethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound C(C)N1N=C(C=C1C)C=1C[C@H]2N(C=1C(=O)OCOC(=O)C(C)(C)OC)C([C@@H]2[C@@H](C)O)=O UUBNUFNJFVNNJS-DAXOMENPSA-N 0.000 claims 1
- YZBQHRLRFGPBSL-RXMQYKEDSA-N carbapenem Chemical group C1C=CN2C(=O)C[C@H]21 YZBQHRLRFGPBSL-RXMQYKEDSA-N 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 90
- 239000000203 mixture Substances 0.000 description 49
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 39
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 20
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 18
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 12
- 125000000217 alkyl group Chemical group 0.000 description 12
- 239000000047 product Substances 0.000 description 12
- 239000000741 silica gel Substances 0.000 description 12
- 229910002027 silica gel Inorganic materials 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 12
- 239000003921 oil Substances 0.000 description 11
- 235000019198 oils Nutrition 0.000 description 11
- 229910052786 argon Inorganic materials 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
- 101150041968 CDC13 gene Proteins 0.000 description 9
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
- 239000010410 layer Substances 0.000 description 8
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 125000001424 substituent group Chemical group 0.000 description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 7
- 235000019341 magnesium sulphate Nutrition 0.000 description 7
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
- 239000003981 vehicle Substances 0.000 description 7
- XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 6
- 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 5
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 5
- 238000006243 chemical reaction Methods 0.000 description 5
- 238000004587 chromatography analysis Methods 0.000 description 5
- 239000000284 extract Substances 0.000 description 5
- 150000002367 halogens Chemical group 0.000 description 5
- 125000000623 heterocyclic group Chemical group 0.000 description 5
- 229910052757 nitrogen Inorganic materials 0.000 description 5
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 229910052708 sodium Inorganic materials 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 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 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 229960004132 diethyl ether Drugs 0.000 description 4
- 235000019441 ethanol Nutrition 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 208000015181 infectious disease Diseases 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 239000003960 organic solvent Substances 0.000 description 4
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 3
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- 239000005864 Sulphur Substances 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 239000007983 Tris buffer Substances 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 125000004442 acylamino group Chemical group 0.000 description 3
- 125000003545 alkoxy group Chemical group 0.000 description 3
- 229940088710 antibiotic agent Drugs 0.000 description 3
- 239000012300 argon atmosphere Substances 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 239000012267 brine Substances 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 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 3
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 235000017557 sodium bicarbonate Nutrition 0.000 description 3
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 3
- 235000019345 sodium thiosulphate Nutrition 0.000 description 3
- 239000000600 sorbitol Substances 0.000 description 3
- 235000010356 sorbitol Nutrition 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- 239000003826 tablet Substances 0.000 description 3
- 235000005074 zinc chloride Nutrition 0.000 description 3
- 239000011592 zinc chloride Substances 0.000 description 3
- UBOXGVDOUJQMTN-UHFFFAOYSA-N 1,1,2-trichloroethane Chemical compound ClCC(Cl)Cl UBOXGVDOUJQMTN-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 108010010803 Gelatin Proteins 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 240000007472 Leucaena leucocephala Species 0.000 description 2
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 2
- 125000004414 alkyl thio group Chemical group 0.000 description 2
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical group COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- RUICJPMXWCDSDL-UHFFFAOYSA-N chloromethyl (1-methylcyclohexyl) carbonate Chemical compound ClCOC(=O)OC1(C)CCCCC1 RUICJPMXWCDSDL-UHFFFAOYSA-N 0.000 description 2
- 239000002024 ethyl acetate extract Substances 0.000 description 2
- 238000011049 filling Methods 0.000 description 2
- 239000008273 gelatin Substances 0.000 description 2
- 229920000159 gelatin Polymers 0.000 description 2
- 235000019322 gelatine Nutrition 0.000 description 2
- 235000011852 gelatine desserts Nutrition 0.000 description 2
- 229960002182 imipenem Drugs 0.000 description 2
- GSOSVVULSKVSLQ-JJVRHELESA-N imipenem hydrate Chemical compound O.C1C(SCCNC=N)=C(C(O)=O)N2C(=O)[C@H]([C@H](O)C)[C@H]21 GSOSVVULSKVSLQ-JJVRHELESA-N 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- YNESATAKKCNGOF-UHFFFAOYSA-N lithium bis(trimethylsilyl)amide Chemical compound [Li+].C[Si](C)(C)[N-][Si](C)(C)C YNESATAKKCNGOF-UHFFFAOYSA-N 0.000 description 2
- 238000011068 loading method Methods 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 235000009518 sodium iodide Nutrition 0.000 description 2
- VYPDUQYOLCLEGS-UHFFFAOYSA-M sodium;2-ethylhexanoate Chemical compound [Na+].CCCCC(CC)C([O-])=O VYPDUQYOLCLEGS-UHFFFAOYSA-M 0.000 description 2
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 2
- 239000008215 water for injection Substances 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- 239000008096 xylene Substances 0.000 description 2
- JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 description 1
- PPKPKFIWDXDAGC-IHWYPQMZSA-N (z)-1,2-dichloroprop-1-ene Chemical compound C\C(Cl)=C\Cl PPKPKFIWDXDAGC-IHWYPQMZSA-N 0.000 description 1
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 1
- JYUXDXWXTPSAEL-UHFFFAOYSA-N 1,4-dioxane;oxolane Chemical compound C1CCOC1.C1COCCO1 JYUXDXWXTPSAEL-UHFFFAOYSA-N 0.000 description 1
- OLIORJQCDXKJQP-UHFFFAOYSA-N 1-(1-ethyl-5-methylpyrazol-3-yl)ethanone Chemical compound CCN1N=C(C(C)=O)C=C1C OLIORJQCDXKJQP-UHFFFAOYSA-N 0.000 description 1
- 125000004776 1-fluoroethyl group Chemical group [H]C([H])([H])C([H])(F)* 0.000 description 1
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- 238000002512 chemotherapy Methods 0.000 description 1
- PJBIHXWYDMFGCV-UHFFFAOYSA-N chloro(chlorosulfonyloxy)methane Chemical compound ClCOS(Cl)(=O)=O PJBIHXWYDMFGCV-UHFFFAOYSA-N 0.000 description 1
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- 239000011777 magnesium Substances 0.000 description 1
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- AUHZEENZYGFFBQ-UHFFFAOYSA-N mesitylene Substances CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 description 1
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- 150000002739 metals Chemical class 0.000 description 1
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- GWUSZQUVEVMBPI-UHFFFAOYSA-N nimetazepam Chemical compound N=1CC(=O)N(C)C2=CC=C([N+]([O-])=O)C=C2C=1C1=CC=CC=C1 GWUSZQUVEVMBPI-UHFFFAOYSA-N 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 229940006093 opthalmologic coloring agent diagnostic Drugs 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 150000002903 organophosphorus compounds Chemical class 0.000 description 1
- 125000004043 oxo group Chemical group O=* 0.000 description 1
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- 125000002217 penem group Chemical group 0.000 description 1
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- DHHVAGZRUROJKS-UHFFFAOYSA-N phentermine Chemical compound CC(C)(N)CC1=CC=CC=C1 DHHVAGZRUROJKS-UHFFFAOYSA-N 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
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- 235000015320 potassium carbonate Nutrition 0.000 description 1
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- 235000013772 propylene glycol Nutrition 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- ZDYVRSLAEXCVBX-UHFFFAOYSA-N pyridinium p-toluenesulfonate Chemical compound C1=CC=[NH+]C=C1.CC1=CC=C(S([O-])(=O)=O)C=C1 ZDYVRSLAEXCVBX-UHFFFAOYSA-N 0.000 description 1
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- 230000004044 response Effects 0.000 description 1
- 238000006798 ring closing metathesis reaction Methods 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 102220090095 rs1042713 Human genes 0.000 description 1
- 102220216906 rs1060505002 Human genes 0.000 description 1
- 102220260512 rs1192077362 Human genes 0.000 description 1
- 229910052701 rubidium Inorganic materials 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 239000008259 solid foam Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
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- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
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- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
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- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000759 toxicological effect Toxicity 0.000 description 1
- 125000004665 trialkylsilyl group Chemical group 0.000 description 1
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
- BDZBKCUKTQZUTL-UHFFFAOYSA-N triethyl phosphite Chemical compound CCOP(OCC)OCC BDZBKCUKTQZUTL-UHFFFAOYSA-N 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- CYTQBVOFDCPGCX-UHFFFAOYSA-N trimethyl phosphite Chemical compound COP(OC)OC CYTQBVOFDCPGCX-UHFFFAOYSA-N 0.000 description 1
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 1
- BPLUKJNHPBNVQL-UHFFFAOYSA-N triphenylarsine Chemical compound C1=CC=CC=C1[As](C=1C=CC=CC=1)C1=CC=CC=C1 BPLUKJNHPBNVQL-UHFFFAOYSA-N 0.000 description 1
- FIQMHBFVRAXMOP-UHFFFAOYSA-N triphenylphosphane oxide Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)(=O)C1=CC=CC=C1 FIQMHBFVRAXMOP-UHFFFAOYSA-N 0.000 description 1
- JQKHNBQZGUKYPX-UHFFFAOYSA-N tris(2,4,6-trimethoxyphenyl)phosphane Chemical compound COC1=CC(OC)=CC(OC)=C1P(C=1C(=CC(OC)=CC=1OC)OC)C1=C(OC)C=C(OC)C=C1OC JQKHNBQZGUKYPX-UHFFFAOYSA-N 0.000 description 1
- UYUUAUOYLFIRJG-UHFFFAOYSA-N tris(4-methoxyphenyl)phosphane Chemical compound C1=CC(OC)=CC=C1P(C=1C=CC(OC)=CC=1)C1=CC=C(OC)C=C1 UYUUAUOYLFIRJG-UHFFFAOYSA-N 0.000 description 1
- DLQYXUGCCKQSRJ-UHFFFAOYSA-N tris(furan-2-yl)phosphane Chemical compound C1=COC(P(C=2OC=CC=2)C=2OC=CC=2)=C1 DLQYXUGCCKQSRJ-UHFFFAOYSA-N 0.000 description 1
- 238000009827 uniform distribution Methods 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052726 zirconium Inorganic materials 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
-
- 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
-
- 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
- C07D477/02—Preparation
- C07D477/06—Preparation from compounds already containing the ring or condensed ring systems, e.g. by dehydrogenation of the ring, by introduction, elimination or modification of substituents
- C07D477/08—Modification of a carboxyl group directly attached in position 2, e.g. esterification
-
- 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)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Molecular Biology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9508964.5A GB9508964D0 (en) | 1995-05-03 | 1995-05-03 | Novel compounds |
| GB9508960.3 | 1995-05-03 | ||
| GBGB9508960.3A GB9508960D0 (en) | 1995-05-03 | 1995-05-03 | Novel compounds |
| GB9508964.5 | 1995-05-03 | ||
| GB9508959.5 | 1995-05-03 | ||
| GBGB9508959.5A GB9508959D0 (en) | 1995-05-03 | 1995-05-03 | Novel compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2217885A1 true CA2217885A1 (en) | 1996-11-07 |
Family
ID=27267697
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002217885A Abandoned CA2217885A1 (en) | 1995-05-03 | 1996-05-02 | Esters of carbapenems |
Country Status (14)
| Country | Link |
|---|---|
| EP (1) | EP0823911A1 (cs) |
| JP (1) | JPH11504912A (cs) |
| KR (1) | KR19990008354A (cs) |
| CN (1) | CN1184480A (cs) |
| AU (1) | AU5814196A (cs) |
| BR (1) | BR9608318A (cs) |
| CA (1) | CA2217885A1 (cs) |
| CZ (1) | CZ347697A3 (cs) |
| HU (1) | HUP9801061A3 (cs) |
| MX (1) | MX9708422A (cs) |
| NO (1) | NO974995L (cs) |
| PL (1) | PL323148A1 (cs) |
| TR (1) | TR199701289T2 (cs) |
| WO (1) | WO1996034869A1 (cs) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100771019B1 (ko) * | 2002-03-20 | 2007-10-29 | 주식회사 만도 | 브레이크 액압제어장치 |
| GB0400329D0 (en) * | 2004-01-08 | 2004-02-11 | Glaxo Group Ltd | Novel processes |
| GB0400405D0 (en) * | 2004-01-09 | 2004-02-11 | Glaxo Group Ltd | Novel processes |
| JP2007039383A (ja) * | 2005-08-03 | 2007-02-15 | Dainippon Sumitomo Pharma Co Ltd | アリールカルバペネム化合物の製造方法 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1593524A (en) * | 1976-11-19 | 1981-07-15 | Merck & Co Inc | 1-carba-2-penem-3-carboxylic acids |
| DK637888A (da) * | 1987-11-24 | 1989-05-25 | Hoffmann La Roche | Carboxylsyreestere |
| GB8809534D0 (en) * | 1988-04-22 | 1988-05-25 | Beecham Group Plc | Novel compounds |
| SK53696A3 (en) * | 1993-10-29 | 1996-10-02 | Smithkline Beecham Plc | Carbapenem derivatives, their preparation, pharmaceutical compositions containing them and their use |
-
1996
- 1996-05-02 MX MX9708422A patent/MX9708422A/es unknown
- 1996-05-02 AU AU58141/96A patent/AU5814196A/en not_active Abandoned
- 1996-05-02 CA CA002217885A patent/CA2217885A1/en not_active Abandoned
- 1996-05-02 CN CN96194015A patent/CN1184480A/zh active Pending
- 1996-05-02 TR TR97/01289T patent/TR199701289T2/xx unknown
- 1996-05-02 JP JP8533022A patent/JPH11504912A/ja active Pending
- 1996-05-02 KR KR1019970707880A patent/KR19990008354A/ko not_active Withdrawn
- 1996-05-02 EP EP96919680A patent/EP0823911A1/en not_active Withdrawn
- 1996-05-02 CZ CZ973476A patent/CZ347697A3/cs unknown
- 1996-05-02 HU HU9801061A patent/HUP9801061A3/hu unknown
- 1996-05-02 BR BR9608318A patent/BR9608318A/pt unknown
- 1996-05-02 PL PL96323148A patent/PL323148A1/xx unknown
- 1996-05-02 WO PCT/EP1996/001882 patent/WO1996034869A1/en not_active Application Discontinuation
-
1997
- 1997-10-30 NO NO974995A patent/NO974995L/no unknown
Also Published As
| Publication number | Publication date |
|---|---|
| BR9608318A (pt) | 1999-01-26 |
| CZ347697A3 (cs) | 1998-06-17 |
| WO1996034869A1 (en) | 1996-11-07 |
| PL323148A1 (en) | 1998-03-16 |
| TR199701289T2 (xx) | 1998-08-21 |
| NO974995D0 (no) | 1997-10-30 |
| HUP9801061A2 (hu) | 1998-08-28 |
| MX9708422A (es) | 1998-02-28 |
| CN1184480A (zh) | 1998-06-10 |
| JPH11504912A (ja) | 1999-05-11 |
| NO974995L (no) | 1997-10-30 |
| HUP9801061A3 (en) | 1999-01-28 |
| EP0823911A1 (en) | 1998-02-18 |
| AU5814196A (en) | 1996-11-21 |
| KR19990008354A (ko) | 1999-01-25 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |