CA1175841A - .beta.-LACTAM ANTIBIOTICS, THEIR PREPARATION AND USE - Google Patents
.beta.-LACTAM ANTIBIOTICS, THEIR PREPARATION AND USEInfo
- Publication number
- CA1175841A CA1175841A CA000357846A CA357846A CA1175841A CA 1175841 A CA1175841 A CA 1175841A CA 000357846 A CA000357846 A CA 000357846A CA 357846 A CA357846 A CA 357846A CA 1175841 A CA1175841 A CA 1175841A
- Authority
- CA
- Canada
- Prior art keywords
- formula
- ester
- pharmaceutically acceptable
- salt
- group
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 28
- 239000003782 beta lactam antibiotic agent Substances 0.000 title description 2
- 150000002148 esters Chemical class 0.000 claims abstract description 176
- 150000003839 salts Chemical class 0.000 claims abstract description 141
- 150000001875 compounds Chemical class 0.000 claims abstract description 118
- 238000000034 method Methods 0.000 claims abstract description 117
- 238000001727 in vivo Methods 0.000 claims abstract description 59
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 39
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 21
- 125000005907 alkyl ester group Chemical group 0.000 claims abstract description 17
- 125000001589 carboacyl group Chemical group 0.000 claims abstract description 15
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 14
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 13
- 229910004727 OSO3H Inorganic materials 0.000 claims abstract description 11
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 10
- 125000000022 2-aminoethyl group Chemical group [H]C([*])([H])C([H])([H])N([H])[H] 0.000 claims abstract description 8
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 7
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 7
- 125000005129 aryl carbonyl group Chemical group 0.000 claims abstract description 7
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract 4
- -1 amino, benzoyl Chemical group 0.000 claims description 87
- 150000003573 thiols Chemical class 0.000 claims description 66
- 239000000460 chlorine Substances 0.000 claims description 63
- 239000002253 acid Substances 0.000 claims description 53
- 125000000217 alkyl group Chemical group 0.000 claims description 45
- 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 claims description 44
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 42
- 239000011734 sodium Substances 0.000 claims description 37
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 36
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 32
- 125000003118 aryl group Chemical group 0.000 claims description 30
- 239000000126 substance Substances 0.000 claims description 24
- 125000004432 carbon atom Chemical group C* 0.000 claims description 22
- 229910052708 sodium Inorganic materials 0.000 claims description 21
- 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 claims description 19
- 229910052739 hydrogen Inorganic materials 0.000 claims description 19
- 239000001257 hydrogen Substances 0.000 claims description 18
- 125000004185 ester group Chemical group 0.000 claims description 17
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 17
- 238000006243 chemical reaction Methods 0.000 claims description 16
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 14
- 125000003545 alkoxy group Chemical group 0.000 claims description 14
- 150000002500 ions Chemical class 0.000 claims description 14
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 13
- 125000001424 substituent group Chemical group 0.000 claims description 12
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 claims description 11
- 125000001434 methanylylidene group Chemical group [H]C#[*] 0.000 claims description 10
- 229910052801 chlorine Inorganic materials 0.000 claims description 9
- 125000004705 ethylthio group Chemical group C(C)S* 0.000 claims description 9
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 claims description 8
- 125000002883 imidazolyl group Chemical group 0.000 claims description 7
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 6
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 6
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 6
- 125000001246 bromo group Chemical group Br* 0.000 claims description 6
- 125000000335 thiazolyl group Chemical group 0.000 claims description 6
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 5
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 claims description 5
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical class [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 claims description 5
- 150000001721 carbon Chemical group 0.000 claims description 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- 239000011737 fluorine Substances 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 125000005843 halogen group Chemical group 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 5
- 125000001544 thienyl group Chemical group 0.000 claims description 5
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 4
- 125000004429 atom Chemical group 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 125000004494 ethyl ester group Chemical group 0.000 claims description 4
- FMVJYQGSRWVMQV-UHFFFAOYSA-N ethyl propiolate Chemical compound CCOC(=O)C#C FMVJYQGSRWVMQV-UHFFFAOYSA-N 0.000 claims description 4
- 125000002541 furyl group Chemical group 0.000 claims description 4
- 125000001436 propyl group Chemical class [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- UORVCLMRJXCDCP-UHFFFAOYSA-M propynoate Chemical compound [O-]C(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-M 0.000 claims description 4
- SARACICUNSZHSR-UHFFFAOYSA-N (4-nitrophenyl)methyl prop-2-ynoate Chemical compound [O-][N+](=O)C1=CC=C(COC(=O)C#C)C=C1 SARACICUNSZHSR-UHFFFAOYSA-N 0.000 claims description 3
- QBAVHEZVBGASER-UHFFFAOYSA-N 1-(2-bromoethyl)pyrrole Chemical compound BrCCN1C=CC=C1 QBAVHEZVBGASER-UHFFFAOYSA-N 0.000 claims description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 3
- KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 3
- 125000004423 acyloxy group Chemical group 0.000 claims description 3
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 3
- 125000001041 indolyl group Chemical group 0.000 claims description 3
- 229910052740 iodine Chemical group 0.000 claims description 3
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 3
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical class [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims description 3
- HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 claims description 3
- AWKLUAZCKWQUNR-UHFFFAOYSA-N 1-bromopropan-1-amine Chemical compound CCC(N)Br AWKLUAZCKWQUNR-UHFFFAOYSA-N 0.000 claims description 2
- QSECPQCFCWVBKM-UHFFFAOYSA-N 2-iodoethanol Chemical compound OCCI QSECPQCFCWVBKM-UHFFFAOYSA-N 0.000 claims description 2
- LXFVAQGRFCZBQL-UHFFFAOYSA-N 4-(iodomethyl)-2-phenyl-1,3-thiazole Chemical compound ICC1=CSC(C=2C=CC=CC=2)=N1 LXFVAQGRFCZBQL-UHFFFAOYSA-N 0.000 claims description 2
- 125000002252 acyl group Chemical group 0.000 claims description 2
- 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 claims description 2
- 238000009938 salting Methods 0.000 claims description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 3
- 125000004414 alkyl thio group Chemical group 0.000 claims 2
- 125000001153 fluoro group Chemical group F* 0.000 claims 2
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims 2
- 125000001624 naphthyl group Chemical group 0.000 claims 2
- ADHFTAKIDKDGBV-UHFFFAOYSA-N (4-nitrophenyl)methyl 2-bromoacetate Chemical compound [O-][N+](=O)C1=CC=C(COC(=O)CBr)C=C1 ADHFTAKIDKDGBV-UHFFFAOYSA-N 0.000 claims 1
- CFPWFQPYKGFQPA-UHFFFAOYSA-N (4-nitrophenyl)methyl n-(2-bromoethyl)carbamate Chemical compound [O-][N+](=O)C1=CC=C(COC(=O)NCCBr)C=C1 CFPWFQPYKGFQPA-UHFFFAOYSA-N 0.000 claims 1
- MGPNVDUZUTUJIP-OOZYFLPDSA-N (5r,6r)-3-(3-aminopropylsulfanyl)-6-[(1s)-1-hydroxyethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound C1C(SCCCN)=C(C(O)=O)N2C(=O)[C@@H]([C@@H](O)C)[C@H]21 MGPNVDUZUTUJIP-OOZYFLPDSA-N 0.000 claims 1
- YRLUXSDRLYEOTC-KWPFTWCOSA-N (5r,6r)-3-[(2-amino-1,3-thiazol-4-yl)methylsulfanyl]-6-[(1s)-1-hydroxyethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound C([C@@H]1[C@@H](C(N1C=1C(O)=O)=O)[C@@H](O)C)C=1SCC1=CSC(N)=N1 YRLUXSDRLYEOTC-KWPFTWCOSA-N 0.000 claims 1
- ZOWUUYAPKVGUOK-DRTXNXNESA-N (5r,6r)-3-[(z)-2-carboxyethenyl]sulfanyl-6-[(1s)-1-hydroxyethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound C1C(S\C=C/C(O)=O)=C(C(O)=O)N2C(=O)[C@@H]([C@@H](O)C)[C@H]21 ZOWUUYAPKVGUOK-DRTXNXNESA-N 0.000 claims 1
- IHKHYLIIRKGQSP-DRTXNXNESA-N (5r,6r)-3-[(z)-2-carboxyethenyl]sulfanyl-7-oxo-6-[(1s)-1-sulfooxyethyl]-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound C1C(S\C=C/C(O)=O)=C(C(O)=O)N2C(=O)[C@@H]([C@@H](OS(O)(=O)=O)C)[C@H]21 IHKHYLIIRKGQSP-DRTXNXNESA-N 0.000 claims 1
- QYLHPDXDYHFWPS-UMNHJUIQSA-N (5r,6r)-6-[(1s)-1-hydroxyethyl]-7-oxo-3-(2-pyrrol-1-ylethylsulfanyl)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound C([C@@H]1[C@@H](C(N1C=1C(O)=O)=O)[C@@H](O)C)C=1SCCN1C=CC=C1 QYLHPDXDYHFWPS-UMNHJUIQSA-N 0.000 claims 1
- SOMNJTKJTKZOJN-ZBINZKHDSA-N (5r,6r)-6-[(1s)-1-hydroxyethyl]-7-oxo-3-[(2-phenyl-1,3-thiazol-4-yl)methylsulfanyl]-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound C([C@@H]1[C@@H](C(N1C=1C(O)=O)=O)[C@@H](O)C)C=1SCC(N=1)=CSC=1C1=CC=CC=C1 SOMNJTKJTKZOJN-ZBINZKHDSA-N 0.000 claims 1
- YIFHJRQMDVEJGF-IQBCPYKGSA-N (5r,6s)-3-[(z)-3-(2-aminoethoxy)-3-oxoprop-1-enyl]sulfanyl-6-[(1s)-1-hydroxyethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid Chemical compound C1C(S\C=C/C(=O)OCCN)=C(C(O)=O)N2C(=O)[C@H]([C@@H](O)C)[C@H]21 YIFHJRQMDVEJGF-IQBCPYKGSA-N 0.000 claims 1
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims 1
- CMJVTFPLMXHGMO-CLFDHOPQSA-M [Na+].C1C(SCC)=C(C([O-])=O)N2C(=O)[C@@H]([C@H](C)O)[C@@H]12 Chemical compound [Na+].C1C(SCC)=C(C([O-])=O)N2C(=O)[C@@H]([C@H](C)O)[C@@H]12 CMJVTFPLMXHGMO-CLFDHOPQSA-M 0.000 claims 1
- UYFPOALPHPVGBM-CLFDHOPQSA-M [Na+].C1C(SCCO)=C(C([O-])=O)N2C(=O)[C@@H]([C@@H](O)C)[C@H]21 Chemical compound [Na+].C1C(SCCO)=C(C([O-])=O)N2C(=O)[C@@H]([C@@H](O)C)[C@H]21 UYFPOALPHPVGBM-CLFDHOPQSA-M 0.000 claims 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims 1
- SYGWYBOJXOGMRU-UHFFFAOYSA-N chembl233051 Chemical compound C1=CC=C2C3=CC(C(N(CCN(C)C)C4=O)=O)=C5C4=CC=CC5=C3SC2=C1 SYGWYBOJXOGMRU-UHFFFAOYSA-N 0.000 claims 1
- HWZDPXZRWQOTGW-NLGINJDKSA-L disodium (5R,6R)-3-ethylsulfanyl-7-oxo-6-[(1S)-1-sulfonatooxyethyl]-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate Chemical compound C(C)SC1=C(N2C([C@H]([C@H]2C1)[C@H](C)OS(=O)(=O)[O-])=O)C(=O)[O-].[Na+].[Na+] HWZDPXZRWQOTGW-NLGINJDKSA-L 0.000 claims 1
- 150000003385 sodium Chemical class 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 120
- 239000000243 solution Substances 0.000 description 97
- 229910001868 water Inorganic materials 0.000 description 94
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 69
- UUFQTNFCRMXOAE-UHFFFAOYSA-N 1-methylmethylene Chemical compound C[CH] UUFQTNFCRMXOAE-UHFFFAOYSA-N 0.000 description 67
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 61
- 239000000203 mixture Substances 0.000 description 55
- 239000000047 product Substances 0.000 description 51
- 239000007787 solid Substances 0.000 description 44
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 41
- 229940093499 ethyl acetate Drugs 0.000 description 40
- 235000019439 ethyl acetate Nutrition 0.000 description 40
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 38
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 36
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 36
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 33
- ZMXDDKWLCZADIW-YYWVXINBSA-N N,N-dimethylformamide-d7 Chemical compound [2H]C(=O)N(C([2H])([2H])[2H])C([2H])([2H])[2H] ZMXDDKWLCZADIW-YYWVXINBSA-N 0.000 description 26
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 21
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 20
- 239000007864 aqueous solution Substances 0.000 description 19
- 229910000027 potassium carbonate Inorganic materials 0.000 description 19
- 239000012267 brine Substances 0.000 description 17
- 235000011181 potassium carbonates Nutrition 0.000 description 17
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 17
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 16
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 15
- 239000000741 silica gel Substances 0.000 description 15
- 229910002027 silica gel Inorganic materials 0.000 description 15
- 229960001866 silicon dioxide Drugs 0.000 description 15
- 238000003756 stirring Methods 0.000 description 15
- FYZUENZXIZCLAZ-UHFFFAOYSA-N 2-methylhept-2-enoic acid Chemical compound CCCCC=C(C)C(O)=O FYZUENZXIZCLAZ-UHFFFAOYSA-N 0.000 description 14
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
- 150000005690 diesters Chemical class 0.000 description 14
- 101150041968 CDC13 gene Proteins 0.000 description 13
- 101100073357 Streptomyces halstedii sch2 gene Proteins 0.000 description 13
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 13
- 239000006260 foam Substances 0.000 description 13
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 13
- VBTQNRFWXBXZQR-UHFFFAOYSA-N n-bromoacetamide Chemical compound CC(=O)NBr VBTQNRFWXBXZQR-UHFFFAOYSA-N 0.000 description 13
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 13
- 159000000000 sodium salts Chemical class 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- 101100167062 Caenorhabditis elegans chch-3 gene Proteins 0.000 description 11
- 238000004587 chromatography analysis Methods 0.000 description 11
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 9
- DBTDEFJAFBUGPP-UHFFFAOYSA-N Methanethial Chemical compound S=C DBTDEFJAFBUGPP-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 238000010828 elution Methods 0.000 description 9
- 239000012044 organic layer Substances 0.000 description 9
- 229930182555 Penicillin Natural products 0.000 description 8
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 8
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 8
- 239000003208 petroleum Substances 0.000 description 8
- 239000000377 silicon dioxide Substances 0.000 description 8
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 8
- 238000005406 washing Methods 0.000 description 8
- 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 7
- 239000000543 intermediate Substances 0.000 description 7
- 239000003921 oil Substances 0.000 description 7
- 235000019198 oils Nutrition 0.000 description 7
- 229940002612 prodrug Drugs 0.000 description 7
- 239000000651 prodrug Substances 0.000 description 7
- 235000017557 sodium bicarbonate Nutrition 0.000 description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 239000003054 catalyst Substances 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- 125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 description 6
- 239000008363 phosphate buffer Substances 0.000 description 6
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 6
- 238000010626 work up procedure Methods 0.000 description 6
- 229930186147 Cephalosporin Natural products 0.000 description 5
- 229910019142 PO4 Inorganic materials 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 241000191967 Staphylococcus aureus Species 0.000 description 5
- 101100054666 Streptomyces halstedii sch3 gene Proteins 0.000 description 5
- 229960003022 amoxicillin Drugs 0.000 description 5
- LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 description 5
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 5
- 229940124587 cephalosporin Drugs 0.000 description 5
- 150000001780 cephalosporins Chemical class 0.000 description 5
- 238000001704 evaporation Methods 0.000 description 5
- 230000008020 evaporation Effects 0.000 description 5
- 238000005984 hydrogenation reaction Methods 0.000 description 5
- 238000007327 hydrogenolysis reaction Methods 0.000 description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 5
- LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 description 5
- 229940049954 penicillin Drugs 0.000 description 5
- 239000010452 phosphate Substances 0.000 description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 4
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
- 241000588724 Escherichia coli Species 0.000 description 4
- 241000588915 Klebsiella aerogenes Species 0.000 description 4
- 239000000370 acceptor Substances 0.000 description 4
- 229940022663 acetate Drugs 0.000 description 4
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 4
- 229960000723 ampicillin Drugs 0.000 description 4
- 230000000844 anti-bacterial effect Effects 0.000 description 4
- DIKBFYAXUHHXCS-UHFFFAOYSA-N bromoform Chemical compound BrC(Br)Br DIKBFYAXUHHXCS-UHFFFAOYSA-N 0.000 description 4
- FPPNZSSZRUTDAP-UWFZAAFLSA-N carbenicillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)C(C(O)=O)C1=CC=CC=C1 FPPNZSSZRUTDAP-UWFZAAFLSA-N 0.000 description 4
- 229960003669 carbenicillin Drugs 0.000 description 4
- 150000007942 carboxylates Chemical class 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- SRCZQMGIVIYBBJ-UHFFFAOYSA-N ethoxyethane;ethyl acetate Chemical compound CCOCC.CCOC(C)=O SRCZQMGIVIYBBJ-UHFFFAOYSA-N 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- OTTZHAVKAVGASB-UHFFFAOYSA-N hept-2-ene Chemical group CCCCC=CC OTTZHAVKAVGASB-UHFFFAOYSA-N 0.000 description 4
- 235000019341 magnesium sulphate Nutrition 0.000 description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
- 235000009518 sodium iodide Nutrition 0.000 description 4
- DWCSXQCXXITVKE-UHFFFAOYSA-N triethyloxidanium Chemical class CC[O+](CC)CC DWCSXQCXXITVKE-UHFFFAOYSA-N 0.000 description 4
- WYRSGXAIHNMKOL-UHFFFAOYSA-N $l^{1}-sulfanylethane Chemical compound CC[S] WYRSGXAIHNMKOL-UHFFFAOYSA-N 0.000 description 3
- GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 description 3
- 101100501247 Caenorhabditis elegans elo-2 gene Proteins 0.000 description 3
- 101100501250 Caenorhabditis elegans elo-3 gene Proteins 0.000 description 3
- 241000588767 Proteus vulgaris Species 0.000 description 3
- 241000588777 Providencia rettgeri Species 0.000 description 3
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 3
- 239000005864 Sulphur Substances 0.000 description 3
- TUCNEACPLKLKNU-UHFFFAOYSA-N acetyl Chemical compound C[C]=O TUCNEACPLKLKNU-UHFFFAOYSA-N 0.000 description 3
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 239000012298 atmosphere Substances 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 125000000219 ethylidene group Chemical group [H]C(=[*])C([H])([H])[H] 0.000 description 3
- 150000002431 hydrogen Chemical group 0.000 description 3
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
- 150000002960 penicillins Chemical class 0.000 description 3
- 125000005633 phthalidyl group Chemical group 0.000 description 3
- 229940007042 proteus vulgaris Drugs 0.000 description 3
- 238000010898 silica gel chromatography Methods 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- QSLPNSWXUQHVLP-UHFFFAOYSA-N $l^{1}-sulfanylmethane Chemical compound [S]C QSLPNSWXUQHVLP-UHFFFAOYSA-N 0.000 description 2
- OKBVVJOGVLARMR-QMTHXVAHSA-N (6R,7R)-7-[[2-(2-amino-4-thiazolyl)-2-(carboxymethoxyimino)-1-oxoethyl]amino]-3-ethenyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound S1C(N)=NC(C(=NOCC(O)=O)C(=O)N[C@@H]2C(N3C(=C(C=C)CS[C@@H]32)C(O)=O)=O)=C1 OKBVVJOGVLARMR-QMTHXVAHSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical class OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- 101100501252 Caenorhabditis elegans elo-4 gene Proteins 0.000 description 2
- 241000588919 Citrobacter freundii Species 0.000 description 2
- 241000588697 Enterobacter cloacae Species 0.000 description 2
- 241000194032 Enterococcus faecalis Species 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 241000588772 Morganella morganii Species 0.000 description 2
- 241000588769 Proteus <enterobacteria> Species 0.000 description 2
- 241000588770 Proteus mirabilis Species 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- SKZKKFZAGNVIMN-UHFFFAOYSA-N Salicilamide Chemical compound NC(=O)C1=CC=CC=C1O SKZKKFZAGNVIMN-UHFFFAOYSA-N 0.000 description 2
- 241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 2
- 241000607715 Serratia marcescens Species 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 description 2
- 241001061127 Thione Species 0.000 description 2
- 101150049278 US20 gene Proteins 0.000 description 2
- 241001342522 Vampyrum spectrum Species 0.000 description 2
- XAKBSHICSHRJCL-UHFFFAOYSA-N [CH2]C(=O)C1=CC=CC=C1 Chemical group [CH2]C(=O)C1=CC=CC=C1 XAKBSHICSHRJCL-UHFFFAOYSA-N 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 150000001342 alkaline earth metals Chemical class 0.000 description 2
- 230000029936 alkylation Effects 0.000 description 2
- 238000005804 alkylation reaction Methods 0.000 description 2
- BHELZAPQIKSEDF-UHFFFAOYSA-N allyl bromide Chemical compound BrCC=C BHELZAPQIKSEDF-UHFFFAOYSA-N 0.000 description 2
- KLOHDWPABZXLGI-YWUHCJSESA-M ampicillin sodium Chemical compound [Na+].C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C([O-])=O)(C)C)=CC=CC=C1 KLOHDWPABZXLGI-YWUHCJSESA-M 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- CZTQZXZIADLWOZ-CRAIPNDOSA-N cefaloridine Chemical compound O=C([C@@H](NC(=O)CC=1SC=CC=1)[C@H]1SC2)N1C(C(=O)[O-])=C2C[N+]1=CC=CC=C1 CZTQZXZIADLWOZ-CRAIPNDOSA-N 0.000 description 2
- 229960003866 cefaloridine Drugs 0.000 description 2
- 229960001139 cefazolin Drugs 0.000 description 2
- MLYYVTUWGNIJIB-BXKDBHETSA-N cefazolin Chemical compound S1C(C)=NN=C1SCC1=C(C(O)=O)N2C(=O)[C@@H](NC(=O)CN3N=NN=C3)[C@H]2SC1 MLYYVTUWGNIJIB-BXKDBHETSA-N 0.000 description 2
- 229960002588 cefradine Drugs 0.000 description 2
- 229940106164 cephalexin Drugs 0.000 description 2
- ZAIPMKNFIOOWCQ-UEKVPHQBSA-N cephalexin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=CC=C1 ZAIPMKNFIOOWCQ-UEKVPHQBSA-N 0.000 description 2
- RDLPVSKMFDYCOR-UEKVPHQBSA-N cephradine Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CCC=CC1 RDLPVSKMFDYCOR-UEKVPHQBSA-N 0.000 description 2
- 229940047583 cetamide Drugs 0.000 description 2
- PYRZPBDTPRQYKG-UHFFFAOYSA-N cyclopentene-1-carboxylic acid Chemical compound OC(=O)C1=CCCC1 PYRZPBDTPRQYKG-UHFFFAOYSA-N 0.000 description 2
- CCGKOQOJPYTBIH-UHFFFAOYSA-N ethenone Chemical compound C=C=O CCGKOQOJPYTBIH-UHFFFAOYSA-N 0.000 description 2
- OONRFAPDKNLTGD-UHFFFAOYSA-N ethyl 2-(2,4-dimethoxyphenyl)-4-hydroxy-5-oxo-1-(4-sulfamoylphenyl)-2h-pyrrole-3-carboxylate Chemical compound CCOC(=O)C1=C(O)C(=O)N(C=2C=CC(=CC=2)S(N)(=O)=O)C1C1=CC=C(OC)C=C1OC OONRFAPDKNLTGD-UHFFFAOYSA-N 0.000 description 2
- UQEAIHBTYFGYIE-UHFFFAOYSA-N hexamethyldisiloxane Chemical compound C[Si](C)(C)O[Si](C)(C)C UQEAIHBTYFGYIE-UHFFFAOYSA-N 0.000 description 2
- CUILPNURFADTPE-UHFFFAOYSA-N hypobromous acid Chemical compound BrO CUILPNURFADTPE-UHFFFAOYSA-N 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
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 2
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 2
- 125000006502 nitrobenzyl group Chemical group 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 159000000001 potassium salts Chemical class 0.000 description 2
- 125000001453 quaternary ammonium group Chemical group 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-L sulfate group Chemical group S(=O)(=O)([O-])[O-] QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 2
- 125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- OHKOGUYZJXTSFX-KZFFXBSXSA-N ticarcillin Chemical compound C=1([C@@H](C(O)=O)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)C=CSC=1 OHKOGUYZJXTSFX-KZFFXBSXSA-N 0.000 description 2
- 229960004659 ticarcillin Drugs 0.000 description 2
- QDNCLIPKBNMUPP-UHFFFAOYSA-N trimethyloxidanium Chemical class C[O+](C)C QDNCLIPKBNMUPP-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 238000001665 trituration Methods 0.000 description 2
- 238000002211 ultraviolet spectrum Methods 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- VOLGAXAGEUPBDM-UHFFFAOYSA-N $l^{1}-oxidanylethane Chemical compound CC[O] VOLGAXAGEUPBDM-UHFFFAOYSA-N 0.000 description 1
- JNUZADQZHYFJGW-JOCHJYFZSA-N (2R)-N-[3-[5-fluoro-2-(2-fluoro-3-methylsulfonylanilino)pyrimidin-4-yl]-1H-indol-7-yl]-3-methoxy-2-(4-methylpiperazin-1-yl)propanamide Chemical compound FC=1C(=NC(=NC=1)NC1=C(C(=CC=C1)S(=O)(=O)C)F)C1=CNC2=C(C=CC=C12)NC([C@@H](COC)N1CCN(CC1)C)=O JNUZADQZHYFJGW-JOCHJYFZSA-N 0.000 description 1
- OIECDSKSPRTZHG-NJBDSQKTSA-N (2s,5r,6r)-3,3-dimethyl-7-oxo-6-[[(2r)-2-phenyl-2-(sulfoamino)acetyl]amino]-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound C1([C@@H](NS(O)(=O)=O)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 OIECDSKSPRTZHG-NJBDSQKTSA-N 0.000 description 1
- XCJNQYRAAWYPIW-UHFFFAOYSA-N (4-nitrophenyl)methyl 2-amino-3-bromopropanoate Chemical compound BrCC(N)C(=O)OCC1=CC=C([N+]([O-])=O)C=C1 XCJNQYRAAWYPIW-UHFFFAOYSA-N 0.000 description 1
- YLRBJYMANQKEAW-UHFFFAOYSA-N 1-bromo-4-(bromomethyl)benzene Chemical compound BrCC1=CC=C(Br)C=C1 YLRBJYMANQKEAW-UHFFFAOYSA-N 0.000 description 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 1
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 description 1
- JPKFEGGMIYULIO-UHFFFAOYSA-N 12-benzyl-N,N-dimethylhexadecan-1-amine Chemical class CN(C)CCCCCCCCCCCC(CCCC)CC1=CC=CC=C1 JPKFEGGMIYULIO-UHFFFAOYSA-N 0.000 description 1
- DQECFVGMGBQCPA-GLCLSGQWSA-N 2,2-dimethylpropanoyloxymethyl (2s,5r,6r)-6-[[(2r)-2-amino-2-phenylacetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylate;hydron;chloride Chemical compound Cl.C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)[C@H](C(S3)(C)C)C(=O)OCOC(=O)C(C)(C)C)=CC=CC=C1 DQECFVGMGBQCPA-GLCLSGQWSA-N 0.000 description 1
- FKJSFKCZZIXQIP-UHFFFAOYSA-N 2-bromo-1-(4-bromophenyl)ethanone Chemical compound BrCC(=O)C1=CC=C(Br)C=C1 FKJSFKCZZIXQIP-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- VOLRSQPSJGXRNJ-UHFFFAOYSA-N 4-nitrobenzyl bromide Chemical compound [O-][N+](=O)C1=CC=C(CBr)C=C1 VOLRSQPSJGXRNJ-UHFFFAOYSA-N 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 101100313763 Arabidopsis thaliana TIM22-2 gene Proteins 0.000 description 1
- 244000063299 Bacillus subtilis Species 0.000 description 1
- 235000014469 Bacillus subtilis Nutrition 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 241000606125 Bacteroides Species 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 1
- 101100379067 Caenorhabditis elegans anc-1 gene Proteins 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- 241000518994 Conta Species 0.000 description 1
- 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 1
- 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 1
- 244000182625 Dictamnus albus Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 101001057156 Homo sapiens Melanoma-associated antigen C2 Proteins 0.000 description 1
- 241000588748 Klebsiella Species 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 102100027252 Melanoma-associated antigen C2 Human genes 0.000 description 1
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- 241001474977 Palla Species 0.000 description 1
- 229930195708 Penicillin V Natural products 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 101100178280 Rattus norvegicus Homer1 gene Proteins 0.000 description 1
- 241000786363 Rhampholeon spectrum Species 0.000 description 1
- 241000607720 Serratia Species 0.000 description 1
- 241000607760 Shigella sonnei Species 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 239000004141 Sodium laurylsulphate Substances 0.000 description 1
- 241000193998 Streptococcus pneumoniae Species 0.000 description 1
- 241000193996 Streptococcus pyogenes Species 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- OKJPEAGHQZHRQV-UHFFFAOYSA-N Triiodomethane Natural products IC(I)I OKJPEAGHQZHRQV-UHFFFAOYSA-N 0.000 description 1
- YZCKVEUIGOORGS-NJFSPNSNSA-N Tritium Chemical group [3H] YZCKVEUIGOORGS-NJFSPNSNSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- CUJRVFIICFDLGR-UHFFFAOYSA-N acetylacetonate Chemical compound CC(=O)[CH-]C(C)=O CUJRVFIICFDLGR-UHFFFAOYSA-N 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
- 229940107816 ammonium iodide Drugs 0.000 description 1
- 229960003311 ampicillin trihydrate Drugs 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 125000003435 aroyl group Chemical group 0.000 description 1
- JTWOMNBEOCYFNV-NFFDBFGFSA-N azlocillin Chemical compound N([C@@H](C(=O)N[C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C=1C=CC=CC=1)C(=O)N1CCNC1=O JTWOMNBEOCYFNV-NFFDBFGFSA-N 0.000 description 1
- 229960003623 azlocillin Drugs 0.000 description 1
- 229960005412 bacampicillin hydrochloride Drugs 0.000 description 1
- IWVTXAGTHUECPN-ANBBSHPLSA-N bacampicillin hydrochloride Chemical compound [H+].[Cl-].C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)[C@H](C(S3)(C)C)C(=O)OC(C)OC(=O)OCC)=CC=CC=C1 IWVTXAGTHUECPN-ANBBSHPLSA-N 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- KDPAWGWELVVRCH-UHFFFAOYSA-M bromoacetate Chemical compound [O-]C(=O)CBr KDPAWGWELVVRCH-UHFFFAOYSA-M 0.000 description 1
- 125000006278 bromobenzyl group Chemical group 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 229960000603 cefalotin Drugs 0.000 description 1
- VUFGUVLLDPOSBC-XRZFDKQNSA-M cephalothin sodium Chemical compound [Na+].N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)COC(=O)C)C([O-])=O)C(=O)CC1=CC=CS1 VUFGUVLLDPOSBC-XRZFDKQNSA-M 0.000 description 1
- QDYLMAYUEZBUFO-UHFFFAOYSA-N cetalkonium chloride Chemical class CCCCCCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 QDYLMAYUEZBUFO-UHFFFAOYSA-N 0.000 description 1
- 229920001429 chelating resin Polymers 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 125000004803 chlorobenzyl group Chemical group 0.000 description 1
- 125000000068 chlorophenyl group Chemical group 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- JJCFRYNCJDLXIK-UHFFFAOYSA-N cyproheptadine Chemical compound C1CN(C)CCC1=C1C2=CC=CC=C2C=CC2=CC=CC=C21 JJCFRYNCJDLXIK-UHFFFAOYSA-N 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 1
- DENRZWYUOJLTMF-UHFFFAOYSA-N diethyl sulfate Chemical compound CCOS(=O)(=O)OCC DENRZWYUOJLTMF-UHFFFAOYSA-N 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 229940092559 enterobacter aerogenes Drugs 0.000 description 1
- FQQFFZPBGYGDSX-NJFHWYBASA-N epithienamycin E Chemical compound C1C(S\C=C\NC(C)=O)=C(C(O)=O)N2C(=O)[C@@H]([C@@H](OS(O)(=O)=O)C)[C@H]21 FQQFFZPBGYGDSX-NJFHWYBASA-N 0.000 description 1
- LJQKCYFTNDAAPC-UHFFFAOYSA-N ethanol;ethyl acetate Chemical compound CCO.CCOC(C)=O LJQKCYFTNDAAPC-UHFFFAOYSA-N 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- HWJHWSBFPPPIPD-UHFFFAOYSA-N ethoxyethane;propan-2-one Chemical compound CC(C)=O.CCOCC HWJHWSBFPPPIPD-UHFFFAOYSA-N 0.000 description 1
- 125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 1
- FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 125000004175 fluorobenzyl group Chemical group 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 208000004396 mastitis Diseases 0.000 description 1
- YPBATNHYBCGSSN-VWPFQQQWSA-N mezlocillin Chemical compound N([C@@H](C(=O)N[C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C=1C=CC=CC=1)C(=O)N1CCN(S(C)(=O)=O)C1=O YPBATNHYBCGSSN-VWPFQQQWSA-N 0.000 description 1
- 229960000198 mezlocillin Drugs 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- AMYQBWGTTRGDLR-UHFFFAOYSA-N n-bromopropanamide Chemical compound CCC(=O)NBr AMYQBWGTTRGDLR-UHFFFAOYSA-N 0.000 description 1
- HSPSCWZIJWKZKD-UHFFFAOYSA-N n-chloroacetamide Chemical compound CC(=O)NCl HSPSCWZIJWKZKD-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 229940073020 nitrol Drugs 0.000 description 1
- 125000006501 nitrophenyl group Chemical group 0.000 description 1
- 229940099990 ogen Drugs 0.000 description 1
- DBSMLQTUDJVICQ-CJODITQLSA-N onametostat Chemical compound NC1=C2C=CN([C@@H]3C[C@H](CCC4=CC=C5C=C(Br)C(N)=NC5=C4)[C@@H](O)[C@H]3O)C2=NC=N1 DBSMLQTUDJVICQ-CJODITQLSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 235000019371 penicillin G benzathine Nutrition 0.000 description 1
- 229940056360 penicillin g Drugs 0.000 description 1
- 229940056367 penicillin v Drugs 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- BPLBGHOLXOTWMN-MBNYWOFBSA-N phenoxymethylpenicillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)COC1=CC=CC=C1 BPLBGHOLXOTWMN-MBNYWOFBSA-N 0.000 description 1
- 229960004632 pivampicillin hydrochloride Drugs 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 239000001253 polyvinylpolypyrrolidone Substances 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 235000015320 potassium carbonate Nutrition 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 125000006233 propoxy propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])OC([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- OSFBJERFMQCEQY-UHFFFAOYSA-N propylidene Chemical compound [CH]CC OSFBJERFMQCEQY-UHFFFAOYSA-N 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003856 quaternary ammonium compounds Chemical class 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- JWEQRJSCTFBRSI-PCLIKHOPSA-N rboxylate Chemical compound COC(=O)C1C(N2C3=O)C4=CC=CC=C4OC1(C)N=C2S\C3=C\C(C=1)=CC=C(OC)C=1COC1=CC=CC=C1C JWEQRJSCTFBRSI-PCLIKHOPSA-N 0.000 description 1
- 230000036647 reaction Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 229940115939 shigella sonnei Drugs 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 229940031000 streptococcus pneumoniae Drugs 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229950007949 suncillin Drugs 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 229960002780 talampicillin Drugs 0.000 description 1
- SOROUYSPFADXSN-SUWVAFIASA-N talampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(=O)OC2C3=CC=CC=C3C(=O)O2)(C)C)=CC=CC=C1 SOROUYSPFADXSN-SUWVAFIASA-N 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005302 thiazolylmethyl group Chemical group [H]C1=C([H])N=C(S1)C([H])([H])* 0.000 description 1
- 150000003568 thioethers Chemical class 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229910052723 transition metal Inorganic materials 0.000 description 1
- 150000003624 transition metals Chemical class 0.000 description 1
- 150000004684 trihydrates Chemical class 0.000 description 1
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- 210000001635 urinary tract Anatomy 0.000 description 1
- 229920002554 vinyl polymer Polymers 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
- C07D477/16—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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA000444974A CA1178278A (en) | 1979-08-10 | 1984-01-09 | .beta.-LACTAM ANTIBIOTICS, THEIR PREPARATION AND USE |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB7927901 | 1979-08-10 | ||
| GB7927901 | 1979-08-10 | ||
| GB8012724 | 1980-04-17 | ||
| GB8012724 | 1980-04-17 |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000444974A Division CA1178278A (en) | 1979-08-10 | 1984-01-09 | .beta.-LACTAM ANTIBIOTICS, THEIR PREPARATION AND USE |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1175841A true CA1175841A (en) | 1984-10-09 |
Family
ID=26272503
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000357846A Expired CA1175841A (en) | 1979-08-10 | 1980-08-08 | .beta.-LACTAM ANTIBIOTICS, THEIR PREPARATION AND USE |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US4473578A (Direct) |
| EP (2) | EP0055990B1 (Direct) |
| AU (1) | AU6119680A (Direct) |
| CA (1) | CA1175841A (Direct) |
| DE (1) | DE3070269D1 (Direct) |
| DK (1) | DK344080A (Direct) |
| ES (2) | ES8106308A1 (Direct) |
| FI (1) | FI802446A7 (Direct) |
| GR (1) | GR69935B (Direct) |
| IL (1) | IL60758A0 (Direct) |
| NO (1) | NO802377L (Direct) |
| NZ (1) | NZ194584A (Direct) |
Families Citing this family (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0072121A1 (en) * | 1981-08-08 | 1983-02-16 | Beecham Group Plc | Beta-lactam antibiotics |
| US4552873A (en) * | 1981-08-19 | 1985-11-12 | Sankyo Company Limited | Carbapenem compounds, and compositions containing them |
| EP0079167A1 (en) * | 1981-11-09 | 1983-05-18 | Beecham Group Plc | A carbapenem compound, preparation and use |
| GB2116540B (en) * | 1981-11-10 | 1985-07-17 | Shionogi & Co | Pluracidomycin b c and d and analogs thereof their production and a microorganism for use therein |
| US4556517A (en) * | 1981-12-29 | 1985-12-03 | Shionogi & Co., Ltd. | Carbapenem derivatives |
| DE3372773D1 (de) * | 1982-03-26 | 1987-09-03 | Hoechst Uk Ltd | 7-oxo-4-thia-1-azabicyclo(3,2,0)heptane derivatives |
| US4683301A (en) * | 1982-04-08 | 1987-07-28 | Bristol-Myers Company | Carbapenem antibiotics |
| US4710568A (en) * | 1982-04-09 | 1987-12-01 | Bristol-Myers Company | Carbapenem antibiotics |
| US4642341A (en) * | 1982-04-09 | 1987-02-10 | Bristol-Myers Company | Carbapenem antibiotics |
| US4536335A (en) * | 1982-06-18 | 1985-08-20 | Bristol-Myers Company | Carbapenem antibiotics |
| US4665170A (en) * | 1982-06-18 | 1987-05-12 | Bristol-Myers Company | Carbapenem antibiotics |
| US4640799A (en) * | 1982-06-18 | 1987-02-03 | Bristol-Myers Company | Carbapenem antibiotics |
| US4732977A (en) * | 1982-09-28 | 1988-03-22 | Bristol Myers Company | Carbapenem antibiotics |
| US4746736A (en) * | 1982-09-28 | 1988-05-24 | Bristol-Myers Company | Carbapenem antibiotics |
| EP0345827A1 (en) * | 1982-11-29 | 1989-12-13 | Schering Corporation | Process for the production of penem compounds |
| US4698339A (en) * | 1983-09-28 | 1987-10-06 | Takeda Chemical Industries, Ltd. | Carbapenems, their production and use |
| EP0137403A3 (en) * | 1983-09-28 | 1987-04-15 | Takeda Chemical Industries, Ltd. | Carbapenems, their production and use |
| ZA848416B (en) * | 1983-11-10 | 1986-06-25 | Dow Chemical Co | Fluorophenoxy compounds,herbicidal compositions and methods |
| US4717728A (en) * | 1983-11-21 | 1988-01-05 | Merck & Co., Inc. | Cyclic amidinyl and cyclic guanidinyl thio carbapenems |
Family Cites Families (19)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1531141A (en) * | 1976-08-17 | 1978-11-01 | Beecham Group Ltd | Beta-lactam antibiotics |
| NL7802826A (nl) * | 1977-04-08 | 1978-10-10 | Merck & Co Inc | Thienamycinederivaat, werkwijze voor het bereiden daarvan, alsmede farmaceutische preparaten. |
| US4235917A (en) * | 1977-05-05 | 1980-11-25 | Merck & Co., Inc. | N-Alkyl-N-acyl derivatives of thienamycin |
| EP0001567B1 (en) * | 1977-10-13 | 1981-12-02 | Sanraku-Ocean Co., Ltd. | Thienamycin related antibiotics ps-6 and ps-7, process for their production and compositions containing them |
| US4347367A (en) * | 1977-10-19 | 1982-08-31 | Merck & Co., Inc. | 3-Substituted-6-(1'-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]-hept-2-ene-2-carboxylic acid |
| US4347368A (en) * | 1977-10-19 | 1982-08-31 | Merck & Co., Inc. | 3-Substituted-6-substituted-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid |
| AU4061378A (en) * | 1977-10-19 | 1980-04-17 | Merck & Co., Inc. | 1-azabicyclo (3.2.0) hept-2-enes |
| EP0030392B1 (en) * | 1978-01-19 | 1984-05-16 | Beecham Group Plc | Intermediates for use in the preparation of carbapenems |
| EP0004132A1 (en) * | 1978-03-04 | 1979-09-19 | Beecham Group Plc | Esters of beta-lactam antibiotics, a process for their preparation pharmaceutical compositions containing them and the compounds for use as antibacterial agents |
| US4203902A (en) * | 1978-04-21 | 1980-05-20 | Merck & Co., Inc. | Process for preparing 6- and 2-substituted-1-carbadethiapen-2-em-3-carboxylic acids |
| DE2963717D1 (en) * | 1978-05-06 | 1982-11-04 | Beecham Group Plc | Carbapenem derivatives, a process for their preparation and pharmaceutical compositions containing them |
| EP0005349A1 (en) * | 1978-05-06 | 1979-11-14 | Beecham Group Plc | Alkylcarbapenems, their preparation, use in pharmaceutical compositions and intermediates |
| DE2963580D1 (en) * | 1978-08-02 | 1982-10-21 | Beecham Group Plc | Beta-lactam antibacterial agents, a process for their preparation and pharmaceutical compositions containing them |
| DE2966187D1 (en) * | 1978-08-23 | 1983-10-27 | Beecham Group Plc | Beta-lactam antibacterial compounds, their preparation and pharmaceutical compositions containing them |
| DE2961882D1 (en) * | 1978-08-25 | 1982-03-04 | Beecham Group Plc | Beta-lactam anti-bacterials, compositions containing them and a process for their preparation |
| EP0008885B1 (en) * | 1978-09-09 | 1983-11-30 | Beecham Group Plc | Beta-lactam compounds, their preparation and use |
| DE2965394D1 (en) * | 1978-11-01 | 1983-06-16 | Sanraku Ocean Co | Process for producing antibiotic beta-lactam compounds |
| EP0082133A3 (en) * | 1979-04-19 | 1983-07-20 | Merck & Co. Inc. | A process for preparing intermediates useful for preparing 2-substituted-6-substituted-1-carbadethiapen-2-em-3-carboxylic acids |
| US4376774A (en) * | 1979-05-29 | 1983-03-15 | Merck & Co., Inc. | Antibiotic N-heterocyclyl thienamycin |
-
1980
- 1980-08-04 EP EP82100683A patent/EP0055990B1/en not_active Expired
- 1980-08-04 EP EP80302659A patent/EP0024832B1/en not_active Expired
- 1980-08-04 DE DE8080302659T patent/DE3070269D1/de not_active Expired
- 1980-08-05 IL IL60758A patent/IL60758A0/xx unknown
- 1980-08-05 FI FI802446A patent/FI802446A7/fi not_active Application Discontinuation
- 1980-08-07 GR GR62627A patent/GR69935B/el unknown
- 1980-08-08 AU AU61196/80A patent/AU6119680A/en not_active Abandoned
- 1980-08-08 ES ES494136A patent/ES8106308A1/es not_active Expired
- 1980-08-08 DK DK344080A patent/DK344080A/da unknown
- 1980-08-08 CA CA000357846A patent/CA1175841A/en not_active Expired
- 1980-08-08 NO NO802377A patent/NO802377L/no unknown
- 1980-08-11 NZ NZ194584A patent/NZ194584A/xx unknown
-
1981
- 1981-02-26 ES ES499856A patent/ES8202010A1/es not_active Expired
-
1982
- 1982-07-29 US US06/403,076 patent/US4473578A/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| AU6119680A (en) | 1981-02-12 |
| FI802446A7 (fi) | 1981-01-01 |
| EP0055990B1 (en) | 1986-06-11 |
| IL60758A0 (en) | 1980-10-26 |
| NZ194584A (en) | 1983-05-31 |
| ES494136A0 (es) | 1981-08-01 |
| GR69935B (Direct) | 1982-07-21 |
| ES499856A0 (es) | 1982-01-16 |
| EP0024832A1 (en) | 1981-03-11 |
| NO802377L (no) | 1981-02-11 |
| EP0024832B1 (en) | 1985-03-13 |
| ES8106308A1 (es) | 1981-08-01 |
| ES8202010A1 (es) | 1982-01-16 |
| DK344080A (da) | 1981-02-11 |
| DE3070269D1 (en) | 1985-04-18 |
| EP0055990A1 (en) | 1982-07-14 |
| US4473578A (en) | 1984-09-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA1175841A (en) | .beta.-LACTAM ANTIBIOTICS, THEIR PREPARATION AND USE | |
| EP0072710B1 (en) | Carbapenem derivatives, their preparation and compositions containing them | |
| US4413000A (en) | β-Lactam antibiotics, their preparation and use | |
| IE59708B1 (en) | Carbapenem derivatives and compositions containing them | |
| GB2107307A (en) | B-lactum antibacterial agents | |
| US4477662A (en) | 2-Substituted thio carbapenem derivatives | |
| US5246926A (en) | Cephalosporin derivatives | |
| US4278686A (en) | Carbapenum derivatives, a process for their preparation and their use in pharmaceutical compositions and intermediates | |
| US6600035B1 (en) | 6-(substituted methylene) penems and intermediates | |
| AU771876B2 (en) | Novel carbapenem derivatives | |
| CA1164460A (en) | Beta-lactam compounds and process for production thereof | |
| NO774180L (no) | Fremgangsmaate for fremstilling av cefalosporin- og penicillinderivater | |
| US6825344B2 (en) | Process for the preparation of cephalosporin compounds and synthetic intermediates | |
| FI89490C (fi) | Foerfarande foer framstaellning av 2-metoximetyl-penemderivat | |
| CA1125292A (en) | Alkylcarbopenems, their preparation, use in pharmaceutical compositions and intermediates | |
| US4387051A (en) | β-Lactam antibiotics, their preparation and their use in pharmaceutical compositions | |
| IE45559B1 (en) | Lactam antibiotics | |
| CA1178278A (en) | .beta.-LACTAM ANTIBIOTICS, THEIR PREPARATION AND USE | |
| KR880001055B1 (ko) | 카르바페넴 유도체의 제조방법 | |
| NZ206893A (en) | Cephalosporin derivatives and pharmaceutical compositions;and 7-amino intermediates | |
| GB2105329A (en) | Penem-3-carboxylic acid derivatives their preparation and their use as antimicrobial agents | |
| AU760249B2 (en) | Novel c-2 s/o- and s/n formaldehyde acetal derivatives of carbapenem-3-carboxylic acids and their use as antibiotics and beta-lactamase inhibitors | |
| JP2708576B2 (ja) | カルバペネム誘導体 | |
| US4416883A (en) | Penicillin derivatives | |
| EP0050927B1 (en) | The preparation of beta-lactam antibiotics |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MKEX | Expiry |