DE3402642C2 - - Google Patents
Info
- Publication number
- DE3402642C2 DE3402642C2 DE3402642A DE3402642A DE3402642C2 DE 3402642 C2 DE3402642 C2 DE 3402642C2 DE 3402642 A DE3402642 A DE 3402642A DE 3402642 A DE3402642 A DE 3402642A DE 3402642 C2 DE3402642 C2 DE 3402642C2
- Authority
- DE
- Germany
- Prior art keywords
- compound
- cephem
- amino
- mixture
- acetamido
- 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
- -1 amino, carboxy Chemical group 0.000 claims description 86
- 150000001875 compounds Chemical class 0.000 claims description 81
- 238000006243 chemical reaction Methods 0.000 claims description 28
- 238000000034 method Methods 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 18
- 229940124587 cephalosporin Drugs 0.000 claims description 17
- 229930186147 Cephalosporin Natural products 0.000 claims description 16
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims description 14
- 239000002253 acid Substances 0.000 claims description 13
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 12
- 125000006239 protecting group Chemical group 0.000 claims description 12
- 239000007788 liquid Substances 0.000 claims description 9
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- 125000002252 acyl group Chemical group 0.000 claims description 5
- 150000001728 carbonyl compounds Chemical class 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 229910052751 metal Inorganic materials 0.000 claims description 4
- 239000002184 metal Substances 0.000 claims description 4
- 150000004714 phosphonium salts Chemical class 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 3
- 239000008177 pharmaceutical agent Substances 0.000 claims description 3
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 2
- 125000001118 alkylidene group Chemical group 0.000 claims description 2
- 239000000969 carrier Substances 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 150000004820 halides Chemical class 0.000 claims description 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
- 101100135641 Caenorhabditis elegans par-3 gene Proteins 0.000 claims 3
- UUFQTNFCRMXOAE-UHFFFAOYSA-N 1-methylmethylene Chemical compound C[CH] UUFQTNFCRMXOAE-UHFFFAOYSA-N 0.000 claims 2
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims 2
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 91
- 239000000203 mixture Substances 0.000 description 62
- 239000000243 solution Substances 0.000 description 60
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 49
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 49
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 39
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 36
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 28
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 27
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 22
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- 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 20
- 125000006519 CCH3 Chemical group 0.000 description 18
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 18
- 239000012141 concentrate Substances 0.000 description 18
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 18
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 17
- 239000000047 product Substances 0.000 description 17
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- 239000000706 filtrate Substances 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
- 230000000694 effects Effects 0.000 description 14
- 229910052739 hydrogen Inorganic materials 0.000 description 14
- 150000001780 cephalosporins Chemical class 0.000 description 13
- 229960001701 chloroform Drugs 0.000 description 13
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 13
- 235000019341 magnesium sulphate Nutrition 0.000 description 13
- 239000002244 precipitate Substances 0.000 description 13
- 230000000875 corresponding effect Effects 0.000 description 12
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 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 10
- 229940106164 cephalexin Drugs 0.000 description 10
- 239000000741 silica gel Substances 0.000 description 10
- 229910002027 silica gel Inorganic materials 0.000 description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
- 241000699670 Mus sp. Species 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- WKJGTOYAEQDNIA-IOOZKYRYSA-N (6r,7r)-7-[[(2r)-2-amino-2-phenylacetyl]amino]-3-chloro-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid;hydrate Chemical compound O.C1([C@H](C(=O)N[C@@H]2C(N3C(=C(Cl)CS[C@@H]32)C(O)=O)=O)N)=CC=CC=C1 WKJGTOYAEQDNIA-IOOZKYRYSA-N 0.000 description 8
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- OAMZXMDZZWGPMH-UHFFFAOYSA-N ethyl acetate;toluene Chemical compound CCOC(C)=O.CC1=CC=CC=C1 OAMZXMDZZWGPMH-UHFFFAOYSA-N 0.000 description 8
- 238000000338 in vitro Methods 0.000 description 8
- 230000002401 inhibitory effect Effects 0.000 description 8
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- 210000002700 urine Anatomy 0.000 description 8
- 239000003643 water by type Substances 0.000 description 8
- WWTBZEKOSBFBEM-SPWPXUSOSA-N (2s)-2-[[2-benzyl-3-[hydroxy-[(1r)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphoryl]propanoyl]amino]-3-(1h-indol-3-yl)propanoic acid Chemical compound N([C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)O)C(=O)C(CP(O)(=O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1C=CC=CC=1)CC1=CC=CC=C1 WWTBZEKOSBFBEM-SPWPXUSOSA-N 0.000 description 7
- TVTJUIAKQFIXCE-HUKYDQBMSA-N 2-amino-9-[(2R,3S,4S,5R)-4-fluoro-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-7-prop-2-ynyl-1H-purine-6,8-dione Chemical compound NC=1NC(C=2N(C(N(C=2N=1)[C@@H]1O[C@@H]([C@H]([C@H]1O)F)CO)=O)CC#C)=O TVTJUIAKQFIXCE-HUKYDQBMSA-N 0.000 description 7
- 241000894006 Bacteria Species 0.000 description 7
- 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
- 229960004841 cefadroxil Drugs 0.000 description 7
- NBFNMSULHIODTC-CYJZLJNKSA-N cefadroxil monohydrate Chemical compound O.C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=C(O)C=C1 NBFNMSULHIODTC-CYJZLJNKSA-N 0.000 description 7
- 229940126208 compound 22 Drugs 0.000 description 7
- 229940125851 compound 27 Drugs 0.000 description 7
- 239000000284 extract Substances 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 229930182555 Penicillin Natural products 0.000 description 6
- 230000000844 anti-bacterial effect Effects 0.000 description 6
- 150000002148 esters Chemical class 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 235000009518 sodium iodide Nutrition 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 5
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 5
- YLOQFPCGJCRAPQ-ITCMONMYSA-N benzhydryl (6r)-3-(hydroxymethyl)-8-oxo-7-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C1([C@@H]2N(C1=O)C(=C(CS2)CO)C(=O)OC(C=1C=CC=CC=1)C=1C=CC=CC=1)NC(=O)CC1=CC=CC=C1 YLOQFPCGJCRAPQ-ITCMONMYSA-N 0.000 description 5
- PBPKDMBQLUWMIO-OTOKDRCRSA-N benzhydryl (6r)-7-amino-3-(chloromethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound S([C@@H]1C(C(N11)=O)N)CC(CCl)=C1C(=O)OC(C=1C=CC=CC=1)C1=CC=CC=C1 PBPKDMBQLUWMIO-OTOKDRCRSA-N 0.000 description 5
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 5
- 229940049954 penicillin Drugs 0.000 description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 5
- 239000008363 phosphate buffer Substances 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 4
- 229920001817 Agar Polymers 0.000 description 4
- 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 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- 241000700159 Rattus Species 0.000 description 4
- 241000295644 Staphylococcaceae Species 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 239000008272 agar Substances 0.000 description 4
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 230000000052 comparative effect Effects 0.000 description 4
- 229940125782 compound 2 Drugs 0.000 description 4
- 229940126214 compound 3 Drugs 0.000 description 4
- HBFXVTVOSLPOEY-UHFFFAOYSA-N ethoxyethane;2-propan-2-yloxypropane Chemical compound CCOCC.CC(C)OC(C)C HBFXVTVOSLPOEY-UHFFFAOYSA-N 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 231100000518 lethal Toxicity 0.000 description 4
- 230000001665 lethal effect Effects 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 230000001681 protective effect Effects 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 4
- 235000019345 sodium thiosulphate Nutrition 0.000 description 4
- VYPDUQYOLCLEGS-UHFFFAOYSA-M sodium;2-ethylhexanoate Chemical compound [Na+].CCCCC(CC)C([O-])=O VYPDUQYOLCLEGS-UHFFFAOYSA-M 0.000 description 4
- AEVBPXDFDKBGLT-YOUFYPILSA-N (2s,3s,4r,5r)-n-[2-[4-(diethoxyphosphorylmethyl)anilino]-2-oxoethyl]-5-(2,4-dioxopyrimidin-1-yl)-3,4-dihydroxyoxolane-2-carboxamide Chemical compound C1=CC(CP(=O)(OCC)OCC)=CC=C1NC(=O)CNC(=O)[C@@H]1[C@@H](O)[C@@H](O)[C@H](N2C(NC(=O)C=C2)=O)O1 AEVBPXDFDKBGLT-YOUFYPILSA-N 0.000 description 3
- XFIMQDGBHJULGY-WFDQOPGTSA-N (6r,7r)-7-[[(2r)-2-amino-2-(4-hydroxyphenyl)acetyl]amino]-8-oxo-3-[(z)-prop-1-enyl]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid;hydrate Chemical compound O.C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)\C=C/C)C(O)=O)=CC=C(O)C=C1.C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)\C=C/C)C(O)=O)=CC=C(O)C=C1 XFIMQDGBHJULGY-WFDQOPGTSA-N 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 3
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 238000002814 agar dilution Methods 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 229940088710 antibiotic agent Drugs 0.000 description 3
- XRWSZZJLZRKHHD-WVWIJVSJSA-N asunaprevir Chemical compound O=C([C@@H]1C[C@H](CN1C(=O)[C@@H](NC(=O)OC(C)(C)C)C(C)(C)C)OC1=NC=C(C2=CC=C(Cl)C=C21)OC)N[C@]1(C(=O)NS(=O)(=O)C2CC2)C[C@H]1C=C XRWSZZJLZRKHHD-WVWIJVSJSA-N 0.000 description 3
- 239000002585 base Substances 0.000 description 3
- 230000003115 biocidal effect Effects 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 230000036765 blood level Effects 0.000 description 3
- 229960005361 cefaclor Drugs 0.000 description 3
- 229960002588 cefradine Drugs 0.000 description 3
- 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 3
- WORJEOGGNQDSOE-UHFFFAOYSA-N chloroform;methanol Chemical compound OC.ClC(Cl)Cl WORJEOGGNQDSOE-UHFFFAOYSA-N 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 229940125961 compound 24 Drugs 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 208000015181 infectious disease Diseases 0.000 description 3
- 239000002054 inoculum Substances 0.000 description 3
- 238000002955 isolation Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 229920006395 saturated elastomer Polymers 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000012360 testing method Methods 0.000 description 3
- 235000015099 wheat brans Nutrition 0.000 description 3
- AOSZTAHDEDLTLQ-AZKQZHLXSA-N (1S,2S,4R,8S,9S,11S,12R,13S,19S)-6-[(3-chlorophenyl)methyl]-12,19-difluoro-11-hydroxy-8-(2-hydroxyacetyl)-9,13-dimethyl-6-azapentacyclo[10.8.0.02,9.04,8.013,18]icosa-14,17-dien-16-one Chemical compound C([C@@H]1C[C@H]2[C@H]3[C@]([C@]4(C=CC(=O)C=C4[C@@H](F)C3)C)(F)[C@@H](O)C[C@@]2([C@@]1(C1)C(=O)CO)C)N1CC1=CC=CC(Cl)=C1 AOSZTAHDEDLTLQ-AZKQZHLXSA-N 0.000 description 2
- SZUVGFMDDVSKSI-WIFOCOSTSA-N (1s,2s,3s,5r)-1-(carboxymethyl)-3,5-bis[(4-phenoxyphenyl)methyl-propylcarbamoyl]cyclopentane-1,2-dicarboxylic acid Chemical compound O=C([C@@H]1[C@@H]([C@](CC(O)=O)([C@H](C(=O)N(CCC)CC=2C=CC(OC=3C=CC=CC=3)=CC=2)C1)C(O)=O)C(O)=O)N(CCC)CC(C=C1)=CC=C1OC1=CC=CC=C1 SZUVGFMDDVSKSI-WIFOCOSTSA-N 0.000 description 2
- UFBXLANKSYJFRF-AJNJCKRNSA-N (6R)-3-[(Z)-2-[[(2R)-2-amino-2-(4-hydroxyphenyl)acetyl]amino]prop-1-enyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound N[C@@H](C(=O)N\C(=C/C=1CS[C@H]2N(C=1C(=O)O)C(C2)=O)\C)C1=CC=C(C=C1)O UFBXLANKSYJFRF-AJNJCKRNSA-N 0.000 description 2
- WJWAMIFNLROXGL-WPZCJLIBSA-N (6r)-3-(hydroxymethyl)-8-oxo-7-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound C1([C@@H]2N(C1=O)C(=C(CS2)CO)C(O)=O)NC(=O)CC1=CC=CC=C1 WJWAMIFNLROXGL-WPZCJLIBSA-N 0.000 description 2
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 2
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- 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 1
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
- 150000008041 alkali metal carbonates Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
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- 239000012736 aqueous medium Substances 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
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- 208000022362 bacterial infectious disease Diseases 0.000 description 1
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- 229910052788 barium Inorganic materials 0.000 description 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
- UPABQMWFWCMOFV-UHFFFAOYSA-N benethamine Chemical compound C=1C=CC=CC=1CNCCC1=CC=CC=C1 UPABQMWFWCMOFV-UHFFFAOYSA-N 0.000 description 1
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
- YLOQFPCGJCRAPQ-UFHPHHKVSA-N benzhydryl (6r,7r)-3-(hydroxymethyl)-8-oxo-7-[(2-phenylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)CO)C(=O)OC(C=1C=CC=CC=1)C=1C=CC=CC=1)C(=O)CC1=CC=CC=C1 YLOQFPCGJCRAPQ-UFHPHHKVSA-N 0.000 description 1
- PBPKDMBQLUWMIO-OXQOHEQNSA-N benzhydryl (6r,7r)-7-amino-3-(chloromethyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound S([C@@H]1[C@@H](C(N11)=O)N)CC(CCl)=C1C(=O)OC(C=1C=CC=CC=1)C1=CC=CC=C1 PBPKDMBQLUWMIO-OXQOHEQNSA-N 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 239000003782 beta lactam antibiotic agent Substances 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
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- 244000309466 calf Species 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
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- 125000006243 carbonyl protecting group Chemical group 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
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- 239000003153 chemical reaction reagent Substances 0.000 description 1
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- 239000003245 coal Substances 0.000 description 1
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- 238000004440 column chromatography Methods 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125773 compound 10 Drugs 0.000 description 1
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- 229940125846 compound 25 Drugs 0.000 description 1
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- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- POLCUAVZOMRGSN-UHFFFAOYSA-N dipropyl ether Chemical compound CCCOCCC POLCUAVZOMRGSN-UHFFFAOYSA-N 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 229920001971 elastomer Polymers 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 230000007071 enzymatic hydrolysis Effects 0.000 description 1
- 238000006047 enzymatic hydrolysis reaction Methods 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 1
- VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 210000003608 fece Anatomy 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 235000011087 fumaric acid Nutrition 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
- 239000001963 growth medium Substances 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 239000002198 insoluble material Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- ZLVXBBHTMQJRSX-VMGNSXQWSA-N jdtic Chemical compound C1([C@]2(C)CCN(C[C@@H]2C)C[C@H](C(C)C)NC(=O)[C@@H]2NCC3=CC(O)=CC=C3C2)=CC=CC(O)=C1 ZLVXBBHTMQJRSX-VMGNSXQWSA-N 0.000 description 1
- 150000002576 ketones Chemical group 0.000 description 1
- 238000011005 laboratory method Methods 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 229940099690 malic acid Drugs 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-N mandelic acid Chemical compound OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical class C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000006916 nutrient agar Substances 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 235000019371 penicillin G benzathine Nutrition 0.000 description 1
- 229940056360 penicillin g Drugs 0.000 description 1
- 229950009506 penicillinase Drugs 0.000 description 1
- 150000002960 penicillins Chemical class 0.000 description 1
- NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 1
- LSMAIBOZUPTNBR-UHFFFAOYSA-N phosphanium;iodide Chemical compound [PH4+].[I-] LSMAIBOZUPTNBR-UHFFFAOYSA-N 0.000 description 1
- XYFCBTPGUUZFHI-UHFFFAOYSA-O phosphonium Chemical compound [PH4+] XYFCBTPGUUZFHI-UHFFFAOYSA-O 0.000 description 1
- 235000002949 phytic acid Nutrition 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- DUIOPKIIICUYRZ-UHFFFAOYSA-N semicarbazide Chemical compound NNC(N)=O DUIOPKIIICUYRZ-UHFFFAOYSA-N 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000012312 sodium hydride Substances 0.000 description 1
- 229910000104 sodium hydride Inorganic materials 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 239000002511 suppository base Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 125000003944 tolyl group Chemical group 0.000 description 1
- 231100000816 toxic dose Toxicity 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 239000002132 β-lactam antibiotic Substances 0.000 description 1
- 229940124586 β-lactam antibiotics Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/14—Compounds having a nitrogen atom directly attached in position 7
- C07D501/16—Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3
- C07D501/20—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/14—Compounds having a nitrogen atom directly attached in position 7
- C07D501/16—Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3
- C07D501/20—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids
- C07D501/22—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids with radicals containing only hydrogen and carbon atoms, attached in position 3
-
- 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)
- Cephalosporin Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US46183383A | 1983-01-28 | 1983-01-28 | |
| US06/564,604 US4520022A (en) | 1983-01-28 | 1983-12-28 | Substituted vinyl cephalosporins |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DE3402642A1 DE3402642A1 (de) | 1984-08-02 |
| DE3402642C2 true DE3402642C2 (en, 2012) | 1989-11-09 |
Family
ID=27040143
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19843402642 Granted DE3402642A1 (de) | 1983-01-28 | 1984-01-26 | Substituierte vinylcephalosporinverbindungen, verfahren zu ihrer herstellung und sie enthaltende pharmazeutische mittel |
Country Status (32)
| Country | Link |
|---|---|
| US (1) | US4520022A (en, 2012) |
| AR (1) | AR240824A1 (en, 2012) |
| AT (1) | AT383351B (en, 2012) |
| BE (1) | BE898778A (en, 2012) |
| CA (3) | CA1233815A (en, 2012) |
| CH (1) | CH661731A5 (en, 2012) |
| CY (1) | CY1528A (en, 2012) |
| CZ (1) | CZ280411B6 (en, 2012) |
| DD (2) | DD222029A5 (en, 2012) |
| DE (1) | DE3402642A1 (en, 2012) |
| DK (1) | DK162052C (en, 2012) |
| ES (2) | ES529171A0 (en, 2012) |
| FI (2) | FI79540C (en, 2012) |
| FR (1) | FR2540117B1 (en, 2012) |
| GB (1) | GB2135305B (en, 2012) |
| GR (1) | GR79791B (en, 2012) |
| HK (1) | HK73690A (en, 2012) |
| HU (1) | HU191990B (en, 2012) |
| IE (1) | IE56784B1 (en, 2012) |
| IL (1) | IL70773A (en, 2012) |
| IT (1) | IT1218842B (en, 2012) |
| LU (1) | LU85184A1 (en, 2012) |
| NL (1) | NL190581C (en, 2012) |
| NO (1) | NO165027C (en, 2012) |
| NZ (1) | NZ206973A (en, 2012) |
| OA (1) | OA07643A (en, 2012) |
| PT (1) | PT78020B (en, 2012) |
| SE (2) | SE458611B (en, 2012) |
| SK (1) | SK278845B6 (en, 2012) |
| SU (1) | SU1407400A3 (en, 2012) |
| YU (1) | YU44393B (en, 2012) |
| ZW (1) | ZW1184A1 (en, 2012) |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZM884A1 (en) * | 1983-01-28 | 1984-10-22 | Bristol Myers Co | Substituted vinyl cephalosporins |
| GB8411954D0 (en) * | 1984-05-10 | 1984-06-13 | Glaxo Group Ltd | Cephalosporin antibiotics |
| US4699979A (en) * | 1985-04-22 | 1987-10-13 | Bristol-Meyers Company | 7-amino-3-propenylcephalosporanic acid and esters thereof |
| FR2580652B1 (fr) * | 1985-04-22 | 1989-01-06 | Bristol Myers Co | Acide 7-amino-3-propenylcephalosporanique et ses esters |
| US4708955A (en) * | 1985-06-24 | 1987-11-24 | Bristol-Myers Company | 3-(substituted)propenyl-7-aminothiazol-ylcephalosporanic acids and esters thereof |
| US4694079A (en) * | 1985-07-29 | 1987-09-15 | Bristol-Myers Company | 3-propenyl cephalosporin solvates |
| US4619925A (en) * | 1985-11-08 | 1986-10-28 | Bristol-Myers Company | 3-Propenyl cephalosporin derivatives |
| US4727070A (en) * | 1985-11-25 | 1988-02-23 | Bristol-Myers Company | 3-Propenzl cephalosporin isomer separation process and derivative |
| US4870168A (en) * | 1987-02-26 | 1989-09-26 | Bristol-Myers Company | 3-Unsaturated alkyl cephems from 3-triflyl cephems |
| DE3734004A1 (de) * | 1987-05-26 | 1988-12-15 | Bayer Ag | Substituierte vinylcephalosporine, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel |
| DE3734005A1 (de) * | 1987-05-26 | 1988-12-15 | Bayer Ag | Substituierte vinylcephalosporine, verfahren zu ihrer herstellung und ihre verwendung als arzneimittel |
| US5128336A (en) * | 1988-03-23 | 1992-07-07 | Eli Lilly And Company | 3-(substituted)-1-carba(dethia)-3-cephems |
| US5245027A (en) * | 1989-11-21 | 1993-09-14 | Bristol-Myers Squibb Company | 3-fluorosulfonyloxyceph-3-em compounds |
| PT630380E (pt) | 1992-02-05 | 2002-02-28 | Biochemie Gmbh | Processo para a purificacao de um derivado do acido 3-cefem-4-carboxilico |
| JP4625637B2 (ja) | 2002-02-22 | 2011-02-02 | シャイア エルエルシー | 活性物質送達系及び活性物質を保護し投与する方法 |
| US7230097B2 (en) * | 2003-03-10 | 2007-06-12 | Lupin Ltd. | Process for preparation of 7-[α-Amino (4-hydroxyphenyl) acetamido]-3-substituted-3-cephem-4-carboxylic acid |
| WO2004110399A2 (en) * | 2003-06-19 | 2004-12-23 | Ranbaxy Laboratories Limited | Solvates of cefprozil |
| EP1678186A4 (en) | 2003-10-30 | 2007-04-25 | Cj Corp | PROCESS FOR THE PREPARATION OF CEPHEM DERIVATIVES |
| US20070072945A1 (en) * | 2004-03-31 | 2007-03-29 | Pohoreski Anton | Sulphur-containing oils for controlling plant pathogens and stimulating nutrient uptake |
| EP1809638B1 (en) | 2004-11-01 | 2010-02-17 | Hetero Drugs Limited | A novel process for preparation of cefprozil intermediate |
| WO2009049086A1 (en) | 2007-10-09 | 2009-04-16 | Larry Sutton | Broad spectrum beta-lactamase inhibitors |
| TR201000689A1 (tr) | 2010-01-29 | 2011-08-22 | Bi̇lgi̇ç Mahmut | Sefprozil içeren katı dozaj formlar. |
| WO2013109201A1 (en) | 2012-01-18 | 2013-07-25 | Mahmut Bilgic | Pharmaceutical compositions comprising cefprozil and clavulanic acid |
| EP2968352B1 (en) | 2013-03-12 | 2018-09-26 | Gladius Pharmaceuticals Corporation | Derivatized 3-styryl-cephalosporins |
Family Cites Families (22)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3507861A (en) * | 1966-09-14 | 1970-04-21 | Lilly Co Eli | Certain 3-methyl-cephalosporin compounds |
| US3351596A (en) * | 1966-09-21 | 1967-11-07 | Lilly Co Eli | 3-formyl cephalosporins |
| US3489752A (en) * | 1967-09-05 | 1970-01-13 | Bristol Myers Co | 7-amino-cephalosporanic and decephalosporanic acid derivatives |
| US3485819A (en) * | 1968-07-02 | 1969-12-23 | Squibb & Sons Inc | Alpha-amino-cyclohexadienylalkylene-penicillins and cephalosporins |
| US3994884A (en) * | 1970-01-23 | 1976-11-30 | Glaxo Laboratories Limited | 3-Vinyl-7β-(2,2-disubstituted acetamido)-cephalosporins |
| US3769277A (en) * | 1970-01-23 | 1973-10-30 | Glaxo Lab Ltd | Preparation of delta3-4 carboxy cephalosporins having a 3-vinyl or substituted 3-vinyl group |
| GB1342241A (en) * | 1970-01-23 | 1974-01-03 | Glaxo Lab Ltd | Cephalosporin compounds |
| US4107431A (en) * | 1970-01-23 | 1978-08-15 | Glaxo Laboratories Limited | Δ3 -3-Vinyl or substituted vinyl-4-carboxy cephalosporins |
| US3674784A (en) * | 1970-07-27 | 1972-07-04 | Lilly Co Eli | 3-formyl cephalosporin sulfoxides |
| US4065620A (en) * | 1971-06-14 | 1977-12-27 | Eli Lilly And Company | 3-(Substituted) vinyl cephalosporins |
| BE789817A (fr) * | 1971-10-07 | 1973-04-06 | Glaxo Lab Ltd | Perfectionnements aux composes de cephalosporine |
| US3925372A (en) * | 1973-02-23 | 1975-12-09 | Lilly Co Eli | Alpha-aminoacyl-3-halo cephalosporins |
| GB1472174A (en) * | 1973-09-22 | 1977-05-04 | Beecham Group Ltd | Dihydroxy amino cephalosporins |
| FR2264021A1 (en) * | 1974-03-13 | 1975-10-10 | Aries Robert | Cephalosporanic acid antibiotics - from alpha amino phenyl acetic acids and phosphorus trihalide then a 7-amino cepheme |
| JPS5129492A (en) * | 1974-09-04 | 1976-03-12 | Sankyo Co | Sefuarosuhorinjudotai no seiho |
| US4049806A (en) * | 1975-08-15 | 1977-09-20 | Syntex (U.S.A.) Inc. | Cephalosporin type antibacterials |
| US3983113A (en) * | 1975-08-15 | 1976-09-28 | Syntex (U.S.A.) Inc. | Cephalosporin type antibacterials |
| US4094978A (en) * | 1976-07-29 | 1978-06-13 | Syntex (U.S.A.) Inc. | 3-propenyl derivatives of cephalosporin, compositions and their use |
| US4112087A (en) * | 1976-11-04 | 1978-09-05 | Syntex (U.S.A.) Inc. | Cephalosporin type antibacterials having a substituted propenyl group in the 3-position |
| US4255423A (en) * | 1977-07-27 | 1981-03-10 | Merck & Co., Inc. | Cephalosporin compounds |
| FR2457297A1 (fr) * | 1979-05-23 | 1980-12-19 | Rhone Poulenc Ind | Nouvelles vinyl-3 cephalosporines, et leur preparation |
| US4409214A (en) * | 1979-11-19 | 1983-10-11 | Fujisawa Pharmaceutical, Co., Ltd. | 7-Acylamino-3-vinylcephalosporanic acid derivatives and processes for the preparation thereof |
-
1983
- 1983-12-28 US US06/564,604 patent/US4520022A/en not_active Expired - Lifetime
-
1984
- 1984-01-05 CA CA000444731A patent/CA1233815A/en not_active Expired
- 1984-01-06 IE IE26/84A patent/IE56784B1/en not_active IP Right Cessation
- 1984-01-10 GR GR73463A patent/GR79791B/el active IP Right Revival
- 1984-01-16 FR FR8400575A patent/FR2540117B1/fr not_active Expired
- 1984-01-25 ZW ZW11/84A patent/ZW1184A1/xx unknown
- 1984-01-25 IL IL70773A patent/IL70773A/xx not_active IP Right Cessation
- 1984-01-25 FI FI840300A patent/FI79540C/fi not_active IP Right Cessation
- 1984-01-25 NL NL8400229A patent/NL190581C/xx not_active IP Right Cessation
- 1984-01-26 OA OA58215A patent/OA07643A/xx unknown
- 1984-01-26 AR AR295535A patent/AR240824A1/es active
- 1984-01-26 DE DE19843402642 patent/DE3402642A1/de active Granted
- 1984-01-26 DK DK035384A patent/DK162052C/da not_active IP Right Cessation
- 1984-01-26 ES ES529171A patent/ES529171A0/es active Granted
- 1984-01-27 GB GB08402255A patent/GB2135305B/en not_active Expired
- 1984-01-27 CZ CS84616A patent/CZ280411B6/cs not_active IP Right Cessation
- 1984-01-27 SK SK616-84A patent/SK278845B6/sk unknown
- 1984-01-27 LU LU85184A patent/LU85184A1/fr unknown
- 1984-01-27 SE SE8400419A patent/SE458611B/sv not_active IP Right Cessation
- 1984-01-27 NZ NZ206973A patent/NZ206973A/en unknown
- 1984-01-27 IT IT19346/84A patent/IT1218842B/it active Protection Beyond IP Right Term
- 1984-01-27 NO NO840334A patent/NO165027C/no not_active IP Right Cessation
- 1984-01-27 HU HU84383A patent/HU191990B/hu unknown
- 1984-01-27 PT PT78020A patent/PT78020B/pt unknown
- 1984-01-27 YU YU140/84A patent/YU44393B/xx unknown
- 1984-01-27 SU SU843698551A patent/SU1407400A3/ru active
- 1984-01-27 BE BE0/212294A patent/BE898778A/fr not_active IP Right Cessation
- 1984-01-27 CH CH388/84A patent/CH661731A5/de not_active IP Right Cessation
- 1984-01-30 DD DD84259716A patent/DD222029A5/de unknown
- 1984-01-30 AT AT0029984A patent/AT383351B/de not_active IP Right Cessation
- 1984-01-30 DD DD84271301A patent/DD228261A5/de unknown
- 1984-09-14 ES ES535953A patent/ES535953A0/es active Granted
-
1986
- 1986-02-03 CA CA000500965A patent/CA1225084A/en not_active Expired
- 1986-02-03 CA CA000500966A patent/CA1241948A/en not_active Expired
-
1987
- 1987-08-13 SE SE8703153A patent/SE466204B/sv not_active IP Right Cessation
-
1988
- 1988-04-25 FI FI881929A patent/FI81356C/fi not_active IP Right Cessation
-
1990
- 1990-09-20 HK HK736/90A patent/HK73690A/xx not_active IP Right Cessation
- 1990-11-16 CY CY1528A patent/CY1528A/en unknown
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