CA1113455A - Acides 7-acylamido-3-(2-carboxyalkyl-2,3-dihydro-3- triazolo ¬4,3-b| pyridazin-3-on-6-ylthiomethyl)-3- cephem-4-carboxyliques - Google Patents

Acides 7-acylamido-3-(2-carboxyalkyl-2,3-dihydro-3- triazolo ¬4,3-b| pyridazin-3-on-6-ylthiomethyl)-3- cephem-4-carboxyliques

Info

Publication number: CA1113455A
Authority: CA; Canada
Prior art keywords: hydrogen; methyl; compound; acid; mixture
Prior art date: 1977-04-05
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

Application number

CA287,569A

Other languages

English (en)

Inventor

Takayuki Naito

Hajime Kamachi

Jun Okumura

Seiji Iimura

Hideaki Hoshi

Masahisa Oka

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Bristol Myers Squibb Co

Original Assignee

Bristol Myers Squibb Co

Priority date (The priority date 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 date listed.)

1977-04-05

Filing date

1977-09-27

Publication date

1981-12-01

1977-04-05 Priority claimed from US05/784,885 external-priority patent/US4082912A/en

1977-09-27 Application filed by Bristol Myers Squibb Co filed Critical Bristol Myers Squibb Co

1981-12-01 Application granted granted Critical

1981-12-01 Publication of CA1113455A publication Critical patent/CA1113455A/fr

Status Expired legal-status Critical Current

Links

229910052739 hydrogen Inorganic materials 0.000 claims abstract description 65
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 65
239000001257 hydrogen Substances 0.000 claims abstract description 63
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 62
150000001875 compounds Chemical class 0.000 claims abstract description 45
150000003839 salts Chemical class 0.000 claims abstract description 27
150000002148 esters Chemical class 0.000 claims abstract description 22
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 16
231100000252 nontoxic Toxicity 0.000 claims abstract description 16
230000003000 nontoxic effect Effects 0.000 claims abstract description 16
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract 9
-1 pivaloyloxymethyl- Chemical group 0.000 claims description 71
238000000034 method Methods 0.000 claims description 64
239000002253 acid Substances 0.000 claims description 31
238000002360 preparation method Methods 0.000 claims description 17
239000000126 substance Substances 0.000 claims description 13
125000005843 halogen group Chemical group 0.000 claims description 3
239000003795 chemical substances by application Substances 0.000 claims description 2
229930186147 Cephalosporin Natural products 0.000 abstract description 14
229940124587 cephalosporin Drugs 0.000 abstract description 14
150000001780 cephalosporins Chemical class 0.000 abstract description 13
208000035143 Bacterial infection Diseases 0.000 abstract description 4
208000022362 bacterial infectious disease Diseases 0.000 abstract description 4
239000000203 mixture Substances 0.000 description 98
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 87
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 63
229910001868 water Inorganic materials 0.000 description 63
239000000243 solution Substances 0.000 description 61
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 58
241001558496 Talpa caeca Species 0.000 description 58
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 57
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 55
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 55
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 54
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 42
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 39
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 35
239000002244 precipitate Substances 0.000 description 28
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 27
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 25
238000001914 filtration Methods 0.000 description 25
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 24
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 22
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 22
239000000706 filtrate Substances 0.000 description 22
239000011541 reaction mixture Substances 0.000 description 21
238000003756 stirring Methods 0.000 description 21
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 20
239000000284 extract Substances 0.000 description 20
229940022682 acetone Drugs 0.000 description 19
229940076134 benzene Drugs 0.000 description 19
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
238000007792 addition Methods 0.000 description 16
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 15
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 15
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
239000003921 oil Substances 0.000 description 15
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 14
CCGKOQOJPYTBIH-UHFFFAOYSA-N ethenone Chemical compound C=C=O CCGKOQOJPYTBIH-UHFFFAOYSA-N 0.000 description 14
125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 description 14
238000002844 melting Methods 0.000 description 14
230000008018 melting Effects 0.000 description 14
HSHGZXNAXBPPDL-HZGVNTEJSA-N 7beta-aminocephalosporanic acid Chemical compound S1CC(COC(=O)C)=C(C([O-])=O)N2C(=O)[C@@H]([NH3+])[C@@H]12 HSHGZXNAXBPPDL-HZGVNTEJSA-N 0.000 description 13
239000000047 product Substances 0.000 description 13
239000000741 silica gel Substances 0.000 description 13
229910002027 silica gel Inorganic materials 0.000 description 13
UFBJCMHMOXMLKC-UHFFFAOYSA-N 2,4-dinitrophenol Chemical compound OC1=CC=C([N+]([O-])=O)C=C1[N+]([O-])=O UFBJCMHMOXMLKC-UHFFFAOYSA-N 0.000 description 12
241000588724 Escherichia coli Species 0.000 description 12
229910052799 carbon Inorganic materials 0.000 description 12
229910052943 magnesium sulfate Inorganic materials 0.000 description 12
239000011780 sodium chloride Substances 0.000 description 12
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 11
239000000872 buffer Substances 0.000 description 11
239000010410 layer Substances 0.000 description 11
239000002904 solvent Substances 0.000 description 11
125000004432 carbon atom Chemical group C* 0.000 description 10
239000000460 chlorine Substances 0.000 description 10
229960001701 chloroform Drugs 0.000 description 10
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 10
229910052757 nitrogen Inorganic materials 0.000 description 10
229920006395 saturated elastomer Polymers 0.000 description 10
229940086542 triethylamine Drugs 0.000 description 10
125000000217 alkyl group Chemical group 0.000 description 9
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
239000011734 sodium Substances 0.000 description 9
239000000725 suspension Substances 0.000 description 9
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 8
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 8
MNFQLEZDACDPLX-UHFFFAOYSA-N ethyl 2-[3-(hydroxyiminomethyl)thiophen-2-yl]acetate Chemical compound CCOC(=O)CC=1SC=CC=1C=NO MNFQLEZDACDPLX-UHFFFAOYSA-N 0.000 description 8
235000019341 magnesium sulphate Nutrition 0.000 description 8
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 8
238000010992 reflux Methods 0.000 description 8
AMUABBXHRJDNHV-UHFFFAOYSA-N 2-[3-(aminomethyl)thiophen-2-yl]acetic acid Chemical compound NCC=1C=CSC=1CC(O)=O AMUABBXHRJDNHV-UHFFFAOYSA-N 0.000 description 7
UCQDVXPNKBWROD-UHFFFAOYSA-N 2-[3-(methylaminomethyl)thiophen-2-yl]acetic acid Chemical compound CNCC=1C=CSC=1CC(O)=O UCQDVXPNKBWROD-UHFFFAOYSA-N 0.000 description 7
229910017974 NH40H Inorganic materials 0.000 description 7
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 7
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 7
125000001539 acetonyl group Chemical group [H]C([H])([H])C(=O)C([H])([H])* 0.000 description 7
229910021529 ammonia Inorganic materials 0.000 description 7
239000007864 aqueous solution Substances 0.000 description 7
238000006243 chemical reaction Methods 0.000 description 7
125000004356 hydroxy functional group Chemical group O* 0.000 description 7
239000012044 organic layer Substances 0.000 description 7
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 7
229910052938 sodium sulfate Inorganic materials 0.000 description 7
235000011152 sodium sulphate Nutrition 0.000 description 7
XXJGBENTLXFVFI-UHFFFAOYSA-N 1-amino-methylene Chemical compound N[CH2] XXJGBENTLXFVFI-UHFFFAOYSA-N 0.000 description 6
RFKWQDSZGBJTLI-UHFFFAOYSA-N 2-[2-[[methyl-(4-methylphenyl)sulfonylamino]methyl]phenyl]acetic acid Chemical compound C=1C=C(C)C=CC=1S(=O)(=O)N(C)CC1=CC=CC=C1CC(O)=O RFKWQDSZGBJTLI-UHFFFAOYSA-N 0.000 description 6
229910014033 C-OH Inorganic materials 0.000 description 6
229910014570 C—OH Inorganic materials 0.000 description 6
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 6
DBTDEFJAFBUGPP-UHFFFAOYSA-N Methanethial Chemical compound S=C DBTDEFJAFBUGPP-UHFFFAOYSA-N 0.000 description 6
125000002252 acyl group Chemical group 0.000 description 6
125000003277 amino group Chemical group 0.000 description 6
150000001732 carboxylic acid derivatives Chemical class 0.000 description 6
239000003153 chemical reaction reagent Substances 0.000 description 6
208000015181 infectious disease Diseases 0.000 description 6
125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 6
239000011347 resin Substances 0.000 description 6
229920005989 resin Polymers 0.000 description 6
229910052708 sodium Inorganic materials 0.000 description 6
229910000104 sodium hydride Inorganic materials 0.000 description 6
239000007787 solid Substances 0.000 description 6
NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 5
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 5
CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 5
239000007832 Na2SO4 Substances 0.000 description 5
238000005917 acylation reaction Methods 0.000 description 5
OLVCFLKTBJRLHI-AXAPSJFSSA-N cefamandole Chemical compound CN1N=NN=C1SCC1=C(C(O)=O)N2C(=O)[C@@H](NC(=O)[C@H](O)C=3C=CC=CC=3)[C@H]2SC1 OLVCFLKTBJRLHI-AXAPSJFSSA-N 0.000 description 5
229960003012 cefamandole Drugs 0.000 description 5
229920001429 chelating resin Polymers 0.000 description 5
239000000499 gel Substances 0.000 description 5
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
229910000041 hydrogen chloride Inorganic materials 0.000 description 5
150000003951 lactams Chemical class 0.000 description 5
125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 description 5
238000003786 synthesis reaction Methods 0.000 description 5
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
150000003573 thiols Chemical class 0.000 description 5
MYRTYDVEIRVNKP-UHFFFAOYSA-N 1,2-Divinylbenzene Chemical compound C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 description 4
241000193738 Bacillus anthracis Species 0.000 description 4
MYVSUXCNQPTGIF-UHFFFAOYSA-N CCOC(=NO)CC=1SC=CC=1C=O Chemical compound CCOC(=NO)CC=1SC=CC=1C=O MYVSUXCNQPTGIF-UHFFFAOYSA-N 0.000 description 4
239000005977 Ethylene Substances 0.000 description 4
241000219470 Mirabilis Species 0.000 description 4
150000007513 acids Chemical class 0.000 description 4
230000010933 acylation Effects 0.000 description 4
125000004429 atom Chemical group 0.000 description 4
HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 4
SLUNEGLMXGHOLY-UHFFFAOYSA-N benzene;hexane Chemical compound CCCCCC.C1=CC=CC=C1 SLUNEGLMXGHOLY-UHFFFAOYSA-N 0.000 description 4
239000004202 carbamide Substances 0.000 description 4
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 4
HOKIDJSKDBPKTQ-GLXFQSAKSA-N cephalosporin C Chemical compound S1CC(COC(=O)C)=C(C(O)=O)N2C(=O)[C@@H](NC(=O)CCC[C@@H](N)C(O)=O)[C@@H]12 HOKIDJSKDBPKTQ-GLXFQSAKSA-N 0.000 description 4
239000003610 charcoal Substances 0.000 description 4
239000012141 concentrate Substances 0.000 description 4
238000001816 cooling Methods 0.000 description 4
239000002024 ethyl acetate extract Substances 0.000 description 4
238000001704 evaporation Methods 0.000 description 4
230000008020 evaporation Effects 0.000 description 4
238000000338 in vitro Methods 0.000 description 4
INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 4
239000003456 ion exchange resin Substances 0.000 description 4
229920003303 ion-exchange polymer Polymers 0.000 description 4
239000007788 liquid Substances 0.000 description 4
229960003424 phenylacetic acid Drugs 0.000 description 4
239000003279 phenylacetic acid Substances 0.000 description 4
229910000029 sodium carbonate Inorganic materials 0.000 description 4
235000017550 sodium carbonate Nutrition 0.000 description 4
239000012312 sodium hydride Substances 0.000 description 4
SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 3
HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 3
GFZLUCAKSHCYNU-UHFFFAOYSA-N 2-[2-(methylaminomethyl)phenyl]acetic acid Chemical compound CNCC1=CC=CC=C1CC(O)=O GFZLUCAKSHCYNU-UHFFFAOYSA-N 0.000 description 3
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 3
241000894006 Bacteria Species 0.000 description 3
101150041968 CDC13 gene Proteins 0.000 description 3
102000004190 Enzymes Human genes 0.000 description 3
108090000790 Enzymes Proteins 0.000 description 3
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 3
238000005481 NMR spectroscopy Methods 0.000 description 3
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 3
229960000583 acetic acid Drugs 0.000 description 3
125000003545 alkoxy group Chemical group 0.000 description 3
150000001413 amino acids Chemical class 0.000 description 3
150000003863 ammonium salts Chemical class 0.000 description 3
239000003242 anti bacterial agent Substances 0.000 description 3
ITHZDDVSAWDQPZ-UHFFFAOYSA-L barium acetate Chemical compound [Ba+2].CC([O-])=O.CC([O-])=O ITHZDDVSAWDQPZ-UHFFFAOYSA-L 0.000 description 3
230000015572 biosynthetic process Effects 0.000 description 3
230000000903 blocking effect Effects 0.000 description 3
238000004440 column chromatography Methods 0.000 description 3
238000005859 coupling reaction Methods 0.000 description 3
125000000753 cycloalkyl group Chemical group 0.000 description 3
230000000694 effects Effects 0.000 description 3
125000000623 heterocyclic group Chemical group 0.000 description 3
239000005457 ice water Substances 0.000 description 3
229910000069 nitrogen hydride Inorganic materials 0.000 description 3
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 3
229940056211 paraffin Drugs 0.000 description 3
239000012188 paraffin wax Substances 0.000 description 3
239000008363 phosphate buffer Substances 0.000 description 3
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 3
125000006239 protecting group Chemical group 0.000 description 3
TVPRCLHSULCNLV-UHFFFAOYSA-N pyridazin-3-one Chemical compound O=C1C=CC=N[N]1 TVPRCLHSULCNLV-UHFFFAOYSA-N 0.000 description 3
PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 3
125000004076 pyridyl group Chemical group 0.000 description 3
238000012552 review Methods 0.000 description 3
150000003335 secondary amines Chemical class 0.000 description 3
238000012360 testing method Methods 0.000 description 3
RMVRSNDYEFQCLF-UHFFFAOYSA-N thiophenol Chemical compound SC1=CC=CC=C1 RMVRSNDYEFQCLF-UHFFFAOYSA-N 0.000 description 3
238000005406 washing Methods 0.000 description 3
OTKFCIVOVKCFHR-UHFFFAOYSA-N (Methylsulfinyl)(methylthio)methane Chemical compound CSCS(C)=O OTKFCIVOVKCFHR-UHFFFAOYSA-N 0.000 description 2
CFGDUGSIBUXRMR-UHFFFAOYSA-N 1,2-dihydropyrrol-2-ide Chemical compound C=1C=[C-]NC=1 CFGDUGSIBUXRMR-UHFFFAOYSA-N 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 description 2
CUYSOJBXRISIRJ-UHFFFAOYSA-N 2-[2-(aminomethyl)cyclohexa-1,4-dien-1-yl]acetic acid Chemical compound NCC1=C(CC(O)=O)CC=CC1 CUYSOJBXRISIRJ-UHFFFAOYSA-N 0.000 description 2
BQUKHFBECFVVQY-UHFFFAOYSA-N 2-[2-[(butoxycarbonylamino)methyl]phenyl]acetic acid Chemical compound CCCCOC(=O)NCC1=CC=CC=C1CC(O)=O BQUKHFBECFVVQY-UHFFFAOYSA-N 0.000 description 2
TUPHDSJSSNMCGK-UHFFFAOYSA-N 2-[2-[[butoxycarbonyl(methyl)amino]methyl]phenyl]acetic acid Chemical compound CCCCOC(=O)N(C)CC1=CC=CC=C1CC(O)=O TUPHDSJSSNMCGK-UHFFFAOYSA-N 0.000 description 2
SSXDJHBUYFUCQH-UHFFFAOYSA-N 3-(dimethoxymethyl)thiophene Chemical compound COC(OC)C=1C=CSC=1 SSXDJHBUYFUCQH-UHFFFAOYSA-N 0.000 description 2
IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
229920001817 Agar Polymers 0.000 description 2
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 2
CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
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150000001734 carboxylic acid salts Chemical class 0.000 description 1
150000001735 carboxylic acids 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
238000010531 catalytic reduction reaction Methods 0.000 description 1
XIURVHNZVLADCM-IUODEOHRSA-N cefalotin Chemical compound N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)COC(=O)C)C(O)=O)C(=O)CC1=CC=CS1 XIURVHNZVLADCM-IUODEOHRSA-N 0.000 description 1
229960000603 cefalotin Drugs 0.000 description 1
YGBFLZPYDUKSPT-MRVPVSSYSA-N cephalosporanic acid Chemical compound S1CC(COC(=O)C)=C(C(O)=O)N2C(=O)C[C@H]21 YGBFLZPYDUKSPT-MRVPVSSYSA-N 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
238000002512 chemotherapy Methods 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
125000001309 chloro group Chemical group Cl* 0.000 description 1
BULLHNJGPPOUOX-UHFFFAOYSA-N chloroacetone Chemical compound CC(=O)CCl BULLHNJGPPOUOX-UHFFFAOYSA-N 0.000 description 1
239000002026 chloroform extract Substances 0.000 description 1
OAIVIYSBZFEOIU-UHFFFAOYSA-N chloroform;propan-2-one Chemical compound CC(C)=O.ClC(Cl)Cl OAIVIYSBZFEOIU-UHFFFAOYSA-N 0.000 description 1
125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
229910052681 coesite Inorganic materials 0.000 description 1
238000009833 condensation Methods 0.000 description 1
230000005494 condensation Effects 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
239000007822 coupling agent Substances 0.000 description 1
229910052906 cristobalite Inorganic materials 0.000 description 1
125000004093 cyano group Chemical group *C#N 0.000 description 1
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
239000008367 deionised water Substances 0.000 description 1
229910021641 deionized water Inorganic materials 0.000 description 1
150000001991 dicarboxylic acids Chemical class 0.000 description 1
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
VLNZUSMTOFYNPS-UHFFFAOYSA-N diethylphosphorylformonitrile Chemical compound CCP(=O)(CC)C#N VLNZUSMTOFYNPS-UHFFFAOYSA-N 0.000 description 1
238000003113 dilution method Methods 0.000 description 1
KUMNEOGIHFCNQW-UHFFFAOYSA-N diphenyl phosphite Chemical compound C=1C=CC=CC=1OP([O-])OC1=CC=CC=C1 KUMNEOGIHFCNQW-UHFFFAOYSA-N 0.000 description 1
MKRTXPORKIRPDG-UHFFFAOYSA-N diphenylphosphoryl azide Chemical compound C=1C=CC=CC=1P(=O)(N=[N+]=[N-])C1=CC=CC=C1 MKRTXPORKIRPDG-UHFFFAOYSA-N 0.000 description 1
238000004821 distillation Methods 0.000 description 1
239000000428 dust Substances 0.000 description 1
238000003379 elimination reaction Methods 0.000 description 1
238000010828 elution Methods 0.000 description 1
230000007071 enzymatic hydrolysis Effects 0.000 description 1
238000006047 enzymatic hydrolysis reaction Methods 0.000 description 1
239000012259 ether extract Substances 0.000 description 1
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
MUYVVJYPUJAPOJ-UHFFFAOYSA-N ethyl 2-(3-formylthiophen-2-yl)acetate Chemical compound CCOC(=O)CC=1SC=CC=1C=O MUYVVJYPUJAPOJ-UHFFFAOYSA-N 0.000 description 1
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 description 1
238000000605 extraction Methods 0.000 description 1
229960004594 fominoben Drugs 0.000 description 1
125000000524 functional group Chemical group 0.000 description 1
238000007429 general method Methods 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
230000005484 gravity Effects 0.000 description 1
125000006331 halo benzoyl group Chemical group 0.000 description 1
UBIJTWDKTYCPMQ-UHFFFAOYSA-N hexachlorophosphazene Chemical compound ClP1(Cl)=NP(Cl)(Cl)=NP(Cl)(Cl)=N1 UBIJTWDKTYCPMQ-UHFFFAOYSA-N 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
239000012442 inert solvent Substances 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
239000000543 intermediate Substances 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
125000002510 isobutoxy group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])O* 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
238000002955 isolation Methods 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
150000003932 ketenimines Chemical class 0.000 description 1
150000002576 ketones Chemical class 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
229940049920 malate Drugs 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
BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
229920003145 methacrylic acid copolymer Polymers 0.000 description 1
TWXDDNPPQUTEOV-FVGYRXGTSA-N methamphetamine hydrochloride Chemical compound Cl.CN[C@@H](C)CC1=CC=CC=C1 TWXDDNPPQUTEOV-FVGYRXGTSA-N 0.000 description 1
GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
239000000401 methanolic extract Substances 0.000 description 1
150000004702 methyl esters Chemical class 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
238000012544 monitoring process Methods 0.000 description 1
150000002762 monocarboxylic acid derivatives Chemical class 0.000 description 1
QAXZWHGWYSJAEI-UHFFFAOYSA-N n,n-dimethylformamide;ethanol Chemical compound CCO.CN(C)C=O QAXZWHGWYSJAEI-UHFFFAOYSA-N 0.000 description 1
125000001038 naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 description 1
230000003589 nefrotoxic effect Effects 0.000 description 1
231100000381 nephrotoxic Toxicity 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
229910052760 oxygen Inorganic materials 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
230000020477 pH reduction Effects 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
229920001467 poly(styrenesulfonates) Polymers 0.000 description 1
229920000172 poly(styrenesulfonic acid) Polymers 0.000 description 1
229940005642 polystyrene sulfonic acid Drugs 0.000 description 1
239000011591 potassium Substances 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
239000000843 powder Substances 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
OVARTBFNCCXQKS-UHFFFAOYSA-N propan-2-one;hydrate Chemical compound O.CC(C)=O OVARTBFNCCXQKS-UHFFFAOYSA-N 0.000 description 1
ZMRUPTIKESYGQW-UHFFFAOYSA-N propranolol hydrochloride Chemical compound [H+].[Cl-].C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 ZMRUPTIKESYGQW-UHFFFAOYSA-N 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
238000000746 purification Methods 0.000 description 1
KOUKXHPPRFNWPP-UHFFFAOYSA-N pyrazine-2,5-dicarboxylic acid;hydrate Chemical compound O.OC(=O)C1=CN=C(C(O)=O)C=N1 KOUKXHPPRFNWPP-UHFFFAOYSA-N 0.000 description 1
125000000168 pyrrolyl group Chemical group 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
238000006722 reduction reaction Methods 0.000 description 1
238000013207 serial dilution Methods 0.000 description 1
210000002966 serum Anatomy 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
235000012239 silicon dioxide Nutrition 0.000 description 1
HYHCSLBZRBJJCH-UHFFFAOYSA-M sodium hydrosulfide Chemical compound [Na+].[SH-] HYHCSLBZRBJJCH-UHFFFAOYSA-M 0.000 description 1
RZWQDAUIUBVCDD-UHFFFAOYSA-M sodium;benzenethiolate Chemical compound [Na+].[S-]C1=CC=CC=C1 RZWQDAUIUBVCDD-UHFFFAOYSA-M 0.000 description 1
FAMFBFJWKFYYLG-UHFFFAOYSA-M sodium;sulfanide;dihydrate Chemical compound O.O.[Na+].[SH-] FAMFBFJWKFYYLG-UHFFFAOYSA-M 0.000 description 1
239000011343 solid material Substances 0.000 description 1
241000894007 species Species 0.000 description 1
239000007858 starting material Substances 0.000 description 1
229910052682 stishovite Inorganic materials 0.000 description 1
239000012607 strong cation exchange resin Substances 0.000 description 1
238000000859 sublimation Methods 0.000 description 1
230000008022 sublimation Effects 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
125000001113 thiadiazolyl group Chemical group 0.000 description 1
150000007970 thio esters Chemical class 0.000 description 1
SRVJKTDHMYAMHA-WUXMJOGZSA-N thioacetazone Chemical compound CC(=O)NC1=CC=C(\C=N\NC(N)=S)C=C1 SRVJKTDHMYAMHA-WUXMJOGZSA-N 0.000 description 1
238000006177 thiolation reaction Methods 0.000 description 1
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
150000003852 triazoles Chemical class 0.000 description 1
125000006000 trichloroethyl group Chemical group 0.000 description 1
229910052905 tridymite Inorganic materials 0.000 description 1
239000008096 xylene Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
- C07D217/24—Oxygen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Cephalosporin Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

CA287,569A 1977-04-05 1977-09-27 Acides 7-acylamido-3-(2-carboxyalkyl-2,3-dihydro-3- triazolo ¬4,3-b| pyridazin-3-on-6-ylthiomethyl)-3- cephem-4-carboxyliques Expired CA1113455A (fr)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US784,885		1977-04-05
US05/784,885 US4082912A (en)	1976-06-30	1977-04-05	Certain 7-acylamido-3-(2-carboxyalkyl-2,3-dihydro-s-triazolo[4,3-b]pyridazin-3-on-6-ylmethyl)-3-cephem-4-carboxylic acids their salts and easily hydrolyzed esters

Publications (1)

Publication Number	Publication Date
CA1113455A true CA1113455A (fr)	1981-12-01

Family

ID=25133827

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA287,569A Expired CA1113455A (fr)	1977-04-05	1977-09-27	Acides 7-acylamido-3-(2-carboxyalkyl-2,3-dihydro-3- triazolo ¬4,3-b\| pyridazin-3-on-6-ylthiomethyl)-3- cephem-4-carboxyliques

Country Status (17)

Country	Link
JP (1)	JPS53124290A (fr)
AU (1)	AU517919B2 (fr)
BE (1)	BE859774A (fr)
CA (1)	CA1113455A (fr)
CH (1)	CH627184A5 (fr)
DE (1)	DE2807847A1 (fr)
DK (1)	DK145497C (fr)
FI (1)	FI60869C (fr)
FR (1)	FR2408614A1 (fr)
GB (1)	GB1572201A (fr)
GR (1)	GR73550B (fr)
IE (1)	IE45613B1 (fr)
LU (1)	LU78323A1 (fr)
NL (1)	NL7711644A (fr)
SE (1)	SE425491B (fr)
YU (1)	YU247977A (fr)
ZA (1)	ZA775781B (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CN114940665A (zh) *	2022-06-10	2022-08-26	河南省科学院高新技术研究中心	一种用作杀菌剂的苯并异噻唑啉酮类化合物及其制备方法

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE3000377A1 (de) *	1980-01-07	1981-07-09	Boehringer Mannheim Gmbh, 6800 Mannheim	Neue sulfonamide, verfahren zu deren herstellung sowie diese verbindungen enthaltende arzneimittel

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3907786A (en) *	1973-09-04	1975-09-23	Bristol Myers Co	7-{8 {60 -(2-aminomethyl-1,4-cyclohexadienyl)acetamido{9 -3-heterocyclic-thiomethyl-3-cephem-4-carboxylic acids and salts
US3946000A (en) *	1973-10-31	1976-03-23	Bristol-Myers Company	7-[α-(2-Aminomethyl-1-cyclohexenyl)-acetamido]-3-heterocyclic thiomethyl-3-cephem-4-carboxylic acids

1977
- 1977-09-26 GB GB39951/77A patent/GB1572201A/en not_active Expired
- 1977-09-27 ZA ZA00775781A patent/ZA775781B/xx unknown
- 1977-09-27 IE IE1969/77A patent/IE45613B1/en unknown
- 1977-09-27 CA CA287,569A patent/CA1113455A/fr not_active Expired
- 1977-09-28 FI FI772860A patent/FI60869C/fi not_active IP Right Cessation
- 1977-09-28 DK DK429577A patent/DK145497C/da not_active IP Right Cessation
- 1977-09-28 SE SE7710823A patent/SE425491B/xx unknown
- 1977-09-28 GR GR54448A patent/GR73550B/el unknown
- 1977-10-04 AU AU29328/77A patent/AU517919B2/en not_active Expired
- 1977-10-10 FR FR7730383A patent/FR2408614A1/fr active Granted
- 1977-10-13 CH CH1249577A patent/CH627184A5/fr not_active IP Right Cessation
- 1977-10-14 BE BE181787A patent/BE859774A/fr not_active IP Right Cessation
- 1977-10-14 YU YU02479/77A patent/YU247977A/xx unknown
- 1977-10-17 LU LU78323A patent/LU78323A1/xx unknown
- 1977-10-24 NL NL7711644A patent/NL7711644A/xx not_active Application Discontinuation
- 1977-10-24 JP JP12688377A patent/JPS53124290A/ja active Pending
1978
- 1978-02-23 DE DE19782807847 patent/DE2807847A1/de not_active Withdrawn

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CN114940665A (zh) *	2022-06-10	2022-08-26	河南省科学院高新技术研究中心	一种用作杀菌剂的苯并异噻唑啉酮类化合物及其制备方法
CN114940665B (zh) *	2022-06-10	2024-05-07	河南省科学院高新技术研究中心	一种用作杀菌剂的苯并异噻唑啉酮类化合物及其制备方法

Also Published As

Publication number	Publication date
ZA775781B (en)	1978-08-30
AU517919B2 (en)	1981-09-03
YU247977A (en)	1982-10-31
FR2408614B1 (fr)	1980-12-05
DK145497C (da)	1983-05-02
DK145497B (da)	1982-11-29
CH627184A5 (en)	1981-12-31
GR73550B (fr)	1984-03-13
FI60869B (fi)	1981-12-31
AU2932877A (en)	1979-04-12
JPS53124290A (en)	1978-10-30
FI772860A7 (fi)	1978-10-06
SE7710823L (sv)	1978-10-06
IE45613B1 (en)	1982-10-06
NL7711644A (nl)	1978-10-09
IE45613L (en)	1978-10-05
BE859774A (fr)	1978-04-14
LU78323A1 (fr)	1978-06-12
SE425491B (sv)	1982-10-04
DK429577A (da)	1978-10-06
GB1572201A (en)	1980-07-23
FI60869C (fi)	1982-04-13
DE2807847A1 (de)	1978-10-19
FR2408614A1 (fr)	1979-06-08

Legal Events

Date	Code	Title	Description
1998-12-01	MKEX	Expiry

Publication	Publication Date	Title
CA1108136A (fr)	1981-09-01	Agent antibacterien
US4118562A (en)	1978-10-03	Azidomethylaryl-substituted cephalosporin derivatives
CA1123840A (fr)	1982-05-18	Nouveaux derives du tetrazole
US3919206A (en)	1975-11-11	7-(Halomethylaryl)acetamidocephalosporin derivatives
EP0055562B1 (fr)	1986-02-12	Dérivés de céphalosporines
US4104469A (en)	1978-08-01	7-(Syn-α-alkoxy-iminofuryl)acetamido-3-(2-methyl-2,3-dihydro-s-triazolo[4,3-b]pyridazin-3-on-6-ylthiomethyl)-3-cephem-4-carboxylic acids
CA1113455A (fr)	1981-12-01	Acides 7-acylamido-3-(2-carboxyalkyl-2,3-dihydro-3- triazolo ¬4,3-b\| pyridazin-3-on-6-ylthiomethyl)-3- cephem-4-carboxyliques
US4031083A (en)	1977-06-21	Cephalosporin antibiotics
US4245107A (en)	1981-01-13	Cephalosporin derivatives and process for preparing the same
US4151352A (en)	1979-04-24	7-Amino-3-(2-carboxyalkyl-2,3-dihydro-s-triazolo[4,3-b]pyridazin-3-on-6-ylthiomethyl)-3-cephem-4-carboxylic acids
US4103085A (en)	1978-07-25	7-(Syn-α-alkoxy-iminofurylacetamido-3-(2-carboxyalkyl-2,3-dihydro-s-triazolo[4,3-b]pyridazin-3-on-6-ylthiomethyl)-3-cephem-4-carboxylic acids
US4093804A (en)	1978-06-06	Pyridiniummethylaryl-substituted cephalosporin derivatives
US4182863A (en)	1980-01-08	7-Amino-3-(1-carboxymethyltetrazol-5-ylthiomethyl)-3-cephem-4-carboxylic acid
CA1041087A (fr)	1978-10-24	Acetamidocephalosporins dont on a substitue le groupe a-carboxy
US4219648A (en)	1980-08-26	7-[[Amino(1,3-dihydrobenzo[c]thienyl)acetyl]amino]cephalosporin derivatives
US4198506A (en)	1980-04-15	2-Carboxyalkyl-2,3-dihydro-6-mercapto-s-triazolo[4,3-b]-pyridazin-3-ones
CA1109460A (fr)	1981-09-22	Cyanoalkylureidocephalosporines
US4113943A (en)	1978-09-12	7β-[(2-Amino-1,2-dioxoethyl)amino]acyl cephalosporins
US3994889A (en)	1976-11-30	3-Heterothio derivatives of (α-thiocarbonylaminol)-7α-methoxy-cephalosporins
KR810000471B1 (ko)	1981-05-09	항균제의 제조 방법
US3996216A (en)	1976-12-07	3-Heterothio derivatives of (formylamino)acetylamino-7-alpha-methoxy cephalosporins
US3994875A (en)	1976-11-30	Antibiotics
CA1121809A (fr)	1982-04-13	Derives de la 7-[(2-amino-1,2-dioxoethyl)amino] acylcephalosporines
IE45614B1 (en)	1982-10-06	Cephalosporins
US4003893A (en)	1977-01-18	3-Heterothio[(thioalkyl)thioacetyl]cephalosporanic derivatives