CA1056814A - Derives de l'acide formyl-(p-acyloxyphenyl) acetamidocephalosporanique - Google Patents

Derives de l'acide formyl-(p-acyloxyphenyl) acetamidocephalosporanique

Info

Publication number: CA1056814A
Authority: CA; Canada
Prior art keywords: acid; alkyl; hydrogen; amino; het
Prior art date: 1974-06-05
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

CA311,176A

Other languages

English (en)

Inventor

Abraham Weber

Daniel Bouzard

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.)

1974-06-05

Filing date

1978-09-13

Publication date

1979-06-19

1974-06-05 Priority claimed from GB2484874A external-priority patent/GB1476981A/en

1978-09-13 Application filed by Bristol Myers Squibb Co filed Critical Bristol Myers Squibb Co

1978-09-13 Priority to CA311,176A priority Critical patent/CA1056814A/fr

1979-06-19 Application granted granted Critical

1979-06-19 Publication of CA1056814A publication Critical patent/CA1056814A/fr

Status Expired legal-status Critical Current

Links

239000002253 acid Substances 0.000 title claims abstract description 56
-1 nitro, amino Chemical group 0.000 claims abstract description 47
150000003839 salts Chemical class 0.000 claims abstract description 45
238000000034 method Methods 0.000 claims abstract description 42
150000001875 compounds Chemical class 0.000 claims abstract description 30
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 30
239000001257 hydrogen Substances 0.000 claims abstract description 29
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 27
239000000047 product Substances 0.000 claims description 34
238000002360 preparation method Methods 0.000 claims description 14
239000003795 chemical substances by application Substances 0.000 claims description 9
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 claims description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
239000000126 substance Substances 0.000 claims description 4
239000012467 final product Substances 0.000 claims description 2
LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 2
229910052736 halogen Inorganic materials 0.000 abstract description 11
150000002367 halogens Chemical group 0.000 abstract description 10
125000002887 hydroxy group Chemical group [H]O* 0.000 abstract description 9
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 abstract description 8
125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract description 7
239000003242 anti bacterial agent Substances 0.000 abstract description 6
125000000623 heterocyclic group Chemical group 0.000 abstract description 6
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract description 6
229930186147 Cephalosporin Natural products 0.000 abstract description 5
229940124587 cephalosporin Drugs 0.000 abstract description 5
229910052760 oxygen Inorganic materials 0.000 abstract description 5
150000007513 acids Chemical class 0.000 abstract description 4
150000001780 cephalosporins Chemical class 0.000 abstract description 4
125000001506 1,2,3-triazol-5-yl group Chemical group [H]N1N=NC([H])=C1[*] 0.000 abstract description 3
125000002373 5 membered heterocyclic group Chemical group 0.000 abstract description 3
125000004070 6 membered heterocyclic group Chemical group 0.000 abstract description 3
125000004429 atom Chemical group 0.000 abstract description 3
125000004432 carbon atom Chemical group C* 0.000 abstract description 3
229910052717 sulfur Inorganic materials 0.000 abstract description 3
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 abstract description 2
125000004183 alkoxy alkyl group Chemical group 0.000 abstract description 2
125000002843 carboxylic acid group Chemical group 0.000 abstract description 2
125000000008 (C1-C10) alkyl group Chemical group 0.000 abstract 2
125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 2
150000001735 carboxylic acids Chemical class 0.000 abstract 1
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 45
239000000243 solution Substances 0.000 description 34
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 23
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 17
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
239000007787 solid Substances 0.000 description 16
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
125000000217 alkyl group Chemical group 0.000 description 15
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
239000000203 mixture Substances 0.000 description 12
108090000371 Esterases Proteins 0.000 description 9
229960000583 acetic acid Drugs 0.000 description 9
239000000460 chlorine Substances 0.000 description 9
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
238000003756 stirring Methods 0.000 description 8
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 7
235000011054 acetic acid Nutrition 0.000 description 7
238000005917 acylation reaction Methods 0.000 description 7
239000003610 charcoal Substances 0.000 description 7
238000006243 chemical reaction Methods 0.000 description 7
238000001914 filtration Methods 0.000 description 7
229910052757 nitrogen Inorganic materials 0.000 description 7
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 6
150000001732 carboxylic acid derivatives Chemical class 0.000 description 6
239000000706 filtrate Substances 0.000 description 6
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 6
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 5
241001465754 Metazoa Species 0.000 description 5
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 5
239000012346 acetyl chloride Substances 0.000 description 5
239000007864 aqueous solution Substances 0.000 description 5
239000012299 nitrogen atmosphere Substances 0.000 description 5
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 5
210000002966 serum Anatomy 0.000 description 5
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
238000005481 NMR spectroscopy Methods 0.000 description 4
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
230000010933 acylation Effects 0.000 description 4
125000003545 alkoxy group Chemical group 0.000 description 4
239000008346 aqueous phase Substances 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
FFUAGWLWBBFQJT-UHFFFAOYSA-N hexamethyldisilazane Chemical compound C[Si](C)(C)N[Si](C)(C)C FFUAGWLWBBFQJT-UHFFFAOYSA-N 0.000 description 4
239000000543 intermediate Substances 0.000 description 4
231100000252 nontoxic Toxicity 0.000 description 4
230000003000 nontoxic effect Effects 0.000 description 4
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 4
230000003389 potentiating effect Effects 0.000 description 4
239000002002 slurry Substances 0.000 description 4
235000017557 sodium bicarbonate Nutrition 0.000 description 4
229910000030 sodium bicarbonate Inorganic materials 0.000 description 4
239000002904 solvent Substances 0.000 description 4
PVGHNTXQMCYYGF-UHFFFAOYSA-N thiadiazol-5-amine Chemical compound NC1=CN=NS1 PVGHNTXQMCYYGF-UHFFFAOYSA-N 0.000 description 4
238000011282 treatment Methods 0.000 description 4
229940086542 triethylamine Drugs 0.000 description 4
241000894006 Bacteria Species 0.000 description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
208000035473 Communicable disease Diseases 0.000 description 3
LJCWONGJFPCTTL-SSDOTTSWSA-N D-4-hydroxyphenylglycine Chemical compound [O-]C(=O)[C@H]([NH3+])C1=CC=C(O)C=C1 LJCWONGJFPCTTL-SSDOTTSWSA-N 0.000 description 3
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 3
125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 3
125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 3
150000001412 amines Chemical class 0.000 description 3
238000003556 assay Methods 0.000 description 3
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 3
230000000903 blocking effect Effects 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
229910052801 chlorine Inorganic materials 0.000 description 3
239000013058 crude material Substances 0.000 description 3
239000012043 crude product Substances 0.000 description 3
238000000354 decomposition reaction Methods 0.000 description 3
125000004185 ester group Chemical group 0.000 description 3
230000007062 hydrolysis Effects 0.000 description 3
238000006460 hydrolysis reaction Methods 0.000 description 3
239000005457 ice water Substances 0.000 description 3
239000012535 impurity Substances 0.000 description 3
229910052740 iodine Inorganic materials 0.000 description 3
150000002500 ions Chemical class 0.000 description 3
239000010410 layer Substances 0.000 description 3
239000000463 material Substances 0.000 description 3
125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 3
239000008363 phosphate buffer Substances 0.000 description 3
235000011007 phosphoric acid Nutrition 0.000 description 3
244000144977 poultry Species 0.000 description 3
238000000746 purification Methods 0.000 description 3
239000011734 sodium Substances 0.000 description 3
229910052708 sodium Inorganic materials 0.000 description 3
239000000725 suspension Substances 0.000 description 3
238000003786 synthesis reaction Methods 0.000 description 3
235000015099 wheat brans Nutrition 0.000 description 3
MLOZJRLUNNFSGD-HZGVNTEJSA-N (6r,7r)-7-azaniumyl-8-oxo-3-(2h-triazol-4-ylsulfanylmethyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound S([C@@H]1[C@@H](C(N1C=1C(O)=O)=O)N)CC=1CSC=1C=NNN=1 MLOZJRLUNNFSGD-HZGVNTEJSA-N 0.000 description 2
125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 description 2
NVIAYEIXYQCDAN-CLZZGJSISA-N 7beta-aminodeacetoxycephalosporanic acid Chemical compound S1CC(C)=C(C(O)=O)N2C(=O)[C@@H](N)[C@@H]12 NVIAYEIXYQCDAN-CLZZGJSISA-N 0.000 description 2
244000063299 Bacillus subtilis Species 0.000 description 2
235000014469 Bacillus subtilis Nutrition 0.000 description 2
241000207199 Citrus Species 0.000 description 2
YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 2
108090000790 Enzymes Proteins 0.000 description 2
102000004190 Enzymes Human genes 0.000 description 2
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
241001024304 Mino Species 0.000 description 2
JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 description 2
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 2
125000000066 S-methyl group Chemical group [H]C([H])([H])S* 0.000 description 2
241000209140 Triticum Species 0.000 description 2
235000021307 Triticum Nutrition 0.000 description 2
229910000147 aluminium phosphate Inorganic materials 0.000 description 2
150000001408 amides Chemical class 0.000 description 2
125000003277 amino group Chemical group 0.000 description 2
150000008064 anhydrides Chemical class 0.000 description 2
239000000872 buffer Substances 0.000 description 2
150000001718 carbodiimides Chemical class 0.000 description 2
229910052799 carbon Inorganic materials 0.000 description 2
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 2
229940106164 cephalexin Drugs 0.000 description 2
235000020971 citrus fruits Nutrition 0.000 description 2
230000000052 comparative effect Effects 0.000 description 2
239000012141 concentrate Substances 0.000 description 2
238000001816 cooling Methods 0.000 description 2
238000005859 coupling reaction Methods 0.000 description 2
238000002425 crystallisation Methods 0.000 description 2
230000008025 crystallization Effects 0.000 description 2
WOAZEKPXTXCPFZ-UHFFFAOYSA-N dimethyl(phenyl)azanium;chloride Chemical compound Cl.CN(C)C1=CC=CC=C1 WOAZEKPXTXCPFZ-UHFFFAOYSA-N 0.000 description 2
YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 2
238000006073 displacement reaction Methods 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
239000011737 fluorine Substances 0.000 description 2
229910052731 fluorine Inorganic materials 0.000 description 2
238000010438 heat treatment Methods 0.000 description 2
235000011167 hydrochloric acid Nutrition 0.000 description 2
229960000443 hydrochloric acid Drugs 0.000 description 2
150000003840 hydrochlorides Chemical class 0.000 description 2
ATADHKWKHYVBTJ-UHFFFAOYSA-N hydron;4-[1-hydroxy-2-(methylamino)ethyl]benzene-1,2-diol;chloride Chemical compound Cl.CNCC(O)C1=CC=C(O)C(O)=C1 ATADHKWKHYVBTJ-UHFFFAOYSA-N 0.000 description 2
238000002329 infrared spectrum Methods 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
238000004519 manufacturing process Methods 0.000 description 2
GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 2
239000012044 organic layer Substances 0.000 description 2
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 2
239000011541 reaction mixture Substances 0.000 description 2
238000010992 reflux Methods 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
150000003573 thiols Chemical class 0.000 description 2
238000001665 trituration Methods 0.000 description 2
DUSZFPWPQILNNQ-XPJFZRNWSA-N (6r)-4-amino-3-[(1-methyltetrazol-5-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound CN1N=NN=C1SCC1=C(C(O)=O)N2C(=O)C[C@H]2SC1N DUSZFPWPQILNNQ-XPJFZRNWSA-N 0.000 description 1
MLOZJRLUNNFSGD-IOJJLOCKSA-N (6r)-7-amino-8-oxo-3-(2h-triazol-4-ylsulfanylmethyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound S([C@@H]1C(C(N1C=1C(O)=O)=O)N)CC=1CSC=1C=NNN=1 MLOZJRLUNNFSGD-IOJJLOCKSA-N 0.000 description 1
CFGDUGSIBUXRMR-UHFFFAOYSA-N 1,2-dihydropyrrol-2-ide Chemical compound C=1C=[C-]NC=1 CFGDUGSIBUXRMR-UHFFFAOYSA-N 0.000 description 1
SGFCVOOJFYBQBO-UHFFFAOYSA-N 1,2-dihydrotriazole-5-thione;potassium Chemical compound [K].SC1=CN=NN1 SGFCVOOJFYBQBO-UHFFFAOYSA-N 0.000 description 1
BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 description 1
LLCOQBODWBFTDD-UHFFFAOYSA-N 1h-triazol-1-ium-4-thiolate Chemical compound SC1=CNN=N1 LLCOQBODWBFTDD-UHFFFAOYSA-N 0.000 description 1
JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 description 1
SOFPIAMTOZWXKT-UHFFFAOYSA-N 2h-1,2,4-triazine-3-thione Chemical compound SC1=NC=CN=N1 SOFPIAMTOZWXKT-UHFFFAOYSA-N 0.000 description 1
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
LJCWONGJFPCTTL-UHFFFAOYSA-N 4-hydroxyphenylglycine Chemical compound OC(=O)C(N)C1=CC=C(O)C=C1 LJCWONGJFPCTTL-UHFFFAOYSA-N 0.000 description 1
NVIAYEIXYQCDAN-UHFFFAOYSA-N 7-amino-3-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound S1CC(C)=C(C(O)=O)N2C(=O)C(N)C12 NVIAYEIXYQCDAN-UHFFFAOYSA-N 0.000 description 1
241000114726 Acetes Species 0.000 description 1
208000035143 Bacterial infection Diseases 0.000 description 1
239000005711 Benzoic acid Substances 0.000 description 1
241000283690 Bos taurus Species 0.000 description 1
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 1
DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 description 1
ZGUNAGUHMKGQNY-ZETCQYMHSA-N L-alpha-phenylglycine zwitterion Chemical compound OC(=O)[C@@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-ZETCQYMHSA-N 0.000 description 1
NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
HTLZVHNRZJPSMI-UHFFFAOYSA-N N-ethylpiperidine Chemical compound CCN1CCCCC1 HTLZVHNRZJPSMI-UHFFFAOYSA-N 0.000 description 1
229910017974 NH40H Inorganic materials 0.000 description 1
PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 1
229930182555 Penicillin Natural products 0.000 description 1
108010013381 Porins Proteins 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
150000008065 acid anhydrides Chemical class 0.000 description 1
230000004913 activation Effects 0.000 description 1
239000004480 active ingredient Substances 0.000 description 1
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229910052782 aluminium Inorganic materials 0.000 description 1
235000010210 aluminium Nutrition 0.000 description 1
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238000004458 analytical method Methods 0.000 description 1
239000000538 analytical sample Substances 0.000 description 1
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239000012736 aqueous medium Substances 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
150000001540 azides Chemical class 0.000 description 1
208000022362 bacterial infectious disease Diseases 0.000 description 1
235000010233 benzoic acid Nutrition 0.000 description 1
QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 1
239000012964 benzotriazole Substances 0.000 description 1
CPEKAXYCDKETEN-UHFFFAOYSA-N benzoyl isothiocyanate Chemical compound S=C=NC(=O)C1=CC=CC=C1 CPEKAXYCDKETEN-UHFFFAOYSA-N 0.000 description 1
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
229910052794 bromium Inorganic materials 0.000 description 1
238000002815 broth microdilution Methods 0.000 description 1
229940043232 butyl acetate Drugs 0.000 description 1
125000004744 butyloxycarbonyl group Chemical group 0.000 description 1
239000011575 calcium Substances 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
235000001465 calcium Nutrition 0.000 description 1
150000001734 carboxylic acid salts Chemical class 0.000 description 1
239000000969 carrier Substances 0.000 description 1
UOCJDOLVGGIYIQ-PBFPGSCMSA-N cefatrizine Chemical compound S([C@@H]1[C@@H](C(N1C=1C(O)=O)=O)NC(=O)[C@H](N)C=2C=CC(O)=CC=2)CC=1CSC=1C=NNN=1 UOCJDOLVGGIYIQ-PBFPGSCMSA-N 0.000 description 1
230000008878 coupling Effects 0.000 description 1
238000010168 coupling process Methods 0.000 description 1
WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical compound C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
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125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
239000003085 diluting agent Substances 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
238000004821 distillation Methods 0.000 description 1
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238000001035 drying Methods 0.000 description 1
230000009977 dual effect Effects 0.000 description 1
239000000839 emulsion Substances 0.000 description 1
NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 description 1
125000002485 formyl group Chemical group [H]C(*)=O 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
229940093915 gynecological organic acid Drugs 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 1
150000004677 hydrates Chemical class 0.000 description 1
150000004678 hydrides Chemical class 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
229910052500 inorganic mineral Inorganic materials 0.000 description 1
238000002955 isolation Methods 0.000 description 1
125000001786 isothiazolyl group Chemical group 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
208000004396 mastitis Diseases 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
150000004702 methyl esters Chemical class 0.000 description 1
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
238000004452 microanalysis Methods 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
239000012452 mother liquor Substances 0.000 description 1
PBMIETCUUSQZCG-UHFFFAOYSA-N n'-cyclohexylmethanediimine Chemical compound N=C=NC1CCCCC1 PBMIETCUUSQZCG-UHFFFAOYSA-N 0.000 description 1
HMIWVANFYYGFHA-UHFFFAOYSA-N n-(thiadiazol-4-yl)benzamide Chemical compound C=1C=CC=CC=1C(=O)NC1=CSN=N1 HMIWVANFYYGFHA-UHFFFAOYSA-N 0.000 description 1
230000007935 neutral effect Effects 0.000 description 1
238000006386 neutralization reaction Methods 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
235000016709 nutrition Nutrition 0.000 description 1
230000035764 nutrition Effects 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
125000001715 oxadiazolyl group Chemical group 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
125000005429 oxyalkyl group Chemical group 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
150000002960 penicillins Chemical class 0.000 description 1
239000008194 pharmaceutical composition Substances 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
239000000825 pharmaceutical preparation Substances 0.000 description 1
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
102000007739 porin activity proteins Human genes 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
235000007686 potassium Nutrition 0.000 description 1
229960003975 potassium Drugs 0.000 description 1
MQXUINLVWYNNJE-UHFFFAOYSA-N potassium;2h-triazole Chemical compound [K].C=1C=NNN=1 MQXUINLVWYNNJE-UHFFFAOYSA-N 0.000 description 1
238000004313 potentiometry Methods 0.000 description 1
239000002244 precipitate 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
125000003373 pyrazinyl group Chemical group 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
125000002098 pyridazinyl group Chemical group 0.000 description 1
125000004076 pyridyl group Chemical group 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
150000003254 radicals Chemical class 0.000 description 1
230000035484 reaction time Effects 0.000 description 1
239000012266 salt solution Substances 0.000 description 1
235000015424 sodium Nutrition 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
239000012265 solid product Substances 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
239000013589 supplement Substances 0.000 description 1
150000003512 tertiary amines Chemical class 0.000 description 1
125000003831 tetrazolyl group Chemical group 0.000 description 1
125000001113 thiadiazolyl group Chemical group 0.000 description 1
125000005307 thiatriazolyl group Chemical group S1N=NN=C1* 0.000 description 1
125000000335 thiazolyl group Chemical group 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
150000007970 thio esters Chemical class 0.000 description 1
125000003396 thiol group Chemical group [H]S* 0.000 description 1
125000005270 trialkylamine group Chemical group 0.000 description 1
229940055764 triaz Drugs 0.000 description 1
125000004306 triazinyl group Chemical group 0.000 description 1
150000003852 triazoles Chemical class 0.000 description 1
125000001425 triazolyl group Chemical group 0.000 description 1

Landscapes

Cephalosporin Compounds (AREA)

CA311,176A 1974-06-05 1978-09-13 Derives de l'acide formyl-(p-acyloxyphenyl) acetamidocephalosporanique Expired CA1056814A (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA311,176A CA1056814A (fr)	1974-06-05	1978-09-13	Derives de l'acide formyl-(p-acyloxyphenyl) acetamidocephalosporanique

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
GB2484874A GB1476981A (en)	1974-06-05	1974-06-05	Substituted penicillanic acids
CA228,229A CA1051799A (fr)	1974-06-05	1975-06-02	Agents antibacteriens
CA311,176A CA1056814A (fr)	1974-06-05	1978-09-13	Derives de l'acide formyl-(p-acyloxyphenyl) acetamidocephalosporanique

Publications (1)

Publication Number	Publication Date
CA1056814A true CA1056814A (fr)	1979-06-19

Family

ID=27163982

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA311,176A Expired CA1056814A (fr)	1974-06-05	1978-09-13	Derives de l'acide formyl-(p-acyloxyphenyl) acetamidocephalosporanique

Country Status (1)

Country	Link
CA (1)	CA1056814A (fr)

1978
- 1978-09-13 CA CA311,176A patent/CA1056814A/fr not_active Expired

Publication	Publication Date	Title
US4012382A (en)	1977-03-15	α-Amino and α-formyl-α-(p-acyloxyphenyl)acetamidocephalosporanic acid derivatives
US3759904A (en)	1973-09-18	Ds and salts thereof 3 - (s-(1,2,3-triazole-5-yl)thiomethyl)-3 - cephem - 4-carboxylic aci7-(d-(alpha-amino-alpha-phenyl-, 2-thienyl- and 3-thienylacetamido))-
US4966900A (en)	1990-10-30	Cephalosporin β-lactam compound and medicinal composition
US3929779A (en)	1975-12-30	Aminopyridinium acetyl cephalosporanes
US4053360A (en)	1977-10-11	Enzymatic preparation of 6-D-(-)-α-amino-α-(p-hydroxyphenylacetamino)penicillin acid
US3813388A (en)	1974-05-28	7-(d-(alpha-amino-alpha-phenyl-,2-thienyl-and 3-thienyl-acetamido))-3-(s-(2-methyl-1,2,3-triazole-4-yl)thiomethyl)-3-cephem-4-carboxylic acids
GB2071654A (en)	1981-09-23	Hydroxamic acid derivatives of 7-(2-amino-4-thiazolyl)oximino cephalosporins
US3907786A (en)	1975-09-23	7-{8 {60 -(2-aminomethyl-1,4-cyclohexadienyl)acetamido{9 -3-heterocyclic-thiomethyl-3-cephem-4-carboxylic acids and salts
PH26857A (en)	1992-11-16	Crystallized cephem-acid addition salts
US4061748A (en)	1977-12-06	7-(α-(4-Hydroxy-1,5-naphthyridine-3-carbonamido)-α-phenylacetamido) cephalosporin derivatives
IL43913A (en)	1977-08-31	Preparation of (-(d-(alpha-amino-alpha-p-hydroxyphenyl)-acetamido)-3-(1,2,3-triazol-5-yl)thiomethyl-3-cephem-4-carboxylic acid and salts thereof
HU212782B (en)	1996-11-28	Water-free acylating process for stereospecifical producing antibioticum cephepim-dihydrochloride-hydrate
US4117126A (en)	1978-09-26	7-(α-(4-Hydroxy-1,5-naphthyridine-3-carbonamido)-α-phenylacetamido) cephalosporin derivatives
HU213267B (en)	1997-04-28	Process for producing stereospecific cefepime-dihydrochloride-hydrate at ph 5-7,5
CA1056814A (fr)	1979-06-19	Derives de l'acide formyl-(p-acyloxyphenyl) acetamidocephalosporanique
EP0019067B1 (fr)	1982-10-06	Acide 5,10-dioxo-5,10-dihydrodiimidazo(1,5-a,1',5'-d)pyrazine-1,6-dicarboxylique et procédé de préparation d'amides d'acide imidazoledicarboxylique
US3850916A (en)	1974-11-26	7-amino-3-(s-(1,2,3-triazole-5-yl)-thiomethyl)-3-cephem-4-carboxylic acid and salts thereof
EP0023045B1 (fr)	1984-04-11	Dérivés de l'acide imidazole-carboxylique de pénicillines et de céphalosporines
RU2201933C2 (ru)	2003-04-10	Антибактериальные замещенные 7-ациламино-3-(метилгидразоно)метилцефалоспорины, способ их получения, фармацевтические композиции на их основе, промежуточные соединения и способ лечения заболеваний, вызванных микроорганизмами
US3910899A (en)	1975-10-07	7-(2-Aminomethylphenyl-acetamido)-3-{8 2-(5-hydroxymethyl-1,3,4-thiadiazolyl)-thiomethyl{9 -3-cephem-4-carboxylic acid
CA1056813A (fr)	1979-06-19	DERIVES DE L'ACIDE .alpha.-AMINO- (P-ACYLOXYPHENYL) ACETAMIDOCEPHALOSPORANIQUE
US3813391A (en)	1974-05-28	7-(beta-(o-aminomethylphenyl)propion-amido)-3-(tetrazolo(4,5-b)pyridazin-6-ylthiomethyl)-3-cephem-4-carboxylic acid
US3910900A (en)	1975-10-07	7-(D-a-hydroxy-2-arylacetamido)-3-(3-hydroxypyridazin-6-ylthiomethyl)-3-cephem-4-carboxylic acids
GB1604740A (en)	1981-12-16	7-isothiazolylthioacetamido-7-methoxycephalosporanic acid derivatives
CA1049432A (fr)	1979-02-27	Procede pour la preparation d'agents bactericides