GB1561236A - Cephalosporins - Google Patents
Cephalosporins Download PDFInfo
- Publication number
- GB1561236A GB1561236A GB29212/77A GB2921277A GB1561236A GB 1561236 A GB1561236 A GB 1561236A GB 29212/77 A GB29212/77 A GB 29212/77A GB 2921277 A GB2921277 A GB 2921277A GB 1561236 A GB1561236 A GB 1561236A
- Authority
- GB
- United Kingdom
- Prior art keywords
- carbon atoms
- formula
- compound
- hydrogen
- pharmaceutically acceptable
- 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
- 229930186147 Cephalosporin Natural products 0.000 title claims description 21
- 229940124587 cephalosporin Drugs 0.000 title claims description 21
- 150000001780 cephalosporins Chemical class 0.000 title claims description 20
- 150000001875 compounds Chemical class 0.000 claims abstract description 103
- -1 trifluoromethvl, amino Chemical group 0.000 claims description 128
- 125000004432 carbon atom Chemical group C* 0.000 claims description 87
- 229910052739 hydrogen Inorganic materials 0.000 claims description 66
- 239000001257 hydrogen Substances 0.000 claims description 65
- 238000000034 method Methods 0.000 claims description 65
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical class CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 61
- 125000000217 alkyl group Chemical group 0.000 claims description 60
- 150000003839 salts Chemical class 0.000 claims description 58
- 239000002253 acid Substances 0.000 claims description 52
- 231100000252 nontoxic Toxicity 0.000 claims description 45
- 230000003000 nontoxic effect Effects 0.000 claims description 45
- 125000003545 alkoxy group Chemical group 0.000 claims description 32
- 150000002431 hydrogen Chemical group 0.000 claims description 31
- 150000002148 esters Chemical class 0.000 claims description 29
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 26
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 25
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 25
- 239000000460 chlorine Chemical group 0.000 claims description 24
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 21
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 20
- 239000011734 sodium Substances 0.000 claims description 20
- 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 claims description 19
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 19
- 229910052708 sodium Inorganic materials 0.000 claims description 19
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 18
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical group [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 18
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 18
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical group BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 18
- 229910052794 bromium Inorganic materials 0.000 claims description 18
- 229910052801 chlorine Inorganic materials 0.000 claims description 18
- 239000011737 fluorine Chemical group 0.000 claims description 18
- 229910052731 fluorine Inorganic materials 0.000 claims description 18
- 150000007513 acids Chemical class 0.000 claims description 15
- 125000001539 acetonyl group Chemical group [H]C([H])([H])C(=O)C([H])([H])* 0.000 claims description 14
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 claims description 14
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 14
- 238000002360 preparation method Methods 0.000 claims description 14
- 125000003277 amino group Chemical group 0.000 claims description 13
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 13
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
- XAKBSHICSHRJCL-UHFFFAOYSA-N [CH2]C(=O)C1=CC=CC=C1 Chemical group [CH2]C(=O)C1=CC=CC=C1 XAKBSHICSHRJCL-UHFFFAOYSA-N 0.000 claims description 11
- 125000006503 p-nitrobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1[N+]([O-])=O)C([H])([H])* 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
- 239000002262 Schiff base Substances 0.000 claims description 9
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 9
- 125000004076 pyridyl group Chemical group 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 7
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 7
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
- 125000000623 heterocyclic group Chemical group 0.000 claims description 7
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 claims description 7
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- SMQUZDBALVYZAC-UHFFFAOYSA-N ortho-hydroxybenzaldehyde Natural products OC1=CC=CC=C1C=O SMQUZDBALVYZAC-UHFFFAOYSA-N 0.000 claims description 6
- 125000001544 thienyl group Chemical group 0.000 claims description 6
- 208000035143 Bacterial infection Diseases 0.000 claims description 5
- 150000004753 Schiff bases Chemical class 0.000 claims description 5
- 239000003242 anti bacterial agent Substances 0.000 claims description 5
- 208000022362 bacterial infectious disease Diseases 0.000 claims description 5
- 125000005843 halogen group Chemical group 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 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 claims description 4
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 4
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- 125000003282 alkyl amino group Chemical group 0.000 claims description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- 125000001246 bromo group Chemical group Br* 0.000 claims description 3
- 125000004799 bromophenyl group Chemical group 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 125000000068 chlorophenyl group Chemical group 0.000 claims description 3
- 125000001153 fluoro group Chemical group F* 0.000 claims description 3
- 238000002347 injection Methods 0.000 claims description 3
- 239000007924 injection Substances 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 239000001301 oxygen Substances 0.000 claims description 3
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 3
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 3
- 125000003944 tolyl group Chemical group 0.000 claims description 3
- 229940123930 Lactamase inhibitor Drugs 0.000 claims description 2
- 229930182555 Penicillin Natural products 0.000 claims description 2
- 229940126574 aminoglycoside antibiotic Drugs 0.000 claims description 2
- 239000002647 aminoglycoside antibiotic agent Substances 0.000 claims description 2
- UCKZMPLVLCKKMO-LHLIQPBNSA-N cephamycin Chemical compound S1CC(C)=C(C(O)=O)N2C(=O)[C@@H](C)[C@]21OC UCKZMPLVLCKKMO-LHLIQPBNSA-N 0.000 claims description 2
- 150000002762 monocarboxylic acid derivatives Chemical class 0.000 claims description 2
- 229940049954 penicillin Drugs 0.000 claims description 2
- 125000006239 protecting group Chemical group 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 abstract description 14
- 230000000844 anti-bacterial effect Effects 0.000 abstract description 6
- 206010061190 Haemophilus infection Diseases 0.000 abstract description 4
- 206010062212 Neisseria infection Diseases 0.000 abstract description 3
- 208000010899 haemophilus infectious disease Diseases 0.000 abstract description 2
- 241000606790 Haemophilus Species 0.000 abstract 1
- 239000000825 pharmaceutical preparation Substances 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 62
- 239000000203 mixture Substances 0.000 description 55
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 47
- 241001558496 Talpa caeca Species 0.000 description 46
- 241000588724 Escherichia coli Species 0.000 description 45
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 39
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 33
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 29
- 239000000047 product Substances 0.000 description 28
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- 238000001914 filtration Methods 0.000 description 25
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 22
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 19
- 239000002244 precipitate Substances 0.000 description 19
- 239000007787 solid Substances 0.000 description 18
- IWYDHOAUDWTVEP-SSDOTTSWSA-N (R)-mandelic acid Chemical class OC(=O)[C@H](O)C1=CC=CC=C1 IWYDHOAUDWTVEP-SSDOTTSWSA-N 0.000 description 17
- 241000588697 Enterobacter cloacae Species 0.000 description 16
- 241000607715 Serratia marcescens Species 0.000 description 16
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 16
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- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 15
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 14
- 238000003756 stirring Methods 0.000 description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
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- 241000193996 Streptococcus pyogenes Species 0.000 description 12
- 230000000694 effects Effects 0.000 description 12
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 12
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 11
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
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- 235000017557 sodium bicarbonate Nutrition 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- 241000100248 Primula stuartii Species 0.000 description 8
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- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
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- 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 8
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- 150000003573 thiols Chemical class 0.000 description 7
- QBRYVEBVCLYGEO-UHFFFAOYSA-N CON=C1OC=CC1CC(O)=O Chemical compound CON=C1OC=CC1CC(O)=O QBRYVEBVCLYGEO-UHFFFAOYSA-N 0.000 description 6
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- 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 6
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- 159000000000 sodium salts Chemical class 0.000 description 6
- PUWQVDWJJCSTLK-UHFFFAOYSA-N 2-hydroxy-2-phenylacetyl chloride Chemical compound ClC(=O)C(O)C1=CC=CC=C1 PUWQVDWJJCSTLK-UHFFFAOYSA-N 0.000 description 5
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- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 1
- COECMMUMGYUNCT-UHFFFAOYSA-N 4,4-dichloro-2-hydroxy-3-oxo-2-phenylbutanoyl chloride Chemical compound ClC(Cl)C(=O)C(C(Cl)=O)(O)C1=CC=CC=C1 COECMMUMGYUNCT-UHFFFAOYSA-N 0.000 description 1
- HGJLLONXGPLCEM-UHFFFAOYSA-N 7-methyl-3-sulfanylidene-1,2-dihydro-[1,2,4]triazolo[4,3-a]pyrimidin-5-one Chemical compound CC1=CC(=O)N2C(=S)NNC2=N1 HGJLLONXGPLCEM-UHFFFAOYSA-N 0.000 description 1
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- XJUZRXYOEPSWMB-UHFFFAOYSA-N Chloromethyl methyl ether Chemical compound COCCl XJUZRXYOEPSWMB-UHFFFAOYSA-N 0.000 description 1
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- PCVIDRUONNIRLS-MRRKDWNQSA-L [Na+].[Na+].CO\N=C(/C(=O)NC1[C@@H]2N(C(=C(CS2)CSC=2C=CC=3N(N2)C(N(N3)C)=O)C(=O)[O-])C1=O)\C=1OC=CC1.CO\N=C(/C(=O)NC1[C@@H]3N(C(=C(CS3)CSC=3C=CC=2N(N3)C(N(N2)C)=O)C(=O)[O-])C1=O)\C=1OC=CC1 Chemical compound [Na+].[Na+].CO\N=C(/C(=O)NC1[C@@H]2N(C(=C(CS2)CSC=2C=CC=3N(N2)C(N(N3)C)=O)C(=O)[O-])C1=O)\C=1OC=CC1.CO\N=C(/C(=O)NC1[C@@H]3N(C(=C(CS3)CSC=3C=CC=2N(N3)C(N(N2)C)=O)C(=O)[O-])C1=O)\C=1OC=CC1 PCVIDRUONNIRLS-MRRKDWNQSA-L 0.000 description 1
- SORGEQQSQGNZFI-UHFFFAOYSA-N [azido(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(N=[N+]=[N-])OC1=CC=CC=C1 SORGEQQSQGNZFI-UHFFFAOYSA-N 0.000 description 1
- 150000001243 acetic acids Chemical class 0.000 description 1
- PBCJIPOGFJYBJE-UHFFFAOYSA-N acetonitrile;hydrate Chemical compound O.CC#N PBCJIPOGFJYBJE-UHFFFAOYSA-N 0.000 description 1
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- PYHXGXCGESYPCW-UHFFFAOYSA-N alpha-phenylbenzeneacetic acid Natural products C=1C=CC=CC=1C(C(=O)O)C1=CC=CC=C1 PYHXGXCGESYPCW-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- BVCZEBOGSOYJJT-UHFFFAOYSA-N ammonium carbamate Chemical compound [NH4+].NC([O-])=O BVCZEBOGSOYJJT-UHFFFAOYSA-N 0.000 description 1
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- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 description 1
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- 239000012964 benzotriazole Substances 0.000 description 1
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- 230000003115 biocidal effect Effects 0.000 description 1
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- 239000001569 carbon dioxide Substances 0.000 description 1
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- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
- 125000005518 carboxamido group Chemical group 0.000 description 1
- 150000001734 carboxylic acid salts Chemical class 0.000 description 1
- CZTQZXZIADLWOZ-CRAIPNDOSA-N cefaloridine Chemical compound O=C([C@@H](NC(=O)CC=1SC=CC=1)[C@H]1SC2)N1C(C(=O)[O-])=C2C[N+]1=CC=CC=C1 CZTQZXZIADLWOZ-CRAIPNDOSA-N 0.000 description 1
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- 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
- VUFGUVLLDPOSBC-XRZFDKQNSA-M cephalothin sodium Chemical compound [Na+].N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)COC(=O)C)C([O-])=O)C(=O)CC1=CC=CS1 VUFGUVLLDPOSBC-XRZFDKQNSA-M 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- OQNGCCWBHLEQFN-UHFFFAOYSA-N chloroform;hexane Chemical compound ClC(Cl)Cl.CCCCCC OQNGCCWBHLEQFN-UHFFFAOYSA-N 0.000 description 1
- 229940061627 chloromethyl methyl ether Drugs 0.000 description 1
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- 238000012937 correction Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 239000007822 coupling agent Substances 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 150000001991 dicarboxylic acids Chemical class 0.000 description 1
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 230000003292 diminished effect Effects 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
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- CCGKOQOJPYTBIH-UHFFFAOYSA-N ethenone Chemical compound C=C=O CCGKOQOJPYTBIH-UHFFFAOYSA-N 0.000 description 1
- XFDQKQTYWOXISW-UHFFFAOYSA-N ethyl 2-(6-chloro-3-oxo-[1,2,4]triazolo[4,3-b]pyridazin-2-yl)acetate Chemical compound C1=CC(Cl)=NN2C(=O)N(CC(=O)OCC)N=C21 XFDQKQTYWOXISW-UHFFFAOYSA-N 0.000 description 1
- 238000003810 ethyl acetate extraction Methods 0.000 description 1
- LKHYFCSSVZVVNF-UHFFFAOYSA-N ethyl hexanoate;sodium Chemical compound [Na].CCCCCC(=O)OCC LKHYFCSSVZVVNF-UHFFFAOYSA-N 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- ZEZBGAPXDASOQU-HCCKASOXSA-N furan-2-yl (6R)-4-acetamido-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate Chemical compound C(C)(=O)NC1S[C@H]2N(C(=C1)C(=O)OC=1OC=CC=1)C(C2)=O ZEZBGAPXDASOQU-HCCKASOXSA-N 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 125000006331 halo benzoyl group Chemical group 0.000 description 1
- 150000002366 halogen compounds Chemical class 0.000 description 1
- 238000010438 heat treatment Methods 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
- XNXVOSBNFZWHBV-UHFFFAOYSA-N hydron;o-methylhydroxylamine;chloride Chemical compound Cl.CON XNXVOSBNFZWHBV-UHFFFAOYSA-N 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- CTAPFRYPJLPFDF-UHFFFAOYSA-N isoxazole Chemical class C=1C=NOC=1 CTAPFRYPJLPFDF-UHFFFAOYSA-N 0.000 description 1
- 150000003932 ketenimines Chemical class 0.000 description 1
- 229960002510 mandelic acid Drugs 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 150000004702 methyl esters Chemical class 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 125000001038 naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 description 1
- 230000003589 nefrotoxic effect Effects 0.000 description 1
- 231100000381 nephrotoxic Toxicity 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- NUXCOKIYARRTDC-UHFFFAOYSA-N o-ethylhydroxylamine;hydron;chloride Chemical compound Cl.CCON NUXCOKIYARRTDC-UHFFFAOYSA-N 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000012074 organic phase Substances 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- 235000019371 penicillin G benzathine Nutrition 0.000 description 1
- 229940056360 penicillin g Drugs 0.000 description 1
- 150000002960 penicillins Chemical class 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000012071 phase 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
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000002243 precursor 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
- 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
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 229940083555 sodium cephalothin Drugs 0.000 description 1
- RPACBEVZENYWOL-XFULWGLBSA-M sodium;(2r)-2-[6-(4-chlorophenoxy)hexyl]oxirane-2-carboxylate Chemical compound [Na+].C=1C=C(Cl)C=CC=1OCCCCCC[C@]1(C(=O)[O-])CO1 RPACBEVZENYWOL-XFULWGLBSA-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
- 239000007858 starting material Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 238000000859 sublimation Methods 0.000 description 1
- 230000008022 sublimation Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 150000007970 thio esters Chemical class 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 150000003852 triazoles Chemical class 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 230000002485 urinary effect Effects 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/38—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D307/54—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
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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 ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
- C07D317/32—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings 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 ring carbon atoms
- C07D317/34—Oxygen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Communicable Diseases (AREA)
- Pharmacology & Pharmacy (AREA)
- Oncology (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Cephalosporin Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US70522676A | 1976-07-13 | 1976-07-13 | |
| US05/771,859 US4103085A (en) | 1977-02-24 | 1977-02-24 | 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 |
| US05/777,986 US4112228A (en) | 1976-07-13 | 1977-03-16 | 7-(D-α-Hydroxy-2-arylacetamido)-3-(2-carboxyalkyl-2,3-dihydro-s-triazolo-[4,3-b]pyridazin-3-on-6-ylthiomethyl)-3-cephem-4-carboxylic acids and derivatives |
| US05/788,056 US4104469A (en) | 1977-04-15 | 1977-04-15 | 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 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| GB1561236A true GB1561236A (en) | 1980-02-13 |
Family
ID=27505490
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB29212/77A Expired GB1561236A (en) | 1976-07-13 | 1977-07-12 | Cephalosporins |
Country Status (16)
| Country | Link |
|---|---|
| JP (1) | JPS5328191A (enExample) |
| AU (1) | AU511805B2 (enExample) |
| BE (1) | BE856785A (enExample) |
| CA (1) | CA1142918A (enExample) |
| CH (1) | CH640239A5 (enExample) |
| DE (1) | DE2731724A1 (enExample) |
| DK (1) | DK143344C (enExample) |
| FI (1) | FI772179A7 (enExample) |
| FR (1) | FR2358411A1 (enExample) |
| GB (1) | GB1561236A (enExample) |
| GR (1) | GR81280B (enExample) |
| IE (1) | IE45548B1 (enExample) |
| LU (1) | LU77756A1 (enExample) |
| NL (1) | NL7707820A (enExample) |
| SE (2) | SE7708053L (enExample) |
| YU (1) | YU171977A (enExample) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0228061A3 (en) * | 1985-12-23 | 1988-12-14 | Takeda Chemical Industries, Ltd. | Cephem compounds |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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
- 1977-07-11 DK DK312677A patent/DK143344C/da not_active IP Right Cessation
- 1977-07-11 IE IE1430/77A patent/IE45548B1/en unknown
- 1977-07-11 SE SE7708053A patent/SE7708053L/xx not_active Application Discontinuation
- 1977-07-11 YU YU01719/77A patent/YU171977A/xx unknown
- 1977-07-12 GB GB29212/77A patent/GB1561236A/en not_active Expired
- 1977-07-12 CA CA000282573A patent/CA1142918A/en not_active Expired
- 1977-07-13 GR GR53959A patent/GR81280B/el unknown
- 1977-07-13 BE BE179319A patent/BE856785A/xx not_active IP Right Cessation
- 1977-07-13 JP JP8301677A patent/JPS5328191A/ja active Pending
- 1977-07-13 FR FR7721814A patent/FR2358411A1/fr active Granted
- 1977-07-13 AU AU26982/77A patent/AU511805B2/en not_active Expired
- 1977-07-13 NL NL7707820A patent/NL7707820A/xx not_active Application Discontinuation
- 1977-07-13 FI FI772179A patent/FI772179A7/fi not_active Application Discontinuation
- 1977-07-13 DE DE19772731724 patent/DE2731724A1/de not_active Withdrawn
- 1977-07-13 LU LU77756A patent/LU77756A1/xx unknown
- 1977-07-13 CH CH868077A patent/CH640239A5/de not_active IP Right Cessation
-
1982
- 1982-09-24 SE SE8205482A patent/SE8205482D0/xx not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| FR2358411B1 (enExample) | 1981-06-12 |
| DK312677A (da) | 1978-01-14 |
| DK143344C (da) | 1981-12-14 |
| AU2698277A (en) | 1979-01-18 |
| JPS5328191A (en) | 1978-03-16 |
| FR2358411A1 (fr) | 1978-02-10 |
| AU511805B2 (en) | 1980-09-04 |
| NL7707820A (nl) | 1978-01-17 |
| CH640239A5 (en) | 1983-12-30 |
| IE45548L (en) | 1978-01-13 |
| IE45548B1 (en) | 1982-09-22 |
| GR81280B (enExample) | 1984-12-11 |
| DE2731724A1 (de) | 1978-01-19 |
| CA1142918A (en) | 1983-03-15 |
| SE7708053L (sv) | 1978-01-14 |
| LU77756A1 (enExample) | 1978-02-08 |
| DK143344B (da) | 1981-08-10 |
| SE8205482L (sv) | 1982-09-24 |
| FI772179A7 (enExample) | 1978-01-14 |
| YU171977A (en) | 1982-06-30 |
| BE856785A (fr) | 1978-01-13 |
| SE8205482D0 (sv) | 1982-09-24 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 429A | Application made for amendment of specification (sect. 29/1949) | ||
| 429C | Application to amend the specification withdrawn (sect. 29/1949) | ||
| PS | Patent sealed [section 19, patents act 1949] | ||
| PCNP | Patent ceased through non-payment of renewal fee |