CH622262A5 - - Google Patents

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Publication number: CH622262A5
Authority: CH; Switzerland
Prior art keywords: triazol; cephem; carboxylic acid; amino; ylthiomethyl
Prior art date: 1974-12-27

Application number

CH1630975A

Other languages

German (de)

English (en)

Inventor

David Alan Berges

Original Assignee

Smithkline Corp

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.)

1974-12-27

Filing date

1975-12-16

Publication date

1981-03-31

1975-12-16 Application filed by Smithkline Corp filed Critical Smithkline Corp

1981-03-31 Publication of CH622262A5 publication Critical patent/CH622262A5/de

Links

150000001875 compounds Chemical class 0.000 description 45
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 42
238000000034 method Methods 0.000 description 39
239000000243 solution Substances 0.000 description 35
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 30
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 29
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 27
239000000203 mixture Substances 0.000 description 21
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 19
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 19
-1 cephalosporin compounds Chemical class 0.000 description 18
239000002253 acid Substances 0.000 description 16
125000002887 hydroxy group Chemical group [H]O* 0.000 description 16
125000006239 protecting group Chemical group 0.000 description 14
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 12
238000002360 preparation method Methods 0.000 description 12
239000011541 reaction mixture Substances 0.000 description 12
150000003839 salts Chemical class 0.000 description 12
125000004432 carbon atom Chemical group C* 0.000 description 11
239000000047 product Substances 0.000 description 11
QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 10
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
238000006243 chemical reaction Methods 0.000 description 9
125000004435 hydrogen atom Chemical group [H]* 0.000 description 9
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
125000003277 amino group Chemical group 0.000 description 8
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 8
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 8
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 7
238000010992 reflux Methods 0.000 description 7
229930186147 Cephalosporin Natural products 0.000 description 6
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
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 6
229940124587 cephalosporin Drugs 0.000 description 6
229910052943 magnesium sulfate Inorganic materials 0.000 description 6
235000019341 magnesium sulphate Nutrition 0.000 description 6
239000002244 precipitate Substances 0.000 description 6
159000000000 sodium salts Chemical class 0.000 description 6
239000007787 solid Substances 0.000 description 6
SYOANZBNGDEJFH-UHFFFAOYSA-N 2,5-dihydro-1h-triazole Chemical compound C1NNN=C1 SYOANZBNGDEJFH-UHFFFAOYSA-N 0.000 description 5
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 5
150000007513 acids Chemical class 0.000 description 5
125000003545 alkoxy group Chemical group 0.000 description 5
239000008346 aqueous phase Substances 0.000 description 5
239000002585 base Substances 0.000 description 5
239000012071 phase Substances 0.000 description 5
230000002829 reductive effect Effects 0.000 description 5
239000011734 sodium Substances 0.000 description 5
125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 4
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
230000010933 acylation Effects 0.000 description 4
238000005917 acylation reaction Methods 0.000 description 4
125000003282 alkyl amino group Chemical group 0.000 description 4
RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 4
239000007864 aqueous solution Substances 0.000 description 4
150000001780 cephalosporins Chemical group 0.000 description 4
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 4
229910052708 sodium Inorganic materials 0.000 description 4
239000000725 suspension Substances 0.000 description 4
125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 description 3
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 3
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
239000004793 Polystyrene Substances 0.000 description 3
239000000853 adhesive Substances 0.000 description 3
230000001070 adhesive effect Effects 0.000 description 3
125000000217 alkyl group Chemical group 0.000 description 3
125000001246 bromo group Chemical group Br* 0.000 description 3
239000000460 chlorine Substances 0.000 description 3
229910052801 chlorine Inorganic materials 0.000 description 3
YWEUIGNSBFLMFL-UHFFFAOYSA-N diphosphonate Chemical compound O=P(=O)OP(=O)=O YWEUIGNSBFLMFL-UHFFFAOYSA-N 0.000 description 3
239000002024 ethyl acetate extract Substances 0.000 description 3
239000011737 fluorine Substances 0.000 description 3
229910052731 fluorine Inorganic materials 0.000 description 3
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 description 3
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
DLYUQMMRRRQYAE-UHFFFAOYSA-N phosphorus pentoxide Inorganic materials O1P(O2)(=O)OP3(=O)OP1(=O)OP2(=O)O3 DLYUQMMRRRQYAE-UHFFFAOYSA-N 0.000 description 3
235000017557 sodium bicarbonate Nutrition 0.000 description 3
229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 3
125000001544 thienyl group Chemical group 0.000 description 3
HRXKRNGNAMMEHJ-UHFFFAOYSA-K trisodium citrate Chemical compound [Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O HRXKRNGNAMMEHJ-UHFFFAOYSA-K 0.000 description 3
125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 description 2
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
GNVKJHXSZWAYFR-UHFFFAOYSA-N 2-(5-sulfanylidene-1h-1,2,4-triazol-4-yl)acetic acid Chemical compound OC(=O)CN1C=NN=C1S GNVKJHXSZWAYFR-UHFFFAOYSA-N 0.000 description 2
OBETXYAYXDNJHR-UHFFFAOYSA-N 2-Ethylhexanoic acid Chemical compound CCCCC(CC)C(O)=O OBETXYAYXDNJHR-UHFFFAOYSA-N 0.000 description 2
125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
241000894006 Bacteria Species 0.000 description 2
241000588724 Escherichia coli Species 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
MXFQITVUNUZTGP-UHFFFAOYSA-N N-amino-N-nitroformamide Chemical compound NN(C=O)[N+](=O)[O-] MXFQITVUNUZTGP-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
150000001782 cephems Chemical group 0.000 description 2
125000004663 dialkyl amino group Chemical group 0.000 description 2
ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 2
150000002148 esters Chemical group 0.000 description 2
239000000284 extract Substances 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
XZBIXDPGRMLSTC-UHFFFAOYSA-N formohydrazide Chemical compound NNC=O XZBIXDPGRMLSTC-UHFFFAOYSA-N 0.000 description 2
125000004464 hydroxyphenyl group Chemical group 0.000 description 2
238000000338 in vitro Methods 0.000 description 2
238000001727 in vivo Methods 0.000 description 2
238000002347 injection Methods 0.000 description 2
239000007924 injection Substances 0.000 description 2
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 2
231100000252 nontoxic Toxicity 0.000 description 2
230000003000 nontoxic effect Effects 0.000 description 2
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 2
125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 2
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 2
238000003756 stirring Methods 0.000 description 2
125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
125000001425 triazolyl group Chemical group 0.000 description 2
125000006000 trichloroethyl group Chemical group 0.000 description 2
UDNNSZLJGQVQOX-HQKHBYFDSA-N (6R)-3-[[4-(carboxymethyl)-1,2,4-triazol-3-yl]sulfanylmethyl]-7-[[(2R)-2-hydroxy-2-phenylacetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound C([C@H](O)C1=CC=CC=C1)(=O)NC1[C@@H]2N(C(=C(CS2)CSC2=NN=CN2CC(=O)O)C(=O)O)C1=O UDNNSZLJGQVQOX-HQKHBYFDSA-N 0.000 description 1
SFWMZWIYIRMOJX-WCRCJTMVSA-N (6R)-7-amino-3-[[5-(3-carboxypropyl)-2H-triazol-4-yl]sulfanylmethyl]-8-oxo-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=1CSC1=NNN=C1CCCC(O)=O SFWMZWIYIRMOJX-WCRCJTMVSA-N 0.000 description 1
PWLGUVUWISJQSV-LESKNEHBSA-N (6r)-7-amino-3-[[5-(2-carboxyethyl)-2h-triazol-4-yl]sulfanylmethyl]-8-oxo-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=1CSC1=NNN=C1CCC(O)=O PWLGUVUWISJQSV-LESKNEHBSA-N 0.000 description 1
125000001506 1,2,3-triazol-5-yl group Chemical group [H]N1N=NC([H])=C1[*] 0.000 description 1
125000001305 1,2,4-triazol-3-yl group Chemical group [H]N1N=C([*])N=C1[H] 0.000 description 1
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 1
QEASJVYPHMYPJM-UHFFFAOYSA-N 1,2-dihydrotriazol-5-one Chemical class OC1=CNN=N1 QEASJVYPHMYPJM-UHFFFAOYSA-N 0.000 description 1
QUKGLNCXGVWCJX-UHFFFAOYSA-N 1,3,4-thiadiazol-2-amine Chemical class NC1=NN=CS1 QUKGLNCXGVWCJX-UHFFFAOYSA-N 0.000 description 1
HRDIKQFHFOTXDL-UHFFFAOYSA-N 1-o,1-o-diethyl 3-o-methyl propane-1,1,3-tricarboxylate Chemical compound CCOC(=O)C(C(=O)OCC)CCC(=O)OC HRDIKQFHFOTXDL-UHFFFAOYSA-N 0.000 description 1
AFBBKYQYNPNMAT-UHFFFAOYSA-N 1h-1,2,4-triazol-1-ium-3-thiolate Chemical class SC=1N=CNN=1 AFBBKYQYNPNMAT-UHFFFAOYSA-N 0.000 description 1
WUEPMEXUMQVEGN-UHFFFAOYSA-N 2,2,2-trifluoroacetic acid;2,2,2-trifluoro-n-[2-[2-[(2,2,2-trifluoroacetyl)amino]ethylamino]ethyl]acetamide Chemical compound OC(=O)C(F)(F)F.FC(F)(F)C(=O)NCCNCCNC(=O)C(F)(F)F WUEPMEXUMQVEGN-UHFFFAOYSA-N 0.000 description 1
OYLWNIRWHSRRDC-UHFFFAOYSA-N 2-(5-sulfanylidene-1,2-dihydro-1,2,4-triazol-3-yl)acetic acid Chemical compound OC(=O)CC1=NN=C(S)N1 OYLWNIRWHSRRDC-UHFFFAOYSA-N 0.000 description 1
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 1
SMJRBWINMFUUDS-UHFFFAOYSA-N 2-thienylacetic acid Chemical compound OC(=O)CC1=CC=CS1 SMJRBWINMFUUDS-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
AZMSMQZKBRVUHB-UHFFFAOYSA-N 5-sulfanylidene-1,2-dihydrotriazole-4-carboxamide Chemical compound NC(=O)C1=NNNC1=S AZMSMQZKBRVUHB-UHFFFAOYSA-N 0.000 description 1
GNCPNAQCXHPXOX-UHFFFAOYSA-N 5-sulfanylidene-1,2-dihydrotriazole-4-carboxylic acid Chemical compound OC(=O)C1=NNNC1=S GNCPNAQCXHPXOX-UHFFFAOYSA-N 0.000 description 1
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 1
238000012404 In vitro experiment Methods 0.000 description 1
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 1
WRQNANDWMGAFTP-UHFFFAOYSA-N Methylacetoacetic acid Chemical compound COC(=O)CC(C)=O WRQNANDWMGAFTP-UHFFFAOYSA-N 0.000 description 1
241000588772 Morganella morganii Species 0.000 description 1
241000699670 Mus sp. Species 0.000 description 1
OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 1
125000000066 S-methyl group Chemical group [H]C([H])([H])S* 0.000 description 1
241000607142 Salmonella Species 0.000 description 1
241000607768 Shigella Species 0.000 description 1
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical class [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
229960000583 acetic acid Drugs 0.000 description 1
229910052783 alkali metal Inorganic materials 0.000 description 1
229910052784 alkaline earth metal Inorganic materials 0.000 description 1
229910021529 ammonia Inorganic materials 0.000 description 1
150000003863 ammonium salts Chemical class 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
230000000844 anti-bacterial effect Effects 0.000 description 1
150000001540 azides Chemical class 0.000 description 1
UDLLFLQFQMACJB-UHFFFAOYSA-N azidomethylbenzene Chemical compound [N-]=[N+]=NCC1=CC=CC=C1 UDLLFLQFQMACJB-UHFFFAOYSA-N 0.000 description 1
244000052616 bacterial pathogen Species 0.000 description 1
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
159000000007 calcium salts Chemical class 0.000 description 1
239000002775 capsule Substances 0.000 description 1
239000004202 carbamide Substances 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 1
150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
239000003153 chemical reaction reagent Substances 0.000 description 1
239000002026 chloroform extract Substances 0.000 description 1
238000003776 cleavage reaction Methods 0.000 description 1
230000008878 coupling Effects 0.000 description 1
238000010168 coupling process Methods 0.000 description 1
238000005859 coupling reaction Methods 0.000 description 1
WZHCOOQXZCIUNC-UHFFFAOYSA-N cyclandelate Chemical class C1C(C)(C)CC(C)CC1OC(=O)C(O)C1=CC=CC=C1 WZHCOOQXZCIUNC-UHFFFAOYSA-N 0.000 description 1
230000000911 decarboxylating effect Effects 0.000 description 1
239000003480 eluent Substances 0.000 description 1
125000004185 ester group Chemical group 0.000 description 1
230000032050 esterification Effects 0.000 description 1
238000005886 esterification reaction Methods 0.000 description 1
UDPBWWFXADBOLQ-UHFFFAOYSA-N ethyl 5-sulfanylidene-1,2-dihydrotriazole-4-carboxylate Chemical compound CCOC(=O)C1=NNNC1=S UDPBWWFXADBOLQ-UHFFFAOYSA-N 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
238000002474 experimental method Methods 0.000 description 1
235000019253 formic acid Nutrition 0.000 description 1
238000001640 fractional crystallisation Methods 0.000 description 1
239000007789 gas Substances 0.000 description 1
FVIZARNDLVOMSU-UHFFFAOYSA-N ginsenoside K Natural products C1CC(C2(CCC3C(C)(C)C(O)CCC3(C)C2CC2O)C)(C)C2C1C(C)(CCC=C(C)C)OC1OC(CO)C(O)C(O)C1O FVIZARNDLVOMSU-UHFFFAOYSA-N 0.000 description 1
239000012362 glacial acetic acid Substances 0.000 description 1
239000001257 hydrogen Substances 0.000 description 1
229910052739 hydrogen Inorganic materials 0.000 description 1
229910000037 hydrogen sulfide Inorganic materials 0.000 description 1
208000015181 infectious disease Diseases 0.000 description 1
230000002401 inhibitory effect Effects 0.000 description 1
239000000543 intermediate Substances 0.000 description 1
239000003456 ion exchange resin Substances 0.000 description 1
229920003303 ion-exchange polymer Polymers 0.000 description 1
150000002500 ions Chemical class 0.000 description 1
239000008101 lactose Substances 0.000 description 1
235000019359 magnesium stearate Nutrition 0.000 description 1
229910052757 nitrogen Inorganic materials 0.000 description 1
230000003287 optical effect Effects 0.000 description 1
230000020477 pH reduction Effects 0.000 description 1
238000010647 peptide synthesis reaction Methods 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
150000005331 phenylglycines Chemical class 0.000 description 1
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
239000008055 phosphate buffer solution Substances 0.000 description 1
239000011574 phosphorus Substances 0.000 description 1
229910052698 phosphorus Inorganic materials 0.000 description 1
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
229920002223 polystyrene Polymers 0.000 description 1
159000000001 potassium salts Chemical class 0.000 description 1
UORVCLMRJXCDCP-UHFFFAOYSA-N propynoic acid Chemical compound OC(=O)C#C UORVCLMRJXCDCP-UHFFFAOYSA-N 0.000 description 1
230000001681 protective effect Effects 0.000 description 1
230000008707 rearrangement Effects 0.000 description 1
230000000717 retained effect Effects 0.000 description 1
230000002441 reversible effect Effects 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
230000007017 scission Effects 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
239000008223 sterile water Substances 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
VLLMWSRANPNYQX-UHFFFAOYSA-N thiadiazole Chemical compound C1=CSN=N1.C1=CSN=N1 VLLMWSRANPNYQX-UHFFFAOYSA-N 0.000 description 1
150000003568 thioethers Chemical class 0.000 description 1
150000003573 thiols Chemical class 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D501/00—Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- C07D501/14—Compounds having a nitrogen atom directly attached in position 7
- C07D501/16—Compounds having a nitrogen atom directly attached in position 7 with a double bond between positions 2 and 3
- C07D501/20—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids
- C07D501/24—7-Acylaminocephalosporanic or substituted 7-acylaminocephalosporanic acids in which the acyl radicals are derived from carboxylic acids with hydrocarbon radicals, substituted by hetero atoms or hetero rings, attached in position 3
- C07D501/36—Methylene radicals, substituted by sulfur atoms
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
- A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles 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
- C07D249/12—Oxygen or sulfur atoms

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Epidemiology (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Cephalosporin Compounds (AREA)

CH1630975A 1974-12-27 1975-12-16 CH622262A5 (ro)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
US05/536,759 US3989694A (en)	1974-12-27	1974-12-27	7-Acyl-3-(substituted triazolyl thiomethyl)cephalosporins

Publications (1)

Publication Number	Publication Date
CH622262A5 true CH622262A5 (ro)	1981-03-31

Family

ID=24139827

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CH1630975A CH622262A5 (ro)	1974-12-27	1975-12-16

Country Status (14)

Country	Link
US (2)	US3989694A (ro)
JP (1)	JPS5188989A (ro)
AU (1)	AU8789275A (ro)
BE (1)	BE837071A (ro)
CA (1)	CA1085822A (ro)
CH (1)	CH622262A5 (ro)
DE (1)	DE2558024A1 (ro)
ES (2)	ES442100A1 (ro)
FR (2)	FR2313068A1 (ro)
GB (2)	GB1539517A (ro)
IE (1)	IE43127B1 (ro)
IT (1)	IT1051939B (ro)
NL (1)	NL7513872A (ro)
ZA (1)	ZA756192B (ro)

Families Citing this family (18)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
JPS612674B2 (ro) *	1974-06-20	1986-01-27	Meiji Seika Co
US4172196A (en) *	1974-09-03	1979-10-23	Bristol-Myers Company	Certain 7-α-substituted-α-hydroxyacetamido-3-(1-carboxymethyltetrazol-5-yl-thiomethyl)-3-cephem-4-carboxylic acids
US4182863A (en) *	1974-09-03	1980-01-08	Bristol-Myers Company	7-Amino-3-(1-carboxymethyltetrazol-5-ylthiomethyl)-3-cephem-4-carboxylic acid
US3989694A (en) *	1974-12-27	1976-11-02	Smithkline Corporation	7-Acyl-3-(substituted triazolyl thiomethyl)cephalosporins
IL49183A0 (en) *	1975-03-27	1976-05-31	Pfizer	Novel cephalosporin derivatives,their preparation and pharmaceutical compositions containing them
US4183925A (en) *	1975-03-27	1980-01-15	Pfizer Inc.	7-Aminophenylacetamido-Δ3 -cephem antibacterial agents and method of use
US4220644A (en) *	1976-05-03	1980-09-02	Smithkline Corporation	7-Acylamino-3-(substituted tetrazolyl thiomethyl) cephalosporins
US4082912A (en) *	1976-06-30	1978-04-04	Bristol-Myers Company	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
JPS5321191A (en) *	1976-08-10	1978-02-27	Shionogi & Co Ltd	7-arylmalonamidocephem derivatives
US4057631A (en) *	1976-09-02	1977-11-08	Smithkline Corporation	7-(α-Substituted phenylacetamido)-3-(1-carboxymethylthioethyltetrazolyl-5-thiomethyl)-3-cephem-4-carboxylic acids
US4083975A (en) *	1976-09-24	1978-04-11	Smithkline Corporation	7-Acylamino-3-(3-sulfomethyl-1,2,4-triazol-5-ylthiomethyl)-3-cephem-4-carboxylic acids
US4117124A (en) *	1977-06-30	1978-09-26	Smithkline Corporation	7-Acylamino-3-[[3-(carboxymethyl)thio-1H-1,2,4-triazol-5-yl]thiomethyl]-3-cephem-4-carboxylic acids
US4174324A (en) *	1977-06-30	1979-11-13	Smithkline Corporation	3-(Carboxymethyl)thio-1H-1,2,4-triazol-5-thione
US4197240A (en) *	1977-12-23	1980-04-08	Yeda Research And Development Co. Ltd.	Penicillin derivatives
US4229575A (en) *	1978-02-27	1980-10-21	Richardson-Merrell Inc.	7-(2,3-Dihydrobenzo-5-furanyl)-acetamido cephalosporin derivatives
US4219648A (en) *	1978-03-06	1980-08-26	Richardson-Merrell Inc.	7-[[Amino(1,3-dihydrobenzo[c]thienyl)acetyl]amino]cephalosporin derivatives
US4749522A (en) *	1985-10-31	1988-06-07	Angio-Medical Corporation	Supercritical fluid extraction of animal derived materials
PT87616B (pt)	1987-06-24	1992-09-30	Smithkline Beecham Corp	Processo de preparacao de antagonistas do leucotrieno e de composicoes farmaceuticas

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
NL173169C (nl)	1969-10-27	1983-12-16	Fujisawa Pharmaceutical Co	Werkwijze voor het bereiden van een farmaceutisch preparaat met antibacteriele werking en werkwijze voor het bereiden van het daarvoor benodigde cephalosporinederivaat.
US3759904A (en) *	1971-07-29	1973-09-18	Bristol Myers Co	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))-
US3796801A (en) *	1971-11-04	1974-03-12	Smithkline Corp	Method of combating enterobacter infections
BE793037A (fr) *	1971-12-23	1973-06-20	Fujisawa Pharmaceutical Co	Procede de preparation de derives d'acide 7-acylamino-3-substitue-3-cephem-4-carboxylique et nouveaux produits ainsi obtenus
US3813388A (en) *	1972-01-31	1974-05-28	L Crast	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
US4007173A (en)	1973-05-07	1977-02-08	Smithkline Corporation	α-amino-α-(ureidophenyl)acetamidocephalosporins
JPS5653557B2 (ro) *	1973-10-15	1981-12-19
GB1476981A (en) *	1974-06-05	1977-06-16	Bristol Myers Co	Substituted penicillanic acids
US3989694A (en) *	1974-12-27	1976-11-02	Smithkline Corporation	7-Acyl-3-(substituted triazolyl thiomethyl)cephalosporins

1974
- 1974-12-27 US US05/536,759 patent/US3989694A/en not_active Expired - Lifetime
1975
- 1975-09-30 ZA ZA00756192A patent/ZA756192B/xx unknown
- 1975-10-25 ES ES442100A patent/ES442100A1/es not_active Expired
- 1975-11-27 NL NL7513872A patent/NL7513872A/xx not_active Application Discontinuation
- 1975-11-28 CA CA240,739A patent/CA1085822A/en not_active Expired
- 1975-12-16 CH CH1630975A patent/CH622262A5/de not_active IP Right Cessation
- 1975-12-17 GB GB51600/75A patent/GB1539517A/en not_active Expired
- 1975-12-17 FR FR7538677A patent/FR2313068A1/fr active Granted
- 1975-12-17 GB GB35032/78A patent/GB1539518A/en not_active Expired
- 1975-12-19 JP JP50152717A patent/JPS5188989A/ja active Pending
- 1975-12-19 IE IE2785/75A patent/IE43127B1/en unknown
- 1975-12-22 DE DE19752558024 patent/DE2558024A1/de not_active Withdrawn
- 1975-12-23 IT IT30742/75A patent/IT1051939B/it active
- 1975-12-24 BE BE163107A patent/BE837071A/xx not_active IP Right Cessation
- 1975-12-24 AU AU87892/75A patent/AU8789275A/en not_active Expired
1976
- 1976-06-03 FR FR7616857A patent/FR2303807A1/fr active Granted
- 1976-10-12 US US05/731,387 patent/US4142046A/en not_active Expired - Lifetime
1977
- 1977-02-26 ES ES456340A patent/ES456340A1/es not_active Expired

Also Published As

Publication number	Publication date
FR2303807A1 (fr)	1976-10-08
ZA756192B (en)	1976-09-29
IE43127B1 (en)	1980-12-31
CA1085822A (en)	1980-09-16
ES442100A1 (es)	1977-07-01
US3989694A (en)	1976-11-02
GB1539518A (en)	1979-01-31
IE43127L (en)	1976-06-27
US4142046A (en)	1979-02-27
IT1051939B (it)	1981-05-20
AU8789275A (en)	1977-06-30
BE837071A (fr)	1976-06-24
JPS5188989A (ro)	1976-08-04
GB1539517A (en)	1979-01-31
ES456340A1 (es)	1978-01-16
FR2303807B1 (ro)	1980-10-24
FR2313068B1 (ro)	1979-09-28
FR2313068A1 (fr)	1976-12-31
DE2558024A1 (de)	1976-07-08
NL7513872A (nl)	1976-06-29

Publication	Publication Date	Title
DE2727753C2 (ro)	1987-11-05
DE2519400C3 (de)	1982-02-11	Penicillinverbindungen, Verfahren zur Herstellung derselben und Mittel mit einem Gehalt derselben
CH622262A5 (ro)	1981-03-31
DE1795292B2 (de)	1974-08-29	Cephalosporinderivate und Verfahren zu deren Herstellung
US4154830A (en)	1979-05-15	Unsaturated derivatives of 7-acylamido-3-cephem-4-carboxylic acid
DE2539664C2 (ro)	1988-09-29
GB1573004A (en)	1980-08-13	Cephalosporin compounds
CH622523A5 (ro)	1981-04-15
US4061748A (en)	1977-12-06	7-(α-(4-Hydroxy-1,5-naphthyridine-3-carbonamido)-α-phenylacetamido) cephalosporin derivatives
US4231928A (en)	1980-11-04	Antibacterial agents
US4220644A (en)	1980-09-02	7-Acylamino-3-(substituted tetrazolyl thiomethyl) cephalosporins
DE2521063A1 (de)	1975-11-27	Phenylacetamidocephalosporin- derivate
US4117126A (en)	1978-09-26	7-(α-(4-Hydroxy-1,5-naphthyridine-3-carbonamido)-α-phenylacetamido) cephalosporin derivatives
DE2527291C2 (ro)	1988-01-14
DE2700271A1 (de)	1977-07-14	Thienopyridinderivate
DE3041160A1 (de)	1981-05-21	1-oxadethia-cephalosporin-derivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende antibakterielle mittel
US4117125A (en)	1978-09-26	7-Acylamino-3-[1-[2-(carboxymethylamino]ethyl) tetrazol-5-ylthiomethyl]-3-cephem-4-carboxylic acids
DE2330307A1 (de)	1974-01-03	Cephalosporinverbindungen, ihre salze, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel
DE2710490A1 (de)	1977-09-22	7-acylamino-3-(5-sulfoalkyl-1,3,4- oxadiazol-2-ylthiomethyl)-3-cephem-4- carbonsaeuren, ihre salze, verfahren zu ihrer herstellung, zwischenprodukte und arzneimittel
US4079134A (en)	1978-03-14	7-Acylamino-3-(5-sulfomethyl-1,3,4-thiadiazol-2-ylthiomethyl)-3-cephem-4-carboxylic acids
US4064242A (en)	1977-12-20	7-Acylamino-3-[1-(2,3-dihydroxypropyl)tetrazole-5-ylthiomethyl]-3-cephem-4-carboxylic acids
CS195680B2 (en)	1980-02-29	Process for preparing derivatives of 7-/substituted phenylglycinamido/-3-substituted-3-cephem-4-carboxylic acid
KR20000076288A (ko)	2000-12-26	항균성 치환 7-아실아미노-3-(메틸히드라조노)메틸-세팔로스포린 및 중간체
US4088761A (en)	1978-05-09	3-[(1,3-Dithiin-5-yl)-acetamido]-cephalosporins and antibacterial compositions containing them
GB1604740A (en)	1981-12-16	7-isothiazolylthioacetamido-7-methoxycephalosporanic acid derivatives

Legal Events

Date	Code	Title	Description
1985-08-30	PL	Patent ceased
2024-10-31	PL	Patent ceased