JPH0689005B2 - ベーターラクタマーゼ阻害剤としての６―アミノアルキルペニシラン酸１，１―ジオキシドおよび誘導体 - Google Patents
ベーターラクタマーゼ阻害剤としての６―アミノアルキルペニシラン酸１，１―ジオキシドおよび誘導体Info
- Publication number
- JPH0689005B2 JPH0689005B2 JP58002768A JP276883A JPH0689005B2 JP H0689005 B2 JPH0689005 B2 JP H0689005B2 JP 58002768 A JP58002768 A JP 58002768A JP 276883 A JP276883 A JP 276883A JP H0689005 B2 JPH0689005 B2 JP H0689005B2
- Authority
- JP
- Japan
- Prior art keywords
- beta
- hydrogen
- formula
- alpha
- title product
- 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 - Lifetime
Links
- 239000002253 acid Substances 0.000 title claims description 11
- 239000003781 beta lactamase inhibitor Substances 0.000 title description 10
- 229940126813 beta-lactamase inhibitor Drugs 0.000 title description 10
- 150000001875 compounds Chemical class 0.000 claims description 86
- -1 cation salt Chemical class 0.000 claims description 84
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 54
- 229910052739 hydrogen Inorganic materials 0.000 claims description 49
- 239000001257 hydrogen Substances 0.000 claims description 36
- 239000000203 mixture Substances 0.000 claims description 35
- 239000003782 beta lactam antibiotic agent Substances 0.000 claims description 32
- 239000002132 β-lactam antibiotic Substances 0.000 claims description 31
- 229940124586 β-lactam antibiotics Drugs 0.000 claims description 31
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 19
- 150000003839 salts Chemical class 0.000 claims description 17
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 11
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 10
- 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 9
- 230000004962 physiological condition Effects 0.000 claims description 8
- LSQZJLSUYDQPKJ-NJBDSQKTSA-N amoxicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=C(O)C=C1 LSQZJLSUYDQPKJ-NJBDSQKTSA-N 0.000 claims description 6
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 claims description 6
- 208000035143 Bacterial infection Diseases 0.000 claims description 5
- 229960003022 amoxicillin Drugs 0.000 claims description 5
- 229960000723 ampicillin Drugs 0.000 claims description 5
- 208000022362 bacterial infectious disease Diseases 0.000 claims description 5
- LSQZJLSUYDQPKJ-UHFFFAOYSA-N p-Hydroxyampicillin Natural products O=C1N2C(C(O)=O)C(C)(C)SC2C1NC(=O)C(N)C1=CC=C(O)C=C1 LSQZJLSUYDQPKJ-UHFFFAOYSA-N 0.000 claims description 5
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000006290 2-hydroxybenzyl group Chemical group [H]OC1=C(C([H])=C([H])C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- 125000006291 3-hydroxybenzyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(=C1[H])C([H])([H])* 0.000 claims description 3
- 125000003143 4-hydroxybenzyl group Chemical group [H]C([*])([H])C1=C([H])C([H])=C(O[H])C([H])=C1[H] 0.000 claims description 3
- GCFBRXLSHGKWDP-XCGNWRKASA-N cefoperazone Chemical compound O=C1C(=O)N(CC)CCN1C(=O)N[C@H](C=1C=CC(O)=CC=1)C(=O)N[C@@H]1C(=O)N2C(C(O)=O)=C(CSC=3N(N=NN=3)C)CS[C@@H]21 GCFBRXLSHGKWDP-XCGNWRKASA-N 0.000 claims description 3
- 229960004682 cefoperazone Drugs 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims description 3
- SBUCDZYLTRYMFG-PBFPGSCMSA-N (6r,7r)-7-[[(2r)-2-amino-2-(4-hydroxyphenyl)acetyl]amino]-3-[(5-methyl-1,3,4-thiadiazol-2-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound S1C(C)=NN=C1SCC1=C(C(O)=O)N2C(=O)[C@@H](NC(=O)[C@H](N)C=3C=CC(O)=CC=3)[C@H]2SC1 SBUCDZYLTRYMFG-PBFPGSCMSA-N 0.000 claims description 2
- GNWUOVJNSFPWDD-XMZRARIVSA-M Cefoxitin sodium Chemical compound [Na+].N([C@]1(OC)C(N2C(=C(COC(N)=O)CS[C@@H]21)C([O-])=O)=O)C(=O)CC1=CC=CS1 GNWUOVJNSFPWDD-XMZRARIVSA-M 0.000 claims description 2
- 229930195708 Penicillin V Natural products 0.000 claims description 2
- JTWOMNBEOCYFNV-NFFDBFGFSA-N azlocillin Chemical compound N([C@@H](C(=O)N[C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C=1C=CC=CC=1)C(=O)N1CCNC1=O JTWOMNBEOCYFNV-NFFDBFGFSA-N 0.000 claims description 2
- 229960003623 azlocillin Drugs 0.000 claims description 2
- PFOLLRNADZZWEX-FFGRCDKISA-N bacampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)[C@H](C(S3)(C)C)C(=O)OC(C)OC(=O)OCC)=CC=CC=C1 PFOLLRNADZZWEX-FFGRCDKISA-N 0.000 claims description 2
- 229960002699 bacampicillin Drugs 0.000 claims description 2
- NZDASSHFKWDBBU-KVMCETHSSA-N carfecillin Chemical group N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)C(C=1C=CC=CC=1)C(=O)OC1=CC=CC=C1 NZDASSHFKWDBBU-KVMCETHSSA-N 0.000 claims description 2
- 229960002543 carfecillin Drugs 0.000 claims description 2
- JIRBAUWICKGBFE-MNRDOXJOSA-N carindacillin Chemical group N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)C(C(=O)OC=1C=C2CCCC2=CC=1)C1=CC=CC=C1 JIRBAUWICKGBFE-MNRDOXJOSA-N 0.000 claims description 2
- 229960000717 carindacillin Drugs 0.000 claims description 2
- 229960004841 cefadroxil Drugs 0.000 claims description 2
- NBFNMSULHIODTC-CYJZLJNKSA-N cefadroxil monohydrate Chemical compound O.C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=C(O)C=C1 NBFNMSULHIODTC-CYJZLJNKSA-N 0.000 claims description 2
- GOFCPYKUMJBHBH-RHSMWYFYSA-N cefaloram Chemical compound N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)COC(=O)C)C(O)=O)C(=O)CC1=CC=CC=C1 GOFCPYKUMJBHBH-RHSMWYFYSA-N 0.000 claims description 2
- 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 claims description 2
- 229960002420 cefatrizine Drugs 0.000 claims description 2
- 229960001139 cefazolin Drugs 0.000 claims description 2
- MLYYVTUWGNIJIB-BXKDBHETSA-N cefazolin Chemical compound S1C(C)=NN=C1SCC1=C(C(O)=O)N2C(=O)[C@@H](NC(=O)CN3N=NN=C3)[C@H]2SC1 MLYYVTUWGNIJIB-BXKDBHETSA-N 0.000 claims description 2
- HJJDBAOLQAWBMH-YCRCPZNHSA-N cefmenoxime Chemical compound S([C@@H]1[C@@H](C(N1C=1C(O)=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1CSC1=NN=NN1C HJJDBAOLQAWBMH-YCRCPZNHSA-N 0.000 claims description 2
- 229960003791 cefmenoxime Drugs 0.000 claims description 2
- 229960004261 cefotaxime Drugs 0.000 claims description 2
- AZZMGZXNTDTSME-JUZDKLSSSA-M cefotaxime sodium Chemical compound [Na+].N([C@@H]1C(N2C(=C(COC(C)=O)CS[C@@H]21)C([O-])=O)=O)C(=O)\C(=N/OC)C1=CSC(N)=N1 AZZMGZXNTDTSME-JUZDKLSSSA-M 0.000 claims description 2
- 229960002682 cefoxitin Drugs 0.000 claims description 2
- ORFOPKXBNMVMKC-DWVKKRMSSA-N ceftazidime Chemical compound S([C@@H]1[C@@H](C(N1C=1C([O-])=O)=O)NC(=O)\C(=N/OC(C)(C)C(O)=O)C=2N=C(N)SC=2)CC=1C[N+]1=CC=CC=C1 ORFOPKXBNMVMKC-DWVKKRMSSA-N 0.000 claims description 2
- 229960000484 ceftazidime Drugs 0.000 claims description 2
- DXVUYOAEDJXBPY-NFFDBFGFSA-N hetacillin Chemical compound C1([C@@H]2C(=O)N(C(N2)(C)C)[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 DXVUYOAEDJXBPY-NFFDBFGFSA-N 0.000 claims description 2
- 229960003884 hetacillin Drugs 0.000 claims description 2
- YPBATNHYBCGSSN-VWPFQQQWSA-N mezlocillin Chemical compound N([C@@H](C(=O)N[C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C=1C=CC=CC=1)C(=O)N1CCN(S(C)(=O)=O)C1=O YPBATNHYBCGSSN-VWPFQQQWSA-N 0.000 claims description 2
- 229960000198 mezlocillin Drugs 0.000 claims description 2
- 229940056360 penicillin g Drugs 0.000 claims description 2
- 229940056367 penicillin v Drugs 0.000 claims description 2
- BPLBGHOLXOTWMN-MBNYWOFBSA-N phenoxymethylpenicillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)COC1=CC=CC=C1 BPLBGHOLXOTWMN-MBNYWOFBSA-N 0.000 claims description 2
- 229960002292 piperacillin Drugs 0.000 claims description 2
- WCMIIGXFCMNQDS-IDYPWDAWSA-M piperacillin sodium Chemical compound [Na+].O=C1C(=O)N(CC)CCN1C(=O)N[C@H](C=1C=CC=CC=1)C(=O)N[C@@H]1C(=O)N2[C@@H](C([O-])=O)C(C)(C)S[C@@H]21 WCMIIGXFCMNQDS-IDYPWDAWSA-M 0.000 claims description 2
- UQLLWWBDSUHNEB-CZUORRHYSA-N Cefaprin Chemical compound N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)COC(=O)C)C(O)=O)C(=O)CSC1=CC=NC=C1 UQLLWWBDSUHNEB-CZUORRHYSA-N 0.000 claims 1
- RRJHESVQVSRQEX-SUYBPPKGSA-N O-formylcefamandole Chemical compound CN1N=NN=C1SCC1=C(C(O)=O)N2C(=O)[C@@H](NC(=O)[C@H](OC=O)C=3C=CC=CC=3)[C@H]2SC1 RRJHESVQVSRQEX-SUYBPPKGSA-N 0.000 claims 1
- 229960003669 carbenicillin Drugs 0.000 claims 1
- FPPNZSSZRUTDAP-UWFZAAFLSA-N carbenicillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)C(C(O)=O)C1=CC=CC=C1 FPPNZSSZRUTDAP-UWFZAAFLSA-N 0.000 claims 1
- 229960003972 cefacetrile Drugs 0.000 claims 1
- RRYMAQUWDLIUPV-BXKDBHETSA-N cefacetrile Chemical compound S1CC(COC(=O)C)=C(C(O)=O)N2C(=O)[C@@H](NC(=O)CC#N)[C@@H]12 RRYMAQUWDLIUPV-BXKDBHETSA-N 0.000 claims 1
- 229960003866 cefaloridine Drugs 0.000 claims 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 claims 1
- 229960000603 cefalotin Drugs 0.000 claims 1
- XIURVHNZVLADCM-IUODEOHRSA-N cefalotin Chemical compound N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)COC(=O)C)C(O)=O)C(=O)CC1=CC=CS1 XIURVHNZVLADCM-IUODEOHRSA-N 0.000 claims 1
- 229960003012 cefamandole Drugs 0.000 claims 1
- 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 claims 1
- 229960002440 cefamandole nafate Drugs 0.000 claims 1
- 229960004350 cefapirin Drugs 0.000 claims 1
- 229960001991 ceftizoxime Drugs 0.000 claims 1
- NNULBSISHYWZJU-LLKWHZGFSA-N ceftizoxime Chemical compound N([C@@H]1C(N2C(=CCS[C@@H]21)C(O)=O)=O)C(=O)\C(=N/OC)C1=CSC(N)=N1 NNULBSISHYWZJU-LLKWHZGFSA-N 0.000 claims 1
- 229960004755 ceftriaxone Drugs 0.000 claims 1
- VAAUVRVFOQPIGI-SPQHTLEESA-N ceftriaxone Chemical compound S([C@@H]1[C@@H](C(N1C=1C(O)=O)=O)NC(=O)\C(=N/OC)C=2N=C(N)SC=2)CC=1CSC1=NC(=O)C(=O)NN1C VAAUVRVFOQPIGI-SPQHTLEESA-N 0.000 claims 1
- 229960001668 cefuroxime Drugs 0.000 claims 1
- JFPVXVDWJQMJEE-IZRZKJBUSA-N cefuroxime Chemical compound N([C@@H]1C(N2C(=C(COC(N)=O)CS[C@@H]21)C(O)=O)=O)C(=O)\C(=N/OC)C1=CC=CO1 JFPVXVDWJQMJEE-IZRZKJBUSA-N 0.000 claims 1
- 229940106164 cephalexin Drugs 0.000 claims 1
- ZAIPMKNFIOOWCQ-UEKVPHQBSA-N cephalexin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=CC=C1 ZAIPMKNFIOOWCQ-UEKVPHQBSA-N 0.000 claims 1
- HGBLNBBNRORJKI-WCABBAIRSA-N cyclacillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)C1(N)CCCCC1 HGBLNBBNRORJKI-WCABBAIRSA-N 0.000 claims 1
- 229960004244 cyclacillin Drugs 0.000 claims 1
- 229960002457 epicillin Drugs 0.000 claims 1
- RPBAFSBGYDKNRG-NJBDSQKTSA-N epicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CCC=CC1 RPBAFSBGYDKNRG-NJBDSQKTSA-N 0.000 claims 1
- 239000008177 pharmaceutical agent Substances 0.000 claims 1
- NONJJLVGHLVQQM-JHXYUMNGSA-N phenethicillin Chemical compound N([C@@H]1C(N2[C@H](C(C)(C)S[C@@H]21)C(O)=O)=O)C(=O)C(C)OC1=CC=CC=C1 NONJJLVGHLVQQM-JHXYUMNGSA-N 0.000 claims 1
- 229960004894 pheneticillin Drugs 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 187
- 239000000047 product Substances 0.000 description 110
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 46
- 238000000034 method Methods 0.000 description 39
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 38
- 239000000243 solution Substances 0.000 description 38
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 33
- 239000003921 oil Substances 0.000 description 33
- 235000019198 oils Nutrition 0.000 description 33
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
- 239000010410 layer Substances 0.000 description 25
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 24
- 239000002904 solvent Substances 0.000 description 24
- 238000006243 chemical reaction Methods 0.000 description 23
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 23
- 239000006260 foam Substances 0.000 description 22
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
- 150000002148 esters Chemical class 0.000 description 19
- 239000011541 reaction mixture Substances 0.000 description 18
- 239000000741 silica gel Substances 0.000 description 17
- 229910002027 silica gel Inorganic materials 0.000 description 17
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 15
- 230000008569 process Effects 0.000 description 15
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- 239000011734 sodium Substances 0.000 description 14
- TVZRAEYQIKYCPH-UHFFFAOYSA-N 3-(trimethylsilyl)propane-1-sulfonic acid Chemical compound C[Si](C)(C)CCCS(O)(=O)=O TVZRAEYQIKYCPH-UHFFFAOYSA-N 0.000 description 13
- 239000003054 catalyst Substances 0.000 description 13
- 238000003756 stirring Methods 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 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
- 239000012044 organic layer Substances 0.000 description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
- 239000003480 eluent Substances 0.000 description 11
- 239000007787 solid Substances 0.000 description 11
- FKENQMMABCRJMK-RITPCOANSA-N sulbactam Chemical compound O=S1(=O)C(C)(C)[C@H](C(O)=O)N2C(=O)C[C@H]21 FKENQMMABCRJMK-RITPCOANSA-N 0.000 description 11
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- 229930182555 Penicillin Natural products 0.000 description 9
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
- 230000000844 anti-bacterial effect Effects 0.000 description 8
- 239000000284 extract Substances 0.000 description 8
- 238000001727 in vivo Methods 0.000 description 8
- 239000012442 inert solvent Substances 0.000 description 8
- 229910052763 palladium Inorganic materials 0.000 description 8
- 150000003254 radicals Chemical class 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- 229940126085 β‑Lactamase Inhibitor Drugs 0.000 description 8
- 108090000204 Dipeptidase 1 Proteins 0.000 description 7
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 7
- 102000006635 beta-lactamase Human genes 0.000 description 7
- 238000004587 chromatography analysis Methods 0.000 description 7
- 238000004440 column chromatography Methods 0.000 description 7
- 230000000694 effects Effects 0.000 description 7
- RBKMMJSQKNKNEV-RITPCOANSA-N penicillanic acid Chemical compound OC(=O)[C@H]1C(C)(C)S[C@@H]2CC(=O)N21 RBKMMJSQKNKNEV-RITPCOANSA-N 0.000 description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
- SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 6
- 239000012452 mother liquor Substances 0.000 description 6
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 6
- 241000894006 Bacteria Species 0.000 description 5
- 239000007818 Grignard reagent Substances 0.000 description 5
- 241000699670 Mus sp. Species 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
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Classifications
-
- 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
-
- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/425—Thiazoles
- A61K31/429—Thiazoles condensed with heterocyclic ring systems
- A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D499/00—Heterocyclic compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula:, e.g. penicillins, penems; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Medicinal Preparation (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Applications Claiming Priority (8)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US33879782A | 1982-01-11 | 1982-01-11 | |
| US338797 | 1982-01-11 | ||
| US38832482A | 1982-06-14 | 1982-06-14 | |
| US06/388,323 US4427678A (en) | 1982-01-11 | 1982-06-14 | 6-Aminomethylpenicillanic acid 1,1-dioxide derivatives as beta-lactamase inhibitors |
| US388323 | 1982-06-14 | ||
| US388324 | 1982-06-14 | ||
| US06/434,371 US4452796A (en) | 1982-06-14 | 1982-10-21 | 6-Aminoalkylpenicillanic acid 1,1-dioxides as beta-lactamase inhibitors |
| US434371 | 1982-10-21 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS58126889A JPS58126889A (ja) | 1983-07-28 |
| JPH0689005B2 true JPH0689005B2 (ja) | 1994-11-09 |
Family
ID=27502592
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP58002768A Expired - Lifetime JPH0689005B2 (ja) | 1982-01-11 | 1983-01-11 | ベーターラクタマーゼ阻害剤としての６―アミノアルキルペニシラン酸１，１―ジオキシドおよび誘導体 |
Country Status (20)
| Country | Link |
|---|---|
| EP (1) | EP0084925B1 (enExample) |
| JP (1) | JPH0689005B2 (enExample) |
| AU (1) | AU538468B2 (enExample) |
| BG (1) | BG42676A3 (enExample) |
| CA (1) | CA1190921A (enExample) |
| DD (2) | DD218365A5 (enExample) |
| DE (1) | DE3362826D1 (enExample) |
| DK (1) | DK166883B1 (enExample) |
| ES (2) | ES8403489A1 (enExample) |
| FI (1) | FI79112C (enExample) |
| GR (1) | GR77152B (enExample) |
| HU (1) | HU189211B (enExample) |
| IE (1) | IE54390B1 (enExample) |
| IL (1) | IL67647A (enExample) |
| NO (6) | NO830046L (enExample) |
| NZ (1) | NZ202982A (enExample) |
| PL (1) | PL142315B1 (enExample) |
| PT (1) | PT76077B (enExample) |
| RO (2) | RO87705A (enExample) |
| YU (1) | YU43646B (enExample) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4499017A (en) * | 1983-06-06 | 1985-02-12 | Pfizer Inc. | Beta-lactamase inhibiting 6-(alkoxyamino-methyl) penicillanic acid 1,1-dioxide and derivatives |
| US4502990A (en) * | 1983-06-06 | 1985-03-05 | Pfizer Inc. | Process for 6-(aminomethyl)penicillanic acid 1,1-dioxide and derivatives thereof |
| JPS60239489A (ja) * | 1984-05-15 | 1985-11-28 | Meiji Seika Kaisha Ltd | ６−エピペニシリンスルホン化合物及びその製造方法 |
| GB2206579B (en) * | 1987-07-10 | 1991-05-29 | Erba Farmitalia | 6a and 6b-(substituted methyl)-penicillanic acid derivatives |
| US8415339B2 (en) * | 2007-05-21 | 2013-04-09 | Hans Rudolf Pfaendler | Bactericidal anti-MRSA active pharmaceutical composition containing carbapenems |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4237051A (en) * | 1979-04-19 | 1980-12-02 | Schering Corporation | Stereospecific production of 6- or 7-carbon-substituted-β-lactams |
| DE2927004A1 (de) * | 1979-07-04 | 1981-05-27 | Bayer Ag, 5090 Leverkusen | Penicillansaeure-1,1-dioxide, ihre herstellung und ihre verwendung als arzneimittel als arzneimittel |
| US4287181A (en) * | 1979-10-22 | 1981-09-01 | Pfizer Inc. | Derivatives of 6β-hydroxyalkylpenicillanic acids as β-lactamase inhibitors |
-
1983
- 1983-01-04 RO RO83113375A patent/RO87705A/ro unknown
- 1983-01-04 RO RO109609A patent/RO84910B/ro unknown
- 1983-01-05 DE DE8383300042T patent/DE3362826D1/de not_active Expired
- 1983-01-05 EP EP83300042A patent/EP0084925B1/en not_active Expired
- 1983-01-07 GR GR70215A patent/GR77152B/el unknown
- 1983-01-07 NO NO830046A patent/NO830046L/no unknown
- 1983-01-10 BG BG059284A patent/BG42676A3/xx unknown
- 1983-01-10 FI FI830081A patent/FI79112C/fi not_active IP Right Cessation
- 1983-01-10 YU YU44/83A patent/YU43646B/xx unknown
- 1983-01-10 CA CA000419181A patent/CA1190921A/en not_active Expired
- 1983-01-10 AU AU10232/83A patent/AU538468B2/en not_active Ceased
- 1983-01-10 PT PT76077A patent/PT76077B/pt not_active IP Right Cessation
- 1983-01-10 IE IE42/83A patent/IE54390B1/en not_active IP Right Cessation
- 1983-01-10 DK DK007483A patent/DK166883B1/da active
- 1983-01-10 HU HU8370A patent/HU189211B/hu not_active IP Right Cessation
- 1983-01-10 IL IL67647A patent/IL67647A/xx not_active IP Right Cessation
- 1983-01-10 NZ NZ202982A patent/NZ202982A/en unknown
- 1983-01-11 DD DD83262053A patent/DD218365A5/de not_active IP Right Cessation
- 1983-01-11 PL PL1983240108A patent/PL142315B1/pl unknown
- 1983-01-11 JP JP58002768A patent/JPH0689005B2/ja not_active Expired - Lifetime
- 1983-01-11 ES ES518912A patent/ES8403489A1/es not_active Expired
- 1983-01-11 DD DD83247166A patent/DD209462A5/de not_active IP Right Cessation
- 1983-08-30 ES ES525238A patent/ES525238A0/es active Granted
- 1983-09-22 NO NO833415A patent/NO833415L/no unknown
- 1983-09-22 NO NO833416A patent/NO833416L/no unknown
-
1984
- 1984-03-20 NO NO841070A patent/NO841070L/no unknown
- 1984-03-20 NO NO841069A patent/NO841069L/no unknown
- 1984-03-20 NO NO841068A patent/NO841068L/no unknown
Also Published As
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| JPH0475238B2 (enExample) |