NO325687B1 - Antibakterielle, substituerte 7-acylamino-3-(metylhydrazono)metyl-cefalosporiner fremgangsmate for fremstilling derav og mellomprodukter, anvendelse av forbindelsene samt farmasoytiske preparater inneholdende disse - Google Patents
Antibakterielle, substituerte 7-acylamino-3-(metylhydrazono)metyl-cefalosporiner fremgangsmate for fremstilling derav og mellomprodukter, anvendelse av forbindelsene samt farmasoytiske preparater inneholdende disse Download PDFInfo
- Publication number
- NO325687B1 NO325687B1 NO19994719A NO994719A NO325687B1 NO 325687 B1 NO325687 B1 NO 325687B1 NO 19994719 A NO19994719 A NO 19994719A NO 994719 A NO994719 A NO 994719A NO 325687 B1 NO325687 B1 NO 325687B1
- Authority
- NO
- Norway
- Prior art keywords
- compound
- methyl
- formula
- alkyl
- piperazine
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims description 80
- -1 methylhydrazono Chemical group 0.000 title claims description 49
- 238000000034 method Methods 0.000 title claims description 13
- 238000002360 preparation method Methods 0.000 title claims description 6
- 230000000844 anti-bacterial effect Effects 0.000 title description 3
- 229940124587 cephalosporin Drugs 0.000 title description 3
- 239000000543 intermediate Substances 0.000 title 1
- 239000008194 pharmaceutical composition Substances 0.000 title 1
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 55
- 150000003839 salts Chemical class 0.000 claims description 27
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 25
- 125000000217 alkyl group Chemical group 0.000 claims description 23
- 125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims description 13
- 239000012453 solvate Substances 0.000 claims description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
- VUWZPRWSIVNGKG-UHFFFAOYSA-N fluoromethane Chemical compound F[CH2] VUWZPRWSIVNGKG-UHFFFAOYSA-N 0.000 claims description 9
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 claims description 7
- 150000003840 hydrochlorides Chemical class 0.000 claims description 7
- 125000004423 acyloxy group Chemical group 0.000 claims description 6
- 125000005194 alkoxycarbonyloxy group Chemical group 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 6
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 6
- 125000005633 phthalidyl group Chemical group 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 5
- 208000035143 Bacterial infection Diseases 0.000 claims description 4
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 4
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 4
- 241000588748 Klebsiella Species 0.000 claims description 4
- 241000194017 Streptococcus Species 0.000 claims description 4
- 150000001768 cations Chemical class 0.000 claims description 4
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
- 241000588914 Enterobacter Species 0.000 claims description 3
- 241000194033 Enterococcus Species 0.000 claims description 3
- 241000606790 Haemophilus Species 0.000 claims description 3
- 241000588621 Moraxella Species 0.000 claims description 3
- 241000588769 Proteus <enterobacteria> Species 0.000 claims description 3
- 241000589516 Pseudomonas Species 0.000 claims description 3
- 241000607142 Salmonella Species 0.000 claims description 3
- 241000607720 Serratia Species 0.000 claims description 3
- 241000191940 Staphylococcus Species 0.000 claims description 3
- 125000006307 alkoxy benzyl group Chemical group 0.000 claims description 3
- 125000003277 amino group Chemical group 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 229910052757 nitrogen Inorganic materials 0.000 claims description 3
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims description 3
- GEXJFIOPGAASTP-UHFFFAOYSA-N $l^{1}-azanylethane Chemical compound CC[N] GEXJFIOPGAASTP-UHFFFAOYSA-N 0.000 claims description 2
- 125000004849 alkoxymethyl group Chemical group 0.000 claims description 2
- 230000001580 bacterial effect Effects 0.000 claims description 2
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
- 238000002955 isolation Methods 0.000 claims description 2
- 125000004043 oxo group Chemical group O=* 0.000 claims description 2
- 241000894007 species Species 0.000 claims description 2
- VNZAURNTTOSQRE-HLPIIRDBSA-N (6R)-7-[[(2Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(fluoromethoxyimino)acetyl]amino]-3-[(E)-[methyl(piperazine-1-carboximidoyl)hydrazinylidene]methyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound NC1=NC(=NS1)/C(/C(=O)NC1[C@@H]2N(C(=C(CS2)/C=N/N(C)C(N2CCNCC2)=N)C(=O)O)C1=O)=N/OCF VNZAURNTTOSQRE-HLPIIRDBSA-N 0.000 claims 1
- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 claims 1
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 33
- 239000000203 mixture Substances 0.000 description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 19
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- 125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 13
- 239000002904 solvent Substances 0.000 description 12
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 150000002148 esters Chemical class 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 241000191967 Staphylococcus aureus Species 0.000 description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 6
- 239000000843 powder Substances 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- 239000012071 phase Substances 0.000 description 4
- 239000011734 sodium Substances 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- KLSJWNVTNUYHDU-UHFFFAOYSA-N Amitrole Chemical compound NC1=NC=NN1 KLSJWNVTNUYHDU-UHFFFAOYSA-N 0.000 description 3
- 241000894006 Bacteria Species 0.000 description 3
- 241000194032 Enterococcus faecalis Species 0.000 description 3
- 241000606768 Haemophilus influenzae Species 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- 241000124008 Mammalia Species 0.000 description 3
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 description 3
- 101100073357 Streptomyces halstedii sch2 gene Proteins 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 229960004261 cefotaxime Drugs 0.000 description 3
- 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 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000012141 concentrate Substances 0.000 description 3
- 229960003085 meticillin Drugs 0.000 description 3
- NOMIHYARNATOBH-UHFFFAOYSA-N n-amino-n-(piperazin-1-ylmethylideneamino)ethanamine Chemical compound CCN(N)N=CN1CCNCC1 NOMIHYARNATOBH-UHFFFAOYSA-N 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- 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 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- 241000588724 Escherichia coli Species 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 241000588747 Klebsiella pneumoniae Species 0.000 description 2
- 241000699670 Mus sp. Species 0.000 description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 2
- 239000000010 aprotic solvent Substances 0.000 description 2
- 229920001429 chelating resin Polymers 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- PMOWTIHVNWZYFI-WAYWQWQTSA-N cis-2-coumaric acid Chemical compound OC(=O)\C=C/C1=CC=CC=C1O PMOWTIHVNWZYFI-WAYWQWQTSA-N 0.000 description 2
- 229940032049 enterococcus faecalis Drugs 0.000 description 2
- 235000019253 formic acid Nutrition 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 239000013067 intermediate product Substances 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 229910052751 metal Inorganic materials 0.000 description 2
- 239000002184 metal Substances 0.000 description 2
- SNVLJLYUUXKWOJ-UHFFFAOYSA-N methylidenecarbene Chemical compound C=[C] SNVLJLYUUXKWOJ-UHFFFAOYSA-N 0.000 description 2
- 230000000813 microbial effect Effects 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 230000004962 physiological condition Effects 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 229960003975 potassium Drugs 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 2
- 229960004919 procaine Drugs 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 238000001256 steam distillation Methods 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- ZSGNKOMGAXONLJ-WTDSWWLTSA-N (2z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-(fluoromethoxyimino)acetyl chloride Chemical compound NC1=NC(C(=N\OCF)\C(Cl)=O)=NS1 ZSGNKOMGAXONLJ-WTDSWWLTSA-N 0.000 description 1
- FZDRVLJSDYQRPO-HWZXHQHMSA-N (6r)-4-methyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound OC(=O)C1=CC(C)S[C@@H]2CC(=O)N21 FZDRVLJSDYQRPO-HWZXHQHMSA-N 0.000 description 1
- TWAHQTDAFGRKLL-HWZXHQHMSA-N (6r)-7-amino-3-formyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound S1CC(C=O)=C(C(O)=O)N2C(=O)C(N)[C@H]21 TWAHQTDAFGRKLL-HWZXHQHMSA-N 0.000 description 1
- 125000004209 (C1-C8) alkyl group Chemical group 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
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 1
- MSSDTZLYNMFTKN-UHFFFAOYSA-N 1-Piperazinecarboxaldehyde Chemical compound O=CN1CCNCC1 MSSDTZLYNMFTKN-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 229930186147 Cephalosporin Natural products 0.000 description 1
- BWLUMTFWVZZZND-UHFFFAOYSA-N Dibenzylamine Chemical compound C=1C=CC=CC=1CNCC1=CC=CC=C1 BWLUMTFWVZZZND-UHFFFAOYSA-N 0.000 description 1
- 241000588697 Enterobacter cloacae Species 0.000 description 1
- 241000194031 Enterococcus faecium Species 0.000 description 1
- 241000588722 Escherichia Species 0.000 description 1
- 241000192125 Firmicutes Species 0.000 description 1
- 241000579664 Grateloupia proteus Species 0.000 description 1
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical class NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 241000588655 Moraxella catarrhalis Species 0.000 description 1
- RKOTXQYWCBGZLP-UHFFFAOYSA-N N-[(2,4-difluorophenyl)methyl]-2-ethyl-9-hydroxy-3-methoxy-1,8-dioxospiro[3H-pyrido[1,2-a]pyrazine-4,3'-oxolane]-7-carboxamide Chemical compound CCN1C(OC)C2(CCOC2)N2C=C(C(=O)NCC3=C(F)C=C(F)C=C3)C(=O)C(O)=C2C1=O RKOTXQYWCBGZLP-UHFFFAOYSA-N 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- 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 description 1
- 241000293869 Salmonella enterica subsp. enterica serovar Typhimurium Species 0.000 description 1
- 206010040047 Sepsis Diseases 0.000 description 1
- 241000607715 Serratia marcescens Species 0.000 description 1
- 240000004922 Vigna radiata Species 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 238000002814 agar dilution Methods 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 230000000845 anti-microbial effect Effects 0.000 description 1
- 239000012296 anti-solvent Substances 0.000 description 1
- 238000009635 antibiotic susceptibility testing Methods 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229910052788 barium Inorganic materials 0.000 description 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
- 150000003939 benzylamines Chemical class 0.000 description 1
- NHOWLEZFTHYCTP-UHFFFAOYSA-N benzylhydrazine Chemical class NNCC1=CC=CC=C1 NHOWLEZFTHYCTP-UHFFFAOYSA-N 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 150000001780 cephalosporins Chemical class 0.000 description 1
- 238000006757 chemical reactions by type Methods 0.000 description 1
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000004663 dialkyl amino group Chemical group 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 238000003818 flash chromatography Methods 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 229940047650 haemophilus influenzae Drugs 0.000 description 1
- 235000012907 honey Nutrition 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical class I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- HVTICUPFWKNHNG-UHFFFAOYSA-N iodoethane Chemical compound CCI HVTICUPFWKNHNG-UHFFFAOYSA-N 0.000 description 1
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- PGWIRNGXENTUQP-UHFFFAOYSA-N n-amino-1-(4-methoxyphenyl)-n-(piperazin-1-ylmethylideneamino)methanamine Chemical compound C1=CC(OC)=CC=C1CN(N)N=CN1CCNCC1 PGWIRNGXENTUQP-UHFFFAOYSA-N 0.000 description 1
- MFKKDOJOXBELPI-UHFFFAOYSA-N n-amino-n,n'-dimethylpiperazine-1-carboximidamide Chemical compound CN=C(N(C)N)N1CCNCC1 MFKKDOJOXBELPI-UHFFFAOYSA-N 0.000 description 1
- HOGSQCNFNURFMD-UHFFFAOYSA-N n-amino-n-(piperazin-1-ylmethylideneamino)methanamine Chemical compound CN(N)N=CN1CCNCC1 HOGSQCNFNURFMD-UHFFFAOYSA-N 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
- 159000000001 potassium salts Chemical class 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 208000013223 septicemia Diseases 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 238000000935 solvent evaporation Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- 125000004954 trialkylamino group Chemical group 0.000 description 1
- 241001148471 unidentified anaerobic bacterium Species 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 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
- C07D501/38—Methylene radicals, substituted by nitrogen atoms; Lactams thereof with the 2-carboxyl group; Methylene radicals substituted by nitrogen-containing hetero rings attached by the ring nitrogen atom; Quaternary compounds thereof
- C07D501/46—Methylene radicals, substituted by nitrogen atoms; Lactams thereof with the 2-carboxyl group; Methylene radicals substituted by nitrogen-containing hetero rings attached by the ring nitrogen atom; Quaternary compounds thereof with the 7-amino radical acylated by carboxylic acids containing hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/20—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof
- C07D295/215—Radicals derived from nitrogen analogues of carbonic acid
-
- 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
-
- 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
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (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)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AT54797A AT405180B (de) | 1997-04-01 | 1997-04-01 | Neue derivate von substituierten 3-cephem-4-carbonsäurederivaten und verfahren zu deren herstellung |
| AT54897 | 1997-04-01 | ||
| AT54697 | 1997-04-01 | ||
| PCT/EP1998/001890 WO1998043981A1 (en) | 1997-04-01 | 1998-04-01 | Antibacterial substituted 7-acylamino-3-(methylhydrazono)methyl -cephalosporins and intermediates |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO994719D0 NO994719D0 (no) | 1999-09-28 |
| NO994719L NO994719L (no) | 1999-09-28 |
| NO325687B1 true NO325687B1 (no) | 2008-07-07 |
Family
ID=27146440
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19994719A NO325687B1 (no) | 1997-04-01 | 1999-09-28 | Antibakterielle, substituerte 7-acylamino-3-(metylhydrazono)metyl-cefalosporiner fremgangsmate for fremstilling derav og mellomprodukter, anvendelse av forbindelsene samt farmasoytiske preparater inneholdende disse |
Country Status (21)
| Country | Link |
|---|---|
| EP (2) | EP0973780B1 (ko) |
| JP (2) | JP3363157B2 (ko) |
| KR (2) | KR20040000380A (ko) |
| CN (1) | CN1117095C (ko) |
| AU (1) | AU734897B2 (ko) |
| BR (1) | BR9807913A (ko) |
| CA (1) | CA2284501C (ko) |
| DE (1) | DE69816057T2 (ko) |
| DK (1) | DK0973780T3 (ko) |
| ES (1) | ES2203955T3 (ko) |
| HK (1) | HK1026692A1 (ko) |
| ID (1) | ID22441A (ko) |
| IL (1) | IL131849A (ko) |
| NO (1) | NO325687B1 (ko) |
| NZ (1) | NZ337732A (ko) |
| PL (1) | PL200130B1 (ko) |
| PT (1) | PT973780E (ko) |
| RU (1) | RU2201933C2 (ko) |
| SK (1) | SK133099A3 (ko) |
| TR (1) | TR199902387T2 (ko) |
| WO (1) | WO1998043981A1 (ko) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AT406772B (de) * | 1998-03-23 | 2000-08-25 | Biochemie Gmbh | Antibakterielle 7-acylamino-3-iminomethyl- cephalosporine und verfahren zu deren herstellung |
| US6504025B2 (en) * | 2000-05-24 | 2003-01-07 | Basilea Pharmaceutica Ag | Process for the preparation of vinyl-pyrrolidinone cephalosporin derivatives |
| AT413282B (de) * | 2002-02-01 | 2006-01-15 | Sandoz Ag | Kristalline salze der 7-(((5-amino-1,2,4-thiadiazol-3-yl) (fluoromethoxy-imino)acetyl)amino)-3- ((imino-1-piperazinylmethyl) |
| BR112022004107A2 (pt) | 2019-09-06 | 2022-05-31 | Nabriva Therapeutics GmbH | Conjugados de cefalosporina de sideróforo e seus usos |
| CN111187281B (zh) * | 2020-02-11 | 2023-03-14 | 广西科技大学 | 含胍基的头孢菌素衍生物及其制备方法 |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| HU190639B (en) * | 1983-12-12 | 1986-09-29 | Gyogyszerkutato Intezet Kv,Hu | Process for production of new aminoguanidin derivatives |
| FI851934L (fi) * | 1984-05-30 | 1985-12-01 | Ici Plc | Kefalosporinderivat. |
| HUP9801387A3 (en) * | 1995-05-11 | 2000-12-28 | Sandoz Ag | Antibacterial cephalosporins |
-
1998
- 1998-04-01 CN CN98803820A patent/CN1117095C/zh not_active Expired - Fee Related
- 1998-04-01 PL PL336004A patent/PL200130B1/pl unknown
- 1998-04-01 KR KR10-2003-7001223A patent/KR20040000380A/ko not_active Application Discontinuation
- 1998-04-01 ES ES98922631T patent/ES2203955T3/es not_active Expired - Lifetime
- 1998-04-01 CA CA002284501A patent/CA2284501C/en not_active Expired - Fee Related
- 1998-04-01 RU RU99122749/04A patent/RU2201933C2/ru not_active IP Right Cessation
- 1998-04-01 KR KR10-1999-7008385A patent/KR100481143B1/ko not_active IP Right Cessation
- 1998-04-01 ID IDW991129A patent/ID22441A/id unknown
- 1998-04-01 NZ NZ337732A patent/NZ337732A/en unknown
- 1998-04-01 DK DK98922631T patent/DK0973780T3/da active
- 1998-04-01 BR BR9807913-1A patent/BR9807913A/pt not_active Application Discontinuation
- 1998-04-01 AU AU75213/98A patent/AU734897B2/en not_active Ceased
- 1998-04-01 EP EP98922631A patent/EP0973780B1/en not_active Expired - Lifetime
- 1998-04-01 IL IL13184998A patent/IL131849A/en not_active IP Right Cessation
- 1998-04-01 DE DE69816057T patent/DE69816057T2/de not_active Expired - Lifetime
- 1998-04-01 PT PT98922631T patent/PT973780E/pt unknown
- 1998-04-01 SK SK1330-99A patent/SK133099A3/sk unknown
- 1998-04-01 WO PCT/EP1998/001890 patent/WO1998043981A1/en not_active Application Discontinuation
- 1998-04-01 JP JP54116298A patent/JP3363157B2/ja not_active Expired - Fee Related
- 1998-04-01 TR TR1999/02387T patent/TR199902387T2/xx unknown
- 1998-04-01 EP EP03000220A patent/EP1300408A1/en not_active Ceased
-
1999
- 1999-09-28 NO NO19994719A patent/NO325687B1/no unknown
-
2000
- 2000-07-24 HK HK00104576A patent/HK1026692A1/xx unknown
-
2002
- 2002-03-08 JP JP2002064270A patent/JP2002316992A/ja not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| EP0973780B1 (en) | 2003-07-02 |
| KR20000076288A (ko) | 2000-12-26 |
| HK1026692A1 (en) | 2000-12-22 |
| AU7521398A (en) | 1998-10-22 |
| NZ337732A (en) | 2001-09-28 |
| BR9807913A (pt) | 2000-02-22 |
| DE69816057T2 (de) | 2004-04-15 |
| DE69816057D1 (de) | 2003-08-07 |
| CA2284501A1 (en) | 1998-10-08 |
| NO994719D0 (no) | 1999-09-28 |
| IL131849A0 (en) | 2001-03-19 |
| ID22441A (id) | 1999-10-14 |
| KR20040000380A (ko) | 2004-01-03 |
| WO1998043981A1 (en) | 1998-10-08 |
| EP0973780A1 (en) | 2000-01-26 |
| EP1300408A1 (en) | 2003-04-09 |
| PL336004A1 (en) | 2000-06-05 |
| JP2000514832A (ja) | 2000-11-07 |
| ES2203955T3 (es) | 2004-04-16 |
| PL200130B1 (pl) | 2008-12-31 |
| CA2284501C (en) | 2007-07-17 |
| KR100481143B1 (ko) | 2005-04-08 |
| AU734897B2 (en) | 2001-06-28 |
| SK133099A3 (en) | 2001-03-12 |
| RU2201933C2 (ru) | 2003-04-10 |
| NO994719L (no) | 1999-09-28 |
| PT973780E (pt) | 2003-11-28 |
| JP3363157B2 (ja) | 2003-01-08 |
| JP2002316992A (ja) | 2002-10-31 |
| TR199902387T2 (xx) | 2000-01-21 |
| IL131849A (en) | 2004-05-12 |
| CN1251591A (zh) | 2000-04-26 |
| DK0973780T3 (da) | 2003-10-27 |
| CN1117095C (zh) | 2003-08-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CS234015B2 (en) | Method of nwew acyloxyalkyl-6-(alpha,alpha-disubstited acetamide)penicillinates making | |
| Alagarsamy et al. | Synthesis, analgesic, anti-inflammatory and antibacterial activities of some novel 2-phenyl-3-substituted quinazolin-4 (3H) ones | |
| RU2183212C2 (ru) | Антибактериальные цефалоспорины, фармацевтическая композиция на их основе и способ лечения | |
| Alagarsamy et al. | Synthesis, analgesic, anti-inflammatory and antibacterial activities of some novel 2-methylthio-3-substituted quinazolin-4-(3H)-ones | |
| NO325687B1 (no) | Antibakterielle, substituerte 7-acylamino-3-(metylhydrazono)metyl-cefalosporiner fremgangsmate for fremstilling derav og mellomprodukter, anvendelse av forbindelsene samt farmasoytiske preparater inneholdende disse | |
| US4080451A (en) | Cephalosporin derivatives | |
| US4183925A (en) | 7-Aminophenylacetamido-Δ3 -cephem antibacterial agents and method of use | |
| US6693095B2 (en) | Antibacterial substituted 7-acylamino-3-(methylhydrazono) methyl-cephalosporins and intermediates | |
| US6440957B1 (en) | Cephalosporines having cyclic aminoguanidine substituents as antibiotics | |
| JPS62209082A (ja) | セフアロスポリン誘導体 | |
| CA1097652A (en) | Eprimerization process | |
| US4144240A (en) | Substituted mercaptothiadiazole compounds | |
| US4091027A (en) | 6'-Amino-spiro(cycloalkane-1,2'-penam)-3'-carboxylic acids | |
| US3847913A (en) | Cephalosporanic acid esters | |
| US20050043289A1 (en) | Crystalline hydrochloride of 7-(((5-amino-1,2,4-thiadiazol-3-yl) (fluoromethoxyimino)acetyl)amino)-3-((imino-1-piperazinylmethyl)methylhydrazono)-methyl-3-cephem-4-carboxylic acid | |
| US6642378B1 (en) | Process for the synthesis of beta-lactam derivatives | |
| CZ345799A3 (cs) | Antibakteriální substituované 7-acylamino-3- (methylhydrazono)methylcefalosporiny a meziprodukty | |
| US20060205938A1 (en) | Monohydrate solvates of loracarbef | |
| EP0429999A1 (de) | Neue Cephalosporine, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel | |
| AU2003206809A1 (en) | Crystalline hydrochloride of 7-(((5-amino-1,2,4-thiadiazol-3-yl)(fluoromethoxyimino) acetyl) amino)-3- ((imino-1-piperazinylmethyl)methylhydrazono)-methyl-3-cephem-4-carboxylic acid | |
| KR20030076760A (ko) | 신규 세팔로스포린 화합물 및 그의 제조 방법 | |
| JPH02279673A (ja) | キノロン誘導体 | |
| JPH05306288A (ja) | セフェムエステル化合物の結晶 |