STUDIES ON CONDENSED-HETEROCYCLIC AZOLIUM CEPHALOSPORINS .2. SYNTHESIS AND ANTIBACTERIAL ACTIVITY OF 7-BETA-[2-(2-AMINOTHIAZOL-4-YL)-2(Z)-ALKOXYIMINOACETAMIDO]-3-(CONDENSED-HETEROCYCLIC AZOLIUM)METHYL-3-CEPHEM-4-CARBOXYLATES

被引:6
作者
YOSHIMURA, Y [1 ]
MIYAKE, A [1 ]
NISHIMURA, T [1 ]
KAWAI, T [1 ]
YAMAOKA, M [1 ]
机构
[1] TAKEDA CHEM IND LTD,DIV RES & DEV,CHEM RES LABS,2-17-85 JUSOHONMACHI,YODOGAWA KU,OSAKA 532,JAPAN
关键词
D O I
10.7164/antibiotics.44.1394
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
From our series of studies on cephalosporins bearing condensed-heterocyclic azolium methyl groups at the 3 position in the cephalosporin nucleus, we describe here the synthesis and antibacterial activity of 7-beta-[2-(2-aminothiazol-4-yl)-2(Z)-alkoxyiminoacetamido]cephalosporins containing imidazo[1,5-a]pyridinium, imidazo[1,2-b]pyridazinium, imidazo[1,2-a]pyrimidinium, imidazo[1,2-c]pyrimidinium, and pyrazolo[1,5-a]pyridinium methyl groups at the 3 position. Among the cephalosporins tested, 7-beta-[2-(2-aminothiazol-4-yl)-2(Z)-methoxyiminoacetamido]-3(imidazo[1,5-a]pyridinium-2-yl) (1), (imidazo[1,2-b]pyridazinium-1-yl) (2), and (pyrazolo[1,5-a]-pyridinium-1-yl) (3)methyl-3-cephem-4-carboxylates showed potent antibacterial activity and broad antibacterial spectrum. The antibacterial activity of these cephalosporins (1 approximately 3) was superior to that of ceftazidime (CAZ). These results imply that the delocalization of the positive charge of the imidazo[1,5-a]pyridinium, pyrazolo[1,5-a]pyridinium and imidazo[1,2-b]pyridazinium groups leads to an expanded antibacterial spectrum and increased activity and that these condensed-heterocyclic compounds as well as imidazo[1,2-a]pyridine are effective moieties for improving antibacterial activity and spectrum.
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页码:1394 / 1405
页数:12
相关论文
共 12 条
[1]   HETEROCYCLIC SYSTEMS RELATED TO PYRROCOLINE .1. 2-3A-DIAZAINDENE [J].
BOWER, JD ;
RAMAGE, GR .
JOURNAL OF THE CHEMICAL SOCIETY, 1955, :2834-2837
[2]   HETEROCYCLIC SYSTEMS RELATED TO PYRROCOLINE .2. THE PREPARATION OF POLYAZAINDENES BY DEHYDROGENATIVE CYCLISATIONS [J].
BOWER, JD ;
RAMAGE, GR .
JOURNAL OF THE CHEMICAL SOCIETY, 1957, (NOV) :4506-4510
[3]  
FENTES O, 1975, J ORG CHEM, V40, P1210
[4]   SYNTHESIS OF PYRIDAZINE DERIVATIVE .15. SOME ELECTROPHILIC SUBSTITUTIONS ON IMIDAZO[1,2-B]-PYRIDAZINES [J].
KOBE, J ;
STANOVNIK, B ;
TISLER, M .
TETRAHEDRON, 1968, 24 (01) :239-+
[5]   SYNTHESIS OF SOME 6-METHOXYIMIDAZO[1,2-B]PYRILDAZINES [J].
LOMBARDINO, JG .
JOURNAL OF HETEROCYCLIC CHEMISTRY, 1968, 5 (01) :35-+
[6]  
MIYAKE A, 1989, 29TH INT C ANT AG CH, P182
[7]   STUDIES ON CONDENSED-HETEROCYCLIC AZOLIUM CEPHALOSPORINS .1. SYNTHESIS AND ANTIBACTERIAL ACTIVITY OF 7-BETA-[2-(2-AMINOTHIAZOL-4-YL)-2(Z)-ALKOXYIMINOACETAMIDO]-3-(IMIDAZO[1,2-A]PYRIDINIUM-1-YL)METHYL-3-CEPHEM-4-CARBOXYLATES [J].
NISHIMURA, T ;
YOSHIMURA, Y ;
YAMAOKA, M ;
KAWAI, T ;
MIYAKE, A .
JOURNAL OF ANTIBIOTICS, 1991, 44 (12) :1371-1393
[8]   10-PI-ELECTRON NITROGEN HETEROCYCLIC COMPOUNDS .8. SEMI-EMPIRICAL CALCULATIONS OF CHEMICAL-SHIFTS OF RING-PROTONS AND OF METHYL-PROTONS [J].
PAUDLER, WW ;
KUDER, JE .
JOURNAL OF HETEROCYCLIC CHEMISTRY, 1966, 3 (01) :33-&
[9]   10-PI-ELECTRON NITROGEN HETEROCYCLIC COMPOUNDS .4. SYNTHESIS BROMINATION AND NUCLEAR MAGNETIC RESONANCE SPECTRA OF SOME IMIDAZO[1,2-A]PYRIMIDINES [J].
PAUDLER, WW ;
KUDER, JE .
JOURNAL OF ORGANIC CHEMISTRY, 1966, 31 (03) :809-&
[10]   SYNTHESIS OF PYRIDAZINE DERIVATIVES .16. METHYL SUBSTITUTED IMIDAZO(1.2-B)PYRIDAZINES BY SYNTHESIS AND HOMOLYTIC METHYLATION [J].
POLLAK, A ;
STANOVNI.B ;
TISLER, M .
TETRAHEDRON, 1968, 24 (06) :2623-&