FLUORONAPHTHYRIDINES AND FLUOROQUINOLONES AS ANTIBACTERIAL AGENTS .3. SYNTHESIS AND STRUCTURE-ACTIVITY-RELATIONSHIPS OF NEW 1-(1,1-DIMETHYL-2-FLUOROETHYL), 1-[1-METHYL-1-(FLUOROMETHYL)-2-FLUOROETHYL], AND 1-[1,1-(DIFLUOROMETHYL)-2-FLUOROETHYL] SUBSTITUTED DERIVATIVES

被引：40

作者：

REMUZON, P ^{[1
]}

BOUZARD, D ^{[1
]}

DICESARE, P ^{[1
]}

ESSIZ, M ^{[1
]}

JACQUET, JP ^{[1
]}

KIECHEL, JR ^{[1
]}

LEDOUSSAL, B ^{[1
]}

KESSLER, RE ^{[1
]}

FUNGTOMC, J ^{[1
]}

机构：

[1] BRISTOL MYERS SQUIBB CO,DIV PHARMACEUT RES & DEV,WALLINGFORD,CT 06492

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1991年 / 34卷 / 01期

关键词：

D O I：

10.1021/jm00105a006

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of novel N-1-(mono-, -(di- and -(trifluoro-tert-butyl)quinolones and -naphthyridines has been prepared. Structure-activity relationship (SAR) studies indicated that the in vitro antibacterial potency was the following order: 1-(1,1-dimethyl-2-fluoroethyl) > 1-[1-methyl-1-(fluoromethyl)-2-fluoroethyl] > 1-[1,1-(difluoromethyl)-2-fluoroethyl] substituents. In the quinolone series the monofluoro-tert-butyl derivatives were found to possess better in vitro antibacterial activity than the nonfluorinated-tert-butyl equivalents. In vivo PD50 values of the 1-fluoro-tert-butyl-substituted derivatives reflect pharmacokinetic behavior and incomplete oral absorption.

引用

页码：29 / 37

页数：9

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