Quantitative Structure-Activity Relationships of Antibacterial Agents, 7-Heterocyclic Amine Substituted 1-Cyclopropyl-6,8-difluoro-4-oxoquinoline-3-carboxylic Acids.

摘要: Quantitative structure-activity relationships (QSAR) of various 7-(3-substituted-azetidin-1-yl)-1-cyclopropyl-6,8-difluoro-1,4-dih ydro-4- oxoquinoline-3-carboxylic acids, 14-25, were studied to clarify the structural requirements for 3-substituted azetidines potentiate antibacterial activity. A good parabolic relationship seemed exist between relative mean activity indices against five representative gram-negative bacteria, GNM, and calculated hydrophobic parameters, CLOG P, these molecules. The P value most potent derivative was predicted be around 2.3. On other hand, gram-positive indices, GPM, remained high rather constant regardless variation in azetidine moiety. In order confirm findings, QSAR analysis extended with success quinolonecarboxylic 26-34, which bear substituted pyrrolidine, piperazine piperidine derivatives instead azetidines. findings showed that introduction any amide substituent group heterocyclic amine moieties would lead marked decrease whereas incorporation some amino groups at a position two or three carbons remote from N-1 resulted great enhancement GNM. As quinolones exhibited somewhat low vivo activities, possibly reflecting their lesser bioavailability, we finally selected 3-amino-4-methoxypyrrolidine as one promising C-7 based on our analysis.