Reference - Detail
|Author||Komoriya S, Odagiri T, Inagaki H, Nagamochi M, Miyauchi R, Yoshida KI, Kitamura T, Takahashi H.|
|Title||Discovery of Novel 7-[(1R,5S)-1-Amino-5-fluoro-3-azabicyclo[3.3.0]octan-3-yl]-6-fluoro-1-[(1R,2S)-2-fluorocyclopropane]-8-(methoxy or methyl)quinolones.|
|Journal||Chem Pharm Bull (Tokyo)|
A series of 8-methoxy or 8-methylquinolones bearing novel 3-aminooctahydrocyclopenta[c]pyrrole derivatives at the C-7 position was synthesized, and the pharmacological, physicochemical, and toxicological properties of the individual compounds were evaluated. Novel 8-methylquinolone 7, which includes a 3-amino-7-fluorooctahydrocyclopenta[c]pyrrole moiety at the C-7 position, showed potent antibacterial activity against both Gram-positive and negative pathogens. Compound 7 also demonstrated favorable pharmacokinetic and pharmacodynamic properties and an acceptably safe toxicological profile. Consequently, compound 7 was selected as a clinical candidate.
|MeSH||Animals Anti-Bacterial Agents / chemical synthesis Anti-Bacterial Agents / chemistry Anti-Bacterial Agents / pharmacology* CHO Cells Cricetulus DNA Topoisomerases / metabolism* Dose-Response Relationship, Drug Drug Discovery Ether-A-Go-Go Potassium Channels / antagonists & inhibitors* Ether-A-Go-Go Potassium Channels / genetics Ether-A-Go-Go Potassium Channels / metabolism Gram-Negative Bacteria / drug effects* Gram-Positive Bacteria / drug effects* Haplorhini Humans Male Mice Microbial Sensitivity Tests Molecular Structure Quinolones / chemical synthesis Quinolones / chemistry Quinolones / pharmacology* Rats Seizures / drug therapy* Stereoisomerism Structure-Activity Relationship Tissue Distribution Topoisomerase Inhibitors / chemical synthesis Topoisomerase Inhibitors / chemistry Topoisomerase Inhibitors / pharmacology*|