Anti-infectives A∥ rights re served Marketed product: rufloxacin CH COOH COOH CH2-N N n vivo P海医药工业研究院 PHARMACEUTCAL NDUSTRY
Anti-infectives All rights re served Marketed product: prufloxacin N O COOH F O CH2 N N S O CH3 O in vivo N O COOH F HN N S
Anti-infectives A∥ rights re served Structure-activity relationships Controls potency, Adds iram Positiye activity NH2>OHSCH3>H ssential for Gyrase Binding . il other gro and Bacterial Tranport No modifi Controls gyrase an less active Bacterial potency 5-100x more active than 5 any other groups F 5 C—OH Controls. Potency, Spectrum. Close to Gyrase fand pharmacokinetics Binding site 5-& 6-membered rings most active. Basic R 7 R2 to R1 or C3 acid are active oral efficacy. Best Gram(+) Potency Controls R Pharmacokinetics. and Anaerobe Activity Controls Potency For Oral Activity Some effect on Pharmacokinetics Best Gram()Potency CF CCbN>COMe>CH For Activity For Best Anaerobe Activity CcCF≥COMe>>CHN 厶 cH1>◇>CH3CH2 Much less active are: CH3 CH3 Ring alkylation CCH3, CCN, CBr, CSR FCH2CH2 improves Gram CNH2, COH, CCH2OH O or N reduce activity activity and Tn P海医药工业研究院 SFPHGRMACEUTCAL NDUSTRY
Anti-infectives All rights re served Structure-activity relationships
Anti-infectives A∥ rights re served Structure-toxicity relationships Influence Phototoxicity and Genetic Toxicity Metal Rinding and chelating site For Phototoxicity Controls interactions with CH3>>H>NH2 antiacids, milk iron supplements Most divalent metals Ca*. Fe++ Zn++ or Genetic Toxicity Effect of F on sidc effect reduce oral absorption CH3>NH>F profile has not been reported R F C-OH Controls gaba binding maior NSAID Interaction Maior). No side effects associated with Maior). genetic Toxicity尽7 R .2 this position For GABA Binding pip>pyrp>subst pip or pyrr For Nsaid interaction pip>>pymsubst pip or pyrr Phototoxicity major For Theophyline Interaction:// and Genetic Toxicity Controls Theophylline pyrr2pip>subst pyrr or pip Minor effect on Interaction and genetic Toxicity For Genetic Toxicity NSAID interactions For Theophylline Interaction pyrr>>pip>subst pyr >subst pip CESCC-NCH)COM, cce For Ge h CH3CH2>2, 4-diFPh>FCH, CH2- CP>CCL>COMe>N>CH >2, 4-diFPh CH2CH PHARMACEU NDUSTRY
Anti-infectives All rights re served Structure-toxicity relationships
Anti-infectives A∥ rights re served 甲磺酸帕珠沙星 pazufloxacin 日本富山化学工业公司开发 2002年4月上市 F COOH HN MP士海医药工业研究院 NDUSTRY
Anti-infectives All rights re served 甲磺酸帕珠沙星 pazufloxacin 日本富山化学工业公司开发 2002年4月 上市 N O O COOH F H2 N