Section 6 Synthetic antimicrobial agents Yun-Bi Lu, PhD 卢韵碧 Dept of Pharmacology, School of Medicine, Zhejiang University yunbi@zju.edu.cn
Synthetic antimicrobial agents Section 6 Yun-Bi Lu, PhD 卢韵碧 Dept. of Pharmacology, School of Medicine, Zhejiang University yunbi@zju.edu.cn
Contents Quinolones(喳诺酮粪) Sulfonamides(磺胺类) Other Synthetic antimicrobial Trimethoprim(甲氧苄) Nitrofurans(确基失喃类
• Quinolones ( 喹诺酮类) • Sulfonamides ( 磺胺类) • Other Synthetic antimicrobial Trimethoprim (甲氧苄啶) Nitrofurans (硝基呋喃类) Contents
Contents Quinolones(诺酮类) Sulfonamides(嘴胺类) Other Synthetic antimicrobial Trimethoprim(甲氧苄咬) Nitrofurans(硝基央喃类)
• Quinolones ( 喹诺酮类) • Sulfonamides ( 磺胺类) • Other Synthetic antimicrobial Trimethoprim (甲氧苄啶) Nitrofurans (硝基呋喃类) Contents
From chloroquine to nalidixic acid nalidixic acid CH o chloroquine CH C? 1939 心1962 1958° C2H5 7-chloroquinoline (synthesis intermediate found to display antibacterial activity)
From chloroquine to nalidixic acid
喹诺酮类( Quinolones) Generation Example time Nalidixic acid纂啶酸1962 2 Pipemidic acid呲哌酸1973 3 Norfloxacin诺氟沙星 4 Clinafloxacin克林泱星1990s
Generation Example time 1 Nalidixic acid 萘啶酸 1962 2 Pipemidic acid 吡哌酸 1973 3 Norfloxacin 诺氟沙星 4 Clinfloxacin 克林沙星 1990’s 喹诺酮类 (Quinolones)
First generation fluoroquinolones norfloxacin ciprofloxacin piperazine cyclo propyl x methyl H3c pefloxacin ofloxacin morpholine
First generation fluoroquinolones
From ofloxacin to levofloxacin Ofloxacin is a racemic mixture H Levofloxacin is the pure(-)S isomer The active form of ofloxacin is the(-)S isomer Eur. pat. 206, 283 to Daiichi, 1987
From ofloxacin to levofloxacin
Fluoroquinolones c H CO sparfloxacin moxifloxacin 0.125-0.5 0.01-0.5 ciprofloxacin 05-2 temafloxacin trovafloxacin 05-1 0.007-0.25
Fluoroquinolones
Fluoroquinolones broad antimicrobial activity effective after oral administration relatively few side effects resistance to their action does not develop rapidly
• broad antimicrobial activity • effective after oral administration • relatively few side effects • resistance to their action does not develop rapidly. Fluoroquinolones
General properties of Quinolones 1. Antimicrobial activity spectrum (1) bactericidal and have significant PAE. (2 aerobic G- bacteria, Pesudomonas aerobic Gt bacteria, Chlamydia spp.(A 原体), Legionella pneumophila(军团菌) anaerobic bacteria, mycobacteria(分枝杆 #), multiple-resistance strains
1. Antimicrobial activity & spectrum: (1) bactericidal and have significant PAE. (2) aerobic G- bacteria, Pesudomonas, aerobic G+ bacteria, Chlamydia spp.（衣 原体）, Legionella pneumophila(军团菌) , anaerobic bacteria, mycobacteria(分枝杆 菌), multiple-resistance strains. General properties of Quinolones