Iclaprim, a novel diaminopyrimidine with potent activity on trimethoprim sensitive and resistant bacteria.
Iclaprim, a new selective dihydrofolate inhibitor was synthesized based on rational drug design. Iclaprim's interaction with a resistant Staphylococcus aureus dihydrofolate reductase (DHFR) is outlined in comparison to trimethoprim (TMP). This compound is active against methicillin, TMP and vancomycin resistant strains. Arpida Ltd. is developing Iclaprim for serious hospital infections from Gram-positive pathogens and respiratory tract infections.
Schneider
Peter
P
Arpida Ltd, Dammstrasse 36, CH-4142, Muenchenstein, Switzerland. pschneider@arpida.ch
Hawser
Stephen
S
Islam
Khalid
K
D000818:Animals; D024881:Drug Resistance, Bacterial; D005493:Folic Acid Antagonists / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000382:microbiology; D016106:Methicillin Resistance; D051379:Mice; D008826:Microbial Sensitivity Tests; D011743:Pyrimidines / Q000494:pharmacology*; D018805:Sepsis / Q000188:drug therapy; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000201:enzymology; D013329:Structure-Activity Relationship; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry* / Q000378:metabolism; D014296:Trimethoprim Resistance; D014640:Vancomycin / Q000009:adverse effects*
D005493:Folic Acid Antagonists; D011743:Pyrimidines; C486448:iclaprim; D014640:Vancomycin; D013762:Tetrahydrofolate Dehydrogenase