Novel antifungals based on 4-substituted imidazole: a combinatorial chemistry approach to lead discovery and optimization.
A series of 4-substituted imidazole sulfonamides has been prepared by solid-phase chemistry. These compounds were found to have good in vitro antifungal activity and constitute the first examples of C-linked azoles with such activity. The most potent inhibitor (30) demonstrated inhibition of key Candida strains at an in vitro concentration of < 100nM and compared favorably with in vitro potency of itraconazole.
Saha
A K
AK
Drug Discovery, Janssen Research Foundation, Spring House, PA 19477, USA. asaha@prius.jnj.com
Liu
L
L
Simoneaux
R L
RL
Kukla
M J
MJ
Marichal
P
P
Odds
F
F
D000935:Antifungal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002175:Candida / Q000187:drug effects*; D020650:Combinatorial Chemistry Techniques; D015195:Drug Design; D004875:Ergosterol / Q000096:biosynthesis; D005658:Fungi / Q000187:drug effects; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D000935:Antifungal Agents; D007093:Imidazoles; D004875:Ergosterol