title: Novel antifungals based on 4-substituted imidazole: a combinatorial chemistry approach to lead discovery and optimization.
abstract: 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.
authors.affiliation: Drug Discovery, Janssen Research Foundation, Spring House, PA 19477, USA. asaha@prius.jnj.com
authors.forename: A K
authors.initials: AK
authors.lastname: Saha
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.forename: R L
authors.initials: RL
authors.lastname: Simoneaux
authors.forename: M J
authors.initials: MJ
authors.lastname: Kukla
authors.forename: P
authors.initials: P
authors.lastname: Marichal
authors.forename: F
authors.initials: F
authors.lastname: Odds
mesh_terms: 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
chemical_list: D000935:Antifungal Agents; D007093:Imidazoles; D004875:Ergosterol