Pyrrolo[1,2-a][1,4]benzodiazepine: a novel class of non-azole anti-dermatophyte anti-fungal agents.
Broad screening revealed compound 1a to be a novel anti-fungal agent with high specificity towards dermatophytes. The anti-fungal structure-activity relationship of this novel class of 5,6-dihydro-4H-pyrrolo[1,2-a][1,4]benzodiazepines is described together with its mode of action that appeared to be the inhibition of squalene epoxidase. Preliminary in vivo results of the most active compounds are also reported.
Meerpoel
Lieven
L
Johnson & Johnson Pharmaceutical Research & Development, A Division of Janssen Pharmaceutica N.V., Turnhoutseweg 30, B-2340 Beerse, Belgium. lmeerpoe@prdbe.jnj.com
Van Gestel
Jef
J
Van Gerven
Frans
F
Woestenborghs
Filip
F
Marichal
Patrick
P
Sipido
Vic
V
Terence
Gilkerson
G
Nash
Roger
R
Corens
David
D
Richards
Ray D
RD
D000935:Antifungal Agents / Q000138:chemical synthesis / Q000145:classification* / Q000494:pharmacology*; D003883:Arthrodermataceae / Q000187:drug effects*; D001381:Azepines / Q000138:chemical synthesis / Q000145:classification / Q000494:pharmacology*; D015195:Drug Design; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011758:Pyrroles / Q000138:chemical synthesis / Q000145:classification / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000935:Antifungal Agents; D001381:Azepines; D011758:Pyrroles; C506245:Pyrrolo(1,2-a)(1,4)benzodiazepine