Synthesis and evaluation of a series of 1,4-diarylbutadienes for anticoccidial activity.
During the course of a collaborative screening program, a set of 1-phenyl-4-pyridyl-butadienes was found to exhibit in vitro activity against Eimeria tenella in a cell-based assay. Activity was dependent on the chain length and degree of unsaturation of the linker between the two aryl groups as well as substitution of the pyridine moiety. Structure-activity relationship studies were subsequently conducted over a larger range of 1,4-diarylbutadienes in order to determine the scope of active compounds, to identify structural patterns governing activity and to enhance in vitro potency against E. tenella. In addition, the efficacy of many compounds for treating coccidiosis in chickens was measured by testing the ability of the compound to prevent or reduce intestinal and cecal lesions when administered by oral gavage. A few compounds in the series were identified that exhibited a moderate degree of in vitro and in vivo activity.
Gage
Jennifer L
JL
Elanco Animal Health Research and Development, A Division of Eli Lilly & Co., 2001 West Main Street, Greenfield, IN 46140-0708, USA. jgage@ceptyr.com
Kirst
Herbert A
HA
O'Neil
Deirdre
D
David
Bridget A
BA
Smith
Charles K
CK
Naylor
Sharon A
SA
D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002070:Butadienes / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D002478:Cells, Cultured; D002645:Chickens; D003048:Coccidiosis / Q000188:drug therapy / Q000662:veterinary; D004353:Drug Evaluation, Preclinical; D016786:Eimeria tenella / Q000187:drug effects*; D066298:In Vitro Techniques; D009593:Nitroimidazoles / Q000737:chemistry / Q000494:pharmacology; D011201:Poultry Diseases / Q000188:drug therapy; D013329:Structure-Activity Relationship
D000981:Antiprotozoal Agents; D002070:Butadienes; D009593:Nitroimidazoles; C009999:benzonidazole