Synthesis and biological activity of imidazopyridine anticoccidial agents: part I.
Coccidiosis is the major cause of morbidity and mortality in the poultry industry. Protozoan parasites of the genus Eimeria invade the intestinal lining of the avian host causing tissue pathology, poor weight gain, and in some cases mortality. Resistance to current anticoccidials has prompted the search for new therapeutic agents with potent in vitro and in vivo activity against Eimeria. Antiparasitic activity is due to inhibition of a parasite specific cGMP-dependent protein kinase (PKG). In this study, we present the synthesis and biological activity of imidazo[1,2-a]pyridine anticoccidial agents. From this series, several compounds showed subnanomolar in vitro activity and commercial levels of in vivo activity. However, the potential genotoxicity of these compounds precludes them from further development.
Scribner
Andrew
A
SCYNEXIS, Inc., Discovery Chemistry, P.O. Box 12878, Research Triangle Park, NC 27709-2878, United States. andrew.scribner@scynexis.com
Dennis
Richard
R
Hong
Jean
J
Lee
Shuliang
S
McIntyre
Donald
D
Perrey
David
D
Feng
Dennis
D
Fisher
Michael
M
Wyvratt
Matthew
M
Leavitt
Penny
P
Liberator
Paul
P
Gurnett
Anne
A
Brown
Chris
C
Mathew
John
J
Thompson
Donald
D
Schmatz
Dennis
D
Biftu
Tesfaye
T
D000818:Animals; D001682:Biological Availability; D003049:Coccidiostats / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004539:Eimeria / Q000187:drug effects* / Q000502:physiology; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D003049:Coccidiostats; D007093:Imidazoles; D011725:Pyridines; D017869:Cyclic GMP-Dependent Protein Kinases