title: Synthesis and biological activity of imidazopyridine anticoccidial agents: Part II.
abstract: 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. Recently, we reported the synthesis and biological activity of potent imidazo[1,2-a]pyridine anticoccidial agents. Antiparasitic activity is due to inhibition of a parasite specific cGMP-dependent protein kinase (PKG). In this study, we report the synthesis and anticoccidial activity of a second set of such compounds, focusing on derivatization of the amine side chain at the imidazopyridine 7-position. 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.
authors.affiliation: SCYNEXIS, Inc., Discovery Chemistry, P.O. Box 12878, Research Triangle Park, NC 27709-2878, USA. andrew.scribner@scynexis.com
authors.forename: Andrew
authors.initials: A
authors.lastname: Scribner
authors.forename: Richard
authors.initials: R
authors.lastname: Dennis
authors.forename: Shuliang
authors.initials: S
authors.lastname: Lee
authors.forename: Gilles
authors.initials: G
authors.lastname: Ouvry
authors.forename: David
authors.initials: D
authors.lastname: Perrey
authors.forename: Michael
authors.initials: M
authors.lastname: Fisher
authors.forename: Matthew
authors.initials: M
authors.lastname: Wyvratt
authors.forename: Penny
authors.initials: P
authors.lastname: Leavitt
authors.forename: Paul
authors.initials: P
authors.lastname: Liberator
authors.forename: Anne
authors.initials: A
authors.lastname: Gurnett
authors.forename: Chris
authors.initials: C
authors.lastname: Brown
authors.forename: John
authors.initials: J
authors.lastname: Mathew
authors.forename: Donald
authors.initials: D
authors.lastname: Thompson
authors.forename: Dennis
authors.initials: D
authors.lastname: Schmatz
authors.forename: Tesfaye
authors.initials: T
authors.lastname: Biftu
mesh_terms: D000818:Animals; D003049:Coccidiostats / Q000138:chemical synthesis* / Q000494:pharmacology*; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004539:Eimeria / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis* / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D003049:Coccidiostats; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D017869:Cyclic GMP-Dependent Protein Kinases; C023666:pyridine