title: Synthesis and SAR studies of very potent imidazopyridine antiprotozoal agents.
abstract: Compounds 10a (IC50 110 pM) and 21 (IC50 40 pM) are the most potent inhibitors of Eimeria tenella cGMP-dependent protein kinase activity reported to date and are efficacious in the in vivo antiparasitic assay when administered to chickens at 12.5 and 6.25 ppm levels in the feed. However, both compounds are positive in the Ames microbial mutagenesis assay which precludes them from further development as antiprotozoal agents in the absence of negative lifetime rodent carcinogenicity studies.
authors.affiliation: Merck Research Laboratories, Department of Medicinal Chemistry, Merck and Co., Inc, PO Box 2000, Rahway, NJ 07065, USA. Tesfaye_Biftu@merck.com
authors.forename: Tesfaye
authors.initials: T
authors.lastname: Biftu
authors.forename: Dennis
authors.initials: D
authors.lastname: Feng
authors.forename: Michael
authors.initials: M
authors.lastname: Fisher
authors.forename: Gui-Bai
authors.initials: GB
authors.lastname: Liang
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Qian
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: Paul A
authors.initials: PA
authors.lastname: Liberator
authors.forename: Chris
authors.initials: C
authors.lastname: Brown
authors.forename: Anne
authors.initials: A
authors.lastname: Gurnett
authors.forename: Penny S
authors.initials: PS
authors.lastname: Leavitt
authors.forename: Donald
authors.initials: D
authors.lastname: Thompson
authors.forename: John
authors.initials: J
authors.lastname: Mathew
authors.forename: Andrew
authors.initials: A
authors.lastname: Misura
authors.forename: Samantha
authors.initials: S
authors.lastname: Samaras
authors.forename: Tamas
authors.initials: T
authors.lastname: Tamas
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Sina
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: McNulty
authors.forename: Crystal G
authors.initials: CG
authors.lastname: McKnight
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Schmatz
authors.forename: Matthew
authors.initials: M
authors.lastname: Wyvratt
mesh_terms: D000821:Animal Feed; D000818:Animals; D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002645:Chickens; D003048:Coccidiosis / Q000188:drug therapy; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D016786:Eimeria tenella / Q000187:drug effects* / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D015394:Molecular Structure; D009152:Mutagenicity Tests; D033661:Oocysts / Q000187:drug effects; D021261:Parasitic Sensitivity Tests; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000981:Antiprotozoal Agents; D004791:Enzyme Inhibitors; D007093:Imidazoles; D011725:Pyridines; D017869:Cyclic GMP-Dependent Protein Kinases