title: Synthesis and SAR studies of diarylpyrrole anticoccidial agents.
abstract: 2-(4-Fluorophenyl)-3-(4-pyridinyl)-5-substituted pyrroles were prepared and evaluated as anticoccidial agents in both in vitro and in vivo assays. Among the compounds evaluated, the dimethylamine-substituted pyrrole 19a is the most potent inhibitor of Eimeria tenella PKG (cGMP-dependent protein kinase). Further SAR studies on the side chain of the 2-pyrrolidine nitrogen did not enhance in vivo anticoccidial activity.
authors.affiliation: Merck Research Laboratories, Department of Medicinal Chemistry Merck and Co., Inc., PO Box 2000, Rahway, NJ 07065, USA. xiaoxia_qian@merck.com
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Qian
authors.forename: Gui-Bai
authors.initials: GB
authors.lastname: Liang
authors.forename: Dennis
authors.initials: D
authors.lastname: Feng
authors.forename: Michael
authors.initials: M
authors.lastname: Fisher
authors.forename: Tami
authors.initials: T
authors.lastname: Crumley
authors.forename: Sandra
authors.initials: S
authors.lastname: Rattray
authors.forename: Paula M
authors.initials: PM
authors.lastname: Dulski
authors.forename: Anne
authors.initials: A
authors.lastname: Gurnett
authors.forename: Penny Sue
authors.initials: PS
authors.lastname: Leavitt
authors.forename: Paul A
authors.initials: PA
authors.lastname: Liberator
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Misura
authors.forename: Samantha
authors.initials: S
authors.lastname: Samaras
authors.forename: Tamas
authors.initials: T
authors.lastname: Tamas
authors.forename: Dennis M
authors.initials: DM
authors.lastname: Schmatz
authors.forename: Matthew
authors.initials: M
authors.lastname: Wyvratt
authors.forename: Tesfaye
authors.initials: T
authors.lastname: Biftu
mesh_terms: D000818:Animals; D003049:Coccidiostats / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; 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; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D003049:Coccidiostats; D004791:Enzyme Inhibitors; D011758:Pyrroles; D017869:Cyclic GMP-Dependent Protein Kinases