Synthesis and SAR studies of diarylpyrrole anticoccidial agents.
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.
Qian
Xiaoxia
X
Merck Research Laboratories, Department of Medicinal Chemistry Merck and Co., Inc., PO Box 2000, Rahway, NJ 07065, USA. xiaoxia_qian@merck.com
Liang
Gui-Bai
GB
Feng
Dennis
D
Fisher
Michael
M
Crumley
Tami
T
Rattray
Sandra
S
Dulski
Paula M
PM
Gurnett
Anne
A
Leavitt
Penny Sue
PS
Liberator
Paul A
PA
Misura
Andrew S
AS
Samaras
Samantha
S
Tamas
Tamas
T
Schmatz
Dennis M
DM
Wyvratt
Matthew
M
Biftu
Tesfaye
T
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
D003049:Coccidiostats; D004791:Enzyme Inhibitors; D011758:Pyrroles; D017869:Cyclic GMP-Dependent Protein Kinases