title: Synthesis and SAR of 2,3-diarylpyrrole inhibitors of parasite cGMP-dependent protein kinase as novel anticoccidial agents.
abstract: Several analogs of 2,3-diaryl pyrroles were synthesized and evaluated as inhibitors of Eimeria tenella cGMP-dependent protein kinase and in in vivo anticoccidial assays. A 4-fluorophenyl group enhances both in vitro and in vivo activities. The most potent analogs are the 5-(N-methyl, N-ethyl, and N-methylazetidine methyl) piperidyl derivatives 12, 23, and 34. These compounds have a broad spectrum of activity. Based on the in vivo efficacy and cost of synthesis, the N-ethyl analog 23 was chosen as a novel anticoccidial agent for a field trial.
authors.affiliation: Merck Research Laboratories, Department of Medicinal Chemistry, Merck and Co., P.O. Box 2000, Rahway, NJ 07065-0900, 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: Mitree
authors.initials: M
authors.lastname: Ponpipom
authors.forename: Narindar
authors.initials: N
authors.lastname: Girotra
authors.forename: Gui-Bai
authors.initials: GB
authors.lastname: Liang
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Qian
authors.forename: Robert
authors.initials: R
authors.lastname: Bugianesi
authors.forename: Joseph
authors.initials: J
authors.lastname: Simeone
authors.forename: Linda
authors.initials: L
authors.lastname: Chang
authors.forename: Anne
authors.initials: A
authors.lastname: Gurnett
authors.forename: Paul
authors.initials: P
authors.lastname: Liberator
authors.forename: Paula
authors.initials: P
authors.lastname: Dulski
authors.forename: Penny Sue
authors.initials: PS
authors.lastname: Leavitt
authors.forename: Tami
authors.initials: T
authors.lastname: Crumley
authors.forename: Andrew
authors.initials: A
authors.lastname: Misura
authors.forename: Terence
authors.initials: T
authors.lastname: Murphy
authors.forename: Sandra
authors.initials: S
authors.lastname: Rattray
authors.forename: Samantha
authors.initials: S
authors.lastname: Samaras
authors.forename: Tamas
authors.initials: T
authors.lastname: Tamas
authors.forename: John
authors.initials: J
authors.lastname: Mathew
authors.forename: Christine
authors.initials: C
authors.lastname: Brown
authors.forename: Don
authors.initials: D
authors.lastname: Thompson
authors.forename: Dennis
authors.initials: D
authors.lastname: Schmatz
authors.forename: Michael
authors.initials: M
authors.lastname: Fisher
authors.forename: Matthew
authors.initials: M
authors.lastname: Wyvratt
mesh_terms: D000818:Animals; D001682:Biological Availability; D002645:Chickens; D003048:Coccidiosis / Q000188:drug therapy; D003049:Coccidiostats / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors*; D004539:Eimeria; D006207:Half-Life; D020128:Inhibitory Concentration 50; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors*; D011758:Pyrroles / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D003049:Coccidiostats; D015800:Protozoan Proteins; D011758:Pyrroles; D017869:Cyclic GMP-Dependent Protein Kinases