Synthesis and SAR of 2,3-diarylpyrrole inhibitors of parasite cGMP-dependent protein kinase as novel anticoccidial agents.

Basic Information

ID: ALA1140243

Journal: Bioorg Med Chem Lett

Title: Synthesis and SAR of 2,3-diarylpyrrole inhibitors of parasite cGMP-dependent protein kinase as novel anticoccidial agents.

Authors: Biftu T, Feng D, Ponpipom M, Girotra N, Liang GB, Qian X, Bugianesi R, Simeone J, Chang L, Gurnett A, Liberator P, Dulski P, Leavitt PS, Crumley T, Misura A, Murphy T, Rattray S, Samaras S, Tamas T, Mathew J, Brown C, Thompson D, Schmatz D, Fisher M, Wyvratt M.

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.

CiteXplore: 15922595

DOI: 10.1016/j.bmcl.2005.04.060

Patent ID: