Synthesis and SAR of 2,3-diarylpyrrole inhibitors of parasite cGMP-dependent protein kinase as novel anticoccidial agents |
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Authors: | Biftu Tesfaye Feng Dennis Ponpipom Mitree Girotra Narindar Liang Gui-Bai Qian Xiaoxia Bugianesi Robert Simeone Joseph Chang Linda Gurnett Anne Liberator Paul Dulski Paula Leavitt Penny Sue Crumley Tami Misura Andrew Murphy Terence Rattray Sandra Samaras Samantha Tamas Tamas Mathew John Brown Christine Thompson Don Schmatz Dennis Fisher Michael Wyvratt Matthew |
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Affiliation: | Merck Research Laboratories, Department of Medicinal Chemistry, Merck and Co., P.O. Box 2000, Rahway, NJ 07065-0900, USA. tesfaye_biftu@merck.com |
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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. |
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