Synthesis and SAR studies of potent imidazopyridine anticoccidial agents

• Published in: Bioorganic & medicinal chemistry letters Vol. 17; no. 13; pp. 3558 - 3561
• Main Authors: Liang, Gui-Bai, Qian, Xiaoxia, Feng, Dennis, Fisher, Michael, Brown, Christine M., Gurnett, Anne, Leavitt, Penny Sue, Liberator, Paul A., Misura, Andrew S., Tamas, Tamas, Schmatz, Dennis M., Wyvratt, Matthew, Biftu, Tesfaye
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01.07.2007; Elsevier
• Subjects: Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiparasitic agents; Biological and medical sciences; Chemistry, Pharmaceutical - methods; Coccidiosis; Coccidiosis - drug therapy; Coccidiostats - chemistry; Coccidiostats - pharmacology; Cyclic GMP-Dependent Protein Kinases - metabolism; Drug Design; Eimeria tenella; Et-PKG; Imidazoles - chemistry; Imidazopyridine; Medical sciences; Models, Chemical; Pharmacology. Drug treatments; Protein Kinase Inhibitors - chemistry; Protein Kinase Inhibitors - pharmacology; Pyridines - chemistry; Pyridines - pharmacology; Structure-Activity Relationship; Et-PKG; Coccidiosis; Imidazopyridine; Protozoal disease; Eimeria; Angular nitrogen heterocycle; Signal transduction; Imidazopyridine derivatives; Structure activity relation; Anticoccidious; Bicyclic compound; Chemical synthesis; Protozoa; Apicomplexa; Enzyme; Transferases; Benzene derivatives; Enzyme inhibitor; Parasitosis; In vitro; Infection; In vivo; Protein kinase; Organic fluorine compounds; Parasiticide; Pyrimidine derivatives
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2007.04.041

Diaryl imidazo[1,2- a]pyridine derivatives bearing N-alkyl amino substituents have been synthesized and evaluated as highly potent Et-PKG inhibitor and efficacious anticoccidial agents. Diaryl imidazo[1,2- a]pyridine derivatives, such as 6a and 7i, have been synthesized and found to be potent inhibitors of parasite PKG activity. The most potent compounds are the 7-isopropylaminomethyl analog 6a and 2-isopropylamino analog 7i. These compounds are also fully active in in vivo assay as anticoccidial agents at 25 ppm in feed.