Identification of tetrahydropyrido [4, 3-d] pyrimidine amides as a new class of orally bioavailable TGR5 agonists

…, KD Freeman-Cook, AT Londregan, L Wei…

Index: Piotrowski, David W.; Futatsugi, Kentaro; Warmus, Joseph S.; Orr, Suvi T. M.; Freeman-Cook, Kevin D.; Londregan, Allyn T.; Wei, Liuqing; Jennings, Sandra M.; Herr, Michael; Coffey, Steven B.; Jiao, Wenhua; Storer, Gregory; Hepworth, David; Wang, Jian; Lavergne, Sophie Y.; Chin, Janice E.; Hadcock, John R.; Brenner, Martin B.; Wolford, Angela C.; Janssen, Ann M.; Roush, Nicole S.; Buxton, Joanne; Hinchey, Terri; Kalgutkar, Amit S.; Sharma, Raman; Flynn, Declan A. ACS Medicinal Chemistry Letters, 2013 , vol. 4, # 1 p. 63 - 68

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Citation Number: 18

Abstract

Takeda G-protein-coupled receptor 5 (TGR5) represents an exciting biological target for the potential treatment of diabetes and metabolic syndrome. A new class of high-throughput screening (HTS)-derived tetrahydropyrido [4, 3-d] pyrimidine amide TGR5 agonists is disclosed. We describe our effort to identify an orally available agonist suitable for assessment of systemic TGR5 agonism. This effort resulted in identification of 16, which ...