1224684-89-2Relevant academic research and scientific papers
Topical Intestinal Aminoimidazole Agonists of G-Protein-Coupled Bile Acid Receptor 1 Promote Glucagon Like Peptide-1 Secretion and Improve Glucose Tolerance
Lasalle, Manuel,Hoguet, Vanessa,Hennuyer, Nathalie,Leroux, Florence,Piveteau, Catherine,Belloy, Lo?c,Lestavel, Sophie,Vallez, Emmanuelle,Dorchies, Emilie,Duplan, Isabelle,Sevin, Emmanuel,Culot, Maxime,Gosselet, Fabien,Boulahjar, Rajaa,Herledan, Adrien,Staels, Bart,Deprez, Benoit,Tailleux, Anne,Charton, Julie
, p. 4185 - 4211 (2017)
The role of the G-protein-coupled bile acid receptor TGR5 in various organs, tissues, and cell types, specifically in intestinal endocrine L-cells and brown adipose tissue, has made it a promising therapeutical target in several diseases, especially type-2 diabetes and metabolic syndrome. However, recent studies have shown deleterious on-target effects of systemic TGR5 agonists. To avoid these systemic effects while stimulating glucagon-like peptide-1 (GLP-1) secreting enteroendocrine L-cells, we have designed TGR5 agonists with low intestinal permeability. In this article, we describe their synthesis, characterization, and biological evaluation. Among them, compound 24 is a potent GLP-1 secretagogue, has low effect on gallbladder volume, and improves glucose homeostasis in a preclinical murine model of diet-induced obesity and insulin resistance, making the proof of concept of the potential of topical intestinal TGR5 agonists as therapeutic agents in type-2 diabetes.
IMIDAZOL- OR 1,2,4-TRIAZOL-DERIVATIVES AND THEIR USE
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Page/Page column 39; 40, (2016/01/01)
The present invention is directed to novel compounds of formula (I), pharmaceutically acceptable salts or solvates thereof, and their use.
Synthesis, in vitro evaluation and cocrystal structure of 4-oxo-[1]benzopyrano[4,3-c]pyrazole cryptosporidium parvum inosine 5′-monophosphate dehydrogenase (Cp IMPDH) inhibitors
Sun, Zhuming,Khan, Jihan,Makowska-Grzyska, Magdalena,Zhang, Minjia,Cho, Joon Hyung,Suebsuwong, Chalada,Vo, Pascal,Gollapalli, Deviprasad R.,Kim, Youngchang,Joachimiak, Andrzej,Hedstrom, Lizbeth,Cuny, Gregory D.
supporting information, p. 10544 - 10550 (2015/02/19)
Cryptosporidium inosine 5′-monophosphate dehydrogenase (CpIMPDH) has emerged as a therapeutic target for treating Cryptosporidium parasites because it catalyzes a critical step in guanine nucleotide biosynthesis. A 4-oxo-[1]benzopyrano[4,3-c]pyrazole derivative was identified as a moderately potent (IC50 = 1.5 μM) inhibitor of CpIMPDH. We report a SAR study for this compound series resulting in 8k (IC50 = 20 ± 4 nM). In addition, an X-ray crystal structure of CpIMPDH·IMP·8k is also presented.
