1795232-59-5Relevant articles and documents
Discovery of LY3104607: A Potent and Selective G Protein-Coupled Receptor 40 (GPR40) Agonist with Optimized Pharmacokinetic Properties to Support Once Daily Oral Treatment in Patients with Type 2 Diabetes Mellitus
Hamdouchi, Chafiq,Maiti, Pranab,Warshawsky, Alan M.,Debaillie, Amy C.,Otto, Keith A.,Wilbur, Kelly L.,Kahl, Steven D.,Patel Lewis, Anjana,Cardona, Guemalli R.,Zink, Richard W.,Chen, Keyue,Cr, Siddaramaiah,Lineswala, Jayana P.,Neathery, Grace L.,Bouaichi, Cecilia,Diseroad, Benjamin A.,Campbell, Alison N.,Sweetana, Stephanie A.,Adams, Lisa A.,Cabrera, Over,Ma, Xiaosu,Yumibe, Nathan P.,Montrose-Rafizadeh, Chahrzad,Chen, Yanyun,Miller, Anne Reifel
, p. 934 - 945 (2018)
As a part of our program to identify potent GPR40 agonists capable of being dosed orally once daily in humans, we incorporated fused heterocycles into our recently disclosed spiropiperidine and tetrahydroquinoline acid derivatives 1, 2, and 3 with the intention of lowering clearance and improving the maximum absorbable dose (Dabs). Hypothesis-driven structural modifications focused on moving away from the zwitterion-like structure. and mitigating the N-dealkylation and O-dealkylation issues led to triazolopyridine acid derivatives with unique pharmacology and superior pharmacokinetic properties. Compound 4 (LY3104607) demonstrated functional potency and glucose-dependent insulin secretion (GDIS) in primary islets from rats. Potent, efficacious, and durable dose-dependent reductions in glucose levels were seen during glucose tolerance test (GTT) studies. Low clearance, volume of distribution, and high oral bioavailability were observed in all species. The combination of enhanced pharmacology and pharmacokinetic properties supported further development of this compound as a potential glucose-lowering drug candidate.
FUSED RING COMPOUND HAVING UREA STRUCTURE
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, (2020/01/31)
The present invention relates to a novel fused ring compound having urea structure that exhibits excellent NAMPT activating effect, and a method using the same for treating / preventing metabolic disorder, cardiovascular and kidney disease, mitochondrial disease, neurodegenerative disease, ocular disease, and muscle wasting disorder. The present invention provides a compound represented by following formula (I) or a pharmacologically acceptable salt: Formula (I) wherein A, B, R, R2 and R3 represent the same meanings as in the claims.
HETEROCYCLIC COMPOUNDS AS IMMUNOMODULATORS
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, (2017/08/01)
Disclosed are compounds of Formula (I'), methods of using the compounds to modulate PD-1/PD-L1 interaction, and pharmaceutical compositions comprising such compounds. The compounds are useful in treating, preventing or ameliorating diseases or disorders such as cancer or viral infections.
