149054-60-4

Upstream product

• 109925-10-2 1,3-dimethyl-5-phenoxypyrazole-4-carbaldehyde 
• 108-95-2 phenol 
• 27006-76-4 5-chloro-4-formyl-1,3-dimethylpyrazole 

Downstream Products

• 355005-59-3 (C₆H₅C(CH₃)2CH₂)3Sn(O₂CC₃N₂(CH₃)2(OC₆H₅)) 
• 1424330-09-5 C₂₂H₂₄N₄O₂ 
• 355005-33-3 (C₆H₅)3SnC₃N₂(CH₃)2(OC₆H₅)COO 
• 355005-45-7 (C₆H₅)2Sn(O₂CC₃N₂(CH₃)2(OC₆H₅))2 
• 355005-48-0 (C₄H₉)2Sn(O₂CC₃N₂(CH₃)2(OC₆H₅))2 

Relevant academic research and scientific papers

Discovery and structure-activity relationship study of 4-phenoxythiazol-5-carboxamides as highly potent TGR5 agonists

A novel therapy that stimulates endogenous glucagon-like peptide-1 (GLP-1) secretion by Takeda G-protein-coupled receptor 5 (TGR5) agonists might be a superior alternative for the treatment of type 2 diabetes mellitus. A series of 4-phenoxythiazol-5-carboxamides were developed as highly potent TGR5 agonists using a bioisosteric replacement strategy based on the scaffold of 4-phenoxynicotinamides. The structure-activity relationship on the bottom phenyl ring and the thiazole ring was extensively studied, and the 2-methylthiazole derivatives 30c and e displayed the best in vitro potency toward human TGR5, with EC50 values of approximately 1 nM. While endowed with excellent in vitro potency, the 2-methyl-thiazoles were flawed with high microsomal clearance.

Discovery of 5-phenoxy-1,3-dimethyl-1H-pyrazole-4-carboxamides as potent agonists of TGR5 via sequential combinatorial libraries

Optimization of a high-throughput screening hit led to the discovery of a new series of 5-phenoxy-1,3-dimethyl-1H-pyrazole-4-carboxamides as highly potent agonists of TGR5. This novel chemotype was rapidly developed through iterative combinatorial library synthesis. It was determined that in vitro agonist potency correlated with functional activity data from human peripheral blood monocytes.