Margathe, Jean-Francois published the artcileStructure-Activity Relationship Studies toward the Discovery of Selective Apelin Receptor Agonists, Quality Control of 64987-16-2, the publication is Journal of Medicinal Chemistry (2014), 57(7), 2908-2919, database is CAplus and MEDLINE.
Apelin is the endogenous ligand for the previously orphaned G protein-coupled receptor APJ. Apelin and its receptor are widely distributed in the brain, heart, and vasculature, and are emerging as an important regulator of body fluid homeostasis and cardiovascular functions. To further progress in the pharmacol. and the physiol. role of the apelin receptor, the development of small, bioavailable agonists and antagonists of the apelin receptor, is crucial. In this context, E339-3D6 was described as the first nonpeptidic apelin receptor agonist. The authors show here that 1 is actually a mixture of polymethylated species, and they describe an alternative and versatile solid-phase approach that allows access to highly pure 27, the major component of 1. This approach was also applied to prepare a series of derivatives in order to identify the crucial structural determinants required for the ligand to maintain its affinity for the apelin receptor as well as its capacity to promote apelin receptor signaling and internalization. The study of the structure-activity relationships led to the identification of ligands 19, 21, and 38, which display an increased affinity compared to that of 27. The latter and 19 behave as full agonists with regard to cAMP production and apelin receptor internalization, whereas 21 is a biased agonist toward cAMP production Interestingly, the three ligands display a much higher stability in mouse plasma (T1/2 > 10 h) than the endogenous apelin-17 peptide 2 (T1/2 < 4 min).
Journal of Medicinal Chemistry published new progress about 64987-16-2. 64987-16-2 belongs to thiazole, auxiliary class Thiazole,Amine,Ester, name is Methyl 2-(2-aminothiazol-4-yl)acetate, and the molecular formula is C6H8N2O2S, Quality Control of 64987-16-2.
Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/thiazole,
Thiazole | chemical compound | Britannica