Johnson, James A. published the artcileDiscovery of a Hydroxypyridinone APJ Receptor Agonist as a Clinical Candidate, Quality Control of 151-10-0, the main research area is APJ receptor agonist pharmacokinetic oral bioavailability pharmacodynamic.
Apelin-13 is an endogenous peptidic agonist of the apelin receptor (APJ) receptor with the potential for improving cardiac function in heart failure patients. However, the low plasma stability of apelin-13 necessitates continuous i.v. infusion for therapeutic use. There are several approaches to increase the stability of apelin-13 including attachment of pharmacokinetic enhancing groups, stabilized peptides, and Fc-fusion approaches. We sought a small-mol. APJ receptor agonist approach to target a compound with a pharmacokinetic profile amenable for chronic oral administration. This manuscript describes sequential optimization of the pyrimidinone series, leading to pyridinone 14(I), with in vitro potency equivalent to the endogenous ligand apelin-13 and with an excellent oral bioavailability and PK profile in multiple preclin. species. Compound 14 exhibited robust pharmacodynamic effects similar to apelin-13 in an acute rat pressure-volume loop model and was advanced as a clin. candidate.
Journal of Medicinal Chemistry published new progress about Apelin receptors Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 151-10-0 belongs to class isoquinoline, name is 1,3-Dimethoxybenzene, and the molecular formula is C8H10O2, Quality Control of 151-10-0.
Referemce:
Isoquinoline – Wikipedia,
Isoquinoline | C9H7N – PubChem