A Scalable Synthesis of Roxadustat (FG-4592)
Ondřej Píša, S. Rádl, Igor Čerňa, Filip Šembera
Abstract
A scalable five-step protocol for synthesis of roxadustat, an orally administered hypoxia-inducible factor-propyl hydroxylase inhibitor (HIF-PHI), was developed with an emphasis placed on aspects of medicinal chemistry. The isoquinoline core of the molecule was prepared using a purposefully designed cyclocondensation in which both the cyclocondensation and demasking of the groups being condensed is promoted by a common acid agent in one step. Roxadustat was obtained pure in a very competitive overall yield across all reaction steps and in compliance with permissible residual Pd level in API.
Topics & Concepts
ChemistryScalabilityCombinatorial chemistryIsoquinolineYield (engineering)Medicinal chemistryComputer scienceDatabaseMaterials scienceMetallurgyCancer, Hypoxia, and MetabolismHistone Deacetylase Inhibitors ResearchSynthetic Organic Chemistry Methods