Synthesis and evaluation of prodrugs of corticotropin-releasing factor-1 (CRF1) receptor antagonist BMS-665053 leading to improved oral bioavailabilit...
Basic Information
ID: ALA3997831
Journal: Bioorg Med Chem Lett
Title: Synthesis and evaluation of prodrugs of corticotropin-releasing factor-1 (CRF1) receptor antagonist BMS-665053 leading to improved oral bioavailability.
Authors: Hartz RA, Vrudhula VM, Ahuja VT, Grace JE, Lodge NJ, Bronson JJ, Macor JE.
Abstract: A series of phosphate and ester-based prodrugs of anilinopyrazinone 1 (BMS-665053) containing either a methylene or an (acyloxy)alkoxy linker was prepared and evaluated in rat pharmacokinetic studies with the goal of improving the oral bioavailability of the parent (1). The prodrugs, in general, had improved aqueous solubility and oral bioavailability compared to 1. Prodrug 12, which contains an (acyloxy)alkoxy linker, showed the greatest improvement in the oral bioavailability relative to the parent (1), with a seven-fold increase (from 5% to 36%) in rat pharmacokinetic studies.
CiteXplore: 28223020
DOI: 10.1016/j.bmcl.2017.02.015
Patent ID: ┄