Efficient, large-scale synthesis and preclinical studies of MRS5698, a highly selective A3 adenosine receptor agonist that protects against chronic neuropathic pain

We reported that 2-(3,4-difluorophenylethynyl)- N 6 -3-chlorobenzyl ( N )-methanocarba adenosine derivative 1 (MRS5698) binds selectively to human and mouse A 3 adenosine receptors (A 3 ARs, K i 3 nM). It is becoming an important pharmacological tool for defining A 3 AR effects and is orally active in a chronic neuropathic pain model. Here, we introduce a new synthetic route for MRS5698 from d -ribose, suitable for a scale-up on a multi-gram scale, and we measure in vitro and in vivo ADME-Tox parameters. MRS5698 was very stable in vitro, failed to inhibit CYPs at