Spiro-1-benzofuranpiperidinylalkanoic acids as a novel and selective sphingosine S1P 5 receptor agonist chemotype

Abstract The synthesis and SAR of a novel class of spirobenzofuranpiperidinyl-derived alkanoic acids 6 – 34 as sphingosine S1P 5 receptor agonists are described. The target compounds generally elicit high S1P 5 receptor agonistic potencies and in general are selective against both S1P 1 and S1P 3 receptor subtypes. The key compound 32 shows a high bioavailability of 73% and a CNS/plasma ratio of 0.8 after oral administration in rats.